Performance of CBNAAT on Pleural Biopsies Obtained by Semirigid Thoracoscopy for Diagnosis of Unexplained Pleural Effusion: A Prospective Study from North India.

BACKGROUND: Exudative pleural effusions are commonly encountered in clinical practice, but in about one-fourth of cases, etiology remains elusive after initial evaluation. Medical thoracoscopy with semirigid thoracoscope is a minimally invasive procedure with high diagnostic yield for diagnosing pleural diseases, especially these undiagnosed exudative pleural effusions. In tubercular endemic areas, often, these effusions turn out to be tubercular, but the diagnosis of tubercular pleural effusion is quite challenging due to the paucibacillary nature of the disease. Although culture is the gold standard, it is time-consuming. Cartridge-based nucleic acid amplification test (CBNAAT) is a novel rapid diagnostic test for tuberculosis (TB) and has been recommended as the initial diagnostic test in patients suspected of having extrapulmonary TB (EPTB). MATERIALS AND METHODS: We conducted a prospective observational study of 50 patients with undiagnosed pleural effusion admitted to our tertiary care hospital. The primary aim of the study is to evaluate the diagnostic performance of CBNAAT on thoracoscopic guided pleural biopsy and compare it with conventional diagnostic techniques like histopathology and conventional culture. RESULTS: Of 50 undiagnosed pleural effusions, TB (50%) was the most common etiology. The overall diagnostic yield of semirigid thoracoscopy in this study was 74%. Our study showed that CBNAAT of pleural biopsies had a sensitivity of 36% only but a specificity of 100%. The sensitivity of CBNAAT was not far superior to the conventional culture. CONCLUSION: Tuberculosis (TB) is a common cause of undiagnosed pleural effusion in our set-up. CBNAAT testing of pleural biopsy, though, is a poor rule-out test for pleural TB, but it may aid in the early diagnosis of such patients.

Clinicopathological Features and Status of Programmed Death Ligand-1 (PD-L1) Expression in Lung Cancer: A Single Centre Study From North India.

Introduction Programmed death ligand-1 (PD-L1) is an immunological checkpoint that supports the inhibition of the anti-tumor immune system. A higher level of PD-L1 expression was also discovered on the cell surfaces of several cancer cells, including non-small cell lung carcinoma (NSCLC). Identifying individuals who would benefit from PD-1/PD-L1 antibody immunotherapy is crucial in the era of precision medicine. The study's objective was to assess the distribution and degree of PD-L1 ligand expression in various forms of lung cancer and examine its link to clinicopathological variables. Methods This prospective, observational, cross-sectional study was done in a tertiary care hospital in North India over 2 years from 2019 to 2021. A total of 100 patients diagnosed with lung cancer through either endobronchial or image-guided biopsies were enrolled. The biopsy specimens of lung cancer patients have been subjected to immunohistochemistry (IHC) staining. PD-L1 expression was positive when at least 1% of tumor cells were stained. In our study, we used the rabbit monoclonal Anti-PD-L1 antibody (CAL10) (ab237726) (Abcam Plc, UK).  Results  Of the 100 patients, Squamous cell carcinoma (SQCC) was the predominant histological pattern. The mean age of the study group was 57.26 ± 10.53 years. High PDL-1 positivity (>50% ) is seen in a total of 10 patients, while low PD-L1 positivity (1-50%) is seen in 24 patients. Of all patients with high PD-L1 positivity (n=10), 80% had stage IV at the time of diagnosis. However, on similar lines, 71 % of patients with low PD-L1 positivity presented with stage IV at the time of diagnosis. (p value=0.09). Among 10 patients with epidermal growth factor receptor (EGFR) positive status, high PD-L1 positivity is seen in 20%. Among 3 patients with anaplastic lymphoma kinase (ALK) positive status, only one patient showed high PD-L1 positivity, whereas negative PDL-1 was seen in 2 patients, which was not statistically significant. Conclusion  The management of lung cancer is driven by precision medicine, including PDL-1 expression, which correlates with immune checkpoint inhibitor response. In our cohort, PD-L1 expression appears to be mostly linked to the squamous cell subtype of lung cancer, with elevated tumor stage and mediastinal lymphadenopathy in Kashmiri people. Other oncogenic driver mutations are not connected to PD-L1 expression. The function of PD-L1 expression in lung tumors requires more study.

