Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis

Chronic hepatitis C virus (HCV) infection outcomes include liver failure, hepatocellular carcinoma (HCC), and liver-related death.

Osmotic diuresis due to urea as the cause of hypernatraemia in critically ill patients

Hypernatraemia is common in critically ill patients and has been shown to be an independent predictor of mortality. Osmotic urea diuresis can cause hypernatraemia due to significant water losses but is often not diagnosed. Free water clearance (FWC) and electrolyte free water clearance (EFWC) were proposed to quantify renal water handling. We aimed to (i) identify patients with hypernatraemia due to osmotic urea diuresis and (ii) investigate whether FWC and EFWC are helpful in identifying renal loss of free water.

Ten novel mutations in the NR5A1 gene cause disordered sex development in 46,XY and ovarian insufficiency in 46,XX individuals

Steroidogenic factor-1 (SF-1/NR5A1) is a nuclear receptor that regulates adrenal and reproductive development and function. NR5A1 mutations have been detected in 46,XY individuals with disorders of sexual development (DSD) but apparently normal adrenal function and in 46,XX women with normal sexual development yet primary ovarian insufficiency (POI).

Novel mutations in the human sucrase-isomaltase gene (SI) that cause congenital carbohydrate malabsorption

Disaccharide intolerance I or congenital sucrase-isomaltase deficiency (CSID) is a disorder leading to maldigestion of disaccharides, which is autosomal recessively inherited. Here we analyzed the sucrase-isomaltase (SI) gene from 11 patients of Hungarian origin with congenital sucrase-isomaltase deficiency. Variants in the SI gene had previously been described in CSID patients, which cause amino acid exchanges that affect the transport, the processing, or the function of the SI protein. None of our patients had known mutations for CSID. Our analyses revealed 43 SI variants in total, 15 within exons and one at a splice site. Eight of the exonic mutations lead to amino acid exchanges, causing hypomorph or null alleles. One new variation affects a splice site, which is also predicted to result in a null allele. All potential pathological alterations were present on one allele only. In six out of the 11 patients the phenotype of CSID could be explained by compound heterozygosity.

A rare cause of fatal right heart failure

Microscopic pulmonary tumor embolism (MPTE) is an uncommon cause of dyspnea in patients with cancer and one of the most difficult to diagnose. MPTE is a syndrome that is pathologically characterized by the occlusion of small pulmonary arteries and arterioles by aggregates of tumor cells. Because the clinical picture resembles that of thromboembolic disease, it is rarely recognized before death. The most common clinical symptom is subacute progressive dyspnea over weeks to months. We recently observed a case of MPTE of exceptional interest as the patient was under aggressive anticoagulant treatment and developed fulminant pulmonary hypertension with fatal right heart failure.

[A rare cause of cardiogenic shock with psychotic symptoms]

A 40-year-old man was admitted to the emergency department with psychotic symptoms and marked hypothermia. He was known to have had a macroadenoma of the pituitary gland which had been excised 10 years before. No information about his current medication was available. Several hours after admission the patient developed signs of acute cardiac failure and cardiogenic shock. He was admitted to the intensive care unit, intubated and treated with vasoactive drugs. Later investigations revealed that the patient had stopped his hormonal therapy (hydrocortisone and thyroxine) at least 3 months previously.

Mutations in Uroplakin IIIA are a rare cause of renal hypodysplasia in humans

BACKGROUND: Renal hypodysplasia, characterized by a decrease in nephron number, small overall kidney size, and maldeveloped renal tissue, is a leading cause of chronic renal failure in young children. Familial clustering and renal hypodysplasia phenotypes observed in transgenic animal models suggest a genetic contribution. Uroplakin IIIa (encoded by UPIIIA) is an integral membrane protein present in urothelial plaques, and the murine UPIIIa knockout is associated with urothelial anomalies and vesicoureteral reflux. De novo UPIIIA mutations recently were identified in 4 of 17 patients with severe bilateral renal adysplasia. METHODS: To evaluate the overall role of UPIIIA in human renal hypodysplasia pathogenesis, we performed UPIIIA mutation analysis in a cohort of 170 pediatric patients affected by severe unilateral or bilateral renal hypodysplasia. Eighty-one patients were affected by bilateral nonobstructive renal hypodysplasia; of these, 61 were without vesicoureteral reflux. Eighty-four patients presented with unilateral nonobstructive renal hypodysplasia, including 24 patients with unilateral multicystic dysplastic kidneys. Family history was positive in 11%. RESULTS: Mutation analysis showed 2 heterozygous mutations not observed in 200 race-matched control chromosomes. In only 1 family was distribution of the UPIIIA mutation consistent with a disease-causing effect. This de novo missense mutation (Gly202Asp) was identified in a patient with unilateral multicystic dysplastic kidneys. The second (intronically located) mutation appeared unlikely to be disease causing because it did not segregate with an obvious disease phenotype in the affected family. CONCLUSION: Our results indicate that de novo mutations in UPIIIA can be involved in defective early kidney development, but probably constitute only a rare cause of human renal hypodysplasia in a minor subset of individuals.

A Spanish founder mutation in the chloride channel gene, CLCNKB, as a cause of atypical Bartter syndrome in adult age

BACKGROUND: Mutations in the chloride channel gene, CLCNKB, usually cause classic Bartter syndrome (cBS) or a mixed Bartter-Gitelman phenotype in the first years of life. METHODS: We report an adult woman with atypical BS caused by a homozygous missense mutation, A204T, in the CLCNKB gene, which has previously been described as the apparently unique cause of cBS in Spain. RESULTS: The evaluation of this patient revealed an overlap of phenotypic features ranging from severe biochemical and systemic disturbances typical of cBS to scarce symptoms and diagnosis in the adult age typical of Gitelman syndrome. The tubular disease caused a dramatic effect on mental, growth and puberal development leading to low IQ, final short stature and abnormal ovarian function. Furthermore, low serum PTH concentrations with concomitant nephrocalcinosis and normocalcaemia were observed. Both ovarian function and serum PTH levels were normalized after treatment with cyclooxygenase inhibitors. CONCLUSIONS: The present report confirms a weak genotype-phenotype correlation in patients with CLCNKB mutations and supports the founder effect of the A204T mutation in Spain. In our country, the genetic diagnosis of adult patients with hereditary hypokalaemic tubulopathies should include a screening of A204T mutation in the CLCNKB gene.

Paradoxical emboli through the patent foramen ovale as the suspected cause of myocardial and renal infarction in a 48-year-old woman

We review the case of a 48-year-old woman who underwent elective percutaneous patent foramen ovale closure following successive renal and myocardial infarction with normal renal and coronary arteries, probably as a consequence of paradoxical emboli.