Class switching is differentially regulated in RBC alloimmunization and vaccination.

BACKGROUND: Studies of human patients have shown that most anti-RBC alloantibodies are IgG1 or IgG3 subclasses, although it is unclear why transfused RBCs preferentially drive these subclasses over others. Though mouse models allow for the mechanistic exploration of class-switching, previous studies of RBC alloimmunization in mice have focused more on the total IgG response than the relative distribution, abundance, or mechanism of IgG subclass generation. Given this major gap, we compared the IgG subclass distribution generated in response to transfused RBCs relative to protein in alum vaccination, and determined the role of STAT6 in their generation. STUDY DESIGN AND METHODS: WT mice were either immunized with Alum/HEL-OVA or transfused with HOD RBCs and levels of anti-HEL IgG subtypes were measured using end-point dilution ELISAs. To study the role of STAT6 in IgG class-switching, we first generated and validated novel STAT6 KO mice using CRISPR/cas9 gene editing. STAT6 KO mice were then transfused with HOD RBCs or immunized with Alum/HEL-OVA, and IgG subclasses were quantified by ELISA. RESULTS: When compared with antibody responses to Alum/HEL-OVA, transfusion of HOD RBCs induced lower levels of IgG1, IgG2b, and IgG2c but similar levels of IgG3. Class switching to most IgG subtypes remained largely unaffected in STAT6 deficient mice in response to HOD RBC transfusion, with the one exception being IgG2b. In contrast, STAT6 deficient mice showed altered levels of all IgG subtypes following Alum vaccination. DISCUSSION: Our results show that anti-RBC class-switching occurs via alternate mechanisms when compared with the well-studied immunogen alum vaccination.

Leptospiral myocarditis and pancreatitis.

While Leptospira are known to cause multi-system dysfunction, cardiac involvement is uncommon. We present a case febrile myocarditis diagnosed to have leptospirosis. The patient also had pancreatitis, jaundice and renal failure but recovered well with timely management.

Class switching is differentially regulated in RBC alloimmunization and vaccination.

Background: Studies of human patients have shown that most anti-RBC alloantibodies are IgG1 or IgG3 subclasses, though it is unclear why transfused RBCs preferentially drive these subclasses over others. Though mouse models allow for the mechanistic exploration of class-switching, previous studies of RBC alloimmunization in mice have focused more on the total IgG response than the relative distribution, abundance, or mechanism of IgG subclass generation. Given this major gap, we compared the IgG subclass distribution generated in response to transfused RBCs relative to protein in alum vaccination, and determined the role of STAT6 in their generation. Study Design and Methods: WT mice were either immunized with Alum/HEL-OVA or transfused with HOD RBCs and levels of anti-HEL IgG subtypes were measured using end-point dilution ELISAs. To study the role of STAT6 in IgG class-switching, we first generated and validated novel STAT6 KO mice using CRISPR/cas9 gene editing. STAT6 KO mice were then transfused with HOD RBCs or immunized with Alum/HEL-OVA, and IgG subclasses were quantified by ELISA. Results: When compared to antibody responses to Alum/HEL-OVA, transfusion of HOD RBCs induced lower levels of IgG1, IgG2b and IgG2c but similar levels of IgG3. Class switching to most IgG subtypes remained largely unaffected in STAT6 deficient mice in response to HOD RBC transfusion, with the one exception being IgG2b. In contrast, STAT6 deficient mice showed altered levels of all IgG subtypes following Alum vaccination. Discussion: Our results show that anti-RBC class-switching occurs via alternate mechanisms when compared to the well-studied immunogen alum vaccination.

Role of Bilastine in Allergic Rhinitis: A Narrative Review.

Allergic rhinitis (AR) is considered a trivial disease and is often self-treated with over-the-counter drugs and home remedies. However, AR is a contributing risk factor for asthma associated with complications, including chronic cough, eosinophilic esophagitis, and otitis media with effusion. In AR, inflammation is primarily mediated by histamines. Guidelines advise using second-generation oral H1 antihistamines as the primary treatment for AR. Second-generation H1 antihistamines strongly prefer the H1 receptor, limiting their ability to enter the central nervous system. Thus, they have minimal adverse effects. Among these H1 antihistamines, bilastine is highly specific for H1 receptors with a slight affinity for other receptors. It has a rapid and prolonged action, which reduces the need for frequent dosing and has better compliance. In the long term, bilastine is well-tolerated with minimal adverse effects. It is not associated with drug interactions, so dosage adjustment is unnecessary. Bilastine does not penetrate the brain and is nonsedating at 80 mg once daily. The low possibility of drug-drug interactions and pharmacokinetics of bilastine makes it suitable for elderly patients, even with compromised hepatic and renal function, without dose adjustment. This review comprehensively discusses the guidelines and the role of bilastine in treating AR. How to cite this article: Tiwaskar M, Vora A, Tewary K, et al. Role of Bilastine in Allergic Rhinitis: A Narrative Review. J Assoc Physicians India 2023;71(11):58-61.

