Glycemic Control in Diabetic Patients Improved Overall Lung Cancer Survival across Diverse Populations.

BACKGROUND: The consequence of diabetes on lung cancer overall survival (OS) is debated. This retrospective study used two large lung cancer databases to assess comprehensively diabetes effects on lung cancer OS in diverse demographic populations, including health disparity. METHODS: The University of Texas MD Anderson Cancer Center database (32,643 lung cancer cases with 11,973 diabetics) was extracted from electronic health records (EHRs) using natural language processing (NLP). Associations were between diabetes and lung cancer prognostic features [age, sex, race, body mass index (BMI), insurance status, smoking, stage, and histopathology]. Hemoglobin A1C (HgbA1c) and glucose levels assessed glycemic control. Validation was with a Louisiana cohort (17,768 lung cancer cases with 4,746 diabetics) enriched for health disparity cases. Kaplan-Meier analysis, log-rank test, multivariable Cox proportional hazard models, and survival tree analyses were employed. RESULTS: Lung cancer patients with diabetes exhibited marginally elevated OS or no statistically-significant difference versus non-diabetic patients. When examining OS for two glycemic levels (HgbA1c > 7.0 or glucose > 154 mg/dL versus HgbA1c > 9.0 or glucose > 215 mg/dL), a statistically significant improvement in OS occurred in lung cancers with controlled versus uncontrolled glycemia (P < 0.0001). This improvement spanned gender, age, smoking status, insurance status, stage, race, BMI, histopathology and therapy. Survival tree analysis revealed that obese and morbidly obese patients with controlled glycemia or no known diabetes had higher lung cancer OS than comparison groups. CONCLUSION: These findings indicate a need for optimal glycemic control to improve lung cancer OS in diverse populations with diabetes.

Prevalence and distribution of primary glomerular diseases in Africa: a systematic review and meta-analysis of observational studies.

Glomerulonephritis (GN) is a predominant cause of kidney failure in Africa. The prevalence of primary GNs varies widely across Africa depending on the relative proportion of secondary GNs and genetic predispositions. We assessed the overall and sub-regional prevalence of primary GN and its histologic subtypes in Africa. We searched PubMed, EMBASE and African Journals Online for studies of biopsy-proven primary GNs across all age groups in Africa published between 2010 and 2022. Data for primary GNs [minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), mesangioproliferative GN (MesPGN), membranoproliferative GN (MPGN), post-infectious GN (PIGN), IgA Nephropathy (IgAN), and crescentic GN (CresGN)] were extracted. Pooled prevalence was determined using the random effects model. Seventeen eligible articles (n = 6,494 individuals) from 8 African countries met the inclusion criteria. The overall pooled prevalence of FSGS, MCD, MN, MPGN, MesPGN, PIGN, IgAN and CresGN was 26.10%, 22.40%, 8.40%, 6.40%, 6.40%, 2.60%, 2.60%, 1.40%, respectively. Only 4 studies (23.5%) used light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM) for diagnosis. There were significant differences in the distribution of histologic subtypes in the paediatric compared to the adult population and across geographic sub-regions, with West Africa having a higher prevalence of FSGS. Overall, the dominance of FSGS across most regions and age groups has implications for disease diagnosis and ongoing care. Research efforts to understand the impact of this trend on kidney disease outcomes and efforts to improve kidney biopsy practice as a means of early disease detection are needed in Africa.

A combination of novel NSC small molecule inhibitor along with doxorubicin inhibits proliferation of triple-negative breast cancer through metabolic reprogramming.

