Low BALF CD4 T cells count is associated with extubation failure and mortality in critically ill covid-19 pneumonia.

BACKGROUND: Critically ill COVID-19 pneumonia is one of the main causes of extubation failure and mortality. Understanding clinical characteristics, laboratory profiles and bronchoalveolar lavage fluid (BALF) immunopathology may help improve outcomes in critically ill COVID-19 pneumonia. We aimed to describe clinical characteristics, laboratory profiles and BALF immunopathology based on lung severity in critically ill COVID-19 pneumonia patients. MATERIALS AND METHODS: Forty critically ill severe pneumonia patients requiring invasive mechanical ventilation in Cipto Mangunkusumo General (National Tertiary Referral Hospital), Indonesia within November 2020-January 2021 were enrolled in this study. Early BALF collection was performed after patients' intubation. Clinical characteristics, laboratory profiles and BALF biomarkers (sTREM-1, alveolar macrophage amount and function, IL-6, IL-17, CD4 T-cells, Tregs, SP-A and Caspase-3) were observed and analysed. Outcomes were measured based on extubation failure (within 19 days) and 28-days mortality. Univariate and bivariate analyses were performed. RESULTS: Early bronchoscopy was performed in an average of 4 h (SD = 0.82) after patients' intubation. Twenty-three and twenty-two patients had extubation failure (within 19 days) and 28-days mortality, respectively. In the baseline clinical characteristics of critically ill COVID-19 patients, we found no significant differences in the extubation and mortality status groups. In the laboratory profiles of critically ill COVID-19 patients, we found no significant differences in the extubation status groups. In critically ill COVID-19 pneumonia patients, there was a significant high D-dimer levels in survived group (p = .027), a significant low BALF CD4 T-cells count in the right lung (p = .001) and a significant low BALF CD4 T-cells count (p = .010 and p = .018) in severely affected lung with extubation failure and mortality. CONCLUSIONS: BALF CD4 T-cells count evaluation of severely affected lung is associated with early extubation failure and mortality in critically ill COVID-19 pneumonia patients. KEY MESSAGEFew studies have been conducted during the peak COVID-19 period analysing combined bronchoalveolar lavage fluid (BALF) immunopathology biomarkers within four hours of intubation to assess extubation failure and mortality. In this study, we reported eight BALF immunopathology biomarkers (sTREM-1, alveolar macrophage, IL-6, IL-17, CD4 T-cells, Tregs, SP-A and Caspase-3).We found significantly low BALF CD4 T-cells count in the right lung, and low BALF CD4 T-cells count in severely affected lung of critically ill COVID-19 pneumonia patients in extubation failure and mortality.

Bayesian latent class analysis produced diagnostic accuracy estimates that were more interpretable than composite reference standards for extrapulmonary tuberculosis tests.

BACKGROUND: Evaluating the accuracy of extrapulmonary tuberculosis (TB) tests is challenging due to lack of a gold standard. Latent class analysis (LCA), a statistical modeling approach, can adjust for reference tests' imperfect accuracies to produce less biased test accuracy estimates than those produced by commonly used methods like composite reference standards (CRSs). Our objective is to illustrate how Bayesian LCA can address the problem of an unavailable gold standard and demonstrate how it compares to using CRSs for extrapulmonary TB tests. METHODS: We re-analyzed a dataset of presumptive extrapulmonary TB cases in New Delhi, India, for three forms of extrapulmonary TB. Results were available for culture, smear microscopy, Xpert MTB/RIF, and a non-microbiological test, cytopathology/histopathology, or adenosine deaminase (ADA). A diagram was used to define assumed relationships between observed tests and underlying latent variables in the Bayesian LCA with input from an inter-disciplinary team. We compared the results to estimates obtained from a sequence of CRSs defined by increasing numbers of positive reference tests necessary for positive disease status. RESULTS: Data were available from 298, 388, and 230 individuals with presumptive TB lymphadenitis, meningitis, and pleuritis, respectively. Using Bayesian LCA, estimates were obtained for accuracy of all tests and for extrapulmonary TB prevalence. Xpert sensitivity neared that of culture for TB lymphadenitis and meningitis but was lower for TB pleuritis, and specificities of all microbiological tests approached 100%. Non-microbiological tests' sensitivities were high, but specificities were only moderate, preventing disease rule-in. CRSs' only provided estimates of Xpert and these varied widely per CRS definition. Accuracy of the CRSs also varied by definition, and no CRS was 100% accurate. CONCLUSION: Unlike CRSs, Bayesian LCA takes into account known information about test performance resulting in accuracy estimates that are easier to interpret. LCA should receive greater consideration for evaluating extrapulmonary TB diagnostic tests.

