Safety and Efficacy of 25 mg/kg and 35 mg/kg vs 10 mg/kg Rifampicin in Pulmonary TB: A Phase IIb Randomized Controlled Trial.

Background: Globally, no trial data are available on head-to-head comparison between 10 mg/kg and 25/35 mg/kg rifampicin in treating pulmonary tuberculosis during study initiation. Methods: A multicentric, phase IIb randomized trial recruited 333 new culture-positive, drug-sensitive adult patients with pulmonary tuberculosis to compare safety and efficacy of high-dose rifampicin (R25/R35), against conventional dose (R10) given daily for 8 weeks followed by standard doses for 16 weeks. Main outcomes were treatment-emergent grade 3/4 adverse events (AEs) and time-to-culture conversion in liquid media, assessed by division of AIDS system for grading the severity of adverse events division of AIDS criteria and Kaplan-Meier methods. Results: In a modified intention-to-treat population of 323 patients (R10: 105/R25: 112/R35: 106), grade 3/4 AEs were reported in 34 patients (R10: 9.5% [10/105], R25: 9.8% [11/112], R35: 12.3% [13/106]) during the intensive phase. Among 23 patients (R10: 3.8% [4/105], R25: 6.3% [7/112], R35: 11.3% [12/106]) with grade 3/4 hepatotoxicity, 15 (R10: 1.9% [2/105], R25: 3.6% [4/112], R35: 8.5% [9/106]) had grade 3/4 hyperbilirubinemia and 9 patients (R10: 1.0% [1/105], R25: 0.9% [1/112], R35: 6.6% [7/106]) developed clinical jaundice. Significant differences observed only between R10 and R35 with hepatotoxicity (P = .039), hyperbilirubinemia (P = .031), clinical jaundice (P = .032), and treatment interruption (P = .039). Eighteen serious AEs and 6 deaths (R10: 3/R25: 1/R35: 2) occurred during study period. Time to stable culture conversion in liquid media was faster in R25 (adjusted hazard ratio, 1.71; 95% confidence interval [CI], 1.26-2.31 [solid: 1.97; 95% CI, 1.46-2.67]) and R35 (1.81; 95% CI, 1.33-2.48 [solid: 2.24; 95% CI, 1.64-3.06]), than R10 (34 vs 44 days). R25 had no failure/relapse. Conclusions: Hepatotoxicity, clinical jaundice, and treatment interruptions occurred significantly higher with R35 than R10. Because R25 was comparably safe as R10 and also highly efficacious than R10, it may be considered for implementation. Clinical Trials Registration. CTRI/2017/12/010951.

Evaluation of medical adherence, adverse drug reactions, and quality of life in post tubercular obstructive airway disease.

Background: Increasing incidence of tuberculosis is intensifying the posttubercular obstructive airway disease (PTOAD) in developing countries. Currently, there are no standard treatment guidelines for the management of PTOAD patients. The present study aims to evaluate the prescribing pattern, adherence, adverse drug reactions (ADRs), and quality of life (QoL) in PTOAD patients. Materials and Methods: A prospective observational study was conducted to evaluate the prescriptions of PTOAD patients, estimating the medical adherence using Morisky 8-Item Medication Adherence Questionnaire, assessing ADRs using Hartwig's Severity Assessment Scale and assessing QoL using St. George's respiratory Questionnaire. Chi-square test, analysis of variance, paired t-test were used to compare the data. The significance of change in adherence status was assessed by Wilcoxon signed-rank test. Results: A total of 94 prescriptions of PTOAD were analyzed. Inhaled long-acting muscarinic antagonist was prescribed to 31.9% of patients. The most common inhaled fixed dose combination was long-acting beta-2 agonist with corticosteroid, prescribed to 52.1% of patients. At final follow-up, maximum percentage of patients were found to be highly adherent, i.e. 56.4%. Overall, 34% of patients have complained about mild category of ADRs. A significant improvement in QoL was observed. At baseline, mean forced expiratory volume in 1 (FEV1) was 64.66% ±23.61%, which increased significantly to 73.34% ±21.60% on final follow-up (P < 0.001). Conclusion: Bronchodilators are the mainstay of treatment of PTOAD patients, since both the QoL and FEV1 were improved with treatments. However, to have good treatment outcome, strict adherence along with safety of the medications must be assured.

