Flexible piezocapacitivesensors utilizing nanomaterial–polymercomposite-based nanofibrous membranes offer an attractive alternativeto more traditional piezoelectric and piezoresistive wearable sensorsowing to their ultralow powered nature, fast response, low hysteresis,and insensitivity to temperature change. In this work, we proposea facile method of fabricating electrospun graphene-dispersed PVAcnanofibrous membrane-based piezocapacitive sensors for applicationsin IoT-enabled wearables and human physiological function monitoring.A series of electrical and material characterization experiments wereconducted on both the pristine and graphene-dispersed PVAc nanofibersto understand the effect of graphene addition on nanofiber morphology,dielectric response, and pressure sensing performance. Dynamic uniaxialpressure sensing performance evaluation tests were conducted on thepristine and graphene-loaded PVAc nanofibrous membrane-based sensorsfor understanding the effect of two-dimensional (2D) nanofiller additionon pressure sensing performance. A marked increase in the dielectricconstant and pressure sensing performance was observed for graphene-loadedspin coated membrane and nanofiber webs respectively, and subsequentlythe micro dipole formation model was invoked to explain the nanofiller-induceddielectric constant enhancement. The robustness and reliability ofthe sensor have been underscored by conducting accelerated lifetimeassessment experiments entailing at least 3000 cycles of periodictactile force loading. A series of tests involving human physiologicalparameter monitoring were conducted to underscore the applicabilityof the proposed sensor for IoT-enabled personalized health care, softrobotics, and next-generation prosthetic devices. Finally, the easydegradability of the sensing elements is demonstrated to emphasizetheir suitability for transient electronics applications. The last two decades have witnessed asignificant growth in thewearable-focused consumer electronics industry, and the rise in theconsumption of smart watches and accessories is a testament to thatfact. Especially, with the rapid incremental progress being made everyday, the field of wearable electronics is hovering around the brinkof science fiction. The Internet of Things (IoT) revolution in thelast decade has pushed wearable sensors to the forefront of researchinterest across the globe. Today, the demands for seamless integrationof wearable sensors which can monitor vital physiological parametershave skyrocketed, and this dramatic rise in demand has been partiallyfueled by the onslaught of the COVID-19 pandemic since late 2019.The need of the hour is reliable, facile, low-powered, and inexpensivesensors fit for seamless integration into various wearable apparelthat will enable nonintrusive acquisition of vital health parameterswith the aim of improving the quality of life of the user. However,for any wearable sensor technology to be considered seriously in thehealthcare domain, parameters such as sensitivity, ease of use, costeffectiveness, long term-reliability, and, most importantly, a lowpower budget, are of paramount importance. In addition to applicationsin human physiological function monitoring, flexible sensors are alsoof great importance in developing artificial skin for next-generationprostheses, soft human–machine interfaces, robotics-assistedmedical facilities, and other similar areas.7 piezoelectric,13 and capacitive.17 Other mechanisms utilizing transistors for pressure sensing havealso been reported in the literature.20 More recently, the triboelectricsensing mechanism has also been employed in the development of pressureand strain sensors.22 Though the piezoelectric sensingmechanism offers the advantage of self-powered sensing, their inabilityto sense static pressure places a major hindrance on their applicationsin tasks requiring both static and dynamic pressure sensing. In contrast,piezoresistive sensing offers functionality in a wide range of pressuresensing conditions, including static, quasi-static, and dynamic pressure/strainsensing. However, resistive sensors have the inherent problems ofthermal drift, high hysteresis, and a relatively higher power budget.Finally, the fundamental problem with transistor-based sensors liesin their complex fabrication process and associated circuitry. Piezocapacitivesensing offers an attractive alternative to more traditional piezoelectricand piezoresistive sensing owing to its ultralow-powered nature dueto the lack of flow of DC current. Furthermore, piezocapacitive sensorsoffer added advantages, such as superior stability, temperature independence,low hysteresis, and fast response time.Historically, strainand pressure sensing devices have relied ondifferent sensing mechanisms, namely piezo-resistive,d) between the electrodes, more recently, methods are beinginvestigated to achieve pressure-induced dielectric constant (εr) changes to achieve enhanced pressure sensitivity.24 Furthermore, it is desirable that the dielectric layer has a lowcompressive modulus, which will further contribute toward enhancingthe pressure sensitivity. In the past, elastomeric materials withmicrostructured air voids have been employed for enhancing the sensingperformance of capacitive sensors.25 For instance,Mannsfeld et al. demonstrated a microstructured polydimethylsiloxane(PDMS)-based large-area flexible capacitive sensor array with fastresponse.23 More recently, researchershave employed ionic hydrogels for developing capacitive sensors forpressure sensing, humidity sensing, and human physiological parametersmonitoring.27 Ding et al. reported a polyvinylalcohol-cellulose nanofiber-based biocompatible, self-healing, breathable,stretchable, and degradable organohydrogel ionic skin with superiorhumidity responsiveness.26Traditional parallel-plateelectrode-based capacitive pressuresensors comprise two conductive electrodes separated by a dielectricmedium. Upon application of external pressure, the distance betweenthe two electrodes changes, thereby leading to a change in capacitancethat can be measured with an external circuit. The structural propertyof the dielectric layer between the two electrodes has a profoundimpact on the sensing performance of the sensor. Though traditionalcapacitive pressure sensors rely on the changing distance (d) between the electrodes reduces, squeezing the sandwicheddielectric layer and replacing the low permittivity air voids withhigh permittivity dielectric material in the process. The change inthe dielectric constant with applied pressure contributes to the enhancedsensing performance. Though dielectric elastomeric structures withmicropatterned air voids offer an attractive proposition, the inherentcomplexity of fabrication involving multistep patterning processesand reliance on expensive machinery place constraints on small andmedium-sized enterprises to develop and commercialize them.In thecase of capacitive sensors employing dielectric layers withair voids, the initial effective dielectric constant is a combinationof the dielectric constants of air and the porous/microstructuredmaterial. Upon application of an external pressure, the gap  and grapheneand MXene nanoflakes, has proven to enhance the dielectric performanceof the polymeric materials.36 Furthermore, the addition of nanomaterial fillers in low volumefractions has the potential to enhance the dielectric property ofthe polymeric materials without compromising their flexibility ormechanical properties. Yang et al. reported CNT-polyvinylidene fluoride(PVDF) nanofibrous membrane-based flexible piezocapacitive tactilesensors for wearable applications.36 However,due to the one-dimensional (1-D) nature of CNTs, they have a lessersurface area in comparison to 2D materials with a larger specificsurface area and tend to form agglomerates that lead to poor dispersionin nanofibers and can subsequently reduce the mechanical performanceof the membranes. Incorporation of 2-D materials like Graphene andMXene (Ti3C2Tx)can potentially alleviate the problems associated with lower-dimensionnanofillers and lead to the fabrication of better performing dielectriclayers. Previously, Sharma et al. reported that MXene dispersed polyvinylidenefluoride-trifluoroethylene (PVDF-TrFe) nanofibers for developing highperformance flexible and wearable capacitive sensors.33 The harsh acid etching used for synthesizing MXene sheetsled to defect sites in the flakes that formed centers of oxidation,leading to the loss of conductivity.38 Furthermore,the presence of hydroxyl groups on the MXene surface (to achieve betterdispersion in water) resulted in a reaction with dissolved oxygenand water molecules, thereby causing oxidation and a subsequent lossof conductive properties.38 In contrast,graphene can prove to be an attractive alternative owing to its superiorstability coupled with excellent electrical and mechanical properties.Piezocapacitive sensors utilizing polymeric nanofibers withnanomaterialfillers are relatively new and must be explored further to assesstheir suitability for applications in wearables. Although polymericnanofibers enable the facile fabrication of flexible and pliant structureswith low compression modulus, their low dielectric permittivity limitstheir usage for applications in supercapacitors and piezocapacitivesensors. Incorporation of fillers in polymeric materials near thepercolation threshold has proven to enhance the dielectric propertiesof the composites.40 polymer having the formula (C4H6O2)n,which makes it a promising candidate for usage in sensors targetedfor human physiological monitoring applications.In contrast to the previous works utilizing materials like PVDFand PVDF-TrFe, in this research, we have employed PVAc, an inexpensiveand degradable polymeric material ,for synthesizing the nanofibrous membranes. PVAc is a rubbery, thermoplasticsynthetic nontoxic−1(∼2.73–56.06 kPa)and 0.00653 kPa−1(∼75.76–318.18 kPa).To stress the robustness and reliability of the sensors for real-lifeapplications, a series of accelerated lifetime assessment tests involvingat least 3000 cycles of tactile force loading are demonstrated. The 0.25 wt % graphene-dispersed PVAc nanofibrousmembrane-based piezocapacitive sensors are chosen for the subsequentapplications demonstrated in this work. The suitability of the sensorsfor applications in wearables and human physiological monitoring hasbeen validated by conducting a series of demonstration experimentsinvolving muscle movement detection, respiratory rate monitoring,sensorized smart shoe insoles for gait detection, and a posture sensingsmart chair for encouraging pressure-relieving maneuvers. The readinessof the proposed piezocapacitive sensors for IoT integration has beenunderscored through custom-written embedded software programs (implementedon Arduino Uno and Nano platforms) and subsequent applications inwireless gait monitoring smart insoles and posture sensing smart chairs.Finally, the degradability and subsequent recyclability of the sensorhave been demonstrated to emphasize the relevance of the sensor forthe circular electronics initiative theme. The facile sensor reportedin this work would inspire a future telemedicine ecosystem comprisingof low-powered, highly sensitive piezocapacitive sensor networks coupledwith IoT hardware for continuous monitoring of human physiologicalvitals, thereby reducing the load on existing healthcare infrastructure,as conceptually shown by the schematic in In this work,we propose a facile method for fabricating graphene-dispersedpolyvinyl acetate (PVAc) electrospun nanofiber-based piezocapacitivesensors for flexible and wearable electronics applications. A methodentailing the sandwiching of graphene-dispersed PVAc nanofibrous membranesbetween two layers of flexible fabric electrodes for fabricating afully flexible and apparel-integrable sensor is demonstrated. Dielectricresponse assessment tests are conducted on both the pristine PVAcand graphene-dispersed PVAc membranes (fabricated by spin coating)to understand the effect of the addition of graphene nanofillers onthe dielectric constant enhancement. The microcapacitor network theoryand microscopic dipole formation model have been invoked to explain the dielectric response enhancement.Material and morphological characterization experiments are conductedon both the pristine