The Trend of Arterial Carboxyhemoglobin in Non-smokers as a Prognostic Tool in Severe COVID-19 Patients: A Single-Centre Prospective Study.

Introduction  Carboxyhemoglobinemia is characterised by decreased oxygen delivery to tissues. In severe and critical coronavirus disease 2019 (COVID-19) illness with hypoxia, this can herald a grave and protracted course of illness. Patients with COVID-19 experience respiratory impairment, lowering the pace at which carbon monoxide (CO) is eliminated and raising the likelihood of carboxyhemoglobinemia. We set out to explore early arterial carboxyhemoglobin (COHb) and COVID-19 patient outcomes in non-smokers and its potential as a predictive tool for mortality. Methods  Forty-five patients, non-smokers with severe/critical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring admission in a North Indian 1200-bedded tertiary care hospital, were recruited prospectively from October 2020 to March 2021. Arterial COHb% was evaluated with arterial blood gases using an analyser, which were taken at the time of admission and then every alternate day for the first 10 days. Carboxyhemoglobinemia was defined as COHb% more than 1%. The primary outcome was defined as the patient's hospital outcome (survivor/non-survivor). Results Of the total 45 subjects, 51.1% (n=23) survived. Patients developed carboxyhemoglobinemia with an incidence of 51% during the course of their hospital stay. The mean ± SD of COHb% on admission was 1.0 ± 0.58 and 1.03 ± 0.8 in non-survivors and survivors, respectively (p=0.870). Maximal individual values of 5.3% and 6.1% were seen in survivors and non-survivors, respectively. On serial COHb measurement, non-survivors had significantly higher COHb% on days 6 and 10. No co-relation of COHb% with inflammatory markers was noted. Conclusion  Arterial COHb levels in non-survivors were significantly higher than in survivors on days 6 and 10. Our study did not show a prognostic value of serial COHb measurement in patients with severe COVID-19. To establish COHb as a predictive marker in severely ill COVID-19 patients, additional research is required.

A Rare Case of Brucellosis With Spontaneous Splenic Rupture Presenting as an Acute Abdomen.

Brucellosis is a common zoonotic infection worldwide caused by the bacterial species Brucella. It has a wide range of presentations from asymptomatic infection to multisystem involvement. Splenomegaly is seen in around 30-60% of cases, however, atraumatic spontaneous splenic rupture is extremely rare. We present a case of a 45-year-old man who presented with acute left upper quadrant pain and fever of five days duration without a history of antecedent trauma. He was hemodynamically stable with examination revealing left upper quadrant tender palpable mass. Ultrasonography followed by computed tomography revealed subcapsular hematoma with perisplenic and perihepatic free fluid. Viral markers (hepatitis B and C, cytomegalovirus {CMV}, Epstein-Barr virus {EBV}, HIV, and dengue) were negative. The autoimmune profile was negative. Brucella serum agglutination test was positive (1: 640) and blood cultures grew Brucella melitensis. He was managed conservatively for splenic hematoma and received one unit blood transfusion and treatment with combination of antibiotics (rifampicin and doxycycline) for brucella for six weeks. On follow-up, the patient reported no further complications. Spontaneous splenic rupture is a clinical rarity and should be considered in patients presenting with acute abdomen and suspected infective, neoplastic, and inflammatory pathology. Spontaneous splenic rupture in acute brucellosis requires prompt clinical recognition and immediate anti-Brucella therapy to prevent the catastrophic progression.

Tuberculosis of Finger Presenting As Non-healing Ulcer of Digit: A Case Report.

