Micromanipulation of Live Microdissected Tissues with a Low-Cost Integrated Robotic Platform.

The small amount of human tissue available for testing is a paramount challenge in cancer drug development, cancer disease models, and personalized oncology. Technologies that combine the microscale manipulation of tissues with fluid handling offer the exciting possibility of miniaturizing and automating drug evaluation workflows. This approach minimizes animal testing and enables inexpensive, more efficient testing of samples with high clinical biomimicry using scarce materials. We have developed an inexpensive platform based on an off-the-shelf robot that can manipulate microdissected tissues (µDTs) into user-programmed positions without using intricate microfluidic designs nor any other accessories such as a microscope or a pneumatic controller. The robot integrates complex functions such as vision and fluid actuation by incorporating simple items including a USB camera and a rotary pump. Through the robot's camera, the platform software optically recognizes randomly-seeded µDTs on the surface of a petri dish and positions a mechanical arm above the µDTs. Then, a custom rotary pump actuated by one of the robot's motors generates enough microfluidic lift to hydrodynamically pick and place µDTs with a pipette at a safe distance from the substrate without requiring a proximity sensor. The platform's simple, integrated construction is cost-effective and compact, allowing placement inside a tissue culture hood for sterile workflows. The platform enables users to select µDTs based on their size, place them in user-programmed arrays, such as multi-well plates, and control various robot motion parameters. As a case application, we use the robotic system to conduct semi-automated drug testing of mouse and human µDTs in 384-well plates. Our user-friendly platform promises to democratize microscale tissue research to clinical and biological laboratories worldwide.

Combined dilute alkali and milling process enhances the functionality and gut microbiota fermentability of insoluble corn fiber.

In this study, we developed a process combining dilute alkali (NaOH or NaHCO3) and physical (disk milling and/or ball milling) treatments to improve the functionality and fermentability of corn fiber. The results showed that combining chemical with physical processes greatly improved the functionality and fermentability of corn fiber. Corn fiber treated with NaOH followed by disk milling (NaOH-DM-CF) had the highest water retention (19.5 g/g), water swelling (38.8 mL/g), and oil holding (15.5 g/g) capacities. Moreover, NaOH-DM-CF produced the largest amount (42.9 mM) of short-chain fatty acid (SCFA) during the 24-hr in vitro fermentation using porcine fecal inoculum. In addition, in vitro fermentation of NaOH-DM-CF led to a targeted microbial shifting to Prevotella (genus level), aligning with a higher fraction of propionic acid. The outstanding functionality and fermentability of NaOH-DM-CF were attributed to its thin and loose structure, decreased ester linkages and acetyl groups, and enriched structural carbohydrate exposure.

Label-Free, Real-Time Monitoring of Cytochrome C Responses to Drugs in Microdissected Tumor Biopsies with a Multi-Well Aptasensor Platform.

Functional assays on intact tumor biopsies can potentially complement and extend genomics-based approaches for precision oncology, drug testing, and organs-on-chips cancer disease models by capturing key determinants of therapeutic response, such as tissue architecture, tumor heterogeneity, and the tumor microenvironment. Currently, most of these assays rely on fluorescent labeling, a semi-quantitative method best suited to be a single-time-point terminal assay or labor-intensive terminal immunostaining analysis. Here, we report integrated aptamer electrochemical sensors for on-chip, real-time monitoring of increases of cytochrome C, a cell death indicator, from intact microdissected tissues with high affinity and specificity. The platform features a multi-well sensor layout and a multiplexed electronic setup. The aptasensors measure increases in cytochrome C in the supernatant of mouse or human microdissected tumors after exposure to various drug treatments. Since the aptamer probe can be easily exchanged to recognize different targets, the platform could be adapted for multiplexed monitoring of various biomarkers, providing critical information on the tumor and its microenvironment. This approach could not only help develop more advanced cancer disease models but also apply to other complex in vitro disease models, such as organs-on-chips and organoids.

Urban-rural disparities in acceptance of human papillomavirus vaccination among women in Can Tho, Vietnam.

