The role of ECLS in the management of congenital diaphragmatic hernia.

In the complex arena of Congenital Diaphragmatic Hernia (CDH) management, Extracorporeal Life Support (ECLS) provides a strategic window for stabilization and surgical correction, during which time marginal gains in patient stability can tip the scales towards survival. In modern neonatal ECLS, the focus is increasingly on minimizing survivor morbidity, which calls for considerable multidisciplinary expertise to enhance patient outcomes. This review will delve into the most up-to-date literature on the management of CDH in the context of ECLS, providing a comprehensive synthesis of current insights.

Exploring the Association of Male Sex With Adverse Outcomes in Severe Bronchopulmonary Dysplasia: A Retrospective, Multicenter Cohort Study.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a significant contributor to morbidity and death in infants who are born premature. Male sex is an independent risk factor for the development of BPD. However, whether male sex is associated with adverse outcomes that occur after formal diagnosis of severe BPD prior to hospital discharge remains unclear. RESEARCH QUESTION: Is male sex associated with a higher risk of adverse outcomes in infants with established severe BPD? STUDY DESIGN AND METHODS: A retrospective, multicenter cohort study of infants enrolled in the BPD Collaborative Registry from January 1, 2015, to June 29, 2022, was performed. Demographics, clinical characteristics, and outcomes were stratified by sex (ie, male vs female). Regression modeling was used to estimate the association of sex with the primary composite outcome of death or tracheostomy at hospital discharge. RESULTS: We identified 1,156 infants with severe BPD, defined at 36 weeks postmenstrual age by the National Institutes of Health 2001 consensus definition. The cohort was predominantly male (59% male infants, 41% female infants). However, rates of mechanical ventilation at 36 weeks postmenstrual age (ie, type 2 severe BPD) did not differ by sex. Overall mortality rates within the cohort were low (male infants, 5.3%; female infants, 3.6%). The OR of death or tracheostomy for male-to-female infants was 1.0 (95% CI, 0.7-1.5). INTERPRETATION: Our results lead us to speculate that, although sex is an important variable that contributes to the development and pathogenesis of severe BPD, it does not appear to be associated with adverse outcomes in this cohort of infants with established disease. The surprising results raise important questions surrounding the temporal role of biological sex in the development of severe BPD and its progression during the neonatal ICU stay. As we explore the phenotypes and endotypes of BPD, it is imperative to consider how sex modulates the disease from birth through hospital discharge.

The impact of urgency of umbilical hernia repair on adverse outcomes in patients with cirrhosis: a population-based cohort study from England.

INTRODUCTION: Umbilical hernia is common in patients with cirrhosis; however, there is a paucity of dedicated studies on postoperative outcomes in this group of patients. This population-based cohort study aimed to determine the outcomes after emergency and elective umbilical hernia repair in patients with cirrhosis. METHODS: Two linked electronic healthcare databases from England were used to identify all patients undergoing umbilical hernia repair between January 2000 and December 2017. Patients were grouped into those with and without cirrhosis and stratified by severity into compensated and decompensated cirrhosis. Length of stay, readmission, 90-day case fatality rate and the odds ratio of 90-day postoperative mortality were defined using logistic regression. RESULTS: In total, 22,163 patients who underwent an umbilical hernia repair were included and 297 (1.34%) had cirrhosis. More patients without cirrhosis had an elective procedure, 86% compared with 51% of those with cirrhosis (P < 0.001). In both the elective and emergency settings, patients with cirrhosis had longer hospital length of stay (elective: 0 vs 1 day, emergency: 2 vs 4 days, P < 0.0001) and higher readmission rates (elective: 4.87% vs 11.33%, emergency:11.39% vs 29.25%, P < 0.0001) than those without cirrhosis. The 90-day case fatality rates were 2% and 0.16% in the elective setting, and 19% and 2.96% in the emergency setting in patients with and without cirrhosis respectively. CONCLUSION: Emergency umbilical hernia repair in patients with cirrhosis is associated with poorer outcomes in terms of length of stay, readmissions and mortality at 90 days.

Molecular insights using spatial transcriptomics of the distal lung in congenital diaphragmatic hernia.