and graphene-loaded PVAc nanofibers to understandthe effect of graphene dispersion on nanofiber properties and morphologies.Electromechanical characterization experiments are conducted on thepristine and graphene-loaded PVAc nanofibrous membrane-based piezocapacitivesensors for assessing the effect of graphene nanofiller addition onpressure sensing performance. The 0.25 wt % graphene-loaded PVAc nanofibrousmembrane-based piezocapacitive sensor demonstrated superior performancewith two distinct linear regimes and pressure sensitivity figuresof 0.01355 kPaIn this work, electrospinning was employed for fabricating pristinePVAc nanofibers. To understand the effect of nanomaterial fillerson the dielectric constant/permittivity, commercially acquired graphenenanoflake dispersion was added to the pristine PVAc polymer solutionto achieve 0.1, 0.25, and 0.50% weight of graphene nanofillers inPVAc. Electrospinning was subsequently conducted to synthesize thegraphene-loaded PVAc nanofibers. More details of the polymer solutionpreparation and subsequent electrospinning process are furnished inthe The as-spunnanofibers on aluminum foil substrate are transferred from the rotatingmandrel collector and diced into 2 cm × 2 cm sections. To developall flexible, wearable, and apparel-integrable sensors, the dicednanofibrous membranes were sandwiched between two layers of circularsilver-plated nylon fabric bonded to single-strand copper wires forsubsequent electrical connections. A complete encapsulation was achievedby employing two layers of optically clear adhesive plate seals. Video SV1). The micrographs in –1) that is triggered by the defectsand a G band (at 1596 cm–1) for the characteristicof graphite/graphene. The intensity ratio of the D band to the G bandis 1.10, indicating that graphene contains many defects.In orderto understand the effect of the addition of graphene nanofillers onthe dielectric characteristics of the polymer composite, pristinePVAc and graphene-loaded PVAc nanofibers were synthesized by electrospinning.Graphene was added in varying concentrations  to a PVAc polymer solution, and electrospinning was conductedto achieve graphene-loaded PVAc nanofibers. 41 However, the graphene fillers used in this workare intended to enhance the dielectric constant of the compositesby harnessing the phenomenon of interfacial polarization. As such,eventual changes in the conductivity of the graphene nanofillers ascompared to the defect-free case do not significantly impact the pressuresensing performance of the resulting sensors. Furthermore, the relativeintensity of the peaks improved progressively with increasing thegraphene loadings, as observed from the plots in Lattice defects are inevitably introduced duringthe production/synthesisprocess of graphene, which lead to deviations from its theoreticalmechanical and electrical properties. The defects introduced duringthe synthesis process lead to changes in the bond length of the interatomicvalence bonds and potentially to changes in their conductivity.36 From the perspective of percolation theory, in the case of conductivefillers dispersed in nonconductive polymers, the dielectric constant(κ) of nanomaterial-polymer composites follows the relation:κ p|f–fc|s–, where κp represents the dielectricconstant of the insulating polymer matrix, s is anexponent with a value of ∼1, f representsthe fractional volume of the nanofiller in the polymer matrix, and fc represents the critical fractional volumeat percolation threshold.42 A number oftheories have been hypothesized to explain the phenomenon of dielectricconstant enhancement in the case of insulating polymeric materialsloaded with nanomaterial fillers.45 In particular, the microcapacitornetwork formation theory has been invoked by several researchers toexplain the giant enhancement of dielectric constant near percolationthreshold.46 The sketch in fc),several microcapacitors are formed by neighboring conductive nanofillersseparated by very thin layers of the polymer insulator. Each of theseindividual microcapacitors demonstrate a very high capacitance figureand subsequently contribute to the overall enhancement of the dielectricconstant of the composite.43 Another mechanism thatalso contributes to the dielectric constant enhancement is the microscopicdipole formation model.47 In this case, applicationof an external electric field to the nanomaterial polymer compositeleads to charge accumulation at the interface between the nanomaterialfillers and the polymer matrix, which subsequently leads to interfacialpolarization (Maxwell–Wagner-Sillars polarization) as depictedby the schematic in Researchworks conducted in the past have established that the incorporationof nanomaterial fillers in polymeric materials generally improvestheir dielectric performance.34 The microscopicdipole model, as discussed earlier, is likely to be the contributingfactor behind the dielectric constant enhancement observed in thiswork.The plot in The piezocapacitivesensors proposed in this work utilize graphene–PVAc nanofibrousmembranes as the dielectric layer. For a nanofibrous membrane-basedcapacitor with air voids, the initial effective dielectric constantis a combination of the dielectric constants of air and the nanofibrousmaterial. Upon application of an external pressure, the gap betweenthe electrodes reduces, thereby squeezing the sandwiched nanofibrousmembrane and replacing the low permittivity air voids with high permittivityof the nanofibrous material in the process. This pressure-induceddensification process increases the effective dielectric constantof the capacitor. The phenomenon of pressure-induced dielectric constantenhancement coupled with the usual thickness change significantlyenhances the sensitivity of the sensor. 33 The relationbetween the external pressure (p) and capacitancechange (ΔC) is given by the following expressionC0 is theinitial capacitance of the sensor and E0 is the Young’s modulus of the dielectric layer.24 For low pressure regimes, the applied pressurebeing less than the Young’s modulus (p ≪ E0), the quadratic term can be neglected, andthe normalized capacitance change is expected to demonstrate a linearbehaviorIn the past, Kim et al. and Sharma et al. independentlyproposed analytical models to explain the dependence of capacitancechange on applied external pressure.24 From the above discussion, it is evident thatnanofibrous membranes with air voids are more likely to be suitablefor the development of wearable piezocapacitive sensors.Kim et al. argued that, atlow pressureregimes, the normalizedcapacitance change for nanofibrous piezocapacitive sensors is doublethat of their bulk dielectric material counterpart (without air voids).Figure S1). The mismatch between the response and recovery times can be attributedto the hysteresis of the graphene–PVAc nanofibrous membrane.To further understand the effect of graphene nanofiller addition,the pressure sensitivity of the pristine PVAc nanofiber-based sensorwas compared with that of the graphene-dispersed nanofiber sensors.The normalized capacitance change versus the applied uniaxial pressurewas plotted, as shown in –1 (in the pressure range 9.85–80.30 kPa)and 0.00135 kPa–1 (in the pressure range 95.45–275kPa) with R-square values of 0.9873 and 0.9833, respectively.Similar uniaxial pressure sensitivity assessment tests were conductedon the graphene-dispersed PVAc nanofiber-based sensors, as shown bythe plots in 33 The dynamic range, sensitivity,response/recovery times, and degradability of the sensor reportedin this work are compared with recent similar piezocapacitive sensorsin the literature and are presented in Toassess the pressure sensing performance of the graphene–PVAcflexible pressure sensor, a series of tests involving tactile pressuresensing were performed. Figure S2a). The plot in 51Owing to its maximum pressure sensitivity,the 0.25wt % graphene–PVAcnanofiber-based sensor was chosen for further mechanical and lifetimeassessment analyses. To assess the compressibility and hysteresisbehavior, the sensor assembly was subjected to a series of 10 cycliccompressive loading and unloading. Further details of the test setupare furnished in the Supporting Information section S2a. The Figure S2b). The plotin st and 10thcycles with the average stress–strain characteristics (averagedover 10 cycles). The average tensile modulus of the nanofiber membranewas determined as 212.69 MPa with an ultimate tensile strength of4.61 MPa at 15.10% strain (elongation at break).Furthermore, the tensile modulus and ultimate tensilestrengthof the 0.25 wt % graphene-loaded PVAc nanofiber membrane were assessedby subjecting it to a series of cyclic tensile loading and unloading.Further details of the test setup are furnished in the SupportingInformation section S2b. The To demonstratethe robustness and reliability of the sensor forlong term applications, accelerated lifetime assessment experimentsinvolving a combined total of 3000 cycles of tactile force loadingat three different force levels  were conducted.The photograph in To demonstrate the applicability of ourpiezocapacitive sensorsfor physiological function monitoring applications, the 0.25 wt %graphene-dispersed nanofiber-based sensors were chosen owing to theirsuperior pressure sensing performance, as demonstrated previously.The plot in N = 107).52 Peak plantar pressures werereported to lie in the range 53–139 kPa. In our previous research,we have demonstrated utilizing graphene–PDMS squeezable sensorsfor developing smart sensorized shoe soles for gait monitoring applications.53 As seen previously, the sensors presented inthis work have been calibrated for pressure sensitivities in the rangeof ∼2–320 kPa that is the regime of interest for plantarpressure sensing. Here, we have utilized the graphene–PVAcnanofiber sensors for demonstrating IoT-enabled gait monitoring. Asdiscussed previously, capacitive sensors are more suitable due totheir low hysteresis, fast response, and low power budget. Three identicalsensors were secured on the heel, lateral midfoot, and toe ball regionsof a soft shoe insole and placed inside a sport sneaker. For dataacquisition, embedded systems software utilizing the Arduino Nanoplatform was employed. The details of the connections are furnishedin the experimental section. For wireless data acquisition, an ArduinoHC05 Bluetooth module utilizing the serial communication protocolwas used. The IoT enabled system utilizing the Arduino nanoplatformis schematically represented in –1 (determined by multiplying the step length by cadence).The sensorized shoe insole demonstrated in this work can potentiallybe used by physicians to determine problems with gait and determineif further diagnostic tests are warranted to find the underlying condition.In the past,Cavanagh et al. have reported standing plantar pressure distributionunder human feet for a heterogeneous sample of feet . The solution was stirred using a hot platemagnetic stirrer at 60 °C to accelerate the decomposition process.The large specific surface area of the nanofibrous membrane providesmore area for the water–ethanol solution to penetrate, therebyfacilitating the decomposition process. At the end of 30 min, cleargraphene dispersion in the solution was observed. The solution wasremoved from the stirrer and allowed to cool to room temperature.By the end of 60 min, graphene precipitation was observed, and thesolution turned whitish, indicating a homogeneous solution of PVAcin the water–ethanol mixture. The photographs in With the growing burden of electronicswaste lately and their detrimental impact on the environment and publichealth, there is a surge in demand for transient electronics.33 can be used in conjunction with flexible andbiodegradable packaging to circumvent the recyclability issue oftenassociated with deposited metal-based thin film electrodes.Though the PVAc-graphene nanofiber membrane isdegradable, thelack of suitable degradable packaging restricts the applicabilityof the reported sensor for applications demanding true, fully degradablesensors. To make the sensor fully degradable yet robust and reliable,water-soluble packaging materials like polyvinyl alcohol (PVA), polyethyleneglycol (PEG), and water-soluble hydrogels can be considered in thefuture. Furthermore, conductive polymer-based flexible electrodes−1 (∼2.73–56.06 