Background: In Vietnam, cervical cancer is a significant public health concern for women. Unfortunately, despite the availability of the HPV vaccine, low vaccination rates persist. Objectives: This study investigates the discrepancy between urban and rural areas in the willingness to receive HPV vaccination with or without fees. Methods: A cross-sectional study was conducted on a sample of 648 women aged between 15 and 49, living in two urban and two rural Vietnamese districts of Can Tho, between May and December 2021. Results: The overall vaccination rate was 4%, with urban women having a higher rate of 4.9% compared to rural women at 3.1%. Among unvaccinated women, those from rural areas expressed a significantly higher desire to receive the free vaccine (91.4%) than urban women (84.4%). However, the intention to vaccinate declined when rural women and urban women were advised to pay the cost (63.4% and 57.1%, respectively). A strong correlation was found between a positive attitude and intention for vaccination, irrespective of its price or free availability. Education and access to information about the HPV vaccine were also identified as the most significant factors influencing the intention to vaccination among urban and rural women. Conclusion: The low HPV vaccination rates among women aged 15-49 living in both urban and rural regions of Vietnam are a notable public health concern. These outcomes emphasize the critical need for effective programs of vaccine laterization, as an introduction to the offer of affordable and accessible HPV vaccines for women in Can Tho, Vietnam.

Laparoscopic percutaneous closure of patent processus vaginalis without hydrocelectomy for childhood primary hydrocele.

PURPOSE: To present our surgical technique and the outcome of single-incision laparoscopic percutaneous extraperitoneal closure (SILPEC) of patent processus vaginalis (PPV) without hydrocelectomy for childhood primary hydrocele (CPH). METHODS: A prospective study was conducted on all cases of CPH treated with SILPEC at our center between June 2016 and December 2021. In our SILPEC procedure, PPV was closed extraperitoneally using a percutaneous needle with a wire lasso. No hydrocelectomy or fenestration of the hydrocele was performed. Percutaneous aspiration was performed when the hydrocele fluid could not be pushed back to the peritoneal cavity. RESULTS: 553 patients were enrolled, with a median age of 34 months (range from 22 months to 13 years). Ipsilateral PPV was present in all cases. There were no intraoperative complications and no conversion. At follow-up 6-72 months, recurrent hydrocele occurred in 0.36%, and subcutaneous stitch inflammatory reaction was noted in 0.7%. There was no case of testicular atrophy or iatrogenic cryptorchidism. Postoperative cosmesis was excellent as all patients were virtually scarless. CONCLUSIONS: Ipsilateral PPV was present in all cases of CPH in our series. Our technique of SILPEC of PPV without hydrocelectomy is feasible and safe, with excellent postoperative cosmesis in the management of CPH.

Laparoscopic versus open Kasai procedure for biliary atresia: long-term results of a randomized clinical trial.

PURPOSE: The role of the laparoscopic approach for the Kasai procedure in the management of biliary atresia is still controversial. The aim of this study is to compare the long-term results of the laparoscopic Kasai procedure (LKP) to the open Kasai procedure (OKP). METHODS: A randomized clinical trial was carried out from October 2009 to March 2017. Patients diagnosed with biliary atresia type III were randomized into 2 groups: one group underwent LKP and the other group-OKP. All the surgical procedures were performed by the same surgeon with the same technical principles. The long-term outcomes were compared between the two groups. RESULTS: 61 patients underwent LKP and 61 patients-OKP, with a median age at the surgery of 79.7 days. The two groups had no significant differences regarding the patients' baseline characteristics. At follow-up up to 142 months, the jaundice-free rate at the 6th postoperative month for LKP and OKP was 52.5% and 60.7%, respectively (p = 0.23). The 10-year cumulative survival after LKP tended to be inferior to OKP, respectively 44.3% vs. 58.9% (p = 0.09). CONCLUSIONS: In this study, the long-term results of LKP tended to be inferior compared to OKP although the differences were not significant.

Reduction of recurrence by peritoneal thermal injury in laparoscopic percutaneous extraperitoneal closure of internal ring for inguinal hernia in children.

