BACKGROUND:Previous in vivo work has demonstrated that the phosphodiesterase type 5 (PDE5)-cyclic guanosine monophosphate-protein kinase G pathway is involved in burn-induced heart dysfunction. PDE5A inhibitors may reverse this dysfunction. It is unknown if circulating factors after burn injury can continue to damage cardiomyocytes and if this can be reversed by PDE5A inhibitors in vitro. This study hypothesized that circulating factors released after burn injury cause mitochondrial damage in cardiomyocytes in vitro. STUDY DESIGN:Human cardiomyocyte cell line-AC16-was divided into 4 groups, which were treated with serum obtained from rats with sham injury, 24 hours post burn (24hpb), sildenafil (SIL) alone, and 24hpb treated with SIL. ELISA, mitochondrial function studies, fluorescence microscopy, gene analysis, and Illumina RNA sequencing were performed. GraphPad Prism 9.2.0 was used for statistical analysis. RESULTS:Cyclic guanosine monophosphate levels were significantly decreased, and cTN1 levels were significantly increased in the 24hpb serum group. Treatment with SIL completely reversed this change, similar to our previous in vivo work. We observed that there was significantly decreased cell viability and cell proliferation and increased cell cytotoxicity, cell apoptosis, and cell reactive oxygen species production in the cells treated with 24hpb serum. Cells treated with 24hpb serum exhibited mitochondrial dysfunction, as demonstrated by decreased ATP production and compromised mitochondrial membrane integrity or potential, along with increased mitochondrial reactive oxygen species. Seahorse and O2K approaches confirmed 24hpb serum treated cardiomyocyte mitochondrial dysfunction as evidenced by decreases in mitochondrial basal respiration, proton leak, ATP production, and maximal respiration. SIL returned these responses to near sham levels. CONCLUSIONS:This study provided data that may improve the understanding of mechanisms driving cardiac dysfunction after burn injury. Our study provided evidence for understanding the pathogenic mechanism of circulating factors released after burn injury.

DEFINE CHALLENGE:Review of applicants to surgery residency is difficult to standardize and is open to bias. In addition, proper assessment and identification can lead to improved retention and performance in residency. TOOL DESCRIPTION:We developed a standardized tool to assess applicants in a holistic manner and stratify them for ranking. METHODS:Applicants were graded on a scale of 0 to 3 on the following characteristics: medical school, USMLE Step Score, class standing, letter writer rank, letter of recommendation content categories (knowledge base, work ethic/teamwork, technical skills), MSPE content, Awards, and other activities. The overall score from the assessment tool was used to determine which applicants were invited for an interview and, in addition to interview scoring, to stratify applicants for the final rank. RESULTS:From 2011 to 2017, a total of 60 residents were assessed and matched into the single ACGME-accredited general surgery residency program General Surgery Program by standard means. Prior to the utilization of this tool, the resident demographics were 58.3% men, 41.7% women, 58.3% under-represented in medicine (URM) with an 18.3% attrition rate, 5% remediation rate, and 64.3% first-time board pass rate. After the implementation of the assessment tool, a total of 38 residents were assessed and matched into the a single ACGME-accredited general surgery residency program from 2017 to 2023. The resident demographics were 57.9% men, 42.1% women, and 68.4% under-represented in medicine (URM), with a 7.9% attrition rate, 2.6% remediation rate, and 92.3% first-time board pass rate. The reduction in attrition rate and increase in first-time board pass rate between new and old methods was statistically significant (p < 0.01). CONCLUSION:Standardized assessment of resident applicants can help improve the identification of residents who will be successful in residency and help improve diversity within the residents. Programs directors can adapt this framework to help prioritize the objective characteristics they would like in their incoming residents and to increase the chances of success in their programs.