Non-arteritic anterior ischaemic optic neuropathy and obstructive sleep apnoea.

Anterior ischaemic optic neuropathies (AIONs) are a common cause of permanent visual loss in the elderly population. The non-arteritic subtype has been intensively studied. While systemic associations such as hypertension and diabetes mellitus are commonly recognized and treated, others such as obstructive sleep apnoea (OSA) are largely overlooked in daily practice. A 60-year-old man who gave no history of any systemic illness presented to us 1 week following an uneventful cataract surgery with posterior chamber intraocular lens implantation in his right eye. The surgery was performed elsewhere by an eye-healthcare professional where the patient presented primarily with a history of progressively worsening diminution of vision in the same eye for 5 days and was diagnosed with a senile cataract. The postoperative visual gain was unsatisfactory; hence he sought another opinion. A diagnosis of non-arteritic AION (NAION) was established. Systemic evaluation revealed elevated diastolic blood pressure, dyslipidaemia and severe OSA. Prompt treatment with systemic steroids and simultaneous management of the accompanying systemic morbid conditions saved some useful vision in the affected eye. This also prevented involvement of the fellow unaffected eye. A comprehensive ocular examination with emphasis on systemic evaluation of the patient for coexisting illness is imperative before proceeding with any medical or surgical intervention. OSA is a definitive risk factor for the development of NAION, though it remains underdiagnosed and untreated. Cataract surgery has been shown to worsen underlying NAION. Systemic stabilization averts potentially blinding sequel in the unaffected eye of these patients.

High-Dose Rifampicin Mediated Systemic Alterations of Cytokines, Chemokines, Growth Factors, Microbial Translocation Markers, and Acute-Phase Proteins in Pulmonary Tuberculosis.

High-dose rifampicin (HDR) is now undergoing clinical trials to improve the efficacy of anti-tuberculosis treatment (ATT). However, the influence of HDR in the modulation of different cytokines, chemokines/growth factors, microbial translocation markers (MTMs), and acute-phase proteins (APPs) in pulmonary tuberculosis (PTB) is not well known. PTB individuals were separated into three different arms (R10, R25, and R35) based on their rifampicin dosage. We examined the circulating levels of Type 1, Type 2, pro-inflammatory/regulatory cytokines, chemokines/growth factors, MTMs, and APPs at baseline and after completion of the second month of ATT by ELISA. The baseline levels of cytokines, chemokines/growth factors, MTMs, and APPs did not (except IL-5, IL-6, IL-17A, MCP-1, MIP-1ß, GCSF, SAA, ⍺2 MG, Hp) significantly differ between the study individuals. However, at the second month, the plasma levels of Type 1 (TNFα and IFNγ), Type 2 (IL-4, IL-5, and IL-13), pro-inflammatory/regulatory cytokines (IL-6, IL-17A, IL-10, and GMCSF), and APPs were significantly decreased in R35 regimen- compared to R25 and/or R10 regimen-treated PTB individuals. In contrast, the plasma levels of IL-2, IL-8, MCP-1, MIP-1ß, GSF, and MTMs were significantly increased in the R35 regimen compared to R25 and/or R10 regimen-treated PTB individuals. Overall, our data reveal that HDR could potentially be beneficial for host immunity by altering different immune and inflammatory markers.

A cross-sectional study to determine the psychological distress among pulmonary tuberculosis patients during COVID-19 pandemic.

