Identification of a novel CTR9 germline mutation in a family with Wilms tumor

Germline mutations in the WT1 gene have been identified in some families with Wilms tumor. Recently, the CTR9 gene was found to be mutated in three families with Wilms tumor, thus representing a novel predisposition gene for this disease. We identified a family with a history of Wilms tumor characterized by three affected siblings, one of them presenting an aggressive bilateral tumor.Here we investigated the involvement of WT1 and CTR9 genes in this family with Wilms tumor. The involvement of WT1 was first evaluated by Next generation sequencing in leukocytes DNA from one affected family member. Subsequently, the CTR9 gene was analyzed by Sanger sequencing in DNA and RNA from patients’ leukocytes and/or tumor. No mutations were detected in WT1. However, we identified a novel CTR9 germline variant, located in a consensus splice acceptor site, which was found to segregate with Wilms tumor in this family. We found that this variant leads to the skipping of the entire exon 9 in the mRNA, which is predicted to encode a truncated CTR9 protein, strongly suggesting that it is pathogenic. Additionally, we also detected loss of heterozygosity in the index case tumor, which is consistent with CTR9 being a tumor suppressor gene, confirming also its contribution to familial Wilms tumor etiology.The identification of a novel CTR9 germline mutation will improve the present knowledge on the molecular basis of familial Wilms tumor. Importantly, it will help in the genetic counselling and may also lead to earlier diagnosis in other family members and future generations.     

Potential determinants of obesity among children and adolescents in Germany: results from the cross-sectional KiGGS study

Background  

Obesity among children and adolescents is a growing public health problem. The aim of the present paper is to identify potential determinants of obesity and risk groups among 3- to 17-year old children and adolescents to provide a basis for effective prevention strategies.     

Selection and persistence of CTX-M-producing Escherichia coli in the intestinal flora of pigs treated with amoxicillin, ceftiofur, or cefquinome

Extended-spectrum β-lactamases (ESBLs), mainly of the CTX-M family, have been associated with Escherichia coli strains of animal origin in Europe. An in vivo experiment was performed to study the effects of veterinary β-lactam drugs on the selection and persistence of ESBL-producing E. coli in the intestinal flora of pigs. Twenty pigs were randomly allocated into three treatment groups and one control group. All pigs were inoculated intragastrically with 10¹⁰ CFU of a nalidixic acid (NAL)-resistant mutant derived from a CTX-M-1-producing E. coli strain of pig origin. Treatment with amoxicillin, ceftiofur, or cefquinome according to the instructions on the product label was initiated immediately after bacterial inoculation. Feces were collected from the rectum before inoculation and on days 4, 8, 15, 22, and 25 after the start of treatment. The total and resistant coliforms were counted on MacConkey agar with and without cefotaxime (CTX). Furthermore, MacConkey agar with CTX and NAL was used to count the number of CFU of the inoculated strain. Significantly higher counts of CTX-resistant coliforms were observed in the three treatment groups than in the control group for up to 22 days after the discontinuation of treatment. Ceftiofur and cefquinome exerted larger selective effects than amoxicillin, and the effects persisted beyond the withdrawal times recommended for these cephalosporins. The inoculated strain was detected in only nine animals on day 25. The increase in the number of CTX-resistant coliforms was mainly due to the proliferation of indigenous CTX-M-producing strains and the possible emergence of strains that acquired CTX-M genes by horizontal transfer. The study provides evidence that the cephalosporins used in pig production select for CTX-M-producing E. coli strains. Their use in animals should be carefully considered in view of the critical importance of cephalosporins and the zoonotic potential of ESBL-producing bacteria.     

Comparison of NB-UVB combination therapy regimens for vitiligo: A systematic review and network meta-analysis

Background

Vitiligo was an autoimmune disease and some guidelines for the management of vitiligo encouraged the use of NB-UVB combination therapies to enhance repigmentation.

Objectives

To compare the effectiveness of current NB-UVB combination regimen at the improvement in repigmentation through a systematic review and network meta-analysis.

Methods

We searched the electronic databases for randomized controlled trials related to NB-UVB combination therapy for vitiligo till October 2022. STATA15.0 software was applied to carrying out data analysis.

Results

A total of 28 eligible studies involving 1194 participants were enrolled in the analysis. The NMA results revealed that compared with NB-UVB, carboxytherapy [OR = 32.35, 95% CI (1.79, 586.05)], Er: YAG laser+ topical 5% 5-FU [OR = 10.74, 95% CI (4.05, 28.49)], needling/micro-needling [OR = 3.42, 95% CI (1.18, 9.88)], betamethasone intramuscular injection [OR = 3.08, 95% CI (1.17, 8.13)], topical tacrolimus [OR = 2.54, 95% CI (1.30, 4.94)], and oral Chinese herbal medicine compound [OR = 2.51, 95% CI (1.40, 4.50)] integrated with NB-UVB were more efficacious in excellent to complete repigmentation response rate (≥75%). Besides, NB-UVB+ Er: YAG laser+ topical 5% 5-FU [OR = 0.17, 95% CI (0.04, 0.67)] and NB-UVB+ needling/micro-needling [OR = 0.24, 95% CI (0.06, 0.88)] were less likely evaluated as ineffective repigmentation response (≤25%).

Conclusions

All combination therapies ranked higher than NB-UVB monotherapy in inducing successful repigmentation and avoiding failed treatment in patients with vitiligo. Comprehensive consideration, NB-UVB+ Er: YAG laser+ topical 5% 5-FU and NB-UVB+ needling/microneedling would be the preferred therapeutic approaches.     

Lithium toxicity

We report a case of severe lithium toxicity precipitated by a thiazide diuretic and compounded by an angiotensin converting enzyme inhibitor. There was severe vasodilatation refractory to noradrenaline.     

Can one stop nucleic acid sampling (OSNA) predict nodal positivity following neoadjuvant chemotherapy? A prospective cohort study of 293 patients

Until recently, axillary node clearance had long been the standard of care in patients with axillary node-positive disease. One stop nucleic acid sampling (OSNA) has been used to guide intraoperative decision-making regarding suitability for axillary node clearance (ANC). The aim of this study is to evaluate the use of OSNA following neoadjuvant chemotherapy (NACT) and whether it can predict lymph node burden in ANC. A single center, prospective cohort study was performed on 297 patients having OSNA between 2016 and 2019. Patients were sub-classified according to node positivity at diagnosis and those treated with NACT and outcomes included copy number and lymph node harvest. Axillary complete pathological response was observed in 24/36 patients (67%) following NACT. 14/16 patients (87%) having axillary node clearance had axillary node disease limited to 4 nodes. OSNA copy numbers were significantly higher in patients showing disease progression following NACT. Overall, 73% of patients with lymph node positivity at diagnosis could be successfully treated with a combination of NACT and lymph node excision of four nodes. De-escalating axillary surgical treatment to resection of four nodes following NACT may be effective in balancing oncological resection and limiting treatment morbidity. ONSA can correctly identify patients experiencing disease progression who would benefit from traditional three-level ANC.