WO2024134592A1

WO2024134592A1 - Device, system and method for monitoring a site of interest internal to a patient body

Info

Publication number: WO2024134592A1
Application number: PCT/IB2023/063129
Authority: WO
Inventors: Erez SHOR; Shai Policker; Matan BEN DAVID; Gilad Lerman; Amir Kraitzer; Tal YERED
Original assignee: Exero Medical Ltd.
Priority date: 2022-12-21
Filing date: 2023-12-21
Publication date: 2024-06-27

Abstract

In some embodiments, a system for monitoring a patient site-of-interest (SOI) of a mammalian subject, system comprises at least one monitoring electrode for sensing a parameter value relating to a patient intervention site; and at least one reference electrode for sensing a parameter value relating to a patient reference site, wherein the patient reference site is located remotely from the patient intervention site. The at least one monitoring electrode and the at least one reference electrode are operable to provide an output signal descriptive of physiological characteristics of the intervention and the reference site. The system is configured to process the output signal for determining, with respect to the patient SOI, whether an adverse physiological phenomenon occurs or not.

Description

DEVICE, SYSTEM AND METHOD FOR MONITORING A SITE OF INTEREST INTERNAL TO A PATIENT BODY

CROSS-REFERENCE TO RELATED APPLICATIONS

CLAIM OF BENEFIT AND PRIORITY

[1] The present application claims priority and benefit from US Provisional Patent Application 63/434,095, filed December 21, 2022, titled "DEVICE, SYSTEM AND METHOD FOR MONITORING A SURGICAL SITE" and which is incorporated by reference herein in its entirety

BACKGROUND

[001] Monitoring physiological processes following surgery is critical toensure complications are addressed as soon as possible for proper recovery, healing and/or to provide guidance for personalized treatment. Anastomotic leak, for example, is a common, life threatening complication in gastrointestinal (Gl) surgeries. Early detection is essential for proper treatment and complete recovery. Current methods of detecting anastomotic leak are either delayed, inaccurate or invasive and may compound patient trauma. Therefore, there is a need for providing efficient alternative systems and methods providing early anastomotic leak detection.

BRIEF DESCRIPTION OF THE DRAWINGS

[002] The figures illustrate generally, by way of example, but not by way of limitation, various embodiments discussed in the present document.

[003] For simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity of presentation. Furthermore, reference numerals may be repeated among the figures to indicate corresponding or analogous elements. References to previously presented elements are implied without necessarily further citing the drawing or description in which they appear. The number of elements shown in the Figures should by no means be construed as limiting and is for illustrative purposes only. The figures are listed below.

[004] Figure l is a schematic block-diagram depiction of a physiological phenomenon detection sequence employable by the monitoring system, according to an embodiment. [005] Figure 2A and Figure 2B depict a monitoring system coupled to a patient, according to various embodiments.

[006] Figure 3 is a schematic block-diagram depiction of a physiological phenomenon detection sequence employable by the monitoring system, according to an alternative embodiment.

[007] Figures 4A to 4C are schematic depictions of various deployment options for deploying a sensing (also: monitoring) electrode into a patient body, according to embodiments.

[008] Figures 5A-B and Figures 5C-D are schematic depictions of different stages for operably deploying and fastening a monitoring electrode of the monitoring system onto patient tissue, according to an embodiment.

[009] Figure 6 is a flowchart of a method for monitoring a patient site of interest, according to some embodiments.

[0010] Figure 7 schematically shows signal propagation in tissue, according to some embodiments.

[0011] Figure 8 shows an impedance plot of a threshold-based leak detection method, according to an embodiment.

[0012] Figure 9 shows a plot of impedance measurement in induced leak, according to an embodiment.

[0013] Figure 10 shows a plot of impedance measurement in sutured leak, according to an embodiment.

[0014] Figure 11 shows representative electrophysiological signals measured by implanted electrodes, according to an embodiment.

[0015] Figure 12 shows cross correlation value of leak animal model vs. control animal model over time, according to an embodiment.

[0016] Figure 13 shows impedance-based leak detection by measuring impedance at the surgical or monitoring site, and by distantly placed reference electrode (e.g., placed 80mm and more, from the intervention or surgical site, of the same organ or tissue as the monitoring electrode. As shown in the example, measured tissue impedance decreased about 10%, about 10 mm to 20 mm from the leak site, about, 2 hours after leak induction at the surgical site, according to an embodiment.

[0017] Figure 14 illustrates the maximum cross correlation between the signal received from at least one electrode engaging with the tissue at the surgical site and at least one reference electrode. For the red graph (the 'leak' classified type) a leak is detected, and in the two blue graphs (the 'control' classified type) there is no leak, according to an embodiment. [0018] Figure 15B illustrates myoelectric data recorded from a pig using the system, according to an embodiment.

[0019] Figure 15C illustrates myoelectric data recorded from viable ex-vivo human colonic tissue under normal (blue) and hypoxia conditions (red) and corresponding contraction force (green). The myoelectric signal was found to be substantially similar to the large animal in-vivo model. Functional parameters changed following induction of hypoxia conditions (simulating leak driving conditions) , according to an embodiment.

[0020] Figure 15D show clinical results from acute surgery (N=5). A system according to an embodiment was used to record impedance and myoelectric data from baseline (intact) and devascularized (hypoxia) colonic tissue. Raw data (left) exhibits similar characteristics compared to animal/ex-vivo data. Spiking is diminished under hypoxia conditions. Spiking activity for all five patients, is shown in the graph to the right, for baseline and ischemia conditions, in which horizontal bars indicate mean, error bars indicate standard deviation, according to an embodiment.

[0021] Reference is made to Figures 16A-16C. Figure 16A: First myoelectric (blue) and contraction data (red) were recorded from a longitudinal colon tissue. Figure 16B: Using data relating to a raw myoelectric signal, spikes were filtered out. Reconstruction of mechanical contractions from the myoelectric (blue) data: spikes are detected using threshold filtering of the time derivative of the original signal (black), then convolved with a window function to generate reconstructed mechanical data (green). Figure 16C: The mechanical contractions were reconstructed using only myoelectric data. The reconstruction was with relatively good fit to the measured data under normal and hypoxia conditions. The qualitative comparison between the actual mechanical data recorded (brown) and the reconstructed contractions calculated is shown using only myoelectric data (green), according to an embodiment.

[0022] Figure 17 (top) and Figure 18 (top), illustrate myoelectric patterns in baseline and drug affected environments, according to an embodiment. The top indicates baseline contractions (red) and myoelectric activity (blue) , according to an embodiment.

[0023] Figure 17 (bottom) shows contractions and myoelectric activity after Carbachaol (CCH) was introduced, and Figure 18 (bottom) contractions and myoelectric activity after the introduction of MON NA (N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid).

[0024] Figure 19 shows a point cloud of slow colonic electrophysiological (EPS) signals (cycles/min) vs. an inflammation index (arbitrary units) vs. spike correlation coefficient value, of 50 subjects. The inflammation index may be equivalent to inflammation (e.g., impedance) correlation between the monitored and reference sites. Such point cloud may be employed for selecting or training a classifier (e.g., a machine learning model), e.g., based on a linear or non-linear threshold applied on the point cloud. In some examples, only one parameter may be taken into consideration by the classifier. In some embodiments, two or more parameters may be taken into consideration by the classifier, according to an embodiment.

[0025] Figure 20 shows a graph of Gl motility data (Ileus in patient 1 (red) and Ileus in patient 2 (gray), in conjunction with an average recovery index, calculated based on temporal recovery of motility signals, and a food intake threshold in arbitrary units (A.U.) calculated using supervised statistical methods, according to some embodiments.

DETAILED DESCRIPTION

[0026] Aspects of the present invention pertain to a patient site of interest (SOI) monitoring system. The system may employ an electronic sensor comprising one or more monitoring and, optionally, reference electrodes. The electrodes may be bipolar and/or monopolar, and are employed for sensing one or more parameter values relating to the patient SOI, which may include an intervention site and, optionally, a reference site that is remote from the intervention site. The one or more parameter values may pertain to an electrical characteristic of patient tissue (e.g., impedance) and/or to electro-physiological signals (e.g., myoelectric activity). It is noted that systems, devices and methods disclosed herein may be applied intra- operatively and/or post-operatively.

[0027] In some embodiments, a "reference site" may pertain to a site of one or more "healthy" mammalian subjects different from the monitored patient SOI but, e.g., of a corresponding organ. Accordingly, processes, methods, and/or procedures described herein with respect to a reference site of the patient SOI, may in some embodiments additionally or alternatively pertain to signals and/or data recorded from reference sites of other mammalian subjects.

[0028] In some embodiments, parameter values one or more indicators are considered for determining whether at least one adverse phenomenon currently occurs, and/or for determining a probability that at least one adverse phenomenon will occur with respect to the patient intervention site. The indicators may also be considered for determining which adverse phenomenon is currently occurring or will occur, e.g., within a certain time period.

[0029] In some embodiments, the monitored parameter values may provide an indication about current normal and/or abnormal tissue healing, and/or a prediction of normal and/or abnormal tissue healing. [0030] Parameter values may pertain to local inflammation, wherein subsiding local inflammation postsurgery may be identified as "normal", and worsening inflammation may be identified a potential cause of post-operative complications ("abnormal"). For example, an inflammation index may be derived from the impedance measurements, collected from, e.g., 8 measurement sites, divided into a group of 4 sites close to the anastomosis and 4 site far from the anastomosis. Inflammatory processes affect impedance as edema and secretion of factors (such as interleukins and lactic acid) change the conductivity of the tissue. The inflammation index accounts for spatial and temporal derivatives of the impedance to filter potential systemic effects. A decline in the inflammation index over time can be indicative of a normal recovery patient, whereas a comparatively a high inflammation index might be indicative of a complication. In some examples, the index value may be derived based on the correlation value.

[0031] Parameter values may pertain to motility. A baseline slow waves of, e.g., 4 cycles/minute or higher may be considered a sign of normal post-operative function. For example, a motility index may be derived from the low frequencies of the measured myoelectric signal. The normal operation of the colon may be characterized by slow waves in the range of, e.g., 2-20 cycles/minute.

[0032] Parameter values may also pertain to propagating contractile activity of the colon. Based on a level of correspondence (e.g., correlation) of the contractile activity between a proximal and distal location with respect to the anastomosis site, it may be determined whether there is normal postoperative function or not, for assessing whether an adverse phenomenon is occurring or will occur. For example, a level of correspondence of spiking activity between proximal site and distal sites of anastomosis may be determined. Depending on the determined level of correspondence, it may be determined whether normal healing is occurring or not. In some examples, spiking activity is derived from the high frequencies of a measured myoelectric signal. In some examples, a spiking correlation index is derived from the correlation of the spiking activity near and farther away from the anastomosis. In some examples, the term "index" may also pertain to "score".

[0033] In some examples, the term "at least one (monitoring/reference) electrode" may pertain to at least one set of electrodes comprising a pair of electrodes that can be operably engaged with a patient intervention site and/or reference site for monitoring, e.g., an electrical characteristic relating to the intervention and/or reference site. Each pair of electrodes may be associated with a respective electrode signal channel. In some examples, one or more electrode signal channels may pertain to an intervention site, and one or more electrode signal channels may pertain to a reference site. [0034] In some embodiments, the device has at least two wires. In some embodiments, the system includes at least one pair of (e.g., bipolar) electrodes, which are conductive wires separate from each other. The two wires may be fused or otherwise coupled with each other to one cable. Each wire of the pair of wires can be exposed to a different tissue location of the patient SOI. The wires may be separated, for example, by a few millimeters from one another. The expressions "reference electrode", "monitoring electrode", "intervention electrode" may each pertain to a pair of (e.g., bipolar) electrodes engageable with a reference and monitoring/intervention site, respectively, for sensing electrical characteristics thereof.

[0035] The SOI monitoring system may herein also be referred to as an (e.g., leakage, hypoxia, and/or inflammation, perfusion, necrosis, and/or fibrosis) monitoring system. Generally, systems and/or methods disclosed herein are configured to detect an adverse (e.g., clinical) phenomenon (e.g., event and/or condition) with respect to the patient SOI and/or determine a probability that such adverse phenomenon is occurring or will occur. In some examples, the system and/or method may also be configured to determine an expected onset time of an adverse phenomenon along with an associated probability. However, merely to simplify the discussion that follows and without be construed in a limiting manner, discussions herein may pertain to "determining", "detecting", and/or the like, of an adverse phenomenon. Therefore, when an example of embodiment describes a scenario for detecting leakage from a surgical tissue connection site, similar or same processes and/or methods and/or methods may be employed for determining and/or detecting occurrence of additional or alternative adverse events and/or conditions, and/or an expected onset time of additional or alternative adverse events and/or conditions, and/or probability of an adverse phenomenon occurring, and/or the onset of time thereof and the associated probability.

[0036] Although some examples disclosed herein may specifically refer to "acute leak", "anastomosis leak", and/or the like, this should by no means be construed in a limiting manner, and the same examples may also pertain to determining additional or alternative adverse phenomenon such as, for example, hypoxia, inflammation, hypoxemia, motility, food intake and digestion control issues.

