A homozygous truncating ETV4 variant in a Nigerian family with congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most prevalent cause of chronic kidney disease that manifests in children. To date ~23 different monogenic causes have been implicated in isolated forms of human CAKUT, but the vast majority remains elusive. In a previous study, we identified a homozygous missense variant in E26 transformation-specific (ETS) Variant Transcription Factor 4 (ETV4) causing CAKUT via dysregulation of the transcriptional function of ETV4, and a resulting abrogation of GDNF/RET/ETV4 signaling pathway. This CAKUT family remains the only family with an ETV4 variant reported so far. Here, we describe one additional CAKUT family with a homozygous truncating variant in ETV4 (p.(Lys6*)) that was identified by exome sequencing. The variant was found in an individual with isolated CAKUT displaying posterior urethral valves and renal dysplasia. The newly identified stop variant conceptually truncates the ETS_PEA3_N and ETS domains that regulate DNA-binding transcription factor activity. The variant has never been reported homozygously in the gnomAD database. To our knowledge, we here report the first CAKUT family with a truncating variant in ETV4, potentially causing the isolated CAKUT phenotype observed in the affected individual.

A systematic review of the effectiveness of journal clubs in undergraduate medicine.

Background: Training future doctors in the skills of evidence-based medicine (EBM) is clearly important. Journal club (JCs) are well-recognized educational interventions for teaching EBM. In contrast to postgraduate medical education, JCs use in undergraduate medical education (UME) has not been adequately explored. We conducted a realist review of the effectiveness of JCs in UME to unpack the underlying mechanisms by which the intervention works (or fails) in teaching EBM. Methods: The scope of review was the evaluation of the effectiveness of JCs in UME settings. We searched major bibliographic databases - MEDLINE, Embase, ERIC, PSYCInfo, CINAHL, Scopus, and Web of Science and found fifteen articles eligible for inclusion. Data was extracted aided by a modified Kirkpatrick framework and presented in evidence tables. Themes and chains of inference were identified, and finally, we formulated new hypotheses on how and why JC intervention works. Results: Mandatory vs. voluntary JC did not differentially impact attendance of JC in UME settings though JC duration beyond two hours decreased attendees' self-reported satisfaction. Coupling lectures to JCs positively impacts knowledge gain and retention. Coupled Mentorship or using critical appraisal worksheets helped the achievement of manuscript writing skills and a positive attitude towards EBM. Conclusions: Journal clubs are effective interventions to teach EBM in UME settings and are well-received by learners. They improve specific learning outcomes of knowledge gain and retention, skills of manuscript writing and critical appraisal. However, we found no evidence that these translates to the practice of EBM nor impacts patient outcomes.

Contexte: Il est important que les compétences enseignées aux futurs médecins soient conformes à l'approche de la médecine fondée sur les données probantes (MFDP) et les clubs de lecture (CL) sont reconnus comme une intervention pédagogique en ce sens. Le recours aux CL dans la formation prédoctorale a été peu étudié, contrairement à la place qu'ils occupent au postdoctorat. Nous avons effectué une revue réaliste de l'efficacité des CL dans la formation de premier cycle pour décortiquer les mécanismes sous-jacents qui déterminent la réussite ou l'échec de cette méthode pédagogique en ce qui a trait à l'enseignement de la MFDP. Méthodes: La revue visait l'évaluation de l'efficacité des CL dans la formation médicale prédoctroale. Nous avons effectué des recherches dans les principales banques de données bibliographiques ­ MEDLINE, Embase, ERIC, PSYCInfo, CINAHL, Scopus et Web of Science ­ et avons trouvé quinze articles répondant à nos critères d'inclusion. Nous avons utilisé le modèle modifié de Kirkpatrick pour la collecte de données, que nous avons présentées sous forme de tableaux de preuves. Nous avons dégagé des thèmes et élaboré des chaînes d'inférences, puis formulé de nouvelles hypothèses sur le comment et le pourquoi de l'efficacité des CL. Résultats: Le caractère obligatoire ou facultatif de l'activité n'a pas eu d'effet différentiel sur la participation des étudiants de premier cycle aux CL, mais leur satisfaction autodéclarée diminuait lorsque la durée de la séance dépassait deux heures. En revanche, le fait de conjuguer les CL à des conférences a eu un effet positif sur l'acquisition et la rétention des connaissances et le fait de les conjuguer au mentorat ou à l'utilisation de feuilles d'évaluation critique a contribué à l'acquisition de compétences en rédaction et à l'adoption par les étudiants d'une attitude positive à l'égard de la MFDP. Conclusions: Les clubs de lecture constituent un moyen efficace et bien accueilli par les apprenants pour enseigner la MFDP au prédoctorat. Ils améliorent les résultats d'apprentissage spécifiques sur le plan de l'acquisition et de la rétention des connaissances, ainsi que les compétences en matière de rédaction et d'évaluation critique. Toutefois, nous n'avons trouvé aucune indication que ces effets puissent se répercuter dans la pratique de la MFDP ou dans les résultats pour les patients.

