Correlation between serum isoniazid concentration and therapeutic response in patients of pulmonary tuberculosis in Central India: A prospective observational study.

BACKGROUND: Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis is one of the top ten causes of death worldwide. Isoniazid (INH) is an important component of anti-tuberculosis therapy (ATT). Low isoniazid levels can serve as a risk factor for the development of treatment failure, relapse of disease and acquired secondary resistance. Hence, serum level of isoniazid becomes a critical factor in determining the treatment outcome of patients on ATT. This study aimed to evaluate the correlation between serum isoniazid concentration and therapeutic response in patients of pulmonary tuberculosis in Central India. METHODS: This was a prospective single cohort observational study conducted at a tertiary care hospital. Therapeutic response in newly diagnosed patients of pulmonary TB was determined based the microbiological, clinical and radiological parameters. Serum INH levels were estimated based on a spectrophotometric method using nano-spectrophotometer. RESULTS: In this study, patients had a significant improvement in treatment outcome as evident by a significant decrease in the TB score I at end of IP (p = 0.001) and a significant decline in the Timika score at end of CP (p = 0.001). Although all patients converted to sputum negative at end of CP, 20% remained positive at end of IP. Lower INH levels were seen in 13.3% of the study population. Higher INH levels were observed in sputum converters, patients with low TB score I and low Timika score, although no statistically significant difference was noted (p > 0.05). CONCLUSION: In this study, we could not find any statistically significant association between serum INH levels and therapeutic outcome of the patients. Further studies on a larger population could provide better understanding about the prevalence of low serum isoniazid levels among the Indian population and establish its relationship with therapeutic outcome. Also, the usage of a comparatively less expensive spectrophotometric method of analysis makes this feasible in almost every district hospital without the need of high-performance liquid chromatography which is costlier and needs more expertise.

Effect of pulmonary rehabilitation in patients with post-tuberculosis sequelae with functional limitation.

BACKGROUND: Pulmonary rehabilitation improves dyspnea, functional limitation and quality of life in patients with chronic respiratory disease especially Chronic obstructive pulmonary disease (COPD). Whether Pulmonary rehabilitation (PR) will have similar effect in patients with post-tuberculosis sequelae or not and whether the two morphological variants will respond similarly or not was the purpose of our study. METHODS: Adult patients fulfilling the inclusion criteria of a diagnosis of post-tuberculosis sequelae with functional limitation (modified medical research council [mMRC] grade 1 or more) were recruited over a period of two years. A baseline health assessment in the different domains of health was done at the beginning and repeated just after the completion of the rehabilitation program at 6 weeks. RESULTS: 26 patients completed the PR protocol of our study. Dyspnea improved from an mMRC grade of 1.5 to 0.7 post-PR (p < 0.001). 6MWD increased by 34 meters from a baseline value of 408.6 meters to 442.7 meters post-PR. (p-value 0.3) St. George's Respiratory Questionnaire (SGRQ) symptom score decreased by 13 points, SGRQ activity score decreased by 18 points, SGRQ impact score decreased by 18 and SGRQ total score decreased by 17 points with p-values of 0.037, 0.002, 0.004 and 0.002 for SGRQ symptom score, SGRQ activity score, SGRQ impact score, SGRQ total score respectively. Depression Anxiety Stress Scale (DASS) Stress score decreased by 6.7, DASS Anxiety score decreased by 6.6, and DASS Depression score decreased by 5.5 points. Intergroup comparison revealed both bronchiectasis predominant group and fibrosis predominant group responded similarly to PR. CONCLUSION: PR improved parameters assessing dyspnea, quality of life and mental health indices significantly. Improvement in functional capacity was not statically significant. Both the morphological variants responded similarly to the PR.

Cytohistological findings and diagnostic challenges in rare pediatric pulmonary mesenchymal malignancies: A report of two cases.

