IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and MethodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

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Importance: An exacerbated inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is believed to be one of the major causes of the morbidity and mortality of the coronavirus disease 2019 (COVID-19). Neuromodulation therapy, based on vagus nerve stimulation, was recently hypothesized to control both the SARS-CoV-2 replication and the ensuing inflammation likely through the inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells pathway and could improve the clinical outcomes as an adjunct treatment. We proposed to test it by the stimulation of the auricular branch of the vagus nerve, i.e., auricular neuromodulation (AN), a non-invasive procedure through the insertion of semipermanent needles on the ears.Objective: The aim of this study was to assess the effect of AN on the clinical outcomes in patients affected by COVID-19.Design, Setting, and Participants: A multicenter, randomized, placebo-controlled, double-blind clinical trial included 31 patients with respiratory failure due to COVID-19 requiring hospitalization. Within 72 h after admission, patients received either AN (n = 14) or sham neuromodulation (SN, n = 15) in addition to the conventional treatments.Main Outcome and Measures: The primary endpoint of the study was the rate of a clinical benefit conferred by AN at Day 14 (D14) as assessed by a 7-point Clinical Progression Scale. The secondary endpoint of the study was the impact of AN on the rate of transfer to the intensive care unit (ICU) and on the survival rate at D14.Results: The AN procedure was well-tolerated without any reported side effects but with no significant improvement for the measures of both primary (p > 0.3) and secondary (p > 0.05) endpoints at the interim analysis. None of the AN-treated patients died but one in the SN group did (81 years). Two AN-treated patients (73 and 79 years, respectively) and one SN-treated patient (59 years) were transferred to ICU. Remarkably, AN-treated patients were older with more representation by males than in the SN arm (i.e., the median age of 75 vs. 65 years, 79% male vs. 47%).Conclusion: The AN procedure, which was used within 72 h after the admission of patients with COVID-19, was safe and could be successfully implemented during the first two waves of COVID-19 in France. Nevertheless, AN did not significantly improve the outcome of the patients in our small preliminary study. It is pertinent to explore further to validate AN as the non-invasive mass vagal stimulation solution for the forthcoming pandemics.Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [NCT04341415].

CASE REPORTAn 87-year-old man was initially hospitalized in the FrancoVietnamese Hospital in Ho Chi Minh City in Vietnam for abdominal pain, fever, chills and anorexia. Laboratory examination showed a leukocyte count of 20,900 cells/mm 3 90% neutrophiles. The C-reactive protein level was 170 mg/L and results of hepatic tests were abnormal with elevated levels of liver enzymes (alkaline phosphatase and γ-glutamyltransferase) 15-fold higher than normal values. A computed tomography (CT) scan of the abdomen showed many focal hepatic lesions.On initial aspiration of the abdominal lesions, 300 mL of brown fluid was obtained, followed by another 150 mL. Pus was sterile, but the amebic serologic results were positive (agglutination and enzyme-linked immunosorbent assay; Biotrin International, Dublin, Ireland). He was treated with metronidazole, 500 mg, three times a day, and ofloxacin, 200 mg twice a day, for five days and then only metronidazole for a week.Because of persistent hepatic pain, he was referred to our infectious and tropical diseases unit in France. The patient was afebrile and had a tender right upper quadrant of the liver, subconjunctival jaundice, and bilateral lower limb pitting edema without any portal hypertension signs. He had a weight gain of 4 kg. A chest radiograph showed pleural effusion, and a contrast abdominal CT scan showed a hypodense filling defect, suggestive of thrombus in the median hepatic vein, after the hepatic and portal venous phase ( Figure 1 ).Congenital and acquired thrombophilia tests were conducted. These tests included autoimmune investigations and a screening for protein C or S deficiency, Factor II, Factor V Leiden gene mutations, myeloproliferative diseases, antiphospholipid syndrome, and hyperhomocysteinemia. All test results were negative. In addition, there were no underlying comorbidities that could facilitate venous thrombosis.Progressive recovery was seen after therapeutic anticoagulation by low molecular weight heparin (enoxaparine) given concomitantly with a vitamin K antagonist (fluindione) for three days and then fluindione alone for six months. The patient also received metronidazole, 500 mg three times a day for 3 days to complete the 14-day therapy initiated in Vietnam. Re-evaluation with an abdominal CT scan six months later showed partial regression of hepatic lesions and total regression of the thrombus.The worldwide incidence of symptomatic amebiasis (colitis and liver abscess) is estimated to be approximately 50 million cases annually, with liver abscess in perhaps 1% of the cases. 1The causative protozoan parasite, Entamoeba histolytica , is a virulent pathogen. Trophozoites of E. histolytica invade the intestinal mucosa, causing amebic colitis, and can breach the mucosal barrier and travel through the portal circulation to the liver.1 Amebic liver abscess is the most common extraintestinal manifestation of amebiasis, and is often characterized by a painful and enlarged liver associated with fever. This abscess consists of a few E. histolytica trophozoi...

Among the diversified etiological spectrum of CMI, cosmopolitan infections are widely predominant, particularly viral infections, followed by tropical causes, of which malaria is the leading disease in returnees from endemic areas. The diagnostic approach should be driven by history and physical examination. Key investigations include: blood smear, cerebrospinal fluid polymerase chain reaction and culture as well as neuroimaging. Management should focus on curable causes.

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