Epidemiology, diagnosis & treatment of non-tuberculous mycobacterial diseases.

Non-tuberculous mycobacteria (NTM) are ubiquitously present in the environment, but NTM diseases occur infrequently. NTM are generally considered to be less virulent than Mycobacterium tuberculosis, however, these organisms can cause diseases in both immunocompromised and immunocompetent hosts. As compared to tuberculosis, person-to-person transmission does not occur except with M. abscessus NTM species among cystic fibrosis patients. Lung is the most commonly involved organ, and the NTM-pulmonary disease (NTM-PD) occurs frequently in patients with pre-existing lung disease. NTM may also present as localized disease involving extrapulmonary sites such as lymph nodes, skin and soft tissues and rarely bones. Disseminated NTM disease is rare and occurs in individuals with congenital or acquired immune defects such as HIV/AIDS. Rapid molecular tests are now available for confirmation of NTM diagnosis at species and subspecies level. Drug susceptibility testing (DST) is not routinely done except in non-responsive disease due to slowly growing mycobacteria ( M. avium complex, M. kansasii) or infection due to rapidly growing mycobacteria, especially M. abscessus. While the decision to treat the patients with NTM-PD is made carefully, the treatment is given for 12 months after sputum culture conversion. Additional measures include pulmonary rehabilitation and correction of malnutrition. Treatment response in NTM-PD is variable and depends on isolated NTM species and severity of the underlying PD. Surgery is reserved for patients with localized disease with good pulmonary functions. Future research should focus on the development and validation of non-culture-based rapid diagnostic tests for early diagnosis and discovery of newer drugs with greater efficacy and lesser toxicity than the available ones.

Miliary Tuberculosis.

Miliary tuberculosis (TB) results from a massive lymphohematogenous dissemination of Mycobacterium tuberculosis bacilli and is characterized by tiny tubercles evident on gross pathology resembling millet seeds in size and appearance. The global HIV/AIDS pandemic and widespread use of immunosuppressive drugs and biologicals have altered the epidemiology of miliary TB. Considered to be predominantly a disease of infants and children in the pre-antibiotic era, miliary TB is increasingly being encountered in adults as well. The clinical manifestations of miliary TB are protean and nonspecific. Atypical clinical presentation often delays the diagnosis. Clinicians, therefore, should have a low threshold for suspecting miliary TB. Focused, systematic physical examination helps in identifying the organ system(s) involved, particularly early in TB meningitis, as this has therapeutic significance. Fundus examination for detecting choroid tubercles offers a valuable clinical clue for early diagnosis, as their presence is pathognomonic of miliary TB. Imaging modalities help in recognizing the miliary pattern, defining the extent of organ system involvement. Examination of sputum, body fluids, image-guided fine-needle aspiration cytology or biopsy from various organ sites, needle biopsy of the liver, bone marrow aspiration, and biopsy should be done to confirm the diagnosis. Cytopathological, histopathological, and molecular testing (e.g., Xpert MTB/RIF and line probe assay), mycobacterial culture, and drug susceptibility testing must be carried out as appropriate and feasible. Miliary TB is uniformly fatal if untreated; therefore, early initiation of specific anti-TB treatment can be lifesaving. Monitoring for complications, such as acute kidney injury, air leak syndromes, acute respiratory distress syndrome, adverse drug reactions such as drug-induced liver injury, and drug-drug interactions (especially in patients coinfected with HIV/AIDS), is warranted.