Pulmonary mesenchymal tumors are uncommon neoplasms and the data available on their clinical, cytohistomorphological, immunohistochemical, and molecular findings are limited, leading to difficulty in timely diagnosis and management. Case 1: A 12-year-old boy presented with a right endobronchial mass. Imprint smears from endobronchial biopsy revealed moderately pleomorphic spindle cell tumor arranged in fascicles and perivascular pattern with attached myxoid material showing occasional mitotic activity suggesting a cytological diagnosis of sarcoma. Biopsy also displayed similar morphology. Extensive immunohistochemistry (IHC) showed diffuse SMA, focal AE1/AE3, and diffuse ALK positivity along with a MIB/Ki67 index of 30%-40% leading to the diagnosis of inflammatory myofibroblastic tumor (IMT; Sarcoma grade). Case 2: A 8-year-old boy presented with a huge left-sided mass replacing the entire lung parenchyma and eroding adjoining ribs. Pleural fluid cytology revealed vague clusters of PAS-positive diastase-sensitive small atypical cells with associated inflammatory cells in the hemorrhagic background, suggesting a diagnosis of malignant small round blue cell tumor. Trucut biopsy from the mass showed spindled to round cells showing diffuse positivity with CD99 and BCL-2. Molecular studies with reverse transcription-PCR (RT-PCR) for SYT-SSX and EWS-FLI1 were negative for synovial sarcoma and Ewing's sarcoma, respectively. Given the clinical setting, PAS positivity, IHC, and molecular studies, the diagnosis of tumors of uncertain differentiation with the possibility of Ewing's sarcoma family of tumors (ESFT) with a translocation between EWS1 and other ETS-family members (ERG, FEV, ETV1, E1AF, etc.) was suggested.

Unilateral complicated pleural empyema in a patient with bronchial asthma due to clindamycin-resistant Prevotella buccae.

Prevotella buccae (P. buccae) is a gram-negative obligate anaerobe mainly associated with infections of odontogenic origin. Non-oral monomicrobial infection by these obligate anaerobic bacteria is rare. Only a few cases of monomicrobial non-oral infections by P. buccae have been reported in the literature. We are reporting a case of unilateral complicated pleural empyema in a patient with bronchial asthma infected by P. buccae. Pleural fluid aerobic culture and blood culture reports were sterile. No acid-fast bacilli were detected by Acid Fast Bacilli (AFB) staining, and cartridge-based nucleic acid assay test (CBNAAT) reports were negative for Mycobacterium tuberculosis. The isolate, P. buccae was found susceptible to Metronidazole (MIC = 3 µg/ml) and resistant to Clindamycin (MIC = 256 µg/ml). In view of rising trends of antimicrobial resistance among anaerobes, it is recommended to perform anaerobic culture and sensitivity testing in clinically suspected cases of pleuropulmonary infection for appropriate diagnosis and optimal patient management. Clindamycin should be used with caution for empiric treatment.

Bronchoalveolar Lavage in Diagnostic Evaluation of Pulmonary Diseases- An Institutional Experience.

Background: Bronchoalveolar lavage (BAL) is a widely accepted investigative tool for the diagnosis of pulmonary lesions. This study was done to find out the usefulness of BAL in diagnosis of pulmonary lesions from central Indian patient population. Methods: A cross-sectional prospective study was performed over a period of three years. All the BAL specimens of patients presenting to Department of Pulmonary Medicine and Tuberculosis during a period of January 2017 to December 2019 were included in the study. Cyto-histopathologic correlation was done, wherever available. Results: Of total 277 cases, there were 178 (64.5%) males and 99 (35.5%) females. The age of patients ranged from 4 years to 82 years. In 92 (33%) cases, specific infective etiology could be identified on BAL cytology, the most common being tuberculosis (26%) followed by fungal infections (2%). Rarely, infections like nocardia, actinomycosis, and hydatidosis were also identified. Eight cases (3%) of malignancy were identified which included two cases of adenocarcinoma, one case of small cell carcinoma, three cases of poorly differentiated carcinoma, and two cases suspicious for malignancy. Some rare diagnoses like diffuse alveolar damage, pulmonary alveolar microlithiasis, and pulmonary alveolar proteinosis could be identified on BAL. Conclusion: BAL is useful in primary diagnosis of infections and malignancies of lower respiratory tract. BAL may aid in diagnostic workup of diffuse lung diseases. A combination of clinical information, high-resolution computed tomography, and BAL analysis may furnish an assured diagnosis to the clinician and obviate need for invasive procedures.

