Agression rénale aigu? du sujet agé

Elderly patients are at high risk for acute kidney injury, the incidence of which is increasing with time. The presence of multiple associated morbidities and age-related changes in kidney physiology are the main reasons for this high susceptibility. Prevention and early diagnosis of renal failure are crucial, especially since long term risks such as death and chronic kidney disease are more frequent in this population.     

Duodenal tumor risk in Lynch syndrome

Background and aims

Lynch syndrome (LS) is associated with an increased risk of small bowel tumors but routine screening is not recommended in international guidelines. The aim of our study was to determinate the prevalence of duodenal tumors in a French cohort of LS patients.

Acute intermittent porphyria and chronic transaminase elevation

Acute intermittent porphyria is an autosomal dominant inherited disorder resulting from a deficiency of porphobilinogen deaminase activity, the third enzyme in the heme biosynthesis pathway. This disease is uncommon, although the prevalence is higher in asymptomatic heterozygotic carriers; however, this prevalence is difficult to establish because of the absence of symptoms. Although acute intermittent porphyria is a multisystemic disease, its most common form of presentation is abdominal pain and neurological or mental symptoms, which can sometimes be due to precipitating factors such as reduced energy intake, smoking, alcohol, some drugs, and stress. Diagnosis can be made by testing urinary porphobilinogen levels, with subsequent measurement of enzyme activity and DNA testing. Treatment is based on prevention of porphyria attacks by avoiding precipitating factors and early administration of intravenous glucose or hemin therapy. We present the case of a patient diagnosed with acute intermittent porphyria based on study of chronic mild alanine aminotransferase (ALT) elevation.     

The loss-of-function PCSK9Q152H variant increases ER chaperones GRP78 and GRP94 and protects against liver injury

Individuals harboring the loss-of-function (LOF) proprotein convertase subtilisin/kexin type 9 Gln152His variation (PCSK9^Q152H) have low circulating low-density lipoprotein cholesterol levels and are therefore protected against cardiovascular disease (CVD). This uncleavable form of proPCSK9, however, is retained in the endoplasmic reticulum (ER) of liver hepatocytes, where it would be expected to contribute to ER storage disease (ERSD), a heritable condition known to cause systemic ER stress and liver injury. Here, we examined liver function in members of several French-Canadian families known to carry the PCSK9^Q152H variation. We report that PCSK9^Q152H carriers exhibited marked hypocholesterolemia and normal liver function despite their lifelong state of ER PCSK9 retention. Mechanistically, hepatic overexpression of PCSK9^Q152H using adeno-associated viruses in male mice greatly increased the stability of key ER stress-response chaperones in liver hepatocytes and unexpectedly protected against ER stress and liver injury rather than inducing them. Our findings show that ER retention of PCSK9 not only reduced CVD risk in patients but may also protect against ERSD and other ER stress–driven conditions of the liver. In summary, we have uncovered a cochaperone function for PCSK9^Q152H that explains its hepatoprotective effects and generated a translational mouse model for further mechanistic insights into this clinically relevant LOF PCSK9 variant.     

Ablation of frequent premature ventricular complex in an athlete

Premature ventricular complex are common findings in the exam of many athletes. There is no extensive scientific evidence in the management of this situation particularly when associated with borderline contractile function of the left ventricle. In this case report, we present a 35‐year‐old asymptomatic healthy athlete with high incidence (over 10 000 beats in 24 h) of premature ventricular complex and left ventricular dilatation with dysfunction, which persisted after a resting period of 6 months without training. We performed radiofrequency ablation of the premature ventricular complex focus. After 1‐year follow‐up, he was asymptomatic without arrhythmia and the left ventricle normalized its size and function as shown by echocardiogram and cardiac magnetic resonance.     

Gastrointestinal peptides,gastrointestinal motility,and anorexia of aging in frail elderly persons

Background The mechanisms involved in anorexia in frail elderly people remain unclear. The objective of this study was to establish whether fasting and postprandial levels of gastrointestinal peptides, gastrointestinal motility, and hunger are modified by age and frailty. Methods Three groups of subjects were studied: (a) frail elderly (>70 years) persons, (b) non‐frail elderly (>70 years) persons, and (c) healthy adults (aged 25–65 years). After an overnight fast, participants ingested a 400 Kcal liquid meal and appetite, hormonal, and gastrointestinal responses were monitored during early (0–60 min) and late (60–240 min) postprandial periods. Key Results Frail persons showed poor nutritional status, sarcopenia, and almost absence of hunger during fasting and postprandial periods. Older persons presented higher levels of glucose and insulin during fasting, enhanced postprandial CCK release in early postprandial period and postprandial hyperglycemia and hyperinsulinemia, but similar ghrelin levels than younger adults. Ultrasound scan showed that the fasting antral area was higher and antral compliance lower in old persons. The paracetamol absorption test showed enhanced postprandial gastric emptying in the frail. Non‐gallbladder contractors showed no CCK peak in younger and non‐frail groups, but the same high CCK peak as contractors in the frail. Conclusions & Inferences Frailty was associated with anorexia, risk of malnutrition, and sarcopenia. Frail persons showed impaired gastric motility (larger antral area at rest, impaired antral compliance, and enhanced postprandial emptying), impaired gallbladder motility, and fasting and/or postprandial alterations in CCK, glucose, and insulin release. Further studies are needed to determine if these factors may contribute to anorexia of aging in frail persons.