Context and Aim: Ventilator-associated pneumonia (VAP) remains to be the commonest cause of hospital morbidity and mortality in spite of advances in diagnostic techniques and management. This project aims to study the various risk factors and the common microbial flora associated with VAP. It also evaluates the use of APACHEIII scores for prognostication. Study Design: A prospective cohort study was conducted over 1 year in medical critical care unit (CCU) of a tertiary-care teaching hospital. Methods and Material: VAP was diagnosed using the clinical pulmonary infection score (CPIS) of more than 6. The study cohort comprised 51 patients. All CCU patients requiring mechanical ventilation for more than 48 h formed the study group. Statistical Analysis Used: Univariate analysis, χ 2-test, and paired "t-test." Results: Twenty four out of fifty-one cases developed VAP. These cases had an average APACHEIII score of more than 55 on admission to critical care unit (CCU). They needed prolonged mechanical ventilation and had lower PaO /FiO ratio as compared with the remaining patients who did not develop VAP. Pseudomonas aeroginosa 2 2 was the commonest and most lethal organism. The mortality in the VAP group was 37% and correlated very well with higher APACHEIII scores on admission. Conclusions: Longer duration of mechanical ven tilation and the need of reintubation are associated with proportionate rise in the incidence of VAP. Deterio rating PaO2/FiO ratio correlated well with the onset of VAP. Higher APACHEIII scores on admission 2 stratify the mortality risk.

Background: Disease progression monitoring through CD4 counts alone can be inadequate in HIV infection as ongoing immune activation may result in Serious non-AIDS events (SNAEs). SNAEs involve monocyte activation driven chronic inflammation with significant sequelae observed even during HAART. Here, we attempted to delineate functional monocyte based signatures across stages of HIV disease progression.Methods: Participants spanning four cohorts were recruited—pre-ART (PA; <7 years of infection; n = 20), long-term non-progressors (LTNP; >7 years of infection, CD4 > 350 cells/μL, n = 20), individuals on therapy (ART; n = 18) and seronegative controls (SN; n = 15). Immunophenotyping of monocyte subsets and evaluation of expression of HIV-binding receptors—CD4 and CCR5, marker of immune activation- HLA-DR and M2 phenotype—mannose receptor (CD206) was followed by association of monocyte-specific parameters with conventional markers of disease progression such as absolute CD4 count, CD4/CD8 ratio, viral load, and T cell activation.Results: A significant expansion of intermediate monocytes (CD14++CD16+) with a concomitant decline in classical subset (CD14++CD16–) was observed in all infected cohorts compared to seronegative controls. In addition, an expansion of the non-classical subset (CD14+CD16++) was observed in long-term non-progressors. Dysregulation in monocyte subsets associated with CD4 count and CD4/CD8 ratio in PAs but not in LTNPs. We report for the first time that expression of CD206 is most prominent on intermediate monocytes which also have the highest expression of CD4, CCR5, and HLA-DR. Despite preserved CD4 counts, LTNPs had similar immune activation profiles to PAs, as evidenced by elevated HLA-DR expression across monocyte subsets. HLA-DR expression, similar to that in SNs, observed in the ART group indicated partial immune restoration within the monocyte compartment. Increased CD206 expression on monocytes together with frequency of activated CD4+ T lymphocytes (HLA-DR+CD38+) showed significant and positive association with viral load in LTNPs, but not PAs.Conclusion: Our results describe for the first time the presence of monocyte dysregulation involving increased activation in LTNPs, who, in spite of preserved CD4 counts, may remain susceptible to prolonged effects of systemic inflammation and highlight CD206, as a unique non-T correlate of viremia, in viremic non-progression.

Aims of this study: Severe acute pancreatitis has been defined recently based on the persistence of organ failure at 48 hours of admission. The bedside index for severity in acute pancreatitis (BISAP) score, a simplified scoring system to predict severity of acute pancreatitis, is proposed to be useful in early risk stratification of acute pancreatitis. Our aim was to prospectively compare BISAP score with the already established acute physiology and chronic health evaluation II (APACHE II) and modified computed tomography severity index (CTSI) scores in predicting the severity of acute pancreatitis. Materials and methods: A total of 87 consecutive cases presenting with the first attack of acute pancreatitis were included in the study. Acute physiology and chronic health evaluation II and BISAP scores were calculated from the worst parameters in the first 24 hours, and modified CTSI was reported at 48 hours of admission. Receiver-operating characteristic (ROC) curves were plotted, and predictive accuracy of each score was calculated from the area under the curve. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each score. Results: A total of 20 patients (23%) had severe acute pancreatitis with a total of 11 mortalities (12.64%), 10 of them in the severe acute pancreatitis group. Acute physiology and chronic health evaluation II, modified CTSI, and BISAP score all correlated well with each other. Modified CTSI and BISAP score also correlated with duration of hospital stay. Areas under the curve for APACHE II (≥8), modified CTSI (≥8), and BISAP score (≥2) were 0.826, 0.806, and 0.811, respectively, suggesting similar predictive accuracy. Conclusion:The BISAP score was similar to APACHE II and modified CTSI in terms of accuracy, sensitivity, specificity, and NPV. It is much easier to calculate and a useful risk stratification tool. It should be used for early triage and referral to a high dependency unit.

