PANGEA: a new gene set enrichment tool for Drosophila and common research organisms.

Gene set enrichment analysis (GSEA) plays an important role in large-scale data analysis, helping scientists discover the underlying biological patterns over-represented in a gene list resulting from, for example, an 'omics' study. Gene Ontology (GO) annotation is the most frequently used classification mechanism for gene set definition. Here we present a new GSEA tool, PANGEA (PAthway, Network and Gene-set Enrichment Analysis; https://www.flyrnai.org/tools/pangea/), developed to allow a more flexible and configurable approach to data analysis using a variety of classification sets. PANGEA allows GO analysis to be performed on different sets of GO annotations, for example excluding high-throughput studies. Beyond GO, gene sets for pathway annotation and protein complex data from various resources as well as expression and disease annotation from the Alliance of Genome Resources (Alliance). In addition, visualizations of results are enhanced by providing an option to view network of gene set to gene relationships. The tool also allows comparison of multiple input gene lists and accompanying visualisation tools for quick and easy comparison. This new tool will facilitate GSEA for Drosophila and other major model organisms based on high-quality annotated information available for these species.

Transoral management of pharyngeal ballistics.

OBJECTIVE: To present a case of a ballistic foreign body in the pharynx after a gunshot wound to the maxillofacial area, an accompanying review of relevant literature, and our approach to management. METHOD: A 68-year-old male with no prior medical history presented to our trauma center with gunshot wounds to the left chin, left wrist, right chest, and sternum. A CT Angiogram of the neck revealed a bullet fragment left neck and additional fragment adjacent to the L hypopharynx at the level of the hyoid. The patient was taken to the operating room for direct laryngoscopy with foreign body removal and esophagoscopy. RESULTS: We document our workup and successful surgical removal of the pharyngeal ballistic foreign body via our video abstract, compiling preoperative imaging, intraoperative imaging, and video. Literature review of the subject accompanying our video abstract highlights the extensive complications that can occur from a retained foreign body in this area, supporting surgical removal of the foreign body if safely possible. CONCLUSION: Given the demonstrated feasibility and success of endoscopic foreign body removal from the pharyngoepiglottic space, in addition to overwhelming support for removal in the literature we recommend surgical extraction of ballistic foreign bodies located in the upper aerodigestive tract in stable patients to avoid early and long-term complications that can impact swallowing function, airway stability and the vital structures contained within the neck.

The Effect of Conflict on Obstetric and Non-Obstetric Surgical Needs and Operative Mortality in Fragile States.

BACKGROUND: Médecins Sans Frontières (MSF) provides surgical care in fragile states, which are more vulnerable to conflict. The primary objective of this study was to compare the indications for operative intervention in surgical projects in fragile states during periods of active conflict (CON) and non-conflict (NON-CON). In addition, risk factors for non-obstetric and obstetric operative mortality were identified. METHODS: This was a retrospective analysis of MSF surgical projects in fragile states January 1, 2008-December 31, 2017. Variables considered in the analysis include age, gender, American Society of Anesthesiology physical status, emergency status, re-intervention status, indication for surgical intervention, and conflict/non-conflict time period. RESULTS: There were 30 surgical projects in 13 fragile states with 87,968 surgical interventions in 68,667 patients. Obstetric needs were the most common indication for surgical intervention (n = 28,060, 31.9%) but were more common during NON-CON (n = 23,142, 35.7%) compared to CON periods (n = 4,918, 21.2%, p < 0.001). Trauma was more common during CON (42.0%) compared to NON-CON (23.0%) periods (p < 0.001). Non-obstetric operative mortality was similar during CON (0.2%) compared to NON-CON (0.2%, p = 0.920), but obstetric operative mortality was higher (0.5%) during CON compared to NON-CON (0.2%, p < 0.001) periods. Risk factors for obstetric and non-obstetric mortality included age ≥ 30 years, ASA greater than 1, and emergency intervention. CONCLUSION: Humanitarian surgeons working in fragile states should be prepared to treat a range of surgical needs including trauma and obstetrics during conflict and non-conflict periods. The mortality in obstetric patients was higher during conflict periods, and further research to understand ways to protect this vulnerable group is needed.

