How Do We Manage Chronic Lymphocytic Leukemia in India.

PURPOSE OF REVIEW: Chronic lymphocytic leukemia was an ignored leukemia in India until a decade back, given its low prevalence and absence of novel drugs to treat it. Healthcare in India is heterogeneous, with variations in population, health systems, and reimbursement options. We have focused on opinions from three hemato-oncologists incorporating an opinion poll from 44 hemato-oncologists across India on the common issues in CLL to give an idea of the practice pan-India. RECENT FINDINGS: More CLL patients are being diagnosed in their early stages. There is an attempt to use prognostic and predictive markers in making shared decisions for managing CLL. There is still a role for chemoimmunotherapy (CIT) in India, given limited health insurance coverage. But with the availability of inexpensive generics, the patient preference for non-CIT options like Bruton's tyrosine kinase (BTK) inhibitors is palpable. The CLL scene in India is changing rapidly. With the wide availability of economical generic small molecule inhibitors, monoclonal antibodies, and coverage by social health insurance schemes, India is poised to cater to most CLL patient needs.

Continuous erector spinae plane block for analgesia and better pulmonary functions in patients with multiple rib fractures: a prospective descriptive study

Abstract Background: The present study explored the role of continuous erector spinae plane (ESP) block for analgesia as well as its impact on pulmonary functions in patients with multiple rib fractures. Methods: Ten patients with multiple rib fractures were enrolled after getting informed and written consent. Ultrasound-guided ESP block was performed at the level midway between the fractured ribs followed by the insertion of the catheter. Pre- and post-block VAS score, hemodynamics, respiratory rate (RR), peripheral oxygen saturation (SpO2), inspiratory capacity (IC), blood gases (PaO2 and PCO2), and complications were compared. Results: Pain scores at rest as well as on movement showed a significant reduction from 5.9 and 7.5 pre block to 1.6 and 2.5 respectively at 96 hours (p < 0.0001). Similarly, RR, SpO2, IC, and PaO2 were significantly better after the block placement (p < 0.001). Conclusion: Continuous ESP block provide adequate analgesia with better respiratory functions in patients with multiple rib fractures.

Clinical Implications of Herbal Supplements in Conventional Medical Practice: A US Perspective.

Herbal supplements are common complementary and alternative medicine (CAM) approaches with an ever-increasing use trend in the last two decades among the US population. Self-medication with herbal supplements which are promoted for general well-being, weight loss, immunity, and memory boost, and mental and physical health claims are very prevalent. There is a misperception that herbal supplements are harmless as they are prepared from natural sources. Unlike conventional drugs, the US Food and Drug Administration (FDA) does not regulate herbal supplements for premarketing purity and potency. Hence, there is a growing concern for health risks due to misbranded toxic ingredients, contaminants, adulterants, and herb-drug interactions (HDI) with co-administered drugs. The spectrum of pharmacological and toxicological effects of herbal supplements includes deranged lab results, allergic reactions, genotoxicity, carcinogenicity, teratogenicity, organ damage, and even fatality contributing to sizable emergency visits and hospitalizations in the US. The use of herbal supplements should be carefully monitored in high-risk groups such as pediatric and geriatric populations, pregnant women, breastfeeding mothers, immunocompromised patients, and surgical candidates. The deleterious health effects of herbal supplements are loosely addressed in conventional medical practice in part due to the limited knowledge of practitioners. This comprehensive narrative review aims to explore the clinical implications of herbal supplements in order to fill the knowledge gaps by summarizing scientific publications. It also highlights the pivotal roles physicians can play in minimizing the health risks of herbal supplements by encouraging patients to disclose usage through a non-judgmental approach, employing HDI screening tools, and reporting adverse reactions to FDA. Formal training of physicians, a standardized pharmacovigilance system, stricter regulation of the herbal industry, and more scientific studies are keys to establishing herbal safety and efficacy in clinical practice.

