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Background Abdominal visceral resections incur relatively higher rates of postoperative bleeding and venous thromboembolism (VTE). While guidelines recommend the use of perioperative chemical thromboprophylaxis, the most appropriate time for its initiation is unknown. Here, we investigated whether early (before skin closure) versus postoperative commencement of chemoprophylaxis affected VTE and bleeding rates following abdominal visceral resection. Methods Retrospective review of all elective abdominal visceral resections undertaken between January 1, 2018, and June 30, 2019, across four tertiary-referral hospitals. Major bleeding was defined as the need for blood transfusion, reintervention, or > 20 g/L fall in hemoglobin from baseline. Clinical VTE was defined as imaging-proven symptomatic disease Results A total of 945 cases were analyzed. Chemoprophylaxis was given early in 265 (28.0%) patients and postoperatively in 680 (72.0%) patients. Mean chemoprophylaxis exposure doses were similar between the two groups. Clinical VTE developed in 14 (1.5%) patients and was unrelated to chemoprophylaxis timing. Postoperative bleeding occurred in 71 (7.5%) patients, with 57 (80.3%) major bleeds, requiring blood transfusion in 48 (67.6%) cases and reintervention in 31 (43.7%) cases. Bleeding extended length-of-stay (median (IQR), 12 (7–27) versus 7 (5–11) days, p p = 0.038) and independently predicted its occurrence. Conclusions The risk of bleeding following elective abdominal visceral resections is substantial and is higher than the risk of clinical VTE. Compared with early chemoprophylaxis, postoperative initiation reduces bleeding risk without an increased risk of clinical VTE.

Obesity is common and adversely impacts quality-of-life and healthcare cost. In Australia, less than 10% of bariatric surgeries are performed in the public sector. This study reports our 10-year experience from a high volume public bariatric service which delivers multi-disciplinary care for primary and revisional procedures with mid- to long-term follow-up.A prospectively maintained database of all patients who underwent bariatric surgery from January 2010 to January 2020 at a tertiary metropolitan hospital was analysed. We analysed patient demographics, comorbidities, perioperative outcomes, 2- and 5-year weight loss as well as comorbidities reduction.A total of 995 patients underwent 1086 (674 primary and 412 revisional) bariatric procedures with mean age of 46.9 years, mean BMI of 49.6 ± 9.1 kg/mThis study confirms that bariatric surgery in Australia can be delivered effectively in resource constrained public health system with outcomes similar to private sector.

Wound complications are a common cause of postoperative morbidity and incur significant healthcare costs. Recent studies have shown that negative pressure wound dressings reduce wound complication rates, particularly surgical site infections, after elective laparotomies. The clinical utility of prophylactic negative pressure wound dressings for closed emergency laparotomy incisions remains controversial. This meta-analysis investigated the rates of wound complications after emergency laparotomy when a negative pressure wound dressing was applied.A systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane Registry, Web of Science, and Clinialtrials.gov databases were searched from January 1, 2005, to April 1, 2022. All studies comparing negative pressure wound dressings to standard dressings on closed emergency laparotomy incisions were included.A total of 1,199 (negative pressure wound dressings: 566, standard dressing: 633) patients from 7 (prospective: 4, retrospective: 3) studies were identified. Overall, the surgical site infection (superficial/deep) rate was 13.6% (77/566) vs 25.1% (159/633) in the negative pressure wound dressing versus standard dressing groups, respectively (odds ratio 0.43, 95% confidence interval 0.30-0.62). Wound breakdown (skin/fascial dehiscence) was significantly lower in the negative pressure wound dressing (7.7%) group compared to the standard dressing (16.9%) group (odds ratio 0.36, 95% confidence interval 0.19-0.72). The incidence of overall wound complications was significantly lower in the negative pressure wound dressing (15.9%) group compared to the standard dressing (30.4%) group (odds ratio 0.41, 95% confidence interval 0.28-0.59). No significant differences were found in hospital length-of-stay and readmission rates.Prophylactic negative pressure wound dressings for closed emergency laparotomy incisions were associated with a significant reduction in surgical site infections, wound breakdown, and overall wound complications, thus supporting its clinical use.