Executive Summary of Evidence and Consensus-Based Clinical Practice Guidelines for Management of Obesity and Overweight in Midlife Women: An AIIMS-DST Initiative.

Weight gain is an independent risk factor for decline in cardiometabolic and overall health-related quality of life in midlife women. The AIIMS-DST initiative aims to develop and validate stepwise recommendations specific for weight management in midlife women. The key clinical questions specific to weight management in midlife women were finalized with the help of a multidisciplinary team of experts in the guideline development group. Phase I including a systematic and/or narrative review, grading of evidence, and expert opinion was sought to develop clinical practice recommendations for each clinical question. Phase II focused on validation of clinical practice recommendations using the peer-review, Delphi method, and GRADE approach. The guidelines provide clinical practice points to address challenges encountered by midlife women in their attempts to manage obesity via lifestyle modification techniques. The initiation of discussion would help the health-care provider to identify the weight management needs of the women, educate women on different modalities of weight management, and empower them to incorporate corrective lifestyle behaviors. Before initiating the management, a comprehensive assessment of clinical and lifestyle-related parameters should be completed. A personalized behavioral lifestyle modification program addressing the midlife-specific barriers for optimal metabolic, musculoskeletal, and mental health should be planned. A consistent follow-up is required for maintenance of corrective eating and activity habits by addressing midlife-specific barriers for sustenance of healthy weight. These recommendations will be useful in opportunistic screening and management of obesity in midlife women across health-care settings.

Role of Ambulatory Glucose Profile in Precision Medicine in Type 2 Diabetes Mellitus.

Assessment of diabetes with daily blood glucose fluctuations including peaks and nadirs forms the crux of the modern management. Use of glycemic variability (GV) as a parameter to assess these fluctuations is emerging. It is important to determine the hyperglycemic and hypoglycemic episodes which are the culprits for increasing glycemic variation. Diabetes mellitus patients follow different clinical trajectories which can be traced by the ambulatory glucose profile (AGP) obtained from flash glucose monitoring system (FGMS). MATERIAL: This comparative observational study enrolled 106 adult (>18 years) type 2 diabetes patients with HbA1c<8%. Patients were divided into two groups (group A & group B) with 53 patients each. Group A included patients on OAD's (oral antidiabetic drug) with insulin and Group B included patients on OAD's without insulin. The patients were put on FGMS for 14 days and their AGP was analysed. Hyperglycemic episodes (level 1- >180 mg/dl, level 2- >250 mg/dl) and hypoglycemic episodes (level 1- 54-70 mg/dl, level 2- <54 mg/dl) were determined between the groups. OBSERVATION: Group A patients had significantly higher (29.99%) total number of hyperglycemic episodes (Level 1+ Level 2) as compared with group B (9.08%) (p <0.0001). Amongst group A, proportion of patients with total number of hyperglycemic episodes was significantly higher in insulin only subgroup (58.11%) followed by insulin +metformin+ 1 OAD (29.14%) & insulin+ metformin (26.82%) (p <0.0001). Amongst group B, total number of hyperglycemic episodes were found to be significantly higher with metformin only subgroup (10.19%) followed by metformin + 1 OAD (9.72%) & metformin + >1 OAD (8.1%) (p<0.0001). Amongst the add on OAD's, sulfonylurea contributed to 61.07% hyperglycemic episodes in group A & 11.63% in group B which was statistically more than DPP-4 inhibitors with 14.91% & 2.84% respectively (p <0.0001). Total number of hypoglycemic episodes seen in group A patients (8.66%) were significantly less as compared with group B (13.27%) (p<0.0001). Sulfonylurea contributed to 7.5% hypoglycemic episodes in group A & 13.2% in group B which was statistically more than DPP-4 inhibitors with 6.49% & 12.35% respectively when added to metformin (p<0.0001). CONCLUSION: Amongst the OAD's used in type 2 diabetes mellitus patients in this study, total number of hyperglycemic and hypoglycemic episodes were found to be more in patients taking sulfonylurea as compared with DPP4 inhibitors when used in combination with metformin with or without insulin.