Abstract Introduction Severe burn injuries frequently result in multi-organ dysfunction, with the lungs being particularly susceptible, leading to substantial morbidity and mortality. However, the mechanisms underlying post-burn pulmonary injury remain to be elucidated. Our objective was to provide a comprehensive transcriptomic profile of lungs following severe burn injury to explore novel biomarker genes and potential therapeutic targets for burn injury induced lung diseases. Methods A severe burn animal model was established in C57BL/6J mice by undergoing 30% total body surface area scald injury to produce a full-thickness burn. A total of twelve C57BL6 male mice (10-weeks-old) were divided into three groups (Sham, 3 days and 7 days post burn). Mouse lung tissues were harvested post-burn and the differential gene expression profiling was performed by RNA-Seq analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to predicate the related pathological pathways and candidate genes. Quantitative RT-qPCR was employed to verify the gene expression and functions in both in vivo and in vitro settings (using human primary small airway epithelial cells, hSAECs). Statistical analysis was conducted using GraphPad Prism version 10.0. Results Transcriptomic data revealed a total of 419 differentially expressed genes (DEGs) in both burned groups compared to the sham group (fold-change > 2 and p value < 0.05). Of these, 265 genes were uniquely changed at 3 days post burn, 87 genes were common, and 67 genes were regulated at 7 days post burn. Additionally, 306 DEGs were identified when comparing the 3-day and 7-day post-burn periods. Pathway analysis highlighted the top three enriched pathways in response to burn injury: Inflammation mediated by chemokine and cytokine signaling, Interleukin signaling and Apoptosis signaling. Notably, Prokineticin-2 (PK2) emerged as the most significantly altered gene in the lungs of burned mice. It was confirmed by qRT-PCR analysis that PK2 was initially detected at 3 days post burn and dramatically increased at 7 days post burn. Treatment of cultured hSAECs with recombinant human PK2 peptide resulted in decreased TNFa-induced inflammation responses (IL-6, IL-8, MMP9, and Grob) and reduced respiratory rhinoviral infection, suggesting the compensatory protective role of PK2 against burn-induced lung inflammation and infection. Conclusions Our study unveils the distinctive gene expression profile in the lungs of scalded mice and identifies a paradigm for compensatory protective PK2 signaling. This finding may serve as a crucial foundation for future in-depth investigations into burn-induced lung injury. Applicability of Research to Practice This research illuminates the protective role of PK2 against pulmonary inflammation following severe burn injuries, offering potential avenues for therapeutic interventions and improved patient care.

Introduction Chronic liver disease is driven by a prolonged wound healing response leading to fibrogenesis, potentially progressing to cirrhosis. Hepatic stellate cells (HSCs) are the primary cells driving hepatic fibrosis because they are major producers of extracellular matrix. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ΚB) pathway is a key regulator of inflammatory signaling, and survival of activated HSCs has been found to be NF-KB dependent. Our team previously synthesized HJC0416—a signal transducer and activator of transcription three inhibitor with potent anti-inflammatory effects. In HSCs, HJC0416 reduced cell viability, extracellular matrix production, and—notably—NF-KB activation. However, HJC0416’s antifibrogenetic mechanism remains unknown. This study examined the effects of HJC0416 on NF-KB and its associate factor HSP-90 in HSCs. Methods The activated human HSC line LX-2 was treated with either HJC0416 or 17-AAG, then exposed to TNFα as indicated. Nuclear and cytosolic proteins were isolated for Western blot or immunofluorescence assay. Results HJC0416 significantly attenuated TNFα-induced IκBα phosphorylation, NF-KBp65 nuclear translocation, and DNA binding activity. Endogenous and TNFα-induced p65 phosphorylation of S536 was suppressed by HJC0416. Notably, HJC0416 dose-dependently attenuated the expression of FAK, IKKα, and signal transducer and activator of transcription three which are Heat Shock Protein 90 (HSP90) interacting proteins. The expression of other HSP90 interacting proteins—RIP1, AKT, FAK, and cyclin-dependent kinase nine—were decreased. HSP90-specific inhibitor 17-AAG significantly attenuated TNFα-induced IκBα phosphorylation and degradation, p65 nuclear translocation, DNA binding, and production of collagen type I and fibronectin. Conclusions The HSP90 chaperone protein may be a key intermediary linking HJC0416’s ability to inhibit NF-κB activity. HJC0416 may be a promising drug candidate for liver fibrosis.