Nonalcoholic Fatty Liver Disease: An Emerging Modern-Day Risk Factor for Cardiovascular Disease.

Nonalcoholic fatty liver disease (NAFLD), also named metabolic dysfunction-associated fatty liver disease (MAFLD), is a progressive disease spectrum encompassing simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. It is a clinically silent disease leading to multiple extra-hepatic complications/comorbidities. It is an independent risk factor for cardiovascular disease (CVD), increasing susceptibility to hypertension, atherosclerosis, arrhythmia, myocardial dysfunction, cardiac valve deformation, and venous thrombosis through putative mechanisms including systemic inflammation, endothelial dysfunction, oxidative stress, insulin resistance, and altered lipid metabolism. Eventually, it increases the CVD prevalence, incident, and fatality, contributing to a huge health care burden. In fact, CVD is becoming the leading cause of mortality among patients with NAFLD. Other cardiometabolic risk factors coexisting with NAFLD may also accelerate the synergistic development of CVD, which warrants assessment targeting hypertension, diabetes mellitus (DM), obesity, and dyslipidemia to be an integral part of NAFLD care. Monitoring metabolic biomarkers (glucose, glycosylated hemoglobin [HbA1c], insulin, lipids, and lipoproteins), cardiovascular (CV) risk scores (American College of Cardiology/American Heart Association [ACC/AHA] or Framingham), and subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness [CIMT], and carotid plaque) are recommended for risk prediction and reduction. There is no universally accepted treatment for NAFLD, and lifestyle changes with weight loss of at least 10% are the mainstay of management. Combination therapy of ezetimibe and statins have a cardioprotective effect and help reduce liver fat. Despite being an emerging risk factor for CVD and its rapidly increasing pattern affecting a quarter of the global population, NAFLD remains overlooked and undetected, unlike the other traditional risk factors. Hence, we conducted a comprehensive narrative review to shed more light on the importance of screening CVD in NAFLD patients. PubMed indexed relevant articles published from 2002 to 2022 (20 years) were searched in April 2022 using medical subject headings (MeSH) as "nonalcoholic fatty liver disease" [Mesh] AND "cardiovascular diseases" [Mesh]. Evidence from 40 observational studies, three clinical trials, one case series, 45 narrative reviews, four systematic reviews and meta-analyses, three systematic reviews, and one meta-analysis were summarized on the epidemiologic data, pathophysiologic mechanisms, clinical features, diagnostic modalities, overlapping management, perceived challenges and health literacy regarding the CVD risk attributed to NAFLD.

Programmed Death-Ligand 1 (PD-L1) Positivity and Factors Associated with Poor Prognosis in Patients with Gastric Cancer: An Umbrella Meta-Analysis.

Gastric cancer (GC) is one of the most common malignancies throughout the world with late diagnosis and poor prognosis. The expression of programmed death-ligand 1 (PD-L1) in GC is attributed to immune evasion and tumor progression. PD-L1 positivity has both predictive and prognostic biomarker potential. Aiming to summarize a large amount of research and to provide a definitive conclusion to the conflicting results on the prognostic significance of PD-L1 expression in GC, we performed an umbrella review based on existing meta-analyses which were published recently (2016-2021) and indexed in the PubMed database. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was used in August 2021 to screen articles, and data extraction with quality assessment was performed on the selected meta-analyses. Review Manager (RevMan) 5.3 software was used to analyze the HR and OR with a 95% confidence interval (CI) among PD-L1 positive GC patients. We also assessed the between-study heterogeneity (I 2). Forest and Funnel plots were obtained, and a P-value of <0.05 was considered statistically significant. A total of 567 articles were screened, and we selected three meta-analyses with a total of 40 studies conducted over a period of 14 years. In our umbrella review, a total of 8,419 GC patients with an average PD-L1 positivity of 39% were analyzed. We found that PD-L1 positivity in GC patients is associated with poor prognosis (pooled HR =1.44, 95% CI: 1.24-1.68, P<0.00001) having higher mortality reducing the chances of overall survival (OS). However, there are no significant differences in PD-L1 expression among different lymph node (LN) metastases (OR=1.31, 95% CI: 0.98-1.74, P=0.07) and tumor, node, and metastasis (TNM) stages (OR=1.13, 95% CI: 0.80-1.58, P=0.50). Early identification of PD-L1 expression may help tailor cost-effective and targeted immunotherapy among GC patients. More research is needed to further understand how PD-L1 affects LN metastasis and tumor invasion.