Interstitial Lung Disease in India. Results of a Prospective Registry.

RATIONALE: Interstitial lung disease (ILD) is a heterogeneous group of acute and chronic inflammatory and fibrotic lung diseases. Existing ILD registries have had variable findings. Little is known about the clinical profile of ILDs in India. OBJECTIVES: To characterize new-onset ILDs in India by creating a prospective ILD using multidisciplinary discussion (MDD) to validate diagnoses. METHODS: Adult patients of Indian origin living in India with new-onset ILD (27 centers, 19 Indian cities, March 2012-June 2015) without malignancy or infection were included. All had connective tissue disease (CTD) serologies, spirometry, and high-resolution computed tomography chest. ILD pattern was defined by high-resolution computed tomography images. Three groups independently made diagnoses after review of clinical data including that from prompted case report forms: local site investigators, ILD experts at the National Data Coordinating Center (NDCC; Jaipur, India) with MDD, and experienced ILD experts at the Center for ILD (CILD; Seattle, WA) with MDD. Cohen's κ was used to assess reliability of interobserver agreement. MEASUREMENTS AND MAIN RESULTS: A total of 1,084 patients were recruited. Final diagnosis: hypersensitivity pneumonitis in 47.3% (n = 513; exposure, 48.1% air coolers), CTD-ILD in 13.9%, and idiopathic pulmonary fibrosis in 13.7%. Cohen's κ: 0.351 site investigator/CILD, 0.519 site investigator/NDCC, and 0.618 NDCC/CILD. CONCLUSIONS: Hypersensitivity pneumonitis was the most common new-onset ILD in India, followed by CTD-ILD and idiopathic pulmonary fibrosis; diagnoses varied between site investigators and CILD experts, emphasizing the value of MDD in ILD diagnosis. Prompted case report forms including environmental exposures in prospective registries will likely provide further insight into the etiology and management of ILD worldwide.

Aetiology, outcomes & predictors of mortality in acute respiratory distress syndrome from a tertiary care centre in north India.

BACKGROUND & OBJECTIVES: Acute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is associated with high mortality. There is a paucity of literature on this condition from developing countries. This prospective observational study was designed to find out the aetiology, outcomes and predictors of mortality in ARDS. METHODS: Sixty four consecutive patients who satisfied American-European Consensus Conference (AECC) definition of ARDS from medical Intensive Care Unit (ICU) of a tertiary care centre in New Delhi, India, were enrolled in the study. Demographic, biochemical and ventilatory variables were recorded for each patient. Baseline measurements of serum interleukin (IL)-1ß, IL-6, tumour necrosis factor-alpha (TNF-α), procalcitonin (PCT) and high sensitivity C-reactive protein (hsCRP) were performed. RESULTS: Common causes of ARDS included pneumonia [44/64 (68.7%)], malaria [9/64 (14.1%)] and sepsis [8/64 (12.5%]. Eight of the 64 (12.5%) patients had ARDS due to viral pneumonia. The 28-day mortality was 36/64 (56.2%).Independent predictors of mortality included non-pulmonary organ failure, [Hazard ratio (HR) 7.65; 95% CI 0.98-59.7, P=0.05], Simplified Acute Physiology Score (SAPS-II) [HR 2.36; 95% CI 1.14-4.85, P=0.02] and peak pressure (P peak ) [HR 1.13; 95% CI 1.00-1.30, P = 0.04] at admission. INTERPRETATION & CONCLUSIONS: Bacterial and viral pneumonia, malaria and tuberculosis resulted in ARDS in a considerable number of patients. Independent predictors of mortality included non-pulmonary organ failure, SAPS II score and P peak at baseline. Elevated levels of biomarkers such as TNF-α, PCT and hsCRP at admission might help in identifying patients at a higher risk of mortality.

Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity.