PURPOSE: To evaluate the impact of peritoneal thermal injury (PTI) in the reduction of recurrence incidence in laparoscopic percutaneous extra-peritoneal closure of internal ring (LPEC) for pediatric inguinal hernia (PIH) in children. METHODS: Medical records of patients undergoing LPEC for PIH at our center were reviewed and divided into 2 groups: Group A (period from June 2017 to December 2017)-without PTI and Group B (period from January 2018 to December 2018) with PTI. The surgical technique and the type of suture used for LPEC were the same for both groups. The outcomes of the two groups were analyzed and compared. RESULTS: 277 patients with 283 IHs in group A were compared to 376 patients with 389 IHs in group B. There were no significant differences between the two groups in terms of age, gender, uni- or bilateral hernia. At a median follow-up period of 48 months, there was no hydrocele, suture granuloma, testicular atrophy, or iatrogenic cryptorchidism in both groups. The recurrence rate in group A was 6.4%, significantly higher than 1.8% in group B (p = 0.002). CONCLUSIONS: Our study showed that PTI in LPEC for PIH is safe and associated with a significant reduction of recurrence incidence.

Cardiac Reoperations in Patients With Transcatheter Aortic Bioprosthesis.

BACKGROUND: Despite the rapid adoption of transcatheter aortic valve replacement (TAVR), the frequency and clinical outcomes of reoperation after TAVR are not well-described. METHODS: Between 2011 and 2020, 1719 patients underwent a TAVR at our institution. Among these, 32 patients (2%) required a reoperation. Additionally, 16 patients who received a TAVR at another institution received a reoperation at our institution. We retrospectively reviewed these 48 patients. The median interval from TAVR to reoperation was 2.3 years. RESULTS: Primary reoperations included 37 TAVR valve explants (TAVR-explant; 77%) with surgical aortic valve replacement (SAVR), 8 mitral repairs/replacements (17%), 2 coronary artery bypass grafting procedures (4%), and 1 tricuspid valve replacement (2%). Forty-nine percent of nonaortic valve cardiac lesions were present at the time of TAVR. Furthermore, 18 TAVR-explant patients (49%) were deemed anatomically unsuitable for repeat TAVR based on the index TAVR imaging. During TAVR-explant, 6 patients (13%) with native TAVR sustained various degrees of aortic trauma. Patients with unplanned aortic repair demonstrated a smaller sinotubular junction diameter than those without unplanned repair. In contrast, no unplanned aortic repair was needed in the 14 patients with previous SAVR or the latest 20 consecutive patients. The overall in-hospital mortality was 15%, with an observed-to-expected morality ratio of 1.8. CONCLUSIONS: The clinical impact of post-TAVR reoperation remains substantial despite the lower frequency of unplanned aortic repair over time. The necessity of reoperations or unfavorable repeat TAVR anatomy appears predictable at the time of the index TAVR, and implanters must be mindful of "lifetime management" strategy during candidate selection.

Aortic valve reintervention after transcatheter aortic valve replacement.

BACKGROUND: Despite the rapid adoption of transcatheter aortic valve replacement (TAVR), there are scant data regarding aortic valve reintervention after initial TAVR. METHODS: Between 2011 and 2019, 1487 patients underwent a TAVR at the University of Michigan. Among these, 24 (1.6%) patients required an aortic valve reintervention. Additionally, 4 patients who received a TAVR at another institution underwent a valve reintervention at our institution. We retrospectively reviewed these 28 patients. RESULTS: The median age was 72 years, 36% were female and 86% of implanted TAVR devices were self-expandable. The leading indications for reintervention were structural valve degeneration (39%) and paravalvular leak (36%). The cumulative incidence of aortic valve reintervention was 4.6% at 8 years. Most (71%) were deemed unsuitable for repeat TAVR because of the need for concurrent cardiac procedures (50%), unfavorable anatomy (45%), or endocarditis (10%). TAVR valve explant was associated with frequent concurrent procedures, consisting of aortic repair (35%), mitral repair/replacement (35%), tricuspid repair (25%), and coronary artery bypass graft (20%). Seventy-one percent of aortic procedures were unplanned but proved necessary because of severe adhesion of the devices to the contacting tissue. There were 3 (15%) in-hospital mortalities in the TAVR valve explant group, whereas there was no mortality in the repeat TAVR group. CONCLUSIONS: Repeat TAVR procedure was frequently not feasible because of unfavorable anatomy and/or the need for concurrent cardiac procedures. Careful assessment of TAVR procedure repeatability should be weighed at the initial TAVR workup especially in younger patients who are expected to require a valve reintervention.

