Seroprofiling of Antibodies Against Endemic Human Coronaviruses and Severe Acute Respiratory Syndrome Coronavirus 2 in a Human Immunodeficiency Virus Cohort in Lesotho: Correlates of Antibody Response and Seropositivity.

BACKGROUND: Serological data on endemic human coronaviruses (HCoVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in southern Africa are scarce. Here, we report on (1) endemic HCoV seasonality, (2) SARS-CoV-2 seroprevalence, and (3) correlates of SARS-CoV-2 seropositivity and strength of SARS-CoV-2 and endemic HCoV serological responses among adults living with human immunodeficiency virus (HIV). METHODS: Plasma samples were collected from February 2020 to July 2021 within an HIV cohort in Lesotho. We used the AntiBody CORonavirus Assay (ABCORA) multiplex immunoassay to measure antibody responses to endemic HCoV (OC43, HKU1, NL63, and 229E) and SARS-CoV-2 antigens. RESULTS: Results for 3173 samples from 1403 adults were included. Serological responses against endemic HCoVs increased over time and peaked in winter and spring. SARS-CoV-2 seropositivity reached >35% among samples collected in early 2021 and was associated with female sex, obesity, working outside the home, and recent tiredness or fever. Positive correlations were observed between the strength of response to endemic HCoVs and to SARS-CoV-2 and between older age or obesity and the immunoglobulin G response to SARS-CoV-2. CONCLUSIONS: These results add to our understanding of the impact of biological, clinical, and social/behavioral factors on serological responses to coronaviruses in southern Africa.

Dolutegravir in real life: Self-reported mental and physical health outcomes after transitioning from efavirenz- to dolutegravir-based antiretroviral therapy in a prospective cohort study in Lesotho.

INTRODUCTION: HIV programmes across many countries in Africa have recently transitioned people living with HIV from efavirenz (EFV)- to dolutegravir (DTG)-containing antiretroviral therapy (ART). As both drugs are associated with neuropsychiatric adverse effects, this study assessed the mental health and HIV/ART-associated symptoms of people living with HIV before and after transition to DTG. METHODS: The prospective DO-REAL cohort enrolled people starting DTG-based ART in Lesotho from February to December 2020. For this analysis within DO-REAL, we included adults changing from tenofovir disoproxil fumarate (TDF)/lamivudine (3TC)/EFV to TDF/3TC/DTG within first-line therapy. At transition and 16 weeks thereafter, participants completed the Patient Health Questionnaire-9 (PHQ-9; depression screening), the 12-item Short-Form Health Survey (SF-12; mental and physical health), and a modified HIV Symptom Index (mHSI; HIV/ART-related symptoms). We also assessed weight change. We used McNemar tests with Bonferroni corrections to assess binary outcomes. CLINICALTRIALS: gov: NCT04238767. RESULTS: Among 1228 participants, 1131 completed follow-up. Of these, 60.0% were female, the median age was 46 years (interquartile range [IQR] 38-55), and the median time taking ART was 5.7 years (IQR 3.5-8.9). No change was observed for weight or overall PHQ-9 or SF-12 outcomes. However, three mHSI items decreased at follow-up: 'feeling sad/down/depressed' (bothered 6.0% vs. 3.3% of participants at least 'a little' before vs. after transition; adjusted p = 0.048); 'feeling nervous/anxious' (7.4% vs. 3.4%; adjusted p = 0.0009); and 'nightmares, strange/vivid dreams' (6.3% vs. 3.5%; adjusted p = 0.027). Individual PHQ-9 or SF-12 items also improved. Being symptom free across all measures increased from 5.1% to 11.4% (p < 0.0001). CONCLUSIONS: We observed no negative impacts and potential moderate improvements with DTG, providing further support for the rollout of DTG.

[Evaluation of the results and feasibility of vibration, diuresis and inversion therapy in the treatment of upper urinary tract stones]. / Évaluation des résultats et de la faisabilité de la posturothérapie (hydratation, inversion, vibration) dans le traitement des calculs des voies urinaires supérieures.