Tuberculosis (TB) is a chronic granulomatous infection which most often localises to the respiratory system. Extra-pulmonary tuberculosis is prevalent in immunocompromised individuals, of which cutaneous tuberculosis is exceedingly rare (0.5-2%). Cutaneous TB presents with varied clinical morphologies, either acquired exogenously via direct inoculation on the skin or endogenously due to systemic dissemination. Diagnosis is particularly challenging due to the multitude of differential diagnoses of skin lesions. Microbiological evidence from biopsy and histopathological findings suggestive of granulomatous inflammation are needed to make a definitive diagnosis. Herein we present a rare case of tuberculosis of the finger in a middle-aged man who presented with an ulcerating and erythematous lesion. As cutaneous TB is usually misdiagnosed at the earlier stages, dermatologists and primary care physicians should keep high suspicion for cutaneous TB in any non-healing ulcers which are otherwise unexplained.

Predictors of Prolonged Hospital Stay in Patients with Acute Pulmonary Thromboembolism- A Hospital Based Cohort Study.

AIMS AND OBJECTIVES: Patients with pulmonary thromboembolism (PTE) are commonly admitted to hospital and generally have a prolonged hospital stay in this part of the world. We aimed to determine different clinical and laboratory parameters that are associated with prolonged hospital stay in our set-up and to analyse effectiveness of Pulmonary Embolism Severity Index (PESI) score as a predictor of prolonged hospital stay in patients with PTE. MATERIALS AND METHODS: It was a hospital based observational prospective study. Confirmed cases of PTE defined as patients with evidence of thrombus on CT pulmonary angiogram (CTPA) were included in this study. Depending on the length of hospital stay, patients were divided into two cohorts: Shorter Hospital stay (less than mean i.e., < 10 Days) and Prolonged Hospital stay (longer than mean i.e., ≥ 10 Days). Logistic regression analysis was done to identify predictors of prolonged hospital stay. RESULTS: 150 patients were included in the study with 67 patients (44.67%) having shorter hospital stay (<10 days) and 83 patients (55.33%) having prolonged hospital stay (≥10 days). On multivariate regression analysis, parameters that were found to be statistically significant were hypotension at presentation, decreased level of consciousness, pco2 < 30 mmHg, presence of S1Q3T3 pattern on electrocardiogram (ECG) and high risk PESI (class III-V). CONCLUSION: PESI class can be effectively used to predict prolonged hospital stay in patients with pulmonary embolism. Patients with hypotension at presentation, decreased level of consciousness, pco2 less than 30 mmHg, and S1Q3T3 on ECG are more likely to have prolonged hospital stay in our healthcare setup.

Vitamin D Toxicity Presenting as Altered Mental Status in Elderly Patients.

Background and objective  Around 25-30% of elderly patients present to emergency departments (ED) with altered mental status (AMS), with hypercalcemia being one of the metabolic causes. Elderly patients, due to their multiple vulnerability factors and relative homeostenosis, are susceptible to alterations in mental state at even milder grades of hypercalcemia. There is a trend of overzealous prescription of higher doses of vitamin D in elderly patients for various ailments, which often exceeds the requirements of the patients. In this study, we aimed to establish vitamin D toxicity (VDT) as an underlying cause of AMS in elderly patients presenting to the hospital. Methods This was a descriptive case study conducted at a tertiary care university hospital in North India, from January 2015 to March 2020 for a total duration of five years. Elderly patients (aged ≥60 years) who were admitted with VDT as a cause for underlying hypercalcemia were included. The evaluation included patient history regarding the dosage of vitamin D received, route of administration, and biochemical parameters, such as serum calcium, intact parathyroid hormone (iPTH), 25-hydroxy vitamin D [25(OH)D], and albumin. All other potential causes for hypercalcemia and AMS were ruled out concurrently. Results A total of 19 patients were enrolled in the study, with a mean age of 72.3 years (range: 62-86 years). All patients had received injectable vitamin D formulation. The mean serum calcium among the patients was 12.52 ± 1.12 mg/dL (range: 11.2-15.7 mg/dL), whereas the mean 25(OH)D was 196.34 ± 70.44 ng/mL (range: 107-356 ng/mL). The mean cumulative vitamin D supplement intake was 2.594 ± 0.841 million IU (range: 1.2 million-4.2 million IU). While six patients had mild hypercalcemia, 12 had moderate, and one person had severe hypercalcemia, with altered sensorium (85%) being the most common complaint for presenting to ED, followed by generalized weakness (15%). Conclusion VDT can manifest with AMS as an initial presenting complaint. The geriatric population, due to various underlying vulnerability factors, is more susceptible than their younger counterparts. We strongly recommend that in elderly patients, higher doses of vitamin D should be prescribed only after checking their serum levels, and frequent monitoring of vitamin D should be performed.

