Fidelity in Academic Global Surgery and Research: Incorporating Trustworthiness in the Development of Research Partnerships, Infrastructure, and Policy.

Academic global surgery consists of collaborative partnerships that address surgical inequities through research, training, education, advocacy, and diplomacy. It has been characterized by increased scholastic production through global surgery publications, dedicated global surgery sessions within scientific conferences, global surgery-specific research grants, database development to support global surgery research, global surgery research fellowships, and global surgery-based academic promotion paradigms. The increased emphasis on global surgery research has been accompanied by multiple ethical challenges. This article reviews critical ethical dilemmas presented by global surgery research efforts and proposes interventions on the partnership, infrastructural, and policy levels to enhance fidelity within research partnerships.

Metal and metalloid maternal transfer in a newborn West Indian manatee (Trichechus manatus) two years after the northeastern oil spill disaster of 2019 in Brazil.

A large-scale oil spill along the northeastern Brazilian coast in 2019-2020 severely impacted primary manatee habitats in Brazil. This study aimed to assess metal and metalloid contamination in a dead manatee calf found following this oil spill. Several elements were detected, including chromium, iron, nickel, lead, and vanadium, which are crude oil components, and thallium, a component of dispersants used to degrade and dissipate crude oil. The presence of these contaminants in the manatee calf is indicative of maternal exposure, metabolism, and newborn transference via placenta and lactation. This is the first report of mother-calf metal transfer in manatees, highlighting the species' vulnerability and potential long-term population dynamics effects, and the first report for several metals and metalloids in these animals, laying the foundation for future research efforts. These findings highlight the urgent need for continued environmental monitoring, ecotoxicological assessments, and conservation initiatives.

Higher prevalence of benign tumors in men with testicular tumors and history of treated cryptorchidism.

OBJECTIVES: To identify if surgically treated cryptorchidism correlated with testicular tumor pathology at presentation. MATERIALS AND METHODS: An institutional database of patients treated for testicular cancer between 2003 and 2020 was reviewed. Inclusion criteria included orchiectomy patients. Exclusion criteria included unknown cryptorchidism history or pathology or laterality of orchiectomy. Data collection included demographics, surgical history, and tumor marker status. RESULTS: A total of 435 patients were included. Thirty-three of these patients had a history of UDT. There was no statistical difference in age at orchiectomy, laterality of orchiectomy, or lymphovascular invasion with regard to UDT history. There was a statistical difference in tumor pathology after orchiectomy, P = 0.03. On secondary analysis, benign pathology was significantly more common in patients with a history of UDT (15.2%) than without (4.7%), P = 0.01. Mixed GCT was also found at a significantly lower rate in patients with a history of UDT (18.2%) compared to those with no history of UDT (37.3%), P = 0.03. There were no statistically significant differences in other pathology. CONCLUSION: Previous studies have shown that there is a greater rate of seminoma in patients with testicular cancer in an undescended testis. This study shows that in patients with a history of UDT compared to those without a history of UDT, there is a greater percentage of patients with benign testicular masses after orchiectomy. Guideline based practices including monthly self-examination and testis-sparing surgery for appropriate patients may reduce rates of radical orchiectomy for benign tumors.

Practice Patterns Affecting Delays in Care of Testicular Torsion.

OBJECTIVES: To compare impact of day or on-call team, pediatric or adult attending, and patient age on testicular torsion management and outcomes. METHODS: A retrospective study of patients with testicular torsion between 2012 and 2022 at a single institution was conducted. Variables impacting management time were assessed using univariate analyses. RESULTS: One hundred and thirty-four patients were included: 49 underwent orchiectomies and 84 underwent orchiopexies. There was no significant difference between efficiency of on-call vs day team regarding time to ultrasound or time to operating room (OR). There were no significant differences between pediatric vs adult attending surgeons for time to surgery, intraoperative length of surgery, or testicular salvage rates. However, when patients were stratified by age greater or younger than 18years, older patients had significantly longer symptom duration (91.9 vs 20.0 minutes, P = .005), time to receive an ultrasound from emergency room registration (152 vs 87 minutes, P < .001), time to OR from emergency room registration (268 vs 185 minutes, P < .001), and time to OR from ultrasound read (187 vs 123 minutes, P = .03). Older patients also had lower rates of testicular salvage approaching significance (orchiectomy rate 48.8% vs 31.5%, P = .057). CONCLUSION: While no significant delays in testicular torsion management were detected between management by on-call vs day team nor pediatric vs adult attending, increased age of patient was associated with delays in definitive surgical management. Greater index of suspicion for testicular torsion diagnosis in adult patients may improve the rate of testicular salvage.