Treatment of patients with triple-negative breast cancer (TNBC) has been challenging due to the absence of well-defined molecular targets and the highly invasive and proliferative nature of TNBC cells. Current treatments against TNBC have shown little promise due to high recurrence rate in patients. Consequently, there is a pressing need for novel and efficacious therapies against TNBC. Here, we report the discovery of a novel small molecule inhibitor (NSC33353) with potent anti-tumor activity against TNBC cells. The anti-proliferative effects of this small molecule inhibitor were determined using 2D and 3D cell proliferation assays. We found that NSC33353 significantly reduces the proliferation of TNBC cells in these assays. Using proteomics, next generation sequencing (NGS), and gene enrichment analysis, we investigated global regulatory pathways affected by this compound in TNBC cells. Proteomics data indicate a significant metabolic reprograming affecting both glycolytic enzymes and energy generation through oxidative phosphorylation. Subsequently, using metabolic (Seahorse) and enzymatic assays, we validated our proteomics and NGS analysis findings. Finally, we showed the inhibitory and anti-tumor effects of this small molecule in vitro and confirmed its inhibitory activity in vivo. Doxorubicin is one of the most effective agents in the treatment of TNBC and resistance to this drug has been a major problem. We show that the combination of NSC33353 and doxorubicin suppresses the growth of TNBC cells synergistically, suggesting that NSC33353 enhances TNBC sensitivity to doxorubicin. In summary, our data indicate that the small molecule inhibitor, NSC33353, exhibits anti-tumor activity in TNBC cells, and works in a synergistic fashion with a well-known chemotherapeutic agent.

Ceritinib is a novel triple negative breast cancer therapeutic agent.

BACKGROUND: Triple-negative breast cancers (TNBCs) are clinically aggressive subtypes of breast cancer. TNBC is difficult to treat with targeted agents due to the lack of commonly targeted therapies within this subtype. Androgen receptor (AR) has been detected in 12-55% of TNBCs. AR stimulates breast tumor growth in the absence of estrogen receptor (ER), and it has become an emerging molecular target in TNBC treatment. METHODS: Ceritinib is a small molecule inhibitor of tyrosine kinase and it is used in the therapy of non-small lung cancer patients. Enzalutamide is a small molecule compound targeting the androgen receptor and it is used to treat prostate cancer. Combination therapy of these drugs were investigated using AR positive breast cancer mouse xenograft models. Also, combination treatment of ceritinib and paclitaxel investigated using AR- and AR low mouse xenograft and patient derived xenograft models. RESULTS: We screened 133 FDA approved drugs that have a therapeutic effect of AR+ TNBC cells. From the screen, we identified two drugs, ceritinib and crizotinib. Since ceritinib has a well- defined role in androgen independent AR signaling pathways, we further investigated the effect of ceritinib. Ceritinib treatment inhibited RTK/ACK/AR pathway and other downstream pathways in AR+ TNBC cells. The combination of ceritinib and enzalutamide showed a robust inhibitory effect on cell growth of AR+ TNBC cells in vitro and in vivo. Interestingly Ceritinib inhibits FAK-YB-1 signaling pathway that leads to paclitaxel resistance in all types of TNBC cells. The combination of paclitaxel and ceritinib showed drastic inhibition of tumor growth compared to a single drug alone. CONCLUSIONS: To improve the response of AR antagonist in AR positive TNBC, we designed a novel combinational strategy comprised of enzalutamide and ceritinib to treat AR+ TNBC tumors through the dual blockade of androgen-dependent and androgen-independent AR signaling pathways. Furthermore, we introduced a novel therapeutic combination of ceritinib and paclitaxel for AR negative or AR-low TNBCs and this combination inhibited tumor growth to a great extent. All agents used in our study are FDA-approved, and thus the proposed combination therapy will likely be useful in the clinic.

Nischarin Deletion Reduces Oxidative Metabolism and Overall ATP: A Study Using a Novel NISCHΔ5-6 Knockout Mouse Model.

Nischarin (Nisch) is a cytosolic scaffolding protein that harbors tumor-suppressor-like characteristics. Previous studies have shown that Nisch functions as a scaffolding protein and regulates multiple biological activities. In the current study, we prepared a complete Nisch knockout model, for the first time, by deletion of exons 5 and 6. This knockout model was confirmed by Qrt-PCR and Western blotting with products from mouse embryonic fibroblast (MEF) cells. Embryos and adult mice of knockouts are significantly smaller than their wild-type counterparts. Deletion of Nisch enhanced cell migration, as demonstrated by wound type and transwell migration assays. Since the animals were small in size, we investigated Nisch's effect on metabolism by conducting several assays using the Seahorse analyzer system. These data indicate that Nisch null cells have lower oxygen consumption rates, lower ATP production, and lower levels of proton leak. We examined the expression of 15 genes involved in lipid and fat metabolism, as well as cell growth, and noted a significant increase in expression for many genes in Nischarin null animals. In summary, our results show that Nischarin plays an important physiological role in metabolic homeostasis.