Background: Cholecystoenteric fistulae are rare complications of gallstone disease, with a reported incidence of 0.5% to 0.9% of cholecystectomies. Cholecystoduodenal is the most common fistula followed by cholecystocolonic fistulae.Summary: We report a case of pneumobilia resulting from a combined cholecystoduodenal and cholecystocolonic fistulae treated with a laparoscopic subtotal cholecystectomy and open repair of the enteric fistulae.Conclusion: Combined cholecystoduodenal and cholecystocolonic fistulae are an extremely rare complication of gallstone disease, and meticulous preoperative planning and operative dexterity are needed to safely manage these unusual fistulae.

Importance Individuals who are incarcerated represent a vulnerable group due to concerns about their ability to provide voluntary and informed consent, and there are considerable legal protections regarding their participation in medical research. Little is known about the quality of surgical care received by this population. Objective To evaluate perioperative surgical care provided to patients who are incarcerated within the Texas Department of Criminal Justice (TDCJ) and compare their outcomes with that of the general nonincarcerated population. Design, Setting, and Participants This cohort study analyzed data from patients who were incarcerated within the TDCJ and underwent general or vascular surgery at the University of Texas Medical Branch (UTMB) from 2012 to 2021. Case-specific outcomes for a subset of these patients and for patients in the general academic medical center population were obtained from the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) and compared. Additional quality metrics (mortality index, length of stay index, and excess hospital days) from the Vizient Clinical Data Base were analyzed for patients in the incarcerated and nonincarcerated groups who underwent surgery at UTMB in 2020 and 2021 to provide additional recent data. Patient-specific demographics, including age, sex, and comorbidities were not available for analysis within this data set. Main Outcome and Measures Perioperative outcomes (30-day morbidity, mortality, and readmission rates) were compared between the incarcerated and nonincarcerated groups using the Fisher exact test. Results The sample included data from 6675 patients who were incarcerated and underwent general or vascular surgery at UTMB from 2012 to 2021. The ACS-NSQIP included data (2012-2021) for 2304 patients who were incarcerated and 602 patients who were not and showed that outcomes were comparable between the TDCJ population and that of the general population treated at the academic medical center with regard to 30-day readmission (6.60% vs 5.65%) and mortality (0.91% vs 1.16%). However, 30-day morbidity was significantly higher in the TDCJ population (8.25% vs 5.48%, P = .01). The 2020 and 2021 data from the Vizient Clinical Data Base included 629 patients who were incarcerated and 2614 who were not and showed that the incarcerated and nonincarcerated populations did not differ with regard to 30-day readmission (12.52% vs 11.30%) or morbidity (1.91% vs 2.60%). Although the unadjusted mortality rate was significantly lower in the TDCJ population (1.27% vs 2.68%, P = .04), mortality indexes, which account for case mix index, were similar between the 2 populations (1.17 vs 1.12). Conclusions and Relevance Findings of this cohort study suggest that patients who are incarcerated have equivalent rates of mortality and readmission compared with a general academic medical center population. Future studies that focus on elucidating the potential factors associated with perioperative morbidity and exploring long-term surgical outcomes in the incarcerated population are warranted.

BACKGROUND:In small US communities, golf cart utilization has become increasingly more common. In the past 3 years, the incidence and severity of pediatric golf cart-related trauma evaluated at our trauma center have noticeably increased. Thus, the aim of this study was to analyze trends, identify risk and protective factors, and provide community-level recommendations to improve golf cart safety for children in a coastal community. METHODS:A retrospective cross-sectional study of our institutional trauma registry was performed. The registry was queried for golf cart injuries between 2012 and 2022. Demographics, accident details, hospital course, and outcomes were reviewed. Data analysis involved quantitative statistics. Incident locations were mapped, including additional data from the County emergency medical service. In addition, customer education at four prominent golf rental shops was observed. RESULTS:Annual golf cart-related traumas doubled starting in 2020. Of 235 total patients, 105 (46%) were children. Median age was 11.5 years (range, 2-17 years). Fifty-five percent were female, and 67% were non-Hispanic White. Eighty percent were out-of-county residents. The most common injury location was extremity (56%). The median Injury Severity Score was 4, and 3% died. Only 10% of children were restrained. Forty-one percent were ejected, and most (84%) were front-facing passengers. Ejection was associated with more severe injury (odds ratio, 4.13; p = 0.01). Most injuries occurred during 5 to 10 pm (47%), weekends, and summertime. Nighttime injuries were more severe than daytime ( p = 0.04). A hotspot of crashes was identified in a zone where golf carts were restricted. Rental stores provided education on seat belt use, car seat use for infants, and off-limit zones. However, rules were not enforced. CONCLUSION:Our results inform the following golf cart injury prevention opportunities: raising awareness of injury risks to children in high-tourist areas, partnering with rental stores to enforce rules, improving signage, adding protected lanes, and adopting a no nighttime operation policy. LEVEL OF EVIDENCE:Prognostic and Epidemiological; Level IV.

