Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models.

Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions.

Kidney damage associated with COVID-19: from the acute to the chronic phase.

Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) infection is well established as a systemic disease including kidney damage. The entry point into the renal cell remains the angiotensin-converting enzyme 2 (ACE-2) receptor and the spectrum of renal lesions is broad, with a clear predominance of structural and functional tubular lesions. The most common form of glomerular injury is collapsing glomerulopathy (CG), which is strongly associated with apolipoprotein L1(APOL-1) risk variants. These acute lesions, which are secondary to the direct or indirect effects of SARS-CoV-2, can progress to chronicity and are specific to long COVID-19 in the absence of any other cause. Residual inflammation associated with SARS-CoV-2 infection, in addition to acute kidney injury (AKI) as a transitional state with or without severe histological lesions, may be responsible for greater kidney function decline in mild-to-moderate COVID-19. This review discusses the evidence for renal histological markers of chronicity in COVID-19 patients and triggers of low-grade inflammation that may explain the decline in kidney function in the post-COVID-19 period.

Range-wide genetic analysis of an endangered bumble bee (Bombus affinis, Hymenoptera: Apidae) reveals population structure, isolation by distance, and low colony abundance.

Declines in bumble bee species range and abundances are documented across multiple continents and have prompted the need for research to aid species recovery and conservation. The rusty patched bumble bee (Bombus affinis) is the first federally listed bumble bee species in North America. We conducted a range-wide population genetics study of B. affinis from across all extant conservation units to inform conservation efforts. To understand the species' vulnerability and help establish recovery targets, we examined population structure, patterns of genetic diversity, and population differentiation. Additionally, we conducted a site-level analysis of colony abundance to inform prioritizing areas for conservation, translocation, and other recovery actions. We find substantial evidence of population structuring along an east-to-west gradient. Putative populations show evidence of isolation by distance, high inbreeding coefficients, and a range-wide male diploidy rate of ~15%. Our results suggest the Appalachians represent a genetically distinct cluster with high levels of private alleles and substantial differentiation from the rest of the extant range. Site-level analyses suggest low colony abundance estimates for B. affinis compared to similar datasets of stable, co-occurring species. These results lend genetic support to trends from observational studies, suggesting that B. affinis has undergone a recent decline and exhibit substantial spatial structure. The low colony abundances observed here suggest caution in overinterpreting the stability of populations even where B. affinis is reliably detected interannually. These results help delineate informed management units, provide context for the potential risks of translocation programs, and help set clear recovery targets for this and other threatened bumble bee species.

The amyloid-ß1-42-oligomer interacting peptide D-AIP possesses favorable biostability, pharmacokinetics, and brain region distribution.

We have previously developed a unique 8-amino acid Aß42 oligomer-Interacting Peptide (AIP) as a novel anti-amyloid strategy for the treatment of Alzheimer's disease. Our lead candidate has successfully progressed from test tubes (i.e., in vitro characterization of protease-resistant D-AIP) to transgenic flies (i.e., in vivo rescue of human Aß42-mediated toxicity via D-AIP-supplemented food). In the present study, we examined D-AIP in terms of its stability in multiple biological matrices (i.e., ex-vivo mouse plasma, whole blood, and liver S9 fractions) using MALDI mass spectrometry, pharmacokinetics using a rapid and sensitive LC-MS method, and blood brain barrier (BBB) penetrance in WT C57LB/6 mice. D-AIP was found to be relatively stable over 3 h at 37 °C in all matrices tested. Finally, label-free MALDI imaging showed that orally administered D-AIP can readily penetrate the intact BBB in both male and female WT mice. Based upon the favorable stability, pharmacokinetics, and BBB penetration outcomes for orally administered D-AIP in WT mice, we then examined the effect of D-AIP on amyloid "seeding" in vitro (i.e., freshly monomerized versus preaggregated Aß42). Complementary biophysical assays (ThT, TEM, and MALDI-TOF MS) showed that D-AIP can directly interact with synthetic Aß42 aggregates to disrupt primary and/or secondary seeding events. Taken together, the unique mechanistic and desired therapeutic potential of our lead D-AIP candidate warrants further investigation, that is, testing of D-AIP efficacy on the altered amyloid/tau pathology in transgenic mouse models of Alzheimer's disease.