Diagnostic Performance of Multiplex PCR for Detection of Mycobacterium tuberculosis Complex in Presumptive Pulmonary Tuberculosis Patients and Its Utility in Smear Negative Specimens.

Objective The primary objective of this study was to assess the diagnostic performance of multiplex polymerase chain reaction (mPCR) for the detection of Mycobacterium tuberculosis complex (MTBC) in presumptive pulmonary TB patients, in the setting of a tertiary level teaching hospital in central India, in comparison to liquid culture using BACTEC mycobacteria growth indicator tubes (MGIT) 960 TB system as the gold standard. The secondary objective was to assess the performance of mPCR for Ziehl Neelsen smear negative samples and ascertain the utility of this assay in smear negative samples. Materials and Methods Sputum or bronchoalveolar lavage samples were collected from patients who were adults, aged 18 years or older, presenting with presumptive pulmonary TB, and subjected to three microbiological investigations, that is, Ziehl Neelsen staining, mycobacterial culture using mycobacterial growth indicator tubes in the BD BACTEC MGIT 960 instrument, and the mPCR. Statistical Analysis For statistical analysis, 2 × 2 contingency tables were prepared and analyzed separately for all samples and for smear-negative samples using GraphPad and MedCalc tools. Sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of mPCR were calculated by taking MGIT culture as the reference standard. Results For all samples ( n = 114), sensitivity of mPCR for the detection of (MTBC) was 93.48% (95% confidence interval [CI]: 82.10-98.63%), specificity was 95.59% (95% CI: 87.64-99.08%), positive predictive value (PPV) was 93.48% (95% CI: 82.54-97.75%), and NPV was 95.59% (95% CI: 87.87-98.48%). For smear negative samples ( n = 80), sensitivity was 80.00% (95% CI: 51.91-95.67%), specificity was 98.46% (95% CI: 91.72-99.96%), PPV was 92.31% (95% CI: 62.80-98.84%), and NPV was 95.52% (95% CI: 88.57-98.33%). Conclusion In this study, we were able to demonstrate the good performance characteristics of the mPCR for the detection of MTBC from clinical samples of patients with presumptive pulmonary tuberculosis, with MGIT liquid culture as the reference standard. It may be concluded that mPCR can be considered equivalent to MGIT culture in terms of clinical decision making and yield of positivity, owing to the good sensitivity and specificity for the detection of MTBC.

Clinico-Epidemio-Microbiological Exploratory Review Among COVID-19 Patients with Secondary Infection in Central India.

Purpose: Secondary infections (SI) in COVID-19 have been documented from 3.6% to 72% in various studies with mortality ranging from 8.1% to 57.6%. There is a gap in knowledge for clinico-epidemio-microbilogical association among COVID-19 patients with concomitant SI. Patients and Methods: This is a retrospective chart review, in central India. The study was undertaken for hospitalized adult patients during 1st June 2020 to 30th November 2020, with laboratory proven COVID-19 infection and secondary infection. Results: Out of the total 2338 number of patients, only 265 (11.3%) patients were investigated for microbiological identification of SI. Male gender was predominant (76.8%) and the mean age was 53.7 ± 17.8 years. Only 3.5% (82/2338) of patients were having microbiologically confirmed (bacterial or fungal) SI. The overall mortality was 50.9% (54/82) with a differential mortality of 88.8% (48/54) in high-priority areas and 21.4% (6/28) in low-priority areas. Blood was the most commonly investigated sample (56%) followed by urine (20.7%) and respiratory secretion (15.8%). A. baumanii complex (20/82, 24.3%) was the most common bacteria isolated followed by K. pneumonia (12/82, 14.6%) and E. coli (11/82, 13.4%). Candida spp. (20/82, 24.3%) was the most common fungal pathogen isolated. Sixty percent (12/20) of Acinetobacter spp. were carbapenam-resistant and 70.3% of Enterobacterales were carbapenam-resistant. Fluconazole resistant Candid a spp. was isolated only in 10% (2/20) of cases. Diabetes was the most common co-morbidity 54.8% (45/82) followed by hypertension (41.4%) and chronic heart disease (13.4%). The negative predictors of secondary infections are urinary catheterization, placement of central line and mechanical ventilation (invasive and non-invasive). Conclusion: There is an urgent need of better anti-microbial stewardship practices in India (institutional and extra institutional) for curtailment of secondary infection rates particularly among COVID-19 patients.

