Plasma Virome of HIV-infected Subjects on Suppressive Antiretroviral Therapy Reveals Association of Differentially Abundant Viruses with Distinct T-cell Phenotypes and Inflammation.

Background: The plasma virome represents the overall composition of viral sequences present in it. Alteration in plasma virome has been reported in treatment naïve and immunocompromised (CD4 count < 200) people with HIV (PWH). However, the effect of ART on virome composition in PWH on ART with preserved CD4 counts is poorly understood. Objectives: We aimed to assess the alterations in plasma virome in PWH on ART in comparison to HIV-negative uninfected controls and to further investigate possible associations of plasma viruses with inflammation and immune dysfunction, namely, immunosenescence and immune exhaustion. Methods: Plasma viral DNA from PWH on ART and controls was used for sequencing on the Illumina Nextseq500 platform, followed by the identification of viral sequences using an automated pipeline, VIROMATCH. Multiplex cytokine assay was performed to measure the concentrations of various cytokines in plasma. Immunophenotyping was performed on PBMCs to identify T cell markers of immunosenescence and immune exhaustion. Results: In our observational, cross-sectional pilot study, chronically infected PWH on ART had significantly different viral species compositions compared to controls. The plasma virome of PWH showed a significantly high relative abundance of species Human gammaherpesvirus 4, also known as Epstein-Barr virus (EBV). Moreover, EBV emerged as a significant viral taxon differentially enriched in PWH on ART, which further correlated positively with the exhaustion phenotype of T cells and significantly increased TNF-α in PWH on ART. Additionally, a significantly increased proportion of senescent T cells and IL-8 cytokine was detected in PWH on ART. Conclusion: Altered plasma virome influenced the inflammatory response and T-cell phenotype in PWH on ART.

Comparison of a Novel Score "NOD-ACLF" to Other Established Prognostic Scores for Prediction of Mortality in APASL-ACLF Patients: A Cohort Study from a Tertiary Care Center of North India.

Background: Commonly used prognostic scores for acute on-chronic liver failure (ACLF) have complex calculations. We tried to compare the simple counting of numbers and types of organ dysfunction to these scores, to predict mortality in ACLF patients. Methods: In this prospective cohort study, ACLF patients diagnosed on the basis of Asia Pacific Association for Study of the Liver (APASL) definition were included. Severity scores were calculated. Prognostic factors for outcome were analysed. A new score, the Number of Organ Dysfunctions in Acute-on-Chronic Liver Failure (NOD-ACLF) score was developed. Results: Among 80 ACLF patients, 74 (92.5%) were male, and 6 were female (7.5%). The mean age was 41.0±10.7 (18-70) years. Profile of acute insult was; alcohol 48 (60%), sepsis 30 (37.5%), variceal bleeding 22 (27.5%), viral 8 (10%), and drug-induced 3 (3.8%). Profiles of chronic insults were alcohol 61 (76.3%), viral 20 (25%), autoimmune 3 (3.8%), and non-alcoholic steatohepatitis 2 (2.5%). Thirty-eight (47.5%) were discharged, and 42 (52.5%) expired. The mean number of organ dysfunction (NOD-ACLF score) was ->4.5, simple organ failure count (SOFC) score was >2.5, APASL ACLF Research Consortium score was >11.5, Model for End-Stage Liver Disease-Lactate (MELD-LA) score was >21.5, and presence of cardiovascular and respiratory dysfunctions were significantly associated with mortality. NOD-ACLF and SOFC scores had the highest area under the receiver operating characteristic to predict mortality among all these. Conclusion: The NOD-ACLF score is easy to calculate bedside and is a good predictor of mortality in ACLF patients performing similar or better to other scores.

Study of pattern and outcome of acute poisoning cases at tertiary care hospital in North India.