The case for increased peritoneal dialysis utilization in low- and lower-middle-income countries.

Peritoneal dialysis (PD) has several advantages compared to haemodialysis (HD), but there is evidence showing underutilization globally, especially in low-income and lower-middle-income countries (LLMICs) where kidney replacement therapies (KRT) are often unavailable, inaccessible, and unaffordable. Only 11% of all dialysis patients worldwide use PD, more than 50% of whom live in China, the United States of America, Mexico, or Thailand. Various barriers to increased PD utilization have been reported worldwide including patient preference, low levels of education, and lower provider reimbursement. However, unique but surmountable barriers are applicable to LLMICs including the excessively high cost of providing PD (related to PD fluids in particular), excessive cost of treatment borne by patients (relative to HD), lack of adequate PD training opportunities for doctors and nurses, low workforce availability for kidney care, and challenges related to some PD outcomes (catheter-related infections, hospitalizations, mortality, etc.). This review discusses some known barriers to PD use in LLMICs and leverages data that show a global trend in reducing rates of PD-related infections, reducing rates of modality switches from HD, and improving patient survival in PD to discuss how PD use can be increased in LLMICs. We therefore, challenge the idea that low PD use in LLMICs is unavoidable due to these barriers and instead present opportunities to improve PD utilization in LLMICs.

Role of Nischarin in the pathology of diseases: a special emphasis on breast cancer.

Nischarin has been demonstrated to have tumor suppressor functions. In this review, we comprehensively discuss up to date information about Nischarin. In addition, this paper aims to report the prognostic value, clinical relevance, and biological significance of the Nischarin gene (NISCH) in breast cancer (BCa) patients using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) datasets. We evaluated NISCH gene expression and its correlation to patient survival, baseline expression, and expression variation based on age groups, tumor stage, tumor size, tumor grade, and lymph node status in different subtypes of BCa. Since NISCH has been extensively reported to inhibit EMT and cancer cell migration, we also checked for the correlation between NISCH and EMT genes in addition to the correlation between NISCH and cell migration genes. Our results indicate that NISCH is a tumor suppressor that plays a critical role in BCa initiation, progression, and tumor development. We find that there is a higher level of NISCH expression in normal breast tissues compared to breast cancer tissues. Also, aggressive subtypes of breast cancers, such as the triple negative/basal category, have decreased levels of NISCH as the disease progresses. Finally, we report that NISCH is inversely correlated with many EMT and cancer cell migration genes in BCa. Interestingly, we identified a significant negative correlation between NISCH expression and its methylation in breast cancer patients. Overall, the goal of this report is to establish a strong clinical basis for further investigation into the cellular, molecular, and physiological roles of NISCH in BCa. Ultimately, NISCH gene expression might be clinically harnessed as a biomarker or predictor of invasiveness and metastasis in BCa.

Association of Serum Magnesium with Blood Pressure in Patients with Hypertensive Crises: A Retrospective Cross-Sectional Study.

The role of magnesium in blood pressure has been studied among hypertensive patients; however, there is a dearth of studies exploring the role of magnesium in hypertensive crises. The primary objective of this study was to evaluate the relationship between serum magnesium and blood pressure in patients with hypertensive crises. This was a single-center, retrospective, chart review, cross-sectional study of patients with hypertensive crises. Patients were included if they were eighteen years of age or older, with an international classification disease ninth revision (ICD-9) code of 401.9 (hypertensive crises: emergency or urgency) and a documented magnesium level on their electronic medical record. The primary outcome of the study was the correlation between serum magnesium and blood pressure (systolic blood pressure and diastolic blood pressure) in patients with hypertensive crises. Two hundred and ninety-three patients were included in the study. The primary outcome result showed that serum magnesium was positively correlated with systolic blood pressure (r = 0.143, p = 0.014), but not diastolic blood pressure. Conclusion: This study found a significant positive association between magnesium and systolic blood pressure, but not diastolic blood pressure, among patients with hypertensive crises. This positive association of serum magnesium with systolic blood pressure was maintained after adjusting for covariates. This study's findings suggest a potential role of magnesium in blood pressure among patients with hypertensive crises.