OBJECTIVES: To evaluate the feasibility, efficiency, and predictive factors of therapeutic success of Vibration, Diuresis and Inversion (VDI) therapy for the removal of upper urinary tract stones. METHODS: It is a retrospective, single-center study at the CHU - La Conception, Marseille, France including all patients treated with VDI from 2013 to 2018. VDI was indicated for stones <6mm in first-line treatment or for residual fragments <6mm after ureteroscopy, PCNL, microPCNL. The protocol included 4 sessions in outpatient care from 2013 to 2015 then 6 sessions from 2015 to 2018 and a final radiological evaluation. RESULTS: In total, 109 patients or 489 sessions are reported: median age was 55 years [14-84], median BMI 25kg/m2 [15-37], average cumulative size of kidney stones 3mm ±4. VDI was performed after flexible ureteroscopy (62%), SWL (20%), percutaneous treatment (9%) or as a first-line treatment (9%). Compliance was 87 %. The median VAS during the session was 0[0-8]. The incidence of post-session renal colic was 4% (all Clavien I). The postoperative fragment-free and microfragment rates were respectively 39% and 21%, i.e. an overall success of 60% for kidney stones, and 43% and 21%, i.e. an overall success of 64% for lower pole kidney stones. CONCLUSION: VDI is a simple, non invasive and well tolerated technique for the elimination of small renal lithiasis after SWL, ureteroscopy, PCNL or as a first-line treatment.

Viral suppression after transition from nonnucleoside reverse transcriptase inhibitor- to dolutegravir-based antiretroviral therapy: A prospective cohort study in Lesotho (DO-REAL study).

OBJECTIVES: Since 2018, the World Health Organization has recommended dolutegravir (DTG)-containing antiretroviral therapy (ART) for most people living with HIV. Country programmes across Africa have subsequently transitioned from other, mostly nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART to DTG-based ART. This study aims to assess the virological impact of programmatic transitioning to DTG-based ART in Lesotho. METHODS: The prospective Dolutegravir in Real-Life in Lesotho (DO-REAL) cohort enrols people living with HIV initiating or transitioning to DTG-based ART in Lesotho. Here, we present data from participants who transitioned from NNRTI- to DTG-based ART between February and December 2020. Blood samples collected at transition and at 16 weeks' follow-up (window 8-32 weeks) were used for viral load (VL) and resistance testing. RESULTS: Among 1347 participants, follow-up data was available for 1225. The majority (60%) were female, median age at transition was 47 years [interquartile range (IQR): 38-56], and median (IQR) time since ART initiation was 5.9 (3.5-9.0) years. Among those with complete VL data, the rate of viral suppression to < 100 copies/mL was 1093/1116 (98%) before, 1073/1116 (96%) at, and 1098/1116 (98%) after transition. Even among those with a VL ≥ 100 copies/mL at transition, 42/44 (95%) achieved suppression to < 100 copies/mL at follow-up. Seven participants had a VL ≥ 1000 copies/mL at follow-up and did not harbour any integrase mutations associated with resistance to DTG. CONCLUSIONS: The high levels of viral suppression observed are encouraging regarding virological outcomes upon programmatic transitioning from NNRTI- to DTG-based ART.

Low rates of active hepatitis B and C infections among adults and children living with HIV and taking antiretroviral therapy: A multicenter screening study in Lesotho.

Lesotho presents the second-highest adult human immunodeficiency virus (HIV) prevalence globally. Among people living with HIV, data on hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection are limited. We report HBV and HCV coinfection data from a multicentre cross-sectional study among adult and pediatric patients taking antiretroviral therapy in 10 health facilities in Lesotho. Among 1318 adults screened (68% female; median age, 44 years), 262 (20%) had immunologically controlled HBV infection, 99 (7.6%) tested anti-HBs positive and anti-HBc negative, indicating vaccination, and 57 (4.3%) had chronic HBV infection. Among the patients with chronic HBV infection, 15 tested hepatitis B envelope antigen (HBeAg) positive and eight had detectable HBV viremia (median, 2 477 400 copies/mL; interquartile range, 205-34 400 000) with a mean aspartate aminotransferase-to-platelet ratio index of 0.48 (SD, 0.40). Prevalence of HCV coinfection was 1.7% (22 of 1318), and only one patient had detectable HCV viremia. Among 162 pediatric patients screened, three (1.9%) had chronic HBV infection, whereby two also tested HBeAg-positive, and one had detectable HBV viral load (210 copies/mL). Six of 162 (3.7%) had anti-HCV antibodies, all with undetectable HCV viral loads. Overall prevalence of chronic HBV/HIV and HCV/HIV coinfection among adults and children was relatively low, comparable to earlier reports from the same region. But prevalence of immunologically controlled HBV infection among adults was high. Of those patients with chronic HBV infection, a minority had detectable HBV-DNA.

Interest of cytology combined with Xpert® HPV and Anyplex® II HPV28 Detection human papillomavirus (HPV) typing: differential profiles of anal and cervical HPV lesions in HIV-infected patients on antiretroviral therapy.

