Recent Evolution of a Maternally Acting Sex-Determining Supergene in a Fly with Single-Sex Broods.

Sex determination is a key developmental process, yet it is remarkably variable across the tree of life. The dipteran family Sciaridae exhibits one of the most unusual sex determination systems in which mothers control offspring sex through selective elimination of paternal X chromosomes. Whereas in some members of the family females produce mixed-sex broods, others such as the dark-winged fungus gnat Bradysia coprophila are monogenic, with females producing single-sex broods. Female-producing females were previously found to be heterozygous for a large X-linked paracentric inversion (X'), which is maternally inherited and absent from male-producing females. Here, we assembled and characterized the X' sequence. As close sequence homology between the X and X' made identification of the inversion challenging, we developed a k-mer-based approach to bin genomic reads before assembly. We confirmed that the inversion spans most of the X' chromosome (∼55 Mb) and encodes ∼3,500 genes. Analysis of the divergence between the inversion and the homologous region of the X revealed that it originated very recently (<0.5 Ma). Surprisingly, we found that the X' is more complex than previously thought and is likely to have undergone multiple rearrangements that have produced regions of varying ages, resembling a supergene composed of evolutionary strata. We found functional degradation of ∼7.3% of genes within the region of recombination suppression, but no evidence of accumulation of repetitive elements. Our findings provide an indication that sex-linked inversions are driving turnover of the strange sex determination system in this family of flies.

GAPS phase II: development and pilot results of the global assessment in pediatric surgery, an evidence-based pediatric surgical capacity assessment tool for low-resource settings.

PURPOSE: Pediatric surgical care in low- and middle-income countries is often hindered by systemic gaps in healthcare resources, infrastructure, training, and organization. This study aims to develop and validate the Global Assessment of Pediatric Surgery (GAPS) to appraise pediatric surgical capacity and discriminate between levels of care across diverse healthcare settings. METHODS: The GAPS Version 1 was constructed through a synthesis of existing assessment tools and expert panel consultation. The resultant GAPS Version 2 underwent international pilot testing. Construct validation categorized institutions into providing basic or advanced surgical care. GAPS was further refined to Version 3 to include only questions with a > 75% response rate and those that significantly discriminated between basic or advanced surgical settings. RESULTS: GAPS Version 1 included 139 items, which, after expert panel feedback, was expanded to 168 items in Version 2. Pilot testing, in 65 institutions, yielded a high response rate. Of the 168 questions in GAPS Version 2, 64 significantly discriminated between basic and advanced surgical care. The refined GAPS Version 3 tool comprises 64 questions on: human resources (9), material resources (39), outcomes (3), accessibility (3), and education (10). CONCLUSION: The GAPS Version 3 tool presents a validated instrument for evaluating pediatric surgical capabilities in low-resource settings.

Treatment and Outcomes of Congenital Ovarian Cysts A Study by the Canadian Consortium for Research in Pediatric Surgery (CanCORPS).

OBJECTIVE: We conducted a multicenter study to assess treatments and outcomes in a national cohort of infants with congenital ovarian cysts. SUMMARY BACKGROUND DATA: Wide variability exists in the treatment of congenital ovarian cysts. The effects of various treatment strategies on outcomes, specifically ovarian preservation, are not known. METHODS: Female infants diagnosed with congenital intra-abdominal cysts between 2013 and 2017 at 10 Canadian pediatric surgical centers were retrospectively evaluated. Sonographic characteristics, median time to cyst resolution, incidence of ovarian preservation, and predictors of surgery were evaluated. Subgroup analyses were performed in patients with complex cysts and cysts ≥40 mm in diameter. RESULTS: The study population included 189 neonates. Median gestational age at diagnosis and median maximal prenatal cyst diameter were 33 weeks and 40 mm, respectively. Cysts resolved spontaneously in 117 patients (62%), 14 (7%) prenatally, and the remainder at a median age of 124 days. Intervention occurred in 61 patients (32%), including prenatal aspiration (2, 3%), ovary sparing resection (14, 23%), or oophorectomy (45, 74%). Surgery occurred at a median age of 7.4weeks. Independent predictors of surgery included postnatal cyst diameter ≥40 mm [odds ratio (OR) 6.19, 95% confidence interval (CI) 1.66-35.9] and sonographic complex cyst character (OR 63.6, 95% CI 10.9-1232). There was no significant difference in the odds of ovarian preservation (OR 3.06, 95% CI 0.86 -13.2) between patients who underwent early surgery (n = 22) and those initially observed for at least 3 months (n = 131). CONCLUSIONS: Most congenital ovarian cysts are asymptomatic and spontaneously resolve. Early surgical intervention does not increase ovarian preservation.