Remote Robotic Surgery and Virtual Education Platforms: How Advanced Surgical Technologies Can Increase Access to Surgical Care in Resource-Limited Settings.

Advanced surgical technologies consist of remote and virtual platforms that facilitate surgical care and education. It also includes the infrastructure necessary to utilize these platforms (e.g., internet access, robotic systems, and simulators). Given that 5 billion people lack access to safe and timely surgical care, the appeal of these technologies to the field of global surgery lies primarily in its ability to eliminate geographical barriers and address surgeon shortages. This article discusses the use of virtual and remote technologies in resource-limited settings, the potential applications of these technologies, the possible barriers to their integration, and the impact these technologies may have on access to surgical care and education. Specifically, it will explore how robotic surgery, telesurgery, virtual education platforms, and simulations have the potential to be instrumental in enhancing worldwide access to safe surgical care.

Practical and Ethical Guidelines for the Involvement of Trainees in Global Surgery: Consensus Statement and Recommendations from the Resident and Associate Society of the American College of Surgeons Global Surgery Work Group.

BACKGROUND: The guidelines provided by US professional surgical organizations for involvement of trainees in global surgery are limited. The aim of this consensus statement is to provide surgical trainees with official recommendations from the Resident and Associate Society of the American College of Surgeons Global Surgery Work Group (GSWG) regarding professional, practical, and ethical guidelines for participation in global surgery endeavors. STUDY DESIGN: A task force was created within the GSWG to review and define the scope of involvement of trainees in global surgery, and a consensus process was undertaken for the group at large to approve a set of proposed guidelines. RESULTS: The list of practical and ethical guidelines for the engagement of trainees in global surgery covering the themes of preparedness, reciprocity and collaboration, ethical considerations, and sustainability was approved with consensus from the GSWG. CONCLUSIONS: This consensus statement from the Resident and Associate Society of the American College of Surgeons GSWG outlines the official recommendations for guidelines for involvement of trainees in global surgery, with an aim to support equitable, sustainable collaborations that center on improving access to safe, timely, and affordable surgical care for the global community at large. Future processes seek to involve representation and perspectives from a larger body of low- to middle-income country surgical trainees.

Metal bioaccumulation and genotoxicity in Oreochromis niloticus reared in farming pools influenced by mining activities in Napo, in the Ecuadorian Amazonia.

Mining areas may suffer long-term metal contamination and represent harmful remnants of former mining activities. In the northern Amazon of Ecuador, former mining waste pits are used in Oreochromis niloticus (Nile tilapia) fish farming. Given the high consumption of this species by the local population, we aimed to estimate human consumption risks by determining Cd, Cu, Cr, Pb, and Zn tissue bioaccumulation (liver, gills, and muscle) and genotoxicity (micronucleus essay) in tilapia cultivated in one former mining waste pit (S3) and compare the findings to tilapias reared in two non-mining areas (S1 and S2); 15 fish total. Tissue metal content was not significantly higher in S3 than in non-mining areas. Cu and Cd were higher in the gills of tilapias from S1 compared to the other study sites. Higher Cd and Zn were detected in the liver of tilapias from S1 compared to the other sampling sites. Cu was higher in the liver of fish from S1 and S2, and Cr, in the gills of fish from S1. The highest frequency of nuclear abnormalities was observed in fish from S3, indicating chronic exposure to metals at this sampling site. The consumption of fish reared at the three sampling sites results in a 200-fold higher Pb and Cd ingestion than their maximum tolerable intake thresholds. Calculated estimated weekly intakes (EWI), hazard quotients (THQ), and Carcinogenic Slope Factors (CSFing) denote potential human health risks, indicating the need for continuous monitoring in this area to ensure food safety not only in areas affected by mining, but in general farms in the region.