Bowel seromuscular flaps used to repair pelvic defects in patients undergoing reoperative surgery.

BACKGROUND: Pedicled seromuscular bowel flaps may serve as an alternative for pelvic floor reconstruction when conventional omental and muscular flaps are not an option in patients undergoing reoperative abdominopelvic surgery. The aim of this study was to evaluate a unique series of bowel seromuscular flaps used to obliterate intrapelvic defects. METHODS: We conducted a retrospective study on all patients in a single tertiary care institutional database who had undergone pelvic reconstruction with a seromuscular bowel flap from January 2006 to December 2018. The primary outcomes measured were the 30-day morbidity and mortality rates. RESULTS: Twelve patients (6 men 6 women, median age 56.5 years [range 33-77 years]) underwent reoperative abdominopelvic surgery requiring the use of a native small or large seromuscular bowel flap to obliterate pelvic defects. The indications for surgery included chronic infections, fistulizing Crohn's disease, and cancer. In all cases, no residual omentum was available and rectus abdominis muscle flaps were not feasible due to prior operative scars. Thirty-day morbidity occurred in 5 patients (42%), and included urine leak from ureteral injury, anastomotic leak, acute kidney injury, and superficial surgical site infection. No flaps became ischemic or required removal in the postoperative setting. No mortality was recorded. CONCLUSIONS: Bowel seromuscular flaps are a feasible and safe alternative for covering pelvic defects in patients who are undergoing reoperative surgery without the option to use traditional omental and muscular flaps.

Surgical Explantation of Transcatheter Aortic Bioprostheses: Balloon vs Self-Expandable Devices.

BACKGROUND: Despite the rapid adoption of transcatheter aortic replacement (TAVR), surgical TAVR valve explantation (TAVR-explant) and the clinical impact of explanted TAVR device type are not well described. METHODS: TAVR-explant from 2016 to 2019 was queried using the Society of Thoracic Surgeons (STS) National Database. A total of 483 patients with documented explanted valve type, consisting of 330 (68%) patients with balloon-expandable and 153 (32%) patients with self-expandable devices, were identified. The primary outcome was 30-day mortality. The secondary outcome was the need for any simultaneous procedures with TAVR-explant. RESULTS: The mean age was 72.8 years, 38% of the patients were female, and 51% demonstrated New York Heart Association functional class III to IV symptoms. During TAVR-explant, 63% of patients required other simultaneous procedures, including aortic repair (27%), mitral procedures (22%), coronary artery bypass grafting (15%), and tricuspid procedures (7%). Patients with a self-expandable device underwent more frequent ascending aortic replacement (22% vs 9%; P < .001) than those with a balloon-expandable device, whereas the aortic root replacement rate was similar (19% vs 24%; P = .22). The overall 30-day mortality was 18% without differences in the mortality or other major complications between the groups. Of the 157 patients with isolated surgical aortic valve replacement and available STS predicted risk of mortality score, the observed-to-expected (O/E) mortality ratio was 2.2. CONCLUSIONS: The TAVR-explant outcomes were comparable between patients with balloon-expandable devices and patients with self-expandable devices, whereas ascending aortic replacement was observed more frequently in patients with self-expandable devices. Younger patients undergoing TAVR should be informed of the future TAVR-explant risk that may accompany a higher O/E ratio and frequent morbid concurrent procedures.

Predictors of long-term mortality in octogenarian veterans following inguinal hernia repair.