kPa)and 0.00653 kPa–1 (∼75.76–318.18 kPa).A series of accelerated lifetime assessment tests involving at least3000 cycles of tactile force loading at three different forces wereconducted to demonstrate the robustness and reliability of the sensor.Finally, the 0.25 wt % graphene-dispersed PVAc nanofibrous membrane-basedsensors were chosen for demonstration experiments. A series of humanphysiological parameter monitoring experiments comprising muscle movementdetection, respiratory rate detection, and gait monitoring were conducted.To further emphasize the readiness of the sensors for IoT applications,a wireless smart gait monitoring shoe insole and a posture sensingsmart chair, coupled with a custom embedded program implemented onArduino Uno and nanoplatforms were demonstrated. Finally, the suitabilityof the proposed sensing element for the circular electronics initiativetheme has been demonstrated through the simple decomposition of thesensor in a water–ethanol solution.In conclusion, this work established afacile method of utilizinggraphene-dispersed PVAc nanofibrous membranes for IoT-enabled wearablepiezocapacitive sensing applications. A series of electrical and materialcharacterization tests involving dielectric response assessment, SEMand TEM observation, and Raman spectral analyses were conducted onthe nanofibers to understand the effect of graphene dispersion onnanofiber morphology, and electrical properties. Microcapacitor networkand microdipole formation mechanisms were invoked to explain the observednanofiller-induced dielectric constant enhancement. A series of dynamicuniaxial pressure sensing performance tests were conducted on thepristine and graphene-dispersed PVAc nanofibrous membrane-based piezocapacitivesensors to observe and understand the effect of graphene nanofilleraddition on pressure sensing performance. The nanofibrous membranewith 0.25 wt % graphene loading showed superior pressure sensing performancewith two distinct linear regimes and pressure sensitivity figuresof 0.01355 kPaMW 500,000 g mol–1), N,N-dimethylformamide (DMF),and electrochemically exfoliated graphene ink (1 mg mL–1 in DMF) purchased from Sigma-Aldrich, the Netherlands, were used.For the pristine PVAc nanofibers, 1.5 g of PVAc was dissolved in 10mL of DMF and stirred at room temperature using a magnetic stirrerto achieve 15% (w/v) solution. For the graphene–PVAc nanofibers,the commercially acquired graphene dispersion was added to the PVAcpolymer solution and subsequently sonicated employing an ultrasonicbath sonicator to achieve 0.1, 0.25, and 0.50% weight of graphenenanofillers in PVAc, while keeping the overall concentration of thesolution fixed at 15% (w/v). An electrospinning setup (NanoSpinnerNE300) from Inovenso electrospinner fitted with a stainless-steelrotating mandrel collector was used for electrospinning the nanofibers.Inovenso IPS-14RS syringe pump fitted with a 10 mL syringe was usedto feed the polymer solution through a needle (20 G) at a constantflow rate of 1 mL h–1. The electrospinning was conductedfor the pristine PVAc solution and different concentrations of thegraphene-loaded solutions by applying a potential difference of 15kV between the tip of the needle and the rotating mandrel collector(rotating at 2200 rpm) separated by 15 cm. The electrospinning processwas conducted for 3 h to obtain a film of uniform nanofibers depositedon the aluminum foil substrate.For electrospinning of pristine PVAc and graphene–PVAc nanofibers,PVAc beads  was employed. Samples havingdimensions of 1 cm × 1 cm were sputtered with gold and placedon appropriate SEM stubs for subsequent imaging. For conducting theimaging experiments, an acceleration voltage of 7 kV and a spot sizeof 3.0 were employed.To confirmthe dispersion ofthe graphene nanoflake fillers within the PVAc nanofibers, Raman spectroscopicanalyses and TEM imaging were conducted. Raman spectra analysis wascarried out on a PerkinElmer Raman station by using 633 nm laser excitation.Raman analyses were conducted on both the pristine and graphene-dispersedPVAc nanofibers. For the TEM measurements, the specimens were preparedby directly transferring the nanofibers from the aluminum foil tocopper grids. Bright-field imaging was performed with a JEOL 2010at an accelerating voltage of 200 kV.Thefabrication flow for developing the pristine PVAc and graphene–PVAcnanofiber pressure sensors is schematically represented in 55 was employed for exporting the data from theArduino serial output to CSV format. For all the experiments involvinghuman motion monitoring and the smart chair, unamplified signal outputswere presented in the article.For demonstrating the capability of the sensorin IoT-enabled humanphysiological monitoring applications, a custom-made capacitance meterutilizing the Arduino Uno and Arduino Nano platforms was developed.The embedded system setup utilizes an open-source Arduino capacitorlibrary that enables the measurement of capacitance in the range 0.2pF–100 μF. For measurement and sensing experiments, eachindividual sensor was connected to an analog pin and a digital pinof the Arduino Uno/Nano board. For data acquisition using the Arduinoplatform, an open-source plug-in code (Ardu Spreadsheet 1.0)


Distal radius fractures are the most prevalent upper extremity fractures, posing a significant public health concern. Recent studies comparing regional and general anesthesia for postoperative pain management after these fractures have yielded conflicting results. This meta-analysis aimed to compare the effectiveness of regional and general anesthesia concerning postoperative pain management and opioid consumption following distal radius fracture surgery. A comprehensive search was conducted in PubMed, Cochrane Library, and EMBASE databases to identify relevant randomized controlled trials. Four randomized trials involving 248 participants were included in the analysis. A pooled analysis revealed that regional anesthesia led to significantly reduced postoperative pain scores at 2 h compared to general anesthesia . However, no significant differences in pain scores were observed between the two anesthesia types after 12 h post-surgery. Regional anesthesia was associated with lower total opioid consumption  and fewer occurrences of nausea and vomiting compared to the general anesthesia. Nonetheless, opioid consumption on the first day post-discharge was significantly higher in the regional anesthesia group . The analgesic superiority of regional anesthesia is confined to the early postoperative hours with overall lower opioid use but a notable increase in opioid consumption on the first day post-discharge, potentially attributable to rebound pain. Distal radius fractures are the most frequently encountered fractures in the upper extremities and pose a significant public health concern, especially among the elderly . NumerouSurgical fixation of distal radial fractures can be performed under general (GA) or regional anesthesia (RA). Regional anesthetic nerve blocks have a positive impact on various aspects of the surgical process, such as reduced acute postoperative pain, decreased opioid consumption, and improved patient satisfaction . HoweverRandomized controlled trials comparing RA with GA for postoperative pain management after distal radius fractures have reported conflicting findings. Two early randomized controlled trials ,13 reporAlthough some reviews have been published on this topic, the studies included mixed levels of evidence and lacked quantitative analysis ,16. TherThis meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement . We did Pubmed, Cochrane Central Register of Controlled Trials, and EMBASE database were searched for articles with language restricted to English. Initially, we did not restrict the research type or year of publication to avoid missing relevant articles. Search algorithms were developed for each database (without a set time limit). A combination of search terms was employed, encompassing the title, abstract, Medical Subject Headings (MeSH), Emtree, and keywords. The search terms included “wrist fracture[MeSH]”, “distal radius fracture[tiab]”, “anesthesia[MeSH]”, “regional anesthesia[tiab]”, “nerve block[tiab]”, “brachial plexus[tiab]” and “general anesthesia[tiab].Two authors  independently conducted the initial database search and screened the titles and abstracts for eligibility. The full manuscript was then reviewed for inclusion and exclusion criteria. Discrepancies were resolved by consensus among the reviewers. We also performed manual searches of the references in the relevant articles and previous systemic reviews to avoid missing eligible articles.We used the Population, Intervention, Comparator, Outcome and Study design (PICOS) framework to formulate eligibility criteria . StudiesThe methodological quality of the studies was evaluated using the Cochrane Collaboration’s Risk of Bias Tools . These cData extraction and outcome measurement were conducted independently by two authors (SGP and SHL). Any discrepancies that emerged were subject to discussion, and final decisions were reached through mutual agreement among the evaluators. We employed a pre-designed data spreadsheet for data extraction. It included key information such as author names, publication year, study design, sample size, patient demographics , anesthesia methods, primary outcomes, and complications.The following outcomes were investigated: postoperative pain levels, opioid consumption , and occurrences of nausea and vomiting.2 statistics. Values > 25%, >50%, and >70% were regarded as low, moderate, and high heterogeneity, respectively. Random effects models for meta-analysis were applied in the presence of moderate to high heterogeneity (I2 > 50%); otherwise, fixed effects models were used. The inverse variance weighting method was employed to derive pooled estimates of SMD or OR, along with their respective 95% CI. The results of the meta-analysis were considered statistically significant at p < 0.05. Subgroup analysis was only conducted for postoperative VAS pain at 24 h to explore potential explanations for the observed heterogeneity, given the limited number of articles available. A sensitivity analysis was conducted by omitting single eligible studies to evaluate the influence of each study in primary outcomes. A funnel plot was originally planned to detect publication bias but was excluded from the analysis owing to its limited interpretability caused by the small number of included studies. Statistical analyses were performed using the Comprehensive Meta-analysis Software version 3  and Review Manager .The primary outcomes of this meta-analysis included postoperative pain levels and opioid consumption, with the secondary outcome being the incidence of nausea and vomiting following distal radius fracture surgery. We conducted a pooled analysis to compare multiple clinical outcome measures between the groups depending on the availability of the data. For all comparisons, standardized mean differences (SMD) with 95% confidence intervals (CI) were used for continuous variables, while odds ratios (OR) with 95% CI were calculated for binary variables. When medians with interquartile ranges were reported without means with standard deviations (SD), SDs were calculated using the quantile estimation approach . BetweenThe initial search yielded 412 articles, 4 of which met the inclusion and exclusion criteria and underwent qualitative analysis . All fouThe postoperative pain score through visual analogue scale (VAS) at 2 h was assessed in the four studies, which involved 247 wrists. All four studies consistently showed that the RA group had lower pain scores than the GA group at 2 h. The meta-analysis demonstrated significantly lower VAS scores in the RA group than the GA group. The standardized mean difference (SMD) was calculated as −2.03, with a 95% confidence interval (CI) ranging from −2.88 to −1.17 A. The re2 = 94%).Two studies involving 108 wrists examined VAS pain scores at 12 h. One study demonstrated significantly higher pain VAS scores in the RA group than the GA group at 12 h, whereas another study found no significant difference in pain scores between the groups. A meta-analysis revealed that the pooled effect size was not significant (2 = 86%). The heterogeneity was resolved when the investigations were