Increased breast cancer mortality due to treatment delay and needle biopsy type: a retrospective analysis of SEER-medicare.

BACKGROUND: Substantial evidence indicates that delay of first treatment after diagnosis is associated with poorer survival outcomes in breast cancer. Accordingly, the Commission on Cancer introduced a quality measure for receipt of therapeutic surgery within 60 days of diagnostic biopsy for stage I-III breast cancer patients in the non-neoadjuvant setting. It is unknown, however, what may contribute to mortality associated with treatment delay. Therefore, we investigated whether biopsy type moderates the effect of the mortality risk posed by treatment delay. METHODS: Retrospective analysis of 31,306 women with stage I-III breast cancer diagnosed between 2003 and 2013 selected from the SEER-Medicare database was performed to determine whether needle biopsy type [core needle biopsy (CNB) or vacuum-assisted biopsy (VAB)] impacts time to treatment (TTT)-associated survival outcomes. Multivariable Fine-Gray competing risk survival models, adjusted for inverse propensity score weights, were used to determine the association between biopsy type, TTT, and breast cancer-specific mortality (BCSM). RESULTS: TTT ≥ 60 days was associated with 45% higher risk of BCSM (sHR = 1.45, 95% CI 1.24-1.69) compared to those with TTT < 60 days in stage I-III cases. Independent of TTT, CNB was associated with 28% higher risk of BCSM compared to VAB in stage II-III cases (sHR = 1.28, 95% CI 1.11-1.36), translating to a 2.7% and 4.0% absolute difference in BCSM at 5 and 10 years, respectively. However, in stage I cases, the BCSM risk was not associated with type of biopsy. CONCLUSIONS: Our results suggest that treatment delay ≥ 60 days is independently associated with poorer survival outcomes in breast cancer patients. In stage II-III, CNB is associated with higher BCSM than VAB. However, type of biopsy does not underlie TTT-associated breast cancer mortality risk.

Future directions in psychiatric neurosurgery: Proceedings of the 2022 American Society for Stereotactic and Functional Neurosurgery meeting on surgical neuromodulation for psychiatric disorders.

OBJECTIVE: Despite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many as 30-40% of patients. Neuromodulation, including deep brain stimulation (DBS), has emerged as a potential therapy for persistent disabling disease, however it has not yet gained widespread adoption. In 2016, the American Society for Stereotactic and Functional Neurosurgery (ASSFN) convened a meeting with leaders in the field to discuss a roadmap for the path forward. A follow-up meeting in 2022 aimed to review the current state of the field and to identify critical barriers and milestones for progress. DESIGN: The ASSFN convened a meeting on June 3, 2022 in Atlanta, Georgia and included leaders from the fields of neurology, neurosurgery, and psychiatry along with colleagues from industry, government, ethics, and law. The goal was to review the current state of the field, assess for advances or setbacks in the interim six years, and suggest a future path forward. The participants focused on five areas of interest: interdisciplinary engagement, regulatory pathways and trial design, disease biomarkers, ethics of psychiatric surgery, and resource allocation/prioritization. The proceedings are summarized here. CONCLUSION: The field of surgical psychiatry has made significant progress since our last expert meeting. Although weakness and threats to the development of novel surgical therapies exist, the identified strengths and opportunities promise to move the field through methodically rigorous and biologically-based approaches. The experts agree that ethics, law, patient engagement, and multidisciplinary teams will be critical to any potential growth in this area.

Bladder capacity and growth in classic bladder exstrophy: A novel predictive tool.