COVID-19 pandemic had adversely affected the services of the National Tuberculosis (TB) Elimination Programme, resulting in psychological distress among pulmonary tuberculosis patients (PTB). This cross-sectional, hospital-based study included 361 PTB patients. Three pre-defined questionnaires were used for the analysis, a questionnaire to evaluate anxiety related to COVID-19, a patient health questionnaire (PHQ-9) for depression, and a fear of COVID-19 scale (FCV-19S) questionnaire. Among 361 PTB patients, 13% (n=47) had COVID-19 infection. Out of the total patients, 69% (n=250) were DR-TB (drug resistance-tuberculosis) cases. Proportion of anxiety, fear and depression due to COVID-19 was found in 49% (n=177), 23% (n=83), 67% (n=247) respectively. Delay in the initiation of anti-tubercular treatment was found in 58% (n=210) of the cases, among which the majority, i.e., 69% (n=172, p=0.011), were DR-TB. This pandemic has led to a sudden step-down of PTB. Trend analysis of the psychological distress showed a peak following the COVID-19 pandemic. Most DR-TB patients had delayed initiation of the anti-tubercular treatment during the pandemic. The preponderance of the younger age group was seen in the pulmonary tuberculosis patients, and a majority of them had DR-TB. Depression was the predominant psychological distress among the study subjects during the pandemic.

Epidermal growth factor receptor mutations in adenocarcinoma lung: Comparison of techniques for mutation detection.

Background: Targeted therapy using tyrosine kinase inhibitors in cases of non-small-cell lung carcinoma (NSCLC) that harbor epidermal growth factor receptor (EGFR) mutations has drastically improved the overall survival rate. The current study estimated the frequency of EGFR mutations in the Indian population by analyzing the diagnostic parameters of various techniques available for the detection of these mutations. Materials and Methods: A case series of 100 histologically diagnosed and immunohistochemically confirmed NSCLC with the adenocarcinoma phenotype comprises the study sample. EGFR mutations were detected using clone-specific immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), and Sanger sequencing. Results: EGFR mutations were identified in 48% cases with 72.78% mutations involving exon 19. Clone-specific IHC had a low sensitivity of 46.43%, and the specificity was 79.17%. Sanger sequencing yielded interpretable results in 16% cases only, which were in concordance with the results of real-time PCR. Conclusion: EGFR mutations are increasingly being explored for targeted therapy and personalized medicine. Real-time PCR was found to be the best and the most accurate method for the detection of somatic EGFR mutations in adenocarcinoma primarily in the lungs.

Concurrent central nervous system involvement in immunocompetent adults with pulmonary miliary TB: a prospective analysis.

BACKGROUND: Wallgren's tuberculosis (TB) timetable demonstrated co-occurrence of miliary TB and tuberculous meningitis in children. To verify the same in immunocompetent adults, we prospectively evaluated the prevalence and spectrum of central nervous system (CNS) involvement in patients with pulmonary miliary TB. MATERIALS AND METHODS: This was a tertiary care, University hospital-based, prospective evaluation performed from December 2018 to June 2020. Newly diagnosed patients with pulmonary miliary TB were subjected to a detailed clinical, laboratory and MRI-based evaluation. All patients received treatment as per WHO guidelines. RESULTS: Out of 342 patients with pulmonary TB, 53 patients met the eligibility criteria. The median age at presentation was 32 y and approximately two-thirds of patients were female. Clinically, only two-fifths of patients had features of CNS involvement. Cerebrospinal fluid (CSF) and imaging abnormalities were noted in 46 patients each. Twelve (23.5%) patients were diagnosed with definite-category tuberculous meningitis. Presence of an infarct significantly correlated with neurological features. Mantoux positivity correlated significantly with the presence of choroid tubercles, CSF changes and brain tuberculomas. CONCLUSION: This is the first study to endorse Wallgren's observations in immunocompetent adults. A high index of suspicion, even in asymptomatic patients, may uncover tuberculous lesions involving the CNS and guide optimal monitoring of patients.

Clinical, radiologic and serologic profile of patients with interstitial pneumonia with autoimmune features: a cross-sectional study.