To provide an updated evaluation of radiology residency program websites in light of virtual interviewing during the COVID-19 pandemic and encourage programs to improve the quality of their online website presence.We evaluated the websites of 197 US radiology residency programs between November and December 2021 for the presence or absence of 30 metrics. The metrics chosen are those considered important by applicants when choosing a program and have been used in other similar papers.Of the 197 programs, 192 (97.5%) had working websites. The average radiology residency website had 16 of 30 (54%) metrics listed on their websites. Five programs did not have accessible websites and were not included in the analysis. The most comprehensive website had 29 of 30 (97%) of metrics listed and the least comprehensive website had 2 of 30 (7%). There is a statistically significant difference in website comprehensiveness between top 20 and non-top 20 radiology program websites.Although radiology residency program websites have generally become more comprehensive over time, there is still room for improvement, especially in times of virtual interviews when residency applicants are becoming more and more reliant on program websites to gain essential information about a program. Some key areas to include are diversity and inclusion initiatives, resident wellness, applicant information, program benefits, and showcase of people in the program.

The purpose of the present study was to validate a new spinal sagittal classification. We retrospectively included 105 consecutive AIS patients who underwent posterior spinal fusion. Preoperative long-standing EOS radiographs were available on all patients. Patients were classified according to the four suggested sagittal patterns: type 1, 2a, 2b or 3. Several predetermined sagittal parameters were compared between the groups. The mean preoperative Cobb angle was 64° ± 12°, and 73% of the patients were female. Of 105 patients, 51 were type 1, 14 were type 2a, one was type 2b and 39 were type 3. The distribution of the four sagittal patterns was significantly different compared with the original publication (p

Major ventral hernia surgeries are commonly performed. Despite guideline recommendations for chemo-thromboprophylaxis in the perioperative period, the optimal timing for its initiation is unknown. We characterized the variability in perioperative chemoprophylaxis in elective major ventral hernia surgery and determine whether timing of chemoprophylaxis affects bleeding and symptomatic venous thromboembolism.Retrospective analysis of all elective major ventral hernia surgery undertaken between January 1, 2014, and December 31, 2019, at 14 hospitals across Australia. Major bleeding was defined as the need for blood transfusion, reoperation, or20 g/L fall in hemoglobin. Clinical venous thromboembolism was defined as imaging-proven symptomatic disease30 days postsurgery. Propensity score matched analysis was used to validate primary findings.In the study, 3,384 hernia repairs were analyzed. Chemoprophylaxis was administered early (before skin closure), postoperatively, or not given in 856 (25.3%), 1,701 (50.3%), and 827 (24.4%) patients, respectively. This varied between surgeons, trainees, and institutions. Clinical venous thromboembolism occurred in 6 (0.2%) patients and was unrelated to chemoprophylaxis timing. 134 (4.0%) patients had postoperative bleeding, with 67 (50%) major bleeds, requiring surgical control in 41 (30.6%) cases. Bleeding extended duration of stay (mean [standard deviation], 7.0 (13.9) vs 2.6 (4.7) days, P.001). Notably, compared with postoperative (odds ratio 1.98; 95% confidence interval, 1.36-2.88; P.001) and no (odds ratio 2.83; 95% confidence interval, 1.70-4.89; P.001) chemoprophylaxis, early initiation significantly increased bleeding risk and independently predicted its occurrence.The incidence of clinical venous thromboembolism after elective major ventral hernia repair is low. Variability in perioperative thromboprophylaxis is high. Early chemoprophylaxis increases bleeding risk without appreciable additional protection from venous thromboembolism.

