Meta-analysis of Genetic polymorphism of Enhancer of Zeste Homolog2 gene in cancer susceptibility.

The alteration in the expression of enhancer of zeste homolog-2 (EZH2) gene is very well known in the progression, severity, and aggressiveness of cancer. Hence, it is important to study the genomic variation of the EZH2 gene. Previously, many association-based studies investigated the association between rs2302427C>G and cancer susceptibility. However, the result had been inconsistent. Therefore, our meta-analysis aimed to identify the association between EZH2 rs2302427 and cancer risk. A systematic literature search was done for databases PubMed, Google Scholar, Science Direct, and Cochrane library up to September 2020 and statistical analysis was performed by RevMan v 5.3. A total of six studies comprised 1876 cases and 2555 controls were included in the current meta-analysis. The pooled analysis showed that overall, there is significant association of rs2302427 C>G change with reduced cancer risk (odds ratio = 0.60, 95% confidence interval [0.35-1.03], P = 0.07) but non-significantly. Further, the subgroup analysis also revealed that there is no significant difference between the Asian and European population, and both exhibit the protective nature of rs2302427 with cancer. The present meta-analysis indicated that EZH2 rs2302427 has an association with cancer in reducing the risk but for the Indian population studies are required as the Indian population comprises various sub-population genetically isolated for long.

EZH2 Expression and Survival for ER+/tamoxifen Treated Breast Cancer Patients with rs2302427 C>G: A Novel Prognostic and Risk Predictive Biomarker.

BACKGROUND AND OBJECTIVES: Overexpression of the EZH2 gene silences several genes involved in DNA repair, cell-cell adhesion, and tumor suppressor genes, resulting in the development of several types of cancers. In the present study, a genetic polymorphism analysis was performed by selecting three SNPs (rs.2302427C>G, rs.3757441C>T, and rs.6950683T>C) of the EZH2 gene based on our previous in silico studies. METHODS: A total of 250 breast cancer patients and 250 healthy individuals were recruited for the study. Patients with pre-operative breast cancer with different clinical-pathological variables and age-matched healthy women were recruited for the EZH2 gene expression analysis. RESULTS: The genetic polymorphism analysis revealed two SNPs (rs.2302427C>G and rs.6950683T>C) of the three studied SNPs of the EZH2 gene have a protective role in all three genetic models. The haplotype analysis predicted that two haplotypes ACGT and ACGC were significantly associated with a lower risk of breast cancer. INTERPRETATION AND CONCLUSIONS: Three significant findings of the SNP rs.2302427C>G (Asp193His) i.e., protective role against breast cancer, survival advantage in ER+/tamoxifen treated breast cancer patients, and decreased expression due to the presence of mutant GG genotype, suggests considering it as an important prognostic biomarker for a good survival outcome of breast cancer patients treated with ER+/tamoxifen. Compared with other studies, the other SNP rs.3757441T>C was observed to have a protective effect in breast cancer biology but plays an antagonistic role in colorectal cancer (CRC) biology. To our knowledge, this is the first detailed study on computationally validated EZH2 SNPs in breast cancer.

Valproic acid-induced eosinophilic pleural effusion: An uncommon occurrence.

A 43-year-old male using valproic acid (VA) for 2 years for seizure disorder presented with right-sided moderate pleural effusion. Pleural fluid analysis revealed exudative effusion with 42% eosinophils. There was no evidence of haemothorax, pneumothorax, malignancy, and parasitic infections. Suspecting a drug-related event, VA was discontinued. The patient showed clinical improvement with resolution of pleural effusion on chest radiograph three weeks later. VA is a popular drug used for variety of disorders like seizures, migraines, and schizophrenia. There is a paucity of literature on VA-induced pleural effusion. Though a rare phenomenon, clinicians should be aware of such a possibility to avoid erroneous diagnosis.

Utility of fine needle aspiration cytology to comprehend the pathogenesis of extrapulmonary tuberculosis.

BACKGROUND: Fine needle aspiration cytology (FNAC) is a precise, cost-effective, and minimal invasive technique for diagnosis of extrapulmonary tuberculosis (EPTB). This study was aimed to analyze clinical and cytological characteristics of EPTB with particular emphasis on pathogenesis. METHODS: This was a retrospective study analyzing 237 cases of EPTB diagnosed on FNAC. Depending on the presence of necrosis and granulomas, cases were divided into three classes. Association of cytomorphology with positivity for acid-fast bacilli was analyzed by Chi-square test to demonstrate any specific pattern. RESULTS: Majority of our patients diagnosed as EPTB (73.8%) were young with male-to-female ratio of 1:1.3. The mean age was 23.2 years (age range 9 months to 81 years). The most frequent site involved was lymph node (89.5%) with predilection for cervical lymph nodes (81.4%). The extranodal sites affected were breast, abdominal wall, chest wall, salivary glands, soft tissue, bone, and genitourinary tract. Detailed cytological examination revealed necrotizing granulomatous inflammation as most common pattern (43%). Acid-fast bacilli were detected only in 43.5% of the cases and bacilli detection was more frequently associated with necrotizing lesions (64.9%). Non-necrotizing lesions showed AFB positivity only in 7.4% of the cases. CONCLUSION: To achieve the goal of tuberculosis eradication, it is essential to understand its different forms of clinical presentation and detailed pathogenesis including host factors, host-pathogen interaction, and molecular mechanisms. Cytomorphological features of the representative lesions might be valuable in providing clues regarding possible pathogenetic mechanisms.