Obesity rates in renal stone formers from various countries.

OBJECTIVE: To collect evidence on the rate of obesity in renal stone formers (RSFs) living in different climatic areas and consuming different diets. MATERIALS AND METHODS: Data of adult renal stone formers were retrospectively collected by members of U-merge from 13 participant centers in Argentina, Brazil, Bulgaria (2), China, India, Iraq (2), Italy (2), Nigeria, Pakistan and Poland. The following data were collected: age, gender, weight, height, stone analysis and procedure of stone removal. RESULTS: In total, 1689 renal stone formers (1032 males, 657 females) from 10 countries were considered. Average age was 48 (±14) years, male to female ratio was 1.57 (M/F 1032/657), the average body mass index (BMI) was 26.5 (±4.8) kg/m2. The obesity rates of RSFs in different countries were significantly different from each other. The highest rates were observed in Pakistan (50%), Iraq (32%), and Brazil (32%), while the lowest rates were observed in China (2%), Nigeria (3%) and Italy (10%). Intermediate rates were observed in Argentina (17%), Bulgaria (17%), India (15%) and Poland (22%). The age-adjusted obesity rate of RSFs was higher than the age-adjusted obesity rate in the general population in Brazil, India, and Pakistan, whereas it was lower in Argentina, Bulgaria, China, Italy, and Nigeria, and similar in Iraq and Poland. CONCLUSIONS: The age-adjusted obesity rate of RSFs was not higher than the age-adjusted obesity rate of the general population in most countries. The relationship between obesity and the risk of kidney stone formation should be reconsidered by further studies carried out in different populations.

Spectrum of Causative Pathogens and Resistance Rates to Antibacterial Agents in Bacterial Prostatitis.

OBJECTIVE: To evaluate spectrum and resistance rates to antibacterial agents in causative pathogens of bacterial prostatitis in patients from Southern Europe, the Middle East, and Africa. MATERIALS: 1027 isolates from cultures of urine or expressed prostatic secretion, post-massage urine or seminal fluid, or urethral samples were considered. RESULTS: Escherichia coli (32%) and Enterococcus spp. (21%) were the most common isolates. Other Gram-negative, Gram-positive, and atypical pathogens accounted for 22%, 20%, and 5%, respectively. Resistance was <15% for piperacillin/tazobactam and carbapenems (both Gram-negative and -positive pathogens); <5% for glycopeptides against Gram-positive; 7%, 14%, and 20% for aminoglycosides, fosfomycin, and macrolides against Gram-negative pathogens, respectively; 10% for amoxicillin/clavulanate against Gram-positive pathogens; <20% for cephalosporins and fluoroquinolones against to Gram-negative pathogens (higher against Gram-positive pathogens); none for macrolides against atypical pathogens, but 20% and 27% for fluoroquinolones and tetracyclines. In West Africa, the resistance rates were generally higher, although the highest rates for ampicillin, cephalosporins, and fluoroquinolones were observed in the Gulf area. Lower rates were observed in Southeastern Europe. CONCLUSIONS: Resistance to antibiotics is a health problem requiring local health authorities to combat this phenomenon. Knowledge of the spectrum of pathogens and antibiotic resistance rates is crucial to assess local guidelines for the treatment of prostatitis.

Determinants of prostate specific antigen screening test uptake in an urban community in North-Central Nigeria.

BACKGROUND: Despite the increasing incidence of Prostate cancer, there has not been any focused screening policy or strategy in sub-Saharan Africa including Nigeria. OBJECTIVES: To assess the level of awareness and uptake of PSA screening test and their determinants in a Nigerian community. METHODS: A cross-sectional population survey of men with no prior history of prostate cancer was carried out. Logistic regression analysis was used to determine the effect of identified variables in predicting awareness and uptake of prostate cancer screening. RESULTS: Mean age was 51.5±9.8 years; a few men (31, 16.9%) had ever heard of the screening test and most got the information from health centers. A low proportion (8, 4.4%) had taken the screening test. Men with incomes above poverty line (OR = 11.7 2.8-50.1, p = .001) or those with health insurance (OR = 2.7 1.2-6.5, p = .023) were significantly more likely to be aware of the test. Only the men with higher incomes (OR = 25.6 5.8-114.2, p = .0001) were significantly more likely to have taken the test. CONCLUSION: Higher incomes and health insurance status impact screening awareness but only income status determines if men subsequently proceed to take the PSA screening test.