pooled within the subgroup on outpatient surgical settings . The sensitivity analysis revealed no change in the result of the original analysis.The pain score at 48 h was assessed in three studies with a total of 176 wrists. One study reported higher pain VAS scores in the GA group than in the RA group, whereas the other two investigations did not find any significant differences between the groups. The results of the meta-analysis showed no significant difference in the VAS pain scores between the two groups at 48 h (2 = 58%).The total amount of opioid consumption after distal radius fracture surgery was reported in three studies that included 132 wrists. Among these studies, two reported a higher total opioid consumption in the GA group than in the RA group, whereas the remaining study did not find a significant difference in opioid consumption between the two groups. The results of the meta-analysis demonstrated that the GA group had significantly greater total opioid consumption than the RA group (2 = 0%).Three studies consistently reported higher opioid consumption in the post-anesthesia care unit (PACU) or before discharge in the GA group than in the RA group. The meta-analysis indicated a significant increase in opioid consumption in the RA group compared to the GA group during this period (2 = 0%).Opioid consumption after postoperative discharge, specifically on the first day, was evaluated in two investigations focusing on ambulatory surgery. Both studies reported higher opioid use in the RA group than in the GA group. The results of the meta-analysis indicated that the patients in the RA group had significantly greater opioid use than those in the GA group (2 = 0%) and vomiting (2 = 0%) in patients who underwent RA compared to those who received GA.Postoperative nausea and vomiting were assessed in two studies involving 140 wrists. Both studies consistently revealed a higher incidence of postoperative nausea and vomiting in the GA group than in the RA group. The results of the meta-analysis indicated a lower risk of postoperative nausea (Prior investigations comparing RA and GA for postoperative pain management have yielded conflicting results, posing a significant challenge to clinicians in deciding which mode of anesthesia to employ in order to enhance post-operative recovery and reduce oral opioid use. In this meta-analysis, we identified four randomized controlled trials that directly compared RA and GA for postoperative pain management after distal radius fracture surgery. This analysis aimed to provide insights into the optimal choice of anesthesia for managing postoperative pain in this specific surgical context. Furthermore, it provides insight into rebound pain following RA, an aspect often overlooked in the context of distal radius fracture fixation. Our meta-analysis revealed significant differences in the early postoperative pain and opioid consumption based on the anesthesia method. Specifically, the GA group had significantly higher pain scores at 2 h compared to the RA group; however, opioid consumption after postoperative discharge on the first day was significantly increased in the RA group compared to in the GA group. The total opioid consumption was greater in the GA group than in the RA group. However, no significant differences were observed between the two groups in the VAS pain scores after 12 h.RA was associated with decreased postoperative pain scores at 2 h compared to GA. However, the association diminished after the early postoperative period, and no significant differences in pain scores were observed between the GA and RA group after 12 h. The early postoperative pain patterns were significantly influenced by the anesthesia method. Patients with RA consistently exhibited a rapid increase in pain scores on the first operative day once the effects of regional anesthesia wore off. Some patients experienced an abrupt increase in pain, necessitating more pain medications. In contrast, patients with GA showed a continuous decrease in pain during the early postoperative period. Patients who received RA for ambulatory wrist fracture surgery reported a higher rate of unplanned healthcare resource utilization caused by post-discharge pain than those undergoing GA . The hetOpioids continue to have a significant role for postoperative pain management, but their use in the postoperative period may elevate the risk of adverse effects, including nausea and vomiting, respiratory depression, sedation, pruritus, urinary retention, and sleep disturbances . Total oThe higher incidence of nausea and vomiting in the GA group could be attributed to the differences in total opioid consumption. Postoperative nausea and vomiting are known to be influenced by various factors associated with the patient, surgery, and anesthesia . PreviouThe main limitation of this meta-analysis is the small number of included studies. The inclusion criteria were limited to randomized controlled trials, resulting in a limited pool of studies eligible for the meta-analysis. However, it was chosen to ensure a high level of evidence and facilitate high-grade recommendations. Additionally, heterogeneity in outcome reporting was observed among the included studies. Not all of the included studies provided data on opioid consumption, and the timing of follow-up assessments varied across studies. Further research with larger sample sizes and diverse study settings is warranted to provide a more comprehensive understanding of this topic. In addition, treatment-related variables, including the time to surgery and initial closed reductions before surgery, and injury characteristics, such as open or closed fractures, could potentially influence postoperative pain level after distal radius fracture ,34, but The use of RA for distal radial fracture surgery was associated with reduced postoperative pain scores during the early postoperative period only. However, after 12 h, no significant differences in the VAS pain scores were observed between the GA and RA groups. Total opioid consumption was higher in the GA group than in the RA group. However, opioid consumption on the first day after discharge was significantly higher in the RA group, potentially because of rebound pain. These findings provide valuable insights for the selection of an appropriate anesthetic method based on patient characteristics and specific trauma surgeries.


Fragility fractures commonly manifest as complications in individuals with diminished bone mineral density and other risk factors. The hip, vertebral body, and wrist are the most documented locations of fragility fractures among patients with osteoporosis or osteopenia. This report presents a rare case of multiple fragility fractures of the right ribs accompanied by an adjacent right chest wall hematoma in an otherwise healthy 60-year-old woman after participating in cardiopulmonary resuscitation (CPR) training. Upon further workup, a diagnosis of osteopenia was established. This report aims to underscore a potential complication in those performing CPR and outline the clinicoradiological presentations, diagnostic workup, and treatment of fragility fractures in patients with no history of prior underlying skeletal conditions or malignancy. Rib fractures, sternal fractures, and lung contusions are well-documented complications in patients undergoing cardiopulmonary resuscitation (CPR) . HoweverThis is a case report of a 60-year-old woman who sustained multiple rib fragility fractures and a chest wall hematoma following participation in CPR training. Subsequent workup confirmed the diagnosis of osteopenia. This report aims to highlight the clinicoradiological presentations of rib fragility fractures as well as the typical diagnostic workup and management in a patient without prior malignancy or underlying skeletal conditions. It also underscores the need for caution among osteopenic or osteoporotic patients when engaging in strenuous activities such as chest compressions.A 60-year-old woman presented to the outpatient clinic with the chief complaint of right shoulder and upper back pain. She reported that the pain began after a CPR class a few days prior. Bruising later developed over the area of pain. An image captured on her phone revealed a small area of bruising on the right posterior flank at the start of the pain. Over a few days, the pain worsened, and the bruised area gradually expanded over the entire right posterior flank, likely over the region of the right trapezius and latissimus dorsi muscles. The patient reported receiving a subacromial steroid injection by an orthopedic specialist within days following the CPR class. She was additionally prescribed cyclobenzaprine hydrochloride and meloxicam, which she denied taking due to concerns about worsening bruising. She admitted to taking acetaminophen and leftover hydrocodone. The remaining review of systems and past medical history at this time were negative for prior trauma, anticoagulant consumption, or diagnosis of cancer or any underlying bone condition. Her surgical, familial, and social histories were non-contributory to the current presentation.The physical exam demonstrated an area of tenderness and muscular distension palpated over the right posterior flank, possibly related to the right trapezius and/or latissimus dorsi muscle, accompanied by significant bruising. The remaining physical exam was normal. The patient's comprehensive blood cell counts with differential were all within normal limits, which suggested against hematological malignancy. X-ray of the right shoulder in the frontal view revealed multiple mildly displaced rib fractures Figure . A magneThe patient was counseled to adopt a bone-healthy lifestyle, incorporating weight training routines and a diverse diet. Vitamin D supplementation and bisphosphonate therapy were initiated. A routine DEXA scan was also recommended every two years. The patient has not had a follow-up visit since the encounter for the diagnostic workup, although no symptom exacerbation was reported.Rib fractures are categorized as traumatic or nontraumatic, with thoracic trauma being the most common cause of all rib fractures . NontrauRadiographs can identify fragility fractures but have many limitations, successfully detecting only 20-38% of such fractures . ConversDEXA scans offer precise evaluation of mineralized bone content in the skeletal system, significantly enhancing the detection of osteopenia and osteoporosis. According to the DEXA evaluation criteria by the World Health Organization (WHO), bone mineral density (BMD) T-scores falling between -1 and -2.5 at the spine or hip indicate osteopenia, whereas T-scores < -2.5 indicate osteoporosis . DEXA scOver 80% of postmenopausal women with fractures have T-scores > -2.5. Since the number of postmenopausal women in the osteopenic range is much higher than those in the osteoporotic range, 82% of fragility fractures occur in the osteopenic range, aligning with our presented case . A patieCPR is essential to basic life support (BLS) or advanced cardiovascular life support (ACLS). However, it can be physically demanding, especially for those with low BMD, leading to a higher fracture risk. Limited data exist on CPR guidelines for high-risk rescuers. Modified CPR methods can be considered, like mechanical devices or increased core and body weight engagement to reduce arm strain. Additionally, rotating rescuers can alleviate fatigue and strain on only one individual. CPR rescuers at high risk should consult a medical professional or certified CPR instructor before performing CPR.This case report highlights the susceptibility to fragility fractures among osteopenic individuals, particularly when participating in physically demanding activities such as CPR. While hip, vertebral body, and wrist fractures are the most frequent fractures associated with osteoporosis, the systemic impact of osteopenia on the skeleton translates to an elevated risk of fractures in various skeletal structures, including less common sites like ribs. Consequently, there is a necessity for enhanced health criteria for CPR rescuers. Moreover, prompt diagnostic evaluations and a multidisciplinary approach to managing fragility fractures are essential in reducing the likelihood of recurrent fractures, thus minimizing subsequent morbidity and mortality.