BACKGROUND & OBJECTIVES: The N-acetyltransferase 2 (NAT2) gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH). METHODS: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. RESULTS: Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8%) and non-DIH (77.2%) patients. However, the genotypic distribution of variant NAT2FNx015/FNx017 amongst slow-acetylator genotypes was significantly higher in DIH (56%) group as compared to non-DIH (39%) group (odds ratio 2.02; P=0.006). INTERPRETATION & CONCLUSIONS: The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.

Miliary tuberculosis: A new look at an old foe.

Miliary tuberculosis (TB), is a fatal form of disseminated TB characterized by tiny tubercles evident on gross pathology similar to innumerable millet seeds in size and appearance. Global HIV/AIDS pandemic and increasing use of immunosuppressive drugs have altered the epidemiology of miliary TB. Keeping in mind its protean manifestations, clinicians should have a low threshold for suspecting miliary TB. Careful physical examination should focus on identifying organ system involvement early, particularly TB meningitis, as this has therapeutic significance. Fundus examination for detecting choroid tubercles can help in early diagnosis as their presence is pathognomonic of miliary TB. Imaging modalities help in recognizing the miliary pattern, define the extent of organ system involvement and facilitate image guided fine-needle aspiration cytology or biopsy from various organ sites. Sputum or BAL fluid examination, pleural, pericardial, peritoneal fluid and cerebrospinal fluid studies, fine needle aspiration cytology or biopsy of the lymph nodes, needle biopsy of the liver, bone marrow aspiration and biopsy, testing of body fluids must be carried out. GeneXpert MTB/RIF, line probe assay, mycobacterial culture and drug-susceptibility testing must be carried out as appropriate and feasible. Treatment of miliary TB should be started at the earliest as this can be life saving. Response to first-line anti-TB drugs is good. Screening and monitoring for complications like acute respiratory distress syndrome (ARDS), adverse drug reactions like drug-induced liver injury, drug-drug interactions, especially in patients co-infected with HIV/AIDS, are warranted. Sparse data are available from randomized controlled trials regarding optimum regimen and duration of anti-TB treatment.

Malignancies in human immunodeficiency virus infected patients in India: Initial experience in the HAART era.

BACKGROUND & OBJECTIVES: Limited data are available on malignancies in human immunodeficiency virus (HIV)-infected patients from India. We undertook this study to assess the frequency and spectrum of malignancies in HIV-infected adult patients during the first eight years of highly active antiretroviral therapy (HAART) rollout under the National ART Programme at a tertiary care centre in New Delhi, India. METHODS: Retrospective analysis of records of patients registered at the ART clinic between May 2005 and December 2013 was done. RESULTS: The study included 2598 HIV-infected adult patients with 8315 person-years of follow up. Malignancies were diagnosed in 26 patients with a rate of 3.1 (IQR 2.1-4.5) cases per 1000 person-years. The median age for those diagnosed with malignancy was 45 (IQR 36-54) yr, which was significantly (P<0.01) higher compared with those not developing malignancies 35 (IQR 30-40) yr. The median baseline CD4+ T-cell count in patients with malignancy was 135 (IQR 68-269) cells/µl compared to 164 (IQR 86-243) cells/µl in those without malignancies. AIDS-defining cancers (ADCs) were seen in 19 (73%) patients, while non-AIDS-defining cancers (NADCs) were observed in seven (27%) patients. Malignancies diagnosed included non-Hodgkin's lymphoma (16), carcinoma cervix (3), Hodgkin's lymphoma (2), carcinoma lung (2), hepatocellular carcinoma (1), and urinary bladder carcinoma (1). One patient had primary central nervous system lymphoma. There was no case of Kaposi's sarcoma. INTERPRETATION & CONCLUSIONS: Malignancies in HIV-infected adult patients were infrequent in patients attending the clinic. Majority of the patients presented with advanced immunosuppression and the ADCs, NHL in particular, were the commonest malignancies.

Consensus and evidence-based Indian initiative on obstructive sleep apnea guidelines 2014 (first edition).