Outcomes After Tracheostomy in COVID-19 Patients.

OBJECTIVE: To determine the outcomes of patients undergoing tracheostomy for COVID-19 and of healthcare workers performing these procedures. BACKGROUND: Tracheostomy is often performed for prolonged endotracheal intubation in critically ill patients. However, in the context of COVID-19, tracheostomy placement pathways have been altered due to the poor prognosis of intubated patients and the risk of transmission to providers through this highly aerosolizing procedure. METHODS: A prospective single-system multi-center observational cohort study was performed on patients who underwent tracheostomy after acute respiratory failure secondary to COVID-19. RESULTS: Of the 53 patients who underwent tracheostomy, the average time from endotracheal intubation to tracheostomy was 19.7 days ±â€Š6.9 days. The most common indication for tracheostomy was acute respiratory distress syndrome, followed by failure to wean ventilation and post-extracorporeal membrane oxygenation decannulation. Thirty patients (56.6%) were liberated from the ventilator, 16 (30.2%) have been discharged alive, 7 (13.2%) have been decannulated, and 6 (11.3%) died. The average time from tracheostomy to ventilator liberation was 11.8 days ±â€Š6.9 days (range 2-32 days). Both open surgical and percutaneous dilational tracheostomy techniques were performed utilizing methods to mitigate aerosols. No healthcare worker transmissions resulted from performing the procedure. CONCLUSIONS: Alterations to tracheostomy practices and processes were successfully instituted. Following these steps, tracheostomy in COVID-19 intubated patients seems safe for both patients and healthcare workers performing the procedure.

Oral Metformin for Treating Dermatological Diseases: A Systematic Review.

Introduction:Metformin is an antihyperglycemic medication most commonly used to treat Type II Diabetes Mellitus with promising off-label application for the treatment of hidradenitis suppurativa, psoriasis, acne, acanthosis nigricans, and hirsutism. Objective: To comprehensively assess evidence regarding the use of metformin for treating primary cutaneous disorders. Materials and Methods: A systematic literature search was conducted through PubMed, Cochrane, Web of Science, and CINAHL to identify the role of metformin in primary skin disease. Results: Sixty-four studies met inclusion criteria. Metformin demonstrates promising clinical response and favorable safety profile for treatment of HS, with most patients experiencing a decrease in frequency or severity of HS flares, and some experiencing full resolution of HS lesions. Patients with psoriasis treated with metformin experienced quantifiable clinical responses. Application of metformin on polycystic ovarian disease (PCOS) related acne, acanthosis nigricans, and hirsutism yielded mixed clinical results. No serious adverse effects were reported. Conclusion: Metformin is safe and efficacious and may be considered as an adjunctive therapy for the treatment of psoriasis and hidradenitis suppurativa in addition to first line therapies as well as PCOS related acne, acanthosis nigricans, and hirsutism. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.4874.

A geospatial evaluation of timely access to surgical care in seven countries.

