Intracranial tuberculous mass lesions treated with thalidomide in an immunocompetent child from a low tuberculosis endemic country: A case report

Rationale: Tuberculous meningitis is a highly morbid, often fatal disease. Patient concern: We describe a case of an Italian child. Diagnoses: we diagnosed early a Tuberculous meningitis complicated by the occurrence of hydrocephalus, stroke, and paradoxical reaction with brain pseudo-abscesses. Interventions: The child started readily a specific therapy associated with steroids and thalidomide was introduced few month later. Outcomes: the patient had a favorable outcome without neurologic sequelae. Lessons: Despite the prompt specific anti-tubercular and adjuvant corticosteroid therapies, only the addition of thalidomide to the treatment allow to a favorable clinical outcome

Higher levels of osteoprotegerin and immune activation/immunosenescence markers are correlated with concomitant bone and endovascular damage in HIV-suppressed patients

HIV-infected patients appear to have a significantly greater risk of non-AIDS comorbidities such as osteoporosis and atherosclerosis. Subjects with osteoporosis are at a higher risk of developing cardiovascular disease than those with normal bone mass, therefore a possible relation between these two conditions can be hypothesized. In the setting of HIV infection, several factors might contribute to bone disease and endothelial dysfunction. The aim of our study was to evaluate the relationship between bone and cardiovascular disease and to investigate the role of traditional factors, T-cell phenotype and osteoprotegerin in HIV positive subjects on effective antiretroviral therapy. We included 94 HIV positive subjects on antiretroviral therapy with virological suppression and 41 healthy subjects matched for age and gender as a control group. Carotid-Intima Media Thickness (c-IMT) and bone mineral density (BMD) were performed by ultrasound and DEXA, respectively. CD4+/CD8+ T-cell activation, senescence and osteoprotegerin plasma levels were measured by flow-cytometry and ELISA, respectively. Among HIV positive patients, 56.4% had osteopenia/osteoporosis and 45.7% had pathological c-IMT (>0.9mm). Subjects with pathological c-IMT and BMD exhibited higher CD4+ and CD8+ activated, CD8+ senescent and osteoprotegerin than subjects with normal c-IMT and BMD. HIV positive subjects with osteopenia/osteoporosis had higher c-IMT than subjects with normal BMD, and linear regression analysis showed a negative correlation between BMD and c-IMT. Several factors are implicated in the pathogenesis of non-AIDS comorbidities in HIV positive patients. Osteoprotegerin together with inflammation and immunosenescence in HIV positive patients could affect bone and vascular system and could be considered as a possible common link between these two diseases

Immunological diagnosis as an adjunctive tool for an early diagnosis of tuberculous meningitis of an immune competent child in a low tuberculosis endemic country: A case report

Background: Pediatric tuberculous meningitis is a highly morbid, often fatal disease. Its prompt diagnosis and treat - ment saves lives, in fact delays in the initiation of therapy have been associated with high mortality rates. Case presentation: This is a case of an Italian child who was diagnosed with tuberculous meningitis after a history of a month of headache, fatigue and weight loss. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis with predominance and decreased glucose concentration. Microscopy and conventional diagnostic tests to identify Myco - bacterium tuberculosis were negative, while a non classical method based on intracellular cytokine flow cytometry response of CD4 cells in cerebral spinal fluid helped us to address the diagnosis, that was subsequently confirmed by a nested polymerase chain reaction amplifying a 123 base pair fragment of the M. tuberculosis DNA. Conclusions: We diagnosed tuberculous meningitis at an early stage through an innovative immunological approach, supported by a nested polymerase chain reaction for detection of M. tuberculosis DNA. An early diagnosis is required in order to promptly initiate a therapy and to increase the patient’s surviva

HIV-2 infection in a migrant from Gambia: the history of the disease combined with phylogenetic analysis revealed the real source of infection

Human immunodeficiency virus type 2 (HIV-2) infection prevalence is increasing in some European countries. The increasing migratory flow from countries where HIV-2 is endemic has facilitated the spread of the virus into Europe and other regions. We describe a case of HIV-2 infection in a migrant individual in the Asylum Seeker Centre (ASC) in Italy. The patient's virus was sequenced, and found to be a typical HIV-2 genotype A virus. Bayesian evolutionary analysis revealed that the HIV-2 sequence from migrant dated back to 1986 in a subcluster including sequences from Guinea Bissau. This was coherent with the migrant history who lived in Guinea Bissau from his birth until 1998 when he was 13 years old. Monitoring for HIV-2 infection in migrants from western Africa is necessary using adequate molecular tools to improve the diagnosis and understand the real origin of infection

Dynamic changes of mmp-9 plasma levels correlate with jvc reactivation and immune activation in natalizumab-treated multiple sclerosis patients

