RIDA®GENE Helicobacter pylori PCR on the ELITe InGenius System

PCR detection of Helicobacter pylori infection in gastric biopsies allows the detection of this bacterium and the mutations associated with macrolide resistance. The aim of this study was to evaluate the performance of RIDA®GENE H. pylori PCR (r-Biopharm) on the ELITe InGenius System (Elitech). Two hundred gastric biopsies were obtained. These biopsies were ground in nutrient broth. Two hundred microliters of this suspension was treated with proteinase K, and then, 200 µL was transferred to an ELITe InGenius sample tube and tested using RIDA®GENE H. pylori PCR reagents. In-house H. pylori PCR was used as a reference. The sensitivity of RIDA®GENE H. pylori PCR with ELITe InGenius was 100%, the specificity was 98% (95% confidence interval (CI), 95.3–100%), the PPV was 98% (95% CI, 95.3–100%), and the NPV was 100% for the detection of H. pylori. All of these parameters were 100% for the categorization of macrolide resistance. The adaptation of RIDA®GENE H. pylori PCR reagents on the ELITe InGenius System was successful. This PCR is easy to use on this system.

     

Associations between postprandial symptoms,hydrogen and methane production,and transit time in irritable bowel syndrome

Background

Abnormal oroanal transit time (OATT) and visceral hypersensitivity are key pathophysiological factors in irritable bowel syndrome (IBS). The lactulose nutrient challenge test (LNCT) has been developed to assess the postprandial symptoms and gut microbial fermentation. We aimed to investigate associations between OATT, rectal sensitivity, and LNCT in IBS patients.

Methods

We included 263 IBS patients from two study cohorts, where the link between pathophysiology and symptoms was investigated. During the LNCT, severity of postprandial symptoms was graded, and breath hydrogen/methane concentrations were measured after ingestion of a combined lactulose nutrient drink every 15 min for 4 h. The patients underwent rectal sensitivity (rectal barostat) and OATT (radiopaque markers) investigations. Comorbid conditions (functional dyspepsia, anxiety, depression, and somatization) were assessed with questionnaires.

Key Results

After controlling for comorbid conditions, rectal sensitivity was associated with abdominal pain (p < 0.05), and more rapid OATT was associated with higher severity of abdominal discomfort, rumbling, nausea, and urgency (p < 0.05 for all) both pre- and post-prandially. Postprandial nausea, urgency, and abdominal pain changed differently over time depending on OATT (p < 0.05 for all). OATT, but not rectal sensitivity, was associated with hydrogen and methane concentrations (p = 0.002 for both). Trajectories over time of postprandial symptoms and exhaled hydrogen/methane concentrations were correlated with different correlations depending on OATT.

Conclusion and Inferences

This study highlights the importance of oroanal transit and hydrogen and methane production in the pathophysiology of IBS and increases our understanding of pathophysiological factors involved in postprandial symptom generation. Treatments targeting oroanal transit and hydrogen and methane production may improve specific postprandial symptoms.     

GDF15 mediates renal cell plasticity in response to potassium depletion in mice

Objective

To understand the mechanisms involved in the response to a low-K⁺ diet (LK), we investigated the role of the growth factor GDF15 and the ion pump H,K-ATPase type 2 (HKA2) in this process.

Methods

Male mice of different genotypes (WT, GDF15-KO, and HKA2-KO) were fed an LK diet for different periods of time. We analyzed GDF15 levels, metabolic and physiological parameters, and the cellular composition of collecting ducts.

Results

Mice fed an LK diet showed a 2–4-fold increase in plasma and urine GDF15 levels. Compared to WT mice, GDF15-KO mice rapidly developed hypokalemia due to impaired renal adaptation. This is related to their 1/ inability to increase the number of type A intercalated cells (AIC) and 2/ absence of upregulation of H,K-ATPase type 2 (HKA2), the two processes responsible for K⁺ retention. Interestingly, we showed that the GDF15-mediated proliferative effect on AIC was dependent on the ErbB2 receptor and required the presence of HKA2. Finally, renal leakage of K⁺ induced a reduction in muscle mass in GDF15-KO mice fed LK diet.

Conclusions

In this study, we showed that GDF15 and HKA2 are linked and play a central role in the response to K⁺ restriction by orchestrating the modification of the cellular composition of the collecting duct.     

The prognostic value of IKZF1plus in B-cell progenitor acute lymphoblastic leukemia: Results from the EORTC 58951 trial

Background

IKZF1 gene deletion is an indicator of poor prognosis in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The AEIOP/BFM group proposed that the prognostic strength of IKZF1 deletion could be remarkably improved by taking into account additional genetic deletions and reported that among patients with an IKZF1 deletion those with deletions in CDKN2A/2B, PAX5, or PAR1 in the absence of ERG deletion, grouped as IKZF1^plus, had the worst outcome.