OBJECTIVE: To assess the consistent availability of basic surgical resources at selected facilities in seven countries. METHODS: In 2010-2014, we used a situational analysis tool to collect data at district and regional hospitals in Bangladesh (n = 14), the Plurinational State of Bolivia (n = 18), Ethiopia (n = 19), Guatemala (n = 20), the Lao People's Democratic Republic (n = 12), Liberia (n = 12) and Rwanda (n = 25). Hospital sites were selected by pragmatic sampling. Data were geocoded and then analysed using an online data visualization platform. Each hospital's catchment population was defined as the people who could reach the hospital via a vehicle trip of no more than two hours. A hospital was only considered to show consistent availability of basic surgical resources if clean water, electricity, essential medications including intravenous fluids and at least one anaesthetic, analgesic and antibiotic, a functional pulse oximeter, a functional sterilizer, oxygen and providers accredited to perform surgery and anaesthesia were always available. FINDINGS: Only 41 (34.2%) of the 120 study hospitals met the criteria for the provision of consistent basic surgical services. The combined catchments of the study hospitals in each study country varied between 3.3 million people in Liberia and 151.3 million people in Bangladesh. However, the combined catchments of the study hospitals in each study country that met the criteria for the provision of consistent basic surgical services were substantially smaller and varied between 1.3 million in Liberia and 79.2 million in Bangladesh. CONCLUSION: Many study facilities were deficient in the basic infrastructure necessary for providing basic surgical care on a consistent basis.

Cost-Effectiveness in Global Surgery: Pearls, Pitfalls, and a Checklist.

INTRODUCTION: Cost-effectiveness analysis can be a powerful policy-making tool. In the two decades since the first cost-effectiveness analyses in global surgery, the methodology has established the cost-effectiveness of many types of surgery in low- and middle-income countries (LMICs). However, with the crescendo of cost-effectiveness analyses in global surgery has come vast disparities in methodology, with only 15% of studies adhering to published guidelines. This has led to results that have varied up to 150-fold. METHODS: The theoretical basis, common pitfalls, and guidelines-based recommendations for cost-effectiveness analyses are reviewed, and a checklist to be used for cost-effectiveness analyses in global surgery is created. RESULTS: Common pitfalls in global surgery cost-effectiveness analyses fall into five categories: the analytic perspective, cost measurement, effectiveness measurement, probability estimation, valuation of the counterfactual, and heterogeneity and uncertainty. These are reviewed in turn, and a checklist to avoid these pitfalls is developed. CONCLUSION: Cost-effectiveness analyses, when done rigorously, can be very useful for the development of efficient surgical systems in LMICs. This review highlights the common pitfalls in these analyses and methods to avoid these pitfalls.

Estimate of the global volume of surgery in 2012: an assessment supporting improved health outcomes.

BACKGROUND: It was previously estimated that 234·2 million operations were performed worldwide in 2004. The association between surgical rates and population health outcomes is not clear. We re-estimated global surgical volume to track changes over time and assess rates associated with healthy populations. METHODS: We gathered demographic, health, and economic data for 194 WHO member states. Surgical volumes were obtained from published studies and other reports from 2005 onwards. We estimated rates of surgery for all countries without available data based on health expenditure in 2012 and assessed the proportion of surgery comprised by caesarean delivery. The rate of surgery was plotted against life expectancy to describe the association between surgical care and this health indicator. FINDINGS: We identified 66 countries reporting surgical data between 2005 and 2013. We estimate that 312·9 million operations (95% CI 266·2-359·5) took place in 2012-a 33·6% increase over 8 years; the largest proportional increase occurred in countries spending US$400 or less per capita on health care. Caesarean delivery comprised 29·8% (5·8 million operations) of the total surgical volume in poor health expenditure countries compared with 10·8% (7·8 million operations) in low health expenditure countries and 2·7% (5·1 million operations) in high health expenditure countries. We noted a correlation between increased life expectancy and increased surgical rates up to 1533 operations per 100 000 people, with significant but less dramatic improvement above this rate. INTERPRETATION: Surgical volume is large and continues to grow in all economic environments. A single procedure-caesarean delivery-comprised almost a third of surgical volume in the most resource-limited settings. Surgical care is an essential part of health care and is associated with increased life expectancy, yet many low-income countries fail to achieve basic levels of service. Improvements in capacity and delivery of surgical services must be a major component of health system strengthening. FUNDING: None.

Size and distribution of the global volume of surgery in 2012.