Transient Elastography of Liver and Serum Hyaluronic Acid Levels In Adult Transfusion Dependent Thalassemia Patients.

Iron overload occurs as a result of multiple blood transfusions and increased iron absorption in thalassemia patients. Iron deposition in liver results in liver stiffness and fibrosis. Non invasive methods including imaging and serum biomarkers have been introduced for assessment of liver fibrosis. We aimed to study liver stiffness using transient elastography and serum hyaluronic acid levels and correlate them with serum ferritin levels in adult transfusion dependent beta thalassemia patients. MATERIAL: 70 transfusion dependent thalassemia patients of age ≥18 years, registered at Thalassemia Day Care Centre were subjected to investigations like CBC, Liver function tests, viral markers, serum ferritin, serum hyaluronic acid levels and transient elastography. Fibrosis indices like FIB-4, AAR and APRI were also calculated. 45 patients had T2*MRI reports with them; which were also included and analysed. Spearman coefficient r was used to test correlations between TE values and serum HA levels with other variables. OBSERVATION: 70 patients (41 male and 29 female) with mean age of 24.09±5.38 years and BMI 20.51 ±3.47 kg/m², were enrolled. Median values of hemoglobin, AST, ALT, TE, serum HA and serum ferritin were, 9.15 g/dl, 42 IU/L, 47.50 IU/L, 9.1 kPa, 284 ng/dl and 1841 ng/ml, respectively . TE values had significant positive correlation with serum ferritin (r=0.5, p < 0.001), ALT (r=0.59, p < 0.001), AST (r=0.58, p< 0.001), APRI (r=0.5, p<0.001) and FIB-4 (p=0.02), respectively and significant negative correlation with T2* MRI (ms) (r= -0.5, p<0.001). No significant correlation of HA was found with any variable. CONCLUSION: Transient elastography can be used as a non expensive, easily accessible and non invasive marker of liver iron overload. Further detailed studies are required to establish the role of serum Hyaluronic acid in thalassemia patients.

Executive summary of evidence and consensus-based clinical practice guideline for management of obesity and overweight in postpartum women: An AIIMS-DST initiative.

INTRODUCTION: Postpartum obesity is a public health concern. There is a need to counsel women about their postpartum weight management, accounting for various barriers they face. Limited literature in the Indian context underscored the need to develop the clinical practice guideline to be used by healthcare providers in Indian healthcare settings. METHODS: The guideline was formulated by following the standardised methodology proposed by the National Health and Medical Research Council. Various steps such as identification of the patient population, assembly of the guideline development groups, identification of the key clinical questions, guideline development methods, grading the quality of evidence and recommendations and guideline translation were carried out to develop and validate the clinical practice recommendations. RESULTS: The evidence and consensus-based clinical practice guideline has been developed, providing recommendations for key topics of interest for first-line treatment of obesity (lifestyle-related management). Recommendations focus on screening and initiating discussion with overweight and obese postpartum women as well as those who had normal pre-pregnancy body mass index but have retained excessive weight in the postpartum period. Recommendations highlight the evaluation and management of dietary, physical activity and breastfeeding behaviour. Recommendations also account for behavioural modification techniques to improve adherence to the prescribed weight management advice. Duration and frequency of follow-ups as well as the advice to be disseminated have also been discussed in the recommendations. CONCLUSION: The guideline provides clinical practice points that can be used by healthcare providers, postpartum women and policymakers for opportunistic screening and management of postpartum obesity.

Executive summary of evidence and consensus-based Clinical Practice Guidelines for management of obesity and overweight in midlife women: An AIIMS-DST initiative.