Introduction: Texas consistently accounts for approximately 10% of annual national births, the second highest of all US states. This temporal study aimed to evaluate incidences of neonatal surgical conditions across Texas and to delineate regional pediatric surgeon accessibility. Methods: The Texas Birth Defects Registry was queried from 1999 to 2018, based on 11 wellestablished regions. Nine disorders (30,476 patients) were identified as being within the operative scope of pediatric surgeons: biliary atresia (BA), pyloric stenosis (PS), Hirschsprung's disease, stenosis/atresia of large intestine/rectum/anus, stenosis/atresia of small intestine, tracheoesophageal fistula/esophageal atresia, gastroschisis, omphalocele, and congenital diaphragmatic hernia. Annual and regional incidences were compared (/10,000 births). Statewide pediatric surgeons were identified through the American Pediatric Surgical Association directory. Regional incidences of neonatal disorder per surgeon were evaluated from 2010 to 2018 as a surrogate for provider disparity. Results: PS demonstrated the highest incidence (14.405/10,000), while BA had the lowest (0.707/10,000). Overall, incidences of PS and BA decreased significantly, while incidences of Hirschsprung's disease and small intestine increased. Other diagnoses remained stable. Regions 2 (48.24/10,000) and 11 (47.79/10,000) had the highest incidence of neonatal conditions; Region 6 had the lowest (34.68/10,000). Three rural regions (#2, 4, 9) lacked pediatric surgeons from 2010 to 2018. Of regions with at least one surgeon, historically underserved regions (#10, 11) along the Texas-Mexico border consistently had the highest defect per surgeon rates. Conclusions: There are temporal and regional differences in incidences of neonatal conditions treated by pediatric surgeons across Texas. Improving access to neonatal care is a complex issue that necessitates collaborative efforts between state legislatures, health systems, and providers.

IntroductionActivated hepatic stellate cells (HSCs) are the primary effector cells in hepatic fibrosis, over depositing extracellular matrix (ECM) proteins. Our previous work found oridonin analog CYD0682 attenuates proliferation, Transforming Growth Factor β (TGFβ)–induced signaling, and ECM production in immortalized HSCs. The underlying mechanism behind these reductions is unclear. The Signal Transduction and Activator of Transcription 3 (STAT3) pathway plays a central role in HSC activation and has been found to be overexpressed in models of hepatic injury. In this study, we will examine the effect of CYD0682 on STAT3 signaling.MethodsImmortalized human (LX-2) and rat (HSC-T6) HSC lines were treated with CYD0682 or Tanespimycin (17-AAG) with or without TGF-β. Nuclear and cytosolic proteins were extracted. Protein expression was analyzed with Western blot. DNA binding activity was assessed with STAT3 DNA Binding ELISA. Cell viability was assessed with Alamar blue assay.ResultsCYD0682 treatment inhibited STAT3 phosphorylation at tyrosine 705 in a dose-dependent manner in LX-2 and HSC-T6 cells. STAT3 DNA binding activity and STAT3 regulated protein c-myc were significantly decreased by CYD0682. Notably, TGFβ–induced STAT3 phosphorylation and ECM protein expression were inhibited by CYD0682. STAT3 is reported to be a Heat Shock Protein 90 (HSP90) client protein. Notably, CYD0682 attenuated the expression of endogenous STAT3 and other HSP90 client proteins FAK, IKKα, AKT and CDK9. HSP90 specific inhibitor 17-AAG suppressed endogenous and TGFβ–induced STAT3 phosphorylation and ECM protein production.ConclusionsCYD0682 attenuates endogenous and TGFβ-induced STAT3 activation and ECM production via an HSP90 dependent pathway in HSCs. Further study of this pathway may present new targets for therapeutic intervention in hepatic fibrosis.

