Shorter Survival of SDF1-3′A/3′A Homozygotes Linked to CD4+ T Cell Decrease in Advanced Human Immunodeficiency Virus Type 1 Infection

The SDF-1 3′A allelic polymorphism has been reported to influence either positively or negatively the progression of human immunodeficiency virus type 1 (HIV-1) disease. Therefore, the SDF-1 genotype of 729 HIV-1-infected individuals pooled from 3 distinct cohorts was determined. A statistically nonsignificant association between the SDF1-3′A/3′A genotype and accelerated disease progression was evident among seroconverters (n = 319), but a striking correlation of decreased survival after either diagnosis of AIDS according to the 1993 definition or loss of CD4+ T cell counts <200 was observed. The relative hazards for SDF1-3′A/3′A homozygotes, compared with heterozygotes and wild-type homozygotes were 2.16 (P = .0047), for time from diagnosis according to the 1993 Centers for Disease Control and Prevention AIDS case definition (AIDS-'93) to death, and 3.43 (P = .0001), for time from CD4+ T cells <200 to death. Because no difference in survival was observed after diagnosis according to AIDS-'87, the association of the SDF1-3′A/3′A genotype with the accelerated progression of late-stage HIV-1 disease appears to be explained for the most part by the loss of CD4+ T lymphocyte

Nef-specific CD45RA+ CD8+ T cells secreting MIP-1β but not IFN-γ are associated with nonprogressive HIV-1 infection

<p>Abstract</p> <p>Background</p> <p>Long-term survival of HIV-1 infected individuals is usually achieved by continuous administration of combination antiretroviral therapy (ART). An exception to this scenario is represented by HIV-1 infected nonprogressors (NP) which maintain relatively high circulating CD4+ T cells without clinical symptoms for several years in the absence of ART. Several lines of evidence indicate an important role of the T-cell response in the modulation of HIV-1 infection during the acute and chronic phase of the disease.</p> <p>Results</p> <p>We analyzed the functional and the differentiation phenotype of Nef- and Tat-specific CD8+ T cells in a cohort of HIV-1 infected NP in comparison to progressors, ART-treated seropositive individuals and individuals undergoing a single cycle of ART interruption. We observed that a distinctive feature of NP is the presence of Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma. This population was present in 7 out of 11 NP. CD45RA+ IFN-gamma^negMIP-1beta+ CD8+ T cells were not detected in HIV-1 infected individuals under ART or withdrawing from ART and experiencing a rebounding viral replication. In addition, we detected Nef-specific CD45RA+ IFN-gamma^negMIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1 infected individuals with untreated progressive disease.</p> <p>Conclusion</p> <p>The novel antigen-specific CD45RA+ IFN-gamma^negMIP-1beta+ CD8+ T cell population represents a new candidate marker of long-term natural control of HIV-1 disease progression and a relevant functional T-cell subset in the evaluation of the immune responses induced by candidate HIV-1 vaccines.</p

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

[Zero-fluoroscopy transcatheter ablation and CRT-D implantation: new frontiers of electroanatomical mapping systems]

In cardiac resynchronization therapy (CRT) implantation procedures, contrast-induced nephropathy risk and ionizing radiation exposure can be eliminated using electroanatomical mapping system (EAMS). Under EAMS guidance, it is possible to place the left ventricular catheter in the branch of the coronary sinus that presents the latest activation. The use of EAMS allows for both arrhythmic ablation and CRT implantation to be obtained in a single, "zero fluoroscopy" procedure. Here we report two cases of successful arrhythmia ablation and CRT-D implantation with "zero fluoroscopy" in a single procedure

Left bundle branch area pacing (LBBAP) Auto Threshold algorithms Evaluation for Conduction System Pacing: The LATECS pilot Trial

BackgroundAutomated threshold measurements (ATM) and output adaptation improved safety and follow-up of cardiac implantable devices (CIED) in the last years. These algorithms were validated for conventional cardiac pacing; however, they were not suitable for permanent His Pacing. Left bundle branch area pacing (LBBAP) is an emerging technique to obtain physiologic cardiac stimulation; we tried to assess if ATM could be applied to this setting. MethodsConsecutive patients receiving ATM-capable CIED and LBBAP in our hospital were enrolled in this prospective, observational trial; they were evaluated 3 months after implant, comparing pacing thresholds manually assessed and obtained via ATM. Subsequent remote follow-up was carried on when available. ResultsForty-five patients were enrolled. ATM for LBBAP lead provided consistent results in all the patients and was therefore activated; mean value of manually obtained LBBAP capture threshold was 0.66 & PLUSMN; 0.19 V versus ATM of 0.64 & PLUSMN; 0.19 V. TOST analysis showed equivalence of the two measures (p = .66). At subsequent follow-up (mean follow up 7.7 & PLUSMN; 3.2 months), ATM was effective in assessing pacing thresholds and no clinical adverse event was observed. ConclusionsATM algorithms proved equivalent to manual testing in determining capture threshold and were reliably employed in patients receiving LBBAP CIED

Idiopathic hydrocephalic dementia in aging brain the neurosurgical approach

On the basis of our 16 years' experience, we have treated 36 patients by extrathecal shunt for idiopathic normal pressure hydrocephalus. All patients were submitted to clinical evaluation, neuroradiological, and neuropsychological (Mini Mental Test) tests. Seventy-six per cent of patients showed a significant clinical improvement. No change was found in 24% of them, including two patients who died. In a group of 13 patients we measured the level of main neurotransmitter metabolites (MHPG, HVA, 5-HIAA) in order to evaluate the functional status of encephalic monoaminergic system. If care is taken to make a correct diagnosis and give adequate treatment with a shunt, hydrocephalic dementia has a good prognosi