[0037] A (e.g., leakage, hypoxia and/or inflammation detection) system according to some embodiments, may comprise one or more communication devices comprising a transmitter, a receiver, and/or a transceiver (for implementing wired and/or wireless communication).

[0038] The communication device can be in communication with an external monitor and the electronic sensor. Optionally, a communication device may be external to the patient body for receiving and/or transmitting signals generated within the patient body and/or for receiving and/or transmitting signals generated outside the patient body. Optionally, a communication device may be an implantable communication device for receiving from and/or transmitting signals outside the patient body while implanted in the patient body via wired and/or wireless communication links. Optionally, a plurality of implantable communication devices implanted within the patient body may communicate with each other via wired and/or wireless communications.

[0039] Wired connections may be removable from a mammalian body (also: patient body) through a port and, as such, may be made or include nonbiodegradable, partially or fully biodegradable conductive material for the implementation of wired connections.

[0040] Optionally, a part of the electronic sensor may be biodegradable and/or biocompatible, and another part of the electronic sensor may be non-biodegradable and/or non-biocompatible.

[0041] Optionally the electronic sensor and/or the communication device components which are in contact with tissue of a patient site of interest (e.g., at a monitoring and/or reference location site) may be constructed, fully or partially, of biocompatible material and may, optionally, be partially or fully biodegradable. Optionally, non-biocompatible components may be housed within a sealed casing. Optionally, the term biodegradable may encompass the meaning of the term "bioresorbable" or "biodegradable yet nonbioresorbable".

[0042] A reference electrode may be operably engagable with a site of interest (SOI) (e.g., internal organ tissue) of the patient at a location which is different from the location of the site of interest to which the tissue-of-interest monitoring electrode is operably deployed, to provide an output that can be used as reference to the output(s) provided by the tissue-of-interest monitoring electrode. For example, the sensing or monitoring electrode may operably engage a surgical site (e.g., a tissue connection site such as, for example, an anastomosis site), and the reference electrode may operably engage a patient site of interest at a location which is remote from the surgical site. For example, the reference electrode may operable engage the patient site of interest at a location at which no anastomotic leak is expected to occur. The two different patient site of interest locations may herein be referred to as "monitoring location site", (or simply: "monitoring site"), to designate, for example, a surgical location site" (or simply: "surgical site") and "reference location site" (or simply: "reference site"). The monitoring and/or reference location sites may be internal and/or external to the patient body. The monitoring and/or reference electrodes may be implantable or non-implantable monitoring and/or reference electrodes, respectively. Optionally, the reference electrode may be located external to the patient body. [0043] The monitoring electrode may be implantable, biocompatible and, optionally, biodegradable in full or in part. In some embodiments, only the tissue-of-interest monitoring electrode is biodegradable in full or in part whereas the reference electrode may be non-biodegradable yet biocompatible. Optionally, a monitoring electrode referred to herein can be a multi-electrode or comprise an arrangement of multiple electrodes. Reading multiple signals from a plurality of electrodes enables better localization of the physiological phenomena and thus allow spatial or temporal-spatial monitoring of the signals, providing for example an indication indicates propagation velocity if the condition further develops. In some embodiments, a monitoring electrode can be referred to as an electrochemically responsive sensing or monitoring electrode.

[0044] According to one embodiment, at least one electrode is a reference electrode. According to one embodiment, the reference electrode is at least partially degradable electrode. According to one embodiment, the reference electrode is at least partially non degradable electrode.

[0045] The reference electrode's role is to engage with healthy tissue and to act as a 'biological reference' to the signal sensed from the remaining electrodes engaging with the same tissue and/or organ (e.g., the colon) that the remaining electrodes engages with.

[0046] According to an embodiment, the at least one reference electrode is adapted to engage with the tissue outside or distal from an intervention site (e.g., surgical site) (e.g., at least 4 cm from the anastomosis site (also referred to as the surgical site), or at least 5 cm from the surgical site), compared to the at least one monitoring electrode which may be placed comparatively proximal to the intervention site (e.g., within 4 cm or within 3 cm or within 2 cm from the intervention site. Disposing the at least one reference electrode, e.g., at least 5 cm, from the intervention site ensures the at least one reference electrode engages with a healthy (intact) tissue (e.g., of the same organ tissue, of the same patient or one or more healthy subjects).

[0047] Based on electrode signals received from the at least one monitoring electrode and the at least one reference electrode, e.g., by comparing (e.g., computing a difference) of a sensed parameter value of the intervention site against a sensed parameter value of the reference site, it may be determined whether the intervention site is experiencing or will likely experience an adverse phenomenon (e.g., leak, hypoxia, inflammation).

[0048] In some embodiments, differences in parameter values between the reference and monitoring signals may be compared with each over time. A decrease in the difference might provide an indication of normal recovery, whereas an increase in the difference might provide an indication about a complication (e.g., occurrence of an adverse phenomenon). [0049] In some embodiments, the comparison may output a score (e.g., inflammation index). A low or declining inflammation index over time may be indicative of a normal recovery patient, whereas a comparatively high or increasing inflammation index might be indicative of a complication.

[0050] For example, leak (mild or acute) may be detected by sensing of and comparing between impedance of the surgical site and the reference site. In some examples, an acute leak may defined as a leak that requires a surgical intervention, whereas a mild leak may be defined as a medicinally treatable leak.

[0051] In some examples, a grade of leak may be defined as described in: Rahbari NN, Weitz J, Hohenberger W, Heald RJ, Moran B, Ulrich A, Holm T, Wong WD, Tiret E, Moriya Y, Laurberg S, den Dulk M, van de Velde C, Buehler MW. Definition and grading of anastomotic leakage following anterior resection of the rectum: a proposal by the International Study Group of Rectal Cancer. Surgery. 2010 Mar;147(3):339-51. doi: 10.1016/j.surg.2009.10.012. Epub 2009 Dec 11. PMID: 20004450.

[0052] In some example, an adverse phenomenon may be detected by placing, for example, a reference electrode about at least 5 mm, about at least 10 mm, about at least 15 mm, about at least 20 mm, about at least, 30 mm, or at least about 80 mm, or more, from the intervention site of the same organ or tissue. In some examples, tissue impedance may decrease by 10%, e.g., about 10 -20 mm from the intervention site, compared to the sensed impedance at the reference site after a certain time period (e.g., about 2 hours) following leak induction. In some example, depending on the type of electrodes employed, a impedance measured at an intervention site may increase as a result of bodily fluid leak, compared to the a measured impedance at the reference site.

[0053] In some examples, an adverse phenomenon (e.g., leak, hypoxia and/or inflammation) may be detected by determining whether one or more sensed characteristics of tissue such as, for example, tissue impedance and/or a sensed electrophysiological signal parameter values, crossed a threshold. However, detecting occurrence of an adverse phenomenon by comparing a sensed parameter value (e.g., electrical characteristic and/or electrophysiological) against a threshold may not be sensitive and/or specific enough. For example, there could be a small and slow rate leak which may not be detected, for example, by determining whether a sensed tissue impedance exceeds above or drops below an impedance threshold. Also, due to natural occurring process (e.g., ischemia/necrosis) , it could very well be that a control signal (a signal from a non-leaking patient) may be beneath the threshold as could be mistakenly identified as a leak.

[0054] It is noted that a "threshold" may be static, or may be an adaptive threshold or a dynamic threshold. Static thresholds are predetermined thresholds that remain constant. Dynamic thresholds are forcefully changed (e.g., at a certain day of the year). Adaptive thresholds may vary depending on a variety of parameters.

[0055] As stated above, since predetermined threshold may not be suitable to provide a reliable and accurate detection of an adverse phenomenon (e.g., leak, hypoxia and/or inflammation), an detection of an adverse phenomenon could be enabled by correlating the sensed signal from the intervention site (e.g., surgical site) with the sensed signal from reference electrode (healthy tissue). Such correlation take into consideration physiological properties of the sensed tissues, as the signal received from the sensed electrode and the signal sensed by the reference electrode are time-phased.

[0056] In some examples, there two competing natural process may concurrently occur at an intervention site (e.g., anastomosis site). A first natural process promotes healing, while a second natural process may pertain to developing an adverse phenomenon (e.g., ischemia, necrosis, and/or inflammatory response resulting in tissue degradation. These first and two natural processes may constantly compete with each other. Accordingly, the (e.g., functional) properties of the intervention site (e.g., anastomosis site) vary over time. Thus, a sensed signal relating to one or more patient SOI parameter values may increase or decrease over time. Therefore, in some embodiments, at least one sensed monitoring signal received from the intervention site may be analyzed in conjunction with at least one reference signal received from a reference site. The analyzing (e.g., comparing) may include cross-correlating between the at least one monitoring and the at least one reference signal to obtain cross-correlation output values for determining, based on the cross-correlation output values, whether an adverse phenomenon occurs or not. In some examples, cross-correlation values obtain from a monitored patient may be compared against one or more control values of cross-correlation values of known, other, non-leaking patients. In some examples, a maximum cross-correlation value of the monitored patient may be compared against a control maximum cross-correlation value relating to one or more other known non-leaking patients. The term "maximum" as used herein refers to a local maximum determined within a certain time period after surgery, e.g., within 20 hours after surgery to within 60 hours or 70 hours, after surgery.

[0057] In some embodiments, the system may be configured to distinguish between an adverse phenomenon (e.g., first anomaly) that may have an acute adverse phenomenon, and an adverse phenomenon that may have a mild effect on the patient (e.g., second anomaly), based on a processing the at least one reference signal and the least one monitoring signal (e.g., by comparing the signals with each other). [0058] It is noted that the expression "leak detection" or "leak detector" should not be construed in a limiting manner, as the devices, and methods disclosed herein may also be configured to detect additional or alternative adverse phenomenons pertaining to tissue reconnection such as, e.g., systemic inflammation, local inflammation, expected onset time of inflammation and/or leak of bodily fluid, onset time of bodily fluid leak, motility (providing indication regarding normal and abnormal Gl peristalsis), local ischemia, local bowel movements whether correlated to the systemic bowel movements or not, food and fluid intake and processing, and/or dehydration.

[0059] In some embodiments, systems and methods may determine a trend (also: tendency) of one or more monitored parameter values relating to one or more adverse phenomenon (e.g., subsiding inflammation, intensifying inflammation). In an example, parameter values indicating subsiding of an adverse phenomenon may not trigger an alert, whereas an upward trend of parameter values relating to an adverse phenomenon may trigger an alert. In an example, system may provide an output in case parameter values are indicative of subsiding adverse phenomenon, and/or an output in case of an upward trend relating to an adverse phenomenon is determined. In an example, based on recorded parameter values from the patient SOI, system may determine an intensification trend rate and/or a subsiding trend rate relating to an adverse phenomenon. The system may provide an output in case of an upward trend of parameter values relating to an adverse phenomenon exceeds a high threshold and/or provide an output in case a subsiding trend drops below a low threshold.

[0060] In some embodiments, system and/or method disclosed herein may be configured to detect hypoxia as an adverse phenomenon relating to the patient intervention site, e.g., based on electrophysiological (e.g., myoelectrical) signal. For instance, hypoxia may be detected on based on monitored myoelectrical activity. For example, myoelectric signal sensed from a patient intervention site may be recorded and then processed (for example, by employing a high-pass filter such as, e.g., time-based derivative) to detect myoelectric signal spikes. Such spikes may be defined as described in: Cheng, H.M., Mah, K.K., Seluakumaran, K. (2020). Gastrointestinal Rhythmic Contractions Electrical Basis: Slow Wave Potential. In: Defining Physiology: Principles, Themes, Concepts. Volume 2. Springer, Cham, https://doi.org/10.1007/978-3-030-62285-5_8

[0061] Based on the number of spikes, it may be determined whether the patient intervention site is experiencing hypoxia or not. A drop in the number of spikes within a time period relative to a control number of spikes by, e.g., about 50-70% relative to the control number (e.g., from about 17 spikes/min to less than 5 spikes/min, or from about 112.64 spikes/min to about 51 spikes/min) in the GI track may provide an indication relating to hypoxia occurring in the track. [0062] In some examples, the number of spikes of a monitoring site (also: intervention site) may be compared against the number of spikes of sensed with respect to a reference site of interest of the same organ and/or against the number of spikes of in healthy patients subjects. If the reference spikes correlate with the intervention site spikes (e.g., in terms of number spikes, spike frequency and/or phase), it may be determined that no adverse phenomenon is occurring. Contrariwise, if the reference spikes do not correlate with the intervention site spikes (e.g., in terms of number spikes, spike frequency and/or phase), the system may determine that an adverse phenomenon is occurring and produce a corresponding output.

[0063] In some examples, the function modeling the spikes of a monitoring site (also: intervention site) may be compared against the function modeling the spikes of sensed with respect to a reference site of interest of the same organ and/or against the number of spikes of in healthy patients subjects. For clarity, the comparison function of the two models describes the correlation of the two models and consequently the spiking in both sites. If the reference spikes correlate with the intervention site spikes (e.g., in terms of number spikes, spike frequency and/or phase), it may be determined that no adverse phenomenon is occurring. Contrariwise, if the reference spikes do not correlate with the intervention site spikes (e.g., in terms of number spikes, spike frequency and/or phase), the system may determine that an adverse phenomenon is occurring and produce a corresponding output.

