Energy Expenditure in Critically Ill Patients with Aneurysmal Subarachnoid Hemorrhage, Intracerebral Hemorrhage, and Traumatic Brain Injury-A Prospective Observational Study.

Background: Energy expenditure (EE) in patients with aneurysmal subarachnoid hemorrhage (SAH) may differ from other intracranial pathologies, such as intracerebral hemorrhage (ICH) or traumatic brain injury (TBI), due to an activation of the sympathetic nervous system. Indirect calorimetry (IC) is recommended, but is not always available. We study EE, catabolism, and metabolic stress in patients with SAH, TBI, ICH, and sepsis as controls.

Genetic insights into fetal kidney development: Variants in HNF1A and PKHD1 genes.

The orchestration of fetal kidney development involves the precise control of numerous genes, including HNF1A, HNF1B and PKHD1. Understanding the genetic factors influencing fetal kidney development is essential for unraveling the complexities of renal disorders. This study aimed to search for disease-causing variants in HNF1A, HNF1B, PKHD1 genes, among fetus and babies or via parental samples, using sanger sequencing, NGS technologie and MLPA.

Loss of phospholipase PLAAT3 causes a mixed lipodystrophic and neurological syndrome due to impaired PPARγ signaling.

Phospholipase A/acyltransferase 3 (PLAAT3) is a phospholipid-modifying enzyme predominantly expressed in neural and white adipose tissue (WAT). It is a potential drug target for metabolic syndrome, as Plaat3 deficiency in mice protects against diet-induced obesity. We identified seven patients from four unrelated consanguineous families, with homozygous loss-of-function variants in PLAAT3, who presented with a lipodystrophy syndrome with loss of fat varying from partial to generalized and associated with metabolic complications, as well as variable neurological features including demyelinating neuropathy and intellectual disability.

Epidemiology, Outcomes, and Complement Gene Variants in Secondary Thrombotic Microangiopathies.

Background: The identification of complement defects as major drivers of primary atypical hemolytic uremic syndrome (HUS) has transformed the landscape of thrombotic microangiopathies (TMAs), leading to the development of targeted therapies and better patient outcomes. By contrast, little is known about the presentation, genetics, and outcomes of TMA associated with specific diseases or conditions, also referred to as secondary TMA.

Methods: In this study, we assessed the relative incidence, clinical and genetic spectra, and long-term outcomes of secondary TMA versus other TMAs in consecutive patients hospitalized with a first episode of TMA from 2009 to 2019 at two European reference centers.

Genotype-phenotype correlations for COL4A3-COL4A5 variants resulting in Gly substitutions in Alport syndrome.

Alport syndrome is the commonest inherited kidney disease and nearly half the pathogenic variants in the COL4A3-COL4A5 genes that cause Alport syndrome result in Gly substitutions. This study examined the molecular characteristics of Gly substitutions that determine the severity of clinical features. Pathogenic COL4A5 variants affecting Gly in the Leiden Open Variation Database in males with X-linked Alport syndrome were correlated with age at kidney failure (n = 157) and hearing loss diagnosis (n = 80).

Autosomal dominant polycystic kidney disease (ADPKD) in Tunisia: From molecular genetics to the development of prognostic tools.

A high prevalence of genetic kidney disease in Tunisia has been detected, and their study provides very important clinical and genetic information. Autosomal dominant polycystic kidney disease (ADPKD) is one of the main causes of morbidity and mortality associated with the kidneys in Tunisia. We present here clinical and genetic characteristics of a cohort of Tunisian patients with ADPKD.

Guidelines for Genetic Testing and Management of Alport Syndrome.

Genetic testing for pathogenic variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history of hematuria or kidney function impairment. Alport syndrome experts now advocate genetic testing for persistent hematuria, even when a heterozygous pathogenic or is suspected, and cascade testing of their first-degree family members because of their risk of impaired kidney function. The experts recommend too that or heterozygotes do not act as kidney donors.

Detection of a novel mutation in a Tunisian child with polycystic kidney disease.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic disease that has an adverse impact on the patients' health and quality of life. ADPKD is usually known as "adult-type disease," but rare cases have been reported in pediatric patients. We present here a 2-year-old Tunisian girl with renal cyst formation and her mother with adult onset ADPKD.

High-throughput sequencing contributes to the diagnosis of tubulopathies and familial hypercalcemia hypocalciuria in adults.

Hereditary tubulopathies are rare diseases with unknown prevalence in adults. Often diagnosed in childhood, hereditary tubulopathies can nevertheless be evoked in adults. Precise diagnosis can be difficult or delayed due to insidious development of symptoms, comorbidities and polypharmacy.

Copy-number variation of the NPHP1 gene in patients with juvenile Nephronophthisis.

: Juvenile nephronophthisis (NPHP) is an autosomal recessive cystic disease of the kidney. It represents the most frequent genetic cause of chronic renal failure in children. : we investigated clinical and molecular features in two children with Juvenile nephronophthisis using firstly Multiplex ligation-dependent probe amplification (MLPA) and secondly multiplex PCR.