Perineural invasion (PNI) in cutaneous squamous cell carcinoma (SCC) of the periocular region is a prognostic marker of adverse tumour outcomes. PNI carries a well-established risk of tumour recurrence, regional metastasis and higher likelihood of mortality. This review will explore and stratify the risks conferred by histological PNI parameters. The radiological features of perineural spread (PNS) and the imaging sequences that delineate these findings will also be highlighted. Surgical excision with en face margin control is the preferred technique for achieving histological clearance. Adjuvant radiotherapy improves treatment outcomes in the setting of concomitant high-risk features. For locally advanced or metastatic cutaneous SCC, immunotherapy represents a novel treatment alternative. This review will provide an algorithm for the diagnosis and management of periocular SCC with PNI and PNS. Squamous cell carcinoma (SCC) is the second most common cutaneous malignancy of the eyelid and periorbital region in the West, while large epidemiological studies from India and China have shown that it is the third most prevalent malignant eyelid tumour –3. SCC iPerineural invasion (PNI) is a histological marker of aggressive disease that is associated with locoregional recurrence, metastasis and reduced tumour-specific survival , 4. It oIt is important to understand the distinction between the terms PNI and perineural spread (PNS) as the latter confers a different prognosis and management paradigm. PNI is a histological term that refers to findings within a resection specimen. PNS refers to clinically manifest symptoms of pain or dysesthesia, and/or radiologically detectable perineural infiltration. PNS has also been termed ‘clinical/radiological PNI’ which may be a source of confusion and, hence, in this review we will use the terms PNI and PNS as defined above in concordance with the current literature.It should be noted that while there is good evidence for the prognostic implications of PNI/PNS, there is a lack of robust randomised controlled trials to provide definitive management guidelines. Furthermore, the majority of evidence is derived from head and neck cSCC rather than the relatively sparse periocular SCC literature which is mostly comprised of retrospective studies.This review aims to provide clinicians with a pragmatic approach to the risk stratification and management of periocular SCC with PNI and PNS. Histological features of PNI and their prognostication will be evaluated. En face margin control techniques are preferable to confirm histological clearance. Adjuvant radiotherapy is warranted in the presence of concomitant high-risk histological and clinical features. The clinico-radiological characteristics and management implications of PNS are also reviewedThe peripheral nerve consists of three layers: (1) the innermost endoneurium encircling axons, (2) the middle perineurium surrounding fascicles, and (3) the outermost epineurium which binds fascicles to form a peripheral nerve . The perAt a cellular level, SCCs may remodel the peri-tumoral environment via neurotrophic growth factor receptors  and nerve cell adhesion molecule (N-CAM), which facilitate the attachment and invasion of tumour cells beyond the perineural sheath , 19. DepPNI is characterised by microscopic tumour invasion into the space between or beneath the interdigitating perineural layers, involving at least one-third of the nerve circumference Fig.  16, 22,,22, 23. The location of PNI relative to the tumour mass has prognostic significance. Intratumoral PNI describes invasion within the bulk of the tumour mass, which appears to have little relevance regarding tumour outcomes Fig. . On the PNI can be further subdivided into ‘focal’ involvement with 1–2 positive nerves, or ‘extensive’ involvement of greater than 2 nerves on the histological field . Focal PCutaneous SCC (cSCC) has been previously associated with so-called perineural skip lesions . TherefoPNI with large-calibre involvement (≥0.1 mm in diameter) is a poor prognostic marker in cSCC and significantly associated with other high-risk histological characteristics. Large-calibre PNI Fig.  is more Histological parameters of PNI have been evaluated to determine if there is a spectrum of PNI ‘severity’ . These pIn a separate multicentre retrospective study of cSCC, depth of nerve involvement was a significant factor associated with lymphatic progression and disease-specific death in univariate analyses. Although deep nerve involvement lost statistical significance on multivariate calculations, it commonly occurs in the presence of other high-risk tumour factors and should nonetheless warrant caution .PNI in cSCC is ubiquitously considered a poor prognostic risk factor in international cancer guidelines –45. HoweThe Australian Cancer Council (2019) and American National Comprehensive Cancer Network (NCCN) Version1.2022 guidelines recognise the periorbital region and eyelid as high-risk locations for overall prognosis in cSCC , 47.Tumour size greater than 2 cm and a higher AJCC T category (defined by tumour size and degree of eyelid margin involvement) are both important determinants of PNI risk , 43, 48.For periocular SCC, longer duration of the lesion is associated with a higher risk of orbital invasion and PNI .PNI is significantly more common in recurrent SCC than primary tumours. Furthermore, lesions that have undergone a greater number of surgical excisions, indicative of recurrent or aggressive disease, are more likely to have PNI .Aggressive SCC phenotypes with atypical histology  and moderate to poor differentiation are associated with a higher incidence of PNI , 48. TheTumour thickness greater than 6 mm is associated with higher risk of recurrence and metastasis .Other risk factors identified for nodal metastasis in head and neck cSCC are lymphovascular invasion, poorly differentiated histology and chronic immunosuppression , 13, 51.The 40-gene expression profiling test is a newly validated assessment that identifies cSCC lesions as low, high or very high-risk, of which the latter group has a ≥50% metastatic risk. Appropriate risk stratification enables judicious use of resources for aggressive surveillance and high-intensity management strategies .Although this review focus is on PNI, it would be remiss not to highlight other parameters that increase the risk of developing PNI and individually contribute to an aggressive tumour profile. A summary of these high-risk parameters is provided in Table PNS predominantly affects the trigeminal and facial nerves due to an extensive plexus of subcutaneous nerves , 4, 53. The median time between onset of primary cSCC and PNS is 16 months . A summaOrbital SCC associated with PNS can occasionally present with a subcutaneous or intraorbital mass in the distribution of the involved nerve. These masses may have a significant cystic component , 58, 60.On MRI, PNS is characterised by asymmetrical thickening and enhancement of the involved nerve , 63. OccOn T1-weighted sequences, effacement of fat pads at the skull base foramina is an important early sign of PNS. Fat signal alterations may be seen along the course of the ophthalmic nerve at the superior orbital fissure, within the orbital roof superior to the superior rectus/levator complex and at the supraorbital foramen. Changes in the peri-antral fat pads near the infraorbital foramen, foramen rotundum and pterygopalatine fossa may indicate PNS along the maxillary nerve and its infraorbital branch. Fat density changes at the stylomastoid foramen are indicative of facial nerve involvement .To detect PNS to the trigeminal and facial nerve branches, a targeted field of view on axial slices should extend from the frontal sinus to the hyoid, and on coronal sections, it should encompass the nasal ala, anterior orbital border and the pons.T1WI is the sequence best placed to visualise effacement of fat pads along the course of involved nerves and at the foramina. Contrast-enhanced T1WI with fat suppression enables the evaluation of nerve enlargement and enhancement. T2WI with fat saturation can detect denervation and secondary atrophy of the muscles of mastication and facial expression. Affected muscles demonstrate a high T2 signal and with time, adipogenic replacement will be evident on non-fat-suppressed sequences , 67.Apparent diffusion coefficient (ADC) has emerged as a useful quantitative measure of the diffusion weighted imaging sequence. Restricted diffusion, and therefore a lower ADC value, may be representative of cytotoxic oedema and hypercellularity from neoplastic infiltration of an involved nerve , 69. TheHigh-resolution MRI performed with a dedicated field of view and smaller slice thickness is the imaging modality of choice for visualising PNS . ExampleComputed tomography has a limited role for detection of PNS. Although enlargement of neural foramina can be visualised on bone windows, this is often a late sign by which time neural enlargement should already be evident on MRI.The role of hybrid CT-PET imaging is still being determined, but it may be useful in advanced disease for evaluation of nodal or distant metastasis and treatment response. The findings on CT-PET indicative of PNS include (a) linear or focal enhancement along the course of the cranial nerves and neural foramina, and (b) asymmetric fluorodeoxyglucose uptake in the pterygopalatine fossa, Meckel’s cave and cavernous sinus .PNI and PNS are risk factors for locoregional and distant metastasis. Patients with palpable lymph nodes can be referred for confirmatory fine needle aspiration or core biopsy, depending on institutional practice. If there is no palpable lymphadenopathy, the indications for nodal imaging are unclear. It should be noted that the false negative rate of clinical examination for regional nodal metastasis is 15–30% . TherefoThe role of sentinel lymph node biopsy (SLNB) in cSCC is ill-defined and there is no data to suggest that SLNB status affects recurrence or survival outcomes . The NCCBoth PNI and PNS are markers of an aggressive tumour profile. However, PNI portends a better prognosis than PNS and has comparatively better local control and cause-specific survival rates  .In the periocular SCC literature, PNI positivity appears to be a strong predictor for regional and distant metastases, though these are small studies with insufficient data on long-term outcomes. In Faustina et al.’s series, 55.6% of PNI-positive tumours (5/9 patients) developed regional nodal metastasis and 22.2% (2/9 patients) had distant metastasis, despite treatment with wide local excision and postoperative radiotherapy . In McNaThe association between PNI, recurrence and disease-specific death can be extrapolated from the head and neck cSCC literature , 76. TheThe periocular region is an inherently high-risk location and PNI is not always apparent in a preoperative biopsy. Therefore, for all periocular SCC lesions, we recommend surgical excision with intraoperative margin control in the first instance. For lesions without orbital invasion, en face margin control techniques such as Mohs micrographic surgery (MMS) or complete circumferential peripheral and deep margin assessment (CCPDMA), are preferred for establishing true histological clearance. In the Australian Mohs database study of periocular SCC, all cases with PNI (4.3% of the cohort) were treated with MMS alone and experienced no recurrence following 4–6 years of follow-up .In the presence of radiologically confirmed orbital invasion, our preference is to perform CCPDMA with fast-track paraffin sections and delayed reconstruction, as appropriate orientation of frozen sections of orbital fat can be difficult. In the context of large tumours with orbital invasion, peripheral margin assessment may be difficult and standard fine breadloaf sections may be utilised. If the resection specimen demonstrates very high risk PNI features or if there are other multiple concurrent high-risk factors, then a multidisciplinary consult should be sought for consideration of adjuvant radiotherapy.1) to superior orbital fissure, infraorbital nerve (V2) to foramen rotundum, mandibular nerve (V3) to foramen