OBJECTIVES: The aim of the study was to assess the interest to combine cytological examination and human papillomavirus (HPV) typing of anal and cervical Papanicolaou (Pap) smears of HIV-infected patients on combination antiretroviral therapy (cART), to evaluate whether differences in prevalence exist between anal and cervical squamous intraepithelial lesions in patients with high-risk oncogenic HPV infection. METHODS: Anal and/or cervical Pap smears were obtained by anoscopy and/or colposcopy in 238 subjects recruited consecutively in 2015: anal smears were obtained from 48 male and female patients [42 men; 35 men who have sex with men (MSM)] and cervical smears from 190 female patients. Cytological Bethesda classification was coupled with HPV typing. HPV typing was performed, on the same smears, using the Xpert® HPV Assay, which detects only high-risk HPV (hrHPV), and the Anyplex® II HPV28 Detection assay, which detects hrHPV and low-risk (lr) HPV. RESULTS: Our data showed clear-cut differences between the anal and cervical samples. Compared with the cervical samples, the anal samples exhibited (1) more numerous cytological lesions, which were histologically proven; (2) a higher hrHPV infection prevalence; (3) a higher prevalence of multiple hrHPV coinfections whatever HPV typing kit was used; (4) a predominance of HPV16 and HPV18/45 types. Overall, there was an almost perfect agreement between the two HPV typing assays (absolute agreement = 90.3%). CONCLUSIONS: Co-testing consisting of cytology and HPV typing is a useful screening tool in the HIV-infected population on cART. It allows detection of prevalence differences between anal and cervical HPV-related lesions. As recently recommended, anal examination should be regularly performed especially in HIV-infected MSM but also in HIV-infected women with genital hrHPV lesions.

The Suboptimal Pediatric HIV Viral Load Cascade: Multidistrict Cohort Study Among Children Taking Antiretroviral Therapy in Lesotho, Southern Africa.

BACKGROUND: Children living with HIV and taking antiretroviral therapy (ART) are a priority group for routine viral load (VL) monitoring. As per Lesotho guidelines, a VL ≥1000 copies/mL ("unsuppressed") should trigger adherence counseling and a follow-up VL; 2 consecutive unsuppressed VLs ("virologic failure") qualify for switching to second-line ART, with some exceptions. Here, we describe the pediatric VL cascade in Lesotho. METHODS: In a prospective open cohort study comprising routine VL results from 22 clinics in Lesotho, we assessed outcomes along the VL cascade for children who had at least 1 VL test from January 2016 through June 2020. Data were censored on February 10, 2021. RESULTS: In total, 1215 children received 5443 VL tests. The median age was 10 years (interquartile range 7-13) and 627/1215 (52%) were female; 362/1215 (30%) had at least 1 unsuppressed VL. A follow-up VL was available for 325/362 (90%), although only for 159/362 (44%) within 6 months of the first unsuppressed VL. Of those with a follow-up VL, 172/329 (53%) had virologic failure and 123/329 (37%) qualified for switching to second-line ART. Of these, 55/123 (45%) were ever switched, although only 9/123 (7%) were switched within 12 weeks of the follow-up VL. Delays were more pronounced in rural facilities. Overall, 100/362 (28%) children with an unsuppressed VL received a timely follow-up VL and, if required, a timely regimen switch. CONCLUSIONS: Despite access to VL monitoring, clinical management was suboptimal. HIV programs should prioritize timely clinical action to maximize the benefits of VL monitoring.

Effects of extracts and molecules derived from medicinal plants of West Africa in the prevention and treatment of gynecological cancers. A Review.

Medicinal plants are a potential source of drug discovery and development of new pharmacological compounds for cancer chemoprevention. More than 80% of the West African population uses medicinal plants. It is estimated that over 60% of approved anti-cancer agents are derived from plants. The plant raw material used in African traditional medicine and particularly in West Africa can be an important source for the research of anti-tumor drugs against gynecological cancers. These tumors have a negative impact on women's general health status and causes enormous health costs as they affect all age groups. Gynecological cancers remain thus a major concern worldwide, especially in West Africa where these cancers are the leading cause of cancer deaths in women. This review reports on the contribution of West African flora to the discovery of potential antiproliferative and/or cytotoxic phytochemical compounds against gynecological cancer cells. Scientific databases such as PubMed, ScienceDirect, Scopus and GoogleScholar were used to extract publications reporting West African plants and/or isolated compounds used in cell models of gynecological cancers. Thresholds of cytotoxicity and modes of action of these phytochemicals have been summarized. This research can serve as a basis for taking medicinal plants into account in the management of these gynecological cancers in resource-limited countries such as those in West Africa.

[Nodular amyloidoma associated with primary pulmonary Malt lymphoma]. / Amyloïdome associé à un lymphome du Malt pulmonaire primitif.