Abnormal pulmonary vascular development and function in congenital diaphragmatic hernia (CDH) is a significant factor leading to pulmonary hypertension. The lung is a very heterogenous organ and has marked cellular diversity that is differentially responsive to injury and therapeutic agents. Spatial transcriptomics provides the unmatched capability of discerning the differences in the transcriptional signature of these distinct cell subpopulations in the lung with regional specificity. We hypothesized that the distal lung parenchyma (selected as a region of interest) would show a distinct transcriptomic profile in the CDH lung compared with control (normal lung). We subjected lung sections obtained from male and female CDH and control neonates to spatial transcriptomics using the Nanostring GeoMx platform. Spatial transcriptomic analysis of the human CDH and control lung revealed key differences in the gene expression signature. Increased expression of alveolar epithelial-related genes (SFTPA1 and SFTPC) and angiogenesis-related genes (EPAS1 and FHL1) was seen in control lungs compared with CDH lungs. Response to vitamin A was enriched in the control lungs as opposed to abnormality of the coagulation cascade and TNF-alpha signaling via NF-kappa B in the CDH lung parenchyma. In male patients with CDH, higher expression of COL1A1 (ECM remodeling) and CD163 was seen. Increased type 2 alveolar epithelial cells (AT-2) and arterial and lung capillary endothelial cells were seen in control lung samples compared with CDH lung samples. To the best of our knowledge, this is the first use of spatial transcriptomics in patients with CDH that identifies the contribution of different lung cellular subpopulations in CDH pathophysiology and highlights sex-specific differences.NEW & NOTEWORTHY This is the first use of spatial transcriptomics in patients with congenital diaphragmatic hernia (CDH) that identifies the contribution of different lung cellular subpopulations in CDH pathophysiology and highlights sex-specific differences.

Fetal malrotation with midgut volvulus: Prenatal diagnosis and planning.

Introduction: Malrotation of the intestinal tract is a congenital malformation commonly found either incidentally or after affected individuals develop signs and symptoms of intestinal obstruction. Malrotation is prone to midgut volvulus that can cause intestinal obstruction and lead to ischemia and necrosis requiring emergent surgical intervention. Rare instances of in utero midgut volvulus have been reported in the literature and carry a high mortality given the difficulty in establishing a diagnosis prior to development of signs of intestinal ischemia and necrosis. Advancements in imaging have made it possible to diagnose in utero malrotation earlier, raising the question of optimal timing of delivery, especially in cases of prenatally diagnosed midgut volvulus. In these cases, the risks of premature birth must be weighed against the risks of fetal intestinal ischemia and potential fetal demise. Case presentation: This case report details an interesting presentation of intestinal malrotation with suspected midgut volvulus found on prenatal imaging at 33 weeks and 4 days' gestation. This prompted delivery of the infant at 34 weeks and 2 days' gestation with urgent operative management, within 3 hours of life, after diagnosis was confirmed postnatally. Intraoperatively, the infant was confirmed to have midgut volvulus without bowel ischemia, the intestines were reduced, and a Ladd procedure was performed without incident. The infant recovered postoperatively without complication, tolerated advancement to full volume feeds and was discharged on day of life 18. Conclusion: Successful management of fetal malrotation with midgut volvulus may be accomplished by early access to a multi-disciplinary team of professionals, prompt postnatal confirmation of diagnosis, and urgent correction to minimize the risk of complications.

Championing inclusive terminology in ecology and evolution.

Amid a growing disciplinary commitment to inclusion in ecology and evolutionary biology (EEB), it is critical to consider how the use of scientific language can harm members of our research community. Here, we outline a path for identifying and revising harmful terminology to foster inclusion in EEB.

Utilizing a Video-Based Learning Platform for Teaching Breastfeeding Medicine.

The American Academy of Pediatrics (AAP) supports exclusive breastfeeding of infants. However, conversations surrounding breastfeeding can be sensitive in nature and cause discomfort for both learners and parents. Additionally, bedside teaching of breastfeeding medicine is a relatively large time commitment which can be difficult for learners rotating through busy delivery centers. These factors along with others have led to known knowledge gaps in medical students, residents, fellows, and even attending knowledge of skill-based breastfeeding competencies supported by the AAP. We aimed to address these gaps by creating a video-based breastfeeding education module working in collaboration with certified lactation consultants at the largest birthing center in Illinois, United States. This technical report describes the utilization of Panopto audio-visual software (Panopto Inc., Seattle, Washington, United States) to successfully create a video-based curriculum for teaching breastfeeding medicine.

