TAB2 c.1398dup variant leads to haploinsufficiency and impairs extracellular matrix homeostasis

Transforming growth factor β‐activated kinase 1 (TAK1) mediates multiple biological processes through the nuclear factor κ‐light‐chain‐enhancer of activated B cells (NF‐κB) and the mitogen‐activated protein kinase (MAPK) signaling pathways. TAK1 activation is tightly regulated by its binding partners (TABs). In particular, binding with TAB2 is crucial for cardiovascular development and extracellular matrix (ECM) homeostasis. In our previous work, we reported a novel multisystem disorder associated with the heterozygous TAB2 c.1398dup variant. Here, we dissect the functional effects of this variant in order to understand its molecular pathogenesis. We demonstrate that TAB2 c.1398dup considerably undergoes to nonsense‐mediated messenger RNA decay and encodes a truncated protein that loses its ability to bind TAK1. We also show an alteration of the TAK1 autophosphorylation status and of selected downstream signaling pathways in patients’ fibroblasts. Immunofluorescence analyses and ECM‐related polymerase chain reaction‐array panels highlight that patient fibroblasts display ECM disorganization and altered expression of selected ECM components and collagen‐related pathways. In conclusion, we deeply dissect the molecular pathogenesis of the TAB2 c.1398dup variant and show that the resulting phenotype is well explained by TAB2 loss‐of‐function. Our data also offer initial insights on the ECM homeostasis impairment as a molecular mechanism probably underlying a multisystem disorder linked to TAB2.     

Comparación entre tromboelastografía y test de coagulación convencionales: ¿deberíamos abandonar los test de coagulación convencional en el paciente politraumatizado?

Introduction

TEG provides an in-vivo assessment of viscoelastic clot strength in whole blood compared with CCT, which may not reflect the influence of platelets. The aim of this study was to compare TEG vs. CCT in trauma patients stratified by mechanism of injury (MOI) and pre-existing coagulation status.

Abordaje y manejo de las lesiones retroperitoneales traumáticas

Traumatic retroperitoneal injuries constitute a challenge for trauma surgeons. They usually occur in the context of a trauma patient with multiple associated injuries, in whom invasive procedures have an important role in the diagnosis of these injuries. The retroperitoneum is the anatomical region with the highest mortality rates, therefore early diagnosis and treatment of these lesions acquire special relevance. The aim of this study is to present current published scientific evidence regarding incidence, mechanism of injury, diagnostic methods and treatment through a review of the international literature from the last 70 years. In conclusion, this systematic review showed an increasing trend towards non-surgical management of retroperitoneal injuries.     

Perioperative and Oncologic Outcomes of Nephrectomy and Caval Thrombectomy Using Extracorporeal Circulation and Deep Hypothermic Circulatory Arrest for Renal Cell Carcinoma Invading the Supradiaphragmatic Inferior Vena Cava and/or Right Atrium

Background

Radical nephrectomy (RN) and caval thrombectomy (CT) for renal cell carcinoma, with extracorporeal circulation (ECC) and deep hypothermic circulatory arrest (DHCA) is a challenging surgical approach.

Necrotizing soft-tissue infections

It has been more than 130 years since NSTIs were first described. Despite the development of various classification systems and progress in surgical management, these infections continue to have high mortality and pose enormous diagnostic and therapeutic challenges. For optimal outcome, treatment involves rapid institution of appropriate antibiotic coverage and early wide surgical debridement. Recovery requires aggressive resuscitation, postoperative nutritional support and wound care that is similar to the care of burn patients in many respects. The entire therapeutic process requires a well-prepared and coordinated team of health care professionals including EPs, general, orthopedic, and other specialist surgeons, infectious disease consultants, specially trained nursing staff, and physical therapists.     

Centronuclear myopathies: genotype–phenotype correlation and frequency of defined genetic forms in an Italian cohort

Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. To date, mutation in 7 different genes has been reported to cause CNMs but 30 % of cases still remain genetically undefined. Genetic investigations are often expensive and time consuming. Clinical and morphological clues are needed to facilitate genetic tests and to choose the best approach for genetic screening. We aimed to describe genotype–phenotype correlation in an Italian cohort of patients affected by CNMs, to define the relative frequencies of its defined genetic forms and to draw a diagnostic algorithm to address genetic investigations. We recruited patients with CNMs from all the Italian tertiary neuromuscular centers following clinical and histological criteria. All selected patients were screened for the four ‘canonical’ genes related to CNMs: MTM1, DNM2, RYR1 and BIN1. Pathogenetic mutations were found in 38 of the 54 screened patients (70 %), mostly in patients with congenital onset (25 of 30 patients, 83 %): 15 in MTM1, 6 in DNM2, 3 in RYR1 and one in TTN. Among the 13 patients with a childhood–adolescence onset, mutations were found in 6 patients (46 %), all in DNM2. In the group of the 11 patients with adult onset, mutations were identified in 7 patients (63 %), again in DNM2, confirming that variants in this gene are relatively more common in late-onset phenotypes. The present study provides the relative molecular frequency of centronuclear myopathy and of its genetically defined forms in Italy and also proposes a diagnostic algorithm to be used in clinical practice to address genetic investigations.