INTRODUCTION: Bladder capacity (BC) is an important metric in the management of patients with classic bladder exstrophy (CBE). BC is frequently used to determine eligibility for surgical continence procedures, such as bladder neck reconstruction (BNR), and is associated with the likelihood of achieving urinary continence. OBJECTIVE: To use readily available parameters to develop a nomogram that could be used by patients and pediatric urologists to predict BC in patients with CBE. STUDY DESIGN: An institutional database of CBE patients was reviewed for those who have undergone annual gravity cystogram 6 months after bladder closure. Candidate clinical predictors were used to model BC. Linear mixed effects models with random intercept and slope were used to construct models predicting log transformed BC and were compared with adjusted R2, Akaike Information Criterion (AIC), and cross-validated mean square error (MSE). Final model evaluated via K-fold cross-validation. Analyses were performed using R version 3.5.3 and the prediction tool was developed with ShinyR. RESULTS: In total, 369 patients (107 female, 262 male) with CBE had at least one BC measurement after bladder closure. Patients had a median of 3 annual measurements (range 1-10). The final nomogram includes outcome of primary closure, sex, log-transformed age at successful closure, time from successful closure, and interaction between outcome of primary closure and log-transformed age at successful closure as the fixed effects with random effect for patient and random slope for time since successful closure (Extended Summary). DISCUSSION: Using readily accessible patient and disease related information, the bladder capacity nomogram in this study provides a more accurate prediction of bladder capacity ahead of continence procedures when compared to the age-based Koff equation estimates. A multi-center study using this web-based CBE bladder growth nomogram (https://exstrophybladdergrowth.shinyapps.io/be_app/) will be needed for widespread application. CONCLUSION: Bladder capacity in those with CBE, while known to be influenced by a broad swath of intrinsic and extrinsic factors, may be modeled by the sex, outcome of primary bladder closure, age at successful bladder closure and age at evaluation.

Postsurgical morbidity and mortality favorably informs deep brain stimulation for new indications including schizophrenia and schizoaffective disorder.

Background: Deep brain stimulation (DBS) shows promise for new indications like treatment-refractory schizophrenia in early clinical trials. In the first DBS clinical trial for treatment refractory schizophrenia, despite promising results in treating psychosis, one of the eight subjects experienced both a symptomatic hemorrhage and an infection requiring device removal. Now, ethical concerns about higher surgical risk in schizophrenia/schizoaffective disorder (SZ/SAD) are impacting clinical trial progress. However, insufficient cases preclude conclusions regarding DBS risk in SZ/SAD. Therefore, we directly compare adverse surgical outcomes for all surgical procedures between SZ/SAD and Parkinson's disease (PD) cases to infer relative surgical risk relevant to gauging DBS risks in subjects with SZ/SAD. Design: In the primary analysis, we used browser-based statistical analysis software, TriNetX Live (trinetx.com TriNetX LLC, Cambridge, MA), for Measures of Association using the Z-test. Postsurgical morbidity and mortality after matching for ethnicity, over 39 risk factors, and 19 CPT 1003143 coded surgical procedures from over 35,000 electronic medical records, over 19 years, from 48 United States health care organizations (HCOs) through the TriNetX Research Network™. TriNetXis a global, federated, web-based health research network providing access and statistical analysis of aggregate counts of deidentified EMR data. Diagnoses were based on ICD-10 codes. In the final analysis, logistic regression was used to determine relative frequencies of outcomes among 21 diagnostic groups/cohorts being treated with or considered for DBS and 3 control cohorts. Results: Postsurgical mortality was 1.01-4.11% lower in SZ/SAD compared to the matched PD cohort at 1 month and 1 year after any surgery, while morbidity was 1.91-2.73% higher and associated with postsurgical noncompliance with medical treatment. Hemorrhages and infections were not increased. Across the 21 cohorts compared, PD and SZ/SAD were among eight cohorts with fewer surgeries, nine cohorts with higher postsurgical morbidity, and fifteen cohorts within the control-group range for 1-month postsurgical mortality. Conclusions: Given that the subjects with SZ or SAD, along with most other diagnostic groups examined, had lower postsurgical mortality than PD subjects, it is reasonable to apply existing ethical and clinical guidelines to identify appropriate surgical candidates for inclusion of these patient populations in DBS clinical trials.

USP9X mediates an acute adaptive response to MAPK suppression in pancreatic cancer but creates multiple actionable therapeutic vulnerabilities.