Prevalence and predictors of pulmonary embolism in patients with acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: The prevalence of pulmonary embolism (PE) in patients of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) varies over a wide range. Early detection and treatment of PE in AECOPD is a key to improve patient outcome. The purpose of the study was to investigate the prevalence and predictors of PE in patients of AECOPD in a high burden region of North India. MATERIALS AND METHODS: This prospective study included patients of AECOPD with no obvious cause of exacerbation on initial evaluation. Apart from routine workup, the participants underwent assessment of D-dimer, compression ultrasound and venous Doppler ultrasound of the lower limbs and pelvic veins, and a multidetector computed tomography pulmonary angiography. RESULTS: A total of 100 patients of AECOPD with unknown etiology were included. PE as a possible cause of AE-COPD was observed in 14% of patients. Among the participants with PE, 63% (n = 9) had a concomitant presence of lower extremity deep venous thrombosis. Hemoptysis and chest pain were significantly higher in patients of AECOPD with PE ([35.7% vs. 7%, P = 0.002] and [92.9% vs. 38.4%, P = 0.001]). Likelihood of PE was significantly higher in patients who presented with tachycardia, tachypnea, respiratory alkalosis (PaCO2 <45 mmHg and pH >7.45), and hypotension. No difference was observed between the two groups in terms of in-hospital mortality, age, sex distribution, and risk factors for embolism except for the previous history of venous thromboembolism (35.7% vs. 12.8% P = 0.03). CONCLUSION: PE was probably responsible for AECOPD in 14% of patients with no obvious cause on initial assessment. Patients who present with chest pain, hemoptysis, tachypnea, tachycardia, and respiratory alkalosis should be particularly screened for PE.

Spirometric abnormalities in patients with sleep-related breathing disorders.

INTRODUCTION: Patients with sleep-related breathing disorders (SRBD) have various structural and functional abnormalities of the upper airway during sleep which may get reflected on their pulmonary function tests. The aim of the study was to find the correlation between the spirometric indices and snoring, grades of apnea-hypoapnea index (AHI), and STOPBANG. There is scarcity of literature showing correlation of STOP BANG with spirometric variables. MATERIAL AND METHODS: Patient with SRBD fulfilling the inclusion and exclusion criteria were enrolled. The pretest probability sleep score STOPBANG and polysomnography (PSG) were calculated for all the patients. Spirometric indices like forced expiratory volume in one sec (FEV1), forced vital capacity (FVC), postbronchodilator ratio FEVI/FVC (PBDR), and peak expiratory flow rate (PEFR) were studied. Their association with snoring, different grades of obstructive sleep apnea (OSA), and STOPBANG were evaluated using statistical analysis. RESULTS: A total of 70 patients were enrolled. Abnormalities of spirometric indices were found to be common in patients with SRBD but their association with snoring, grades of OSA, and STOPBANG were not statistically significant. There is no statistically significant correlation between body mass index (BMI) and grades of AHI. CONCLUSION: This study found no statistically significant correlation between spirometric parameters and STOPBANG and degree of AHI. Primary care physicians should be aware that obstructive lung disease does coexist with the sleep disordered breathing but as per this study, their statistically significant association needs further validation.

Healthcare-Associated Pneumonia and Hospital-Acquired Pneumonia: Bacterial Aetiology, Antibiotic Resistance and Treatment Outcomes: A Study From North India.