OBJECTIVE: To estimate global surgical volume in 2012 and compare it with estimates from 2004. METHODS: For the 194 Member States of the World Health Organization, we searched PubMed for studies and contacted key informants for reports on surgical volumes between 2005 and 2012. We obtained data on population and total health expenditure per capita for 2012 and categorized Member States as very-low, low, middle and high expenditure. Data on caesarean delivery were obtained from validated statistical reports. For Member States without recorded surgical data, we estimated volumes by multiple imputation using data on total health expenditure. We estimated caesarean deliveries as a proportion of all surgery. FINDINGS: We identified 66 Member States reporting surgical data. We estimated that 312.9 million operations (95% confidence interval, CI: 266.2-359.5) took place in 2012, an increase from the 2004 estimate of 226.4 million operations. Only 6.3% (95% CI: 1.7-22.9) and 23.1% (95% CI: 14.8-36.7) of operations took place in very-low- and low-expenditure Member States representing 36.8% (2573 million people) and 34.2% (2393 million people) of the global population of 7001 million people, respectively. Caesarean deliveries comprised 29.6% (5.8/19.6 million operations; 95% CI: 9.7-91.7) of the total surgical volume in very-low-expenditure Member States, but only 2.7% (5.1/187.0 million operations; 95% CI: 2.2-3.4) in high-expenditure Member States. CONCLUSION: Surgical volume is large and growing, with caesarean delivery comprising nearly a third of operations in most resource-poor settings. Nonetheless, there remains disparity in the provision of surgical services globally.

Systematic review of laparoscopic surgery in low- and middle-income countries: benefits, challenges, and strategies.

BACKGROUND: Laparoscopy may prove feasible to address surgical needs in limited-resource settings. However, no aggregate data exist regarding the role of laparoscopy in low- and middle-income countries (LMICs). This study was designed to describe the issues facing laparoscopy in LMICs and to aggregate reported solutions. METHODS: A search was conducted using Medline, African Index Medicus, the Directory of Open Access Journals, and the LILACS/BIREME/SCIELO database. Included studies were in English, published after 1992, and reported safety, cost, or outcomes of laparoscopy in LMICs. Studies pertaining to arthroscopy, ENT, flexible endoscopy, hysteroscopy, cystoscopy, computer-assisted surgery, pediatrics, transplantation, and bariatrics were excluded. Qualitative synthesis was performed by extracting results that fell into three categories: advantages of, challenges to, and adaptations made to implement laparoscopy in LMICs. PRISMA guidelines for systematic reviews were followed. RESULTS: A total of 1101 abstracts were reviewed, and 58 articles were included describing laparoscopy in 25 LMICs. Laparoscopy is particularly advantageous in LMICs, where there is often poor sanitation, limited diagnostic imaging, fewer hospital beds, higher rates of hemorrhage, rising rates of trauma, and single income households. Lack of trained personnel and equipment were frequently cited challenges. Adaptive strategies included mechanical insufflation with room air, syringe suction, homemade endoloops, hand-assisted techniques, extracorporeal knot tying, innovative use of cheaper instruments, and reuse of disposable instruments. Inexpensive laboratory-based trainers and telemedicine are effective for training. CONCLUSIONS: LMICs face many surgical challenges that require innovation. Laparoscopic surgery may be safe, effective, feasible, and cost-effective in LMICs, although it often remains limited in its accessibility, acceptability, and quality. This study may not capture articles written in languages other than English or in journals not indexed by the included databases. Surgeons, policymakers, and manufacturers should focus on plans for sustainability, training and retention of providers, and regulation of efforts to develop laparoscopy in LMICs.

Surgical Care in Liberia and Implications for Capacity Building.