The irreversible termination of individual life activities and metabolism means all fatal problems ultimately terminate the heart function. It’s very important to protect the patient’s life if we have treatment to maintain heart function and care about patients’ heart response. It is known that many diseases induced heart dysfunction including Chagas disease, burn injury, smoking and other bad stresses. Chronic stress causes these physical symptoms and emotional symptoms. Due to the awareness created by the media and internet, patients are generally aware that they should seek help immediately for chest pain. Therefore, attention and studies on stress-induced heart dysfunction would help uncover the pathophysiological mechanisms of cardiac response to non-heart diseases and provide an insight of heart-protection drugs. At the same time, physicians should be aware of this new condition and how to diagnose and treat it, even though the causal mechanisms are not yet fully understood. This special chapter will discuss on the cardiac response to the stresses especially on our associated research in recent decades such as Trypanosoma cruzi (T. cruzi)-induced cardiomyopathy and burn injury–induced cardiomyopathy, and on some very popular stresses such as behavior, motion, mental, and smoking.

Abstract Introduction Cardiac function has been found to decrease within the first 24 hours after burn injury and has been documented to stay depressed for up to 72 hours. Cardioprotective drugs such as sildenafil, PJ34, MitoTEMPO, and ZLN005 have been shown to counteract this dysfunction when administered 1 hour before burn injury. However, there remains limited knowledge on the effects of cardioprotective drugs in the early phase of burn injury. Methods Sprague-Dawley rats were divided into 6 groups. In 5 groups, a 60% TBSA scald burn was performed. Cardioprotectors Sildenafil, PJ34, MitoTEMPO, and ZLN005 were administered to 6 rats per group. A control group of 6 unburned rats was maintained in synchrony. Burned and unburned rats were sacrificed after measurement of heart function using echocardiography (ECHO, Vevo2100 echocardiograph). Heart rate (HR), left ventricular ejection fraction (LVEF), fractional shortening (FS), cardiac output (CO), intraventricular septum (IVS), left ventricular (LV) mass, left ventricular wedge pressure (LVWP) and left ventricular internal diameter (LVID) were assessed with the Vevo2100 echocardiograph software. Results Compared to sham control, heart rat (HR), diastolic LVID significantly increased at 3 hours post burn. CO, EF, FS, IVS in systole and diastole decreased at 3 hours post burn. LVID after administration of Sildenafil reduced heart rate at 3 hours post burn. ZLN005 restored burn-induced IVS systolic and diastolic decrease at 3 hours post burn. All drugs improved burn-induced EF, FS. Sildenafil and TEMPO recovered CO at 3 hours post burn. Conclusions In this study, cardiac function was found to be reduced up to 13 days after initial injury. Sildenafil, ZLN005, and TEMPO were shown to recover cardiac function at 3 hours post-injury, showing improvements in EF and FS. Sildenafil reduced HR and CO while ZLN005 restored burn-induced IVS during systole and diastole. This suggests the cardioprotective utility of these medications if administered early after burn injury. Applicability of Research to Practice Will help improve critical care and understanding of cardiac function.