BACKGROUND AND AIMS: Weight gain is an independent risk factor for decline in cardiometabolic and overall health-related quality of life in midlife women. The AIIMS-DST initiative aims to develop and validate stepwise recommendations specific for weight management in midlife women. METHODS: The key clinical questions specific to weight management in midlife women were finalised with the help of a multidisciplinary team of experts in the guideline development group (GDG). Phase I included a systematic and/or narrative review to gather evidence, grading of evidence and expert opinion was sought to develop clinical practice recommendations for each clinical question. Phase II focused on validation of clinical practice recommendations using the peer-review, Delphi method and GRADE approach. RESULTS: -The guidelines provide clinical practice points to address challenges encountered by midlife women in their attempts to manage obesity via lifestyle modification techniques. The initiation of discussion would help the healthcare provider to identify the weight management needs of the women, educate women on different modalities of weight management, and empower them to incorporate corrective lifestyle behaviours. Before initiating the management, a comprehensive assessment of clinical and lifestylerelated parameters should be completed. A personalised behavioural lifestyle modification program addressing the midlife specific barriers for optimal metabolic, musculoskeletal, and mental health should be planned. A consistent follow-up is required for maintenance of corrective eating and activity habits by addressing midlife specific barriers for sustenance of healthy weight. CONCLUSION: These recommendations will be useful in opportunistic screening and management of obesity in midlife women across healthcare settings.

Ethambutol toxicity: Expert panel consensus for the primary prevention, diagnosis and management of ethambutol-induced optic neuropathy.

Ethambutol use may lead to permanent vision loss by inducing a dose- and duration-dependent optic neuropathy. This has been of concern to ophthalmologists and physicians both; however, ethambutol continues to be used because of its anti-mycobacterial action with relative systemic safety. Recently, the guidelines of the Revised National Tuberculosis Control Programme of India have been revised to allow for fixed dose and longer duration of ethambutol use; this is likely to result in an increase in vision-threatening adverse effects. Taking cognizance of this, neuro-ophthalmologists, infectious disease specialists, and scientists met under the aegis of the Indian Neuro-Ophthalmology Society to deliberate on prevention, early diagnosis, and management of ethambutol-related toxic optic neuropathy. The recommendations made by the expert group focus on early suspicion of ethambutol toxicity through screening at the physician's office and opportunistic screening by the ophthalmologist. Further, they focus on an early diagnosis through identification of specific clinical biomarkers and on management in way of early stoppage of the drug and supportive therapy. This statement also describes the mechanism of reporting a case of toxic optic neuropathy through the Pharmacovigilance Programme of India and emphasizes the need for spreading awareness regarding vision-threatening adverse effects among patients and healthcare workers.

Coagulation Profile and its Correlation with Severity of Liver Dysfunction and Gastrointestinal Bleed in Alcoholic Liver Disease Patients.

INTRODUCTION: The study aimed to determine coagulation factor abnormalities in alcoholic liver disease (ALD) and correlate these with severity of liver dysfunction (Child's class) and gastrointestinal (GI) bleeding. METHODS: 60 patients of ALD (alcohol intake >10years and clinical, biochemical or radiological evidence of chronic liver disease) were included. Patients with Hepatitis B, Hepatitis C, HIV infection, DIC, low platelet count due to other causes, or on drugs which affect coagulation profile were excluded. OBSERVATIONS: Age was 44.42 ± 10.26 years (100% males), 53% in Childs class C. Severity of liver dysfunction showed a significant association (p<0.05) with prolongation of prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), increasing factor VIII and D-Dimer level, low platelet counts, low protein S and factor VII activity; as well as decreasing fibrinogen levels, protein C and antithrombin (AT) III. GI bleed is associated significantly (p<0.05) with PT >20 sec and decreased plasma fibrinogen levels, while normal protein C, normal AT III, normal factor VII, normal factor VIII, normal TT, increased plasma fibrinogen levels, normal PT and normal platelet count appeared to be protective. CONCLUSIONS: Several coagulation parameters are altered in ALD variably. Alterations in PT, aPTT, TT, factor VIII, D-Dimer, fibrinogen, protein C and AT III levels can be used for grading severity of liver disease. Decreased fibrinogen, protein C activity, AT III activity, factor VII activity, and increased factor VIII activity, are associated with GI bleed.

Ethambutol Optic Neuropathy: Vigilance and Screening, the Keys to Prevent Blindness with the Revised Anti-tuberculous Therapy Regimen.

There has been change in the guidelines for the management of tuberculosis in India. The new guidelines advocate the daily use of Ethambutol for both intensive and continuation phase of the treatment. This may be a matter of concern as increased cumulative dose may lead to increase in incidence of toxic optic neuropathy due to ethambutol. Indian Neuro-Ophthalmology Society has taken cognizance of the issue and has come-up with guidelines for prevention and early detection of the toxic optic neuropathy.