Procedure

Between 1998 and 2008, 1636 patients under 18 years of age with previously untreated BCP-ALL were registered in the EORTC 58951 trial. Those with multiplex ligation-dependent probe amplification data were included in this analysis. Unadjusted and adjusted Cox model was used to investigate the additional prognostic value of IKZF1^plus.

Results

Among 1200 patients included in the analysis, 1039 (87%) had no IKZF1 deletion (IKZF1^WT), 87 (7%) had an IKZF1 deletion but not IKZF1^plus (IKZF1^del) and 74 (6%) had IKZF1^plus. In the unadjusted analysis, both patients with IKZF1^del (hazard ratio [HR] = 2.10, 95% confidence interval [CI]: 1.34–3.31) and IKZF1^plus (HR = 3.07, 95% CI: 2.01–4.67) had a shorter event-free survival compared with IKZF1^WT. However, although the IKZF1^plus status was associated with patients’ characteristics indicating poor prognosis, the difference between IKZF1^plus and IKZF1^del was not statistically significant (HR = 1.46, 95% CI: 0.83–2.57, p = .19). The results of the adjusted analysis were similar to the unadjusted analysis.

Conclusions

In patients with BCP-ALL from the EORTC 58951 trial, the improvement of the prognostic importance of IKZF1 by considering IKZF1^plus was not statistically significant.     

Diagnosis and Outcomes of Late-Onset Wilson's Disease: A National Registry-Based Study

Background

Wilson's disease (WD) is usually diagnosed in children and young adults; limited data exist on late-onset forms.

Objective

The aim was to characterize the clinical and paraclinical presentations, therapeutic management, and outcomes in patients with late-onset WD.

Methods

Patients diagnosed with WD after age 40 years were identified from the French Wilson's Disease Registry (FWDR). Clinical, laboratory, and imaging findings and treatment were reported at diagnosis and last follow-up.

Results

Forty-five patients were identified (median age: 49, range: 40–64) and placed in three groups according to their clinical presentation: neurological (n = 20, median diagnostic delay: 20 months), hepatic (n = 13, diagnostic delay: 12 months), and family screening (n = 12), all confirmed genetically. Six neurological patients had an atypical presentation (1 torticollis, 2 writer's cramps, 2 functional movement disorders, and 1 isolated dysarthria), without T2/fluid-attenuated inversion recovery brain magnetic resonance imaging (MRI) hyperintensities; 5 of 6 had no Kayser–Fleischer ring (KFR); 5 of 6 had liver involvement. In the neurological group, 84% of patients improved clinically, and 1 developed copper deficiency. In the hepatic group, 77% had cirrhosis; 6 patients required liver transplantation. In the screened group, 43% had mild liver involvement; 3 were not treated and remained stable; 24-h urinary copper excretion was normal in 33% of patients at diagnosis.

Conclusions

In the FWDR, late-onset forms of WD affect 8% of patients, mostly with neurological presentations. Thirty percent of the neurological forms were atypical (isolated long-lasting symptoms, inconspicuous brain MRI, no KFR). With personalized treatment, prognosis was good. This study emphasized that WD should be suspected at any age and even in cases of atypical presentation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Continuous glucose monitoring assessment in patients suffering from anorexia nervosa reveals chronic prolonged mild hypoglycemia all over the nycthemeron

Objective

Anorexia nervosa (AN) is an eating disorder characterised by voluntary dietary restriction leading to severe undernutrition. Hypoglycaemia is mostly described through severe case reports and is always evaluated by fasting or post-meal blood glucose, showing nothing about hypoglycaemia's length or duration. The interest of continuous interstitial glucose monitoring (CGM), largely used in diabetes mellitus, has never been evaluated in AN patients.

Method

Glycaemia cycles in AN patients were assessed using CGM over 5 days and then analysed according to food intake.

Results

Mean glycaemia was within normal range. 91% of the patients presented with at least one episode with glycaemia under 70 mg/dl. Within the 24 h, the percentage of time spent with a glycaemia under 70 mg/dl was of 20.82 ± 3.90% with a maximum of 52%. We found 2.52 ± 0.33 hypoglycaemia events per 24 h, including 21.11 ± 3.76% at night. CGM parameters correlated with cortisol and IGF1 plasma levels. Comparison with estimated carbohydrate intakes discriminated concordant and non-concordant estimations depending on patient.

Conclusions

AN patients display chronic prolonged mild hypoglycaemia all over the nycthemeron despite normal fasting glycaemia. Associated adaptive increased counter-regulatory hormones might protect AN patients from deeper hypoglycaemia. CGM allowed testing food intake self-estimation reliability of AN patients and could be a very useful biofeedback tool.