Why put all your eggs in one basket? Evolutionary perspectives on the origins of monogenic reproduction.

Sexual reproduction is ubiquitous in eukaryotes, but the mechanisms by which sex is determined are diverse and undergo rapid turnovers in short evolutionary timescales. Usually, an embryo's sex is fated at the moment of fertilisation, but in rare instances it is the maternal genotype that determines the offspring's sex. These systems are often characterised by mothers producing single-sex broods, a phenomenon known as monogeny. Monogenic reproduction is well documented in Hymenoptera (ants, bees and wasps), where it is associated with a eusocial lifestyle. However, it is also known to occur in three families in Diptera (true flies): Sciaridae, Cecidomyiidae and Calliphoridae. Here we review current knowledge of monogenic reproduction in these dipteran clades. We discuss how this strange reproductive strategy might evolve, and we consider the potential contributions of inbreeding, sex ratio distorters, and polygenic control of the sex ratio. Finally, we provide suggestions on future work to elucidate the origins of this unusual reproductive strategy. We propose that studying these systems will contribute to our understanding of the evolution and turnover of sex determination systems.

Perioperative management of infant inguinal hernia surgery; a review of the recent literature.

Inguinal hernia surgery is one of the most common electively performed surgeries in infants. The common nature of inguinal hernia combined with the high-risk population involving a predominance of preterm infants makes this a particular area of interest for those concerned with their perioperative care. Despite a large volume of literature in the area of infant inguinal hernia surgery, there remains much debate amongst anesthetists, surgeons and neonatologists regarding the optimal perioperative management of these patients. The questions asked by clinicians include; when should the surgery occur, how should the surgery be performed (open or laparoscopic), how should the anesthesia be conducted, including regional versus general anesthesia and airway devices used, and what impact does anesthesia choice have on the developing brain? There is a paucity of evidence in the literature on the concerns, priorities or goals of the parents or caregivers but clearly their opinions do and should matter. In this article we review the current clinical surgical and anesthesia practice and evidence for infants undergoing inguinal hernia surgery to help clinicians answer these questions.

The evidence mismatch in pediatric surgical practice.

PURPOSE: Outpatient pediatric surgical practice often involves conditions of limited morbidity but significant parental concern. We explore existing evidence-based management recommendations and the mismatch with practice patterns for four common outpatient pediatric surgical conditions. METHODS: Using the Cochrane Rapid Review Group recommendations and librarian oversight, we conducted a rapid review of four outpatient surgical conditions: dermoid cysts, epigastric hernias, hydroceles, and umbilical hernias. We extracted patient demographics, intervention details, outcome measures and evaluated justifications presented for chosen management options. A metric of evidence volume (patient/publication ratio) was generated and compared between diagnoses. RESULTS: Out of 831 articles published since 1990, we identified 49 cohort studies (10-dermoid cyst, 6-epigastric hernia, 25-hydrocele, and 8-umbilical hernia). The 49 publications included 34,172 patients treated across 18 countries. The evidence volume for each outpatient condition demonstrates < 1 cohort/condition/year. The evidence mismatch rate varied between 33 and 75%; many existing recommendations are not evidence-based, sometimes conflicting and frequently misrepresentative of clinical practice. CONCLUSIONS: Published literature concerning common outpatient pediatric surgical conditions is sparse and demonstrates wide variations in practice. All individual practice choices were justified using either risk of complications or patient preference. Most early intervention practices were based on weak or outdated studies and "common wisdom" rather than genuine evidence. LEVEL OF EVIDENCE: III.

Genomic Evidence of In-Flight SARS-CoV-2 Transmission, India to Australia, April 2021.