Heart and systemic sclerosis-findings from a national cohort study.

OBJECTIVES: Heart involvement is one of the leading causes of death in systemic sclerosis (SSc). The prevalence of SSc-related cardiac involvement is poorly known. Our objective was to investigate the prevalence and prognosis burden of different heart diseases in a nationwide cohort of patients with SSc. METHODS: We used data from a multicentric prospective study using the French SSc national database. Focusing on SSc-related cardiac involvement, we aimed to determine its incidence and risk factors. RESULTS: Over the 3528 patients with SSc 312 (10.9%) had SSc-related cardiac involvement at baseline. They tended to have a diffuse SSc subtype more frequently, more severe clinical features, and presented more cardiovascular risk factors. From the 1646 patients available for follow-up analysis, SSc-related cardiac involvement was associated with an increased risk of death. There was no significant difference in overall survival between SSc-related cardiac involvement, ischaemic heart disease or pulmonary arterial hypertension. Regarding survival analysis, 98 patients developed SSc-related cardiac involvement at five years (5-year event rate: 11.15%). Regarding reduced LVEF < 50% and left ventricular diastolic dysfunction, the 5-year event rate was 2.49% and 5.84% respectively. Pericarditis cumulative incidence at five years was 3%. Diffuse SSc subtype was a risk factor for SSc-related cardiac involvement and pericarditis. Female sex was associated with less left ventricular diastolic dysfunction incidence. CONCLUSIONS: Our results describe the incidence and prognostic burden of SSc-related cardiac involvement at a large scale, with gender and diffuse SSc subtype as risk factors. Further analyses should assess the potential impact of treatment on these various cardiac outcomes.

SARS-CoV2 mutations and impact on mortality: observational study in a sub-saharan Africa hospital.

BACKGROUND: One year after the coronavirus disease 2019 (COVID-19) pandemic, the focus of attention has shifted to the emergence and spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs). The aim of the study was to assess the frequency of VOCs in patients followed for COVID-19 at Kinshasa university hospital (KUH) during the 3rd and 4th waves of the pandemic in Kinshasa. Hospital mortality was compared to that of the first two waves. METHOD: The present study included all patients in whom the diagnosis of SARS-CoV-2 infection was confirmed by the polymerase chain reaction (PCR). The laboratory team sequenced a subset of all SARS-CoV-2 positive samples with high viral loads define as Ct < 25 to ensure the chances to generate complete genome sequence. RNA extraction was performed using the Viral RNA Mini Kit (Qiagen). Depending on the platform, we used the iVar bioinformatics or artic environments to generate consensus genomes from the raw sequencing output in FASTQ format. RESULTS: During the study period, the original strain of the virus was no longer circulating. The Delta VOC was predominant from June (92%) until November 2021 (3rd wave). The Omicron VOC, which appeared in December 2021, became largely predominant one month later (96%) corresponding the 4th wave. In-hospital mortality associated with COVID-19 fell during the 2nd wave (7% vs. 21% 1st wave), had risen during the 3rd (16%) wave before falling again during the 4th wave (7%) (p < 0.001). CONCLUSION: The Delta (during the 3rd wave) and Omicron VOCs (during the 4th wave) were very predominant among patients followed for Covid-19 in our hospital. Contrary to data in the general population, hospital mortality associated with severe and critical forms of COVID-19 had increased during the 3rd wave of the pandemic in Kinshasa.

