Use of transverse penile fasciocutaneous flap in management of long segment anterior urethral stricture at the Jos university teaching hospital, Jos Nigeria

Background: Urethral stricture may be defined as a narrowing of the lumen of the urethra due to scar tissue formation. It results from fibrosis and loss of compliance of the urethra leading to bladder outlet obstruction. Treatment of long segment urethral stricture is a huge challenge to the reconstructive Urologist. This study is to determine the aetiology of long segment urethral stricture, location of the stricture, use of distal transverse penile fasciocutaneous flap and the complications associated with the use of the flap.Methods: Twenty two patients with long segment anterior urethral stricture from 2014 to 2017 at the Jos University teaching hospital were included in the study. Patient assessment included complete history including past interventions for the urethral stricture disease, physical examination and radiological examination. Patient’s age, aetiology of stricture, stricture length, location of stricture, surgical management and complications were recorded.Results: Twenty two consecutive patients were involved in the study. The mean age was 48.8years with a range of 35 to 70 years. Post infection accounted for 64% of the strictures while catheter induced inflammatory stricture accounted for 36%. The mean length of the stricture was 9.4cm, with a range of 5cm to 15cm. Penile fasciocutaneous flap was used in all the repairs. Overall complication was 27.3%.Conclusions: Transverse penile fasciocutaneous flap is a well-vascularized pedicle and skin island. It is mobile and can be adapted to repair long segment anterior urethral strictures. Surgical complications include ring stenosis, penile skin necrosis and urethrocutaneous fistula

Correlation of Level of Serum 25-Hydroxy Vitamin D and Gleason Score as a Measure of Aggressiveness of Prostate Cancer in Black Africans

Background Cancer of the prostate (CaP) is the second most commonly diagnosed cancer worldwide and the sixth leading cause of death from cancer in males. . Black men of African descent have higher risk for developing prostate cancer and are most likely to present at a younger age with more advanced disease and a poorer disease prognosis. Objective To determine if there is a relationship between the level of serum 25 hydroxy vitamin D and aggressiveness of prostate cancer using the Gleason score in black Africans in Jos. Methods A cross sectional study conducted among fifty patients presenting at the urological surgical out-patient clinics of the Jos University Teaching Hospital who were evaluated to have a clinical diagnosis of prostate cancer and scheduled for prostate biopsy. Blood samples for serum 25-hydroxy vitamin D were assayed using the ELISA technique, prostate biopsy was done and only those histologically confirmed to be prostate cancer were analysed. Data was collected using a proforma with statistical analysis done using SPSS(R) version 23 and Spearman’s rank correlation test used with a p-value < 0.05 considered significant. Results Fifty patients with histologically proven prostate cancer was studied whose age ranged from 50-89 years with a predominant age group 70-79 years (70.0±7.9).The mean level of serum 25-hydroxy vitamin D was 37.90ng/ml±17.92. All patients in the study had adenocarcinoma as the histologic type with a mean Gleason score of 9.36±13.14. A Spearman’s rank order correlation was statistically significant (rs (50) = -0.423, p = 0.002). Conclusion A Spearman’s rank order correlation shows a moderate negative correlation between the serum 25- hydroxy vitamin D and Gleason score (rs (50) = -0.423, p = 0.002.Thus, serum 25-hydroxy vitamin D assay can be used to prognosticate in patients with cancer of the prostate

Baseline PI susceptibility by HIV-1 Gag-protease phenotyping and subsequent virological suppression with PI-based second-line ART in Nigeria

Objectives: Previous work showed that gag-protease-derived phenotypic susceptibility to PIs differed between HIV-1 subtype CRF02_AG/subtype G-infected patients who went on to successfully suppress viral replication versus those who experienced virological failure of lopinavir/ritonavir monotherapy as first-line treatment in a clinical trial. We analysed the relationship between PI susceptibility and outcome of second-line ART in Nigeria, where subtypes CRF02_AG/G dominate the epidemic. Methods: Individuals who experienced second-line failure with ritonavir-boosted PI-based ART were matched (by subtype, sex, age, viral load, duration of treatment and baseline CD4 count) to those who achieved virological response (‘successes’). Successes were defined by viral load <400 copies of HIV-1 RNA/mL by week 48. Full-length Gag-protease was amplified from patient samples for in vitro phenotypic susceptibility testing, with PI susceptibility expressed as IC50 fold change (FC) relative to a subtype B reference strain. Results: The median (IQR) lopinavir IC50 FC was 4.04 (2.49–7.89) for virological failures and 4.13 (3.14–8.17) for virological successes (P = 0.94). One patient had an FC >10 for lopinavir at baseline and experienced subsequent virological failure with ritonavir-boosted lopinavir as the PI. There was no statistically significant difference in single-round replication efficiency between the two groups (P = 0.93). There was a moderate correlation between single-round replication efficiency and FC for lopinavir (correlation coefficient 0.32). Conclusions: We found no impact of baseline HIV-1 Gag-protease-derived phenotypic susceptibility on outcomes of PI-based second-line ART in Nigeria