Epidemiologic and genomic investigation of SARS-CoV-2 infections associated with 2 repatriation flights from India to Australia in April 2021 indicated that 4 passengers transmitted SARS-CoV-2 to >11 other passengers. Results suggest transmission despite mandatory mask use and predeparture testing. For subsequent flights, predeparture quarantine and expanded predeparture testing were implemented.

Virtual curriculum delivery in the COVID-19 era: the pediatric surgery boot camp v2.0.

PURPOSE: We evaluated the impact of a virtual Pediatric Surgery Bootcamp curriculum on resource utilization, learner engagement, knowledge retention, and stakeholder satisfaction. METHODS: A virtual curriculum was developed around Pediatric Surgery Milestones. GlobalCastMD delivered pre-recorded and live content over a single 10-h day with a concluding social hour. Metrics of learner engagement, faculty interaction, knowledge retention, and satisfaction were collected and analyzed during and after the course. RESULTS: Of 56 PS residencies, 31 registered (55.4%; 8/8 Canadian and 23/48 US; p = 0.006), including 42 learners overall. The virtual BC budget was $15,500 (USD), 54% of the anticipated in-person course. Pre- and post-tests were administered, revealing significant knowledge improvement (48.6% [286/589] vs 66.9% [89/133] p < 0.0002). Learner surveys (n = 14) suggested the virtual BC facilitated fellowship transition (85%) and strengthened peer-group camaraderie (69%), but in-person events were still favored (77%). Program Directors (PD) were surveyed, and respondents (n = 22) also favored in-person events (61%). PDs not registering their learners (n = 7) perceived insufficient value-added and concern for excessive participants. CONCLUSIONS: The virtual bootcamp format reduced overall expenses, interfered less with schedules, achieved more inclusive reach, and facilitated content archiving. Despite these advantages, learners and program directors still favored in-person education. LEVEL OF EVIDENCE: III.

Training low-middle-income (LMIC) pediatric surgeons in a high-income country (HIC) program.

BACKGROUND: A popular paradigm to support surgical education for low- and middle-income countries (LMICs) is partnering with high-income country (HIC) surgeons. These relationships may, however, be asymmetric and fail to optimally address the most pressing curricular needs. We explored the effectiveness of our LMIC-HIC educational partnership. METHODS: Through a partnership between a HIC (Canada) and a LMIC (Uganda), three candidate surgeons were commissioned for a custom designed 1-year training experience at our HIC accredited pediatric surgical training centre as part of their overall formal education. The training curriculum was developed in collaboration with the LMIC pediatric surgeon and utilized competency-based medical education principles. A Likert and short-answer survey tool was administered to these trainees upon completion of their training. RESULTS: All prescribed milestones as well as specialty certification by examination of the College of Surgeons of East, Central and Southern Africa was achieved by participating fellows, each of whom have begun clinical practice, leadership and teaching roles in their home country. Although several obstacles were identified by fellows, all agreed that the experience boosted their clinical and teaching abilities, and was worth the effort. CONCLUSION: This endeavour in global pediatric surgical training represents a significant innovation in surgical education partnerships and would be reproducible across different surgical subspecialties and contexts. Such collaborative efforts represent a feasible upskilling opportunity towards addressing global surgical service capacity. LEVEL OF EVIDENCE: V.

Evaluation of Interventions Addressing Timely Access to Surgical Care in Low-Income and Low-Middle-Income Countries as Outlined by the LANCET Commission 2030 Global Surgery Goals: A Systematic Review.

BACKGROUND: In 2015, the Lancet Commission on Global Surgery published six global surgery goals, one of which was to provide 80% of the world's population with timely access to the Bellwether Surgical procedures. Little is known about the prevalence or efficacy of subsequent interventions implemented in under-resourced countries to increase timely access to Bellwether surgical procedures. METHODS: A systematic review of articles and grey literature published in MEDLINE, Embase, Cochrane, CINAHL, and Web of Science databases was conducted. Two independent reviewers evaluated 1923 captured abstracts using explicit inclusion and exclusion criteria. Following a thematic analysis, two reviewers conducted data extraction on the eleven manuscripts included in the final review. RESULTS: The studied innovations, sparse in number, centred on improved educational resources, the development of orthopaedic devices, and models for assessing surgical access disparity. Eight papers were centred around timely access to caesarean sections, three around open fracture reduction, and three around laparotomy; all focused on adult populations. Five papers addressed innovations in West Africa, two in East Africa, two in South Asia, and one in Southeast Asia. Common outcome metrics were not used to assess improvements to timely surgical access. CONCLUSIONS: Few published interventions have been implemented since the publication of the 2015 Lancet Commission on Global Surgery goals that have or will longitudinally increase the availability of timely surgical access in Low and Middle-Income Countries (LMIC). Tangible outcome measures in existing literature are lacking. An up-scaling and wider adoption of successful strategies is necessary and possible.

