Complications hépatobiliaires associées à l’insuffisance intestinale chez l’adulte et l’enfant

The treatment of chronic intestinal failure, of which the main cause is the short bowel syndrome, is based on parenteral nutrition. Intestinal failure-associated liver disease, which may worsen toward cirrhosis, is the most threatening intestinal failure-associated complication. Risk factors for intestinal failure-associated liver disease are related to parenteral nutrition modalities and to the underlying disease. Bowel rest and short bowel syndrome are risk factors for biliary lithiasis. Steatosis is mainly secondary to nutritional factors (excess of glucose and/or lipids, continuous parenteral nutrition). The main risk factors of cholestasis are intestinal resection, intestinal bacterial overgrowth, excess of long-chain polyunsaturated ω6 fatty acids and phytosterols from some lipid emulsions. Liver chronic inflammation, another risk factor for intestinal failure-associated liver disease, is related to recurrent infections, bacterial or toxinic translocation, high intake of long-chain polyunsaturated ω6 fatty acids as precursors of inflammatory mediators. Fibrosis, secondary to any lesions, could progress toward cirrhosis with portal hypertension and liver failure. In such condition, the only life-saving treatment is a combined liver-intestinal transplantation. The prevention is based on the identification of patients with high risk of complicated liver disease, and on the optimal management of both underlying disease and parenteral nutrition. Routine surveillance is based on biological markers of variable sensitivity and specificity, and ultrasonography. Liver biopsy is required to diagnose fibrosis, especially prior to decide for an isolated intestinal transplantation or combined intestine-liver transplantation.     

Low molecular weight heparin treatment in elderly subjects with or without renal insufficiency: new insights between June 2002 and March 2004

PURPOSE OF REVIEW: Low molecular weight heparin has become the treatment of choice for venous thromboembolism events and acute coronary syndromes. In contrast to unfractionated heparin, low molecular weight heparins are mainly excreted by the kidney. Thus, repeated administration of therapeutic doses of low molecular weight heparins may lead to overdosage and/or an accumulation effect in patients with renal impairment, such as the elderly. Moreover, older patients are often excluded from clinical trials. Little evidence is available to assess the risk/benefit ratio of low molecular weight heparins used at therapeutic dosages in elderly patients with or without renal insufficiency in normal clinical practice. RECENT FINDINGS: Pharmacovigilance data, case reports, and observational studies reporting major bleeding complications in the elderly highlight the potential risk of using low molecular weight heparins at therapeutic dosages in these patients. An evaluation of renal function is thus essential before therapy with low molecular weight heparins is begun. Moreover, multiple-dose pharmacokinetic studies in the elderly have shown that the pharmacokinetic response to impaired renal function, especially the risk of accumulation effect, may differ among preparations of low molecular weight heparins. SUMMARY: Three approaches to improve the safety of low molecular weight heparins in the elderly are discussed: (1) to replace low molecular weight heparin therapy with monitored unfractionated heparin therapy in cases of severe renal insufficiency, but comparative studies are necessary to clarify whether unfractionated heparin offers better safety in this setting; (2) to use initial reduced dosages in elderly patients with or without renal failure, but these regimens have to be validated for each low molecular weight heparin in terms of efficacy in controlled trials; and (3) to monitor anti-Xa activity to detect any overdosage and/or any accumulation effect of low molecular weight heparins.     

