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.

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.

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.

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.

Fibrotic Cytokine Interplay in Evaluation of Disease Activity in Treatment Naïve Systemic Sclerosis Patients from Western India.

BACKGROUND: : Systemic sclerosis (SSc) is a demyelinating disease of skin, subcutaneous tissue, muscles and internal organs, with fibrosis as an important pathological event. AIM: : To understand cytokine interplay of IL-1ß, IL-4 and IL-6 and their association with disease activity in treatment naïve active cases of systemic sclerosis from Western India. METHODS: Twenty-five SSc patients as per ACR-EULAR 2013 criteria (classified based on pulmonary fibrosis and generalized fibrosis) and 25 age-sex matched controls were enrolled. Serum cytokine levels of IL-1ß, IL-4 and IL-6 were assessed by multiplex bead based immunoassay. RESULTS: Ten patients had Interstitial lung disease (ILD), whereas, 16 patients had generalized fibrosis. Anti-nuclear antibodies were seen in 22 patients (88%); antiScl70 in 15 patients (60%) and anti-Centromere antibodies in 5 patients (20%). Serum levels of IL-1ß in patients were significantly higher than healthy controls (p=0.0006). IL-4 levels in all SSc patients were marginally raised (p=0.0102), while IL-6 levels were significantly raised (p<0.0001). IL-4 was found to be significantly raised in SSc patients with ILD (p=0.021) as compared to patients without ILD. IL-1ß (p=0.0293) and IL-4 (p<0.0001) were significantly higher in SSc patients with fibrosis. On the contrary, IL-6 levels in patients with fibrosis were found to be lower than in patients without fibrosis. CONCLUSION: Significantly raised cytokine levels among treatment naïve systemic sclerosis patients were found to be associated with higher disease severity in our study. Higher levels of IL-1ß and IL-6 indicated an active inflammatory status, whereas significantly raised IL-4 levels indicated at higher fibrotic activity.

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.

Glucose-6-Phosphate Dehydrogenase Deficiency Unveiled by Diabetic Ketoacidosis: A Dual Dilemma.

An 18 year old male, known case of Type 1 Diabetes Mellitus was admitted in view of diabetic ketoacidosis. With normalization of blood sugars patient developed gross reddish discoloration of urine. Urine routine microscopy did not reveal RBCs or RBC casts. Peripheral blood smear revealed bite cells, Heinz bodies and spherocytes. Thus a diagnosis of hemolytic anemia with hemoglobinuria was made. Patient's glucose-6-phosphate dehydrogenase (G6PD) levels were below the normal range. G6PD, an enzyme of the HMP shunt, is the most common enzyme defect causing hemolytic anemia. G6PD deficiency related hemolytic crisis is most commonly precipitated by infection, drugs or fava beans. Its association with DKA has been seldom reported.

Indian College of Physicians (ICP) Position Statement on Pharmacovigilance.

Pharmacovigilance is the art and science of detection, understanding and prevention of adverse drug reactions and not merely a critical analysis of prescriptions and errors. This field starts with reporting by clinicians of a suspected adverse drug reaction (ADR) to the pharmacologist followed by joint causality analysis and ends at the application of new information by a clinician for benefit of patients. There are a number of ways, which can be utilised for reporting adverse effects using pen and paper format to software applications for smart phones. Varied types of activities spreading from systematic reviews to the mechanistic evaluation of ADR can be performed under the umbrella of pharmacovigilance. It is of utmost importance for clinicians to understand how to identify, communicate and understand adverse effects of drugs with an aim to prevent harm to patients.

Indian College of Physicians Position Statement: Addictive Disorders Among Persons with Diabetes Mellitus.

