Burden of atrial fibrillation among adults with heart failure in sub-Saharan Africa: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to estimate the prevalence of atrial fibrillation (AF) in adults with heart failure (HF) and summarise the all-cause mortality ratio among adult patients with coexisting HF and AF in sub-Saharan Africa (SSA). SETTING: This was a systematic review and meta-analysis of cross-sectional and cohort studies with primary data on the prevalence and incidence of AF among patients with HF and the all-cause mortality ratio among patients with HF and AF in SSA. We combined text words and MeSH terms to search MEDLINE, PubMed and Global Health Library through Ovid SP, African Journals Online and African Index Medicus from database inception to 10 November 2021. Random-effects meta-analysis was used to estimate pooled prevalence. PRIMARY OUTCOME MEASURES: The prevalence and incidence of AF among patients with HF, and the all-cause mortality ratio among patients with HF and AF. RESULTS: Twenty-seven of the 1902 records retrieved from database searches were included in the review, totalling 9987 patients with HF. The pooled prevalence of AF among patients with HF was 15.6% (95% CI 12.0% to 19.6%). At six months, the all-cause mortality was 18.4% (95% CI 13.1% to 23.6%) in a multinational registry and 67.7% (95% CI 51.1% to 74.3%) in one study in Tanzania. The one-year mortality was 48.6% (95% CI 32.5% to 64.7%) in a study in the Democratic Republic of Congo. We did not find any study reporting the incidence of AF in HF. CONCLUSION: AF is common among patients with HF in SSA, and patients with AF and HF have poor survival. There is an urgent need for large-scale population-based prospective data to reliably estimate the prevalence, incidence and risk of mortality of AF among HF patients in SSA to better understand the burden of AF in patients with HF in the region. PROSPERO REGISTRATION NUMBER: CRD42018087564.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, full version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version intégrale.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, short version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version courte.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

Atrial fibrillation among adults with heart failure in sub-Saharan Africa - prevalence, incidence and all-cause mortality: a systematic review and meta-analysis protocol.

INTRODUCTION: Heart failure (HF) remains a major non-communicable disease in sub-Saharan Africa (SSA) associated with high rates of readmission, mortality and loss of economic productivity as it affects mostly young and economically active adults. Atrial fibrillation (AFib) is a major determinant of mortality among patients with HF in SSA. Meanwhile, the use of anti-arrhythmic medications in the region remains unacceptably low. This review aims to evaluate the prevalence and incidence of AFib in adult patients with HF in SSA, and the all-cause mortality rate among patients with HF and AFib. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015 statement was used to prepare this protocol. All eligible studies from database inception to December, 31 2018 in MEDLINE, Embase, Google Scholar, Web of science and Africa-specific databases (AFROLIB, African Index Medicus and African Journals Online) will be included without language restrictions. The process of study screening, selection, data extraction and assessment of risk of bias will be conducted independently by two reviewers. Disagreements will be arbitrated by a third reviewer. Study-specific estimates will be pooled using random-effect meta-analysis and summary measures obtained will be presented in forest plots. The χ2 test on Cochrane's Q and the I2 statistics will be used to assess and quantify heterogeneity, respectively. The Egger's test and funnel plots will be used to assess publication bias. ETHICS AND DISSEMINATION: Since our review will be based on already published data, an ethical approval is not required. The findings of this review will be presented in conferences and peer-reviewed journals and shared on social media such as Researchgate, Facebook, WhatsApp and Twitter. PROSPERO REGISTRATION NUMBER: CRD42018087564.

The general public's knowledge of diabetes mellitus: A cross-sectional study in Cameroon.

OBJECTIVE: To assess the general public's level of knowledge on diabetes mellitus (DM) and identify related sources of information in Cameroon. STUDY DESIGN: This was a cross-sectional study conducted in 2015 in two health facilities in Yaoundé and Edéa. METHODS: We included consenting adults, except health professionals. The level of knowledge on DM was evaluated on 24 points corresponding to 24 questions addressing either DM definition, signs and symptoms, risk factors or complications. RESULTS: Overall, 1524 persons (40.2% males) were included. Almost 99% of respondents had already heard of DM, but only 16.3% had ever received education on DM. The median score for the global knowledge was 79% (IQR 67-88). A person in the close entourage (71.3%) or a health professional (58.8%) constituted the major sources of information; school (13.3%) and media (television (23.6%), newspaper/magazine (10.0%), radio (9.6%) and internet (6.8%) were less common. Younger ages (<45years), lower levels of education, semi-urban residency, were independently associated with a lower level of knowledge on DM. CONCLUSIONS: The general public's level of knowledge on DM may be satisfactory, though needing to be improved. Schools and media should be capitalized to educate people on DM, targeting especially young adults and the less educated.