Pd and photoredox dual catalysis assisted decarboxylative ortho-benzoylation of N-phenyl-7-azaindoles.

The directing group assisted decarboxylative ortho-benzoylation of N-aryl-7-azaindoles with α-keto acids has been achieved by synergistic visible light promoted photoredox and palladium catalysis. The approach tenders rapid entry to aryl ketone architectures from simple α-keto acid precursors via the in situ generation of a benzoyl radical intermediate. The transformation provides a range of ortho-benzoylated N-aryl-7-azaindoles, with excellent site-selectivity and good functional group compatibility under mild reaction conditions. Biological target predictions indicate that these molecules may serve as potential anti-cancer and anti-viral agents.

Impact of Vitamin D Supplementation on Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune disease affecting a large number of people every year. The exact causal factor for this disease is unclear, but it commonly affects middle-aged women, with known triggers like stress, childbirth, infections, poor diet, lack of sleep, etc. Many epidemiological studies have indicated that various genetic abnormalities are also critical drivers of the onset of MS. The major risk factors of MS identified include hypovitaminosis D while environmental protective factors include allele HLA DRB1 1501, obesity, Epstein-Barr virus infection, sexual hormones, and smoking. Our article explores the correlation between the deficiency of vitamin D and the onset and progression of MS. The study uses a systematic review methodology by researching and reviewing scholarly articles exploring the topic. We conducted online searches of literature on Google Scholar and PubMed using the keywords "vitamin D deficiency" and "multiple sclerosis" and accessed the relevant secondary literature sources for review. The variables under study included vitamin D insufficiency as the dependent variable while MS was the independent variable. Causal variables included environmental, genetic, and protective factors. We hypothesized that there is indeed a correlation between vitamin D deficiency and MS. The findings from our review indicate a strong correlation between the insufficiency of vitamin D and the onset and progression of MS. These results are essential in devising interventions to accomplish primary and secondary prevention of MS, as well as integrating vitamin D supplementation in current treatment protocols for MS.

Long-term outcomes in patients with advanced adrenocortical carcinoma after image-guided locoregional ablation or embolization.

BACKGROUND: To evaluate outcomes and survival rates in patients with metastatic adrenocortical carcinoma (ACC) who were treated with image-guided locoregional treatments (IGLTs). PURPOSE: To evaluate the overall survival (OS) and clinical impact of IGLT in the management of patients with advanced metastatic ACC. METHODS: Retrospective review of 39 patients treated with IGLT between 1999 and 2018 was performed. Short- and long-term efficacy of treatments were defined based upon imaging and clinical data. Subgroup survival analysis was performed on patients with metastatic disease at diagnosis (N = 17) and compared with the same stage group from the most recent National Cancer Database (NCDB) report. Statistical analysis was performed using Cox proportional hazards model. RESULTS: Treatments were performed at different anatomic sites including liver (N = 46), lung (N = 14), retroperitoneum (N = 5), bone (N = 4), subcutaneous (N = 2), and intracaval (N = 1). Radiofrequency, microwave, cryoablation, or a combination of two modalities (45, 18, 3, 3, respectively) were used in 69 ablation sessions. Intra-arterial procedures were performed in 12 patients in 18 treatment cycles (range 1-3 per patient). As of a 2019 analysis, 11 patients were alive with a mean follow-up of 169 months (range 63-292 months) from diagnosis. Two- and 5-year OS rates for all patients were 84.5% and 51%, respectively, and 76.5% and 59% for patients with metastatic disease at diagnosis (N = 17). This compares favorably with an NCDB report of 35% 5-year survival rate for patients with metastatic disease. Female gender and longer time from diagnosis to first IGLT were found to be predictors of prolonged survival with hazard ratios of 0.23 (p < 0.001) and 0.66 (p = 0.001), respectively. CONCLUSION: IGLT may be associated with prolonged life expectancy in select patients with metastatic ACC.