[0064] In some examples, a control number of spikes may be measured by employing manometry, and/or by employing a high-pass filter on myoelectric signals. Investigating myoelectric signals Hypoxia may thus , leak detection using impedance and myoelectric signal patterns is shown to be promising to detect leaks and/or ischemic conditions likely to cause a leak.

[0065] In some embodiments, a signal relating to bowel movement may be assessed (e.g., reconstructed) based on monitoring myoelectric activity. Based on reconstructed bowel movement, one or more adverse phenomenon may be detected including, for example, anastomotic leak; low anterior resection syndrome, e.g., for applying a method of rehabilitation thereof by stimulation of the tissue to enhance healing and/or monitor efficacy of the healing process; Ileus; one or more inflammatory bowel diseases (e.g., Crohn's); and/or the like. Furthermore, based on reconstructed bowel movement, treatment efficacy of an adverse phenomenon of inflammatory bowel diseases may be determined.

[0066] Reconstruction of mechanical bowel movement, e.g., based on monitoring physiological signals such as, for example, myoelectric activity, may obviate the need for employing manometry. The at least one monitoring and/or reference electrode may be employed for recording physiological signals for reconstructing, e.g., mechanical bowel activity. [0067] Mechanical bowel movement (e.g., slow and/or fast movements) may be reconstructed based on myoelectric activity, for example, by sensing and recording myoelectric signals, e.g., with the at least one reference and/or monitoring electrode.

[0068] Events pertaining to contraction activity may be detected by applying a high-pass filter (e.g., by applying a time-based derivative) on data descriptive of the myoelectric activity to obtain a high-pass filtered myoelectric signal (also: "spike signal") containing "spikes". These spikes may pertain to propagating contractile bowel activity.

[0069] Motility or colonic EPS may be determined by applying a low-pass filter on measured myoelectric signals. Normal operation of the colon may be characterized by slow waves in the range of, for example, 2-20 cycles/minute.

[0070] As mentioned herein, inflammation may for example be detected based on electrical tissue characteristics such as, for example, tissue impedance.

[0071] In some embodiments, the system may be configured to compare between tissue impedance at the monitoring site and the reference site, spiking activity at the monitoring site and the reference site, and/or colon EPS at the monitoring site and the reference site. Based on the comparison(s) (e.g., determining a level of correspondence, e.g., correlation value(s)), the system may determine whether an adverse phenomenon is occurring or not with respect to the patient SOI (e.g., the intervention site).

[0072] In some embodiments, a high-pass filtered myoelectric signal may be additionally filtered to filter out the spikes. Once spikes are filtered out, the temporal spike occurrence sequence can be convolved with a bowel transfer function. The bowel transfer function may be derived for instance, through manometric pressure measurement that was performed on another mammalian subject. The result of the convolution of the patient's temporal spike occurrence sequence with the bowel transfer function may about correspond to the patient's mechanical bowel movement.

[0073] In some embodiments, a machine learning (ML) model may be trained, based on one or more values (e.g., parameter values, indices, and/or scores) described herein, for realizing a classifier configured for detecting occurrence of an adverse phenomenon (also: complication) such as, for example, ischemic conditions. In some examples, the classifier may be trained to classify leaks into one of Grade B, and Grade C leaks, and/or "acute leak" and "non-acute leak". [0074] As used herein the term "machine learning" refers to a procedure embodied as a computer program configured to induce patterns, regularities, and/or rules from previously collected data to develop an appropriate response to future data or describe the data in some meaningful way.

[0075] Examples of machine learning procedures suitable for the present embodiments, include, without limitation, clustering, association rule algorithms, feature evaluation algorithms, subset selection algorithms, support vector machines, classification rules, cost-sensitive classifiers, vote algorithms, stacking algorithms, Bayesian networks, decision trees, neural networks, instance-based algorithms, linear modeling algorithms, k-nearest neighbors (KNN) analysis, ensemble learning algorithms, probabilistic models, graphical models, logistic regression methods (including multinomial logistic regression methods), gradient ascent methods, singular value decomposition methods and principle component analysis.

[0076] The machine learning procedure used according to some embodiments of the present invention is a trained machine learning procedure, which provides output that is related non-linearly to the parameters with which it is fed.

[0077] In some embodiments, a machine learning procedure can be trained according to some embodiments by feeding a machine learning training program with parameter values that characterize each of a cohort of subjects that has been diagnosed as either experiencing or not experiencing an adverse phenomenon relating to a patient intervention site, and/or experience various grades of adverse phenomenon relating to the patient site of interest. Once the data is fed, the machine learning training program generates a trained machine learning procedure or forms a part of a ML module. In some examples, the trained ML module can be used without the need to re-train it. In some other examples, the trained ML module may be further trained and tested, e.g., on-the-fly, by training the ML module with data relating to the patient currently being monitored. In some embodiments, the ML model may trained with additional labels including, for example, medical information (e.g., medical images); with labels relating to physiological and/or socio-economic and/or behavioral patient characteristics such as, for example, gender, age, race, height, BMI, smoking habits, drinking habits, medical history, and/or the like.

[0078] An ML model that may be employed by the system may be trained using supervised and/or unsupervised learning. In some examples, the machine learning model may be adapted by evaluating labels produced by a test dataset. The validation measures may include, for example, accuracy, recall and/or precision, with respect to real labels on a dataset of labeled data. [0079] In some embodiments, the ML model may be trained based on impedance, motility, and/or spike activity values obtained with respect to known leaking and non-leaking patients.

[0080] It is further noted that the term "detection" as well as grammatical variations thereof may encompass any processes that enable such "detection", including sensing, determining and/or monitoring. In some examples, processes described herein with respect to the analysis of signals may provide output in "real-time".

[0081] Referring now to Figure 1, a patient site of interest monitoring system 1000 comprises a monitoring sensor 1100 comprising at least one monitoring electrode that is communicably coupled with a monitoring subsystem 1200. The patient site of interest monitoring system 1000 may in some embodiments also include a reference sensor 1300 comprising at least one reference electrode 1310 that is communicably coupled with monitoring subsystem 1200.

[0082] According to some embodiments, monitoring subsystem 1200 may include a processor 1210, a memory 1220, an input device 1230, an output device 1240, a communication device 1250, an analysis engine 1260, and a power module 1270 for powering the various components of patient site of interest monitoring system 1000 for the implementation of various applications 2000.

[0083] The various components of patient site of interest monitoring system 1000 may communicate with each other over one or more communication buses (not shown) and/or wired and/or wireless communication links.

[0084] Monitoring subsystem 1200 may be operatively coupled with monitoring sensor 1100 so that changes of electrical properties or characteristics of monitoring electrodes 1110 are measurable by monitoring subsystem 1200, as outlined herein below in greater detail.

[0085] Monitoring subsystem 1200 may be operable to enable the implementation of a method, process and/or operation for allowing, for example, the detection of leakage from the lumen of an organ through an organ wall. Such method, process and/or operation may herein be implemented by an "analysis engine" of monitoring subsystem 1200, referenced by alphanumeric label "1260". Analysis engine 1260 may be realized by one or more hardware, software and/or hybrid hardware/software modules, e.g., as outlined herein. A module may be a self-contained hardware and/or software component that interfaces with a larger system and may comprise a machine or machines executable instructions. For example, a module may be implemented as a controller programmed to, or a hardware circuit comprising, e.g., custom VLSI circuits or gate arrays, off-the-shelf semiconductors such as logic chips, transistors, or other discrete components, configured to cause patient site of interest monitoring system 1000 to implement the method, process and/or operation as disclosed herein. A module may also be implemented in programmable hardware devices such as field programmable gate arrays, programmable array logic, programmable logic devices or the like. For example, memory 1220, may include instruction which, when executed e.g. by processor 1210, may cause the execution of the method, process and/or operation for enabling, for example, the detection of leakage from a Gl tract of the patient.

[0086] In some examples, analysis engine 1260 may be operable to supply artificial intelligence (e.g., machine learning functionalities) for determining if leakage occurs or not. Artificial intelligence and machine learning functionalities may be implemented, for example, by employing supervised and/or unsupervised machine learning using Support Vector Machine and/or an Artificial Neural Network. For example, a Support Vector Machine may be trained with a vector representing, for instance, 2-15 min of impedance measurement data and, optionally, with dimensionality reduced additional electrophysiological signals. For instance, the Support Vector Machine may be trained with electrophysiological signals (e.g., electrogastrography signals and/or other electro-physiological signals recorded from the site of interest), for example, in the frequency domain and from which phase shifts are removed and/or which are otherwise processed to reduce dimensionality. In some embodiments, electro-physiological data representing phase, and/or phase shifts over time and/or phase differences between the signals recorded from the reference site and the signals recorded from the monitoring site may also be used as an input to analysis engine 1260.

[0087] Power module 1270 may comprise an internal power supply (e.g., a rechargeable battery) and/ or an interface for allowing connection to an external power supply.

[0088] Input device 1230 of monitoring subsystem 1200 may be communicably coupled with monitoring electrodes 1110, e.g., in a wired or wireless manner to allow subjecting the patient site of interest, via one or more electrode of monitoring sensor 1100, with an input signal for stimulating the patient site of interest and, concurrently, measuring the voltage drop between at least two different locations of the same electrode(s). Monitoring subsystem 1200 may in some embodiments also be operable to sense an electrophysiological signal (e.g., electrogastrography and/or other electrophysiological signals) recorded by operably engaging electrodes with tissue of a patient site of interest. For example, specific variance characteristics (e.g., patterns) of EGG and/or other electrophysiological signals may be indicative of increased likelihood of onset of anastomotic leak and/or provide indication of an anastomotic leak occurring.

[0089] Input signals provided by input device 1230 may be direct current (DC) or alternating current (AC) signals. AC input signals may be provided at an input signal frequency ranging, for example, from 1 to 120 Hz. In some embodiments, frequency sweeping may be employed, and the output may be based on analysis of the response signal obtained over the swept input signal frequency range. Alternatively, step function input signals may also be used to obtain impedance measurement.

[0090] In some embodiments, signal processing may be employed for sensing or measuring impedance as well as, for example, for sensing a signal descriptive of electrophysiological activity of the tissue with which the electrode is operable engaged. An impedance signal may be received or sensed responsive to subjecting the electrode to an input (also: stimulation) signal. The frequency of the impedance signal corresponds with the frequency of the stimulation signal. The frequency of the stimulation signal may be selected such that the frequency of the obtained response signal (also: impedance signal) is outside the range of the frequency of the electrophysiological signal of interest. This way, the response signal and the electrophysiological signal can be separated from one another using signal filtering to allow concurrent sensing or measurement of the response signal and the electrophysiological signal using the same tissue-engaging electrode. For example, the frequency of the stimulation signal may be selected to range from 20 to 40 Hz and include, for example, 31 Hz resulting in response signals having frequencies in the range of 20 to 40 Hz, while the frequency of the electrophysiological signal may range from 0 to 12 Hz. Analysis engine 1260 may separate the signal components using signal filtering to allow for separate interpretation of the superpositioned response and electrophysiological signal components. For example, a notch filter may filter out the frequency of 31 Hz of impedance signals for allowing interpretation thereof, and a low-pass filter may be employed for filtering out a frequency range of 0-12 Hz for allowing interpretation of electrophysiological signals descriptive of, for example, Gl activity.

[0091] In some embodiments, separate electrodes may be employed for measuring different types of signals such as impedance signals and electrophysiological signals

[0092] Electrical characteristics of input signals are controlled by analysis engine 1260 so that the magnitudes of electrical energy in the mammalian body are within physiologically tolerable values. A physiologically tolerable value may be, for example, an alternating current of 5nAto 800 pAat a frequency range of 5-120Hz.

[0093] Generally, impedance measurements may be sufficient to reliably estimate tissue condition and status. Electro-physiological signals may also be sufficient to monitor certain physiological conditions. The system may record impedance and electrophysiological information simultaneously, allowing flexibility for analysis engine 1260 which can be implemented using only a sub set of the signals (e.g., to allow comparatively lower computational complexity and smaller training datasets), or using all recorded data for enabling, for example, better sensitivity and faster detection.

[0094] Monitoring sensor 1100 may be operably coupled with the patient site of interest so that a sufficiently significant change in the material properties of monitoring electrodes 1110 causes a change in an electrical characteristic or property of the monitoring electrode which is measurable and analyzable by analysis engine 1260. Information indicative of a detection in a change in the electrical characteristic or property of monitoring electrodes 1110 may be conveyed to a user (not shown) via output device 1240. In some embodiments, analysis engine 1260 may be configured to cause output device 1240 to display values (e.g., auditory and/or visually) of the electrical characteristics (also: properties) as a function of time, e.g., within a calibrated scale, and/or provide an output of the analysis performed by analysis engine 1260 (e.g., provide an audible and/or visual alert).