The current study aimed to characterize patients from a rheumatology referral center in north India, who satisfied the definition of interstitial pneumonia with autoimmune features (IPAF) as given by the American Thoracic Society and European Respiratory Society (ATS/ERS) consensus committee in 2015. Thirty-five adult patients aged 18 years and above, fulfilling the 2015 ATS/ERS criteria for IPAF were included in the study. The clinical and immunological profile, and radiologic findings on high-resolution computerized tomography thorax were noted. Antinuclear antibody (ANA) by indirect immunofluorescence at 1:320 titer and myositis-specific antibody (MSA) assays were performed. Non-parametric tests were used to compare variables between groups. The study cohort included predominantly female patients with a mean age of 50.6 ± 13 years and mean duration of disease of 38.8 ± 28.4 months. Majority of patients (49%) fulfilled the morphologic and serologic domains as per the IPAF consensus criteria and 31% patients had features in all three domains. Non-specific interstitial pneumonia was the most common pattern observed in 77% patients. Raynaud's phenomenon and inflammatory arthritis were the predominant autoimmune features. Pulmonary arterial hypertension was documented in 60% of patients on echocardiography. Positive ANA at 1:320 dilution was present in all 26 patients tested, whereas extractable nuclear antigen and MSA assays detected autoantibodies in 49% and 51% of patients respectively. IPAF predominantly affected females in the age group of 50 years and above, with varied autoimmune manifestations and autoantibody profile.

Aggressive oral granular cell tumor with periorbital involvement: An unusual case.

Granular cell tumor (GCT) of the oral cavity is rare and so is the involvement of the eye, orbit, and ocular adnexa. A 65-year-old male developed a posttraumatic ulceroproliferative mass over his left cheek for the past 1 year. The mass involved the periorbital region with accompanying blood-stained purulent discharge from multiple sinus tracts over this lesion for the past 6 months. Radiographs of the orbit suggested chronic osteomyelitis. The lesion was not responsive to treatment with antibiotics. Enlarged submandibular lymph node demonstrated reactive lymphadenitis on cytological examination. However, computed tomography scan of the paranasal sinus (PNS) revealed possibly a malignant mass extending into the maxillary sinus and left extraconal space. Surprisingly, histopathological examination and immunohistochemistry from a growth involving the left upper retromolar region that extended up to the midline and periorbital region suggested a diagnosis of GCT. This unusual and new presentation of GCT is not well known to the dentists and also to the ophthalmologists. It is imperative to examine anatomically neighboring structures, especially the eye, nasal cavity, PNSs, and oval cavity among other structures in an underlying pathology in either of these sites.

Spectrum of interstitial lung diseases and their association with pulmonary hypertension.

Interstitial lung diseases (ILDs) are an intriguing group of pulmonary disorders, which still require the study of epidemiological, genetic, pathophysiological, clinical, and radiological parameters. Pulmonary hypertension (PH) is an underreported complication in interstitial lung diseases which is associated with worse outcome. In our study, we have reported the spectrum of ILDs and estimated the prevalence of pulmonary hypertension among these subjects at a tertiary care centre. A cross-sectional study was performed in which demographical, clinical, radiological, and histological data of subjects with ILD, attending the department of Respiratory Medicine in the University was collected from 1st September 2018 to 31st August 2019. Serological tests were done wherever indicated. Standard criteria along with multidisciplinary opinion were needed to arrive at the final diagnosis. All subjects were screened for pulmonary hypertension via 2-D echocardiography. Mean pulmonary artery pressure ≥20 mmHg was used to define PH. In the defined period, 239 subjects were enrolled (58% females, n=141; mean age 52.38±13.40 years). A tissue diagnosis was obtained in 34% cases.  The most common ILD was hypersensitivity pneumonitis (32.2%), followed by autoimmune-ILD (31.4%), idiopathic pulmonary fibrosis (IPF) (15.9%) and sarcoidosis (12.6%), non-IPF idiopathic interstitial pneumonitis (2.1%) and rest 21 (5.9%) subjects were diagnosed as other types of ILD.  Pulmonary hypertension was seen in 46.0% of subjects.

Severe COVID-19: A distinct entity.

Severe coronavirus disease-2019 (COVID-19) is a distinct entity that rapidly evolves and may abruptly culminate in to a critical illness. As per Chinese experience, approximately, 15% of patients of COVID-19 progress to severe disease and 5% become critically ill. The incidence of severe and critical illness is higher among men, patients older than 65 years of age and in persons with other medical comorbidities. Cytokine storm cause pronounced lung damage and multiorgan failure. Coagulopathy is a key component of severe COVID-19. Critically ill patients are generally predisposed to a high risk of thromboembolism as well. Lymphopenia predisposes to severe disease. None of the antiviral or immunomodulators has proven efficacy in severe COVID-19. Supplemental oxygen need be administered in patients with hypoxemia. Excessive breathing effort, acute respiratory distress syndrome (ARDS), encephalopathy, and multiorgan failure are indications for mechanical ventilation. In a large number of patients, the overall outcome is poor. Health care workers in intensive care units are exposed to the enormous risk of acquiring hospital acquired SARS-COV-2 infection.