INTRODUCTION: Pulmonary amyloïdoma is a nodular formation containing amyloid deposits, which can mimick a pulmonary carcinoma. Its etiologic diagnosis require the search of an underlying infectious disease, a connective tissue disorder or a lymphoma. CASE REPORT: We report the case of a 73 year old woman, asymptomatic, presenting an incidental pulmonary opacity in the left upper lobe, associated with hilar lymphadenopathies, positive on PET scan. The patient underwent a left superior lobectomy with mediastinal lymphadenectomy. Histologically, the nodule was composed of amylodosis deposits. It was surrounded by a dense lymphoïd infiltrate. The phenotype (CD20+, CD5-, CD3-, CD23-) of the lymphoïd cells, like the demonstration of a lambda light chain restriction permited to pose the diagnostic of pulmonary Malt lymphoma and to characterize the AL lambda type of the amyloïdosis CONCLUSION: Association of amyloïdoma and Malt lymphoma is a rare condition. The histologic diagnosis of lymphoma may be difficult in this case, the lymphomatous process being concealed by the volume of the amyloïd mass. Therefore it is necessary in case of amyloïdoma to search histological signs of Malt lymphoma and to confirm diagnosis by demonstrating a B clonality and a immunoglobulin light chains restriction.

[Epidemiology and delays in the management of 355 patients with lung cancer]. / Epidémiologie et délais de prise en charge de 355 patients atteints de cancer bronchique.

BACKGROUND: The epidemiology of patients with lung cancer in a Seine-Saint-Denis hospital are reported, as well as causes of diagnostic and therapeutic delays in their management. MATERIAL AND METHODS: Retrospective analysis of cases diagnosed from January 1, 1997 to December 31, 2003. RESULTS: Of 355 cases, 15.8% were women; the average age was 62 +/- 11. Mean smoking history was 50 +/- 24 pack years. Women were more likely to be non-smokers than men (16% and 1% respectively, p < 0.01) and were more likely to present at a young age (under the age of 50: 26.8% and 13.7% respectively, p < 0.05). Among women, adenocarcinoma was more frequent (41% vs. 25%, p < 0.05), and often presented with stage IV disease (74%). Squamous cell carcinoma occurred more frequently with increasing age (18.7% vs. 32.2% before and after the age of 60, p < 0.01). The median pre hospital, diagnostic and treatment delays were respectively 30, 10 and 9 days, the global delay from first symptom to treatment was 62 days. Surgery increased therapeutic delay by 20 days. CONCLUSION: Our results are complementary to those found in KBP-2000-CPHG study. Young women are diagnosed at a late stage. Influence of delays on prognosis is not proved and require others studies.

Postural therapy for renal stones in children: A Rolling Stones procedure.

INTRODUCTION: Despite many advances, the management of renal stones - especially lower caliceal stones (LCS) - remains a challenge. The gravity-dependent location of the lower calices hinders the spontaneous clearance of fragments, which can be a nidus for future growth and symptomatic recurrence. Currently, there is no standard adjunctive therapy to facilitate fragment passage. OBJECTIVES: To report the safety and effectiveness of mechanical percussion diuresis and inversion (PDI) therapy for eliminating renal stones in children. PATIENTS AND METHODS: Since November 2013, children with residual fragments (after shock wave lithotripsy or flexible ureteroscopy) or native symptomatic renal stones were prospectively included in a protocol of four PDI sessions. After giving written consent, the children drank 10 ml/kg of water 30 min before therapy. They then laid in a prone Trendelenburg position on a couch angled at 45° and received continuous 10-min mechanical percussion applied over the affected flank by a physiotherapist (Figure summary). Tolerance stone burden reduction and stone clearance were documented with ultrasound 4 weeks after the last session. RESULTS: Seventeen participants, with a median age of 10.8 years (range 18 months to 18 years), received 82 PDI sessions performed over 22 months. The median stone diameter was 5 mm (range 3-9). All children tolerated the PDI therapy well. Over a median follow-up of 11 months (range 3-18), no significant adverse effects were noted. The overall stone-free rate was 65%. Four of the six patients with residual fragment passed their fragments. The patients who did not become stone free by PDI experienced a decrease in fragment size of 57% (range 34-71). The observance rate was 100%. DISCUSSION: Many studies have demonstrated that the gravity-dependent position of the lower calyces appears to be an important factor limiting the clearance of LCS. Positioning patients with a degree of inversion in order to put the collecting system beyond the horizontal plane affected the LCS through gravitational force. Complications were rare. PDI appeared to save costs and have similar success rates as shock wave lithotripsy for native small renal stones in children. CONCLUSION: PDI is safe and effective for facilitating gravity-dependent drainage of renal stones and provides an opportunity to treat children in a quick, non-invasive, economic, painless, non-radiative and diverting fashion. This therapy is a valuable alternative in the pattern of stone management. In case of persistent fragments, it is recommend that the number of sessions be increased to six.