OBJECTIVES: Migraine, a common primary headache disorder which can be severely disabling, associated with poor health-related quality of life (HRQoL) amongst affected patients. The present study was performed to provide adequate clinical data on migraine and the management practices in India. MATERIAL AND METHODS: A cross-sectional study was designed to assess disease burden, HRQoL, symptom profile, management trends and comorbidities associated with migraine patients across ten centres in India. This study assessed HRQoL using Migraine Specific Quality of life (MSQ) and Migraine Disability Assessment Scores (MIDAS) questionnaire. Categorical variables were summarized as frequency, and percentage and continuous variables as mean and standard deviation respectively. RESULTS: A total of 705 patients were enrolled with a mean age of 35.2 years. Hypertension (7.0%) was the highest co-morbid illness associated with migraine. A higher MSQ score was observed in females as compared to males (39.3±12.4 and 37.4±11.6) while MIDAS showed a comparable score (27.7±47.6 and 27.2±35.4). Majority of migraine patients were unemployed (61.6%) and in profession, females had poor HRQoL than males by MIDAS and MSQ. Majority of patients had pulsating, bilateral attacks for the duration of 4h to 72 h. Paracetamol (47.1%) and propranolol (50.9%) was most commonly prescribed drugs for acute attack and prophylaxis, respectively. CONCLUSION: The quality of life was superior in males as compared to females amongst migraine patients in India. Hypertension was the commonest comorbidity associated with migraine. KEY MESSAGES: Migraine is associated with substantial disability with higher prevalence in females and older people (age >40 years). NSAIDs and propanol was widely prescribed drug in acute attacks and prophylaxis of migraine respectively. Cardiovascular diseases, diabetes mellitus and anxiety were common comorbidities associated with migraine.

Association of Physicians of India: Position Statement on Role of Chirally Pure Molecules in Clinical Practice.

Chirally pure molecules or enantiomers are non-superimposable mirror images of each other with a chiral center (such as carbon, sulphur, nitrogen or phosphorous atom). An equimolar mixture of enantiomers forms a racemate. Chirally pure molecules (single enantiomers) are important in the field of drug discovery as the drug targets such as enzymes and receptors are enantioselective in nature. Clinical studies have demonstrated that chirally pure drugs exhibit different pharmacokinetic and metabolic profiles, reduced adverse events, improved safety profiles and similar therapeutic activity at lowered drug dosage as compared with the racemate in many therapeutic areas. However, since there is a low level of awareness on the advantages of chirally pure molecules among clinicians, pharmacists and patients in India, the Association of Physicians of India (API) developed this position statement to increase awareness on the concept of chirality and the associated advantages of using chirally pure drugs in certain therapeutic areas to maximize patient outcomes. This includes the clinical evidence associated with single enantiomers such as S-metoprolol, S-amlodipine, esomeprazole, escitalopram, levobupivacaine, cisatracurium, S-etodolac, dexketoprofen, levofloxacin in terms of efficacy and safety as compared with their racemates. In addition, the API also provides some tactical recommendations for clinicians, pharmacists, patients, regulatory body and pharmaceutical companies to increase awareness on chirally pure drugs and puts forth the need for expedited availability of chirally pure drugs in the Indian market.

Zika Virus Infection, the Recent Menace of the Aedes Mosquito.

Mosquito-borne infections and viral outbreaks have bewildered physicians and population at large from time to time, there seems to be a constant cat and mouse race between the medical fraternity and these mosquito menaces. Zika virus and its vector Aedes aegyti are currently bothering the world population, this infection has affected pregnant women causing microcephaly in their new-borns and also has caused GBS-like manifestations in affected individuals. Currently the outbreak is concentrated in the countries of South American continent, but the omnipresence of its vector has made the world community cautious about the potential of its spread; thus the great emphasis is on prevention and vector control strategies to counter Zika virus attack. Consequently, Ministry of Health, Government of India has also taken cognizance of this and issued guidelines to tackle this problem.

Mesenteric Vasculitis in a Case of Systemic Lupus Erythematosus.

We present a case of mesentric vasculitis with systemic lupus erythematosus who relapsed after high dose steroids but achieved subsequent remission after starting pulse cyclophosphamide therapy. 38 years old female who had earlier polyserositis and cerebral venous thrombosis was admitted with provisional diagnosis of SLE and developed acute abdominal pain during hospital stay. She was diagnosed as mesenteric vasculitis and initially responded to pulse methylprednisolone. However, she had relapse which subsequently responded to pulse cyclophosphamide and steroids. During the ward course she also developed acute thyroiditis and was diagnosed to have class IV lupus nephritis on renal biopsy.

Myasthenia Gravis with Amyotropic Lateral Sclerosis: A Rare Co-existence.

The co-occurrence of myasthenia gravis with motor neurone disease is not a very common association and may pose problem and confusion in the minds of the treating physician because of the gamut of neurological symptoms. This case intends to highlight these dilemmas.