Patients with scleroderma often suffer from dysphagia and gastroesophageal reflux disease (GERD). Partial fundoplication is a validated anti-reflux procedure for GERD but may worsen dysphagia in scleroderma patients. Its utility in these patients is unknown. Here, we evaluate the efficacy and acceptability of partial fundoplication for the treatment of medically refractory GERD in patients with scleroderma.Analysis of a prospectively maintained database of patients who underwent fundoplication across 14 hospitals between 1991 and 2019. Perioperative outcomes, reintervention rates, heartburn, dysphagia, and patient satisfaction were assessed at 3 months, 1- and 3-years post-surgery.A total of 17 patients with scleroderma were propensity score matched to 526 non-scleroderma controls. All underwent a partial fundoplication. Perioperative outcomes including complication rate, length of stay, and need for reoperation were similar between the two groups. Compared to baseline, both groups reported significantly improved heartburn at 3 months, 1- and 3-years following partial fundoplication. Surgery was equally effective at controlling heartburn across all follow-up timepoints in patients with or without scleroderma. Dysphagia to solids was more common in patients with scleroderma than controls at 3-months post-surgery, but was not significantly different to controls at 1- and 3-year follow-up. Satisfaction scores were high and comparable between both groups across all postoperative timepoints, with 100% of patients with scleroderma reporting that their initial choice to undergo surgery was correct.Partial fundoplication controls reflux and is associated with a transient period of dysphagia to solids in patients with scleroderma. This approach is safe, effective and acceptable for patients with scleroderma and medically refractory GERD.

Surgery is the only effective treatment strategy for a symptomatic pharyngeal pouch. However, octo- and nonagenarians are often denied referral to a surgeon because of perceived increased risks. Here, we compare the outcomes of pharyngeal pouch surgery in octo- and nonagenarians with patients under 80 years-of-age and determine the factors which predict post-operative complications and improvement in swallowing.Analysis of a prospectively maintained database of patients who underwent pharyngeal pouch surgery across seven hospitals over 15 years.In total, 113 patients (≥80 years-of-age: 27,80 years-of-age: 86) underwent endoscopic or open pharyngeal pouch surgery. Despite more comorbidities and a longer hospital stay (median: one extra day), patients ≥80 years-of-age had comparable operative time, complication profile, intensive care admission, emergency reoperation, and revisional pouch surgery as their younger counterparts. Furthermore, the severity of complications was not significantly different between the two age cohorts. No surgical mortality was recorded. Multivariate analysis demonstrated that diverticulectomy combined with cricopharyngeal myotomy independently predicted higher rates of complications (OR: 4.53, 95% CI: 1.43-14.33, p = 0.010), but also greater symptomatic improvement (OR: 4.36, 95% CI: 1.50-12.67, p = 0.007). Importantly, a greater proportion of octo- and nonagenarians experienced improved swallowing than patients 80 years-of-age (96.3% vs. 74.4%, p = 0.013). Moreover, advanced age was not predictive of post-operative complications on multivariate analysis.Pharyngeal pouch surgery in octo- and nonagenarians is safe and effective. Surgical correction in this age group alleviates symptoms and improves quality-of-life for most patients. These patients should not be denied surgery on the basis of advanced age alone.

APR-246 (eprenetapopt) is in clinical development with a focus on hematologic malignancies and is promoted as a mutant-p53 reactivation therapy. Currently, the detection of at least one

Purpose :Genitopatellar syndrome and Say–Barber–Biesecker–Young–Simpson syndrome are caused by variants in the KAT6B gene and are part of a broad clinical spectrum called KAT6B disorders, whose variable expressivity is increasingly being recognized. Methods: We herein present the phenotypes of 32 previously unreported individuals with a molecularly confirmed diagnosis of a KAT6B disorder, report 24 new pathogenic KAT6B variants, and review phenotypic information available on all published individuals with this condition. We also suggest a classification of clinical subtypes within the KAT6B disorder spectrum. Results: We demonstrate that cerebral anomalies, optic nerve hypoplasia, neurobehavioral difficulties, and distal limb anomalies other than long thumbs and great toes, such as polydactyly, are more frequently observed than initially reported. Intestinal malrotation and its serious consequences can be present in affected individuals. Additionally, we identified four children with Pierre Robin sequence, four individuals who had increased nuchal translucency/cystic hygroma prenatally, and two fetuses with severe renal anomalies leading to renal failure. We also report an individual in which a pathogenic variant was inherited from a mildly affected parent. Conclusión: Our work provides a comprehensive review and expansion of the genotypic and phenotypic spectrum of KAT6B disorders that will assist clinicians in the assessment, counseling, and management of affected individuals. Sin financiación 8.822 JCR(2020) Q1, 15/176 Genetics & Heredity 3.509 SJR (2020) Q1, 7/96 Genetics (clinical) No data IDR 2020 UEM