Benign schwannoma of the digestive tract: a clinicopathologic and immunohistochemical study of five cases, including a case of esophageal tumor.

We report five cases of schwannomas of the digestive tract. The patients were two men and three women, whose ages ranged from 56 to 74 years. Three cases arose in the stomach, one in the ascending colon, and one in the esophagus; the latter was a hitherto unreported location for this tumor. The schwannomas ranged from 2 to 11 cm in diameter. They were well circumscribed but not encapsulated, with interlacing bundles of spindle cells, nuclear atypia and no mitosis, interspersed with collagenous strands. Inflammatory cells were scattered throughout the tumors and a peripheral cuff of lymphoid aggregates was observed in all cases. Intracellular periodic acid-Schiff (PAS)-positive crystalloids were found in three cases; no skeinoid fibers were seen. A diffuse and intense positivity for vimentin and S-100 protein was detected in all five cases together with a variable and sometimes focal positivity for glial fibrillary acidic protein and neuron-specific enolase. None of the tumors showed expression of CD34 or the smooth muscle antigens tested. The four cases with a sufficient follow-up had a favorable outcome without any recurrence or metastasis. The morphologic and immunohistochemical features of digestive schwannomas were compared with those of other gastrointestinal stromal tumors. Schwannomas have many differences. Digestive schwannomas can be readily recognized on histologic and immunohistochemical examination. They are spindle cell tumors without epithelioid features, with a peripheral cuff of lymphoid tissue. Specific intracellular needle-shaped PAS-positive crystalloids are found in some cases, whereas skeinoid fibers are not. These tumors always express S-100 protein in a diffuse and strong manner, and they express glial fibrillary acidic protein but not express CD34. Digestive schwannomas usually are gastric tumors and have never been reported in the small bowel. They pursue a benign course and are far rarer than gastrointestinal autonomic nerve tumors.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): two case reports.

Sinus histiocytosis with massive lymphadenopathy or Destombes-Rosai-Dorfman's syndrome is a rare benign disease of unknown etiology, usually seen in younger patients. The cases reported concerned a 15-month old Caucasian boy and an 8 year old black boy with unilateral cervical enlargement, occasional fever and without any extranodal involvement. Diagnosis was performed by superficial lymph node biopsy. No immunodeficiency was found. The patients received no therapy and a complete spontaneous resolution was seen after a few months in the two cases. The clinical presentation, histologic characteristics, pathogenesis and treatment of the Destombes-Rosai-Dorfman's syndrome are discussed.

[Clear cell sarcoma of the kidney in a young adult]. / Sarcome à cellules claires du rein chez un jeune adulte.

We report a case of clear cell sarcoma of kidney (CCSK), in a young adult. This highly malignant renal tumor usually arises in children of one or two year old and represents 4% of renal tumors. The aggressivity of this tumor and its affinity to give bone metastasis imply to recognize it in order to institute appropriate chemotherapy.

[Multiple clear cell kidney cysts and in situ renal clear cell carcinoma in a case of Hippel-Lindau disease]. / Kystes rénaux multiples à cellules claires et carcinome in situ à cellules claires dans un cas de maladie de von Hippel-Lindau.

Multiple cystic clear cell renal tumors and in situ renal clear cell carcinoma occurred in a woman with von Hippel-Lindau disease. Kidney lesions in von Hippel-Lindau disease are one of the main features including renal cysts and renal cell carcinoma. In situ renal clear cell carcinoma has not yet been reported.

[A rare etiology of hepatic steatosis associated with lactic acidosis: the toxicity of antiviral nucleoside analogues]. / Une étiologie rare de stéatose hépatique avec acidose lactique: la toxicité des analogues nucléosidiques anti-viraux.

We report three cases of hepatic steatosis associated with lactic acidosis occurring in HIV positive patients and due to a toxicity of antiviral nucleoside analogues. The clinico-pathological presentation was similar associating digestive signs (vomiting and abdominal pain), polypnea, lactic acidosis, a lethal clinical course, and an hepatomegaly with a diffuse macrovacuolar steatosis. The ultrastructural study performed in two cases showed mitochondrial alterations in hepatocytes. The toxicity of antiviral nucleoside analogues is due to a mitochondrial DNA polymerase inhibition. The incidence of this disease is actually low but probably underestimated. The diagnosis should be rapidly performed and the treatment immediatly interrupted.