Giant congenital melanocytic nevus in a Cameroonian child: a case report.

BACKGROUND: Giant congenital melanocytic nevus is a very rare condition characterized by a large skin lesion and an increased risk of complications like neurocutaneous melanosis and malignant transformation. Reports of giant congenital melanocytic nevus are scarce in the sub-Saharan African literature and here we present a case of this disease in a Cameroonian adolescent. CASE PRESENTATION: A 12-year-old Cameroonian girl from the "Baka" ethnic group, with no relevant family and medical histories presented with a progressively extensive brownish-black nodular hypertrophic skin lesion of approximately 45 cm, which she had had since she was 2-days old. The lesion covered her entire back giving an appearance of "turtle child", which was highly suggestive of a giant congenital melanocytic nevus. She was booked in for a surgical intervention organized by a health campaign within her community. Meanwhile she was provided with psychological support and her family was counseled on warning signs of complications which would warrant an urgent consultation. CONCLUSIONS: Here we presented a case of giant congenital melanocytic nevus, apparently the first in the Cameroonian literature. In view of the potential severe complications as well as psychological trauma of this pathology, we draw clinicians' attention to this extremely rare but real pathology in our country, for a timely diagnosis and management.

Assessment of the general public's knowledge of stroke: A cross-sectional study in Yaoundé, Cameroon.

BACKGROUND: Stroke knowledge and awareness in the general public is important to improve stroke prevention and ensure prompt response to disease onset. Addressing the dearth of data in Africa, this study aimed to determine the level of knowledge on stroke definition, symptoms, risk factors and complications in the general population living in Yaoundé, Cameroon. METHODS: From February to April 2015, we conducted a cross-sectional study at the Nicolas Barre Hospital Centre. With the exception of the health personnel, we recruited all individuals aged ≥18years who visited the Centre for one reason or another and who volunteered to answer our questionnaire. The level of knowledge on stroke was evaluated on 28 points corresponding to 28 questions addressing either stroke definition, warning signs and symptoms, risk factors or complications. RESULTS: In total, 1.025 participants (57.4% females) were enrolled. The median age was 34years (interquartile range: 26-48); 14.9% and 9.8% of the participants were known hypertensive and diabetes patients, respectively. Overall, 99% of participants had already heard about stroke. The mean score of knowledge was 81.3±11.1%. The main sources of information on stroke were the close entourage (83.0%) and the health personnel (73.0%); media (television (16.4%), newspaper (8.0%), internet (7.7%), and radio (2.2%)) and school (8.0%) were the least represented. Speech disturbances (98.3%) and weakness, numbness or paralysis of one part of the body (98.0%) were the major warning signs and symptoms cited. Hypertension (98.5%) and overweight/obesity (97.8%) were the most known risk factors; 98.7% of people were aware of stroke common complications. Younger age (<45years), male sex, lower level of education and previous experience of stroke education were independently associated with a lower level of knowledge on stroke. CONCLUSION: The general public's level of knowledge on stroke in Yaoundé is good, though still needing to be improved. Media and schools should be capitalized to communicate on stroke, as these means will help to reach the youngest and the least educated who seem to have lower levels of knowledge.

Diagnosis of primary antibody and complement deficiencies in young adults after a first invasive bacterial infection.

OBJECTIVES: Screening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults. METHODS: Eligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening. RESULTS: The study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively. CONCLUSION: PID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults.

Effects of paternal and peripubertal stress on aggression, anxiety, and metabolic alterations in the lateral septum.