BACKGROUND: Data regarding the comparative profiling of HCAP and HAP from developing countries like India are scant. We set out to address the microbial aetiology, antibiotic resistance and treatment outcomes in patients with HCAP and HAP. METHODS: 318 consenting patients with HCAP (n = 165, aged 16-90 years; median 60 years; 97 males) or HAP (n = 153; aged 16-85 years; median 45 years; 92 males) presenting to a tertiary care hospital in North India from 2013 to 2015 were prospectively recruited for the study. Data on patient characteristics, microbial aetiology, APACHE II scores, treatment outcomes and mortality were studied. Clinical outcomes were compared with various possible predictors employing logistic regression analysis. RESULTS: Patients in HCAP had more comorbidity. Escherichia coli (30, 18%) and Acinetobacter baumannii (62, 41%) were the most commonly isolated bacteria in HCAP and HAP, respectively. Multidrug-resistant bacteria were isolated more frequently in HCAP, only because the incidence of extensively drug-resistant bacteria was markedly high in HAP (p = 0.00). The mean APACHE II score was lower in HCAP (17.55 ± 6.406, range 30) compared to HAP (19.74 ± 8.843, range 37; p = 0.013). The length of stay ≥ 5 days (p = 0.036) and in-hospital mortality was higher in HAP group (p = 0.002). The most reliable predictors of in-hospital mortality in HCAP and HAP were APACHE II score ≥ 17 (OR = 14, p = 0.00; HAP: OR = 10.8, p = 0.00), and septic shock (OR = 4.5, p = 0.00; HAP: OR = 6.9, p = 0.00). CONCLUSION: The patient characteristics in HCAP, treatment outcomes, bacterial aetiology, and a higher incidence of antibiotic-resistant bacteria, suggest that HCAP although not as severe as HAP, can be grouped as a separate third entity.

A disintegrin and metalloprotease 33 polymorphism association with COPD in long-term tobacco smokers of the ethnic Kashmiri population of India.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by an interaction of various environmental influences especially cigarette smoking and genetic determinants. The prevalence of this disease is ever increasing and characterization of the genetic determinants of the disease has been undertaken globally. The 'A disintegrin and metalloprotease 33' (ADAM 33) gene is one candidate gene that has been studied. OBJECTIVE: Our objective was to investigate whether single nucleotide polymorphisms in ADAM33 gene are associated with COPD in long-term tobacco smokers in the ethnic Kashmiri population of northern India. MATERIALS AND METHODS: This was a randomized case-control study, which included 78 stable COPD (GOLD stage11-IV) patients, who were compared with 77 age- and sex-matched long-term tobacco smokers (>20 pack years) without any evidence of COPD. Polymorphic analysis for three single nucleotide polymorphisms (SNPs), (T1, T2, and Q1) of the ADAM33 gene was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by sequencing. The data were analyzed by descriptive statistics and comparative evaluation was done by parametric/non-parametric tests. RESULTS: The analysis of the T1, T2, and Q1 SNPs, revealed that the frequencies of the T2GG, T1GG, and the Q1AG genotypes were significantly higher in patients with COPD in comparison with the controls (P < 0.001). Similarly, the T1G and T2G allele frequency was higher in the patients than in the controls (p = 0.177 and 0.43, respectively). CONCLUSION: Three SNPs of the ADAM33 gene were significantly associated with COPD in the Kashmiri population of India. This study establishes the possible role of ADAM33 SNPS in the causation of COPD. Further studies across different geographical areas in the country will unravel the contribution of this gene in the causation of COPD in India.

Cleidocranial dysplasia: a rare cause of disproportionate severe short stature.

Skeletal dysplasia is an uncommon cause of short stature in children. An 11-year-old girl was evaluated for severe short stature in a tertiary care hospital. Clinical examination revealed severe disproportionate short stature and classical triad of multiple supernumerary teeth, and complete absence of clavicles and open sagittal sutures and fontanelles. Skeletal survey confirmed these findings, in addition to other features associated with the syndrome.