Perioperative concerns in Pott's spine: A review.

Pott's disease is the most common granulomatous spine infection caused by tubercle bacilli and is a common site of osseous tuberculosis, accounting for 50-60% of cases. The delay in establishing diagnosis and management results in complications such as spinal cord compression and spinal deformity. The aim of this narrative review is to discuss the perioperative concerns in patients for spine surgery. The literature source for this review was obtained via PubMed, Medline, Google Scholar, Cochrane database of systematic reviews, and textbooks until December 2019. On the literature search, we could not retrieve any review article specifically discussing the perioperative concerns of spinal tuberculosis. Therefore, the aim of the present narrative review is to discuss the perioperative concerns of patients for spine surgery along with the specific concerns related to spinal tuberculosis.

Acetylated Benzothiazolone as Homobivalent SPECT Metallo-Radiopharmaceutical 99mTc-(6-AcBTZ)2DTPA: Design, Synthesis, and Preclinical Evaluation for Mapping 5-HT1A/7 Receptors.

Mapping different structural forms of serotonin subtypes 5-HT1A-5-HT7 using a selective-specific ligand with good pharmacokinetics and brain permeability can open avenues for personalized medication in depressed population. Herein, the selective 5-HT1A/7 antagonist, modified for enhanced brain permeation, is developed as a homobivalent ligand, (6-AcBTZ)2DTPA. After in-depth computational studies to probe the binding mechanism, two-step synthesis lead to (6-AcBTZ)2DTPA. Biocompatibility studies indicated cytocompatibility with 3.6-1.64% cell death (0.1 mM-1 pM) and hemocompatibility with 2.33% hemolysis of human erythrocytes. When 99mTc-radiolabeled in a quantitative yield (98%), a stable preparation was obtained with 7.4 and 3.5% dissociation upon incubation with human serum and excess cysteine. The single-photon-emission computed tomography (SPECT) tracer 99mTc-(6-AcBTZ)2DTPA showed biphasic clearance (t 1/2, distribution = 0.5 min and t 1/2, elimination = 482 min) and maximum brain uptake of 0.42 ± 0.02% ID/g with the regional localization (hippocampus: 11.38% ID/g; cortex: 26.42% ID/g; cerebellum: 25.23% ID/g). Thus, the 99mTc-metal-based SPECT neurotracer holds potential for neuroreceptor mapping.

Relation of Obesity to Outcomes of Hospitalizations for Atrial Fibrillation.

Obesity has been linked with increased incidence of atrial fibrillation (AF), but impact of presence of obesity on outcomes of hospitalizations for AF has not been investigated. We used the National Inpatient Sample database 2010 to 2014 to identify all adult hospitalizations aged ≥18years with a primary diagnosis of AF. Obese patients were identified using the co-morbidity variable for obesity, as defined in National Inpatient Sample databases. Multivariable logistic regression was used to compare in-hospital outcomes (mortality, acute stroke events) between obese and non-obese patients with AF. Of 431, 734 hospitalizations for AF, 66,138 (15.3%) were obese. Obese patients were younger and more likely to be African-Americans compared with non-obese patients. Despite being younger, obese patients had significantly higher prevalence of cardiovascular co-morbidities such as hypertension, diabetes mellitus, dyslipidemia, smoking, heart failure, and chronic renal failure (p <0.001 for all). After multivariate risk-adjustment, obese patients had a lower observed in-hospital mortality (0.5% vs 1.0%; unadjusted odds ratio = 0.52, 95% confidence interval [CI] 0.46 to 0.58, p <0.001; adjusted odds ratio = 0.83, 95% CI 0.73 to 0.94, p <0.001) and acute stroke events (0.4% vs 0.7%, unadjusted odds ratio = 0. 65, 95% CI 0.57 to 0.73, p < 0.001; adjusted odds ratio = 0.82, 95% CI 0.72 to 0.94) compared with non-obese patients. In conclusion, in this large retrospective analysis of an unselected nationwide cohort of patients hospitalized for AF, obese patients demonstrated lower risk-adjusted odds of in-hospital mortality and stroke events, consistent with an "obesity paradox."