Systematic review of grading systems for adverse surgical outcomes.

Background: Grading scales for adverse surgical outcomes have been poorly characterized to date. The primary aim of this study was to conduct a systematic review to enumerate the various frameworks for grading adverse postoperative outcomes; our secondary objective was to outline the properties of each grading system, identifying its strengths and weaknesses. Methods: We searched 9 databases (Africa Wide Information, Biosis, Cochrane, Embase, Global Health, LILACs, Medline, PubMed and Web of Science) from 1992 (the year the Clavien-Dindo classification system was developed) until Mar. 2, 2017, for studies that aimed to develop or improve on an already existing generalizable system for grading adverse postoperative outcomes. Study selection was duplicated as per PRISMA recommendations. Procedure-specific grading systems were excluded. We assessed the framework, strengths and weaknesses of the systems qualitatively. Results: We identified 9 studies on 8 adverse outcome grading systems with frameworks generalizable to any surgical procedure. Most systems have not been widely incorporated in the literature. Seven of the 8 systems were produced without including patients' perspectives. Four allowed the derivation of a composite morbidity score, which had limited tangible significance for patients. Conclusion: Although each instrument identified offered its own advantages, none satisfied the need for a patient-centred tool capable of generating a composite score of all possible postoperative adverse outcomes (complications, sequelae and failure) that enables comparison of noninterventional and surgical management of disease. There is a need for development of a more comprehensive, patient-centred grading system for adverse postoperative outcomes.

Contexte: Jusqu'ici, les systèmes de classification des issues postopératoires indésirables n'ont pas encore fait l'objet d'une analyse comparative. Cette étude avait pour objectif principal de recenser, au moyen d'une revue systématique de la littérature, les divers systèmes de classification des issues postopératoire indésirables, et pour objectif secondaire de dégager les propriétés, les forces et les faiblesses de chaque système. Méthodes: Nous avons interrogé 9 bases de données (Africa Wide Information, Biosis Previews, Cochrane, Embase, Global Health, LILACS, Medline, PubMed et Web of Science) pour trouver des articles publiés entre 1992 (année de la mise au point du système de classification de Clavien­Dindo) et le 2 mars 2017. Ces articles devaient porter sur la création d'un système généralisable de classification des issues postopératoires indésirables, ou l'amélioration d'un système existant. La sélection des études a été faite en double, conformément aux recommandations PRISMA. Les systèmes de classification visant une seule intervention ont été exclus. Nous avons évalué, d'un point de vue qualitatif, le cadre, les forces et les faiblesses des systèmes retenus. Résultats: Nous avons retenu 9 études sur 8 systèmes de classification accompagnés d'un cadre pouvant être appliqué à n'importe quelle intervention chirurgicale. La plupart des systèmes n'avaient pas été largement étudiés. Sept des 8 systèmes avaient été développés sans tenir compte du point de vue des patients, et 4 permettaient de calculer un score de morbidité composite ayant des retombées concrètes limitées pour les patients. Conclusion: Tous les systèmes retenus s'accompagnaient d'avantages, mais aucun ne pouvait servir d'outil centré sur le patient permettant de calculer un score composite pour toutes les issues postopératoires possibles (complications, séquelles et échec), score qui pourrait servir à comparer les prises en charge conservatrice et chirurgicale des maladies. La création d'un système de classification des issues postopératoires indésirables exhaustif centré sur le patient est nécessaire.

Comparison of the Pediatric Resuscitation and Trauma Outcome (PRESTO) Model and Pediatric Trauma Scoring Systems in a Middle-Income Country.