Prevalence of Chronic Kidney Disease as a Marker of Hypertension Target Organ Damage in Africa: A Systematic Review and Meta-Analysis.

INTRODUCTION: Hypertension is a major global cause of cardiovascular disease and death with rising worldwide prevalence, particularly in low-income countries. With low awareness, poor treatment, and low control of hypertension in Africans, there is an increased number of patients with target organ damage (TOD), especially chronic kidney disease (CKD), as a consequence of hypertension. The aim of our study is to assess the prevalence of CKD from studies in Africa reporting TOD related to hypertension. METHODS: We performed a search of PubMed/MEDLINE, Web of Science, EBSCOhost, and African Journals Online (AJOL) for studies reporting on CKD as TOD in patients with hypertension. The pooled estimate of CKD was then presented by subregions, age group, eGFR equations, and urban or rural location. RESULTS: We identified 1,334 articles from which 12 studies were included for quantitative analysis. The studies included 5297 participants from 6 countries (Ghana, Nigeria, Uganda, Tanzania, Democratic Republic of Congo, and South Africa). The pooled prevalence of CKD was 17.8% (95% CI 13.0-23.3%), and CKD was significantly more prevalent in West Africa (21.3% (95% CI: 16.1-27.0); p < 0.0001) and in studies conducted in urban settings (p < 0.001). CKD prevalence was not significantly different by type of GFR equation or age. CONCLUSION: This study reports a high prevalence of CKD related to hypertension with a higher prevalence in urban than rural areas. This emphasizes the role of hypertension in causing kidney damage, and the need for strategies to improve awareness, treatment, and control of hypertension in Africans. This study is registered with PROSPERO registration number CRD42018089263.

Evaluation of serum calcium differences in hypertensive crises and control patients: A randomly matched case-control study.

The role of calcium in blood pressure has been widely studied among hypertensive patients; however, no study has explored the role of calcium in hypertensive crises. The primary objective of this study is to evaluate the differences in serum calcium levels between hypertensive crises patients and a 1:1 random matched controls (age-, sex-, race-, diabetes, and body mass index matched). This study is a single-center, retrospective, chart review, case-control study of patients with hypertensive crises (case group) and patients without hypertensive crises (control group). Patients were included in the case group if they were 18 years of age or older with hypertensive crises and have a documented calcium level. The control group patients were required to be 18 years of age or older, have a documented calcium level, and have no diagnosis of hypertensive crises. The primary outcome of the study was to compare the mean serum calcium in patients with hypertensive crises vs patients without hypertensive crises. Five hundred and sixty-six patients were included in the study: 283 patients in both the case group and control group. The primary outcome results showed that serum calcium concentration was not significantly different between the case group (8.99 ± 0.78 mg/dL) and control group (8.96 ± 0.75 mg/dL) (P = .606). This study found no significant difference in serum calcium levels in patients with hypertensive crises compared to a random matched control group. Larger observational or experimental studies may be useful to evaluate the effect of calcium on blood pressure in hypertensive crises.

Evaluation of serum magnesium differences in hypertensive crises and control patients: A randomly matched case-control study.

Although the role of magnesium in blood pressure has been well studied among hypertensive patients, no study has explored the role of magnesium in hypertensive crises. The primary objective of this study is to evaluate the differences in serum magnesium levels between hypertensive crises patients and matched controls (age-, sex-, race-, and diabetes-matched) in a 1:1 random match. This study is a single-center, retrospective, chart review, case-control study of patients with hypertensive crises (case group) and patients without hypertensive crises (control group). Patients were included in the case group if they were 18 years of age or older with hypertensive crises and have a documented magnesium level. The control group patients were required to be 18 years of age or older, have no diagnosis of hypertensive crises, and have a documented magnesium level. The primary outcome of the study was to compare the mean serum magnesium in patients with hypertensive crises versus patients without hypertensive crises. Three hundred and fifty-eight patients were included in the study: 179 patients in both the case group and control group. The primary outcome results showed that serum magnesium concentration was not significantly different between the case group (1.89 ± 0.29 mg/dl) and control group (1.90 ± 0.31 mg/dl) (p = .787). This study found no significant difference in serum magnesium levels in patients with hypertensive crises compared to a random matched control group. Larger observational or experimental studies may be useful to evaluate the effect of magnesium on blood pressure in hypertensive crises.