BACKGROUND: While elective inguinal hernia repair (IHR) in octogenarians carries a low 30-day mortality rate, long-term outcomes are uncharted. If on average, veteran octogenarians are expected to succumb to pre-existing cardiopulmonary disease within a year of diagnosis, watchful waiting might be advisable. This study interrogated long-term mortality and its predictors following elective IHR in veteran octogenarians. MATERIALS AND METHODS: This is a retrospective analysis of 109 veterans (≥ 80 years of age), ten of which were nonagenarians who had an elective IHR. Data were dichotomized between deceased vs. non-deceased patients for univariable and multivariable analyses. Patient characteristics were also assessed in patients undergoing general (GA) vs. local (LA) anesthesia and corrected for unilateral repair and age. Kaplan-Meier curves were generated in corrected and uncorrected cohorts receiving GA vs. LA. RESULTS: At the time of analysis, 46 (45.0%) octogenarians were deceased. The average time to death following IHR was 3.7 ± 2.9 years [range (37 days-12.4 years)]. Univariable analysis showed renal disease (19.9% vs. 5.3%), operative time (67.9 ± 29.0 vs. 56.1 ± 14.4 min) and use of GA (73.0% vs. 34.8%) associated with long-term mortality (all p < 0.01). Renal disease [odds ratio (95% confidence intervals) 4.1 (1.2-13.8)] and use of GA [5.0 (2.0-10.0)] were independent predictors of mortality. Patients undergoing LA (n = 62) were older, were more likely to have cardiac disease, and had a higher ASA compared to patients receiving GA (n = 47). After correcting for age, cardiac disease and higher ASA remained more common in patients submitting to LA. Long-term mortality was significantly higher in both matched and unmatched octogenarians undergoing GA. CONCLUSION: Octogenarian veterans with a high burden of comorbid conditions are unlikely to experience short-term mortality because of their pre-existing conditions. Inguinal hernia repair should be offered to octogenarian veterans, but GA should be avoided whenever possible.

IMPACT OF DIFFERENT VENTILATION STRATEGIES ON GAS EXCHANGES AND CIRCULATION DURING PROLONGED MECHANICAL CARDIO-PULMONARY RESUSCITATION IN A PORCINE MODEL.

ABSTRACT: Background: Optimal ventilation during cardio-pulmonary resuscitation (CPR) is still controversial. Ventilation is expected to provide sufficient arterial oxygen content and adequate carbon dioxide removal, while minimizing the risk of circulatory impairment. The objective of the present study was to compare three ventilation strategies in a porcine model during mechanical continuous chest compressions (CCC) according to arterial oxygenation and hemodynamic impact. Method: Ventricular fibrillation was induced and followed by five no-flow minutes and thirty low-flow minutes resuscitation with mechanical-CCC without vasopressive drugs administration. Three groups of eight Landras pig were randomized according to the ventilation strategy: 1. Standard nonsynchronized volume-control mode (SD-group); 2. synchronized bilevel pressure-controlled ventilation (CPV-group); 3. continuous insufflation with Boussignac Cardiac-Arrest Device (BC-group). We assessed 1. arterial blood gases, 2. macro hemodynamics, 3. tissular cerebral macro and micro-circulation and 4. airway pressure, minute ventilation at baseline and every 5 minutes during the protocol. Results: Arterial PaO2 level was higher at each measurement time in SD-group (>200 mm Hg) compare to CPV-group and BC-group ( P < 0.01). In BC-group, arterial PaCO2 level was significantly higher (>90mm Hg) than in SD and CPV groups ( P < 0.01). There was no difference between groups concerning hemodynamic parameters, cerebral perfusion and microcirculation. Conclusion: Ventilation modalities in this porcine model of prolonged CPR influence oxygenation and decarboxylation without impairing circulation and cerebral perfusion. Synchronized bi-level pressure-controlled ventilation' use avoid hyperoxia and was as efficient as asynchronized volume ventilation to maintain alveolar ventilation and systemic perfusion during prolonged CPR.

miR-181a Promotes Multiple Protumorigenic Functions by Targeting TGFßR3.