Early-life stress and biological predispositions are linked to mood and personality disorders related to aggressive behavior. We previously showed that exposure to peripubertal stress leads to increased anxiety-like behaviors and aggression against males and females, as well as increased aggression against females in their male offspring. Here, we investigated whether paternal (pS) and individual (iS) exposure to peripubertal stress may exert additive effects on the long-term programming of anxiety-like and aggressive behaviors in rats. Given the key role of the lateral septum (LS) in the regulation of anxiety and aggressive behaviors and the hypothesized alterations in balance between neural excitation and inhibition in aggression-related disorders, markers for these processes were examined in the LS. Peripubertal stress was applied both in naïve male rats and in the offspring of peripubertally stressed males, and anxiety-like and aggressive behaviors were assessed at adulthood. Proton magnetic resonance spectroscopy at 6-months, and post-mortem analysis of glutamic acid decarboxylase 67 (GAD67) at 12-months were conducted in LS. We confirmed that aggressive behavior was increased by pS and iS, while only iS increased anxiety-like behavior. Individual stress led to reduced GABA, confirmed by reduced GAD67 immunolabelling, and increased glutamate, N-acetyl-aspartate, phosphocholine and creatine; while pS specifically led to reduced phosphocreatine. pS and iS do not interact and exert a differential impact on the analyzed aspects of brain function and anxiety-like behaviors. These data support the view that early-life stress can affect the behavioral and neurodevelopmental trajectories of individuals and their offspring, which may involve different neurobiological mechanisms.

XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer.

The limitations of cancer cell lines have led to the development of direct patient-derived xenograft models. However, the interplay between the implanted human cancer cells and recruited mouse stromal and immune cells alters the tumor microenvironment and limits the value of these models. To overcome these constraints, we have developed a technique to expand human hematopoietic stem and progenitor cells (HSPCs) and use them to reconstitute the radiation-depleted bone marrow of a NOD/SCID/IL2rg(-/-) (NSG) mouse on which a patient's tumor is then transplanted (XactMice). The human HSPCs produce immune cells that home into the tumor and help replicate its natural microenvironment. Despite previous passage on nude mice, the expression of epithelial, stromal and immune genes in XactMice tumors aligns more closely to that of the patient tumor than to those grown in non-humanized mice-an effect partially facilitated by human cytokines expressed by both the HSPC progeny and the tumor cells. The human immune and stromal cells produced in the XactMice can help recapitulate the microenvironment of an implanted xenograft, reverse the initial genetic drift seen after passage on non-humanized mice and provide a more accurate tumor model to guide patient treatment.

Improving tumour heterogeneity MRI assessment with histograms.

By definition, tumours are heterogeneous. They are defined by marked differences in cells, microenvironmental factors (oxygenation levels, pH, VEGF, VPF and TGF-α) metabolism, vasculature, structure and function that in turn translate into heterogeneous drug delivery and therapeutic outcome. Ways to estimate quantitatively tumour heterogeneity can improve drug discovery, treatment planning and therapeutic responses. It is therefore of paramount importance to have reliable and reproducible biomarkers of cancerous lesions' heterogeneity. During the past decade, the number of studies using histogram approaches increased drastically with various magnetic resonance imaging (MRI) techniques (DCE-MRI, DWI, SWI etc.) although information on tumour heterogeneity remains poorly exploited. This fact can be attributed to a poor knowledge of the available metrics and of their specific meaning as well as to the lack of literature references to standardised histogram methods with which surrogate markers of heterogeneity can be compared. This review highlights the current knowledge and critical advances needed to investigate and quantify tumour heterogeneity. The key role of imaging techniques and in particular the key role of MRI for an accurate investigation of tumour heterogeneity is reviewed with a particular emphasis on histogram approaches and derived methods.

Oxidative stress-mediated iNKT-cell activation is involved in COPD pathogenesis.

Chronic obstructive pulmonary disease (COPD) is a major clinical challenge mostly due to cigarette smoke (CS) exposure. Invariant natural killer T (iNKT) cells are potent immunoregulatory cells that have a crucial role in inflammation. In the current study, we investigate the role of iNKT cells in COPD pathogenesis. The frequency of activated NKT cells was found to be increased in peripheral blood of COPD patients relative to controls. In mice chronically exposed to CS, activated iNKT cells accumulated in the lungs and strongly contributed to the pathogenesis. The detrimental role of iNKT cells was confirmed in an acute model of oxidative stress, an effect that depended on interleukin (IL)-17. CS extracts directly activated mouse and human dendritic cells (DC) and airway epithelial cells (AECs) to trigger interferonγ and/or IL-17 production by iNKT cells, an effect ablated by the anti-oxidant N-acetylcystein. In mice, this treatment abrogates iNKT-cell accumulation in the lung and abolished the development of COPD. Together, activation of iNKT cells by oxidative stress in DC and AECs participates in the development of experimental COPD, a finding that might be exploited at a therapeutic level.