Two novel GJA1 variants in oculodentodigital dysplasia.

Background: Oculodentodigital dysplasia (ODDD) is a rare disorder with pleiotropic effects involving multiple body systems, caused by mutations in the gap junction protein alpha 1 (GJA1) gene. GJA1 gene encodes a polytopic connexin membrane protein, Cx43, that is a component of connexon membrane channels.

Methods: We describe two unrelated female probands referred for a genetic review in view of a dysmorphic clinical phenotype.

Mutational analysis in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD): Identification of five mutations in the PKD1 gene.

Autosomal Dominant Polycystic Kidney Disease (ADPKD), the most frequent genetic disorder of the kidneys, is characterized by a typical presenting symptoms include cysts development in different organs and a non-cysts manifestations. ADPKD is caused by mutations in PKD1 or PKD2 genes. In this study, we aimed to search for molecular causative defects among PKD1 and PKD2 genes.

Genotype and Outcome After Kidney Transplantation in Alport Syndrome.

Introduction: Alport syndrome (AS) is caused by mutations in α3/α4/α5 (IV) collagen genes, the severity of which determine the progression of AS. Posttransplantation outcome is good, although anti-glomerular basement membrane (anti-GBM) glomerulonephritis occurs in 3% to 5% of recipients, clustering in patients with a severe mutation. We assessed whether the severity of the underlying AS mutation affects graft and patients outcome after transplantation, including the occurrence of anti-GBM nephritis.

Micronutrient treatment for children with emotional and behavioral dysregulation: a case series.

Introduction: In clinical studies of adults and children, broad-spectrum micronutrients (minerals and vitamins) have proven beneficial for improving mood regulation and attention. We report here pilot work whose primary objective was to evaluate the feasibility of studying micronutrient treatment in school-aged children with emotional and behavioral problems. Issues examined included feasibility of participant recruitment from a culturally diverse population, probability of sample retention for a 12-week trial, acceptability of the outcome measures, supplement adherence, as well as trends in treatment benefit.

Congenital generalized lipodystrophy: identification of novel variants and expansion of clinical spectrum.

Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder with two major subtypes. Variants in AGPAT2 result in CGL type 1 with milder manifestations, whereas BSCL2 variants cause CGL type 2 with more severe features. Muscle hypertrophy caused by lack of adipose tissue is present early in life in CGL patients.

Identification by array comparative genomic hybridization of a new amplicon on chromosome 17q highly recurrent in BRCA1 mutated triple negative breast cancer.

Introduction: Triple Negative Breast Cancers (TNBC) represent about 12% to 20% of all breast cancers (BC) and have a worse outcome compared to other BC subtypes. TNBC often show a deficiency in DNA double-strand break repair mechanisms. This is generally related to the inactivation of a repair enzymatic complex involving BRCA1 caused either by genetic mutations, epigenetic modifications or by post-transcriptional regulations.

[Anesthesia in a patient after endoscopic lung volume reduction. First anesthesiological experiences with implanted endobronchial valves].

Chronic obstructive pulmonary disease (COPD) is a disease with a high incidence and extensive comorbidities that make COPD a key challenge for anesthesiologists. A new treatment strategy, such as endoscopic lung volume reduction (ELVR) with implantation of endobronchial valves is a rapidly developing area which is still unknown to many anesthesiologists. This article therefore describes first experiences in a patient with five endobronchial valves in the right upper lobe who needed urgent surgery due to lumbar disc herniation with neurological impairment.

Improving mutation screening in familial hematuric nephropathies through next generation sequencing.

Alport syndrome is an inherited nephropathy associated with mutations in genes encoding type IV collagen chains present in the glomerular basement membrane. COL4A5 mutations are associated with the major X-linked form of the disease, and COL4A3 and COL4A4 mutations are associated with autosomal recessive and dominant forms (thought to be involved in 15% and 1%-5% of the families, respectively) and benign familial hematuria. Mutation screening of these three large genes is time-consuming and expensive.

Li-Fraumeni syndrome: multiple distinct brain tumours in two brothers.

Li-Fraumeni syndrome is a rare autosomal dominant cancer-prone condition characterized by the occurrence of a large set of different types of cancer in a patient and their family. A germline disease-causing mutation of the gene encoding the p53 protein is associated with the syndrome. We report on a family in which segregation of a TP53 mutation in two generations was associated with two brain tumours, a leiomyosarcoma and a thyroid carcinoma in four male patients.

[Trauma bay haemoglobin level. Predictor of coagulation disorder in major trauma].

Background: Trauma-induced coagulopathy is common in patients with major trauma and requires early and appropriate treatment for bleeding control. Even in emergency laboratory, the availability of standard coagulation tests is associated with certain latencies and devices for viscoelastic haemostasis diagnosis (thromboelastometry) are not routinely established in major trauma centres.

Purpose: We searched for a laboratory parameter with fast availability by point of care blood gas analysis and reliable correlation with coagulation parameters.