Global Sex Disparity of COVID-19: A Descriptive Review of Sex Hormones and Consideration for the Potential Therapeutic Use of Hormone Replacement Therapy in Older Adults.

The 2019-2020 SARS-related coronavirus-2 (SARS-CoV-2) pandemic has brought unprecedented challenges to healthcare sectors around the world. As of November 2020, there have been over 64 million confirmed cases and approaching 2 million deaths globally. Despite the large number of positive cases, there are very limited established standards of care and therapeutic options available. To date, there is still no Food and Drug Administration (FDA) approved vaccine for COVID-19, although there are several options in various clinical trial stages. Herein, we have performed a global review evaluating the roles of age and sex on COVID-19 hospitalizations, ICU admissions, deaths in hospitals, and deaths in nursing homes. We have identified a trend in which elderly and male patients are significantly affected by adverse outcomes. There is evidence suggesting that sex hormone levels can influence immune system function against SARS-CoV-2 infection, thus reducing the adverse effects of COVID-19. Since older adults have lower levels of these sex hormones, we therefore speculate, within rational scientific context, that sex steroids, such as estrogen and progesterone, needs further consideration for use as alternative therapeutic option for treating COVID-19 elderly patients. To our knowledge, this is the first comprehensive article evaluating the significance of sex hormones in COVID-19 outcomes in older adults.

Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study.

BACKGROUND AND OBJECTIVE: We tested whether the prostacyclin analog inhaled iloprost modulates dead space, dynamic hyperinflation (DH), and systemic inflammation/oxidative stress during maximal exercise in subjects with chronic obstructive pulmonary disease (COPD) who were not selected based on pulmonary hypertension (PH). METHODS: Twenty-four COPD patients with moderate-severe obstruction (age 59 ± 7 years, FEV1 53 ± 13% predicted) participated in a randomized, double-blind, placebo-controlled crossover trial. Each subject received a single nebulized dose of 5.0 µg iloprost or placebo on non-consecutive days followed by maximal cardiopulmonary exercise tests. The primary outcome was DH quantified by end-expiratory lung volume/total lung capacity ratio (EELV/TLC) at metabolic isotime. RESULTS: Inhaled iloprost was well-tolerated and reduced submaximal alveolar dead-space fraction but did not significantly reduce DH (0.70 ± 0.09 vs 0.69 ± 0.07 following placebo and iloprost, respectively, p = 0.38). Maximal exercise time (9.1 ± 2.3 vs 9.3 ± 2.2 min, p = 0.31) and peak oxygen uptake (17.4 ± 6.3 vs 17.9 ± 6.9 mL/kg/min, p = 0.30) were not significantly different following placebo versus iloprost. CONCLUSIONS: A single dose of inhaled iloprost was safe and reduced alveolar dead space fraction; however, it was not efficacious in modulating DH or improving exercise capacity in COPD patients who were not selected for the presence of PH.

A Systematic Review of Complications Associated With Percutaneous Native Kidney Biopsies in Adults in Low- and Middle-Income Countries.

INTRODUCTION: Kidney biopsy is an important tool for making diagnoses and for assessing the drug treatment requirements and disease prognosis in the management of kidney diseases. There are variations in the rate of complications associated with kidney biopsies across countries, and this depends on various clinical and technical factors. The aim of this study is to report on complications associated with kidney biopsy performed in low- and middle-income countries. METHODS: Two reviewers searched studies in MEDLINE, Embase, Cochrane Reviews, and African Journals Online. A random effects meta-analysis method was used to pool estimates of complications. RESULTS: We identified 39 studies reporting on 19,500 kidney biopsies with overall complications (major + minor) rate of 14.9% (95% confidence interval = 11.4%-18.7%). Fewer complications were reported in biopsies performed with real-time ultrasound scans compared to those pre-marked using ultrasound or blind procedures (12.4% vs. 14.9% vs. 24.5%; P = 0.037), respectively. Complications, albeit lower for procedures performed with automated needles (13.3%), were not significantly different from those performed with nonautomated needles (17.3%; P = 0.588). Major complications included macroscopic hematuria (1.48%), nephrectomy (0.04%), blood loss requiring red cell transfusion (0.24%), angiographic intervention (0.22%), and death (0.01%). CONCLUSION: Complications associated with kidney biopsy in low- and middle-income countries are low, are comparable to those in other settings, and occur more sparingly when real-time ultrasound techniques or automated kidney biopsy needles are used. This suggests the need to expand the use of this procedure to improve diagnosis of kidney pathologies and choice of therapy when indicated.

