Clinical Practice Guidelines for Management of Pain, Agitation, Delirium, Immobility, and Sleep Disturbance in the Intensive Care Unit: The ABCDEF Bundle.

It is crucial to prevent and manage intensive care unit (ICU) distress caused by a pentad of pain, agitation, delirium, immobility, and sleep disturbance (PADIS) to optimize immediate and longterm recovery and outcomes of critically ill patients. This clinical practice guideline provides an update on the prevention, management, and liberation of PADIS in adult ICU patients using an integrated, evidence-based, multidisciplinary ICU protocol: the ABCDEF bundle. ABCDEF bundle incorporates assessment, prevention, and management of pain; both spontaneous awakening trial (SAT) and spontaneous breathing trial (SBT); choice of sedation and analgesia; delirium: assessment, prevention and management, and early mobility and exercise; family involvement and empowerment (ABCDEF) together as a PADIS care bundle. This is a multidimensional ICU liberation bundle which is a patient-oriented, holistic team approach to the management of critically ill patients aimed at reducing ICU distress and immediate and long-lasting consequences of PADIS.

A comparative study of modulatory interaction between cytokines and apoptotic proteins among Scleroderma patients with and without pulmonary involvement.

BACKGROUND: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the most eminent forms of pulmonary involvement in Scleroderma. In this study we investigate the interaction between cytokines and apoptotic proteins in treatment naive Scleroderma (SSc) patients with and without pulmonary involvement. METHODS: Newly diagnosed treatment naïve Scleroderma (SSc) patients (n = 100) and healthy controls (n = 100) were enrolled. Patients were classified as ILD-SSc, PAH-SSc and non-pulmonary SSc (np-SSc). Study variables like mRSS score, autoantibody profile, serum cytokines, serum TGF-ß (1,2,3) and apoptotic proteins were assessed for these patients. RESULTS: Scleroderma patients showed elevated levels of serum cytokines, but significantly lower IL-22 and TGF- ß1 when compared to healthy controls (p < 0.05). Apoptotic proteins were significantly elevated among Scleroderma patients, but the patient groups also showed significant lower caspase 1/3/9 levels when compared to healthy controls (p < 0.05). ILD-SSc patients reported higher mRSS score (p = 0.0436) when compared with PAH-SSc and np-SSc. In ILD-SSc patients, finger tightening (p = 0.0481) and calcinosis/lesions (p = 0.0481) were significant clinical presentations whereas, digital ulcers were significantly prominent in np-SSc patients (p = 0.0132). Elevated TGF-ß3 levels (p = 0.02) in SSC-ILD and reduced IL-4 levels (p = 0.02) in SSC-PAH were significant cytokines as compared to np-SSc. Significant correlations were obtained among serum cytokines and apoptotic proteins in Scleroderma patients with and without pulmonary involvement. (p < 0.05) CONCLUSION: Our study highlights the correlation between mRSS score, cytokines and apoptotic proteins in SSc patients with pulmonary involvement. A longitudinal follow up in these patients with assessment of these immunological parameters may be helpful in monitoring the disease.

Mannose Binding Lectin Levels and its Association with Systemic Lupus Erythematosus Disease Severity: An Indian Report.

BACKGROUND: Dysregulated serum levels of Mannan binding lectin (MBL) has a probable role in Systemic Lupus Erythematosus (SLE) pathogenesis. OBJECTIVE: To evaluate the association between serum MBL levels in SLE patients from western India with the severity of disease Methods: SLE patients (n=70) from Western India were included. Based on MBL levels, patients were classified into four categories, viz. low (<100 ng/ml), mild (100-500 ng/ml), moderate (500-1000 ng/ml) and high (>1000 ng/ml). Correlation of serum MBL levels with disease severity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). MBL levels and circulating immune complex levels were detected by ELISA. C3, C4 and CRP levels were detected by nephelometer. RESULTS: Serum MBL levels of SLE patients (1954 ± 202.4 ng/ml) was lower than that of healthy controls (2388 ± 205.0 ng/ ml). There was no significant correlation between MBL levels with severity of SLE on the basis of ACR criteria and SLEDAI scores (p> 0.05). No significant difference was observed among MBL levels and SLE patients with (1847 ± 246.7) or without (1900 ± 246.8) Lupus Nephritis. SLE patients without infections (n= 33) had low MBL levels (1700 ± 301.0 ng/ ml) as compared with SLE patients with infection (n= 37) (2189 ± 284.6 ng/ ml) (p=0.30) Conclusion: Present study indicated that low MBL levels were not associated with disease severity, haematological manifestations and infections among SLE patients from Western India.