BACKGROUND: The pediatric resuscitation and trauma outcome (PRESTO) model was developed to aid comparisons of risk-adjusted mortality after injury in low- and middle-income countries (LMICs). We sought to validate PRESTO using data from a middle-income country (MIC) trauma registry and compare its performance to the Pediatric Trauma Score (PTS), Revised Trauma Score, and pediatric age-adjusted shock index (SIPA). METHODS: We included children (age < 15 years) admitted to a single trauma center in South Africa from December 2012 to January 2019. We excluded patients missing variables necessary for the PRESTO model-age, systolic blood pressure, pulse, oxygen saturation, neurologic status, and airway support. Trauma scores were assigned retrospectively. PRESTO's previously high-income country (HIC)-validated optimal threshold was compared to MIC-validated threshold using area under the receiver operating characteristic curves (AUROC). Prediction of in-hospital death using trauma scoring systems was compared using ROC analysis. RESULTS: Of 1160 injured children, 988 (85%) had complete data for calculation of PRESTO. Median age was 7 (IQR: 4, 11), and 67% were male. Mortality was 2% (n = 23). Mean predicted mortality was 0.5% (range 0-25.7%, AUROC 0.93). Using the HIC-validated threshold, PRESTO had a sensitivity of 26.1% and a specificity of 99.7%. The MIC threshold showed a sensitivity of 82.6% and specificity of 89.4%. The MIC threshold yielded superior discrimination (AUROC 0.86 [CI 0.78, 0.94]) compared to the previously established HIC threshold (0.63 [CI 0.54, 0.72], p < 0.0001). PRESTO showed superior prediction of in-hospital death compared to PTS and SIPA (all p < 0.01). CONCLUSION: PRESTO can be applied in MIC settings and discriminates between children at risk for in-hospital death following trauma. Further research should clarify optimal decision thresholds for quality improvement and benchmarking in LMIC settings.

North-South surgical training partnerships: a systematic review.

Background: Fostering the success of surgical trainees from low- and middle-income countries (LMICs) plausibly addresses the existing workforce deficit in a sustainable manner, but it is unclear whether and how these trainees are targeted as strategic learners for educational exchanges. The purpose of this review was to assess the quality and outcomes of existing literature on exchanges of surgical trainees between high-income countries (HICs) and LMICs. Methods: We conducted a systematic review of reported instances of surgical training exchanges between HICs and LMICs. After database searching, 2 independent reviewers evaluated titles, abstracts and manuscripts. Selected studies were critically appraised with the use the Critical Assessment Skills Programme Qualitative Checklist and analyzed for trainee level, institutions, countries and subspecialties, as well as reported outcomes of the exchange. Results: Twenty-eight reports met the inclusion criteria and were analyzed. Most publications (18 [64%]) detailed North-to-South exchanges; 1 exchange was bidirectional. General surgery was the most common discipline identified, with 9 other subspecialties described involving learners at all phases of training. Reports were generally of good quality, although outcomes were reported variably, and most authors failed to acknowledge the ethical implications of their study. Conclusion: The articles identified described a variety of surgical exchanges across disciplines, learner types and host/home countries. Few of the exchanges prioritized the learning of surgical trainees from LMICs. There is an increasing need to formalize these exchanges via clear goals and objectives, as well as to prioritize the proper matching of educational goals with local clinical needs. Level of evidence: V - Evidence from systematic reviews of descriptive and qualitative studies.