Value of the visual prostate symptom score in evaluation of symptomatic benign prostatic enlargement: prospective study in a Nigerian population

Background: To evaluate the correlation of Visual Prostate Symptom Score (VPSS) with International Prostate Symptom Score (IPSS) and Maximum Urinary Flow (Qmax). To investigate the effect of educational level on the ability to independently complete the VPSS versus the IPSS and time taken to do so.Methods: Bio data was taken from men with lower urinary tract symptoms (LUTS) due to Benign Prostatic Enlargement (BPE) who presented at the Urology clinic of Jos University Teaching Hospital. They were administered the IPSS questionnaire and VPSS pictogram, which they completed with or without physician assistance and the time taken to do so was noted. They subsequently had uroflowmetry done on same visit and the data was recorded in a structured proforma. Statistical analysis was done using SPSS(R) version 20. Correlation test was done for VPSS, IPSS and Qmax while the paired t-test was used for the average time spent in completing both questionnaires. A p-value <0.05 was considered as significant.Results: Eighty-five men (aged 42 to 94 years) were enrolled in the study. The VPSS correlated significantly with the IPSS in terms of total score (r = +0.684, p<0.001) and QoL (r = +0.570, p<0.001), as well as with the Qmax (r = -0.222, p = 0.041). A greater proportion (21.2%) of men with limited education could complete the VPSS without physician assistance as compared to the IPSS (6.0%) and the average time taken to complete the VPSS (170.51 seconds) was significantly shorter than the time taken to complete the IPSS (406.42 seconds).Conclusions: The VPSS correlates significantly with the IPSS and Qmax. It can be completed without physician assistance by a greater proportion of men with limited education within a shorter time period

Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria

BACKGROUND: Deep sequencing could improve understanding of HIV treatment failure and viral population dynamics. However, this tool is often inaccessible in low- and middle-income countries. OBJECTIVES: To determine the genetic patterns of resistance emerging in West African HIV-1 subtypes during first-line virological failure, and the implications for future antiretroviral options. PATIENTS AND METHODS: Participants were selected from a Nigerian cohort of people living with HIV who had failed first-line ART and subsequently switched to second-line therapy. Whole HIV-1 genome sequences were generated from first-line virological failure samples with Illumina MiSeq. Mutations detected at ≥2% frequency were analysed and compared by subtype. RESULTS: HIV-1 sequences were obtained from 101 participants (65% female, median age 30 years, median 32.9 months of nevirapine- or efavirenz-based ART). Thymidine analogue mutations (TAMs) were detected in 61%, other core NRTI mutations in 92% and NNRTI mutations in 99%. Minority variants (<20% frequency) comprised 18% of all mutations. K65R was more prevalent in CRF02_AG than G subtypes (33% versus 7%; P = 0.002), and ≥3 TAMs were more common in G than CRF02_AG (52% versus 24%; P = 0.004). Subtype G viruses also contained more RT cleavage site mutations. Cross-resistance to at least one of the newer NNRTIs, doravirine, etravirine or rilpivirine, was predicted in 81% of participants. CONCLUSIONS: Extensive drug resistance had accumulated in people with West African HIV-1 subtypes, prior to second-line ART. Deep sequencing significantly increased the detection of resistance-associated mutations. Caution should be used if considering newer-generation NNRTI agents in this setting

In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix.

Protease inhibitors (PIs) are the second- and last-line therapy for the majority of HIV-infected patients worldwide. Only around 20% of individuals who fail PI regimens develop major resistance mutations in protease. We sought to explore the role of mutations in gag-pro genotypic and phenotypic changes in viruses from six Nigerian patients who failed PI-based regimens without known drug resistance-associated protease mutations in order to identify novel determinants of PI resistance. Target enrichment and next-generation sequencing (NGS) with the Illumina MiSeq system were followed by haplotype reconstruction. Full-length Gag-protease gene regions were amplified from baseline (pre-PI) and virologic failure (VF) samples, sequenced, and used to construct gag-pro-pseudotyped viruses. Phylogenetic analysis was performed using maximum-likelihood methods. Susceptibility to lopinavir (LPV) and darunavir (DRV) was measured using a single-cycle replication assay. Western blotting was used to analyze Gag cleavage. In one of six participants (subtype CRF02_AG), we found 4-fold-lower LPV susceptibility in viral clones during failure of second-line treatment. A combination of four mutations (S126del, H127del, T122A, and G123E) in the p17 matrix of baseline virus generated a similar 4-fold decrease in susceptibility to LPV but not darunavir. These four amino acid changes were also able to confer LPV resistance to a subtype B Gag-protease backbone. Western blotting demonstrated significant Gag cleavage differences between sensitive and resistant isolates in the presence of drug. Resistant viruses had around 2-fold-lower infectivity than sensitive clones in the absence of drug. NGS combined with haplotype reconstruction revealed that resistant, less fit clones emerged from a minority population at baseline and thereafter persisted alongside sensitive fitter viruses. We used a multipronged genotypic and phenotypic approach to document emergence and temporal dynamics of a novel protease inhibitor resistance signature in HIV-1 matrix, revealing the interplay between Gag-associated resistance and fitness