Obstructive sleep apnea (OSA) and obstructive sleep apnea syndrome (OSAS) are subsets of sleep-disordered breathing. Awareness about OSA and its consequences among the general public as well as the majority of primary care physicians across India is poor. This necessitated the development of the Indian initiative on obstructive sleep apnea (INOSA) guidelines under the auspices of Department of Health Research, Ministry of Health and Family Welfare, Government of India. OSA is the occurrence of an average five or more episodes of obstructive respiratory events per hour of sleep with either sleep-related symptoms or co-morbidities or ≥15 such episodes without any sleep-related symptoms or co-morbidities. OSAS is defined as OSA associated with daytime symptoms, most often excessive sleepiness. Patients undergoing routine health check-up with snoring, daytime sleepiness, obesity, hypertension, motor vehicular accidents, and high-risk cases should undergo a comprehensive sleep evaluation. Medical examiners evaluating drivers, air pilots, railway drivers, and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA. Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study. Supervised overnight polysomnography is the "gold standard" for evaluation of OSA. Positive airway pressure (PAP) therapy is the mainstay of treatment of OSA. Oral appliances (OA) are indicated for use in patients with mild to moderate OSA who prefer OA to PAP, or who do not respond to PAP or who fail treatment attempts with PAP or behavioral measures. Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy.

Seroprevalence and determinants of Kaposi sarcoma-associated human herpesvirus 8 in Indian HIV-infected males.

In India Kaposi's sarcoma is rarely seen in AIDS patients. Hence the current belief is that the incidence of human herpesvirus-8 (HHV-8) is very low in this subcontinent, most probably due to the heterosexual route of HIV transmission. However, there is a scarcity of data on the prevalence of HHV-8 in India. In India the primary mode of HIV transmission is the heterosexual route. Therefore we aimed to determine the prevalence of antibodies against HHV-8 in North Indian HIV-infected men naive of antiretroviral therapy (ART). In a prospective study, 165 Indian adult males were recruited from an ART clinic. Blood samples were collected before administering any antiretroviral drug. The sera were tested for antibodies against HHV-8 using a commercial enzyme-linked immunosorbent assay (ELISA) kit, which detects IgG antibodies to lytic antigens of HHV-8. All positive samples were confirmed for the presence of anti-HHV-8 antibodies using an indirect immunofluorescence assay (IFA). The IFA kit is intended to detect primary, latent, persistent, or reactivated infection of HHV-8. Of the 165 males, 43 (26.06%) were positive by ELISA while 26 (15.8%) were also positive by IFA. Seroprevalence decreased with increasing age (p<0.05). Factors independently associated with HHV-8 infection were younger age group and alcohol consumption. These findings suggest that even in a heterosexual population, HHV-8 can be transmitted frequently.

Consensus & evidence-based INOSA Guidelines 2014 (first edition).

Obstructive sleep apnoea (OSA) and obstructive sleep apnoea syndrome (OSAS) are subsets of sleep-disordered breathing. Awareness about OSA and its consequences amongst the general public as well as the majority of primary care physcians across India is poor. This necessiated the development of the INdian initiative on Obstructive sleep apnoea (INOSA) guidelines under the auspices of Department of Health Research, Ministry of Health & Family Welfare, Government of India. OSA is the occurrence of an average five or more episodes of obstructive respiratory events per hour of sleep with either sleep related symptoms or co-morbidities or ≥ 15 such episodes without any sleep related symptoms or co-morbidities. OSAS is defined as OSA associated with daytime symptoms, most often excessive sleepiness. Patients undergoing routine health check-up with snoring, daytime sleepiness, obesity, hypertension, motor vehicular accidents and high risk cases should undergo a comprehensive sleep evaluation. Medical examiners evaluating drivers, air pilots, railway drivers and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA. Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study. Supervised overnight polysomnography (PSG) is the "gold standard" for evaluation of OSA. Positive airway pressure (PAP) therapy is the mainstay of treatment of OSA. Oral appliances are indicated for use in patients with mild to moderate OSA who prefer oral appliances to PAP, or who do not respond to PAP or who fail treatment attempts with PAP or behavioural measures. Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy.