ovale, facial nerve to stylomastoid foramen.Zone 1: ophthalmic nerve  [For Zone 2 disease, orbital exenteration with resection of the relevant ganglion is appropriate. Although there have only been small cohorts of ≤50 patients reported with such extensive disease, surgical resection combined with postoperative radiotherapy can achieve feasible long-term survival outcomes, with 5-year disease-specific survival of 64–75% , 82. A l 0.0001) .Aggressive surgical resection is often deemed unsuitable for Zone 3 disease due its inherent association with lower survival likelihood and the risk of significant perioperative morbidity , 83.For periocular SCC, some authors recommend adjuvant radiotherapy for all lesions with PNI or PNS , 57. TheIn the head and neck cSCC literature, PNS portends a poor prognosis and therefore combined resection and elective radiotherapy to the first echelon of regional lymph nodes has been advocated regardless of the margin status , 82. HowThere is a paucity of data on the utility of chemotherapy in periocular or head and neck cSCC. Theoretically, chemotherapy should only have a limited role. Nerves affected by PNI undergo axonal degeneration and segmental infarction. As a result, blood supply to the perineural vascular plexuses is compromised, which inhibits the delivery of chemotoxins to tumour cells within the perineural space .Individual case reports of multi-agent chemotherapy using methotrexate, bleomycin and cisplatin have found promising results for orbital perineural spread, but in the setting of progressive intracranial disease, there is no evidence of definitive improvement , 90. It Immune checkpoint inhibitors represent a novel treatment option for surgically unresectable cSCC with locally advanced or distant metastatic disease. In Migden et al.’s seminal paper on immunotherapy in metastatic cSCC, cemiplimab, a monoclonal antibody directed against the PD-1 receptor pathway, elicited a 50% response rate . There iIn 2018, cemiplimab received approval from the US Federal Drug Administration to treat locally advanced or metastatic cSCC that did not meet criteria for curative surgical resection or curative radiotherapy. The following year, cemiplimab was approved by the European Commission and NICE advisory committees, the latter of which has made it available on the National Cancer Drugs Fund. In Australia, it is provisionally approved by the Therapeutic Goods Administration for similar candidates. The decisions for approval are largely due to encouraging results from a phase 2 single-arm trial with 44% of the cohort experiencing an objective clinical response and demonstrating a tolerable safety profile .The evidence for immunotherapy in periocular SCC with PNI has been promising, but scant. There was one case report of a primary suprabrow SCC with orbital extension that recurred following radical surgical resection and radiotherapy, and was eventually amenable to cemiplimab . A separPeriocular regionFocal PNI Small-calibre nerve <0.1 mmDermal invasion onlyHigh riskNamed nerve involvement or large-calibre nerve ≥0.1 mmExtensive PNI Deep invasion beyond subcutaneous fatVery high riskAny symptoms of PNSFocal PNI with multiple high-risk histological or clinical features Tables  and 2Extensive PNIMRI is the recommended imaging modality for detecting PNS. The indications are as follows:Nerve thickening or enlargementNerve enhancementObliteration of fat pads along the course of the involved nerveErosion and widening of neural foraminaMuscle denervation atrophy and adipogenic replacementThe most useful imaging sequences are T1-weighted, T1WI fat-suppressed contrast-enhanced, and T2-weighted with fat saturation. The salient radiological signs of PNS are as follows:A flowchart demonstrating our management algorithm is outlined in Fig. All tumours with suspicion of PNS should undergo a 3T MRI with the protocols outlined in Table A vigilant follow-up schedule is an essential part of postoperative care for patients with periocular SCC and PNI, due to the risk of recurrence and perineural spread into the orbit and cranial fossa. It is estimated that 85% of recurrences occur within the first 2 years following initial treatment . RoutinePerineural invasion is an established adverse prognostic marker which confers a higher risk of local recurrence and regional and distant metastasis. A thorough clinical evaluation of periocular SCC with PNI should include risk stratification of PNI parameters and MRI with PNI protocols to detect perineural spread. Surgical excision with intraoperative en face margin control is strongly encouraged. Adjuvant radiotherapy for high-risk lesions improves the cure rate, but its utility in the periocular region should be balanced by visual morbidity risk. PD-1 inhibitor immunotherapy is suitable for non-surgical candidates with locally advanced or distant metastatic disease. Further studies, particularly randomised controlled trials, are necessary for the development of evidence-based oncology protocols.


Individual cancer cells are not equal but are organized into a cellular hierarchy in which only a rare few leukemia cells can self-renew in a manner reminiscent of the characteristic stem cell properties. The PI3K/AKT pathway functions in a variety of cancers and plays a critical role in the survival and proliferation of healthy cells under physiologic conditions. In addition, cancer stem cells might exhibit a variety of metabolic reprogramming phenotypes that cannot be completely attributed to the intrinsic heterogeneity of cancer. Given the heterogeneity of cancer stem cells, new strategies with single-cell resolution will become a powerful tool to eradicate the aggressive cell population harboring cancer stem cell phenotypes. Here, this article will provide an overview of the most important signaling pathways of cancer stem cells regarding their relevance to the tumor microenvironment and fatty acid metabolism, suggesting valuable strategies among cancer immunotherapies to inhibit the recurrence of tumors. Many research findings have suggested the importance of a small proportion of cancer cells with extraordinary resistance to the conventional cancer therapies that target the highest proportion of cancer cells ,2,3,4. TThe cancer stem cell model, thus, contrasts with the stochastic model in that it reflects the hierarchical cellular organization of healthy individuals . These fCancer stem cells are identified and can be isolated based on the expression of specific cell-surface proteins that act as molecular biomarkers, among which the most frequent markers are CD44, CD133, CD24, EpCAM, and LGR5 . The expThe PI3K/AKT pathway functions in a variety of cancers and plays a critical role in the survival and proliferation of healthy cells under physiologic conditions ,26,27 F. For examyc, NF-κB, cyclin D1, p21, p27, and PPAR, which regulate cell fate, including that of cancer stem cell-like cells [WNT-β-catenin pathway is another signaling axis in which fatty acid desaturation could contribute to the maintenance of cancer stem cell function . WNT sigke cells . For theke cells .The adaptation of cancer stem cells in a heterogeneous tumor microenvironment, including a low pH, hypoxic conditions, and nutritional state, is a characteristic of cancer stem cells ,32. SpecRecently, it has been widely accepted that the adoption of a glycolytic metabolism may be an unforced event that can occur even when oxygen is available in the microenvironment and in cells lacking mitochondrial dysfunction . This reThe development of secondary tumors at sites in the body distant from the primary tumor is termed metastasis. Although metastasis accounts for the greatest proportion of cancer-associated deaths, it remains the most complex and least understood aspect of cancer biology . In the In healthy adult tissues, stem cells reside in niches—microenvironments comprising various cells and ECM components. These niches are discrete and dynamic functional domains that influence stem cell behavior in the maintenance of tissue homeostasis under diverse physiologic and pathologic conditions ,45. StemThe cancer stem cell model proposes that the elimination of cancer stem cells has great potential as an effective strategy for therapeutically overwhelming malignancies because cancer stem cells residing within tumors are essential to cancer initiation and maintenance, and to driving cancer progression and metastasis. Despite the attractiveness of cancer stem cells as targets, evidence supporting their functionality within the model is limited. However, new findings have shown that cancer stem cells and non-cancer stem cells both have plastic features and are, thus, capable of phenotype transition in response to the tumor microenvironment. Recently, the plasticity of cancer stem cells was shown to hamper the cancer stem cell targeting strategy. Cell ablation experiments in xenografted human cancers  with theMultiple therapies have been developed to treat cancers; the major treatments are chemotherapy, which uses anticancer drugs to kill cancer cells, and radiation therapy, which uses sufficiently high radiation doses to kill cancer cells and shrink tumors. Other therapies include the surgical removal of cancerous tumors and targeted therapy using molecularly targeted drugs. However, resistance to chemotherapy and radiation is frequently observed, likely because of the intrinsic properties of cancer stem cells acquired through multiple interactions with the tumor microenvironment, including dysregulation of the drug–efflux pump system and DNA repair capacity ,53,54. TChimeric T-cell receptors (CAR) are the cell surface receptors artificially engineered in combination with antigen-binding and T-cell activating functions to target a specific antigen for cell therapy . In CAR Immune checkpoint blockade therapy was recently proposed as a promising approach for cancer treatment. This therapy may provide opportunities for the targeted elimination of cancer stem cell subsets to complete the regression of malignant tumors. Cancer stem cells exhibit characteristics that circumvent attacks by the immune system, including altered antigen expression leading to reduced recognition by the immune system. The approach of the immune checkpoint blockade can be used to target cancer stem cells. One major breakthrough in cancer immunotherapy has been the identification of immune checkpoint molecules in tumors, namely cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), the programmed cell death-1 (PD-1), and its ligands programmed death-ligand 1 (PD-L1) and PD-L2 . When T The fatty acid synthesis pathway consists of iterative cycles which elongate two-carbon units in a consecutive manner to form long chain fatty acids (LCFAs). This process begins with the conversion of citrate into acetyl-CoA and oleanolic acid acetate catalyzed by ATP-citrate lyase (ACLY). Acetyl-CoA is then carboxylated to form malonyl-CoA, and then entered into the iterative cycles as the building block for fatty acid synthesis. Monounsaturated fatty acid (MUFA) is synthesized by stearoyl-CoA desaturase (SCD1) and acts as a major component of the plasma membrane. The essential fatty acids, polyunsaturated fatty acids (PUFAs), might be preferentially incorporated by cancer cells from the tumor microenvironment. Conversely, fatty acids are metabolized through the β-oxidation pathway in which ATP is generated as an energy source. The fatty acid is desaturated by an enzyme, fatty acid desaturase, to form a carbon–carbon double bond.Several reports indicate that cancer stem cells accumulate unsaturated lipids, such as MUFAs, which are precursors for several plasma membrane lipids . The uptActivated fatty acids are not only incorporated into membranes or storage but are also used as substrates to synthesize signaling lipids or for energy production: high activity of this pathway has been reported for aggressive tumor cells and cancer stem cells, especially in nutrient-scarce environments . In addiThe complexity of foods and eating patterns is well established. Therefore, the assessment of dietary patterns, rather than the traditional reductionist approach focused on specific dietary factors, is a new and more promising strategy when investigating relationships with cancer . Diet isA high-fat diet is associated with detrimental effects on the fitness of the stem cell compartment through cell-autonomous or niche-dependent mechanisms . Indeed,Calorie restriction is the major nutritional strategy recognized for its effects on stem cell function. The beneficial effects of calorie restriction include enhanced longevity and reduced disease burden. Calorie restriction reduced tumorigenesis in breast tissues and inhibited the self-renewal of stem cells  and limiAs mentioned above, cancer stem cells exhibit a variety of metabolic reprogramming phenotypes that cannot be completely attributed to the intrinsic heterogeneity of cancer. Given the heterogeneity of cancer stem cells, new strategies with single-cell resolution will become a powerful tool to eradicate the aggressive cell population harboring cancer stem cell phenotypes.