Prevalence of risk and factors associated with obstructive sleep apnea-hypopnea syndrome in an adult population in Kinshasa, Democratic Republic of Congo.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an underdiagnosed and lesser known disease in sub-Saharan Africa. We believe that this is the first descriptive and analytical cross-sectional study in Kinshasa (from February 1 to October 31, 2021), which included respondents aged ≥18 years. The study aimed to determine the prevalence of the risk and factors associated with OSAHS. Each participant signed a free and informed consent. Statistical analyses were performed using XLStat 2020 and the Statistical Package for the Social Sciences version 24 for Windows. Odds ratios (ORs) were calculated to determine the degree of association between these variables and a high risk of OSAHS. The significance threshold was p < 0.05 and confidence interval (CI) at 95%. There were 4,162 participants, including 2,287 men (54.9%), with an mean (SD) age of 32 ± 12.6 years. The prevalence of OSAS risk was 17.4% and 7.9% for men and women, respectively. The associated risk factors were male sex (OR 4, 95% CI 3.20-5.54), hypertension (OR 6.7, 95% CI 4.87-9.30), age ≥60 years (OR 8.7, 95% CI 4.07-18.88), obesity/overweight (OR 1.94, 95% CI 1.13-3.78), and excessive daytime sleepiness (OR 2.63, 95% CI 2.05-3.56). The risk of OSAS in Kinshasa is high and it increases with age, male sex, obesity, and hypertension. The Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and male Gender (STOP-BANG) questionnaire is an easy-to-use tool for diagnostic orientation.

Factors associated with acute kidney injury (AKI) and mortality in COVID-19 patients in a Sub-Saharan African intensive care unit: a single-center prospective study.

INTRODUCTION: Acute kidney injury (AKI) is a complication of severe coronavirus disease 2019 (COVID-19). Kidney damage associated with COVID-19 could take specific features due to environmental and socio-cultural factors. This study evaluates the incidence of AKI, the associated factors, and mortality in COVID-19 patients in a Sub-Saharan African intensive care unit. METHODS: In a prospective cohort study conducted in the intensive care unit (ICU) of the Centre Médical de Kinshasa (CMK), consecutive patients admitted for COVID-19 were screened for the presence of AKI between 27 March, 2020 and 27 January 2022. AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines. The primary outcome was occurrence of AKI. The secondary outcome was 48 days' mortality and recovery of the renal function at intensive care unit (ICU) discharge. Survival (time-to death) curves were built using the Kaplan Meier methods. Multivariate analyses were performed by logistic regression to identify factors associated with AKI and Cox regression to explore the association between AKI and in-hospital mortality. The significance level of the p-value was set at 0.05. RESULTS: The median(IQR) sequential organ failure assessment score (SOFA) score and mean age of patients (215) including in our cohort were respectively 3(2-4) and 58.9 ± 14.9 years. The incidence of AKI was 28.4% with stages 1, 2, or 3 AKI accounted for 39.3%, 11.5%, and 49.2%, respectively. Hemodialysis was required in 16 out 215 (7.4%) patients. Dyspnea (adjusted odds ratio (aOR):2.27 [1.1--4.57] p = 0.021), SOFA ≥5 (aOR:3.11[1.29-7.53] p = 0.012), AST/ALT ratio (aOR: 1.53 [1.09-1.79] p = 0.015), N/L ratio (aOR:2.09 [1.09-3.20] p = 0.016), mechanical ventilation (aOR: 3.20 [1.66-10.51] p = 0.005) and Amikacin (aOR: 2.91 [1.37-6.18] p = 0.006) were the main factors associated with AKI. Patients with AKI had a mortality rate of 52.5% and 67.2% of the survivors did not recover kidney function at the end of hospitalization. Adjusted Cox regression analysis revealed that COVID-19-associated AKI was independently associated with in-hospital death (HR:2.96 [1.93-4.65] p = 0.013) compared to non-AKI patients. CONCLUSIONS: AKI was present in three out of ten COVID-19 patients. The most significant factors associated with AKI were dyspnea, SOFA ≥ 5, AST/ALT and N/L ratio, mechanical ventilation and Amikacin. AKI has been associated with an almost threefold increase in overall mortality and seven out of ten survivors did not recover kidney function after AKI.

Madurastatins with Imidazolidinone Rings: Natural Products or Side-Reaction Products from Extraction Solvents?