Midgut volvulus complicating congenital malrotation is a rare but life-threatening condition that can occur in pregnancy. We present a case of intestinal infarction resulting from midgut volvulus in a healthy 32-week pregnant woman who underwent emergency laparotomy and small bowel resection in the setting of fetal death in utero. This case highlights several challenging issues in diagnosing and managing this uncommon condition which leads to increased adverse perinatal outcomes. Prompt investigation and definitive surgical treatment are required when pregnant women present with bilious vomiting and new-onset abdominal or back pain especially beyond the first trimester.

Two Argentinean siblings (a boy and a girl) from a nonconsanguineous family presented with hypercalcemia, hypercalciuria, hypophosphatemia, low parathyroid hormone (PTH), and nephrocalcinosis.The goal of this study was to identify genetic causes of the clinical findings in the two siblings.Whole exome sequencing was performed to identify disease-causing mutations in the youngest sibling, and a candidate variant was screened in other family members by Sanger sequencing. In vitro experiments were conducted to determine the effects of the mutation that was identified.Affected siblings (2 y.o. female and 10 y.o male) and their parents were included in the study. Informed consent was obtained for genetic studies.A novel homozygous mutation in the gene encoding the renal sodium-dependent phosphate transporter SLC34A1 was identified in both siblings (c.1484GA, p.Arg495His). In vitro studies showed that the p.Arg495His mutation resulted in decreased phosphate uptake when compared to wild-type SLC34A1.The homozygous GA transition that results in the substitution of histidine for arginine at position 495 of the renal sodium-dependent phosphate transporter, SLC34A1, is involved in disease pathogenesis in these patients. Our report of the second family with two mutated SLC34A1 alleles expands the known phenotype of this rare condition.

Shohat-type spondyloepimetaphyseal dysplasia (SEMD) is a skeletal dysplasia that affects cartilage development. Similar skeletal disorders, such as spondyloepiphyseal dysplasias, are linked to mutations in type II collagen (COL2A1), but the causative gene in SEMD is not known. Here, we have performed whole-exome sequencing to identify a recurrent homozygous c.408+1G>A donor splice site loss-of-function mutation in DDRGK domain containing 1 (DDRGK1) in 4 families affected by SEMD. In zebrafish, ddrgk1 deficiency disrupted craniofacial cartilage development and led to decreased levels of the chondrogenic master transcription factor sox9 and its downstream target, col2a1. Overexpression of sox9 rescued the zebrafish chondrogenic and craniofacial phenotype generated by ddrgk1 knockdown, thus identifying DDRGK1 as a regulator of SOX9. Consistent with these results, Ddrgk1-/- mice displayed delayed limb bud chondrogenic condensation, decreased SOX9 protein expression and Col2a1 transcript levels, and increased apoptosis. Furthermore, we determined that DDRGK1 can directly bind to SOX9 to inhibit its ubiquitination and proteasomal degradation. Taken together, these data indicate that loss of DDRGK1 decreases SOX9 expression and causes a human skeletal dysplasia, identifying a mechanism that regulates chondrogenesis via modulation of SOX9 ubiquitination.

The advent of multi-omic profiling of tumors, together with the increasing affordability of high-throughput drug screening programs, has helped usher in a new era of molecular targeted therapies for many solid malignancies. However, there has been limited success in esophageal adenocarcinoma. Until recently, preclinical drug development for this cancer has been largely limited to a small number of cell line models. Now, the increasing availability of patient-derived xenografts and novel metastatic models are helping to bridge the gap between scientific discovery and patient care. These platforms are valuable adjuncts for drug testing. Nevertheless, further work is required to develop systems that model the tumor microenvironment, including cancer cell interactions with the immune system, which will be particularly relevant for the translation of novel immunotherapies for esophageal adenocarcinoma.