Hepatocellular Carcinoma Evaluation and Management for Physicians: Joint Gastroenterology Research Society and Association of Physicians of India Guidelines.

Hepatocellular carcinoma (HCC) is the most common cause of, and accounts for almost 90% of all liver cancers. Data from India is limited especially due to cancer not being a reportable disease and in view of wide variation in diagnostic modalities. This document is a result of a consensus meeting comprising Hepatologists, Interventional Radiologists, Hepatobiliary surgeons, medical and surgical Oncologists nominated by the Association of Physicians of India and Gastroenterology Research Society of Mumbai. The following Clinical Practice Guidelines for practicing physicians is intended to act as an up to date protocol for clinical management of patients with hepatocellular carcinoma. The document comprises seven sections with statements and sub-statements with strength of evidence and recommendation.

Platypnea-orthodeoxia Syndrome (POS) in Moderate COVID-19: An Uncommonly Common Bedside Sign?

Platypnoea-Orthodeoxia syndrome (POS) is the presence of postural hypoxaemia along with breathlessness in recumbent position. It is an uncommon syndrome with elusive pathophysiologic mechanisms. We observed POS in patients of moderate COVID-19 who required hospital admission to our indoor facility and oxygen supplementation when saturation was documented in sitting and supine positions for evaluation of platypnea. MATERIALS AND METHODS: We conducted an observational, cross sectional, retrospective analysis of pulse oximetry readings of patients with stage 2 COVID-19 admitted in ward during the period from 15th May 2020 to 30th May 2020. The difference in the peripheral oxygen saturation in sitting and supine positions, documented as a routine standard of care, especially in patients with platypnea, was calculated and demographic details and co-morbidities were noted from indoor record forms. RESULTS: Of the 53 patients of stage 2 COVID-19 who were included in the study, 15 (28%) had platypnoea-orthodeoxia syndrome at the time of presentation and 18(33.9%) patients with platypnoea had ≥ 3% desaturation in sitting position as compared to supine position. Rest of the 20 (37.7%) patients had neither platypnoea nor orthodeoxia. All the patients presenting with platypnoea-orthodeoxia required oxygen therapy during the course of treatment. Amongst the 33 patients who were hypoxic and required oxygen supplementation, 15 patients (45.4%) had oxygen saturation of ≥94% in the supine position at presentation. CONCLUSION: Platypnoea-orthodeoxia syndrome is common in patients with stage 2 COVID 19 infection who require oxygen therapy. POS can be easily documented by using pulse oximeter without the need of any specialised equipment. Hence, we propose that documentation of POS at the time of admission in primary health care or resource depleted settings would help in successful triage of the patients needing oxygen therapy. We also propose that oxygen saturation in sitting position be documented as far as possible. Further clinical studies are necessary to validate this observation.

Impact of Autoantibodies to Complement Components on the Disease Activity in SLE.

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is a chronic multi-system autoimmune disease with varied clinical presentations. Complement components are the major players in disease pathogenesis. This retrospective cross-sectional study was aimed at assessing the role of autoantibodies to these complement components and their association disease activity in newly diagnosed SLE patients from India. METHOD: Clinically diagnosed SLE patients (n=57) classified as per 2015 ACR/SLICC revised criteria were enrolled between November 2016 to April 2017. Patients' sera were tested for C3 and C4 by nephelometry, while serum levels of factor H, factor P (properdin) as well as autoantibodies to C3, C4, factor H and factor P were detected by ELISA. GraphPad Prism Version 6.01 was used for statistical analysis. Mean, SD, SEM were calculated. Mann Whittney U-test, ANOVA, Chi-square test, Odd's Ratio were calculated. Pearson's correlation was used to study relativeness of the study parameters. RESULTS: Among the 57 SLE patients, low C3 were seen in 51% patients, low C4 in 49%, low factor H in 19% and low factor P in 49% patients. Positivity for autoantibodies against complement components, anti-C3 were seen in 42% patients, anti-C4 in 7%, anti-factor H in 19% and anti-factor P in 28% patients. Serum levels of C3 (p=0.0009), C4 (p=0.0031) and anti-C3 autoantibodies (p=0.0029) were significantly associated with ACR/SLICC 2015 scores. CONCLUSION: Hypocomplementemia was found to be associated with higher disease damage score in newly diagnosed SLE patients. This study adds novel arguments for the importance of the anti-C3 autoantibodies as a marker of SLE.