Introduction: The WHO 2021 data estimate that 2 million lives and 53 million disability-adjusted life-years were lost in 2019 due to exposures to selected chemicals. It is important to know the pattern and outcome of acute poisoning cases for proper planning, prevention and management. Knowing the pattern will also help in designing training modules for primary care physicians to make them aware about newer poisons and their management. Awareness regarding newer poisons consumed is necessary for early identification, initial management and timely referral to higher centres by primary care physicians. This study was performed to see the pattern and outcome of acute poisoning cases in North Indian population and various factors related to outcome. Materials and Methods: This study was conducted in department of medicine of a teaching institute in North India after approval by the Institutional Review Board. Patients admitted in the department during the study and fulfilling the inclusion criteria were enrolled in the study after obtaining consent. Results: A total of 417 patients with poisoning were recruited in the study. Out of 417 patients, majority were males (59.5%). Maximum number of patients were in the age group of 21-30 years (33.8%), and rural population (79.9%) was found to be more affected. Most of the patients were students and private employees. Most common types of poisoning were snakebite (n = 109, 26.1%), organophosphate (n = 49, 11.8%) and aluminium phosphide (n = 39, 9.3%). Out of 417 patients, 349 (83.69%) improved, while 68 (16.3%) expired. Requirement of ventilatory support was most commonly associated with aluminium phosphide poisoning (30.12%) followed by organophosphate poisoning (24.1%). Conclusion: Poisoning was more common in young males and more prevalent in rural population. Pesticides and snakebite were major causes of poisoning. Among suicidal cases, family conflict (problem/altercation with family members/marital discord) was main reason for the consumption of poison. There is need for creation of poison information centre along with separate toxicological units in tertiary care hospitals.

Is International HIV Dementia Scale good enough to diagnose HIV-associated neurocognitive disorders?

Introduction: Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) comprise impairment of multiple cognitive domains and cause significant morbidity. International HIV Dementia Scale (IHDS) is a quite sensitive and specific method for screening for HAND, and Modified Mini-Mental State Examination (3MS), though nonspecific, contains more parameters for screening for neurocognition. Hence, we compared 3MS and IHDS as screening tools for HAND with an aim to find out which was a better screening tool for HAND. Methods: Using 3MS and IHDS, we assessed the cognitive status of 200 HIV-positive patients (65% males) and 84 controls, presenting to the Department of Medicine, King George's Medical University, Lucknow, India from September 2015 to September 2019. Results: According to 3MS, 42 (21%) HIV-positive patients were neurocognitively impaired (mean 76.24 ± 1.51), and 158 (79%) patients were not (mean 87.02 ± 4.16). As per IHDS, 185 (92.5%) HIV patients were neurocognitively impaired (mean 8.45 ± 0.88), and 15 (7.5%) patients were not (mean 11.13 ± 0.35). The mean 3MS score of controls was 87.56 ± 4.26, and the IHDS score was 9.73 ± 1.00. According to Patient Health Questionnaire-9 (PHQ-9), moderate depression occurred in only 3.5% of the patients, and the rest had only minimal or mild depression. In IHDS, psychomotor speed was the most affected parameter, whereas in 3MS, similarities were the most affected. Conclusion: IHDS may be over diagnosing neurocognitive impairment in HIV patients due to difficulty in understanding the test, especially psychomotor speed testing. 3MS may be more accurate for detecting neurocognitive impairment in HIV patients, and scale combining both these methods may be a still better choice.

Prevalence of obstructive sleep apnea in diabetic patients.

Context: Obstructive sleep apnea (OSA)-related hypoxemia stimulates release of acute-phase proteins and reactive oxygen species that exacerbate insulin resistance and lipolysis and cause an augmented prothrombotic and proinflammatory state which can leads to premature death. Aims: This study aims to study the prevalence of OSA in diabetic patients. Setting and Design: It was a cross-sectional study, done over a period of 1 year in a tertiary care hospital. Materials and Methods: A total of 149 type 2 diabetic patients were enrolled after taking written consent. All patients were subjected to STOP BANG questionnaire and patients falling in intermediate-high risk (score 3-8), were taken for overnight polysomnography to confirm the diagnosis of OSA (apnea hypopnea index ≥ 5). Statistical Analysis Used: Statistical Package for Social Sciences (SPSS) Version 21.0 statistical analysis software. Results: Fifty-five percent of our diabetic population were having OSA. The age of patients enrolled in the study ranged between 30 and 86 years and prevalence increases with an increase in age groups. Majority (61.7%) of our cases were males. Incremental trend in weight, body mass index (BMI), neck circumference, and waist circumference of OSA cases were found with increasing in severity of OSA. Mean levels of raised blood sugar and HbA1c were higher in severe OSA cases. Conclusions: OSA has a high prevalence in patients with type 2 diabetes mellitus. Patients with type 2 diabetes should be screened for OSA, even in the absence of symptoms, especially in individuals with higher waist circumference and BMI.