“The fourth paradigm” of data-intensive scientific discovery, presented by the excellent computer scientist Jim Gray in 2009, refers to the intelligent data management techniques and computational systems needed to manipulate and analyze “big data” acquired through research across multiple scientific fields . Under tVarious technological inventions are associated with single-cell technologies. First are the (1) approaches to examine genome-wide chromatin accessibility of thousands of cells at the single-cell resolution  . Second,This article provides an overview of the most important signaling pathways of cancer stem cells with their relevance to the EMT and tumor microenvironment. We also suggest emerging strategies within cancer immunotherapies targeting cancer stem cells as protection from tumor recurrence. Diversity within tumor cells at the genetic and functional levels and their coexistence with the microenvironment also increases tumor fitness, enabling tumor cells to offset the survival pressures imposed by therapy . Fatty a


Recent advancements in AI have revolutionized cancer research, especially in the analysis of histopathological imaging data with minimal human involvement. Early detection of lymph node metastasis in breast cancer is vital for treatment outcomes. This paper introduces a novel approach that combines representation learning and deep learning (DL) to detect small tumors (STs) without neglecting larger ones. The proposed method uses representation learning to identify STs in histopathology images, followed by DL algorithms for breast cancer detection. Extensive evaluation shows remarkable accuracy in detecting STs without compromising larger-lesion detection. This approach enables early detection, timely intervention, and potentially improved treatment outcomes. The integration of representation learning and DL offers a promising solution for ST detection in breast cancer. By reducing human involvement and leveraging AI capabilities, the proposed method achieves impressive accuracy in identifying STs. Further research and validation could enhance diagnostic capabilities and personalized treatment strategies, ultimately benefiting breast cancer patients.The early diagnosis of lymph node metastasis in breast cancer is essential for enhancing treatment outcomes and overall prognosis. Unfortunately, pathologists often fail to identify small or subtle metastatic deposits, leading them to rely on cytokeratin stains for improved detection, although this approach is not without its flaws. To address the need for early detection, multiple-instance learning (MIL) has emerged as the preferred deep learning method for automatic tumor detection on whole slide images (WSIs). However, existing methods often fail to identify some small lesions due to insufficient attention to small regions. Attention-based multiple-instance learning (ABMIL)-based methods can be particularly problematic because they may focus too much on normal regions, leaving insufficient attention for small-tumor lesions. In this paper, we propose a new ABMIL-based model called normal representative keyset ABMIL (NRK-ABMIL), which addresseses this issue by adjusting the attention mechanism to give more attention to lesions. To accomplish this, the NRK-ABMIL creates an optimal keyset of normal patch embeddings called the normal representative keyset (NRK). The NRK roughly represents the underlying distribution of all normal patch embeddings and is used to modify the attention mechanism of the ABMIL. We evaluated NRK-ABMIL on the publicly available Camelyon16 and Camelyon17 datasets and found that it outperformed existing state-of-the-art methods in accurately identifying small tumor lesions that may spread over a few patches. Additionally, the NRK-ABMIL also performed exceptionally well in identifying medium/large tumor lesions. Histopathological tissue analysis is a crucial tool for diagnosing various diseases . With thTo address these challenges, recent algorithms ,9 have eCurrent methods for MIL in analyzing WSIs assume that all patches within a WSI are equally important for slide-level prediction. These methods compute attention weights for each patch and use weighted combinations of patch features to derive a meta-representation of the WSI ,9,10,14.To address this issue, we propose a new MIL model and demonstrate its effectiveness through the problem of breast cancer metastasis classification in the lymph nodes (BCLNM). The key idea of the proposed method is the use of normal patches that are part of normal WSIs to learn a keyset of representative normal patches. We then design a keyset-based approach that can guide the MIL model to select discriminative patches from WSIs intelligently. The systematic overview of the normal representative keyset generation module (NRKG) is presented in The rest of the manuscript is organized as follows. We discuss related work in Several machine learning methods that use multiple-instance learning (MIL) techniques employ an attention mechanism for aggregating patch embeddings ,10,17. OOur experiments see : ResultsIn one of our previous works, we proposed attention2majority , which tThese approaches highlight the challenges of identifying small lesions in MIL-based WSI classification and the importance of addressing the noisy training problem. They also demonstrate the potential of unsupervised learning and representation learning to improve the selection of informative patches for MIL models. In this work, we address the limitations of these methods and develop more effective strategies for identifying and classifying small lesions in WSIs.This section presents a novel attention-based MIL method that uses patch-level labels from normal WSIs to improve the accuracy of WSI-level label classification. We first introduce the dataset used in our experiments and some detail of the clinical problem that we are aiming to solve. We then provide a brief overview of MIL and attention-based MIL (ABMIL) methods for WSI-level label classification. Next, we describe how we leverage known patch-level labels of normal WSIs to create an accurate representative bag for all normal WSI patches, which we refer to as the normal representative keyset (NRK). We explain how we use the NRK to enhance the classification of WSI-level labels. Finally, we discuss how the proposed method identifies and separates patches with high similarity scores to the NRK when given a WSI at inference time. The proposed method utilizes known patch-level labels from normal WSIs to create a representative bag of normal WSI patches. This allows for improved classification of WSI-level labels, particularly in cases where small lesions may be present. We discuss the specific details of the approach, including how we leverage the NRK to enhance classification accuracy and how we effectively identify and separate patches with high similarity scores to the NRK during inference.We evaluate the efficiency of the proposed method on publicly available WSI datasets of lymph node metastasis from breast cancer, namely, Camelyon16  and CameWe now describe how the MIL method  learns t ith WSI . If yij However, for a tumor WSI (positive bag) Following the MIL paradigm, the attention-based MIL method  first utSince attention scores obtained via Equation (4) are always nonzero, ABMIL methods (even well-performing ones) assign positive attention scores to normal patches within a tumor WSI. For medium and large tumor WSIs (WSIs with medium and large lesions), assigning positive attention scores to normal patches may not affect the overall ABMIL-based WSI-level label prediction because there is a relatively proper balance between the numbers of normal and tumor patch-level embeddings. However, when it comes to small tumor WSIs , positive attention scores to normal patches can lessen the impacts of a few tumor-patch-level embeddings in the WSI-level embedding given in Equation (3). As a result, the WSI-level embedding of a small tumor WSI becomes similar to a WSI-level embedding of a normal WSI. Therefore, fewer tumor patches  within a tumor WSI raise the likelihood of a false-negative decision.To maintain adequate attention to tumor-patch-level embeddings within a tumor WSI, and ensure that they have a strong effect on the WSI-level embedding given in Equation (3), we need to assign a zero-attention score to normal-patch-level embeddings. Due to SoftMax function properties and derived attention scores in Equation (4), we must identify normal patches within tumor WSIs and remove them before SoftMax function is applied to them. However, this is not directly possible because of the lack of patch-level annotation within tumor WSIs. One way to identify normal-patch-level embeddings within a tumor WSI is to roughly learn their underlying distribution using all normal patches cropped from all normal WSIs. Note that we leverage known patch-level labels of normal WSIs to construct an optimal normal representative keyset.We now introduce a novel method for constructing the normal representative keyset (NRK) using an NRKG module that consists of distinct normal-patch-level embeddings. In other words, via a controlled cosine similarity-based contrastive process among normal-patch-level embeddings of all normal WSIs, the NRK is constructed to be the smallest distinct set representing the normal patch-level embeddings containing all distinct normal-patch-level embeddings. Note that the NRK construction process is offline, and hence it does not add any online computational cost. Without loss of generality, suppose there are rithm A1  demonstrrithm A1 . Figure r percentile of r) percentile of r percentile embeddings (uncertain patch-level embeddings) of a WSI are selected and fed into the ABMIL model for a WSI-level label prediction.In this section, we discuss how to employ the NRK obtained in Algorithm A1 to assign zero attention to certain normal patches, which are patches whose feature embeddings are lying in the negative  subspace far from the positive (tumor) subspace. Note that at both training and inference times, the NRK singles out certain normal patches for both normal and tumor WSIs. Given the set of patch-level embeddings, To extract the tissue region from the WSI, we apply the color thresholding method to extract the foreground tissue patches and discard the patches with more than 25% of the background region. Then, we crop the tissue region into 224 × 224 non-overlapping patches under 20× magnification. We used the ResNet50 model  that genFor the experimentation involving the combined Camelyon16 and Camelyon17  datasetsIn this section, we evaluate the experimental results of the proposed method with the state-of-the-art methods and conduct an ablation study, and interpretability of the patch-selection method using NRK.We evaluated the effectiveness of the proposed method by comparing it to existing deep learning methods ,9,10 on The goal of an ablation study is to investigate the impact of individual hyperparameters on the performance of a model, helping to determine their relative importance and optimize their values using a validation set. We conducted an ablation study to validate the effectiveness of key hyperparameters: The importance of removing the normal