Cytologic and flowcytometric findings in a case of myelomatous pleural effusion: A rare and ominous presentation of multiple myeloma.

Plasma cell myeloma is a hematologic malignancy characterized by multifocal clonal proliferation of plasma cells usually associated with M protein secretion in serum and/or urine and evidence of organ damage. Generally, the presenting features are related to anemia, bone lesions, and renal failure. Pleural effusion is rare in multiple myeloma and when present is often due to nonmalignant causes. Myelomatous pleural effusion that is, effusions directly due to pleural infiltration by plasma cells is even rarer. We present a case of a patient presenting with dyspnea due to myelomatous pleural effusion. The fluid in such a case may be subjected to cytology examination, protein electrophoresis, flowcytometric analysis, and cytogenetics. The case highlights the utility of cytomorphology and flowcytometry in the diagnosis of myelomatous pleural effusion and also highlights that this type of presentation portends a poor prognosis to the patient.

Pulmonary rehabilitation in COVID-19 pneumonia sequelae: so near yet so far.

To evaluate the benefit of pulmonary rehabilitation, a control group is a must to mitigate the effect of confounding factors like spontaneous resolution of lung damage, learning effect and better mental status https://bit.ly/3qy5sfe.

Determinants of lymph node resolution in patients of tubercular lymphadenitis treated with anti tuberculous chemotherapy: A hospital based longitudinal study.

INTRODUCTION: The variable course of illness in patients of Tubercular lymphadenitis remains a therapeutic challenge to treating physicians in a significant proportion of patients. This study was aimed to explore the possible determinants which could predict the outcome of this subgroup of patients. METHODOLOGY: This was a prospective cohort study where 94 patients of TB lymphadenitis were enrolled who could be followed up till the end of treatment. They were evaluated in the beginning and monitored till the end of treatment keeping into account the clinical behaviour of lymph nodes during the course of Anti tubercular chemotherapy. RESULTS: Out of 94 patients, 60 had their lymph nodes resolved at the end of prescribed treatment duration wheras 34 were classified as partial responders. Another 26 amongst them had their nodes resolved by an extension of continuation phase by 3-6 months. Presence of bilateral and multiple lymph nodes, necrosis on Fine needle aspiration at initial diagnosis and occurrence of Paradoxical upgrading reaction were associated with the partial resolution of lymph nodes at the end of stipulated ATT duration. CONCLUSION: Treatment duration should be individualized by the treating physicians. Certain parameters mentioned above can be taken as warning signals of patients ending up as partial responders and hence the need of a prolonged extension phase.

Chemotherapy as cause of refractory severe headache in a case of small-cell lung cancer.

Small-cell lung cancer (SCLC) is a very fast growing form of cancer and is characterised by early metastasis. As a result, chemotherapy is the mainstay of treatment. Platinum-containing combination regimens are the current treatment of choice for limited stage-SCLC and extensive stage SCLC. Various adverse effects after cisplatin and etoposide chemotherapy include nausea, nephrotoxicity, cardiotoxicity, hepatotoxicity, neurotoxicity, alopecia, gastrointestinal toxicity and myelosuppression. However, severe headache has not been reported yet. Here, we report one such case of severe refractory headache postcisplatin and etoposide chemotherapy which responded only to change in chemotherapy regime. All pertinent causes of headache were ruled out prior to changing the chemotherapy regimen.

Type-5 Bartter syndrome presenting with metabolic seizure in adulthood.