[0095] In some embodiments, communication device 1250 may be equipped with a transmitter (not shown) and, optionally, with a receiver and/or a transceiver, e.g., for allowing the transmission of inputs or stimulation signals to monitoring electrodes 1110 and, optionally, to reference electrodes 1310. Analysis engine 1260 may control the generation of the input signals.

[0096] In some embodiments, communication device 1250 enables the transmission of response signals carrying data ("electric-property-data") that is descriptive of a change of the electrical characteristics of monitoring sensor 1100 from monitoring electrodes 1110 to analysis engine 1260.

[0097] In some embodiments, electrophysiological (e.g., electro-gastric) signals may be transmitted via communication device 1250 to analysis engine 1260 for the analysis thereby.

[0098] It is noted that although components of patient site of interest monitoring system may be illustrated as being implemented by a single component, this should by no means be construed in a limiting manner. For example, components of patient of site of interest monitoring system can be deployed to be executed on one site or distributed across multiple sites and operably interconnected. For instance, separate processors and memories may be allocated to analysis engine 1260, and separate communication devices may be implemented for implementing communication device 1250.

[0099] It is noted that in some embodiments, one or more components of monitoring subsystem 1200 may be internal and one or more components may be external to the mammalian body. For example, certain processors, memories, input devices, communication devices and/or our power sources may be internal to the mammalian body and certain processors, memories, input devices, communication devices and/or our power sources may be outside the mammalian body. [00100] For example, communication device 1250 may be coupled with or include a transmitter (not shown) that may be operably positionable within mammalian body. Optionally, electric-property-data may be transmitted from within the mammalian body to the outside of mammalian body wired and/or wirelessly over communication link (not shown) for further analysis by analysis engine 1260.

[00101] In embodiments, some of monitoring subsystem 1200 functionalities may be implemented by a multifunction mobile communication device also known as "smartphone", a personal computer, a laptop computer, a tablet computer, a server (which may relate to one or more servers or storage systems and/or services associated with a business or corporate entity, including for example, a file hosting service, cloud storage service, online file storage provider, peer-to-peer file storage or hosting service and/or a cyberlocker), personal digital assistant, a workstation, a wearable device, a handheld computer, a notebook computer, a vehicular device, a stationary device and/or a home appliances control system.

[00102] The term "processor" as used herein may additionally or alternatively refer to a controller. Such processor may relate to various types of processors and/or processor architectures including, for example, embedded processors, communication processors, graphics processing unit (GPU)-accelerated computing, soft-core processors and/or embedded processors.

[00103] According to some embodiments, memory 1220 may include one or more types of computer- readable storage media. Memory 1220 may include transactional memory and/or long-term storage memory facilities and may function as file storage, document storage, program storage, or as a working memory. The latter may for example be in the form of a static random access memory (SRAM), dynamic random access memory (DRAM), read-only memory (ROM), cache or flash memory. As working memory, memory 1220 may, for example, process temporally -based instructions. As long-term memory, memory 1220 may for example include a volatile or non-volatile computer storage medium, a hard disk drive, a solid state drive, a magnetic storage medium, a flash memory and/or other storage facility. A hardware memory facility may for example store a fixed information set (e.g., software code) including, but not limited to, a file, program, application, source code, object code, and the like.

[00104] Communication device 1250 may for example include I/O device drivers (not shown) and network interface drivers (not shown). A device driver may for example, interface with a keypad or to a USB port. A network interface driver may for example execute protocols for the Internet, or an Intranet, Wide Area Network (WAN), Local Area Network (LAN) employing, e.g., Wireless Local Area Network (WLAN)), Metropolitan Area Network (MAN), Personal Area Network (PAN), extranet, 2G, 3G, 3.5G, 4G including for example Mobile WIMAX or Long Term Evolution (LTE) advanced, and/or any other current or future communication network, standard, and/or system.

[00105] Reference is now made to Figures 2A and 2B, schematically illustrating various embodiments of a patient site of interest monitoring system 1000. One embodiment of patient site of interest monitoring system 1000 is herein designated by alphanumeric reference "1000A", and another embodiment of monitoring system 1000 is herein designated by alphanumeric reference "1000B". Merely to simplify the discussion that follows, without be construed in a limiting manner, the description may refer to "monitoring system 1000".

[00106] As shown in Figures 2A and 2B, patient site of interest monitoring system 1000 includes a tissue-of- interest or SOI monitoring electrode 1110 that is operably couplable adjacent to or such to engage with a site of interest internal to an animal (e.g., human) body, herein also referred to as "patient body". Such site of interest may include, for example, an internal organ, a surgical intervention site (e.g., a tissue reconnection site such as an anastomosis site, a sleeve gastrectomy site, etc., a site which is prone to wound dehiscence or other tissue breakdown (e.g., due to tissue reconnection by employing, for example, staples, sutures, etc.), a hernia closure site, and/or any other physiological phenomenon expected or suspected to occur at the site of interest, and which physiological phenomenon may, for example, cause a measurable change in a characteristic (e.g., an electrical characteristic) of a monitoring electrode, e.g., due to corrosion, (bio- )degradation, mechanical failure of the electrode(s) and/or the like. For example, a monitoring electrode may start bio-degrading or its biodegradation profile or its physical properties may otherwise change (e.g., accelerate or decelerate) as a result of and, e.g., in correspondence, with the onset or occurrence of a physiological phenomenon being monitored. Hence, occurrence and timing of the physiological phenomenon at the site of interest may be measurable by detecting a change in one or more characteristics of the monitoring electrode.

[00107] In some embodiments, tissue-of-interest monitoring electrode 1110 may, for example, be implantable in proximity of operably engaged with an anastomosis site of the Gl track or any other surgical tissue connection site or other internal body site of interest, and may be implanted during Gastrointestinal (Gl) surgery, for example. In some other embodiments, tissue-of-interest monitoring electrode 1110 may be operably integrated with a device extending from the internal body site of interest (or vicinity thereof) inside the patient's body to the outside of the patient's body, e.g., to the vicinity of the patient's skin surface. Such device may include, for example, a fluid drainage catheter that is operably positioned to drain fluids from the internal site of interest to the outside of the patient's body. [00108] In some embodiments, a monitoring electrode 1110 and/or reference electrode 1310 may be biodegradable and/or biocompatible in full or in part. In some embodiments, a partially biodegradable monitoring electrode(s) 1110 and/or reference electrode(s) 1310 may comprise at least two parts, namely, a fully biodegradable part for engaging with tissue of a site of interest until the biodegradable part is degraded, and a partially bio-degradable or non-biodegradable part that can be retracted or removed after the monitoring period is completed. In some embodiments, a reference electrode is non-biodegradable.

[00109] In some embodiments, tissue-of-interest monitoring electrode 1110 may be biodegradable in full or in part yet not necessarily implantable (e.g., biocompatible) if it is designed to be operably positioned outside the patient's body, e.g., inside or as part of the fluid drainage catheter. For example, monitoring electrode 1110 may be operably coupled (e.g., embedded in the fluid drainage catheter such that the monitoring electrode can make contact with fluid flowing in the fluid path of the fluid drainage catheter.

[00110] A reference electrode 1310 may be employed for deployment at a different site of interest to provide an output that can be used as reference to the outputs provided by tissue-of-interest monitoring electrode 1110. Reference electrode 1310 may also be implantable, biocompatible and optionally biodegradable in full or in part. Reference electrode 1310 may for example be employed to improve accuracy of a specificity test, provide reference for spatial or temporal-spatial propagation of monitoring electrode dynamic electrical characteristics and/or of other methods that may be employed for performing diagnostic tests. In implementations where tissue-of-interest monitoring electrode 1110 is incorporated in a fluid drainage catheter, reference electrode 1310 may be located downstream and/or upstream of tissue-of-interest monitoring electrode 1110. The terms "upstream" and "downstream" as used herein in the context of a drainage catheter refers to a fluid drainage direction. In some embodiments, reference electrode 1310 may be deployed in a different, "reference" catheter that is operably coupled with the patient. Optionally, reference electrode 1310 may be biodegradable (fully or partially) or non-biodegradable and, in addition, not necessarily biocompatible), for example, if it is designed to be operably positioned outside the patient body, e.g., inside or as part of another fluid drainage catheter.

[00111] In some embodiments, signals received from the reference electrode may be used for performing self-calibration of components of the patient site of interesting monitoring system. For example, signals received from the reference electrode may be used for adapting at least one adverse-phenomenon output criterion based on which, for example, an output is provided for indicating that anastomotic leak occurs or not. [00112] In some embodiments, monitor 1004 may provide artificial intelligence (including, e.g., machine learning) functionalities for adaptively changing the at least one adverse-phenomenon output criterion. The artificial intelligence functionalities may be based on patient-related characteristics.

[00113] As shown in Figures 2A and 2B, monitoring system 1000 may optionally include one or more communication devices 1250 for communicably linking between tissue-of-interest monitoring with a monitor 1004 and further for communicably linking reference electrodes 1310 with monitor 1004.

[00114] Communication device 1250 can include an active and/or a passive transmitter, receiver and/or transceiver. In some embodiments, communication device 1250 can be selectively switchable from an active to passive transmission mode and vice versa. Some or all components of communication device 1250 may be fully or partially biodegradable.

[00115] Monitor 1004 may incorporate functionalities of analysis engine 1260 and of output device 1240 which were outlined with respect to Figure 1.

[00116] In patient site of interest monitoring system 1000A, a communication device 1250 may be communicably coupled with tissue-of-interest monitoring and reference electrodes 1110 and 1310. In another example of monitoring system 1000B, a first communication device 1250A may be communicably coupled with tissue-of-interest monitoring electrodes 1110, and a second communication device 1250B may be communicably coupled with reference electrodes 1310. First and second communication devices 1250A and 1250B may be communicably linked with each other in a wired and/or wireless communication to allow for in-body transmission of signals between the communication devices. In-body signal transmission may be employed to implement, for example, calibration, feedback, data fusion, noise-reduction, and/or other signal processing and/or analysis applications, for example, by analysis engine 1260 implemented by one or more implanted processors and/or memories.

[00117] As schematically shown in Figure 3 and mentioned herein with respect to Figure 2A and Figure 2B, components of a monitoring subsystem 1301 may be configured to implement a communication device 1250 and a monitor 1004 to controllably subject tissue-of-interest monitoring with input signals via tissue-of- interest (TOI) monitoring and reference electrodes 1110 and 1310, respectively, with input or stimulation signals, and is further operable to communicate response signals relating to the input signals and which are received from tissue-of-interest monitoring and reference electrodes 1110 and 1310, respectively, to monitor 1004 which may be located outside the patient body.

[00118] For example, one or more tissue-of-interest monitoring electrodes 1110 and, optionally, one or more reference electrodes 1310, may be in communication with communication device 1250. Communication device 1250 may be communicably linked (wired and/or wirelessly) with monitor 1004 for providing monitor 1004 with signals generated by tissue-of-interest monitoring electrodes 1110 and, if applicable, by reference electrodes 1310. Monitor 1004 may be operable to process signals received from tissue-of-interest monitoring electrodes 1110 and, if employed or applicable, may also be operable to process signals received from reference electrodes 1310.

[00119] Monitor 1004 is operable to automatically or semi-automatically provide, based on the received response signals, an output pertaining to a physiological phenomenon (e.g., an or potentially adverse physiological phenomenon or condition) that may, for example, adversely affect the patient's health (e.g., wound dehiscence, anastomotic leakage, etc.) such as, for example, a warning upon detection of anastomotic leakage.

[00120] Response signals sent to monitor 1004 may be descriptive of, for example, impedance, capacitance, current flow and/or change thereof in response to detected changes of a physiological condition of the patient. In some embodiments the response signal sensed by any of the electrodes can be communicated based on the principle of electromagnetic induction. For example, patient site of interest monitoring system 1000 may comprise an implanted or implantable conductive coil (not shown). The implantable conductive coil may be part of communication device 1250, for example. Leak detection may further comprise an external conductive coil (not shown). The external coil may be part of or otherwise be operably coupled with monitor 1004. The internal and external coil are positioned or are operably positionable relative to each other such that a change in current in one coil is picked up by the other coil through electromagnetic induction. The internal coil may be biocompatible and can be partially or fully biodegradable. In some embodiments, the internal coil may be responsive to changes in the patient's physiological characteristics. For example, the internal coil biodegrades or biodegrades at an accelerated or slower pace when being subjected to matter or (e.g., biological) substance that is a manifestation in a physiological phenomenon occurring in the patient's body. For example, characteristics (e.g., conductive or other electric characteristics) of the internal coil may change when coming in contact with fluid leaking from the Gl tract. Changes in the internal coil's electric characteristics may manifest themselves in measurable variations of the electrical output signals that are output by the external coil. The implantable internal coil may thus embody a monitoring electrode, and the internal/external coil arrangement may embody an electronic sensor for detecting Gl leak, for example.