BACKGROUND: Situational needs of health care facilities inform the optimal allocation of resources and quality improvement efforts. This study examines surgical care delivery metrics at a tertiary care institution in Liberia. METHODS: We retrospectively reviewed operative and ward logbooks from January 1 to December 31, 2012. Data parameters included patients' age, diagnosis, procedure, mortality, and perioperative provider information. RESULTS: In 2012, 1,036 operations were performed. The breakdown of adult surgical cases reveals 452 (45.1%) general surgery operations, 192 (18.5%) orthopedic operations, and 180 (17.4%) ophthalmic operations. Other significant case volume included urologic 53 (5.1%), ENT 36 (3.5%), neurosurgical 31 (3.0%), vascular 24 (2.3%), and plastic 14 (1.4%) operations. Pediatric patients accounted for 24.5% (243) of surgical cases, and 9% of pediatric surgical cases were for hydrocephalus. General, spinal, and total intravenous anesthesia was provided by non-physician personnel, except when surgeons provided their own anesthesia. Ward logs documented 7.4% mortality among all patients admitted to the surgical ward, most of which occurred after exploratory laparotomy (44%), in burn (14%) patients, and in patients with head/neck emergencies (12%). CONCLUSIONS: This operative log review can be used to identify surgical practice patterns, needs, and deficits in order to inform the growth of surgical capacity at Liberia's only tertiary medical institution. Using this data to identify critical areas of high-yield operations (e.g., for pediatric hydrocephalus), or excessively high mortality rates (e.g., in burn care), can focus the direction of limited resources toward areas of need. While the heavy reliance on non-consultant surgeons reflects human capacity shortages and a pressing need for postgraduate training programs, identifying the breadth of surgical expertise demonstrated in these operative logs reveals the proficiencies required of surgeons to provide comprehensive surgical care in this setting.

Utilizing augmented reality for reconstruction of fractured, fragmented and damaged craniofacial remains in forensic anthropology.

Forensic anthropologists are often confronted with human remains that have been damaged due to trauma, fire, or postmortem taphonomic alteration, frequently resulting in the fracture and fragmentation of skeletal elements. The augmented reality (AR) technology introduced in this paper builds on familiar 3D visualization methods and utilizes them to make three dimensional holographic meshes of skeletal fragments that can be manipulated, tagged, and examined by the user. Here, CT scans, neural radiance fields (NeRF) artificial intelligence software, and Unreal Engine production software are utilized to construct a three-dimensional holographic image that can be manipulated with HoloLens™ technology to analyze the fracture margin and reconstruct craniofacial elements without causing damage to fragile remains via excessive handling. This allows forensic anthropologists a means of assessing aspects of the biological profile and traumatic injuries without risking further damage to the skeleton. It can also be utilized by students and professional anthropologists to practice refitting before reconstructing craniofacial fragments if refitting is necessary. Additionally, the holographic images can be used to explain complicated concepts in a courtroom without the emotional response related to using bony elements as courtroom exhibits.

Conceptualizing Fit in Surgical Residency Selection: The Experience in Otolaryngology-Head and Neck Surgery.

OBJECTIVE: Fit is a crucial factor in surgical residency selection, but how this abstract concept is applied in practice is poorly understood. Person-environment (PE) fit theory suggests that there are multiple fit domains that can clarify usage: person-job, person-organization, and person-workgroup fit. We used PE fit theory to explore how otolaryngology residency selection committee (RSC) members operationalize the concept of fit. DESIGN: One-hour focus groups were conducted in November 2022. Interview questions explored participants' definitions and uses of fit in the resident selection process. Transcripts were analyzed using directed qualitative content analysis to generate themes and evaluate how these align with PE fit domains. SETTING: Society of University Otolaryngologists Annual Meeting breakout session in November 2022. PARTICIPANTS: 21 RSC members from 20 different otolaryngology-head and neck surgery departments participated in three seven-person focus groups. RESULTS: Participants described aspects of fit that aligned with PE fit domains. Person-job included how applicants fit as both surgeons and residents. Person-organization included how applicants fit with the program's characteristics, program's mission, and the local community. Person-workgroup emphasized how applicants fit with current residents. Various challenges in the selection process limited the extent to which PE fit was operationalized, including 1) ambiguous uses of fit, 2) unique features of the match process, 3) lack of outcomes data for selection decisions, and 4) interactions with diversity, equity, and inclusion goals. CONCLUSIONS: Fit manifests in various ways during the surgical residency selection process that parallel domains of PE fit theory. Recommendations are made to assist programs in using fit in resident selection, including clearly articulating definitions of fit to increase transparency in conversations. Further work on selection challenges is needed to maximize the utility of fit in practice.