Clinical and Radiological Presentations of Various Pulmonary Infections in Hospitalized Diabetes Mellitus Patients: A Prospective, Hospital-Based, Comparative, Case Series Study.

BACKGROUND: Diabetes mellitus is associated with increased rate of respiratory tract infections. The objective was to compare demographic, clinical, serum biochemical, and typical and atypical radiological profiles among hospitalized diabetics and nondiabetics with lower respiratory tract infection. Material and Methods. A prospective, hospital-based, consecutive, comparative observational study of 12-month study duration was conducted. Patients aged 13-90 years diagnosed with lower respiratory tract infection with or without diagnosed diabetes mellitus participated in the study. Demographic, clinical, serum biochemistry, and radiological profiles of diabetics (n = 44) and nondiabetics (n = 53) were compared. RESULTS: Diabetics were older than nondiabetics at presentation (p < 0.0001). Difference in mean random blood sugar (RBS) (p < 0.001), fasting blood sugar (FBS) (p < 0.001), and postprandial blood sugar (PPBS) (p < 0.0001) was significant between diabetics and nondiabetics. Nondiabetics more frequently presented with fever (p = 0.0032), chest pain (p = 0.0002), and hemoptysis (p = 0.01) as compared to diabetics. Diabetics more frequently presented with extreme temperatures (hypothermia or hyperpyrexia) (p = 0.022), lower serum sodium levels (p = 0.047), and lower partial arterial pressure (p < 0.001) than nondiabetics. The mean pneumonia patient outcomes research team (PORT) risk score was higher in diabetics (124.84 ± 41.31) compared to nondiabetics (77.85 ± 39.77) (p < 0.001). Diabetics more commonly displayed bilateral lesions with multilobe or lower lobe involvement, the most common type of lesion being exudative. CONCLUSION: Diabetic patients usually had severe pulmonary infection and poor prognosis as suggested by higher mean PORT risk score. They also more frequently presented with bilateral lesions with multilobe or lower lobe involvement as evidenced by radiography as compared to nondiabetic patients.

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.

Vitamin D, C-reactive protein, and oxidative stress markers in chronic obstructive pulmonary disease.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Systemic inflammation and oxidant/antioxidant imbalance has been seen to play a key role in pathogenesis of COPD. The present study investigated the levels of inflammatory and antioxidant/oxidative stress biomarker in COPD patients and healthy subjects. MATERIALS AND METHODS: The present study enrolled seventy COPD patients and seventy healthy controls from Department of Respiratory Medicine at a tertiary care hospital. Vitamin D, C-reactive protein (CRP), superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) levels were measured in both cases and control. GraphPad PRISM version 6.01 was used for analysis of data. RESULTS: The levels of Vitamin D, SOD, Catalase, were found to be significantly lower among the COPD patients in comparison to healthy controls while levels of MDA and CRP were significantly higher (P = 0.0001). CONCLUSION: The results showed oxidant/antioxidant imbalance and Vitamin D deficiency in COPD patients. Higher levels of CRP and oxidative stress markers were observed in COPD patients in comparison to healthy controls. A biomarker based study testing the efficacy of novel antioxidant or other agents will be helpful that can modify the course of this disease.

Fluroquinolone drug resistance among MDR-TB patients increases the risk of unfavourable interim microbiological treatment outcome: An observational study.