A longitudinal study of antibody responses to selected host antigens in rheumatic fever and rheumatic heart disease.

Introduction. Group A streptococci can trigger autoimmune responses that lead to acute rheumatic fever (ARF) and rheumatic heart disease (RHD).Gap Statement. Some autoantibodies generated in ARF/RHD target antigens in the S2 subfragment region of cardiac myosin. However, little is known about the kinetics of these antibodies during the disease process.Aim. To determine the antibody responses over time in patients and healthy controls against host tissue proteins - cardiac myosin and peptides from its S2 subfragment, tropomyosin, laminin and keratin.Methodology. We used enzyme-linked immunosorbent assays (ELISA) to determine antibody responses in: (1) healthy controls; (2) patients with streptococcal pharyngitis; (3) patients with ARF with carditis and (4) patients with RHD on penicillin prophylaxis.Results. We observed significantly higher antibody responses against extracellular proteins - laminin and keratin in pharyngitis group, patients with ARF and patients with RHD when compared to healthy controls. The antibody responses against intracellular proteins - cardiac myosin and tropomyosin were elevated only in the group of patients with ARF with active carditis. While the reactivity to S2 peptides S2-1-3, 8-11, 14, 16-18, 21-22 and 32 was higher in patients with ARF, the reactivity in the RHD group was high only against S2-1, 9, 11, 12 when compared to healthy controls. The reactivity against S2 peptides reduced as the disease condition stabilized in the ARF group whereas the reactivity remained unaltered in the RHD group. By contrast antibodies against laminin and keratin persisted in patients with RHD.Conclusion. Our findings of antibody responses against host proteins support the multistep hypothesis in the development of rheumatic carditis. The differential kinetics of serum antibody responses against S2 peptides may have potential use as markers of ongoing cardiac damage that can be used to monitor patients with ARF/RHD.

A two-arm, randomized, controlled, multi-centric, open-label phase-2 study to evaluate the efficacy and safety of Itolizumab in moderate to severe ARDS patients due to COVID-19.

Objective: Efficacy and safety of Itolizumab, an immunomodulatory mAb, in treating moderate-to-severe acute respiratory distress syndrome (ARDS) due to cytokine release in COVID-19 patients was evaluated in a multi-centric, open-label, two-arm, controlled, randomized, phase-2 study.Methods: Patients were randomized (2:1) to Arm-A (best supportive care [BSC]+Itolizumab) and Arm-B (BSC). Primary outcome of interest was reduction in mortality 30-days after enrollment.Results: Thirty-six patients were screened, five treated as first-dose-sentinels and rest randomized, while four patients were screen-failures. Two patients in Arm-A discontinued prior to receiving one complete infusion and were replaced. At end of 1-month, there were three deaths in Arm-B, and none in Arm-A (p = 0.0296; 95% CI = -0.3 [-0.61, -0.08]). At end of study, more patients in Arm-A had improved SpO2 without increasing FiO2 (p = 0.0296), improved PaO2 (p = 0.0296), and reduction in IL-6 (43 vs 212 pg/ml; p = 0.0296) and tumor necrotic factor-α (9 vs 39 pg/ml; p = 0.0253) levels. Transient lymphopenia (Arm-A: 11 patients) and infusion reactions (7 patients) were commonly reported treatment-related safety events.Conclusion: Itolizumab is a promising, safe and effective immunomodulatory therapy for treatment of ARDS due to cytokine release in COVID-19 patients, with survival and recovery-benefit.

Association of PON1 gene polymorphisms and enzymatic activity with risk of coronary artery disease.

Background: The present case-control study evaluated the association of PON1 gene polymorphisms and enzyme activity in the western Indian population. Materials & methods: Angiographically proven coronary artery disease (CAD) formed the cases. PON1 polymorphisms (Q192R, L55M) and enzymatic activity (paraoxonase) were assessed. Results: A total of 502 participants (251 per group) were studied. PON1 Q192R and L55M polymorphisms were not associated with the risk of CAD. Notably, a weak association was observed between Q192R polymorphisms and the risk of CAD. CAD patients had significantly lower PON1 enzymatic activity (U/L) as compared with the controls regardless of the genotype. Conclusion: Low serum PON1 activity was confirmed to be an independent predictor for the risk of CAD.