[00121] Monitor 1004, which may be handheld, may comprise circuitry (e.g., a memory and a processor) for processing and/or analyzing response signals received from tissue-of-interest monitoring electrode 1110 and, optionally, of reference electrode 1310) to determine, based on the received signals, an output pertaining to a physiological condition of the site of interest internal to the patient body. [00122] For example, monitor 1004 may be operable to employ a bandpass filter on the received signals. For instance, if electrodes are subjected to a stimulation input signal at 31 Hz, response signals may be bandpass or lowpass filtered at 0.5-15 Hz. The band pass filter on the received signals recorded from the site of interest can be adaptively calibrated to consider characteristics of the signals recorded from the reference site for a computationally efficient reference-based condition detection algorithm.

[00123] For example, monitor 1004 may determine, based on the received signals, if leakage occurs or not. For instance, monitor 1004 may provide, based on the received signals, a warning if characteristics of the received signals meet at least one adverse-phenomenon output criterion such as, for example, an adverse leak warning output criterion (e.g., an output indicating that anastomotic leak occurs); an output indicative of the likelihood or probability of an adverse physiological phenomenon leak to occur within a certain time period (i.e., predicting the onset of anastomotic leak); provide an output indicative of how a current treatment condition should be altered such to reduce (e.g., minimize) the likelihood or probability of an adverse physiological phenomenon (e.g., condition or state) to occur or develop, or prevent occurrence of anastomotic leak; provide an output indicative of supplementary diagnostic test to be performed for determining if leakage occurs or not; and/or the like.

[00124] Such adverse-phenomenon output criterion may pertain to sensed variations in electrical signal characteristics and may be static, a dynamic or adaptive leak-related output criterion. A static criterion is predetermined that remains constant. A dynamic criterion is forcefully changed, for example, at a certain time of day, or a certain day of the year. An adaptive criterion is changed in response to changes in, for example, physiological characteristics of the patient body and/or the patient body's environment, and may vary depending on a variety of parameters.

[00125] For example, a leakage warning may be provided if monitor 1004 detects a voltage drop below or voltage increase above a corresponding "low or high electrical characteristic warning threshold"; and/or if monitor 1004 detects a drop below or increase above a corresponding "low or high electrical characteristic warning threshold range". The term "threshold" as used herein may refer to a predetermined threshold, a reference calibrated threshold, a moving threshold (e.g., linearly and/or non-linearly moving threshold) and/or any combination thereof. An adverse-phenomenon output criterion may in some implementations additionally or alternatively relate to a threshold relating to electrophysiological (e.g., electrogastrography) signal variance and/ or other signal characteristics. For example, comparatively lower cross-correlation between electrophysiological signals recorded from the reference site and signals recorded received from the monitoring site may be indicative of increased likelihood of onset of anastomotic leak and/or provide indication of an anastomotic leak occurring. [00126] For example, cross-correlation between signals received from a healthy reference site and the damaged / leaking intervention or monitoring (leaking) site of the same organ may over time decrease while, on the contrary, cross-correlation between signals received from a healthy reference site and a non-leaking intervention site may increase over time.

[00127] Based on a determined cross-correlation between at least one monitoring site signal and at least one reference site signal, system 1000 may provide an output indicative of an expected onset of leakage, or that leakage is currently occurring. In some examples, system 1000 may provide an output indicative that no leakage is occurring or expected to occur.

[00128] While embodiments and/or example discussed herein may refer to the detection of leakage of bodily fluid through a tissue reconnection, this may not be construed as limiting. Accordingly, systems and methods disclosed herein may also pertain to additional and/or alternative adverse phenomenon such as, for example, tissue inflammation, hypoxia and/or the like. The systems and methods disclosed herein may also determine cross-correlation between at least one monitoring signal and at least reference signal for determining occurrence or expected onset time of additional and/or alternative adverse phenomenon.

[00129] In some examples, determining and/or detecting occurrence of an adverse phenomenon (also: complication) may encompass determining a probability of an adverse phenomenon presently occurring or to occur, e.g., at an expected onset time.

[00130] Optionally, analysis engine 1260 takes into account food intake when taking into account electrophysiological to determine if an adverse-phenomenon output criterion is met.

[00131] For example, a leakage warning may be provided if monitor 1004 detects an impedance drop below or impedance increase above a corresponding "low or high electrical characteristic warning threshold"; and/or if monitor 1004 detects a drop below or increase above a corresponding "low or high electrical characteristic warning threshold range".

[00132] In certain embodiments, monitor 1004 and/or communication device 1250 may be operable to communicate with additional computing devices for providing expanded range of monitoring. Such computing device can include, for example, a multifunction mobile communication device also known as "smartphone", a personal computer, a laptop computer, a tablet computer, a server (which may relate to one or more servers or storage systems and/or services associated with a business or corporate entity, including for example, a file hosting service, cloud storage service, online file storage provider, peer-to-peer file storage or hosting service and/or a cyberlocker), personal digital assistant, a workstation, a wearable device, a handheld computer, a notebook computer, a vehicular device and/or a stationary device. [00133] In some embodiments, patient site of interest monitoring system 1000 is operative at low currents which are considered or known to be safe to the patient such as, for example, below 10mA. For example, patient site of interest monitoring system 1000 is operative at low currents below low-threshold limits in the sense that such currents will have minimal effect on nerves or muscles including, for example, electrical currents below 1mA (e.g., for muscles), or with currents below, for example, lOnA (e.g., for nerves). In some embodiments, narrow current pulses may be utilized known to have reduced, minimal or no effect on muscles such as pulse widths shorter than, for example, 1ms or pulse widths which are shorter than, for example, lOOus or other pulse widths known to have reduced, minimal or no effect on, e.g., human nerves, such as pulse widths shorter than, for example, lOOus. Low-threshold effects may be assured by applying currents at sufficiently low pulse widths. In some embodiments, a pulse width may exceed low-thresholds pulse-width limit, if the applied current is sufficiently low. In some embodiments, the applied current may exceed subthreshold current limits if the pulse width with the currents are applied is sufficiently narrow. In some embodiments, electric pulses applied may be applied at frequencies which are below a corresponding low- threshold frequency limit.

[00134] Additional reference is made to Figure 3. In some embodiments, one or more tissue-of-interest monitoring electrodes 1110 and reference electrodes 1310 may be operably coupled to a monitoring electrode carrier structures 1140 and a reference electrode carrier structure 1340, respectively. The electrode carrier structures facilitate securely and operably engaging (e.g., operably non-removably or removably coupling or fastening) the tissue-of-interest monitoring and reference electrodes 1110 and 1310, respectively, with organ tissue.

[00135] Optionally, the one or more TOI monitoring electrodes 1110 may herein be referred to in the singular as a "tissue-of-interest monitoring sensor 1100", and the one or more TOI reference electrodes 1310 may be referred to in the singular as a "reference sensor 1300". Optionally, the one or more tissue-of-interest monitoring electrodes 1110 and a tissue-of-interest monitoring electrode carrier structure 1140 to which the one or more tissue-of-interest monitoring electrodes 1110 are coupled, may herein be referred to as a "tissue-of-interest monitoring sensor 1110". Analogously, the one or more reference electrodes 1310 and a reference electrode carrier structure 1340 to which the one or more reference electrodes 1310 may be coupled may herein be referred to as "reference sensor 1300". Such (leak or reference) electrode carrier structure can be in the form of a mesh, for example. In some embodiments, tissue-of-interest monitoring electrodes 1110 may be operably coupled with monitoring electrode carrier structure 1140 to form a tissue- of-interest monitoring sensor 1100. Analogously, reference electrodes 1310 may be operably coupled with a reference electrode carrier structure 1340 to form reference sensor 1300. [00136] In some embodiments, material(s) that are used for constructing a mesh may constitute a part of tissue-of-interest monitoring an7d/or reference electrodes 1110 and 1310. In some embodiments, tissue-of- interest monitoring and/or reference electrodes 1110 and 1310 may be arranged to form, respectively, tissue-of-interest monitoring and reference carrier structures 1140 and 1340.

[00137] In some embodiments, sensing elements of an (e.g., implantable) electronic sensor such as the monitoring electrode and/or a mesh may have a material thickness and/or other properties to ensure detectability of changes of a physiological phenomenon in a patient. The sensing element(s) may be implantable or non-implantable. Optionally, a part of a sensing element may be implantable, and a part may be non-implantable. Optionally, a part of the sensing element may be biodegradable, and another part may be non-biodegradable. For example, to attain a detectable corrosion rate for a desired period of time while retaining mechanical properties of the monitoring electrode, for instance, a metal alloy wire of the monitoring electrode may have a diameter ranging, for example, from, 100 pm to 800 pm. In this case, analysis engine 1260 may consider the non-linear corrosion pattern of the electrode and its effect on the sensor's impedance. It is noted that the electrode or components thereof may include a cable, a sheath metal, a film, a single wire, and/or the like. The sensing elements may include one or more electrodes, meshes, rods, strings, wires, cables, machined sheath metals, film, and/or the like..

[00138] The term "mesh" as used herein, may refer to a two- or multidimensional semipermeable structure of closely-spaced holes, which is composed of a plurality of elongated and interconnected elements, such as fibers, strands, struts, spokes, rungs made of a flexible/ductile material, which are arranged in an ordered (matrix, circular, spiral) or random fashion to form e.g., a two-dimensional sheet or a three-dimensional object. In some embodiments, the term "mesh" is intended to include an element having an openwork fabric or structure, and may include but is not limited to, an interconnected network of wire-like segments, a sheet of material having numerous apertures and/or portions of material removed, or the like. Accordingly, the term "mesh" may also refer to a matrix or a net structure. A wire-like segment may for example comprise monofilaments and/or braided fibers. In some embodiments, the mesh may comprise or embed one or more electrodes.

[00139] In some embodiments, by "closely-spaced holes" it is meant to refer to a spacing of e.g., 1 mm, 2 mm, 5 mm, 10 mm, 15, mm, 20 mm, 30 mm, 40 mm, 50 mm, 60 mm, 70 mm, 80 mm, 90 mm, 100 mm, 110 mm, 120 mm, 130 mm, 140 mm, 150 mm, 160 mm, 170 mm, 180 mm, 190 mm, or 200 mm, including any value and range therebetween. [00140] According to some embodiments, certain meshes may be composed of fibrous elements which come in direct physical contact with each other at each intercrossing junction constituting the mesh.

[00141] In some embodiments, tissue-of-interest monitoring electrodes 1110, reference electrodes 1310, monitoring electrode carrier structure 1140 and/or electrode carrier structure 1340 comprise or are made of conductive, biocompatible and/or (bio-) degradable material(s). For example, the mesh or the wire structure comprises a core structure coated with conductive, biocompatible and/or biodegradable material(s). In some embodiments, the core comprises one or more metals. Optionally, the mesh structure comprises non- conductive polymer fibers that are interwoven with conductive, biocompatible and/or biodegradable material(s). Optionally, the wire (or the mesh) has a uniformly porous architecture so that degradation of the wire (or the mesh) can be progressed uniformly. Optionally, the mesh has a dimension of 0.1 mm to 500 mm x 0.1 mm to 500 mm, including any value and range therebetween.

[00142] Tissue-of-interest monitoring electrodes 1110, reference electrodes 1310, monitoring electrode carrier structure 1140 and reference electrode carrier structure 1340 can be made of any suitable material including, for example, non-biodegradable, partially biodegradable, or fully biodegradable material such as, for example, magnesium-based material, magnesium alloys, stainless steel, carbon tip, platinum, platinumiridium alloy, gold, and/or any type of biodegradable and/or biocompatible alloy or metal. Tissue-of-interest monitoring electrode carrier structures 1140 and reference electrode carrier structures 1340 may for example comprise, in addition to the metal components, Vicryl, Polyglycolicacid:Trimethylene (PGA:TMC), PGA, and/or non-(bio)degradable materials that are employable in implantable devices, and/or any other suitable material.

[00143] Mg impedance for example is increasing due to the generation of corrosion products (metal oxides and metal hydroxides) covering some of the effective surface area of the electrode. Due to corrosion, effective electrode surface area is changing, mainly decreasing, thus making the conductive contact area of the electrode with the tissue smaller.

[00144] Tissue-of-interest monitoring electrode carrier structure 1140 and reference electrode carrier structure 1340 may be operably fastened to organ tissue by employing, for example, various fixation elements and/or methods including, e.g., glue, adhesives and/or sutures. For example, barbed Polyglyconate biodegradable suture may be threaded into a mesh to facilitate local fastening and for stabilizing monitoring sensor 1100 and reference sensor 1300 in place of corresponding sites of interest, without puncturing or otherwise inadvertently damaging tissue structure such as the Gl tract. [00145] As noted, monitor 1004 comprises circuitry (e.g., a processor and a memory) that is configured to adaptively change at least one adverse-phenomenon output criterion. The at least one adverse-phenomenon output criterion may be changed adaptively based on, for example, patient-related characteristics deemed relevant to proper evaluation of patient recovery. Patient-related characteristics can include, for example, information about the patient's medical history (e.g., type(s) of surgical Gl procedure(s) which the patient underwent); social characteristics (e.g., gender; age; profession; income), and/or the like. Patient-related characteristics may also include measured physiological characteristics such as, for example, biometric data; systolic blood pressure; diastolic blood pressure; mean arterial pressure; pulse rate; breathing rate; breathing pattern; oxygen saturation level; glucose level; electrical property of the patient's skin (e.g., conductivity, resistance); weight, body-mass index (BMI) pH level; concentration of one or more selected analytes in bodily fluid (e.g., magnesium, calcium, sodium, salts, glucose, and/or hormones); motor function; body temperature; sweat rate; electrocardiogram; myocardiogram; electro-encephalography; capnography values; a cognitive ability of the patient; and/or the like. Bodily fluid can include blood, sweat, tears and/or saliva. In some embodiments, environmental parameters may be taken into account which can include, for example, location, temperature, humidity, room particle count, pressure level of the environment in which the patient is located and/or the like. In some embodiments, patient-related characteristics may pertain to third party data descriptive of information that may be deemed relevant for assessing patient recovery. Such third party data include data of other patients, data associated with relatives of the patient, and/or the like.