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up. Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes. Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.

The palliative management of non-islet cell tumour hypoglycaemia with glucocorticoids and somatostatin analogues in an unresectable hepatocellular carcinoma.

Non-islet cell tumour hypoglycaemia (NICTH) results from paraneoplastic insulin-like growth factor-II (IGF-II) secretion and its potent insulin-like effect. It causes recurrent, often severe, hypoglycaemic episodes, which is detrimental to quality of life. There is limited evidence regarding best supportive care in unresectable tumours. A 76-year-old woman presented with hypoglycaemic collapse. A new diagnosis of unresectable hepatocellular carcinoma (HCC) was made. The IGF-II:IGF-I ratio was 11.0, which confirmed NICTH. The octreoscan showed avid disease. The main problem was symptomatic nocturnal hypoglycaemia. Curative treatment options were not possible in this case and treatment focused on preventing symptomatic hypoglycaemia. Inpatient treatment was with high carbohydrate nasogastric (NG) feeds, prednisolone and somatostatin analogue (octreotide) infusion. Once stabilised, the patient was discharged with NG feeds, prednisolone and a long-acting somatostatin analogue (sandostatin). The patient received successful end-of-life care with her family as per her wishes, without requiring readmission. The treatments were well-tolerated and effective in preventing symptomatic hypoglycaemic episodes. The combination of high carbohydrate NG feed with prednisolone and somatostatin analogues was effective in preventing symptomatic hypoglycaemia. Somatostatin analogues had a useful steroid sparing role. Larger case series are warranted to clarify the management of NICTH patients with placebo-controlled studies to determine the role of somatostatin analogues.

Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking. METHODS: We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial. RESULTS: Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time (P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years (P = .015). Dry mouth scores were higher in RT patients over time (P = .041). CONCLUSION: On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355).

Development of polymorphic markers in the immune gene complex loci of cattle.

The addition of cattle health and immunity traits to genomic selection indices holds promise to increase individual animal longevity and productivity, and decrease economic losses from disease. However, highly variable genomic loci that contain multiple immune-related genes were poorly assembled in the first iterations of the cattle reference genome assembly and underrepresented during the development of most commercial genotyping platforms. As a consequence, there is a paucity of genetic markers within these loci that may track haplotypes related to disease susceptibility. By using hierarchical assembly of bacterial artificial chromosome inserts spanning 3 of these immune-related gene regions, we were able to assemble multiple full-length haplotypes of the major histocompatibility complex, the leukocyte receptor complex, and the natural killer cell complex. Using these new assemblies and the recently released ARS-UCD1.2 reference, we aligned whole-genome shotgun reads from 125 sequenced Holstein bulls to discover candidate variants for genetic marker development. We selected 124 SNPs, using heuristic and statistical models to develop a custom genotyping panel. In a proof-of-principle study, we used this custom panel to genotype 1,797 Holstein cows exposed to bovine tuberculosis (bTB) that were the subject of a previous GWAS study using the Illumina BovineHD array. Although we did not identify any significant association of bTB phenotypes with these new genetic markers, 2 markers exhibited substantial effects on bTB phenotypic prediction. The models and parameters trained in this study serve as a guide for future marker discovery surveys particularly in previously unassembled regions of the cattle genome.

Students' Engagement in and Perceptions of Blended Learning in a Clinical Module in a Veterinary Degree Program.

Blended learning has received much interest in higher education as a way to increase learning efficiency and effectiveness. By combining face-to-face teaching with technology-enhanced learning through online resources, students can manage their own learning. Blended methods are of particular interest in professional degree programs such as veterinary medicine in which students need the flexibility to undertake intra- and extramural activities to develop the range of competencies required to achieve professional qualification. Yet how veterinary students engage with blended learning activities and whether they perceive the approach as beneficial is unclear. We evaluated blended learning through review of student feedback on a 4-week clinical module in a veterinary degree program. The module combined face-to-face sessions with online resources. Feedback was collected by means of a structured online questionnaire at the end of the module and log data collected as part of a routine teaching audit. The features of blended learning that support and detract from students' learning experience were explored using quantitative and qualitative methods. Students perceived a benefit from aspects of face-to-face teaching and technology-enhanced learning resources. Face-to-face teaching was appreciated for practical activities, whereas online resources were considered effective for facilitating module organization and allowing flexible access to learning materials. The blended approach was particularly appreciated for clinical skills in which students valued a combination of visual resources and practical activities. Although we identified several limitations with online resources that need to be addressed when constructing blended courses, blended learning shows potential to enhance student-led learning in clinical courses.