OBJECTIVES: Sputum culture conversion at the end of the intensive phase of multidrug-resistant tuberculosis (MDR-TB) treatment is a key predictor for successful treatment outcome. This observational study was undertaken to assess the interim microbiological outcome of a cohort of rifampicin-resistant (RR)-TB patients with variable resistance to second-line drugs. METHODS: During Jan-Apr 2018, we consecutively enrolled 100 RR-TB patients, who underwent phenotypic drug susceptibility testing (DST) to assess baseline resistance to second-line drugs. Following RR-TB diagnosis, these patients were started on MDR-TB treatment. After 6 months of treatment, sputum culture conversion status was determined. Data were analysed to assess the impact of resistance to second-line drugs on culture conversion. RESULTS: DST of 100 RR-TB patients showed a high resistance to fluoroquinolones (FQs; levofloxacin 56%; moxifloxacin 44%) followed by kanamycin (8%) and capreomycin (6%). None of the patients were resistant to the other drugs tested (amikacin, clofazimine and linezolid). At 6-month treatment follow-up, 28 patients had been lost to follow-up and eight had died. Microbiological outcome was obtained from the remaining 64 patients, but successful culture conversion was achieved in only 62.5% of the patients. FQ resistance was found to be a strong predictor (P<0.001) for unfavourable microbiological outcome. CONCLUSION: The rate of FQ resistance in RR/MDR-TB is high and has strong association with unsuccessful interim microbiological outcome of conventional MDR-TB treatment.

Hospital-based study on demographic, hematological, and biochemical profile of lung cancer patients.

BACKGROUND: Lung cancer is considered as the most commonly diagnosed cancer. It is the leading cause of cancer-related mortality. Smoking and environmental pollutants act as important risk factors in majority of lung cancer cases (80%-90%). MATERIAL AND METHODS: This is a hospital-based study carried on in lung cancer patients of North India. Demographic profile of lung cancer patients was recorded. Hematological and biochemical profiles of lung cancer patients and healthy controls were compared. RESULTS: Highest proportion of lung cancer was found in the age group of 46-60 years. Lung cancer was seen in highest number in male gender (76.63%) and also in those patients belonging to the rural category (84.58%). In this study, only 3.98% lung cancer patients having the past history of cancer and 5.47% showing the family history of cancer. Significant differences were found in weight and body mass index (BMI) of lung cancer patients when compared to healthy control (P < 0.0001). Hemoglobin (Hb) was found lower in lung cancer patients as compared with healthy controls. Significant difference was also observed in Hb levels of these two groups (P < 0.000). The serum protein level was lower in lung cancer patients than healthy controls. A significant difference was also observed in the protein levels of these two groups (P < 0.0001). Serum alkaline phosphatase (ALP) levels were higher in lung cancer patients in comparison to healthy controls. A significant difference was also observed in serum ALP levels in lung cancer patients as compared with healthy controls (P < 0.0001). CONCLUSIONS: Significant difference between BMI, Hb, serum albumin, and total protein was found in this study. These biomarkers may be helpful in the diagnosis of lung cancer at early stage and also in the follow-up assessment of the effects of treatment.

Extra-central nervous system tuberculosis in HIV-uninfected patients of tuberculous meningitis: A prospective evaluation.

OBJECTIVE: Disseminated tuberculosis is characterized with involvement of two or more non-contiguous sites. In this work we evaluated patients of tuberculous meningitis for possible extra-central nervous system tuberculosis. METHOD: This prospective observational study was performed at a tertiary care institute in Northern India. We included consecutive HIV-uninfected cases of TBM. Patients were evaluated for extra-central nervous system (CNS) tuberculosis. We focussed on peripheral lymph nodes, chest, abdomen, and spinal involvement. All patients were subjected to MRI brain and spine. Patients were also subjected to CT thorax and abdomen. Enlarged lymph nodes, if present, were biopsied. Ascitic and pleural fluid were subjected to biochemical, cellular analysis as well as cartridge-based nucleic acid amplification test (CBNAAT) for detection of Mycobacterium tuberculosis and rifampicin resistance. RESULTS: We enrolled 110 patients of TBM. After cerebrospinal fluid examination alone, 14 (12.7%) patients had microbiologically-confirmed TBM. After planned work-up for extra CNS tuberculosis, 5 additional cases were microbiologically confirmed. Similarly, before work-up for extra CNS tuberculosis, 29 (26.4%) patients were categorized as probable TBM. The number of probable cases increased to 72 (65.5%) (P<0.001) with identification of tuberculosis elsewhere. Lung (83.6%) was the most involved site. Abdominal tuberculosis was noted in 29 (26.4%) patients. On imaging spine, 17 (15.5%) patients demonstrated presence of spinal tuberculous. Lymph adenopathy recorded in 2 cases. Lymph node biopsy revealed tuberculous granuloma in both the cases. All 7 patients, who died, had disseminated tuberculosis. CONCLUSION: Extra CNS tuberculous involvement is common in TBM. Search for extra CNS tuberculous enables upgrading diagnostic accuracy.