Extracorporeal membrane oxygenation (ECMO) is utilized in the management of severe respiratory and circulatory failure. Advanced malignancy is a relative contraindication, but the indication for ECMO in the oncologic population has not been clearly established because of the wide spectrum of malignant disease and prognoses. The Extracorporeal Life Support Organization database was queried for patients older than 18 years with an International Classification of Diseases code of neoplasm over the past 2 decades (2000–2019). The data were divided into 2 decades to analyze and compare the trends with background and outcomes. One thousand six-hundred ninety-seven patients met inclusion criteria from the latest decade which is over 15 times the previous decade (n = 110). Compared with the previous decade, ECMO was used more in patients with older age (56 vs . 50.5 years old; p < 0.001), cardiac and extracorporeal cardiopulmonary resuscitation (ECPR) support type ( p = 0.011), and lower oxygenation index (23.0 vs . 35.6; p < 0.001) in the latest decade. Although overall survival did not show significant improvement overall (38.9% vs . 33.6%; p = 0.312), survival in pulmonary ECMO has significantly improved in the latest decade (41.6% vs . 29.1%; p = 0.032). Compared with the previously reported data for all adult ECMO, our patients had a significantly lower survival with pulmonary (41.6% vs . 61.1%; p < 0.001) and cardiac (38.4% vs . 44.3%; p = 0.008) support while not with ECPR.

Background Liver tumors exhibiting hepatocellular, cholangiocarcinoma, and neuroendocrine features are extremely rare, with only five cases reported in the literature. Case presentation We present an unusual case of a combined hepatocellular-cholangiocarcinoma (cHCC-CC) with neuroendocrine features in a pediatric patient. A 16-year-old presented with abdominal pain and a 21.0 cm mass in the right hepatic lobe with extension into the left lobe. Histology showed a poorly differentiated tumor with a solid, tubuloglandular, and microcystic architecture. Immunohistochemistry results were negative for hepatic markers, positive for markers of biliary differentiation, and positive for neuroendocrine differentiation. The neoplasm was reviewed at several institutions with differing diagnoses. Single nucleotide polymorphism (SNP) chromosomal microarray (CMA) showed large deletions within chromosomes 6q and 13q in both the hepatocellular-like areas and the cholangiocarcinoma-like areas, with additional large deletions in the cholangiocarcinoma-like areas, supporting origin from hepatocellular carcinoma. The final diagnosis was a cHCC-CC with neuroendocrine features. Conclusions Diagnosis of cHCC-CCs relies predominately on histomorphology, as per the 2018 International Consensus Group on the nomenclature of cHCC-CC. These findings in this case support that the pathological classification of these lesions be based on molecular data, which could better direct treatment. Further classification of cHCC-CCs and determination of their clinicopathological relevance will require more interobserver consistency and continued molecular profiling of these lesions.

Introduction: Social media utilization is expanding within graduate medical education and academic surgery. This study aims to quantify the current social media footprint of pediatric surgery (PS) fellowship training programs.Methods: United States PS fellowship programs from the American Pediatric Surgical Association website and social media accounts on three platforms (Facebook, Instagram, Twitter) were identified. Authors quantified subject matter within public program content and compared PS social media utilization to other surgical training programs. A public Twitter survey was disseminated to evaluate recent PS applicant Twitter use and perceptions about content posted by programs.Results: Of 51 PS fellowship programs, 23 (45.1%) had active Twitter accounts, 2 (3.9%) had active Facebook accounts, and 1 (2.0%) had an active Instagram account. Cumulatively, 5162 organic posts were published across all 26 accounts (90.4% on Twitter). Most commonly posted content included research/conference presentations (31.3%) and faculty accolades (15.1%), while clinical/OR experience (3.6%), gender/ethnic diversity (2.4%) had the least content. Compared to other training programs, PS has lower utilization of Facebook (p < 0.001) and Instagram (p < 0.001), but similar Twitter utilization (p 1/4 0.09). Twenty-four recent applicants responded to the public Twitter survey. Most (62.5%) used Twitter intentionally for recruitment and networking purposes when applying to fellowship. They expressed desire for increased content related to clinical/OR experiences, program ethnic/gender diversity and recruitment information. Conclusion: Amongst PS training programs, Twitter is the most commonly utilized platform. Expanding Twitter usage to more programs and posting more varied content may facilitate opportunities for diverse applicant recruitment and serve as a platform to share clinical knowledge, which will ultimately move the needle towards growth and equity.Level of Evidence: IV.(c) 2023 Elsevier Inc. All rights reserved.