Cutaneous squamous cell carcinoma (cSCC) comprises 15‒20% of all skin cancers and has a well-defined progression sequence from precancerous actinic keratosis to invasive cSCC. To identify targets for chemoprevention, we previously reported a cross-species analysis to identify the transcriptional drivers of cSCC development and identified miR-181a as a potential oncomiR. We show that the upregulation of miR-181a promotes multiple protumorigenic properties by targeting an understudied component of TGFß signaling, TGFßR3. miR-181a and TGFßR3 are upregulated and downregulated, respectively, in cSCC. miR-181a overexpression (OE) and TGFßR3 knockdown (KD) significantly suppresses UV-induced apoptosis in HaCaT cells and in primary normal human epidermal keratinocytes. In addition, OE of miR-181a or KD of TGFßR3 by short hairpin RNA enhances anchorage-independent survival. miR-181a OE or TGFßR3 KD enhances cellular migration and invasion and upregulation of epithelial‒mesenchymal transition markers. Luciferase reporter assays demonstrate that miR-181a directly targets the 3'-untranslated region of TGFßR3. miR-181a upregulates phosphorylated SMAD3 levels after TGFß2 administration and results in elevated SNAIL and SLUG expression. Finally, we confirm in vivo that miR-181a inhibition compromises tumor growth. Importantly, these phenotypes can be reversed with TGFßR3 OE or KD in the context of miR-181a OE or KD, respectively, further highlighting the physiologic relevance of this regulation in cSCC.

Long-term absorbable versus non-absorbable suture in laparoscopic percutaneous extraperitoneal closure of internal ring for inguinal hernia in children.

AIM: To compare the results of using long-term absorbable (LTAS) versus non-absorbable suture (NAS) in laparoscopic percutaneous extraperitoneal closure of internal ring (LPEC) for indirect inguinal hernia (IH) in children METHODS: Prospectively collected data from children undergoing LPEC for IH at our center were retrospectively reviewed to compare group A repaired with NAS (2.0 monofilament polypropylene or braided polytetrafluoroethilene) to group B repaired with LTAS 2.0 polydioxanone. RESULTS: 481 patients with 499 IHs in group A were compared to 277 patients with 283 IHs in group B. There were no significant differences in terms of age, bodyweight and laterality of IH between the two groups. At a median follow up period of 30 months, the incidence of suture knot reaction (SKR) and hernia recurrence were 3.1% and 1.0% in group A vs. 0% and 6.4% in group B with p = 0.002 and p<0.001, respectively. Monofilament NAS was associated with a low rate of both recurrence and SKR. CONCLUSIONS: LPEC repair for pediatric IH using LTAS is associated with no SKR but a higher recurrence rate compared to NAS. Monofilament NAS such as Prolene could be a good choice in LPEC because of its low rate of both recurrence and SKR.

Cytotoxicity activities and chemical characteristics of exopolysaccharides and intracellular polysaccharides of Physarum polycephalum microplasmodia.

BACKGROUND: Microbial polysaccharides have been reported to possess remarkable bioactivities. Physarum polycephalum is a species of slime mold for which the microplasmodia are capable of rapid growth and can produce a significant amount of cell wall-less biomass. There has been a limited understanding of the polysaccharides produced by microplasmodia of slime molds, including P. polycephalum. Thus, the primary objectives of this research were first to chemically characterize the exopolysaccharides (EPS) and intracellular polysaccharides (IPS) of P. polycephalum microplasmodia and then to evaluate their cytotoxicity against several cancer cell lines. RESULTS: The yields of the crude EPS (4.43 ± 0.44 g/l) and partially purified (deproteinated) EPS (2.95 ± 0.85 g/l) were comparable (p > 0.05) with the respective crude IPS (3.46 ± 0.36 g/l) and partially purified IPS (2.45 ± 0.36 g/l). The average molecular weight of the EPS and IPS were 14,762 kDa and 1788 kDa. The major monomer of the EPS was galactose (80.22%), while that of the IPS was glucose (84.46%). Both crude and purified IPS samples showed significantly higher cytotoxicity toward Hela cells, especially the purified sample and none of the IPSs inhibited normal cells. Only 38.42 ± 2.84% Hela cells remained viable when treated with the partially purified IPS (1 mg/ml). However, although only 34.76 ± 6.58% MCF-7 cells were viable when exposed to the crude IPS, but the partially purified IPS displayed non-toxicity to MCF-7 cells. This suggested that the cytotoxicity toward MCF-7 would come from some component associated with the crude IPS sample (e.g. proteins, peptides or ion metals) and the purification process would have either completely removed or reduced amount of that component. Cell cycle analysis by flow cytometry suggested that the mechanism of the toxicity of the crude IPS toward MCF-7 and the partially purified IPS toward Hela cells was due to apoptosis. CONCLUSIONS: The EPS and IPS of P. polycephalum microplasmodia had different chemical properties including carbohydrate, protein and total sulfate group contents, monosaccharide composition and molecular weights, which led to different cytotoxicity activities. The crude and partially purified IPSs would be potential materials for further study relating to cancer treatment.