Madurastatins are a group of pentapeptides containing an oxazoline moiety, and, in a few cases, an imidazolidinone ring as an additional structural feature. In our search for new potential antiparasitic metabolites from natural sources, we studied the acetone extracts from a culture of Actinomadura sp. CA-135719. The LC/HRMS analysis of this extract identified the presence of the known madurastatins C1 (1), D1 (4), and D2 (5) together with additional members of the family that were identified as the new madurastatins H2 (2) and 33-epi-D1 (3) after isolation and spectroscopic analysis. The planar structures of the new compounds were established by HRMS, ESI-qTOF-MS/MS, and 1D and 2D NMR data, and their absolute configuration was proposed using Marfey's and bioinformatic analyses of the biosynthetic gene cluster (BGC). A revision of the absolute configuration of madurastatins D1 and D2 is proposed. Additionally, madurastatins containing imidazolidinone rings are proved to be artifacts originating during acetone extraction of the bacterial cultures.

Determinants of the unmet needs for information, education and communication on sexual health among single youths in Burundi.

The prevalence of HIV/AIDS among young people aged 15-24 in urban areas is at least 12 times higher among girls than boys in Burundi, while it is twice as high in Rwanda. The gap between the two countries could be narrowed if Burundi's single young people were provided with sufficient information about their sexual health through appropriate channels. The aim of this study was to examine the social and individual "determinants" of unmet needs for sexual health information, education and communication (IEC) among unmarried young boys and girls aged 15-24 in Burundi, using data from the 2016 Demographic and Health Survey (DHS). Data were analyzed at the bivariate level using cross-tabulations and chi-squared tests, and at the multivariate level using binary logistic regression methods. According to the results of the study, the 'determinants' of the phenomenon studied are, for both sexes, the size of the household, the age of the youths, their level of education, their knowledge of where to take the HIV/AIDS test and their region of residence; only in the case of boys do we find, in addition, the age of the head of the household, his level of education and the adolescents' exposure to the media; similarly, only in the case of girls do we find their economic activity and their perception of HIV/AIDS. Multisectoral IEC actions on sexual health for young people should therefore be strengthened in Burundi.

Au Burundi, en milieu urbain, la prévalence du VIH/SIDA est, chez les jeunes de 15-24 ans, au moins douze fois plus élevée chez les jeunes filles que chez les jeunes garçons, alors qu'au Rwanda elle est deux fois plus élevée. L'écart entre les deux pays serait réduit si les jeunes célibataires burundais recevaient suffisamment d'information sur leur santé sexuelle par des canaux appropriés. L'objectif de cette étude était de chercher au Burundi, chez les jeunes garçons et filles célibataires âgés de 15-24 ans, les « déterminants ¼ sociaux et individuels des Besoins Non Satisfaits (BNS) en Information, Education et Communication (IEC) en santé sexuelle à partir des données de l'Enquête Démographique et de Santé (EDS) de 2016. Ces dernières ont été analysées, au niveau bivarié, en recourant aux tableaux croisés et tests de chi-deux, et, au niveau multivarié, en recourant aux méthodes de régression logistique binaire. A en croire les résultats de l'étude, dans les deux sexes, les « déterminants ¼ du phénomène étudié sont la taille du ménage, l'âge du jeune, son niveau d'instruction, sa connaissance de l'endroit où faire le test de VIH/SIDA et sa région de résidence ; seulement, chez les garçons, on retrouve en plus l'âge du chef de ménage, son niveau d'instruction et l'exposition aux médias ; de même, seulement, chez les filles, on retrouve leur activité économique et leur perception du VIH/SIDA. Les actions multisectorielles d'IEC en santé sexuelle concernant les jeunes devraient alors être renforcées au Burundi.

Women's autonomy and fertility in Chad.