[00146] Although, embodiments of the present application pertain to the detection of anastomotic leak, the systems and methods disclosed herein may also be applied in the monitoring of various other health applications in which internal (e.g., adverse) physiological phenomena effecting electronic parameters or characteristics like impedance, phase shift, capacitance, and/or current flow voltage potential, can be rendered into electronic data. In particular the system and method described herein translates physiological conditions into data, allowing close monitoring of a surgical site for healing and recovery, and early detection of complications, namely inflammatory and/or infectious complications. Various example set forth in under "applications" 2000, include, inter alia, lumen leak detection 2100, orthopedic implant integration 2200, eye pressure 2300, and/or (e.g., head, sternum) other internal and/or external wound monitoring 2500. Further applications 2000 may include, for example, monitoring healing; post tumor resection monitoring of organs with respect to recurrence; monitoring indications related to signs of rejection of transplanted organs to adjust medication such as immune-depressive pharmacological therapy dosing; monitoring for infections adjacent to any foreign surgical implants; monitoring high-risk surgical wounds (e.g., contaminated wound areas, groin, trauma wounds; monitoring areas of lymphatic dissections; monitoring areas of lymph node resections; monitoring urinary bladder function; monitoring stomach, small bowel and/or large bowel functions; monitoring sphincters including, for example, lower esophageal sphincter, pylorus, anal sphincter, and/or the like; monitoring vascular functions including, for example, renal artery and/or carotid tone monitoring; monitoring of the peritoneum, e.g., for detecting postoperative peritonitis; monitoring the mediastinum and/orthe pleural cavity for postoperative mediastinitis and pleuritis and/or empyema; and/or the like.

[00147] It should be noted that while certain aspects of the present disclosure pertains to the detection of Gl leaks, this should by no means be construed in a limiting manner. Accordingly, devices, systems and methods described herein may also be employed for detecting other physiological phenomenon occurring at or in the vicinity of a site of interest and which can have a measurable effect on electrical characteristics of monitoring electrodes. For example, system and methods disclosed herein can be employed in the monitoring of internal organs such as the pancreas, liver or bladder to detect a leak, evaluate healing and/or changes in inflammatory and/or malignant conditions. Furthermore, a monitoring electrode can be implanted in a site in which eminent physiological changes are expected or suspected in order to detect occurrence timing of said changes or to provide an indication that such changes are not occurring as expected.

[00148] In some embodiments the rate of biodegradation of a part of entirety of the system will be set in line with the expected timing of expected leak or other said expected or suspected physiological changes. Specifically, in some embodiments the implantable parts in the vicinity of the internal body site of interest in which the leak or other physiological phenomenon is expected or suspected are designed to bio-degrade at a similar timing of the expected physiological phenomenon, whereas the other implantable parts that reach away from the said site may be made to be biocompatible but not biodegradable.

[00149] As shown in Figure 4A, a first Option 1 is directed at placing a monitoring electrode in a mesh and operably fastening them to a site of interest for the monitoring thereof.

[00150] As shown in Figure 4B, a second Option 2 is directed to embedding a sensing or monitoring electrode in a catheter, for example, a post-surgical drain catheter, to bring the sensing in contact with liquids that may be drained from the site of interest. Liquids drained from the site of interest may reflect a physiological condition such as, for example, tissue breakdown, wound dehiscence, which may manifest itself in anastomotic leak.

[00151] As shown in Figure 4C, a third Option 3 is directed to securing the monitoring electrodes to an body site of interest with staples, e.g., as is known in the art. [00152] Figures 5A-5B depict different stages of stapling tissue-of-interest monitoring and/or reference electrode 1110/1310 of patient site of interest monitoring system 1000 into a deployment position in patient tissue 5300 with a surgical stapler 5000, according to some embodiments. Staple drive element 5600 is operable to drive staples 5500 (e.g., staples 5500A and 5500B) against an anvil 5100 of surgical stapler 5000 subjecting, in turn, the application of a force onto staple 5500 causing the staple to contort upon contact with anvil 5100 such that the legs of the staple are bent within staple clinching pockets (not shown) of anvil 5100 relative to the staple's backspan while and/or after the legs traverse the patient's tissue to thereby secure distal buttress material 5200A against tissue 5300 and to secure the backspan to proximal buttress material 5200B against the patient's proximal tissue portion 5300.

[00153] As shown schematically in FIGs 5A-5B, each staple 5500 may in some embodiments be applied in alignment with the monitoring electrode(s) such that the staple directly engages with the monitoring electrode(s) for the fastening thereof with the patient's tissue. Sensing/monitoring electrode may be present at both sides of the staple line, or only one side.

[00154] As shown schematically in Figures 5C-5D, the monitoring electrode(s) may in some embodiments be positioned between two staples 5500 such that the monitoring electrodes are secured to the patient's tissue merely by the force the staples apply for securing the proximal and distal buttress materials to the tissue. For example, the monitoring electrodes are not directly fastened onto the patient tissue but secured through the fastening of the buttress material. In some embodiments, no buttress material may be employed. It should be appreciated that in certain deployments a circular stapler may be employed. A swine model was employed in which retractable and resorbable monitoring electrodes were implanted and engaged with a leak site at a descending colon location, and in which also retractable and resorbable reference electrodes were implanted at a reference site in the ascending/spiral colon.

[00155] Further referring to Figure 6, a method of monitoring a patient site of interest comprises, according to some embodiments, operably engaging one or more electrodes with a patient site of interest (block 602).

[00156] In embodiments, the method may further comprise subjecting the patient site of interest, via the one or more electrodes, with input signals (block 604).

[00157] In embodiments, may comprise receiving response signals as a result of subjecting the patient site of interest with input signals (block 606).

[00158] In embodiments, the method may further comprise determining, based on the received response signals, an output pertaining to a physiological phenomenon with respect to the patient site of interest (block 608). [00159] Additional reference is made to Figure 7. In some embodiments, an adverse phenomenon relating to an intervention site may be detected, and/or a probability of such event and/or condition occurring or to occur may be determined based on propagation velocity of signals between at least one proximal monitoring electrode (proximal to the intervention site) and at least one distal reference electrode (distal to the intervention site).

[00160] Considering for example a first distance LI of the at least one monitoring electrode, and a second distance L2 of the at least one reference electrode, where L1<L2 as measured from the intervention site. Signal propagation velocity of a signal received from the at least one monitoring electrode can be defined as Ll/tl , and from for the signal picked up from at least one reference electrode: L2/t2. In healthy mammalian subjects with no adverse phenomenon relating to the patient intervention site (e.g., no leak and/or no inflammation), the propagation velocity = Ll/tl =L2/t2, whereas in suspected patients experiencing an adverse phenomenon relating to the intervention site, t2 may be comparatively high or low or cannot be computed.

[00161] In some embodiments, the system may be configured to determine, based on the processing of the signals received from the at least one monitoring electrode and the at least one reference electrode, a time (e.g., days after surgical intervention) when it is safe to resume normal food intake. For example, the system may determine that it is safe for a patient to resume food intake, if a value relating to a patient's recovery (e.g., a value indicative of a drop in severity of an adverse phenomenon) drops below a food intake threshold value. The food intake threshold value may be determined based on (e.g., statistical) analysis of parameter values of a cohort patients not experiencing, post-operatively, one or more adverse phenomenon.

[00162] The term "post operative" may pertain to day 1, day 2, day 3, day 4, day 6, day 7, or day 8 after surgery. Accordingly, the cohort may pertain to patients not experiencing an adverse condition, immediately or not immediately following surgery. For the cohort, the analysis for determining the intake threshold may be performed starting from the days of normal food intake.

[00163] In some examples, the food intake threshold value may be determined based on statistical analysis of a cohort of patients not experiencing a certain adverse phenomenon, e.g., not experiencing post-operative Ileus. For example, a daily recovery index may be determined based on the patients' motility and spiking activity, e.g., by computing, for each day, a ratio between a value pertaining to motility (e.g., motility index) and spiking energy, or between the motility index and spiking index for each patient of the cohort. For each day (e.g., 7 days) following surgery, the recovery index may be determined for the patient cohort. In some examples, the highest standard deviation of the recovery index computed for the cohort of patients may be selected as the "food intake threshold". In other examples, a highest average recovery index may be selected as the food intake threshold.

[00164] Referring now to Figure 8, the solid line shows impedance as a function of time. The horizontal dashed line indicates a leak detection threshold and the vertical dashed line indicates a time of laceration. When measured impedance crosses the threshold for a certain period of time (e.g., > lOmin), an output indicative of anastomotic leak is provided. The threshold can for example be fixed, predetermined, or can change in a linear or a non-linear manner.

[00165] Further reference is made to Figure 9 in which the dashed line indicates the impedance difference from baseline measured 10mm from the leak site prior and after the induction of the defect. The sold line indicates impedance of two reference electrodes recorded at a distance >100mm from the defect. The error bars represent standard deviation of impedance measured over 2 minutes per sample. Overall separation 10 minutes after the induction of the defect reflects p<0.001

[00166] Figure 10 shows impedance measurement in an animal with a sutured defect (no leak). In this case there is no separation over time between the recorded impedance before and after the induction of the leak.

[00167] Figure 11 show representative electrophysiological signals from electrodes implanted 10mm, 20mm and >100mm from the defect in a chronic leak animal model and control animal model with healing defect. It is noted that there is typically better correlation between the reference and defect signals recorded in the control animal compared to the leak animal model.

[00168] Figure 12 shows maximum cross correlation value ("correlation coeff") of leak animal model vs. control animal model over time. The leak model shows declining correlation between the healthy reference site and the damaged site while the correlation improves on the control model, in line with the physiological condition in the respective animals.

[00169] Figure 13 shows impedance-based leak detection by measuring impedance at the surgical or monitoring site, and by distantly placed reference electrode (e.g., placed 80mm and more, from the intervention or surgical site, of the same organ or tissue as the monitoring electrode. As shown in the example, measured tissue impedance decreased about 10%, about 10 mm to 20 mm from the leak site, about, 2 hours after leak induction at the surgical site. [00170] Figure 14 illustrates the maximum cross correlation between the signal received from at least one electrode engaging with the tissue at the surgical site and at least one reference electrode. For the red graph (the 'leak' classified type) a leak is detected, and in the two blue graphs (the 'control' classified type) there is no leak.

[00171] Figure 15B illustrates myoelectric data recorded from a pig using the system, according to some embodiments.

[00172] Figure 15C illustrates myoelectric data recorded from viable ex-vivo human colonic tissue under normal (blue) and hypoxia conditions (red) and corresponding contraction force (green). The myoelectric signal was found to be substantially similar to the large animal in-vivo model. Functional parameters changed following induction of hypoxia conditions (simulating leak driving conditions).

[00173] Figure 15D show clinical results from acute surgery (N=5). A system according to an embodiment was used to record impedance and myoelectric data from baseline (intact) and devascularized (hypoxia) colonic tissue. Raw data (left) exhibits similar characteristics compared to animal/ex-vivo data. Spiking is diminished under hypoxia conditions. Spiking activity for all five patients, is shown in the graph to the right, for baseline and ischemia conditions, in which horizontal bars indicate mean, error bars indicate standard deviation.

[00174] Reference is made to Figures 16A-16C. Figure 16A: First myoelectric (blue) and contraction data (red) were recorded from a longitudinal colon tissue. Figure 16B: Using data relating to a raw myoelectric signal spikes were filtered out. Reconstruction of mechanical contractions from the myoelectric (blue) data: spikes are detected using threshold filtering of the time derivative of the original signal (black), then convolved with a window function to generate reconstructed mechanical data (green). Figure 16C: The mechanical contractions were reconstructed using only myoelectric data. The reconstruction was with relatively good fit to the measured data under normal and hypoxia conditions. The qualitative comparison between the actual mechanical data recorded (brown) and the reconstructed contractions calculated is shown using only myoelectric data (green).

[00175] Figure 17 (top) and Figure 18 (top), illustrate myoelectric patterns in baseline and drug affected environments. The top indicates baseline contractions (red) and myoelectric activity (blue).