Diagnostic performance of glomerular PLA2R and THSD7A antibodies in biopsy confirmed primary membranous nephropathy in South Africans.

BACKGROUND: Serum and tissue-based tests using phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain containing 7A (THSD7A) are established immune biomarkers for the diagnosis of primary membranous nephropathy (PMN). This study assessed the diagnostic performance of these biomarkers in the diagnosis of PMN in South Africans. METHODS: This was a cross-sectional analysis from a single centre in Cape Town, South Africa. Relevant biodata was collected from all patients. Histology, including slides for PLA2R and THSD7A were processed and assessed by typical microscopic and immunohistochemical features. Biopsy tissues of patients with membranous lupus nephritis (LN-V) and diabetic nephropathy (DN) were used as controls. The diagnostic accuracy for diagnosis of PMN using positive PLA2R and THSD7A were evaluated. RESULTS: Of the 88 patients included, 41 had PMN with a mean age of 44.5 ± 17.5 years and 61.0% were female. Histologically, PLA2R and THSD7A were only positive in the PMN group (51.2% and 4.9%, respectively) but negative in both control groups. The sensitivity of PLA2R and THSD7A for identifying PMN was 51.2% and 4.9%, respectively. The sensitivity of both tests together was 53.7% while the specificity and positive predictive values (PPV) for any of the tests (alone or in combination) was 100%. There was no difference in the sensitivity and specificity when using PLA2R alone compared to combining the two tests (p=0.32). CONCLUSION: Glomerular staining of PLA2R and THSD7A could have potential diagnostic values in South Africans. This has implications on how immunotherapies can be initiated and used in these settings.

Repurposing existing drugs for the treatment of COVID-19/SARS-CoV-2 infection: A review describing drug mechanisms of action.

The outbreak of a novel coronavirus (SARS-CoV-2) has caused a major public health concern across the globe. SARS-CoV-2 is the seventh coronavirus that is known to cause human disease. As of September 2020, SARS-CoV-2 has been reported in 213 countries and more than 31 million cases have been confirmed, with an estimated mortality rate of ∼3%. Unfortunately, a drug or vaccine is yet to be discovered to treat COVID-19. Thus, repurposing of existing cancer drugs will be a novel approach in treating COVID-19 patients. These drugs target viral replication cycle, viral entry and translocation to the nucleus. Some can enhance innate antiviral immune response as well. Hence this review focuses on comprehensive list of 22 drugs that work against COVID-19 infection. These drugs include fingolimod, colchicine, N4-hydroxycytidine, remdesivir, methylprednisone, oseltamivir, icatibant, perphanizine, viracept, emetine, homoharringtonine, aloxistatin, ribavirin, valrubicin, famotidine, almitrine, amprenavir, hesperidin, biorobin, cromolyn sodium, and antibodies- tocilzumab and sarilumab. Also, we provide a list of 31 drugs that are predicted to function against SARS-CoV-2 infection. In summary, we provide succinct overview of various therapeutic modalities. Among these 53 drugs, based on various clinical trials and literature, remdesivir, nelfinavir, methylpredinosolone, colchicine, famotidine and emetine may be used for COVID-19. SIGNIFICANCE: It is of utmost important priority to develop novel therapies for COVID-19. Since the effect of SARS-CoV-2 is so severe, slowing the spread of diseases will help the health care system, especially the number of visits to Intensive Care Unit (ICU) of any country. Several clinical trials are in works around the globe. Moreover, NCI developed a recent and robust response to COVID-19 pandemic. One of the NCI's goals is to screen cancer related drugs for identification of new therapies for COVID-19. https://www.cancer.gov/news-events/cancer-currents-blog/2020/covid-19-cancer-nci-response?cid=eb_govdel.

Prevalence of peritonitis and mortality in patients with ESKD treated with chronic peritoneal dialysis in Africa: a systematic review.