Askin's tumour in pregnancy with dismal prognosis.

Askin's tumour is a rare malignant neoplasm of the chest wall. A 23-year-old primigravida patient was admitted to the hospital with complaints of chest wall swelling, cough and dyspnoea. Radiological examination showed a chest wall mass in right hemithorax with erosion of ribs and moderate pleural effusion. Fine-needle aspiration cytology was suggestive of malignant small round cell tumour. Immunohistochemical analysis together with the clinical and radiological findings led to the definitive diagnosis of Askin's tumour. Despite receiving multimodality therapy, she had residual soft tissue mass and died after 6 months. Rarity of this malignancy during pregnancy renders the case unique.

Spectrum of Clinical Presentation of Pulmonary Alveolar Microlithiasis: Case Series from North India.

We describe five cases of pulmonary alveolar microlithiasis (PAM) from North India with characteristic radiological and histopathological features. All patients were symptomatic with variable severity and duration of the symptoms and one patient developed cor-pulmonale during the course of follow-up. Diagnosis of PAM was suspected on the basis of classical sand-storm appearance on radiological examination and confirmed by transbronchial lung biopsy in four of the five cases. Apart from other features, presence of pleural and pericardial calcification in one case makes this discussion valuable. Awareness of this specific entity among the clinicians is essential to avoid unnecessary investigations.

Guidelines for Diagnosis and Management of Bronchial Asthma: Joint Recommendations of National College of Chest Physicians (India) and Indian Chest Society.

Bronchial asthma is an important public health problem in India with significant morbidity. Several international guidelines for diagnosis and management of asthma are available, however there is a need for country-specific guidelines due to vast differences in availability and affordability of health-care facilities across the globe. The Indian Chest Society (ICS) and the National College of Chest Physicians (NCCP) of India have collaborated to develop evidence-based guidelines with an aim to assist physicians at all levels of health-care in diagnosis and management of asthma in a scientific manner. Besides a systematic review of the literature, Indian studies were specifically analysed to arrive at simple and practical recommendations. The evidence is presented under these five headings: (1) definitions, epidemiology and impact, (2) diagnosis, (3) pharmacologic management of stable disease, (4) management of acute exacerbations, and (5) non-pharmacologic management and special situations. The modified grade system was used for classifying the quality of evidence as 1, 2, 3, or usual practice point (UPP). The strength of recommendation was graded as A or B depending upon the level of evidence.

Medical education in India: current challenges and the way forward.

Medical education in India is suffering from various shortcomings at conceptual as well as implementation level. With the expansion in medical education, the doctor to patient ratio has increased but these numbers do not align well with the overall quality of medical care in the country. To address this issue, a comprehensive analysis of various associated factors is essential. Indian medical education is suffering from a maldistribution of resources, unregulated growth in the private sector, lack of uniform admission procedures and traditional curricula lacking innovative approaches. To achieve higher standards of medical education, our goal should be to re-evaluate each and every aspect; create an efficient accreditation system; promote an equal distribution of resources, redesign curricula with stricter implementation and improved assessment methodologies; all of which will generate efficient medical graduates and consequently better health care delivery, and resulting in desired change within the system.

Challenges in endobronchial tuberculosis: from diagnosis to management.

Despite the rapid advancement in diagnostic and therapeutic modalities, endobronchial tuberculosis (EBTB), defined as tuberculous infection of the tracheobronchial tree, continues to remain challenging for clinicians. Nonspecific respiratory symptoms along with normal chest radiograph in 10-20% of cases may be alleged for the diagnostic delay. Variable diagnostic yield with sputum microscopy might further compound the problem. In such cases, high resolution computed tomography (HRCT) works as a more sensitive tool and demonstrates involvement of tracheobronchial tree described classically as "tree-in-bud" appearance. Bronchoscopic biopsy is considered the most reliable method for confirmation of the diagnosis with 30% to 84% positivity in different series. Evolution of the disease is also unpredictable with frequent progression to bronchostenosis, therefore requiring regular follow-up and early intervention to halt the natural course. This review article elaborates various aspects of the disease with specific focus on diagnostic dilemma and recent advances in interventional bronchoscopy. In addition, this discussion evokes optimism for further research and introduction of innovative therapeutic modalities.