Comparative evaluation of cost effective extraction free molecular technique for detection of SARS-CoV-2 with reference to standard VTM based RT-qPCR method.

BACKGROUND AND OBJECTIVES: The entire globe is undergoing an unprecedented challenge of COVID-19. Considering the need of rapid and accurate diagnostic tests for SARS-CoV-2, this study was planned to evaluate the cost effective extraction free RT-PCR technique in comparison to the standard VTM based RT-qPCR method. MATERIALS AND METHODS: Paired swabs from nasopharynx and oropharynx were collected for SARS-CoV-2 testing, from 211 adult patients (≥18 years) in VTM and plain sterile tubes (dry swabs). These samples were processed and RT-qPCR was carried out as per standard protocols. RESULTS: 54.5% of the patients were females and 45.5% were males with sex ratio 1:1.19 (M: F). 38.86% were symptomatic, of which fever (86.59%), cough (79.23%) and breathlessness (46.34%) were the most common symptoms. The positivity by VTM based method and index method was 31.27% and 13.27% respectively. Of the 27 inconclusive results from index method, 37.04% were positive, 48.15% were negative by VTM based method. However, in 40 inconclusive results by VTM based method, 90% were negative and rest remained inconclusive by index method. The sensitivity and specificity of the index method were 39.39% and 85.71% respectively. The overall agreement between VTM based method and index method was 49.59% with estimated Kappa value of 0.19. CONCLUSION: VTM based method showed higher sensitivity compared to the index method. The higher positivity by VTM based method, suggests that VTM based method could plausibly be a better detection method of SARS-CoV-2. Still, the index method might add value in a resource limited setups for detection of SARS-CoV-2.

The Syndromic Spectrum of COVID-19 and Correlates of Admission Parameters with Severity-outcome Gradients: A Retrospective Study.

BACKGROUND: Clinical and laboratory features of COVID-19 may have regional variations. This study aimed to discern their association with severity of illness and mortality in tertiary setup of Delhi, India. METHODS: Retrospective data of hospitalised COVID-19 patients over 3 months (end March to June 2020) were evaluated for symptom profile, blood investigations and chest radiograph data and classified according to COVID-19 severity and as survivors and non-survivors. RESULTS: Average age (n=182) was 46.1 years, male to female ratio 1.4:1. Fever (51.1%), cough (49.4%) and breathlessness (48.3%) were the commonest symptoms, and frequency of all the three increased with severity of COVID-19. Fever duration, leucocytosis, neutrophilia, elevated blood urea, transaminitis and higher Brixia score on chest X-ray were also more in severe COVID-19 compared to mild and moderate categories. Higher age, more comorbidities, fever, breathlessness and chest pain; longer duration of fever, leucocytosis, neutrophilia, lymphopenia, high neutrophil to lymphocyte ratio, elevated serum urea, creatinine, transaminases and hyperglycemia, and higher radiographic Brixia score were observed in non-survivors compared to survivors. CONCLUSION: Greater prevalence of symptoms (alone and in combination) and derangements in blood biochemistry are seen in severe COVID-19 compared to mild or moderate cases, and also in non-survivors compared to survivors.

Pancreatic Injury in COVID-19 Patients.

BACKGROUND AND AIM: Coronavirus disease 2019 (COVID 2019) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause multisystem dysfunction. We studied pancreatic injury (serum amylase and serum lipase levels) in COVID-19 patients. METHODS: A retrospective study involving 42 COVID-19 patients (diagnosed by real-time PCR) admitted to a tertiary care hospital was conducted. Serum amylase and serum lipase levels were analysed in relation to severity of COVID-19 and mortality. RESULTS: Mean age of patients was 50 ± 16 years, with male to female ratio of 3.7:1. Serum amylase was elevated in 14 patients (33%). Serum lipase was elevated in 7 out of 29 patients (24.1%). Mortality was seen in 18 patients (42.8%). Serum amylase or lipase did not correlate with severity of COVID-19 or its mortality. However, both patients who had high lipase (>3times) died. CONCLUSION: The prevalence of hyperamylasemia in patients of COVID-19 was 33%, while that of elevated lipase was 24.1%. Pancreatic injury failed to show any statistically significant relation to severity or outcome of COVID-19.