Dandy-Walker-Like Malformation in a Free-Ranging Atlantic Harbour Seal Pup (Phoca vitulina concolor).

An 88.5 cm long, 12.9 kg, 3-week-old stranded male Atlantic harbour seal (Phoca vitulina concolor) presented with cerebellar ataxia, delayed postural reactions, hyperaesthesia and nystagmus. The skull was enlarged and domed. Ultrasound through a persistent fontanelle in the frontal bone revealed hydrocephalus. Magnetic resonance imaging showed diffuse enlargement of the ventricular system, an absent cerebellar vermis, hypertrophy of the choroid plexus of the fourth ventricle and enlargement of the caudal fossa. Throughout rehabilitation, the seal failed to achieve milestones critical for successful release or placement in a managed care facility, including the ability to feed independently and haul out. Three months into rehabilitation it began to regurgitate and staff had difficulty administering food to the seal. The seal was euthanized due to a poor prognosis. Post-mortem examination confirmed a) aplasia of the dorsal cerebellar vermis and hypoplasia of the most dorsal portions of the right and left cerebellar hemispheres, b) severe, diffuse, congenital communicating hydrocephalus, and c) aplasia of the interthalamic adhesion and corpus callosum. This case represents the first report of Dandy-Walker-like malformation (DWLM) in a marine mammal and illustrates the importance of advanced imaging and thorough post-mortem examination in free-ranging pinnipeds that strand with evidence of neurological disease.

NWChem: Past, present, and future.

Specialized computational chemistry packages have permanently reshaped the landscape of chemical and materials science by providing tools to support and guide experimental efforts and for the prediction of atomistic and electronic properties. In this regard, electronic structure packages have played a special role by using first-principle-driven methodologies to model complex chemical and materials processes. Over the past few decades, the rapid development of computing technologies and the tremendous increase in computational power have offered a unique chance to study complex transformations using sophisticated and predictive many-body techniques that describe correlated behavior of electrons in molecular and condensed phase systems at different levels of theory. In enabling these simulations, novel parallel algorithms have been able to take advantage of computational resources to address the polynomial scaling of electronic structure methods. In this paper, we briefly review the NWChem computational chemistry suite, including its history, design principles, parallel tools, current capabilities, outreach, and outlook.

Preaching to the choir or composing new verses? Toward a writerly climate literacy in introductory undergraduate biology.

Climate change is one of the most pressing issues facing society today, yet a wide range of misconceptions exist in society about whether or why climate change is happening, what its consequences are, and what can be done to address it. Large introductory biology courses present an opportunity to teach a large number of students-some of whom may never take another course focused on climate, ecology, or the environment-about climate change. However, content knowledge alone may not be enough to prepare students to transform their knowledge into action. To begin understanding how content knowledge interacts with student constructions of climate change solutions, we administered and quantitatively analyzed a survey that examined student views of climate change and how they shifted with instruction during an undergraduate introductory biology course at a large Midwestern university. Almost all participants entered the course agreeing that climate change is occurring, and their certainty about the science of climate change increased after instruction. After taking the course, more participants described climate change as having more immediate impacts, reporting that climate change is already harming people and that climate change will harm them personally. However, both at the beginning and end of the course, participants tended to think that humans would either be unable or unwilling to reduce climate change. They were also more worried about climate change at the end of the course than they were before. Increased concern might result from students becoming more certain of the science and severity of climate change, while remaining pessimistic that humans will effectively act on climate change. This pattern suggests instructors have opportunities to modify curricula in ways that leave students with a greater sense of empowerment and efficacy; we suggest questions that instructors can ask themselves in order to modify their courses with this goal in mind.

Viral emergence in marine mammals in the North Pacific may be linked to Arctic sea ice reduction.