Factors influencing early health facility contact and low default rate among new sputum smear positive tuberculosis patients, India.

Early case identification and prompt treatment of new sputum smear positive case are important to reduce the spread of tuberculosis (TB). Present study was planned to study the associated factors for duration to contact the health facility since appearance of symptoms and treatment default. Methodology. It was prospective cohort study of TB patients already registered for treatment in randomly selected TB units (TUs) in Himachal Pradesh, India. Relative risk (RR) was calculated as risk estimate to find out the explanatory variables for early contact and default. Results. Total 1607 patients were recruited and 25 (1.5%) defaulted treatment. Patients from nuclear family (aRR: 1.37; 1.09-1.73), ashamed of TB (aRR: 1.32; 1.03-1.70), wishing to disclose disease status (aRR: 1.79; 1.43-2.24), but aware of curable nature (aRR: 1.67; 1.17-2.39) and preventable (aRR: 1.35; 1.07-1.70) nature of disease, contacted health facility early since appearance of symptoms. Conclusion. Better awareness and less misconceptions about disease influences the early contact of health facility and low default rate in North India.

Medical marijuana: A panacea or scourge.

Marijuana (Cannabis sativa) has been used for recreational and medical purposes since ages. Marijuana smoking is an evil, which is on the rise with about 180.6 million active users worldwide. The recent legalization of marijuana in Uruguay has generated global interest. The purpose of this short review is to describe the various preparations, uses and adverse effects of medical marijuana. It also deals with the adverse effects of marijuana smoking when used for recreational purposes. ased on the current literature, medical use of marijuana is justified in certain conditions as an alternative therapy.

Electronic cigarettes: facts and myths.

E-cigarettes are devices designed to deliver nicotine to users without burning tobacco. These are being marketed globally as a healthier substitute to the conventional cigarettes and as smoking quitting aids. The use of these devices has increased recently in developed countries with approximately 1.3 million users reported in the United Kingdom in 2013. Perception of these products as a safe alternative, appealing advertisements, and lax regulatory policies have helped gain popularity among the public. Despite all these claims, a debate is on-going because of insufficient scientific data regarding safety and efficacy of e-cigarettes as well as awareness of the potential health hazards. To solve the dilemma, more scientific studies in this field are required. Prompt regulatory response with strict vigilance on marketing and advertising may be desirable in the interest of users and public at large.

Cytohistological correlation in diagnosis of lung tumors by using fiberoptic bronchoscopy: study of 200 cases.

BACKGROUND: Examination of specimens obtained through flexible fiberoptic bronchoscope is an important and often the initial diagnostic technique performed in patients with suspected malignant lung lesion. AIMS: To evaluate the correlation of cytological findings of bronchial washings, bronchial brushing and imprint smear of bronchial biopsy in the diagnosis of lung tumors, with histopathology of bronchial biopsy taking the latter as the confirmatory diagnostic test. MATERIALS AND METHODS: A total of 200 patients with lung mass were included in the study. Bronchial brushings were obtained from all 200 cases. In the first 100 cases, pre-biopsy bronchial washing (washing collected before the brushing and biopsy procedure) while post-biopsy washing (washing at the end of the procedure) was procured in all 200 cases. Imprint smears of bronchial biopsy were prepared in 150 cases. RESULTS: Sensitivity and specificity of brushing was 76.58% and 77.78% respectively and that of imprint smear was 81.35% and 78.12% respectively. Pre-biopsy and post-biopsy washing showed high specificity of 88.89%, but low sensitivity of 30.14 and 36.77% respectively. No significant difference was found in sensitivity between brushing and imprint smear (Chi-square; P = 0.4187); and between pre-biopsy and post-biopsy washing (Chi-square; P = 0.7982). However, there was a significant difference between sensitivity of brushing and washing (Chi-square; P = 0.0001). The sensitivity of combination of three cytological diagnostic techniques was 87.29%. CONCLUSION: Bronchial brushing and washing cytology in combination with imprint cytology aids in the diagnosis of lung tumors. Therefore, all these techniques may be used concurrently along with bronchial biopsy to diagnose lung tumors.

Pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is a rare, chronic lung disease with bilateral intra-alveolar calcium and phosphate deposition throughout the lung parenchyma with predominance to lower and midzone. Although, etiology and pathogenesis of PAM is not fully understood, the mutation in SLC34A2 gene that encodes a sodium-phosphate co-transporter in alveolar type II cells resulting in the accumulation and forming of microliths rich in calcium phosphate (due to impaired clearance) are considered to be the cause of the disease. Chest radiograph and high-resolution CT of thorax are nearly pathognomonic for diagnosing PAM. HRCT demonstrates diffuse micronodules showing slight perilobular predominance resulting in calcification of interlobular septa. Patients with PAM are asymptomatic till development of hypoxemia and cor-pulmonale. No therapy has been proven to be beneficial except lung transplantation.