TP53, a critical tumour suppressor gene, is mutated in over half of all cancers resulting in mutant-p53 protein accumulation and poor patient survival. Therapeutic strategies to target mutant-p53 cancers are urgently needed. We show that accumulated mutant-p53 protein suppresses the expression of SLC7A11, a component of the cystine/glutamate antiporter, system xC−, through binding to the master antioxidant transcription factor NRF2. This diminishes glutathione synthesis, rendering mutant-p53 tumours susceptible to oxidative damage. System xC− inhibitors specifically exploit this vulnerability to preferentially kill cancer cells with stabilized mutant-p53 protein. Moreover, we demonstrate that SLC7A11 expression is a novel and robust predictive biomarker for APR-246, a first-in-class mutant-p53 reactivator that also binds and depletes glutathione in tumours, triggering lipid peroxidative cell death. Importantly, system xC− antagonism strongly synergizes with APR-246 to induce apoptosis in mutant-p53 tumours. We propose a new paradigm for targeting cancers that accumulate mutant-p53 protein by inhibiting the SLC7A11–glutathione axis., Efficient therapeutic strategies to target mutant-p53 cancers are needed. Here, the authors demonstrate the molecular mechanism through which mutant-p53 tumours are susceptible to oxidative damage and propose a potential strategy for targeting such cancers by inhibiting the SLC7A11-glutathione axis.

Czech dysplasia, metatarsal type is an autosomal dominant skeletal disorder that is characterized by early-onset, progressive arthritis, brachydactyly of the 3rd and 4th toes, and characteristic radiographic findings in patients of normal stature. Patients with Czech dysplasia typically present in late childhood or later. In the present report, whole exome sequencing identified a mutation in COL2A1 (c.823C>T, p.R275C) known to be associated with Czech dysplasia in a 3.5 year old female who had a family history of early-onset arthritis and who was asymptomatic except for prominent knees. The use of whole exome sequencing facilitated diagnosis of this rare disease (less than 15 families in the literature) in the presymptomatic period and thus enabled us to provide early anticipatory guidance and genetic counseling for the family.

The purpose of this study was to develop a biofeedback tilt-table for automatic tilt-table training, helping patients with spinal cord injury (SCI) to recover more rapidly from orthostatic hypotension, and increasing safety to avoid syncope during training. This biofeedback tilt-table implemented automatic training maneuvers and included three closed feedback loops to monitor the acquisition of physiological signals from patients and the feedback of presyncope symptoms (PS) to regulate the angle of tilt. The results of clinical testing revealed that the mean blood pressure and oxygen saturation represented the most useful physiological signals for determining PS feedback and the quantitative criteria adopted were practicable and useful in describing the level of PS. This novel biofeedback tilt-table system offered higher patient throughput, faster training and safety in training of SCI patients to overcome their orthostatic hypotension than traditional tilt-table training, and could provide quantitative information of PS to assist medical staff in studying the mechanism of orthostatic syncope.

To examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone(®) ) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol(®) ) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.This multi-centered, double-blind, placebo-controlled study, conducted under the auspices of the National Drug Abuse Treatment Clinical Trials Network, randomly assigned 302 participants at sites in California, Oregon, Washington, Colorado, Texas, Georgia, Ohio, New York and Washington DC, USA to one of three conditions provided with XR-NTX: 4 mg/day BUP (BUP4, n = 100), 16 mg/day BUP (BUP16, n = 100, or no buprenorphine (placebo; PLB, n = 102). Participants received pharmacotherapy for 8 weeks, with three clinic visits per week. Cognitive behavioral therapy was provided weekly. Follow-up assessments occurred at 1 and 3 months post-intervention. The planned primary outcome was urine drug screen (UDS)-corrected, self-reported cocaine use during the last 4 weeks of treatment. Planned secondary analyses assessed cocaine use by UDS, medication adherence, retention and adverse events.No group differences were found between groups for the primary outcome (BUP4 versus PLB, P = 0.262; BUP16 versus PLB, P = 0.185). Longitudinal analysis of UDS data during the evaluation period using generalized linear mixed equations found a statistically significant difference between BUP16 and PLB [P = 0.022, odds ratio (OR) = 1.71] but not for BUP4 (P = 0.105, OR = 1.05). No secondary outcome differences across groups were found for adherence, retention or adverse events.Buprenorphine + naloxone, used in combination with naltrexone, may be associated with reductions in cocaine use among people who meet DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.