patches is depicted in In this article, we introduce NRK-ABMIL, a weakly supervised learning model designed for tumor WSI classification. The proposed method uses a novel discriminative normal representation learning approach that identifies the discriminative normal representations from each WSI using a DFI module and generates a normal representation keyset (NRK). We then compare the NRK with WSI feature vectors for the selection of potential tumor patches within the WSIs. The identified patch embeddings are then fed into the MIL model for slide-level classification, enhancing the classification performance.The proposed model achieved an average AUC of 0.8967 and 0.9540 using ResNet50 Feature Extractor  and histA limitation of the proposed method is that our NRK module and the subsequent instance selection module rely on feature embeddings generated by a fixed ResNet encoder or pretrained CTranspath encoder without fine tuning on a target dataset, which can result in selection of patches that might not be separable in this feature space. Therefore, while our current method provides excellent performance for the driving problem we studied in this paper, there is room for improvement through the exploration of self-supervised learning models ,31. AnotDespite the limitations, the proposed NRK-ABMIL provides a powerful automatic solution for tumor WSI classification. The proposed method can not only provide accurate slide-level prediction but also generate sparser and more tumor-oriented attention maps than other MIL methods.The clinical significance of this method lies in its potential to help oncologists accurately identify breast cancer metastasis to lymph nodes, which is crucial for determining the stage of breast cancer. This method can be utilized in the development of improved treatment plans, as the detection of lymph node metastasis of small lesions is critical for improving the prognosis. An interesting application of the proposed method could be for the detection in the frozen section slides. These frozen slides often pose challenges in recognizing such small metastatic deposits, making their detection difficult. False-negative cases in frozen tissue can have serious consequences for patients and complicate care planning. This method can also lighten the burden on pathologists by offering highly precise ROI suggestions in areas where there is a shortage of skilled pathologists.In this study, we propose a novel approach for classifying whole slide images (WSIs) with small lesions in a more precise and accurate manner. Specifically, we introduced a distinct feature vector identifier module as part of our normal representative keyset-based MIL approach, which allows for the selection of patches that are most relevant for accurately classifying WSIs. To evaluate the effectiveness of the proposed method, we conducted comprehensive experiments on the Camelyon16 and Camelyon17 datasets, which are widely used as benchmark datasets for evaluating computer-aided diagnosis systems for breast cancer metastasis. Our results demonstrated that the proposed NRK-ABMIL approach with the DFI module achieved excellent performance for accurately identifying small tumor regions within WSIs. The proposed method needs to be refined and validated for multiclass classification problems and using other medical use cases. We expect that the proposed method will generalize well, especially in accurately detecting small lesions within WSIs. In our future studies, we plan to test our proposed method for other types of cancer.


Urinomas are an accumulation of urine in the perirenal or paraureteral space due to urinary tract leakage. Stimulation of an inflammatory response results in the formation of a thick wall that encapsulates the urine. Etiologies of urinomas include trauma, surgery, or spontaneous occurrence. Complications when untreated vary and include peritonitis, fibrosis, abscess formation, and septic shock. We present a 52-year-old male with a neurogenic bladder who developed a rectus urinoma from the thorax to the scrotum. This likely developed from urethral trauma from intermittent self-catheterization. The patient received antibiotic therapy and percutaneous drainage catheters were placed in the rectus and pelvis, resolving the urinoma. We conclude that patients who perform intermittent self-catheterization may be more susceptible to formation of urinomas due to improper catheter usage. The intricate fascial connections between the pelvis and abdomen make proper interventions for suspected urinary tract injury crucial in patients who self-catheterize. Various complications can occur following trauma to the urinary tract and collecting system; however, these occurrences are infrequent and consist of less than 1% of genitourinary cases . AnterioEarly complications include extravasation of urine and abscess formation while late complications include urethral stricture, urethrocutaneous fistula, urinary incontinence, and erectile dysfunction . UrinomaWe report a case of a patient who developed a urinoma leading to abscess within the rectus sheath extending to the scrotal sac likely due to urethral trauma by habitual self-catheterization. This unique presentation of urethral urinoma emphasizes the complex anatomic relationship within the abdominal and pelvic cavities and how they may be impacted by iatrogenic trauma and exacerbated by chronic inflammation. Informed consent to publish this case has been obtained from the patient.This article was previously presented as a meeting abstract at the 2023 ACOS-MSS Spring Meeting on April 29, 2023.A 52-year-old male presented to the emergency department (ED) with right-sided abdominal pain, hematuria, and decreased urine output during self-catheterizations. His past medical history included gunshot injury at age 20 causing T6 spinal cord injury, neurogenic bladder maintained with clean intermittent catheterization (CIC), hemicolectomy requiring sigmoid colostomy, and bilateral above the knee amputation, as well as left renal cell carcinoma status post partial nephrectomy at age 41. The patient reported symptom onset two weeks prior to presentation when he began reusing urinary catheters due to medical supply issues. Five days prior, he saw his primary doctor who prescribed a five-day course of ciprofloxacin for a presumed urinary tract infection (UTI). On presentation, the patient was afebrile with abdominal distention and right upper and lower quadrant tenderness without rebound or guarding. White blood cell (WBC) count and lactate were elevated to 26.1 x 103 per microliter (uL) and 2.4 milligrams (mg)/deciliter (dL), respectively. Serum creatinine was elevated to 2.83 mg/dL compared to a baseline measurement of 0.92 mg/dL three months prior. Urinalysis showed bacteria, greater than 100 WBCs, and 21-50 red blood cells (RBCs). CT abdomen and pelvis (CTAP) without contrast revealed a complex collection measuring 10 x 10 x 20 centimeters (cm) consistent with right rectus abscess -guided 8-French percutaneous catheter was placed into the right rectus which initially drained 15 cubic centimeters (cc) of sanguineous fluid Figure  and was Over the next three days, the patient’s abdominal pain improved, yet he continued to have persistently low urine output on CIC. Repeated labs showed downtrending of WBC and normalization of serum creatinine. Urine culture was negative for UTIs, and blood culture revealed contamination with Staphylococcus epidermidis without significant bacterial growth. Evaluation with bedside cystoscopy demonstrated a large bulbar urethral false passage. A 16-French council tip catheter was placed via a wire for urine drainage.On admission day five, the patient remained afebrile. New abdominal distention was observed, and the rectus catheter began draining purulent blood-tinged fluid. WBC increased to 20.2 x 103/uL, and the sepsis protocol was reactivated. Repeat CTAP without contrast showed a persistent collection in the lower anterior abdominal wall measuring 10 x 5 x 16 cm. The 8-French rectus drain was replaced with a 16-French catheter in order to increase drainage. Reassessment of rectus fluid creatinine showed a decrease to 0.5 mg/dL, indicating resolution of the urinary tract leak at this site. CT cystogram was also performed, which showed contrast filling the scrotum, suggesting a urethral leak at the level of the prostatic urethra (Figure With continued drainage, the patient’s abdominal pain and urinary output continued to stabilize. He was ultimately discharged on day ten with both 16-French percutaneous catheters and the 16-French urethral catheter in place. Oral amoxicillin-clavulanate was continued. Two weeks later, outpatient CTAP revealed resolution of all collections, and the percutaneous catheters were removed. One month after discharge, outpatient cystoscopy revealed adequate false passage healing with no signs of extravasation. The urethral catheter was exchanged for a Foley catheter. The patient was referred for urological reconstruction with consideration of long-term suprapubic catheter placement.In complex urology patients, the importance of detailed care instructions, consistent access to medical supplies, and regular follow-up is crucial. These are necessary to prevent injury when performing catheterization at home. In addition, the acute inflammatory state due to UTI, in the context of a chronic inflammatory environment resulting from gunshot trauma and CIC, likely led to vulnerability in the local environment and surrounding tissue allowing for a fistulous connection. The inflammatory response, which aims to restore homeostasis in response to damage or infection, is largely beneficial but can lead to opportunities for dismantled integrity when the body cannot properly recuperate. Fascial networks and connections between the abdomen and the genitourinary tract provide insight into the development of the extensive urinoma in this patient. Scarpa’s fascia of the anterior abdominal wall is contiguous with the external oblique, linea alba, pubis symphysis, and fascia lata and continues distally into the scrotum as Dartos fascia . From thTrauma to the lower genitourinary tract requires significant force due to the bony structures that function to protect the lower tract structures. Urethral injuries have an incidence of 10% of pelvic trauma, as pelvic fractures are the primary cause of urethral injury . With urUpon retrospective analysis of this patient and his prognostic factors, there are multiple steps that were taken to improve the outcome for this patient. The early treatment of his UTI with subsequent negative urine cultures upon admission likely had a significant impact on pharmaceutical stewardship, tissue integrity, and overall recovery. Within his admission, protecting the existing kidney function was prioritized by adjusting antibiotic dosing and avoiding the use of contrast in order to preserve quality of life and delay the need for hemodialysis. We also observe proper reassessment of the patient’s condition such as the reactivation of sepsis protocol, the adjustment of drains, and utilization of various imaging modalities in order to investigate the extent of extravasation. Considering his improper self-catheterization due to catheter reuse leads us to question whether there is indication for alternative options for management such as a suprapubic catheterization instead of CIC. Due to a possible risk of limited resources and reinfection in the future, we suggest that this patient would be a better candidate for long-term catheterization, better addressing his needs and minimizing a similar event from recurring.This report details the uncommon occurrence of a urinoma found within the rectus sheath with involvement of the scrotal sac secondary to iatrogenic trauma of the urethra from clean intermittent self-catheterization. This presentation details the intricate fascial connections between the pelvis and the abdomen, making further diagnostic investigations and proper interventions for suspected UTIs crucial in patients with a history of blunt trauma to the urethra. We recommend increased surveillance and education to patients who perform self-catheterization.