Clinical profile & predictors of poor outcome of adult HIV-tuberculosis patients in a tertiary care centre in north India.

BACKGROUND & OBJECTIVES: There is a paucity of data from India on response to treatment of tuberculosis (TB) in patients with human immunodeficiency virus (HIV)-TB co-infection. This study was done to assess the frequency and pattern of TB, outcome of anti-tuberculosis treatment, and the factors related to poor outcome of TB treatment in adult patients with HIV infection. METHODS: Retrospective review of case records of HIV-TB co-infected patients attending the antiretroviral therapy (ART) clinic in a tertiary care centre in north India was done. RESULTS: Of the 1754 patients included in the study, 583 (33.2%) were diagnosed with active TB and 466 (79.9%) of them had CD4 count less than 200/΅l at diagnosis. Extrapulmonary TB was diagnosed in 372 (63.8%) patients [76 (20.4%) had disseminated TB], and pulmonary TB in 211 (36.2%) patients. "Favourable outcome" (cure and completed treatment) was observed in 332 (77%) patients. Unfavourable outcome included default (8.1%), treatment failure (1.6%), and death (13.2%). At 1-year post-treatment follow up, 12 (3.6%) patients had disease relapse. CD4 count of less than 200/ ΅l at diagnosis [OR-2.32, CI (1.06-5.09)], and retreatment cases [OR-2.91, CI (1.22-6.89)] were independent predictors of unfavourable outcome. INTERPRETATION & CONCLUSIONS: There is an urgent need to strengthen the information, education, communication activities and expand the ART services to meet the requirement of early testing and treatment initiation in patients co-infected with HIV-TB. The findings highlight the need for performing drug susceptibility testing (DST) for patients starting retreatment regimen to improve treatment outcome.

Vitamin D rescues impaired Mycobacterium tuberculosis-mediated tumor necrosis factor release in macrophages of HIV-seropositive individuals through an enhanced Toll-like receptor signaling pathway in vitro.

Mycobacterium tuberculosis disease represents an enormous global health problem, with exceptionally high morbidity and mortality in HIV-seropositive (HIV(+)) persons. Alveolar macrophages from HIV(+) persons demonstrate specific and targeted impairment of critical host cell responses, including impaired M. tuberculosis-mediated tumor necrosis factor (TNF) release and macrophage apoptosis. Vitamin D may promote anti-M. tuberculosis responses through upregulation of macrophage NO, NADPH oxidase, cathelicidin, and autophagy mechanisms, but whether vitamin D promotes anti-M. tuberculosis mechanisms in HIV(+) macrophages is not known. In the current study, human macrophages exposed to M. tuberculosis demonstrated robust release of TNF, IκB degradation, and NF-κB nuclear translocation, and these responses were independent of vitamin D pretreatment. In marked contrast, HIV(+) U1 human macrophages exposed to M. tuberculosis demonstrated very low TNF release and no significant IκB degradation or NF-κB nuclear translocation, whereas vitamin D pretreatment restored these critical responses. The vitamin D-mediated restored responses were dependent in part on macrophage CD14 expression. Importantly, similar response patterns were observed with clinically relevant human alveolar macrophages from healthy individuals and asymptomatic HIV(+) persons at high clinical risk of M. tuberculosis infection. Taken together with the observation that local bronchoalveolar lavage fluid (BALF) levels of vitamin D are severely deficient in HIV(+) persons, the data from this study demonstrate that exogenous vitamin D can selectively rescue impaired critical innate immune responses in vitro in alveolar macrophages from HIV(+) persons at risk for M. tuberculosis disease, supporting a potential role for exogenous vitamin D as a therapeutic adjuvant in M. tuberculosis infection in HIV(+) persons.

Challenges in the diagnosis & treatment of miliary tuberculosis.