The aim of the study was to investigate the changes of matrix metalloproteinase (MMP)-2 and MMP-9 plasma levels during natalizumab treatment and their correlation with JC virus (JCV) reactivation and T-lymphocyte phenotypic modifications in peripheral blood samples from 34 relapsing-remitting multiple sclerosis (RRMS) patients. MMP-9 levels were assessed by zymography in plasma samples. JCV-DNA was detected through quantitative real time PCR in plasma samples. T-lymphocyte phenotype was assessed with flow cytometry. MMP-9 plasma levels resulted increased from 12 to 24 natalizumab infusions. Stratifying plasma samples according to JCV-DNA detection, MMP-9 plasma levels were significantly increased in JCV-DNA positive than JCV-DNA negative samples. MMP-9 plasma levels resulted positively correlated with JCV viral load. CD4 immune senescence, CD8 immune activation and CD8 effector percentages were positively correlated to MMP-9 plasma levels, whereas a negative correlation between CD8 naïve percentages and MMP-9 plasma levels was found. Our data indicate an increase of MMP-9 plasma levels between 12 and 24 natalizumab infusions and a correlation with JCV-DNA detection in plasma, T-lymphocyte immune activation and senescence. These findings could contribute to understand PML pathogenesis under natalizumab treatment, suggesting a potential role of MMP-9 as a predictive marker of PML in RRMS patients

Application of machine learning approach in emergency department to support clinical decision making for SARS-CoV-2 infected patients

Abstract To support physicians in clinical decision process on patients affected by Coronavirus Disease 2019 (COVID-19) in areas with a low vaccination rate, we devised and evaluated the performances of several machine learning (ML) classifiers fed with readily available clinical and laboratory data. Our observational retrospective study collected data from a cohort of 779 COVID-19 patients presenting to three hospitals of the Lazio-Abruzzo area (Italy). Based on a different selection of clinical and respiratory (ROX index and PaO2/FiO2 ratio) variables, we devised an AI-driven tool to predict safe discharge from ED, disease severity and mortality during hospitalization. To predict safe discharge our best classifier is an RF integrated with ROX index that reached AUC of 0.96. To predict disease severity the best classifier was an RF integrated with ROX index that reached an AUC of 0.91. For mortality prediction the best classifier was an RF integrated with ROX index, that reached an AUC of 0.91. The results obtained thanks to our algorithms are consistent with the scientific literature an accomplish significant performances to forecast safe discharge from ED and severe clinical course of COVID-19

Modeling the contribution of male testosterone levels to the duration of positive COVID testing among hospitalized male COVID-19 patients

Background: A growing body of evidence is emerging suggesting testosterone can affect all cells involved in the immune response to both bacterial and viral infections, and the testosterone effect on the immune response could explain the greater susceptibility of men to infections including COVID-19. We aimed to explore the predictive role of male serum total testosterone (TT) levels on the time till viral negativity testing among hospitalized COVID-19 patients. Methods: The univariate effect of risk factors for the duration of COVID-19 viral positivity was evaluated using the log-rank test and Kaplan-Meier estimates. A multivariable Cox regression model was developed to test the role of TT levels and the subsequent odds for shorter viral positivity intervals. Results: Increasing serum TT levels and the need for an oxygen administration strategy were independently predictive for respectively reduced and increased days to negativization (Hazard Ratio [HR]: 1.39, 95% CI: 0.95-2.03 and HR: 0.19, 95% CI: 0.03-1.18). Conclusion: Baseline higher TT levels for male COVID-19 patients at hospital admission are associated with shorter durations of positive COVID-19 testing and thus viral clearance. Our preliminary findings might play a relevant to help pandemic control strategies if these will be verified in future larger multicentric and possibly randomized trials

Longitudinal virological and immunological profile in a case of human monkeypox infection

In a male with severe proctitis, monkeypox virus DNA was detected in skin lesions, blood, nasopharynx, and rectum, underlying the generalized viral spreading. Rectal involvement was still found when skin lesions disappeared. At the early-stage, increase of cytotoxic and activated T-cells, while reduction of CD56dimCD57+NK cells compared to recovery time-point was observed

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

The mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to vaccination

Blood biomarkers from the emergency department disclose severe omicron covid-19-associated outcomes

Background: Since its outbreak, Coronavirus disease 2019 (COVID-19), a life-threatening respiratory illness, has rapidly become a public health emergency with a devastating social impact. Lately, the Omicron strain is considered the main variant of concern. Routine blood biomarkers are, indeed, essential for stratifying patients at risk of severe outcomes, and a huge amount of data is available in the literature, mainly for the previous variants. However, only a few studies are available on early routine biochemical blood biomarkers for Omicron-afflicted patients. Thus, the aim and novelty of this study were to identify routine blood biomarkers detected at the emergency room for the early prediction of severe morbidity and/or mortality. Methods: 449 COVID-19 patients from Sapienza University Hospital of Rome were divided into four groups: (1) the emergency group (patients with mild forms who were quickly discharged); (2) the hospital ward group (patients that after the admission in the emergency department were hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients that after the admission in the emergency department required intensive assistance); (4) the deceased group (patients that after the admission in the emergency department had a fatal outcome). Results: ANOVA and ROC data showed that high-sensitivity troponin-T (TnT), fibrinogen, glycemia, C-reactive protein, lactate dehydrogenase, albumin, D-dimer myoglobin, and ferritin for both men and women may predict lethal outcomes already at the level of the emergency department. Conclusions: Compared to previous Delta COVID-19 parallel emergency patterns of prediction, Omicron-induced changes in TnT may be considered other early predictors of severe outcomes