Chad's total fertility rate (TFR) is 6.4 children per woman, compared with no more than 5.5 in neighbouring countries: Cameroon and the Central African Republic. Scientific research on the determinants of fertility in Chad should therefore be carried out in order to show decision-makers how they can strengthen their actions in this area. This is the aim of this study, which focuses on the influence of women's autonomy on fertility in Chad. Analyses of data from the Multiple Indicator and Demographic and Health Survey (DHS/MICS) conducted in Chad in 2014/2015 and a qualitative survey conducted in the same country in 2020 show, among other things, that 1) in socio-cultural groups characterised by strong gender inequalities, women's autonomy is positively associated with their desired fertility; 2) in these and other groups characterised by less gender inequality, women's autonomy is negatively associated with their actual fertility, all things being equal; 3) the hypotheses explaining this relationship differ across sociocultural groups: In highly gender- inegalitarian groups, the frequent death of children leads couples in which women have either little or no autonomy to compensate with high fertility, whereas in less gender- inegalitarian groups, the negative association between women's autonomy and fertility is due to late union formation, union dissolution, the fertility-reducing effects of breastfeeding and modern contraception, and other intermediate fertility variables not considered here. These findings highlight both the importance of designing development programmes in Chad that focus on women's empowerment and the need for such programmes to take sufficient account of the socio-cultural contexts in which the populations concerned live.

Au Tchad, l'Indice Synthétique de Fécondité (ISF) est de 6,4 enfants par femme, alors que chez ses voisins, comme le Cameroun et la RCA, il ne dépasse pas 5,5. Il est alors très important de réaliser des recherches scientifiques sur les déterminants de la fécondité dans le premier pays, afin de montrer à ses décideurs comment ils devraient renforcer leurs actions dans ce domaine. La recherche réalisée ici en est un exemple et porte spécifiquement sur l'influence de l'autonomie de la femme sur sa fécondité dans ce pays. Les analyses des données de l'Enquête Démographique et de Santé et à Indicateurs Multiples (EDS/MICS) qui y a été menée en 2014/2015, et de celles de l'enquête qualitative, menée dans le même pays en 2020, ont, entre autres, révélé, ce qui suit : 1) dans les groupes socioculturels très inégalitaires en matière de genre, l'autonomie de la femme est positivement associée à sa fécondité désirée ; 2) dans ces groupes et dans ceux moins inégalitaires, toutes choses égales par ailleurs, l'autonomie de la femme est associée négativement à sa fécondité effective ; 3) les hypothèses d'explication de cette relation varie selon les groupes socioculturels : dans les premiers, les décès fréquents d'enfants entraînent les couples où les femmes ont une autonomie nulle ou faible à les compenser par une fécondité élevée ; dans les derniers, ce sont les entrées tardives en union, les ruptures d'unions, les effets réducteurs d'allaitement et de la contraception moderne et d'autres variables intermédiaires de la fécondité, non prises en compte, qui justifient pourquoi l'autonomie de la femme y est négativement associée à sa fécondité. Les résultats de cette étude témoignent non seulement de la pertinence des programmes de développement focalisés dans ce pays sur l'autonomisation de la femme, mais aussi du fait que pour être efficaces ces programmes devraient prendre suffisamment en compte les contextes dans lesquels vivent les populations concernées.

Predictors of Relapses or Recurrences in Patients With Giant Cell Arteritis: A Medical Records Review Study.

OBJECTIVE: Giant cell arteritis (GCA) is the most common systemic vasculitis in individuals aged ≥50 years. Its course is marked by a high relapse rate requiring long-term glucocorticoid use with its inherent adverse effects. We aimed to identify factors associated with relapses or recurrences in GCA at diagnosis. METHODS: We reviewed the medical records of consecutive patients with GCA diagnosed between 2009 and 2019 and followed for at least 12 months. We recorded their characteristics at onset and during follow-up. Factors associated with relapses or recurrences were identified using multivariable analysis. RESULTS: We included 153 patients, among whom 68% were female with a median age of 73 (47-98) years and a median follow-up of 32 (12-142) months. Seventy-four patients (48.4%) had at least 1 relapse or recurrence. Headache and polymyalgia rheumatica were the most frequent manifestations of relapses. The first relapse occurred at a median time of 13 months after the diagnosis, with a median dose of 5.5 (0-25) mg/d of glucocorticoids.In multivariable analysis, patients with relapses or recurrences had a higher frequency of cough and scalp tenderness at diagnosis (20.3% vs 5.1%; odds ratio [OR], 4.73; 95% confidence interval [CI], 1.25-17.94; p = 0.022; and 41.9% vs 29.1%; OR, 2.4; 95% CI, 1.07-5.39; p = 0.034, respectively). Patients with diabetes mellitus at diagnosis had fewer relapses or recurrences during follow-up (5.4% vs 19%; OR, 0.24; 95% CI, 0.07-0.83; p = 0.024). CONCLUSIONS: Cough and scalp tenderness at diagnosis were associated with relapses or recurrences, whereas patients with diabetes experienced fewer relapses or recurrences.