Bartter syndrome is a very rare and heterogeneous disease with variable age of onset and symptom severity. Genotypically they have inherited disorders of the thick ascending limb in the renal tubular system, which manifest phenotypically as electrolyte imbalance due to loss of sodium, chloride and potassium. Gain of function mutations in the calcium-sensing receptor has been described in some patients with Bartter's syndrome (type-5 Bartter syndrome or autosomal dominant hypocalcaemia with Bartter syndrome) associated with hypocalcaemia and hypercalciuria differentiating it from Gitelman syndrome. This phenotype has been reported to present in adulthood with metabolic abnormalities. We present a case of a middle-aged woman who presented with metabolic seizures and on evaluation was found to have profound electrolyte abnormalities which were corrected with supplements and led to the resolution of symptoms.

Unusual presentation of chronic eosinophilic pneumonia with mild peripheral eosinophilia.

Chronic eosinophilic pneumonia (CEP) is a rare disorder of unknown aetiology which comes under the class of diffuse parenchymal lung diseases with eosinophilia. It is classically characterised by blood and pulmonary eosinophilia, peripheral consolidation on chest radiograph and prompt response to corticosteroid therapy. We report a case of CEP in a 66-year-old man, smoker showing bilateral pulmonary infiltrates with mild peripheral eosinophilia. Our study shows that CEP can be kept as a possibility if radiological pictures are consistent, even if peripheral blood eosinophilia is mild.

Recurrent episodes of pneumonia in a toddler: Don't forget chronic granulomatous disease.

A 4-year-old boy presented with community acquired pneumonia, hepatosplenomegaly and bilateral cervical lymphadenopathy. The peripheral blood film showed significant monocytosis and bone marrow examination revealed multiple histiocytic granulomas. Presence of CD 68 positive granulomas supported by cytological findings enabled us to make a diagnosis of chronic granulomatous disease.

What is New in Management of Pediatric Tuberculosis ?

Tuberculosis continues to haunt mankind since its discovery more than a century ago. Although commendable advancements have been made in the diagnosis as well as treatment, especially in the last couple of decades, the healthcare burden of this disease worldwide is immense. Continuously evolving medical science has provided recent changes in national guidelines along with discovery of newer anti-tubercular drugs after many decades. In view of WHO declaring tuberculosis as a global health emergency and strong commitment being reflected by Government of India whereby National Strategic Plan aims to eliminate tuberculosis by 2025, it is high time that we work collectively on the goal of tuberculosis elimination. This article sums up the updates on newer anti-tubercular drugs as well as the recent changes adopted in Revised National Tuberculosis Control Program.

Correcting inhaler technique decreases severity of obstruction and improves quality of life among patients with obstructive airway disease.

BACKGROUND: Asthma and chronic obstructive lung disease (COPD) together constitute a huge burden on healthcare all around the world. Treatment of these patients is largely dependent on the way the inhalation devices are used. This study aimed at measuring the impact of rectification of inhalation technique on quality of life and severity of obstruction in patients with asthma and COPD. MATERIALS AND METHODS: A total of 45 asthma (partly controlled) and 38 patients with COPD (categories B and C) were enrolled after applying optimal exclusion criteria. These patients underwent Asthma Control Test (ACT)/COPD Assessment Test (CAT) questionnaire as a measure of quality of life and forced expiratory volume in one second (FEV1) as a measure of severity of obstruction at 0 and 4 weeks, respectively. RESULTS: In asthmatics, the mean FEV1 improved from 2.0 to 2.15 L after 4 weeks of technique correction (P < 0.001). In addition, the mean ACT scores improved from 18.0 to 20.75 (P < 0.001). In patients with COPD, the mean FEV1 improved slightly from 1.54 to 1.56 L after 4 weeks of technique correction (P = 0.28). In addition, the mean CAT scores improved from 21.86 to 19.83 (P < 0.001). CONCLUSION: Demonstration of correct inhalation technique should be an indispensible part of the treatment prescription of patients with obstructive airway disease. This simple and important task can be undertaken at the level of primary care physicians in a community-based setting to improve patient compliance.