Viremic non-progressors (VNPs), a distinct group of HIV-1-infected individuals, exhibit no signs of disease progression and maintain persistently elevated CD4+ T cell counts for several years despite high viral replication. Comprehensive characterization of homeostatic cellular immune signatures in VNPs can provide unique insights into mechanisms responsible for coping with viral pathogenesis as well as identifying strategies for immune restoration under clinically relevant settings such as antiretroviral therapy (ART) failure. We report a novel homeostatic signature in VNPs, the preservation of the central memory CD4+ T cell (CD4+ T CM) compartment. In addition, CD4+ T CM preservation was supported by ongoing interleukin-7 (IL-7)-mediated thymic repopulation of naive CD4+ T cells leading to intact CD4+ T cell homeostasis in VNPs. Regulatory T cell (Treg) expansion was found to be a function of preserved CD4+ T cell count and CD4+ T cell activation independent of disease status. However, in light of continual depletion of CD4+ T cell count in progressors but not in VNPs, Tregs appear to be involved in lack of disease progression despite high viremia. In addition to these homeostatic mechanisms resisting CD4+ T cell depletion in VNPs, a relative diminution of terminally differentiated effector subset was observed exclusively in these individuals that might ameliorate consequences of high viral replication. VNPs also shared signatures of impaired CD8+ T cell cytotoxic function with progressors evidenced by increased exhaustion (PD-1 upregulation) and CD127 (IL-7Rα) downregulation contributing to persistent viremia. Thus, the homeostatic immune signatures reported in our study suggest a complex multifactorial mechanism accounting for non-progression in VNPs.

BackgroundHIV-2 infection is characterised by a longer asymptomatic phase and slower AIDS progression than HIV-1 infection. Identifying unique immune signatures associated with HIV-2 pathogenesis may thus provide therapeutically useful insight into the management of HIV infection. This study examined the dynamics of the CD4+T cell compartment, critical in disease progression, focussing on chronic HIV-2 and HIV-1 infected individuals at various stages of disease progression.MethodsA total of 111 participants including untreated and treated HIV infected individuals and seronegative individuals were enrolled in this study. The relative proportion of CD4+T cell subsets, expressing CD25 (IL-2Rα) and CD127 (IL-7R), in HIV infected individuals and seronegative controls were assessed by multiparametric flow cytometry. Additionally, levels of immune activation and cytotoxic T lymphocytes in both the CD4+T and CD8+T cell compartments was evaluated.ResultsBoth treated and untreated, HIV-1 and HIV-2 infected individuals showed apparent dysregulation in CD4+ T cell subset frequency that was associated with disease progression. Furthermore, longitudinal sampling from a group of HIV-1 infected individuals on virologically effective ART showed no significant change in dysregulated CD4+T cell subset frequency. For both ART naïve and receiving groups associations with disease progression were strongest and significant with CD4+ T cell subset frequency compared to per cell expression of IL-2Rα and IL-7Rα. In untreated HIV-2 infected individuals, T cell activation was lower compared to ART naïve HIV-1 infected individuals and higher than seronegative individuals. Also, the level of Granzyme-B expressing circulating T cells was higher in both ART-naïve HIV-1 and HIV-2 infected individuals compared to seronegative controls.ConclusionDysregulation of IL-2 and IL-7 homeostasis persists in CD4+T cell subsets irrespective of presence or absence of viremia or antiretroviral therapy in HIV infection. Furthermore, we report for the first time on levels of circulating Granzyme-B expressing CD4+T and CD8+T cells in chronic HIV-2 infection. Lower immune activation in these individuals indicates that persistent immune activation driven CD4+T cell depletion, as observed in untreated HIV-1 infected individuals, may not be as severe and provides evidence for a disparate pathogenesis mechanism. Our work also supports novel immunomodulatory therapeutic strategies for both HIV-1 and HIV-2 infection.Electronic supplementary materialThe online version of this article (10.1186/s12879-019-3743-7) contains supplementary material, which is available to authorized users.