Outcomes of obese compared to non-obese veterans undergoing open inguinal hernia repair: a case-control study.

BACKGROUND: The optimal approach for inguinal hernia repair in the obese remains elusive. Minimally invasive techniques show equivocal results compared to the open method. None of the current analyses include a non-obese control group because the differences in factors leading to complications vary widely between these two cohorts. MATERIALS AND METHODS: In the present study, we matched (1:1) obese to non-obese patients undergoing an open inguinal hernia repair. Matching was performed by age, hernia type (bilateral, inguinal, femoral, recurrent, primary, direct, pantaloon, and scrotal component), type of repair (tissue repair vs. mesh), concurrent umbilical hernia repair, current smoking, ASA Class, a history of DM and COPD. RESULTS: Demographics in the unmatched cohorts demonstrated significantly (p < 0.05) wide differences between obese (n = 319) and non-obese (n = 1137) veterans: age (58.0- vs. 63.4-year-old), indirect hernia (37.7% vs. 45.5%), scrotal component (14.4% vs. 9.9%), current smoking (23.5% vs. 34.4%), DM (20.8% vs. 13.1%), OSA (13.2% vs. 3.6%), COPD (12.2% vs. 18.5%), and BPH (16.9% vs. 23.3). After matching, there were 300 obese and 300 non-obese patients available for analysis. There was no difference in 30-day morbidity between obese and non-obese patients in the unmatched (11.0% vs. 7.9%; p = 0.09) and matched (10.7% vs. 8.1%, p = 0.27) cohorts. Similarly, no differences in inguinodynia and recurrence were observed in either matched or unmatched cohorts. CONCLUSION: Obese patients pose no further risk in outcomes compared to non-obese veterans undergoing open inguinal hernia repair. The best technique for an inguinal hernia repair in obese patients should rest on the comfort and the experience of the surgeon.

Integrative transcriptomic analysis for linking acute stress responses to squamous cell carcinoma development.

Cutaneous squamous cell carcinoma (cuSCC) is the second most common skin cancer and commonly arises in chronically UV-exposed skin or chronic wounds. Since UV exposure and chronic wounds are the two most prominent environmental factors that lead to cuSCC initiation, we undertook this study to test whether more acute molecular responses to UV and wounding overlapped with molecular signatures of cuSCC. We reasoned that transcriptional signatures in common between acutely UV-exposed skin, wounded skin, and cuSCC tumors, might enable us to identify important pathways contributing to cuSCC. We performed transcriptomic analysis on acutely UV-exposed human skin and integrated those findings with datasets from wounded skin and our transcriptomic data on cuSCC using functional pair analysis, GSEA, and pathway analysis. Integrated analyses revealed significant overlap between these three datasets, thus highlighting deep molecular similarities these biological processes, and we identified Oncostatin M (OSM) as a potential common upstream driver. Expression of OSM and its downstream targets correlated with poorer overall survival in head and neck SCC patients. In vitro, OSM promoted invasiveness of keratinocytes and cuSCC cells and suppressed apoptosis of irradiated keratinocytes. Together, these results support the concept of using an integrated, biologically-informed approach to identify potential promoters of tumorigenesis.