Enterogenous Cyst Presenting as Mediastinal Mass in a Newborn.

Duplication cyst is a rare congenital malformation. Enterogenous cyst are foregut duplication cyst with or without a vertebral defect. We report a case of a 36hr old neonate with mediastinal enterogenous cyst associated with vertebral defects. The embryology, differentials, and management of enterogenous cyst in the newborn have been discussed.

Challenges in Management of Autoimmune Hepatitis With Concurrent Graves Thyrotoxicosis.

The management of concurrent Graves thyrotoxicosis and autoimmune hepatitis (AIH) can be challenging. We present a 37-year-old woman with a recent diagnosis of Graves disease and acute liver injury. Laboratory workup was concerning for AIH. Liver biopsy showed plasma cell infiltration and interface hepatitis consistent with AIH, and treatment with methylprednisolone was initiated. Azathioprine was started after thiopurine methyltransferase testing, and prednisone was tapered down. Thionamide use was contraindicated, so clinical euthyroidism was achieved with the use of cholestyramine and glucocorticoids. Our case highlights the complexities of management when patients are affected by 2 concurrent illnesses.

Maintain Your Brain: Protocol of a 3-Year Randomized Controlled Trial of a Personalized Multi-Modal Digital Health Intervention to Prevent Cognitive Decline Among Community Dwelling 55 to 77 Year Olds.

BACKGROUND: Maintain Your Brain (MYB) is a randomized controlled trial of an online multi-modal lifestyle intervention targeting modifiable dementia risk factors with its primary aim being to reduce cognitive decline in an older age cohort. METHODS: MYB aims to recruit 8,500 non-demented community dwelling 55 to 77 year olds from the Sax Institute's 45 and Up Study in New South Wales, Australia. Participants will be screened for risk factors related to four modules that comprise the MYB intervention: physical activity, nutrition, mental health, and cognitive training. Targeting risk factors will enable interventions to be personalized so that participants receive the most appropriate modules. MYB will run for three years and up to four modules will be delivered sequentially each quarter during year one. Upon completing a module, participants will continue to receive less frequent booster activities for their eligible modules (except for the mental health module) until the end of the trial. DISCUSSION: MYB will be the largest internet-based trial to attempt to prevent cognitive decline and potentially dementia. If successful, MYB will provide a model for not just effective intervention among older adults, but an intervention that is scalable for broad use.

Adolescent and Young Adult Chronic Myeloid Leukemia in Real-World Settings: Experience from a Tertiary Care Institute in Northern India.

The data on adolescent and young adult chronic myeloid leukemia (AYA-CML) from the Indian subcontinent are scarce. We studied characteristics of AYA-CML through a retrospective analysis of 1950 CML patients registered to a tertiary care hospital in Northern India. AYA-CML represented 22.1% of all CML patients, with cumulative overall survival (OS) of 84%, and 1 and 8 years OS of 94.2% and 74.2%, respectively. Of all cases, 8.91% patients had advanced disease at the time of diagnosis, and 13.95% had myelofibrosis in the diagnostic marrow, 79.6% had complete cytogenetic response (CCyR), and 84.5% had major molecular response (MMR). Loss of CCyR and MMR was noted in 37.2% and 28.4%, respectively. The cumulative OS was significantly better in patients on patient assistance program, and they were initiated on therapy within 3 months of symptom onset.