[00176] Figure 17 (bottom) shows contractions and myoelectric activity after Carbachaol (CCH) was introduced, and Figure 18 (bottom) contractions and myoelectric activity after the introduction of MONNA (N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid). [00177] Figure 19 shows a point cloud of slow colonic electrophysiological (EPS) signals (cycles/min) vs. an inflammation index (arbitrary units) vs. spike correlation coefficient value, of 50 subjects. The inflammation index may be equivalent to inflammation (e.g., based on impedance spatial and temporal analysis) between the monitored and reference sites where higher values are indicative of higher probability for local inflammation. Such point cloud may be employed for selecting or training a classifier (e.g., a machine learning model), e.g., based on a linear or non-linear threshold applied on the point cloud. In some examples, only one parameter may be taken into consideration by the classifier. In some embodiments, two or more parameters may be taken into consideration by the classifier.

[00178] Figure 20 shows a graph of Gl motility data (Ileus in patient 1 (red) and Ileus in patient 2 (gray), in conjunction with an average recovery index, calculated based on temporal recovery of motility signals, and a food intake threshold in arbitrary units (A.U.) calculated using supervised statistical methods.

[00179] In some examples, a food intake threshold value was determined as the highest standard deviation found for days 0-6, i.e., at day 5.

[00180] Additional Examples:

[00181] Examples pertain to a monitoring system for detecting or predicting the onset of adverse physiological phenomenon in a patient, the system comprising an electronic sensor having electrical characteristics that are responsive to changes in physiological characteristics of a patient with which the electronic sensor is operably coupled, the electronic sensor being operable to provide an output descriptive of changes in physiological characteristics of the patient; and processing circuitry that is configured to process the output to determine if the output meets at least one adverse-phenomenon output criterion or not. The output can include an electronic or otherwise measurable signal.

[00182] Example 1 includes a monitoring system for detecting or predicting the onset of adverse physiological phenomenon in a patient, the monitoring system comprising an electronic sensor having electrical characteristics that are responsive to changes in physiological characteristics of a patient with which the electronic sensor is operably coupled; a communication device that is in communication with the electronic sensor and operative to receive an electric signal from the electronic sensor, the electric signal being indicative of changes in the physiological characteristics of the patient, wherein the communication device is further operative to transmit (wired and/or wirelessly) a signal relating to the received electric signal; and processing circuitry that is configured to process the received electric signal to determine if the received electric signal meets at least one adverse-phenomenon output criterion or not. [00183] Example 2 includes the subject matter of Example 1 and, optionally, wherein the processing circuitry is configured to process the received signal to determine if anastomotic leakage occurs or not.

[00184] Example 3 includes the subject matter of examples 1 or 2 and, optionally, wherein the electronic sensor comprises an implantable electrode.

[00185] Example 4 includes the subject matter of Example 3 and, optionally, wherein the electronic sensor comprises a sensing element that includes, for example, an implantable mesh, wire, sheath metal and/ or cable.

[00186] Example 5 includes the subject matter of Examples 4 and, optionally, wherein the sensing element comprises biodegradable material.

[00187] Example 6 includes the subject matter of any one or more of the Examples 4 or 5 and, optionally, wherein the sensing element comprise biocompatible material.

[00188] Example 7 includes the subject matter of any one or more of Examples 3 to 6 and, optionally, wherein the sensing element comprises biocompatible material and which is deployable and coupleable adjunct to the site of interest.

[00189] Example 8 includes the subject matter of any one or more of Examples 1 to 7 and, optionally, further comprising a fluid drainage catheter that is operably positionable to drain fluids from an internal body site of interest to outside the body of the patient, wherein the electronic sensor is operably integrated in and/or fluidly coupled with the fluid path of the bodily fluid drainage catheter for measuring changes in the physiological characteristics of the patient.

[00190] Example 9 comprises a patient site of interest monitoring system for detecting or predicting the onset of adverse physiological phenomenon in a patient, the system comprising: a monitoring sensor for operably engaging a patient site of interest, the monitoring sensor having electrical characteristics that are responsive to changes in physiological characteristics of the patient site of interest; an input device for generating and subjecting the patient of interest with an input signal via the monitoring electrode to generate a response signal; a communication device that is in communication with the monitoring sensor and operative to receive the response signal from the electronic sensor, the response signal being indicative of changes in the physiological characteristics of the patient; and an analysis engine that is configured to receive the response signal from the communication device and to process data relating to the received response signal to determine if the response signal meets at least one adverse-phenomenon output criterion or not. [00191] Example 10 includes the subject matter of example 9 and, optionally, wherein the analysis engine is configured to process the received signal to determine if leakage from a body organ occurs or not.

[00192] Example 11 includes the subject matter of examples 9 and/or 10 and, optionally, wherein the monitoring sensor comprises a sensing element.

[00193] Example 12 includes the subject matter of any one or more of the Examples 9 to 11, wherein the monitoring sensor is fully implantable, partially implantable, or non-implantable monitoring sensor, and, optionally, a reference sensor that is a fully implantable, partially implantable, or non-implantable reference sensor.

[00194] Example 13 includes the subject matter of Examples 11 and/or 12, wherein the sensing element comprises biodegradable material.

[00195] Example 14 includes the subject matter of Examples 12 and/or 13 and, optionally, wherein the sensing element comprises biocompatible material.

[00196] Example 15 includes the subject matter of any one or more of the examples 12 to 14 and, optionally, wherein the monitoring sensor comprises biocompatible material.

[00197] Example 16 includes the subject matter of any one or more of the examples 9 to 15, and, optionally, further comprising a fluid drainage catheter that is operably positionable to drain fluids from an internal body site of interest to outside the body of the patient, wherein the monitoring sensor is operably integrated in the fluid path of the bodily fluid drainage catheter for measuring changes in the physiological characteristics of the patient.

[00198] Example 17 includes the subject matter of Example 16 and, optionally, wherein the monitoring sensor is operably integrated in the fluid path of the bodily fluid drainage catheter for measuring changes in the physiological characteristics of the patient site of interest.

[00199] Example 18 includes the subject matter of any one or more of the Examples 9 to 17 and, optionally, wherein the input device is operable to subject the patient site of interest with an alternating input signal at an automatically or manually selected input frequency

[00200] Example 19 includes the subject matter of Example 18 and, optionally, wherein the alternating input signal is pre-selected, dynamically selected or adaptively selected. [00201] Example 20 includes the subject matter of Examples 18 and/or 19 and, optionally, wherein the input device is operable to subject the patient site of interest with an alternating input signal at a plurality of automatically or manually selected frequencies.

[00202] Example 21 includes the subject matter of any one or more of the Examples and, optionally, 9 to 20, further comprising a reference sensor for providing a reference signal, the reference sensor optionally comprising a fully implantable, partially implantable, and/or non-implantable sensing element.

[00203] Example 22 includes the subject matter of any one or more of the examples 9 to 21 and, optionally, wherein a characteristic of the input signal is selected automatically based on the reference signal.

[00204] Example 23 includes the subject matter of Example 22 and, optionally, wherein a characteristic of the input signal and/or response signal comprises amplitude, frequency and/or phase of the signal.

[00205] Example 24 includes the subject matter of Example 23 and, optionally, wherein a characteristic of the input signal further comprises input signal and/or response signal filter characteristics.

[00206] Example 25 includes the subject matter of Example 24 and, optionally, wherein the input and/or response signal filter characteristics are predetermined, dynamically selected or adaptively selected.

[00207] Example 26 includes the subject matter of any one or more of examples 20 to 25, and, optionally, wherein the input device is operable to sweep a plurality of frequencies of the input signal.

[00208] Example 27 includes the subject matter of Example 26 and, optionally, wherein the sweeping is performed through a predetermined range, a dynamically selected or adaptively selected frequency range.

[00209] Example 28 includes the subject matter of any one or more of the Examples 9 to 27 and, optionally, wherein when an output that is provided by the monitoring sensor has characteristics meeting at least one adverse-phenomenon output criterion, then the output is indicative of anastomotic leak. The at least one adverse-phenomenon output criterion may, for example, relate to a measured variation in impedance such as, for example, increase above a threshold. Optionally, the monitoring sensor output may be analyzed together with (e.g., compared against) a reference sensor output, and the at least one adverse-phenomenon output criterion may pertain to a result of the comparison between the two outputs. For example, a difference between a monitoring sensor outputs value and a reference sensor output value exceeding a threshold may be indicative of anastomotic leak. [00210] Example 29 includes the subject matter of any one or more of the Examples 9 to 28 and, optionally, further comprising a reference sensor.

[00211] Example 30 includes the subject matter of any one or more of the Examples 9 to 20 and, optionally, wherein the monitoring and/or reference sensors include a monitoring and/or reference electrode, respectively.

[00212] Example 31 includes the subject matter of Example 30 and, optionally, wherein the monitoring and/or reference electrodes comprise Magnesium.

[00213] Example 32 includes the subject matter of any one or more of the Examples 9 to 31, and, optionally, wherein the monitoring and/or reference sensor is configured such that a change in measured impedance (e.g., change in pattern of measured impedance, is indicative of leak).

[00214] Example 33 includes the subject matter of any one or more of the Examples 9 to 32 and, optionally, wherein the analysis engine determines based on the electrophysiological signals if the response signal meets one or more adverse-phenomenon output criteria or not.

[00215] Example 34 includes the subject matter of any one or more of the Examples 9 to 33 and, optionally, wherein the analysis engine employs artificial intelligence functionalities for determining if the response signal meets one or more adverse-phenomenon output criteria or not.

[00216] Example 35 includes the subject matter of any one or more of the Examples 30 to 34 and, optionally, wherein the monitoring and/or reference electrodes are arranged in alignment with a staple such that the staple directly engages with the electrode for the fastening thereof with the patient's tissue.

[00217] Example 36 includes the subject matter of any one or more of the Examples 30 to 35 and, optionally, wherein monitoring and/or reference electrodes are positioned between two staples such that the electrodes are secured to the patient's tissue merely by the force of the staples for securing a proximal and distal buttress materials to the tissue.

[00218] Example 36 is method for monitoring a patient site of interest, comprising operably engaging one or more electrodes with a patient site of interest; subjecting the patient site of interest, via the one or more electrodes, with input signals; receive response signals as a results of subjecting the patient site of interest with input signals; and determining, based on the received response signals, an output pertaining to a physiological phenomenon with respect to the patient site of interest, wherein the physiological phenomenon pertains to anastomotic leak. [00219] Examples pertain to system for monitoring a patient site-of-interest (SOI) of a mammalian subject, system comprising:

[00220] at least one monitoring electrode for sensing a parameter value relating to a patient intervention site; and

[00221] at least one reference electrode for sensing a parameter value relating to a patient reference site, wherein the patient reference site is located remotely from the patient intervention site,

[00222] wherein the at least one monitoring electrode and the at least one reference electrode are operable to provide an output signal descriptive of physiological characteristics of the intervention and the reference site; at least one processor; and at least one memory configured to store data and software code portions executable by the at least one processor to cause to perform:

[00223] processing the output signal for determining, with respect to the patient SOI, whether an adverse physiological phenomenon occurs or not.

[00224] In some examples, the adverse physiological phenomenon includes: anastomotic leak, hypoxia, Ileus, inflammation, ischemia, fibrosis, or any combination of the aforesaid.

[00225] In some examples, system is configured to determine an expected onset time of experiencing an adverse physiological phenomenon associated with the patient SOI.

[00226] In some examples, the output signals pertains to myoelectric activity, and the processing includes determining mechanical bowel activity in the mammalian subject, based on the sensed myoelectric activity.

[00227] In some examples, the system is configured to determine, based on the processing of the output signal, a time period after completion of a surgical procedure, when it is safe for the mammalian subject to resume normal food intake.

[00228] In some examples, the system comprising at least one classifier, wherein the processing of the signal output includes applying the at least one classifier for determining, with respect to the patient SOI, whether an adverse physiological phenomenon occurs or not.

[00229] In some examples, the classifier is trained machine learning (ML) model.

[00230] In some examples, wherein the processing of the output signal includes determining an electrical characteristic of the patient SOI, and/or a gastric activity. [00231] In some examples, the gastric activity includes myoelectric activity, and wherein the electrical characteristic pertains to tissue impedance of the patient SOI.

[00232] In some examples, the myoelectric activity is determined based on a high-pass filtered signal relating to the myoelectric activity for determining spiking activity; a low-pass filtered signal relating to the myoelectric activity for determining slow bowel movement activity, or both.

[00233] In some examples, the ML model is trained using impedance, spiking activity, slow bowel movement activity parameter values of a plurality of mammalian subjects with known leak and no leak.

[00234] In some examples, the leak may include acute and mild leak, or various grades of leak.

[00235] In some examples, the system is configured to distinguish between acute and mild leak.

[00236] In some examples, the system is configured to provide an output indicating when an adverse phenomenon occurs.

[00237] In some examples, the system is configured to provide an output indicating that no adverse phenomenon occurs.

[00238] In some examples, the comparing of signals received from the at least one monitoring electrode and the at least one reference electrode reduces a false-positive rate of an adverse phenomenon identified relating to the patient SOI, compared to a false-positive rate that is obtained if only signals received from the at least one monitoring electrode were processed.