OBJECTIVE: The aim of this study was to report the prevalence of peritonitis and mortality in patients with end-stage kidney disease (ESKD) treated with chronic peritoneal dialysis (PD) in Africa. DESIGN: Systematic review. SETTING: Africa. PARTICIPANTS: Patients with ESKD in Africa. INTERVENTIONS: PD in its varied forms. PRIMARY AND SECONDARY OUTCOMES: PD-related peritonitis rate (primary outcome), time-to-discontinuation of PD, mortality. DATA SOURCES: Four databases, including PubMed, Embase, Web of Science and Africa Journal Online were systematically searched from 1 January 1980 to 31 December 2019. ELIGIBILITY CRITERIA: Studies conducted in Africa reporting peritonitis rate and mortality in patients treated with PD. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted and synthesised the data using Microsoft Excel. The quality of included data was also assessed. RESULTS: We included 17 studies from seven African countries representing 1894 patients treated with PD. The overall median age was 41.4 years (IQR: 38.2-44.7) with a median time on PD of 18.0 months (17.0-22.6). An overall median peritonitis rate of 0.75 (0.56-2.20) episodes per patient-year (PPY) was observed and had declined with time; peritonitis rate was higher in paediatric studies than adult studies (1.78 (1.26-2.25) vs 0.63 (0.55-1.87) episodes PPY). The overall median proportion of deaths was 21.1% (16.2-25.8). Culture negative peritonitis was common in paediatric studies and studies that reported combined outcomes of continuous ambulatory PD and automated PD. Both 1-year and 2-year technique survival were low in all studies (83.6% and 53.0%, respectively) and were responsible for a high proportion of modality switch. CONCLUSIONS: Our study identifies that there is still high but declining peritonitis rates as well as low technique and patient survival in PD studies conducted in Africa. Sustained efforts should continue to mitigate factors associated with peritonitis in patients with ESKD treated with PD in Africa. PROSPERO REGISTRATION NUMBER: CRD42017072966.

Comparing the Efficacy and Safety of Induction Therapies for the Treatment of Patients with Proliferative Lupus Nephritis in South Africa.

BACKGROUND: Lupus nephritis (LN) can be complicated with requirement for kidney replacement therapy and death. Efficacy of induction therapies using mycophenolate mofetil (MMF) or intravenous cyclophosphamide (IVCYC) has been reported from studies, but there is limited data in Africans comparing both treatments in patients with proliferative LN. METHODS: This was a retrospective study of patients with biopsy-proven proliferative LN diagnosed and treated with either MMF or IVCYC in a single centre in Cape Town, South Africa, over a 5-year period. The primary outcome was attaining complete remission after completion of induction therapy. RESULTS: Of the 84 patients included, mean age was 29.6 ± 10.4 years and there was a female preponderance (88.1%). At baseline, there were significant differences in estimated glomerular filtration rate (eGFR) and presence of glomerular crescents between both groups (p ≤ 0.05). After completion of induction therapy, there was no significant difference in remission status (76.0% versus 87.5%; p=0.33) or relapse status (8.1% versus 10.3%; p=0.22) for the IVCYC and MMF groups, respectively. Mortality rate for the IVCYC group was 5.5 per 10,000 person-days of follow-up compared to 1.5 per 10,000 person-days of follow-up for the MMF group (p=0.11), and there was no significant difference in infection-related adverse events between both groups. Estimated GFR at baseline was the only predictor of death (OR: 1.0 [0.9-1.0]; p=0.001). CONCLUSION: This study shows similar outcomes following induction treatment with MMF or IVCYC in patients with biopsy-proven proliferative LN in South Africa. However, a prospective and randomized study is needed to adequately assess these outcomes.

Bilateral Vascular Repair in a Patient with Multiple Upper Extremity Injury Presenting at a Teaching Hospital-Case Report and Literature Review.

Penetrating trauma to the upper extremity will usually result in vascular injuries, which mostly also involves nerves and tendons. Morbidity related to upper extremity vascular injuries usually occurs due to the associated injuries of the nerves, tendons, and bone. Early presentation to a trauma centre and prompt intervention will reduce morbidity associated with upper extremity vascular injuries.