Association of Serum Ferritin Levels with Hematological Manifestations in Systemic Lupus Erythematosus Patients from Western India.

OBJECTIVE: To identify the hematological manifestations and its association with serum ferritin levels in SLE patients from Western India. METHODS: Ninety clinically diagnosed SLE patients fulfilling ACR criteria were included. Disease activity was assessed at the time of evaluation using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Sera were tested for serum ferritin levels by ELISA (Calbiotech, USA). Autoantibodies such as ANA, anti-dsDNA by indirect immunofluorescence test (IFA- Bio-Rad, USA) and anti-cardiolipin antibodies (ACA) to IgG and IgM isotypes and Anti-ß2 GP antibodies to IgG and IgM isotypes were detected by ELISA using commercially available kits (Euroimmun, Lubeck, Germany). RESULTS: Out of 90 SLE patients studied, 41 patients (45.6%) showed hematological abnormalities, where anemia (82.9%), leucopenia (26.8%), autoimmune hemolytic anemia (AIHA) (14.6%) and idiopathic thrombocytopenic purpura (ITP) were noted in (34.1%) patients. Mean±SD serum ferritin levels among SLE patients were 270.2±266.0 ng/ml as compared to 29.0±15.8 ng/ml healthy normal controls (p<0.0001). A positive correlation between serum ferritin levels and SLEDAI scores (r= 0.2640, p=0.0124) and anti-dsDNA positivity was noted (r=0.32, p<0.0001). Serum ferritin levels were negatively correlated with hemoglobin levels (r=-0.5964, p=0.0001), WBC count (r=-0.1705, p=0.2316), platelet count ((r=-0.1701, P=0.2375), C3 levels (r=-0.4417, p=0.0034) and C4 levels (r=-0.0363, p=0.8215). CONCLUSIONS: Serum ferritin is an excellent marker of SLE which can be used for an evaluation of disease activity particularly in active stage of the disease mainly in patients having hematological and renal manifestations.

Recommendations for Vaccination Against Seasonal Influenza in Adult High Risk Groups: South Asian Recommendations.

Influenza is a global public health problem and concern especially in high risk people. Prevention plays a key role in avoiding complications of influenza related illnesses. Despite the existing prevalence of influenza, and documented importance of vaccination, the uptake of influenza vaccine is very poor. This document provide recommendations for influenza vaccination in high-risk individuals and help implement best practices in the South Asian region and improve coverage of influenza vaccination to achieve better outcomes in this population.

Codeine: A Relook at the Old Antitussive.

Cough is the most frequent complaint of patients seeking medical attention in general and hospital practice. Cough is controlled by treating the cause, however, when no cause can be found, symptomatic relief of cough must be considered. Treatment of dry cough resulting from increased sensitivity of the cough reflex remains a challenge in some subjects. Codeine in combination with other medicines has been a mainstay for the effective short-term symptomatic relief of dry or nonproductive cough in clinical practice. This article focuses on the current status of codeine as an antitussive formulation in the treatment of dry cough. Codeine is one of the centrally acting narcotic opioids approved for use as an antitussive, a prodrug that is bioactivated by CYP2D6 into morphine in the liver. The opioid effects of codeine are related to plasma morphine concentrations. Codeine is one of the most frequently used antitussive in clinical practice and has been widely regarded as the standard cough suppressant against which newer drugs are being evaluated. Codeine has an advantage as an antitussive because of its multifaceted effect as an analgesic and sedative along with cough suppression. However, codeine may have efficacy to suppress cough in humans only in specific situations. Caution is also needed to limit its use only when and as long as it is clinically necessary, particularly in children.

Recurrent Hypoglycaemia due to Insulin Autoimmune Disease (Hirata Disease) Associated with Monoclonal Gammopathy of Unknown Significance.

Hirata disease is a rare disease characterised by recurrent episodes of hypoglycaemia due to anti-insulin antibody. In most of these cases causative agents were sulfhydryl containing compounds like Penicillamine, Glutathione, and Methimazole. The presentation of disease closely mimics insulinoma. We report 52 years female patient presenting with recurrent episodes of hypoglycaemia due to anti-insulin antibody. On evaluation, underlying cause of antibody was found to be monoclonal gammopathy of unknown significance (MGUS).