Prevalence of hypertension among patients aged 50 and older living with Human Immunodeficiency Virus

Background: Hypertension is one of the common medical conditions observed among patients aged 50 years and elder living with HIV (EPLWH) and to date no systematic review has estimated its global prevalence. Purpose: To conduct a systematic review to estimate the global prevalence of hypertension among EPLWH. Data Sources: PubMed/MEDLINE, Embase, the Cochrane Library, and Global Health databases for relevant publications up till May 25, 2018. Study Selection: Observational studies (cohort or cross-sectional studies) that estimated the prevalence of hypertension among EPLWH. Data Extraction: Required data were extracted independently by three reviewers and the main outcome was hypertension prevalence among EPLWH. Data Synthesis: The 24 (n = 29,987) eligible studies included were conducted in North America, Europe, Africa, and Asia. A low level bias threat to the estimated hypertension prevalence rates was observed. The global prevalence of hypertension among EPLWH was estimated at 42.0% (95% CI 29.6%–55.4%), I 2 = 100%. The subgroup analysis showed that North America has the highest prevalence of hypertension 50.2% (95% CI 29.2% –71.2%) followed by Europe 37.8% (95% CI 30.7%–45.7%) sub-Saharan Africa 31.9% (95% CI 18.5% –49.2%) and Asia 31.0% (95% CI 26.1%–36.3%). We found the mean age of the participants explaining a considerable part of variation in hypertension prevalence. Conclusion: This study demonstrated that two out of five EPLWH are hypertensive. North America appears to have the highest prevalence of hypertension followed by Europe, sub-Saharan Africa (SSA) and Asia respectively. Findings from this study can be utilized to integrate hypertension management to HIV management package. (Registration number: CRD42018103069

High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.

OBJECTIVES: HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa. METHODS: We studied a Nigerian cohort of recipients prior to and during receipt of second-line PI-based therapy, who were integrase inhibitor-naive. Illumina next-generation sequencing with target enrichment was used on stored plasma samples. Drug resistance was interpreted using the Stanford Resistance Database and the IAS-USA 2019 mutation lists. RESULTS: Of 115 individuals, 59.1% harboured CRF02_AG HIV-1 and 40.9% harboured subtype G HIV-1. Four participants had major IAS-USA integrase resistance-associated mutations detected at low levels (2%-5% frequency). Two had Q148K minority variants and two had R263K (one of whom also had L74I). L74I was detected in plasma samples at over 2% frequency in 40% (46/115). Twelve (26.1%) had low-level minority variants of between 2% and 20% of the viral population sampled. The remaining 34 (73.9%) had L74I present at >20% frequency. L74I was more common among those with subtype G infection (55.3%, 26/47) than those with CRF02_AG infection (29.4%, 20/68) (P = 0.005). CONCLUSIONS: HIV-1 subtypes circulating in West Africa appear to have very low prevalence of major integrase mutations, but significant prevalence of L74I. A combination of in vitro and clinical studies is warranted to understand the potential implications.K.E.B. is supported by Wellcome Trust award number 170461. N.N. is supported by NIH R01 AI147331-01. R.K.G. is supported by a Wellcome Trust Senior Fellowship in Clinical Science (WT108082AIA). This study was supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of U2G GH002099-01 and PA GH17-1753 (ACHIEVE)

Review of prostate cancer research in Nigeria

Prostate cancer (CaP) disparities in the black man calls for concerted research efforts. This review explores the trend and focus of CaP research activities in Nigeria, one of the ancestral nations for black men. It seeks to locate the place of the Nigerian research environment in the global progress on CaP disparities. Literature was reviewed mainly through a Pubmed search with the terms “prostate cancer”and “Nigeria”, as well as from internet and hard copies of journal pages