Contexte: Le soutien à la réussite des chirurgiens en formation des pays à revenu faible ou moyen (PRFM) pourrait concrètement aider à remédier au manque d'effectifs actuel de façon durable. On ignore toutefois si ces apprenants sont ciblés par les programmes d'échanges en tant que candidats stratégiques et quelles sont les méthodes de recrutement employées. La présente revue vise à évaluer la qualité et les résultats des publications sur les échanges entre pays à revenu élevé (PRE) et PRFM auxquels participent des chirurgiens en formation. Méthodes: Nous avons procédé à une revue systématique des cas rapportés d'échanges étudiants en chirurgie entre PRE et PRFM. Après une recherche dans les bases de données, 2 évaluateurs indépendants ont passé en revue les titres, les résumés et les manuscrits retenus. Les études sélectionnées ont fait l'objet d'une évaluation critique d'après la liste de contrôle pour la recherche qualitative CASP (Critical Assessment Skills Programme Qualitative Checklist); les critères d'analyse comprenaient le niveau de scolarité des apprenants, les établissements, les pays et les surspécialités, ainsi que les résultats rapportés pour l'échange. Résultats: Au total, 28 rapports répondaient aux critères d'inclusion et ont donc été analysés. La plupart d'entre eux (18 [64%]) traitaient d'échanges du nord au sud; un échange était bidirectionnel. La chirurgie générale était la discipline la plus souvent recensée; on a aussi décrit la participation d'apprenants à différentes étapes de leur formation pour 9 autres surspécialités. Les rapports étaient en général de bonne qualité, mais la présentation des résultats variait, et la majorité des auteurs ont omis de rendre compte des considérations éthiques de leur étude. Conclusion: Les articles évalués décrivaient des échanges étudiants en chirurgie se rapportant à une multitude de disciplines, de types d'apprenants et de pays d'origine et d'accueil. Peu de programmes d'échanges priorisaient l'apprentissage des chirurgiens en formation issus des PRFM. Il est de plus en plus pressant de baliser les échanges étudiants en établissant des buts et des objectifs clairs, et de faire une priorité de la juste correspondance des objectifs pédagogiques et des besoins cliniques locaux. Niveau de preuve: V ­ Preuve issue de revues systématiques d'études descriptives et qualitatives.

Derivation of a complication burden score based on disability-adjusted life years to assess patient burden following surgery: a pilot study.

BACKGROUND: Comparing adverse outcomes following alternative surgical interventions is a complex process for both patients and providers. Disability-adjusted life years (DALYs) are used globally as a quantitative indicator of burden of disease. However, DALYs have not been applied to the burden of postoperative complications. This study explores the feasibility and utility of DALYs in measuring the burden of postoperative complications, using 2 pediatric surgical procedures as a test model. METHODS: A literature review was undertaken of postoperative complications following pediatric inguinal hernia repair and intestinal atresia repair. Relevant studies were included, and incidence rates and durations of all key complications were identified. Using existing disability weights of equivalent health states to the complications, we estimated the burden in DALYs of each complication. These estimates were combined into a unitary procedure-specific complication burden score. RESULTS: The key complications contributing to the postoperative burden following inguinal hernia repair were recurrence (0.016 DALYs), hydrocele (0.010), metachronous hernia (0.014) and port-site hernia (0.012). In the case of intestinal atresia repair, death (6.278), reoperation (12.100), stenosis (5.025) and anastomotic stricture (5.327) accounted for most of the postoperative DALYs. The complication burden score was 0.06 DALYs for inguinal hernia and 36.86 for intestinal atresia repair. CONCLUSION: As a proof of concept, this study supports the feasibility of using DALYs to derive a complication burden score following surgical intervention, and to our knowledge it represents the first application of burden of disease metrics to postoperative adverse outcomes. Future studies should focus on deriving de novo disability weights for common postoperative complications and adverse outcomes.

CONTEXTE: La comparaison des issues indésirables découlant d'interventions chirurgicales de substitution est complexe, tant pour les patients que pour les fournisseurs de soins. Partout au monde, les années de vie ajustées en fonction de l'incapacité (AVAI) sont utilisées comme indicateur quantitatif du fardeau de la maladie. Or, les AVAI n'ont jamais été appliquées au fardeau des complications postopératoires. La présente étude porte sur la faisabilité et l'utilité du recours aux AVAI pour mesurer le fardeau des complications postopératoires. Elle se sert de 2 interventions chirurgicales pédiatriques comme modèles. MÉTHODES: Nous avons mené une revue de la littérature sur les complications postopératoires suivant une réparation de hernie inguinale et une correction d'atrésie intestinale chez des populations pédiatriques. Nous avons retenu les études pertinentes et dégagé le taux d'incidence ainsi que la durée des principales complications. Nous nous sommes également servis du fardeau pondéré de l'incapacité liée à un trouble de santé équivalent à chacune des complications pour estimer le fardeau, en AVAI, des complications. Les estimations ont ensuite été combinées pour obtenir un score unitaire correspondant au fardeau des complications associées à chaque intervention. RÉSULTATS: Les principales complications contribuant au fardeau postopératoire associé à la réparation de hernie inguinale étaient la récurrence (0,016 AVAI), l'hydrocèle (0,010 AVAI), la hernie métachrone (0,014 AVAI) et la hernie au site de laparoscopie (0,012). En ce qui a trait à la correction d'atrésie intestinale, le décès (6,278 AVAI), la réopération (12,100 AVAI), la sténose (5,025 AVAI) et le rétrécissement anastomotique (5,327 AVAI) étaient à l'origine de la plupart des AVAI postopératoires. Le score du fardeau des complications était de 0,06 AVAI pour la réparation de hernie inguinale et de 36,86 AVAI pour la correction d'atrésie intestinale. CONCLUSION: Cette étude, comme validation de principe, montre qu'il est possible d'utiliser les AVAI pour obtenir un score correspondant au fardeau des complications associées à une intervention chirurgicale. Elle est également la première, à notre connaissance, à appliquer un score de fardeau de la maladie aux issues postopératoires indésirables. Des études ultérieures devraient être axées sur le calcul de nouveaux fardeaux pondérés pour les complications postopératoires et les issues indésirables courantes.