Pancreatic ductal adenocarcinomas (PDACs) frequently harbor KRAS mutations. Although MEK inhibitors represent a plausible therapeutic option, most PDACs are innately resistant to these agents. Here, we identify a critical adaptive response that mediates resistance. Specifically, we show that MEK inhibitors upregulate the anti-apoptotic protein Mcl-1 by triggering an association with its deubiquitinase, USP9X, resulting in acute Mcl-1 stabilization and protection from apoptosis. Notably, these findings contrast the canonical positive regulation of Mcl-1 by RAS/ERK. We further show that Mcl-1 inhibitors and cyclin-dependent kinase (CDK) inhibitors, which suppress Mcl-1 transcription, prevent this protective response and induce tumor regression when combined with MEK inhibitors. Finally, we identify USP9X as an additional potential therapeutic target. Together, these studies (1) demonstrate that USP9X regulates a critical mechanism of resistance in PDAC, (2) reveal an unexpected mechanism of Mcl-1 regulation in response to RAS pathway suppression, and (3) provide multiple distinct promising therapeutic strategies for this deadly malignancy.

First description of a Gammaherpesvirus in a common dolphin (Delphinus delphis) from the Eastern Mediterranean Sea.

In September 2020, a male common dolphin (Delphinus delphis) was found dead on a beach near Bat-Yam, Israel. A small, raised, well circumscribed penile lesion (i.e., mass) was identified and removed for histology and molecular characterizations. By histology, the penile mass presented focal keratinization of the squamous epithelium and a mild ballooning of acanthocytes in lower epithelium levels, as well as features compatible with viral plaques, and tested positive for a gammaherpesvirus through molecular characterization analyses. Tissue samples from the lungs, liver, and spleen, however, tested negative for herpesvirus infection. The gammaherpesvirus detected herein is similar to other isolates found in several areas worldwide in different cetacean species. This is the first reported case of gammaherpesvirus infection in dolphins from the eastern Mediterranean Sea, indicative of the need for long-term assessments to create viral infections databases in cetaceans, especially in a climate change context, which is likely to intensify infectious disease outbreaks in marine mammals in the future.

Suicide in Deep Brain Stimulation for Parkinson's Disease: A Retrospective Case-Control Study.

Deep brain stimulation (DBS), a treatment of Parkinson's disease (PD), has been associated with suicidality. We conducted a case-control study comparing suicide in four pairs of cohorts: PD patients with DBS or not, epilepsy patients with resection surgery or not, subjects with BMI≥30 with bariatric surgery or not, and patients with chronic kidney disease with transplantation or not. PD patients with DBS demonstrated a lower risk of suicide relative to PD patients without DBS. Findings from other elective surgeries indicate that patients receiving operative treatments do not possess predictable differences in suicide rates relative to their medically managed counterparts.

A pilot study of multi-modal pain management for same-day discharge after minimally invasive repair of pectus excavatum (Nuss procedure) in children.

BACKGROUND: Despite advancements in minimally invasive repair of pectus excavatum (MIRPE), Nuss procedure, postoperative pain control remains challenging. This report covers a multimodal regimen using bilateral single-shot paravertebral block (PVB) and bilateral thoracoscopic intercostal nerve (T3-T7) cryoablation, leading to significant reduction in length of stay (LOS) and high rate of same-day discharge. METHODS: This is a comparative study of pain management protocols for patients undergoing the Nuss procedure at a single center from 2016 through 2020. All patients underwent the the same surgical technique for the treatment of pectus excavatum at a single center. Patients received bilateral PVB with continuous infusion (Group 1, n = 12), bilateral PVB with infusion and right-side cryoablation (Group 2, n = 9), or bilateral single-shot PVB and bilateral cryoablation (Group 3, n = 17). The primary outcome was LOS with focus on same-day discharge, and the secondary outcome was decreased opioid usage. RESULTS: Eleven of 17 patients in Group 3 (65%) (bilateral single-shot PVB and bilateral cryoablation) were discharged the same day as surgery. The remaining Group 3 patients were discharged the following day with no complications or interventions. Compared to Group 1 (no cryoablation), Group 3 had shorter LOS (median 4.4 days vs. 0.7 days, respectively, p < 0.001) and significantly decreased median opioid use on the day of surgery (0.92 mg/kg vs. 0.47 mg/kg, p = 0.006). CONCLUSION: Findings demonstrate the feasibility of multimodal pain management for same-day discharge after the Nuss procedure. Future multisite studies are needed to investigate the superiority of this approach to established methods. LEVEL OF EVIDENCE: III.

Serious lesions in Green turtles (Chelonia mydas) afflicted by fatal Spirorchiidiasis found stranded in south and southeastern Brazil.