RésuméContexte: L'hypoxémie liée à l'apnée obstructive du sommeil (AOS) stimule la libération de protéines de phase aiguë et d'espèces réactives de l'oxygène qui exacerber la résistance à l'insuline et la lipolyse et provoquer un état prothrombotique et pro-inflammatoire accru qui peut conduire à un décès. Objectifs: Cette étude vise à étudier la prévalence de l'AOS chez les patients diabétiques. Cadre et conception: il s'agissait d'une étude transversale, réalisée sur une période d'un an dans un hôpital de soins tertiaires. Matériels et méthodes: Un total de 149 patients diabétiques de type 2 ont été recrutés après avoir pris consentement écrit. Tous les patients ont été soumis au questionnaire STOP BANG et les patients à risque intermédiaire-élevé (score 3-8), ont été prise pour une polysomnographie nocturne pour confirmer le diagnostic d'AOS (index d'apnée hypopnée ≥ 5). Analyse statistique utilisée: statistique Package for Social Sciences (SPSS) Version 21.0 du logiciel d'analyse statistique. Résultats: Cinquante-cinq pour cent de notre population diabétique étaient souffrant d'AOS. L'âge des patients inclus dans l'étude variait entre 30 et 86 ans et la prévalence augmente avec l'augmentation des tranches d'âge. La majorité (61,7 %) de nos cas étaient des hommes. Tendance progressive du poids, de l'indice de masse corporelle (IMC), du tour de cou et du tour de taille des cas d'AOS ont été trouvés avec une augmentation de la sévérité de l'AOS. Les taux moyens de glycémie élevée et d'HbA1c étaient plus élevés dans les cas graves d'AOS. Conclusions: L'AOS a une prévalence élevée chez les patients atteints de diabète de type 2. Les patients atteints de diabète de type 2 doivent subir un dépistage de l'AOS, même en l'absence de symptômes, en particulier chez les personnes ayant un tour de taille et un IMC plus élevés.

Flow cytometric analysis of aneuploidy and S-phase fraction in chronic myeloid leukemia patients: role in early detection of accelerated phase.

We studied S-phase fraction (SPF) and aneuploidy in peripheral blood leucocytes of patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP, n=41), accelerated phase (CML-AP, n=6), and control subjects (n=12) with an aim to find out their role in early detection of accelerated phase. The SPF and aneuploidy were studied through flow-cytometry using LT-Mod. Fit software. Mean SPF value in CML-AP (9.28+/-3.46%) and in CML-CP (4.76+/-2.30%) were significantly higher than in normal controls (0.28+/-0.21%), (P<0.005, P<0.001). CML-CP patients having higher SPF (>7%) converted to accelerated phase within 18 months of follow-up while those with lower SPF (<7%) did not. Aneuploidy was present in 34.14% of CML-CP and all patients of CML-AP whereas no control subjects showed aneuploidy. Among CML-CP patients having SPF >7%, 86% developed aneuploidy during follow-up as compared to 18.50% of CML-CP with less than 7% SPF. We conclude that peripheral blood SPF and aneuploidy could be important parameters for prediction of evolution to accelerated phase in CML patients.

Peripheral blood leucocytes ornithine decarboxylase activity in chronic myeloid leukemia patients: prognostic and therapeutic implications.

Leukocytes ornithine decarboxylase (ODC) activity was measured in normal individuals and in patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP) as well as in accelerated phase (CML-AP), with an aim to examine the role of ODC activity in prognostic evaluation of CML patients. Our results showed that ODC activity was significantly higher in CML-CP (41.02+/-25.57nmol/h per 10(7) cells, P<0.005) and CML-AP (67.71+/-44.42nmol/h per 10(7) cells, P<0.001) patients than in normal subjects (3.12+/-1.34nmol/h per 10(7) cells). Furthermore, patients with CML-AP showed higher ODC activity than CML-CP patients (P<0.005). Patients with CML-CP who converted to accelerated phase within 24 months had higher ODC activity (84.58+/-12.81nmol/h per 10(7) cells) than patients who did not convert to accelerated phase (31.13+/-18.24nmol/h per 10(7) cells). The high value of ODC activity was also associated with less clinico-hematological response. We suggest that ODC activity reflects the neoplastic proliferative activity in CML patients and may serve as an additional prognostic marker.