Readmission after pancreaticoduodenectomy: Birmingham score validation.

BACKGROUND: The Birmingham score predicts the risk of hospital readmission after pancreaticoduodenectomy (PD). This study aimed to validate the risk score in a different healthcare cohort. METHODS: From 2017 to 2021, 301 patients underwent PD. The Birmingham score was applied to 276 patients. Postoperative deceased patients (n = 7) or those requiring a completion of pancreatectomy (n = 18) were excluded. RESULTS: Forty-seven (17%) patients were readmitted after a median delay of 9 (range 1-49) days and stayed for 5 (range 1-27) days; 4 (8.5%) died during the hospital stay. The leading cause of readmission was a septic condition (53%), mostly resolved by medical treatment (77%). A multivariate analysis identified the occurrence of a clinically relevant postoperative pancreatic fistula, the score criteria, and the score itself as independent factors favouring readmission. Readmission rates in patients with low [n = 97 (35%)], intermediate [n = 98 (36%)], and high [n = 81 (29%)] scores were 5%, 17%, and 31%, respectively (P < 0.01). CONCLUSION: This study confirmed the relevance and robustness of the Birmingham risk score. Patients with a high risk of readmission after PD, identified based on the score, were discharged to a partnership medical centre close to the pancreatic centre to plan readmission and avoid futile unplanned hospitalisation.

Preoperative liver arterial conditioning in patients scheduled for a Mayo Clinic class Ia distal pancreatectomy: embolization or ligation?

BACKGROUND: Liver ischemia may occur during intraoperative common hepatic artery ligation in Mayo Clinic class I distal pancreatectomy with en bloc celiac axis resection (DP-CAR). Preoperative liver arterial conditioning could be used to avoid this outcome. This retrospective study compared arterial embolization (AE) or laparoscopic ligation (LL) of the common hepatic artery before class Ia DP-CAR. METHODS: From 2014 to 2022, 18 patients were scheduled for class Ia DP-CAR after neoadjuvant FOLFIRINOX treatment. Two were excluded due to hepatic artery variation, six underwent AE, ten underwent LL. RESULTS: Two procedural complications occurred in the AE group: an incomplete dissection of the proper hepatic artery and a distal migration of coils in the right branch of the hepatic artery. Neither complication prevented surgery. The median delay between conditioning and DP-CAR was 19 days; decreased to five days in the last six patients. None required arterial reconstruction. Morbidity and 90-day mortality rates were 26.7% and 12.5%, respectively. No patient developed postoperative liver insufficiency after LL. CONCLUSION: Preoperative AE and LL seem comparable in averting arterial reconstruction and postoperative liver insufficiency in patients scheduled for class Ia DP-CAR. However, serious complications that may arise during AE led us to prefer the LL technique.

Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial Autologous AD-SVF versus placebo in systemic sclerosis.

OBJECTIVE: To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients. METHODS: We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution 800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hand function, vasculopathy, hand pain, skin fibrosis, sensitivity of the finger pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction, and safety. RESULTS: Forty patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 months' follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 [12.2] in the AD-SVF group vs -7.6 [13.2] in the placebo group). At 6 months, hand function improved in both groups. CONCLUSION: This study showed an improvement of hand function in both groups over time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap should be encouraged to accurately assess the benefit of AD-SVF therapy. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.

