A case of bowel entrapment after penetrating injury of the pelvis: don't forget the omentumplasty

Bowel entrapment within a pelvic injury is rare and difficult to diagnose. Usually, it is diagnosed late because of concomitant abdominal injuries. It may present itself as an acute intestinal obstruction or, more commonly, as a prolonged or intermittent ileus. Therefore, one should be aware of this late complication and primarily take measures for avoiding bowel entrapment. This report describes an unusual case of bowel entrapment within a pelvic fracture after a penetrating injury, and discusses options for preventing such a complication

Modulation of the tumour promoting functions of cancer associated fibroblasts by phosphodiesterase type 5 inhibition increases the efficacy of chemotherapy in human preclinical models of esophageal adenocarcinoma

Background and aims: Esophageal adenocarcinoma (EAC) is chemoresistant in the majority of cases. The tumor-promoting biology of cancer associated fibroblasts (CAF) make them a target for novel therapies. Phosphodiesterase type 5 inhibitors (PDE5i) have been shown to regulate the activated fibroblast phenotype in benign disease. We investigated the potential for CAF modulation in EAC using PDE5i to enhance the efficacy of chemotherapy. Methods: EAC fibroblasts were treated with PDE5i and phenotypic effects examined using immunoblotting, immunohistochemistry, gel contraction, transwell invasion, organotypics, single cell RNAseq and shotgun proteomics. The combination of PDE5i with standard-of-care chemotherapy (Epirubicin, 5-Fluorouracil and Cisplatin) was tested for safety and efficacy in validated near-patient model systems (3D tumor growth assays (3D-TGAs) and patient derived xenograft (PDX) mouse models). Results: PDE5i treatment reduced alpha-SMA expression in CAFs by 50% (p<0.05), associated with a significant reduction in the ability of CAFs to contract collagen-1 gels and induce cancer cell invasion, (p<0.05). RNAseq and proteomic analysis of CAF and EAC cell lines revealed PDE5i specific regulation of pathways related to fibroblast activation and tumor promotion. 3D-TGA assays confirmed the importance of stromal cells to chemoresistance in EAC, which could be attenuated by PDE5i. Chemotherapy+PDE5i in PDX-bearing mice was safe and significantly reduced PDX tumor volume (p<0.05). Conclusion: PDE5 is a candidate for clinical trials to alter the fibroblast phenotype in esophageal cancer. We demonstrate the specificity of PDE5i for fibroblasts to prevent transdifferentiation and revert the CAF phenotype. Finally, we confirm the efficacy of PDE5i in combination with chemotherapy in close-to-patient in vitro and in vivo PDX-based model systems

Bi-allelic loss-of-function CACNA1B mutations in progressive epilepsy-dyskinesia

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants.Peer reviewe

The UK10K project identifies rare variants in health and disease.

The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results

Temperature dependence of the electrooptical Kerr effect: Anisotropic electric dipole polarizabilities of NH3, CH3NH2, (CH3)2NH, and (CH3)3N

The study that is reported here is concerned with the development of an experimental route to the four independent components of the electric dipole polarizability of species of Cs symmetry and, in particular, with the specification of the anisotropic polarizabilities of NH3, CH3NH2, (CH3)2NH, and (CH3)3N, for which a consistent set of data has not been available. It is shown that the four equations required to evaluate the four components of the optical-frequency (λ = 632.8 nm) polarizabilities of CH3NH2 and (CH3)2NH can be drawn from measurements of (1) the temperature dependence of the electrooptical Kerr effect, (2) the Rayleigh depolarization ratio, and (3) the refractive index of the gas together with (4) a simple bond-additivity model of the polarizability. The model uses the polarizabilities of the C3v species NH3 and (CH3)3N to estimate the off-diagonal polarizabilities of the Cs species CH3NH2 and (CH3)2NH. To this end, improved equipment has been used to record the vapor-phase Kerr effects of NH3, CH3NH2, (CH3)2NH, and (CH3)3N over ranges of temperature and pressure. An analysis of the data yields precise values of the anisotropic polarizabilities and, as a bonus, less precise values of the Kerr hyperpolarizabilities of all four molecules and provides a clear demonstration of the utility of the method

Rupture of the brachioradialis muscle following blunt trauma. A case report

A 50-year old healthy male lost control over the pull string of a milling machine, which strangulated his right elbow and forearm with high velocity. Magnetic resonance imaging of the right upper extremity revealed a substantial tear in the muscle belly of the musculus brachioradialis with multiple small defects in the surrounding musculature of the forearm. The affected arm was immobilized for 1 week with an above the elbow cast. In the following months, guided training and strengthening exercises were performed. The patient could return to his physically demanding work after 10 months and regained full function of his hand and wrist after 18 months. This case report demonstrates that short immobilization followed by extensive and guided strength training has been observed to result in persisting weakness of elbow flexion but good functional outcome for the wrist and hand

Xiphodynia as an Unusual Cause of Chest Pain: A Case Series

Abstract Introduction Treatment options for xiphodynia are injections with local corticosteroid injections or surgical resection of the xiphoid process. Currently, there is no consensus as to which treatment is the most optimal. Objectives The aim of this case series was to compare the safety and efficacy of conservative and surgical treatment for patients with xiphodynia. Patients and Methods A retrospective case series was performed. All patients presenting with xiphodynia between 2016 and 2021 were eligible. Demographic data and treatment regimes, including preoperative work-up and surgical technique, were extracted from the electronic patient files. In addition, all patients received a follow-up phone call with a questionnaire. Patient satisfaction was measured using the Numeric Rating Scale. Results A total of five patients, suffering from xiphodynia for up to 10 years, completed the follow-up questionnaire (median patient age, 57 years; range 51–68 years). Three of these patients initially received conservative treatment with local injections with corticosteroids for at least 6 months. One patient was satisfied with the results and did not opt for surgical treatment. Eventually, four patients were treated surgically by removing the xiphoid process. No postoperative complications were recorded and 100% of the patients who underwent a xiphoidectomy were free of symptoms and satisfied with the results. Conclusion Symptoms related to xiphodynia can be relieved using conservative or surgical treatment, where the latter seems to be a safe and effective solution.</jats:p