Several diseases have been reported as affecting endangered wild sea turtle population worldwide, including spirorchiidiasis. This parasitic infection results in serious circulatory disorders in sea turtles, as well as tissue damage due to the presence of spirorchiids eggs. However, few reports of organs severely affected by tissue replacement caused by granulomatous inflammatory processes due to spirorchiidiasis in sea turtles are available. In this regard, this study describes massive lesions in 16 juvenile green turtles from southeastern Brazil presenting no other detectable diseases or injuries, associated to parasitic compression of air spaces, parasitic thyroid atrophy, parasitic encephalic compression and parasitic splenic lymphoid depletion. These rare injuries were categorized as extremely severe, affecting most spirorchiidiasis-infected organs. Spirorchiidiasis was, thus, noted herein as capable of causing a variety of lethal injuries to vital or extremely important organs in sea turtles. Spirorchiidiasis should, therefore, also be considered a potential cause of death in stranded green sea turtle monitoring efforts.

Sustained Inflammation of Breast Tumors after Needle Biopsy.

INTRODUCTION: Needle biopsy is essential for definitive diagnosis of breast malignancy. Significant histologic changes due to tissue damage have been reported in solid tumors. This study investigated the association between time from needle biopsy and inflammation in breast tumors. METHODS: A total of 73 stage I-II invasive breast cancer cases diagnosed by image-guided needle biopsy who had surgery as their first definitive treatment were retrospectively analyzed. Time from biopsy to surgical excision ranged from 8 to 252 days. Histological sections of surgically resected tumors with a visible needle tract were reviewed by histologic evaluation. Data were analyzed by McNemar's test for proportional differences, and the Benjamini-Hochberg procedure was used to assess the association between immune cell prevalence and clinical variables. RESULTS: Characteristic histology changes, including foreign body giant-cell reaction, synovial-cell metaplasia, desmoplastic repair changes, granulation tissue, fat necrosis, and inflammation, were frequently detected adjacent to the needle tract. Spatial comparison indicated that a higher proportion of cases had neutrophils, eosinophils, and macrophages adjacent to the needle tract than tumors distant from it. The presence of inflammatory cells adjacent to the needle tract was not associated with time from biopsy or subtype. Still, plasma cells were associated with residual carrier material from biopsy markers. CONCLUSION: Macrophages and eosinophils are highly abundant and retained adjacent to the needle tract regardless of time from the biopsy.

Pharmaceuticals, natural and synthetic hormones and phenols in sediments from an eutrophic estuary, Jurujuba Sound, Guanabara Bay, Brazil.

A screening for microcontaminants performed by gas chromatography detected several microcontaminants in 12 sediment samples from the eutrophic estuary Guanabara Bay (GB) in southeastern Brazil. Bisphenol A (BPA) ranged from 1.4 to 20.3 ng g-1, 4-octylphenol, from

Toxic Metals and Metalloids in Infant Formulas Marketed in Brazil, and Child Health Risks According to the Target Hazard Quotients and Target Cancer Risk.

Children are highly vulnerable to chemical exposure. Thus, metal and metalloid in infant formulas are a concern, although studies in this regard are still relatively scarce. Thus, the presence of aluminum, arsenic, cadmium, tin, mercury, lead, and uranium was investigated in infant formulas marketed in Brazil by inductively coupled plasma mass spectrometry, and the Target Hazard Quotients (THQ) and Target Cancer Risk (TCR) were calculated in to assess the potential risk of toxicity for children who consume these products continuously. Aluminum ranging from 0.432 ± 0.049 to 1.241 ± 0.113 mg·kg-1, arsenic from 0.012 ± 0.009 to 0.034 ± 0.006 mg·kg-1, and tin from 0.007 ± 0.003 to 0.095 ± 0.024 mg·kg-1 were the major elements, while cadmium and uranium were present at the lowest concentrations. According to the THQ, arsenic contents in infant formulas showed a THQ > 1, indicating potential health risk concerns for newborns or children. Minimal carcinogenic risks were observed for the elements considered carcinogenic. Metabolic and nutritional interactions are also discussed. This study indicates the need to improve infant formula surveillance concerning contamination by potentially toxic and carcinogenic elements.