Functional and genetic testing in adults with HLH reveals an inflammatory profile rather than a cytotoxicity defect.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition. Primary HLH occurs early in life as a result of monogenic biallelic mutations affecting lymphocyte cytotoxicity. Secondary HLH occurs mostly in adults secondary to infection, lymphoma, or rheumatic disease. In this latter setting, lymphocyte cytotoxicity status is not known. We conducted a systematic evaluation of natural killer (NK) cell cytotoxicity in adult patients with secondary HLH. Adult patients with secondary HLH were prospectively studied ex vivo for total lymphocyte count and subtype, NK cell phenotype, perforin expression and degranulation, and natural or antibody-dependent cell cytotoxicity, in comparison with patients affected by the same underlying disease without HLH (disease controls [DCs]) and with healthy controls (HCs). Screening for variants of cytotoxity genes was systematically performed. 68 patients were included in the HLH group and 34 each in the DC and HC groups. In HLH patients, severe and transient lymphopenia, activated NK cell phenotype (eg, increased CD69, ICAM-1, HLADR, and CCR5 expression), and decreased capacity of interferon γ production were observed; mean perforin expression was normal; and degranulation tests and NK cell cytotoxicity were not different from those in DCs. A monoallelic variant of uncertain significance affecting a lymphocyte cytotoxicity gene or the perforin variant A91V was observed in almost 50% of the patients. We detected no major intrinsic cytotoxicity dysfunction in secondary HLH patients compared with DCs and no predicted pathogenic gene variant. The activated NK phenotype profile associated with decreased interferon γ production seems similar to those of other hyperinflammatory diseases such as sepsis or systemic juvenile idiopathic arthritis.

Importance of temporality and context in relation to life habit restrictions among patients with systemic lupus erythematosus: A psychosocial qualitative study.

OBJECTIVE: Life habits (LH) encompass an individual's engagement in daily activities such as nutrition, fitness, personal care, communication, housing, and mobility, along with his/her social role (responsibility, interpersonal relationships, community life, education, employment, and recreation). This qualitative study explores the nature and context of LH restrictions in systemic lupus erythematosus (SLE) individuals across their SLE journey. METHODS: Narrative interviews were conducted with adult SLE patients. Interview transcripts were subjected to a thematic content analysis, using the Disability Creation Process model as a framework. RESULTS: Forty participants were interviewed. Three major themes were highlighted: (1) Temporality, capabilities, and environmental contexts: although all participants experienced LH restrictions at some point, the expression of these limitations depended on the individual's and SLE disease characteristics as well as on temporal (time of life and lupus course) and environmental (material, social, and societal) contexts. (2) Identity issues, illness stigma, and (fear of) discriminations: LH were discussed through the lens of participants' social roles and identities. While illness stigma can influence social relations, it is also expressed at a societal level. (3) Masking and minimizing strategies: due to illness stigma and fear of discrimination, participants developed strategies to manage their relationships, including masking and minimization. Their use was both advantageous and disadvantageous regarding LH. CONCLUSIONS: For individuals with SLE, LH restrictions must be considered as an ongoing process that takes place within specific contexts. Our findings provide many opportunities for interventions that can benefit patients and their families, as well as healthcare providers.

SARS-CoV2 infection in symptomatic patients: interest of serological tests and predictors of mortality: experience of DR Congo.