API-ISG Consensus Guidelines for Management of Gastrooesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a common problem in the community. The Indian Society of Gastroenterology and Association of Physicians of India have developed this evidence-based practice guideline for management of GERD in adults. A modified Delphi process was used to develop this consensus containing 43 statements, which were generated by electronic voting iteration as well as face-to-face meeting, and review of the supporting literature primarily from India. These statements include 4 on epidemiology, 9 on clinical presentation, 11 on investigations, 18 on treatment (including medical, endoscopic, and surgical modalities), and one on complications of GERD. The statement was regarded as accepted when the proportion of those who voted either to accept completely or with minor reservation was 80% or higher. The prevalence of GERD in large population-based studies in India is approximately 10% and is probably increasing due to lifestyle changes and increase in obesity. The diagnosis of GERD in the community should be mainly based on presence of classical symptoms like heartburn and sour regurgitation, and empiric treatment with a proton pump inhibitor (PPI) or H2 receptor antagonist should be given. All PPIs in equipotent doses are similar in their efficacy in the management of symptoms. Patients in whom symptoms do not respond adequately to PPI are regarded as having PPIrefractory GERD. Invasive investigations should be limited to patients with alarm symptoms and those with refractory GERD.

Role of MMP-2 and its inhibitor TIMP-2 as biomarkers for susceptibility to systemic lupus erythematosus.

Aim: To investigate the possible association between MMP-2 (-1575 G/A, -1306 C/T) and its inhibitor TIMP-2 (-418 G/C) functional polymorphisms with development of severity in systemic lupus erythematosus (SLE) patients. Materials & methods: 150 SLE patients and matched healthy controls were recruited. Polymorphisms were detected by PCR-RFLP and serum levels by ELISA. Results: Mean MMP-2 and TIMP-2 serum level and mRNA expression were significantly increased in SLE cases as compared with controls (p < 0.0001). The concomitant presence of both MMP-2 1575A and its inhibitor TIMP-2 418C alleles synergistically increased the risk of SLE by 3.25-fold (CI: 1.44-7.34, p = 0.003). Conclusion: MMP-2, TIMP-2 and MMP-2/TIMP-2 ratios may act as biomarkers for susceptibility to SLE.

The 2019 Novel Coronavirus Outbreak - A Global Threat.

The 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international significance. There are significant knowledge gaps in the epidemiology, transmission dynamics, investigation tools and management. In this article, we review the available evidence about this disease. Every decade has witnessed the evolution of a new coronavirus epidemic since the last three decades. The varying transmission patterns, namely, nosocomial transmission and spread through mildly symptomatic cases is an area of concern. There is a spectrum of clinical features from mild to severe life threatening disease with major complications like severe pneumonia, ARDS, acute cardiac injury and septic shock. Presence of bilateral ground glass opacity and consolidation on imaging in appropriate clinical background should raise a suspicion about COVID 19. Poor prognostic factors include Multilobular infiltration on chest imaging, Lymphopenia, Bacterial co-infection, Smoking history, Chronic medical conditions like Hypertension and age >60 years (MuLBSTA score). Diagnosis is confirmed with PCR based testing of appropriate respiratory samples. Management is primarily supportive, with newer antivirals (lopinavir ritonavir and Remdesivir) under investigation. Role of steroids is still inconclusive. Standard infection control and prevention techniques should be followed. Vigilant screening of suspected cases and their contacts is important. Isolation of symptomatic cases and home quarantine of asymptomatic contacts is recommended. To conclude, controlling this highly transmissible disease requires international co-ordination.

Clinical Benefits of Fixed Dose Combinations Translated to Improved Patient Compliance.

Pharmacotherapy with fixed dose combination (FDC) drugs is becoming popular as evidence-based clinical guidelines recommend using multiple therapeutic agents in complex regimens for many chronic diseases including type 2 diabetes mellitus (T2DM). FDC formulations have unique advantages such as complementary mechanism of action, synergistic effects, better tolerability, elongated product life-cycle management, and cost savings. Polypharmacy is a frequent problem in T2DM patients having hypertension, dyslipidemia, and other comorbidities. Use of FDCs is a rational approach for achieving optimal therapeutic benefits while minimizing pill-burden. Greater convenience with decreased pill-burden leads to improved adherence, resulting in superior clinical outcomes and greater cost-effectiveness. However, the general guidance for the clinical development and approval of FDC drugs in India is not much standardized. For rationale approval, the central and state regulators must harmonize their procedures for licensing FDCs. Because regulatory approval of FDCs is based on bioavailability data, similar to the way generic medications are approved, the lack of prospective, randomized controlled trials directly comparing FDCs with their component drugs administered as separate pills should not be considered a limitation to their use. Nevertheless, all new and existing FDC products should be subjected to submission of longterm safety surveillance through closely monitored national level postmarketing studies.