Unifying Children's Surgery and Anesthesia Stakeholders Across Institutions and Clinical Disciplines: Challenges and Solutions from Uganda.

BACKGROUND: There is a significant unmet need for children's surgical care in low- and middle-income countries (LMICs). Multidisciplinary collaboration is required to advance the surgical and anesthesia care of children's surgical conditions such as congenital conditions, cancer and injuries. Nonetheless, there are limited examples of this process from LMICs. We describe the development and 3-year outcomes following a 2015 stakeholders' meeting in Uganda to catalyze multidisciplinary and multi-institutional collaboration. METHODS: The stakeholders' meeting was a daylong conference held in Kampala with local, regional and international collaborators in attendance. Multiple clinical specialties including surgical subspecialists, pediatric anesthesia, perioperative nursing, pediatric oncology and neonatology were represented. Key thematic areas including infrastructure, training and workforce retention, service delivery, and research and advocacy were addressed, and short-term objectives were agreed upon. We reported the 3-year outcomes following the meeting by thematic area. RESULTS: The Pediatric Surgical Foundation was developed following the meeting to formalize coordination between institutions. Through international collaborations, operating room capacity has increased. A pediatric general surgery fellowship has expanded at Mulago and Mbarara hospitals supplemented by an international fellowship in multiple disciplines. Coordinated outreach camps have continued to assist with training and service delivery in rural regional hospitals. CONCLUSION: Collaborations between disciplines, both within LMICs and with international partners, are required to advance children's surgery. The unification of stakeholders across clinical disciplines and institutional partnerships can facilitate increased children's surgical capacity. Such a process may prove useful in other LMICs with a wide range of children's surgery stakeholders.

Raising the Stakes: Loss of Efflux Pump Regulation Decreases Meropenem Susceptibility in Burkholderia pseudomallei.

Background: Burkholderia pseudomallei, the causative agent of the high-mortality disease melioidosis, is a gram-negative bacterium that is naturally resistant to many antibiotics. There is no vaccine for melioidosis, and effective eradication is reliant on biphasic and prolonged antibiotic administration. The carbapenem drug meropenem is the current gold standard option for treating severe melioidosis. Intrinsic B. pseudomallei resistance toward meropenem has not yet been documented; however, resistance could conceivably develop over the course of infection, leading to prolonged sepsis and treatment failure. Methods: We examined our 30-year clinical collection of melioidosis cases to identify B. pseudomallei isolates with reduced meropenem susceptibility. Isolates were subjected to minimum inhibitory concentration (MIC) testing toward meropenem. Paired isolates from patients who had evolved decreased susceptibility were subjected to whole-genome sequencing. Select agent-compliant genetic manipulation was carried out to confirm the molecular mechanisms conferring resistance. Results: We identified 11 melioidosis cases where B. pseudomallei isolates developed decreased susceptibility toward meropenem during treatment, including 2 cases not treated with this antibiotic. Meropenem MICs increased from 0.5-0.75 µg/mL to 3-8 µg/mL. Comparative genomics identified multiple mutations affecting multidrug resistance-nodulation-division (RND) efflux pump regulators, with concomitant overexpression of their corresponding pumps. All cases were refractory to treatment despite aggressive, targeted therapy, and 2 were associated with a fatal outcome. Conclusions: This study confirms the role of RND efflux pumps in decreased meropenem susceptibility in B. pseudomallei. These findings have important ramifications for the diagnosis, treatment, and management of life-threatening melioidosis cases.