BACKGROUND: In symptomatic patients, the diagnostic approach of COVID-19 should be holistic. We aimed to evaluate the concordance between RT-PCR and serological tests (IgM/IgG), and identify the factors that best predict mortality (clinical stages or viral load). METHODS: The study included 242 patients referred to the University hospital of Kinshasa for suspected COVID-19, dyspnea or ARDS between June 1st, 2020 and August 02, 2020. Both antibody-SARS-CoV2 IgM/IgG and RT-PCR method were performed on the day of admission to hospital. The clinical stages were established according to the COVID-19 WHO classification. The viral load was expressed by the CtN2 (cycle threshold value of the nucleoproteins) and the CtE (envelope) genes of SARS- CoV-2 detected using GeneXpert. Kappa test and Cox regression were used as appropriate. RESULTS: The GeneXpert was positive in 74 patients (30.6%). Seventy two patients (29.8%) had positive IgM and 34 patients (14.0%) had positive IgG. The combination of RT-PCR and serological tests made it possible to treat 104 patients as having COVID-19, which represented an increase in cases of around 41% compared to the result based on GeneXpert alone. The comparison between the two tests has shown that 57 patients (23.5%) had discordant results. The Kappa coefficient was 0.451 (p < 0.001). We recorded 23 deaths (22.1%) among the COVID-19 patients vs 8 deaths (5.8%) among other patients. The severe-critical clinical stage increased the risk of mortality vs. mild-moderate stage (aHR: 26.8, p < 0.001). The values of CtE and CtN2 did not influence mortality significantly. CONCLUSION: In symptomatic patients, serological tests are a support which makes it possible to refer patients to the dedicated COVID-19 units and treat a greater number of COVID-19 patients. WHO Clinical classification seems to predict mortality better than SARS-Cov2 viral load.

Protective peritoneal patch for arteries during pancreatoduodenectomy: good value for money.

PURPOSE: This study proposes and details a simple and inexpensive protective technique of wrapping the hepatic and gastroduodenal artery stumps with a peritoneal patch during pancreatoduodenectomy (PD) in order to decrease post-pancreatectomy hemorrhage (PPH). METHODS: Among the 85 patients who underwent PD between July 2020 and March 2021, 16 patients with high-risk pancreatic anastomosis received a peritoneal patch. The Updated Alternative Fistula Risk Score (ua-FRS) was calculated. Post-operative pancreatic fistula (POPF) and PPH were diagnosed and graded according to the International Study Group of Pancreatic Surgery. The mortality rate was calculated up to 90 days after PD. RESULTS: The mean ua-FRS of the 16 patients was 43% (range: 21-63%). Among them, 6 (38%) experienced clinically relevant-POPF, and a PPH was observed in two patients (13%). In these two patients who required re-intervention, the peritoneal patch was remarkably intact, and neither the gastroduodenal stump nor hepatic artery was involved. None of the patients experienced 90-day mortality. CONCLUSION: Although the outcomes are encouraging, the evaluation of a larger series to assess the effectiveness of the peritoneal protective patch for arteries in a high-risk pancreatic anastomosis is ongoing.

Intraoperative frozen section analysis of para-aortic lymph nodes after neoadjuvant FOLFIRINOX: will it soon become useless?

PURPOSE: Positive para-aortic lymph nodes (PALN) (station 16) are commonly detected in the final pathologic examination (ranging from 15 to 26%) among patients who undergo upfront pancreatoduodenectomy for resectable pancreatic ductal adenocarcinoma. However, after neoadjuvant treatment (NAT) the role of positive PALN as a watershed for surgical resection remains unclear. We aimed to determine the incidence of intraoperative detection of PALN after NAT with FOLFIRINOX for pancreatic head adenocarcinoma and its impact on survival, as our policy was to not resect the tumor in such situations. METHODS: From January 2014 to December 2020, 136 patients with non-metastatic cancer who received neoadjuvant FOLFIRINOX and underwent explorative laparotomy were included. RESULTS: Intraoperative positive PALN were observed in 7 patients (5%). Patients had resectable (n = 5) or locally advanced (n = 2) disease at the time of surgery, but none of them underwent surgical resection. Positive PALN were significantly associated with a lower median number of FOLFIRINOX cycles (4 vs. 6, P = 0.05). There was no significant difference in overall survival between patients with positive loco-regional lymph nodes after resection and patients with non-resection owing to positive PALN (22 versus 16 months, P = 0.16), Overall survival with positive PALN, carcinomatosis, and liver metastasis was 16, 14, and 10 months, respectively (P > 0.05). CONCLUSIONS: Our results suggest that NAT may lower PALN involvement. We have modified our policy, positive PALN after NAT are no longer a contraindication to resection, rather a holistic picture of the disease guides management.