Climate change-driven alterations in Arctic environments can influence habitat availability, species distributions and interactions, and the breeding, foraging, and health of marine mammals. Phocine distemper virus (PDV), which has caused extensive mortality in Atlantic seals, was confirmed in sea otters in the North Pacific Ocean in 2004, raising the question of whether reductions in sea ice could increase contact between Arctic and sub-Arctic marine mammals and lead to viral transmission across the Arctic Ocean. Using data on PDV exposure and infection and animal movement in sympatric seal, sea lion, and sea otter species sampled in the North Pacific Ocean from 2001-2016, we investigated the timing of PDV introduction, risk factors associated with PDV emergence, and patterns of transmission following introduction. We identified widespread exposure to and infection with PDV across the North Pacific Ocean beginning in 2003 with a second peak of PDV exposure and infection in 2009; viral transmission across sympatric marine mammal species; and association of PDV exposure and infection with reductions in Arctic sea ice extent. Peaks of PDV exposure and infection following 2003 may reflect additional viral introductions among the diverse marine mammals in the North Pacific Ocean linked to change in Arctic sea ice extent.

Network meta-analysis comparing techniques and outcomes of stump closure after distal pancreatectomy.

BACKGROUND: The incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy remains high, and different pancreatic stump closure techniques have been used to reduce the incidence. A network meta-analysis was undertaken to compare the most frequently performed pancreatic stump closure techniques after distal pancreatectomy and determine the technique associated with the lowest POPF rate. METHODS: A systematic search of the Scopus, PubMed, MEDLINE and Embase databases was conducted to identify eligible RCTs. The primary outcome was the occurrence of clinically relevant POPF. Secondary outcomes were duration of operation, blood loss, intrabdominal collections, postoperative complications and 30-day mortality. RESULTS: Sixteen RCTs including 1984 patients and eight different pancreatic stump closure techniques were included in the network meta-analysis. Patch coverage of the pancreatic stump (round ligament or seromuscular patch) after stapler or suture closure ranked best, with the lowest rates of clinically relevant POPF, lowest volume of intraoperative blood loss, fewer intra-abdominal abscesses, and lower rates of overall complications and 30-day mortality. Round ligament patch closure outperformed seromuscular patch closure in preventing clinically relevant POPF with a significantly larger cohort for comparative analysis. Pancreaticoenteric anastomotic closure consistently ranked poorly for most reported postoperative outcomes. CONCLUSION: Patch coverage after stapler or suture closure has the lowest POPF rate and best outcomes among stump closure techniques after distal pancreatectomy.

ANTECEDENTES: La incidencia de fístula pancreática (postoperative pancreatic fistula, POPF) tras una pancreatectomía distal sigue siendo alta y se han utilizado diferentes técnicas para el cierre del muñón pancreático con la intención de reducir su incidencia. Se realizó un metaanálisis en red para comparar las técnicas de cierre del muñón pancreático realizadas con más frecuencia después de la pancreatectomía distal y determinar qué técnica se asocia a una menor tasa de POPF. MÉTODOS: Se realizó una búsqueda sistemática en las bases de datos Scopus, PubMed, Medline y EMBASE de los RCTs que podían ser incluidos en estudio. La variable principal fue la aparición de POPF clínicamente relevante. Las variables secundarias fueron el tiempo operatorio, la pérdida de sangre, las colecciones intraabdominales, las complicaciones postoperatorias y la mortalidad a los 30 días. RESULTADOS: En el metaanálisis se incluyeron 16 RCTs con 1.984 pacientes y 8 técnicas diferentes de cierre del muñón pancreático. Los mejores resultados (menor tasa de POPF clínicamente relevante, menor pérdida sanguínea intraoperatoria, menor número de abscesos intraabdominales, menor tasa de complicaciones generales y menor mortalidad a los 30 días) se obtuvieron con el refuerzo del muñón pancreático con parches (de ligamento redondo o seromuscular), seguidos del grapado quirúrgico o la sutura simple. El cierre con parche del ligamento redondo fue superior al parche seromuscular en la prevención de POPF clínicamente relevante en una cohorte suficiente para el análisis estadístico comparativo. Los peores resultados en la mayoría de las variables postoperatorias se obtuvieron con el cierre simple. CONCLUSIÓN: En la pancreatectomía distal, la menor tasa de POPF y los mejores resultados perioperatorios se obtuvieron con el refuerzo con parches, seguidos del grapado quirúrgico o la sutura simple.

Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial.

BACKGROUND: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment. METHODS: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting. FINDINGS: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS. INTERPRETATION: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options. FUNDING: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.