Role of Chemiluminescence examination as non-invasive diagnostic tool in early detection of Leukoplakia.

OBJECTIVES: To assess the efficacy of Chemiluminescent light (Vizilite plus) in enhancing visualization and its ability to highlight Leukoplakia lesion. MATERIAL AND METHODS: This was a cross-sectional study done on 40 study subjects. Subjects were inducted into the study irrespective of age and sex based on the specific inclusion and exclusion criteria. The lesion parameters like the location of the lesion, the shape of lesion, the size, the extent, borders and the presence or absence of any adjacent satellite lesions were assessed under Incandescent light followed by Toluidine blue and Vizilite plus examinations. Histopathological examination results were considered as the gold standard and TBLU and CHEM outcomes were compared to them. RESULTS: Vizilite plus examination method was most effective in assessing the size, borders and shape of the lesions followed by Toluidine blue and Incandescent light examinations. Toluidine blue and Vizilite plus examination methods demonstrated the sensitivity of 100% and specificity of 97.3%. They also demonstrated PPV of 100% and NPV of 75% with reliable accuracy of 97.5%. CONCLUSION: Chemiluminescent light is a stepping stone and has the potential to revolutionize the diagnostic protocol for patients with potentially premalignant lesions. The device can be used as a general oral mucosal examination system and may in particular improve the visualization of potentially premalignant lesions.

Mass spectrometry-assisted venom profiling of Hypnale hypnale found in the Western Ghats of India incorporating de novo sequencing approaches.

Hypnale hypnale (hump-nosed pit viper) is considered to be one among the medically important venomous snake species of India and Sri Lanka. In the present study, venom proteome profiling of a single Hypnale hypnale from Western Ghats of India was achieved using SDS-PAGE based protein separation followed by LC-MS/MS analysis. The identities of the proteins that were not established using the Mascot search were determined through de novo sequencing tools such as Novor followed by MS-BLAST based sequence similarity search algorithm and PEAKS proteomics software. The combined proteomics analysis revealed a total of 37 proteins belonging to nine different snake venom families, in which 7 proteins were exclusively identified through de novo strategies. The enzymatic and non-enzymatic venom protein families identified include serine proteases, metalloproteases, phospholipase A2, thrombin-like enzymes, phospholipase B, C-type lectins/snaclecs, disintegrins, cysteine rich secretory proteins and nerve growth factor. Among these, disintegrins, nerve growth factor, phospholipase B and cysteine rich secretory protein families were identified for the first time in HPV venom. This could possibly explain the regiospecific venom variation seen across snake species. Taken together, the venom proteome profiling on Indian Hypnale hypnale venom correlates with the clinical manifestations often seen in the envenomed victims.

Nlrp12 Mediates Adverse Neutrophil Recruitment during Influenza Virus Infection.

Exaggerated inflammatory responses during influenza A virus (IAV) infection are typically associated with severe disease. Neutrophils are among the immune cells that can drive this excessive and detrimental inflammation. In moderation, however, neutrophils are necessary for optimal viral control. In this study, we explore the role of the nucleotide-binding domain leucine-rich repeat containing receptor family member Nlrp12 in modulating neutrophilic responses during lethal IAV infection. Nlrp12-/- mice are protected from lethality during IAV infection and show decreased vascular permeability, fewer pulmonary neutrophils, and a reduction in levels of neutrophil chemoattractant CXCL1 in their lungs compared with wild-type mice. Nlrp12-/- neutrophils and dendritic cells within the IAV-infected lungs produce less CXCL1 than their wild-type counterparts. Decreased CXCL1 production by Nlrp12-/- dendritic cells was not due to a difference in CXCL1 protein stability, but instead to a decrease in Cxcl1 mRNA stability. Together, these data demonstrate a previously unappreciated role for Nlrp12 in exacerbating the pathogenesis of IAV infection through the regulation of CXCL1-mediated neutrophilic responses.