Radiation Exposure and Attributable Cancer Risk in Patients With Esophageal Atresia.

OBJECTIVES: Cases of esophageal carcinoma have been documented in survivors of esophageal atresia (EA). Children with EA undergo considerable amounts of diagnostic imaging and consequent radiation exposure potentially increasing their lifetime cancer mortality risk. This study evaluates the radiological procedures performed on patients with EA and estimates their cumulative radiation exposure and attributable lifetime cancer mortality risk. METHODS: Medical records of patients with EA managed at a tertiary care center were reviewed for demographics, EA subtype, and number and type of radiological investigations. Existing normative data were used to estimate the cumulative radiation exposure and lifetime cancer risk per patient. RESULTS: The present study included 53 patients with a mean follow-up of 5.7 years. The overall median and maximum estimated effective radiation dose in the neonatal period was 5521.4 µSv/patient and 66638.6 µSv/patient, respectively. This correlates to a median and maximum estimated cumulative lifetime cancer mortality risk of 1:1530 and 1:130, respectively. Hence, radiation exposure in the neonatal period increased the cumulative cancer mortality risk a median of 130-fold and a maximum of 1575-fold in EA survivors. CONCLUSIONS: Children with EA are exposed to significant amounts of radiation and an increased estimated cumulative cancer mortality risk. Efforts should be made to eliminate superfluous imaging.

Molecular Antimicrobial Resistance Surveillance for Neisseria gonorrhoeae, Northern Territory, Australia.

Neisseria gonorrhoeae antimicrobial resistance (AMR) is a globally recognized health threat; new strategies are needed to enhance AMR surveillance. The Northern Territory of Australia is unique in that 2 different first-line therapies, based primarily on geographic location, are used for gonorrhea treatment. We tested 1,629 N. gonorrhoeae nucleic acid amplification test-positive clinical samples, collected from regions where ceftriaxone plus azithromycin or amoxicillin plus azithromycin are recommended first-line treatments, by using 8 N. gonorrhoeae AMR PCR assays. We compared results with those from routine culture-based surveillance data. PCR data confirmed an absence of ceftriaxone resistance and a low level of azithromycin resistance (0.2%), and that penicillin resistance was <5% in amoxicillin plus azithromycin regions. Rates of ciprofloxacin resistance and penicillinase-producing N. gonorrhoeae were lower when molecular methods were used. Molecular methods to detect N. gonorrhoeae AMR can increase the evidence base for treatment guidelines, particularly in settings where culture-based surveillance is limited.

Changing epidemiology of candidaemia in Australia.

Objectives: Knowledge of contemporary epidemiology of candidaemia is essential. We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal susceptibilities of Candida spp. causing candidaemia in Australia. Methods: These data were collected from nationwide active laboratory-based surveillance for candidaemia over 1 year (within 2014-2015). Isolate identification was by MALDI-TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed using Sensititre YeastOne™. Results: A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/105 population. The median patient age was 63 years (56% of cases occurred in males). Of 498 isolates with confirmed species identity, Candida albicans was the most common (44.4%) followed by Candida glabrata complex (26.7%) and Candida parapsilosis complex (16.5%). Uncommon Candida species comprised 25 (5%) isolates. Overall, C. albicans (>99%) and C. parapsilosis (98.8%) were fluconazole susceptible. However, 16.7% (4 of 24) of Candida tropicalis were fluconazole- and voriconazole-resistant and were non-WT to posaconazole. Of C. glabrata isolates, 6.8% were resistant/non-WT to azoles; only one isolate was classed as resistant to caspofungin (MIC of 0.5 mg/L) by CLSI criteria, but was micafungin and anidulafungin susceptible. There was no azole/echinocandin co-resistance. Conclusions: We report an almost 1.7-fold proportional increase in C. glabrata candidaemia (26.7% versus 16% in 2004) in Australia. Antifungal resistance was generally uncommon, but azole resistance (16.7% of isolates) amongst C. tropicalis may be emerging.