Natural history of castration-resistant prostate cancer in sub-Saharan African black men: a single-centre study of Nigerian men.

PURPOSE: Native sub-Saharan African black men (SSBM) are disproportionately impacted by higher stage and incurable forms of prostate cancer (PCa). This study evaluates the natural history and survival of a cohort of SSBM with castration-resistant prostate cancer (CRPC). METHODS: A retrospective study of patients with CRPC as defined by the Prostate Cancer Working Group 2 managed at a centre in sub-Saharan Africa between January 2011 and December 2015 was conducted. The principal endpoint was overall survival (OS). Potential prognostic variables were evaluated using Cox proportional hazard regression models. RESULTS: A total of 48 patients were identified. Median (IQR) age and prostate-specific antigen (PSA) at diagnosis were 70 (64-74.5) years and 42 (8.0-123.6) ng/mL, respectively. Only 15 (31.3%) patients received docetaxel and one patient each received the novel drugs enzalutamide and abiraterone. Twenty-eight patients (58.3%) died during follow-up with a median OS of 11 (95% CI: 8-14) months. Docetaxel chemotherapy and ECOG performance status were found to be prognostic (docetaxel use: hazard ratio 0·25, 95% CI 0·10-0·67, p = 0·006; ECOG 0-2: 0·26, 0·11-0·62, p = 0·003). CONCLUSION: This study of SSBM with CRPC revealed a mainly unmodulated clinical course with poor access to active treatments and poor survival. Improving access to new active therapies would improve survival.

An appraisal of a technical modification for prevention of bladder neck stenosis in retropubic prostatectomy: An initial report.

OBJECTIVE: To report the experience with our technical modification of the trigone-bladder neck complex management in the prevention of bladder neck stenosis (BNS) following open simple retropubic prostatectomy. MATERIALS AND METHODS: It was a retrospective review of data of patients that underwent open simple retropubic prostatectomy with technical modification of the trigone-bladder neck complex in two Nigerian tertiary hospitals, by a single surgeon, from January 2007 to December 2011. The data analysed included the demographic variables, the modes of presentation, need for blood transfusion, duration of catheterization and the duration of hospital stay. The primary end-point was the development or otherwise of BNS. RESULTS: Eighty-seven patients' data were available for analysis from a total of 91 patients. The mean age (±standard deviation [SD]) was 65.14 years (±10.55). Preoperative urinary retention was present in 58% of the patients. The maximal flow rate (Qmax) was 12.05 ml/s among the 20 patients that had preoperative uroflowmetry. The transfusion rate was 35%, but almost two-third of them had only one unit of blood transfused. The mean weight (±SD) of the enucleated adenoma was 82.64 g (±36.63). Bladder irrigation was required in 14% of the patients, majority of the patients had urethral catheter removed after 96 h and the mean hospital stay was 6.52 days. No patient developed BNS after a mean follow-up duration of 16.39 months. CONCLUSION: Bladder neck stenosis can be a distressing complication of prostatectomy. The result of our technical modification of managing the trigone-bladder-neck complex looks promising for prevention or delaying the onset of BNS. A long-term observation and a prospective randomised control trial to ascertain this initial experience is needed.

Management dilemma of a recurrent huge fibrosarcoma in a 25-year-old African: a case report.

INTRODUCTION: Soft tissue sarcomas are rare tumours that are infrequently seen in most surgical practices. They can occur in any anatomic region of the body. The size of a soft tissue sarcoma is an important prognostic variable and so affects the quality of tumour resection. CASE PRESENTATION: A 25-year-old Nigerian African presented with recurrent huge fibrosarcoma measuring about 55 x 40 x 10 cm at his posterior trunk. The patient's clinical condition was poor; the tumour seemed unresectable and the patient looked inoperable. He had an extensive excision of the tumour but could not afford adjuvant therapies. He was discharged home against medical advice but may succumb to metastases. CONCLUSION: Sarcomas in black people can present as extremely large masses; the dilemma in management is not only limited to the delay in presentation but also the poor socio-economic status of the patients and the frequent non-availability of supporting services. Treatment grants or subsidies from government may go a long way to ensuring that patients receive appropriate care.