Nivolumab as adjuvant treatment for a spinal melanocytoma: A case report

Rationale:Meningeal melanocytoma is a rare benign melanocytic tumor of the central nervous system. We report for the first time a case of meningeal melanocytoma treated with immunotherapy.Patient concerns:A 70-year-old man with no medical history was admitted to the Emergency Room. He suffered from a motor and sensory deficit in his left lower limb and a bilateral upper arm neuralgia.Diagnoses:A contrast-enhanced magnetic resonance imaging (MRI) was performed. It showed a C7-T1 bleeding intramedullary tumor. Laminectomy was decided and performed. The results of the pathologic examination showed a melanocytic tumor harboring GNAQ mutation. Meningeal melanocytoma was the final diagnosis.Interventions:The patient was treated with 10 radiotherapy sessions and 6 cycles of nivolumab. A year later, the patient experienced neuralgia again with severe pain and an increasing sensory motor deficit. He underwent a second surgery that was incomplete. As the tumor kept growing, he received temozolomide. But the 6th cycle had to be interrupted due to bedsore infection in the hip area.Outcomes:Disease progression finally led to the patient''s death 3 years after diagnosis.Lessons:This case report is the first about a patient with meningeal melanocytoma treated with immunotherapy. Treatment based on biomolecular mutations will probably change spinal melanocytoma therapeutic approach in the next few years.     

Biosynthesis of proopiomelanocortin-derived peptides in prohormone convertase 2 and 7B2 null mice

Prohormone convertases (PCs) are thought to represent the major proteinases involved in the biosynthetic processing of peptide hormone precursors to bioactive peptide products. The maturation of PC2 requires the aid of a helper protein, 7B2, in order for the zymogen to become an active enzyme species. The 7B2 and PC2 nulls should thus be functionally equivalent with regard to deficits in precursor processing. In this article, we have examined this proposition through the study of proopiomelanocortin (POMC) biosynthesis and granule content in both null models. RIA data indicate that both PC2 and 7B2 nulls lack pituitary alpha-MSH; interestingly, 7B2 nulls are still able to generate beta-endorphin from beta-lipotropin, whereas PC2 nulls contain little if any beta-endorphin. Labeling experiments demonstrate a build-up of POMC, high molecular weight intermediates, and intact ACTH, as well as the disappearance of alpha-MSH, in both null models. Electron microscopy of neurointermediate lobe melanotrophs reveals the presence of a significantly greater number of secretory granules in both 7B2 and PC2 nulls compared with wild-type controls. However, PC2 null melanotrophs contain twice as many granules as 7B2 null melanotrophs. Another difference between the two null models is a relatively enhanced accumulation of precursors in the PC2 null compared with the 7B2 null; these include not only PC2 substrates, but also presumed PC1 substrates. These data indicate that the two nulls are not phenotypically equivalent.     

New indicators for delay in initiation of antiretroviral treatment: estimates for Cameroon

Objective

To propose two new indicators for monitoring access to antiretroviral treatment (ART) for human immunodeficiency virus (HIV); (i) the time from HIV seroconversion to ART initiation, and (ii) the time from ART eligibility to initiation, referred to as delay in ART initiation. To estimate values of these indicators in Cameroon.

Methods

We used linear regression to model the natural decline in CD4+ T-lymphocyte (CD4+ cell) numbers in HIV-infected individuals over time. The model was fitted using data from a cohort of 351 people in Côte d’Ivoire. We used the model to estimate the time from seroconversion to ART initiation and the delay in ART initiation in a representative sample of 4154 HIV-infected people who started ART in Cameroon between 2007 and 2010.

Findings

In Cameroon, the median CD4+ cell counts at ART initiation increased from 140 cells/μl (interquartile range, IQR: 66 to 210) in 2007–2009 to 163 cells/μl (IQR: 73 to 260) in 2010. The estimated average time from seroconversion to ART initiation decreased from 10.4 years (95% confidence interval, CI: 10.3 to 10.5) to 9.8 years (95% CI: 9.6 to 10.0). Delay in ART initiation increased from 3.4 years (95% CI: 3.1 to 3.7) to 5.8 years (95% CI: 5.6 to 6.2).

Conclusion

The estimated time to initiate ART and the delay in ART initiation indicate that progress in Cameroon is insufficient. These indicators should help monitor whether public health interventions to accelerate ART initiation are successful.     

Effectiveness of Exercise Programs in Ankylosing Spondylitis: A Meta-Analysis of Randomized Controlled Trials

Objective

To assess the effectiveness of exercise programs on disease activity and function in ankylosing spondylitis (AS) by a systematic review and meta-analysis of randomized controlled trials (RCTs).