Aspergillus sensitization in bronchial asthma: A separate phenotype.

Background: Bronchial asthma is one of the common chronic respiratory illnesses worldwide, with a global disease burden that affects approximately 300 million individuals. It affects 5-10% of the population in developed countries. India constitutes approximately one-tenth of the global disease burden, where an estimated 7 million children are affected by this illness. Airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. In India, the most important endogenous stimuli is considered to be fungal antigens from the genus, Aspergillus. Positive skin reactions to Aspergillus fumigatus among individuals with atopic asthma is 10 to 20%; however, a causal relationship is yet to be established. A separate entity, termed "severe asthma with fungal sensitivity," is often used to describe milder allergic reactions to fungal aeroallergens that has fungal sensitization as the starting point of pathogenesis than allergic bronchopulmonary aspergillosis. Methods: A total of 57 patients with bronchial asthma were prospectively enrolled and evaluated for Aspergillus sensitization and its impact on asthma control. Results: Symptoms were well controlled in a majority of patients (57.89%) and partly controlled in 14.04%. Uncontrolled symptoms were observed in only 28.07% of patients. The proportion of patients with uncontrolled symptoms was higher among patients who were sensitized (45.00%) compared with patients who were not sensitized (18.92%). The proportion of patients with well-controlled symptoms was higher in individuals who were not sensitized compared with individuals who were sensitized (62.16% versus 50.00%). Conclusion: The severity of asthma was associated with fungal sensitization, with sensitization to Aspergillus as a part of the pathogenesis. Aspergillus sensitization is significantly associated with bronchiectasis, even in the absence of clinical features.

Kirsten rat sarcoma virus protein overexpression in adenocarcinoma lung: Association with clinicopathological and histomorphological features.

CONTEXT: Lung cancer is the leading cause of cancer-related deaths worldwide. The constitutive activation of multiple signaling pathways is the major cause of carcinogenesis. AIMS: The study evaluates the frequency of Kirsten rat sarcoma virus (KRAS) protein overexpression and correlates with clinicopathological and histomorphological features in non-small cell lung carcinoma (NSCLC)-adenocarcinoma. SETTINGS AND DESIGN: Tertiary hospital-based retrospective and prospective case series included 100 cases of NSCLC-adenocarcinoma. MATERIALS AND METHODS: The basic panel of Immunohistochemistry including Napsin-A, thyroid transcription factor-1 (TTF-1), and markers for squamous differentiation, p-40 was used in formalin-fixed paraffin-embedded tissue blocks. The KRAS monoclonal antibody (9.13, Thermo Fisher Scientific, USA) was used. STATISTICAL ANALYSIS USED: The IBM-Statistical Package for the Social Sciences (SPSS) (SPSS, International Business Machines Corporation, New York, NY, USA) analysis software, version 16 was used for all statistical calculations. RESULTS: KRAS protein expressed in 28.0% (28/100) cases. Cases were grouped as KRAS positive and negative. TTF-1 and Napsin-A were expressed in 89.25% (n = 25) and 92.86% (n = 26) cases, respectively. Stage IV clinical disease was identified in 55% of cases, and 36.84% of cases had a mean survival between 6 and 12 months. In KRAS positive group, the most common pattern of cellular arrangement was acinar/loose clusters pattern present in 64.29% (n = 21) and 75.0% (n = 18) cases followed by the solid pattern present in 42.86% of cases (n = 12), respectively. Necrosis was identified in 57.14% (n = 16) cases. Mucin pattern was present in 32.14% of cases (n = 9), which was significantly different when compared with the KRAS negative group (P = 0.036). CONCLUSIONS: This finding may imply that KRAS mutations may not be entirely triggered by alterations induced by carcinogens in smoke. KRAS gene is frequently mutated in pulmonary tumors. It should be tested in NSCLC owing to its predictive and prognostic effects.