Angioembolization for splenic injuries: does it help? Retrospective evaluation of grade III-V splenic injuries at two level I trauma centers.

Background: Splenic angioembolization (SAE) has increased in utilization for blunt splenic injuries. We hypothesized lower SAE usage would not correlate with higher rates of additional intervention or mortality when choosing initial non-operative management (NOM) or surgery. Study design: Trauma registries from two level I trauma centers from 2010 to 2020 were used to identify patients aged >18 years with grade III-V blunt splenic injuries. Results were compared with the National Trauma Data Bank (NTDB) for 2018 for level I and II centers. Additional intervention or failure was defined as any subsequent SAE or surgery. Mortality was defined as death during admission. Results: There were 266 vs 5943 patients who met inclusion/exclusion criteria at Stanford/Santa Clara Valley Medical Center (SCVMC) versus the NTDB. Initial intervention differed significantly between cohorts with the use of SAE (6% vs 17%, p=0.000). Failure differed significantly between cohorts (1.5% vs 6.5%, p=0.005). On multivariate analysis, failure in NOM was significantly associated with NTDB cohort status, age 65+ years, more than one comorbidity, mechanism of injury, grade V spleen injury, and Injury Severity Score (ISS) 25+. On multivariate analysis, failure in SAE was significantly associated with Shock Index >0.9 and 10+ units blood in 24 hours. On multivariate analysis, a higher risk of mortality was significantly associated with NTDB cohort status, age 65+ years, no private insurance, more than one comorbidity, mechanism of injury, ISS 25+, 10+ units blood in 24 hours, NOM, more than one hospital complications, anticoagulant use, other Abbreviated Injury Scale ≥3 abdominal injuries. Conclusions: Compared with national data, our cohort had less SAE, lower rates of additional intervention, and had lower risk-adjusted mortality. Shock Index >0.9, grade V splenic injuries, and increased transfusion requirements in the first 24 hours may signal a need for surgical intervention rather than SAE or NOM and may reduce mortality in appropriately selected patients. Level of evidence: Level II/III.

Multivalent GU-rich oligonucleotides sequester TDP-43 in the nucleus by inducing high molecular weight RNP complexes.

TDP-43 nuclear clearance and cytoplasmic aggregation are hallmarks of TDP-43 proteinopathies. We recently demonstrated that binding to endogenous nuclear GU-rich RNAs sequesters TDP-43 in the nucleus by restricting its passive nuclear export. Here, we tested the feasibility of synthetic RNA oligonucleotide-mediated augmentation of TDP-43 nuclear localization. Using biochemical assays, we compared the ability of GU-rich oligonucleotides to engage in multivalent, RRM-dependent binding with TDP-43. When transfected into cells, (GU)16 attenuated TDP-43 mislocalization induced by transcriptional blockade or RanGAP1 ablation. Clip34nt and (GU)16 accelerated TDP-43 nuclear re-import after cytoplasmic mislocalization. RNA pulldowns confirmed that multivalent GU-oligonucleotides induced high molecular weight RNP complexes, incorporating TDP-43 and possibly other GU-binding proteins. Transfected GU-repeat oligos disrupted TDP-43 cryptic exon repression, likely by diverting TDP-43 from endogenous RNAs, except for Clip34nt which contains interspersed A and C. Thus, exogenous multivalent GU-RNAs can promote TDP-43 nuclear localization, though pure GU-repeat motifs impair TDP-43 function.