[00239] In some examples, the system is configured to determine a probability that an adverse phenomenon occurs, and/or a probability with respect to an onset time of an adverse phenomenon to occur.

[00240] In some examples, the system is configured to process data relating to behavioral parameters, social parameter and/or additional medical parameter values of the mammalian subject for determining, with respect to the patient SOI, whether an adverse physiological phenomenon occurs or not.

[00241] In some examples, the system is configured to provide a treatment recommendation for treating a detected adverse phenomenon.

[00242] In some examples, the determining is based on cross-correlating between an output signal produced by the at least one monitoring electrode and the output signal produced by the at least one reference signal. [00243] In some examples, the system is configured to concurrently sense impedance and an electrophysiological signal using the same at least one monitoring and/or reference electrode.

[00244] In some examples, the concurrent sensing is realized through signal filtering and/or multiplexing.

[00245] In some examples, a method for monitoring a patient site-of-interest (SOI) of a mammalian subject, comprises:

[00246] sensing at parameter value relating to at least one parameter of a patient intervention site; and

[00247] sensing a parameter value relating to at least one parameter of a patient reference site, wherein the patient reference site is located remotely from the patient intervention site,

[00248] receiving an output signal relating to the parameter values of the intervention and the reference site;

[00249] processing the output signal for determining, with respect to the patient SOI, whether an adverse physiological phenomenon occurs or not.

[00250] The method may additionally or alternatively include applying any one or more of the processes and/or steps disclosed herein.

[00251] The various features and steps discussed above, as well as other known equivalents for each such feature or step, can be mixed and matched by one of ordinary skill in this art to perform methods in accordance with principles described herein. Although the disclosure has been provided in the context of certain embodiments and examples, it will be understood by those skilled in the art that the disclosure extends beyond the specifically described embodiments to other alternative embodiments and/or uses and obvious modifications and equivalents thereof. Accordingly, the disclosure is not intended to be limited by the specific disclosures of embodiments herein.

[00252] Any digital computer system, module and/or engine exemplified herein can be configured or otherwise programmed to implement a method disclosed herein, and to the extent that the system, module and/or engine is configured to implement such a method, it is within the scope and spirit of the disclosure. Once the system, module and/or engine are programmed to perform particular functions pursuant to computer readable and executable instructions from program software that implements a method disclosed herein, it in effect becomes a special purpose computer particular to embodiments of the method disclosed herein. The methods and/or processes disclosed herein may be implemented as a computer program product that may be tangibly embodied in an information carrier including, for example, in a non-transitory tangible computer-readable and/or non-transitory tangible machine-readable storage device. The computer program product may directly loadable into an internal memory of a digital computer, comprising software code portions for performing the methods and/or processes as disclosed herein. The term "non-transitory" is used to exclude transitory, propagating signals, but to otherwise include any volatile or non-volatile computer memory technology suitable to the application.

[00253] Additionally or alternatively, the methods and/or processes disclosed herein may be implemented as a computer program that may be intangibly embodied by a computer readable signal medium. A computer readable signal medium may include a propagated data signal with computer readable program code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including, but not limited to, electro-magnetic, optical, or any suitable combination thereof. A computer readable signal medium may be any computer readable medium that is not a non- transitory computer or machine-readable storage device and that can communicate, propagate, or transport a program for use by or in connection with apparatuses, systems, platforms, methods, operations and/or processes discussed herein.

[00254] The terms "non-transitory computer-readable storage device" and "non-transitory machine- readable storage device" encompasses distribution media, intermediate storage media, execution memory of a computer, and any other medium or device capable of storing for later reading by a computer program implementing embodiments of a method disclosed herein. A computer program product can be deployed to be executed on one computer or on multiple computers at one site or distributed across multiple sites and interconnected by one or more communication networks.

[00255] These computer readable and executable instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks. These computer readable and executable program instructions may also be stored in a computer readable storage medium that can direct a computer, a programmable data processing apparatus, and/or other devices to function in a particular manner, such that the computer readable storage medium having instructions stored therein comprises an article of manufacture including instructions which implement aspects of the function/act specified in the flowchart and/or block diagram block or blocks.

[00256] The computer readable and executable instructions may also be loaded onto a computer, other programmable data processing apparatus, or other device to cause a series of operational steps to be performed on the computer, other programmable apparatus or other device to produce a computer implemented process, such that the instructions which execute on the computer, other programmable apparatus, or other device implement the functions/acts specified in the flowchart and/or block diagram block or blocks.

[00257] In the discussion, unless otherwise stated, adjectives such as "substantially" and "about" that modify a condition or relationship characteristic of a feature or features of an embodiment, are to be understood to mean that the condition or characteristic is defined to within tolerances that are acceptable for operation of the embodiment for an application for which it is intended.

[00258] Unless otherwise specified, the terms 'about' and/or 'close' with respect to a magnitude or a numerical value may imply to be within an inclusive range of -10% to +10% of the respective magnitude or value.

[00259] "Coupled with" means indirectly or directly "coupled with".

[00260] It should be noted that where an embodiment refers to a condition of "above a threshold", this should not be construed as excluding an embodiment referring to a condition of "equal or above a threshold". Analogously, where an embodiment refers to a condition "below a threshold", this should not to be construed as excluding an embodiment referring to a condition "equal or below a threshold". It is clear that should a condition be interpreted as being fulfilled if the value of a given parameter is above a threshold, then the same condition is considered as not being fulfilled if the value of the given parameter is equal or below the given threshold. Conversely, should a condition be interpreted as being fulfilled if the value of a given parameter is equal or above a threshold, then the same condition is considered as not being fulfilled if the value of the given parameter is below (and only below) the given threshold.

[00261] It should be understood that where the claims or specification refer to "a" or "an" element and/or feature, such reference is not to be construed as there being only one of that element. Hence, reference to "an element" or "at least one element" for instance may also encompass "one or more elements".

[00262] As used herein the term "configuring" and/or 'adapting' for an objective, or a variation thereof, implies using materials and/or components in a manner designed for and/or implemented and/or operable or operative to achieve the objective.

[00263] Unless otherwise stated or applicable, the use of the expression "and/or" between the last two members of a list of options for selection indicates that a selection of one or more of the listed options is appropriate and may be made, and may be used interchangeably with the expressions "at least one of the following", "any one of the following" or "one or more of the following", followed by a listing of the various options.

[00264] As used herein, the phrase "A,B,C, or any combination of the aforesaid" should be interpreted as meaning all of the following: (i) A or B or C or any combination of A, B, and C, (ii) at least one of A, B, and C; and (iii) A, and/or B and/or C. This concept is illustrated for three elements (i.e., A,B,C), but extends to fewer and greater numbers of elements (e.g., A, B, C, D, etc.).

[00265] As used herein, "biodegradable" materials include materials that at least partially resorb into the body or otherwise break down over time while not necessarily being absorbed within the body, and "non- biodegradable" materials include those that maintain substantial mechanical integrity over their lifetime in a body. Such "biodegradable" or "nonbiodegradable" materials are well known to those having skill in the art. In some embodiments, these materials will be biocompatible, while in other embodiments, they may be partially or fully constructed from non-biocompatible materials.

[00266] It is noted that the terms "operable to" or "operative to" can encompass the meaning of the term "adapted or configured to". In other words, a machine "operable to" or "operative to" perform a task can in some embodiments, embrace a mere capability (e.g., "adapted") to perform the function and, in some other embodiments, a machine that is actually made (e.g., "configured") to perform the function.

[00267] Throughout this application, various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[00268] Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases "ranging/ ranges between" a first indicate number and a second indicate number and "ranging/ranges from" a first indicate number "to" a second indicate number are used herein interchangeably and are meant to include the firstand second indicated numbers and all the fractional and integral numerals therebetween.

[00269] It should be appreciated that combination of features disclosed in different embodiments are also included within the scope of the present inventions. [00270] While certain features of the invention have been illustrated and described herein, many modifications, substitutions, changes, and equivalents will now occur to those of ordinary skill in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention.

Claims

CLAIMS What is claimed is:

1. A system for monitoring a patient site-of-interest (SOI) of a mammalian subject, system comprising: at least one monitoring electrode for sensing a parameter value relating to a patient intervention site; and at least one reference electrode for sensing a parameter value relating to a patient reference site, wherein the patient reference site is located remotely from the patient intervention site, wherein the at least one monitoring electrode and the at least one reference electrode are operable to provide an output signal descriptive of physiological characteristics of the intervention and the reference site; at least one processor; and at least one memory configured to store data and software code portions executable by the at least one processor to cause to perform: processing the output signal for determining, with respect to the patient SOI, whether an adverse physiological phenomenon occurs or not.

2. The system of claim 1, wherein the adverse physiological phenomenon includes: anastomotic leak, hypoxia, Ileus, inflammation, or any combination of the aforesaid.

3. The system of claim 1, wherein the system is further configured to determine an expected onset time of experiencing an adverse physiological phenomenon associated with the patient SOI.

4. The system of claim 1, wherein the output signals pertains to myoelectric activity, and the processing includes determining mechanical bowel activity in the mammalian subject, based on the sensed myoelectric activity.

5. The system of claim 1, further configured to determine, based on the processing of the output signal, a time period after completion of a surgical procedure, when it is safe for the mammalian subject to resume normal food intake.

6. The system of claim 1, comprising at least one classifier, wherein the processing of the signal output includes applying the at least one classifier for determining, with respect to the patient SOI, whether an adverse physiological phenomenon occurs or not.

7. The system of claim 6, wherein the classifier is trained machine learning (ML) model.

8. The system of claim 1, wherein the processing of the output signal includes determining an electrical characteristic of the patient SOI, and/or a gastric activity.

9. The system of claim 8, wherein the gastric activity includes myoelectric activity, and wherein the electrical characteristic pertains to tissue impedance of the patient SOI.

10. The system of claim 9, wherein the myoelectric activity is determined based on a high-pass filtered signal relating to the myoelectric activity for determining spiking activity; a low-pass filtered signal relating to the myoelectric activity for determining slow bowel movement activity, or both.

11. The system of claim 10, wherein the ML model is trained using impedance, spiking activity, slow bowel movement activity parameter values of a plurality of mammalian subjects with known leak and no leak.

12. The system of claim 11, wherein the leak may include acute and mild leak, or various grades of leak.

13. The system of claim 1, configured to distinguish between acute and mild leak.

14. The system of claim 1, configured to provide an output indicating when an adverse phenomenon occurs.

15. The system of claim 1, configured to provide an output indicating that no adverse phenomenon occurs.

16. The system of claim 1, wherein the comparing of signals received from the at least one monitoring electrode and the at least one reference electrode reduces a false-positive rate of an adverse phenomenon identified relating to the patient SOI, compared to a false-positive rate that is obtained if only signals received from the at least one monitoring electrode were processed.

17. The system of claim 1, configured to determine a probability that an adverse phenomenon occurs, and/or a probability with respect to an onset time of an adverse phenomenon to occur.

18. The system of claim 1, further configured to process data relating to behavioral parameters, social parameter and/or additional medical parameter values of the mammalian subject for determining, with respect to the patient SOI, whether an adverse physiological phenomenon occurs or not.

19. The system of claim 1, configured to provide a treatment recommendation for treating a detected adverse phenomenon.

20. The system of claim 1, wherein the determining is based on cross-correlating between an output signal produced by the at least one monitoring electrode and the output signal produced by the at least one reference signal.

21. The system of claim 1, configured to concurrently sense impedance and an electrophysiological signal using the same at least one monitoring and/or reference electrode.

22. The system of claim 21, wherein the concurrent sensing is realized through signal filtering and/or multiplexing.

23. A method for monitoring a patient site-of-interest (SOI) of a mammalian subject, the method comprising: sensing at parameter value relating to at least one parameter of a patient intervention site; and sensing a parameter value relating to at least one parameter of a patient reference site, wherein the patient reference site is located remotely from the patient intervention site, receiving an output signal relating to the parameter values of the intervention and the reference site; processing the output signal for determining, with respect to the patient SOI, whether an adverse physiological phenomenon occurs or not.

24. The method of claim 23, wherein the adverse physiological phenomenon includes: anastomotic leak, hypoxia, Ileus, inflammation, or any combination of the aforesaid.

25. The method of claim 23, further comprising determining an expected onset time of experiencing an adverse physiological phenomenon associated with the patient SOI.

26. The method of claim 23, wherein the output signals pertains to myoelectric activity, and the processing includes determining mechanical bowel activity in the mammalian subject, based on the sensed myoelectric activity.

27. The method of claim 23, further comprising determining, based on the processing of the output signal, a time period after completion of a surgical procedure, when it is safe for the mammalian subject to resume normal food intake.

28. The method of claim 23, further comprising processing of the signal output includes applying the at least one classifier for determining, with respect to the patient SOI, whether an adverse physiological phenomenon occurs or not.

29. The method of claim 23, further comprising distinguishing between acute and mild anastomotic leak.

30. The method of claim 23, further comprising determining a probability that an adverse phenomenon occurs, and/or a probability with respect to an onset time of an adverse phenomenon to occur.