Miliary tuberculosis (TB) is a potentially lethal disease if not diagnosed and treated early. Diagnosing miliary TB can be a challenge that can perplex even the most experienced clinicians. Clinical manifestations are nonspecific, typical chest radiograph findings may not be evident till late in the disease, high resolution computed tomography (HRCT) shows randomly distributed miliary nodules and is relatively more sensitive. Ultrasonography, CT and magnetic resonance imaging (MRI) are useful in discerning the extent of organ involvement by lesions of miliary TB in extra-pulmonary locations. Fundus examination for choroid tubercles, histopathological examination of tissue biopsy specimens, conventional and rapid culture methods for isolation of Mycobacterium tuberculosis, drug-susceptibility testing, along with use of molecular biology tools in sputum, body fluids, other body tissues are useful in confirming the diagnosis. Although several prognostic markers have been described which predict mortality, yet untreated miliary TB has a fatal outcome within one year. A high index of clinical suspicion and early diagnosis and timely institution of anti-tuberculosis treatment can be life-saving. Response to first-line anti-tuberculosis drugs is good but drug-induced hepatotoxicity and drug-drug interactions in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients pose significant problems during treatment. However, sparse data are available from randomized controlled trials to define the optimum regimen and duration of treatment in patients with drug-sensitive as well as drug-resistant miliary TB, including those with HIV/AIDS.

Delayed resolution of inflammatory response compared with clinical recovery in patients with acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: The temporal profile of inflammatory markers during acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and their relationship to clinical response are not well characterized. The aim was to assess the changes in levels of inflammatory markers in AECOPD and correlate these with clinical and laboratory indices of recovery. METHODS: Serum levels of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen were measured in patients with AECOPD within 24 h of hospitalization and pre-discharge (stable state). RESULTS: Ninety-seven patients were evaluated (79 males; mean (SD) age, 61.4 (10.3) years). Eighty eight (90.7%) were current or former smokers, with a median consumption of 15 (0-75) packs/year. The median duration of COPD was 8 (2-25) years. Forty-six patients (56.9%) required mechanical ventilation for a median of 5 days (1-34) while in hospital. The median duration of hospital stay was 13 days (1-77). At reassessment before planned discharge, the levels of dyspnoea, leucocyte counts, erythrocyte sedimentation rate, creatinine, partial pressure of oxygen, and albumin normalized. The levels of CRP, IL-6 and fibrinogen reduced significantly but did not reach the normal range. Changes in IL-6 and fibrinogen levels correlated significantly with the acute physiologic assessment and chronic health evaluation II score, smoking history, blood pressure and leucocyte counts. Baseline IL-6 and fibrinogen levels significantly predicted a prolonged duration of mechanical ventilation. CONCLUSIONS: During AECOPD, the inflammatory response lags behind clinical and biochemical improvement. Fibrinogen and IL-6 are potentially useful markers for monitoring clinical response following an acute episode.

Histoplasmosis presenting as bilateral adrenal masses: cytomorphological diagnosis of three cases.

Histoplasmosis is a worldwide infectious disease caused by inhalation of spores of a fungus, called Histoplasma capsulatum.Adrenals can be involved as a part of disseminated infection in immunocompromized patients. However, histoplasmosis presenting primarily as a bilateral adrenal masses in an immunocompetent patient is very unusual and rare. We encountered three such cases in which fine-needle aspiration (FNA) performed under ultrasonographic (USG) guidance from bilateral adrenal masses primarily established the diagnosis. This report emphasizes the importance of considering localized fungal infection as differential diagnoses of mass lesions involving bilateral adrenals even if the patients are immunocompetent, along with the commoner lesions at these sites.

Clinical characteristics of tuberculosis-associated immune reconstitution inflammatory syndrome in North Indian population of HIV/AIDS patients receiving HAART.

BACKGROUND & OBJECTIVE: IRIS is an important complication that occurs during management of HIV-TB coinfection and it poses difficulty in diagnosis. Previous studies have reported variable incidence of IRIS. The present study was undertaken to describe the pattern of TB-associated IRIS using recently proposed consensus case-definitions for TB-IRIS for its use in resource-limited settings. METHODS: A prospective analysis of ART-naïve adults started on HAART from November, 2008 to May, 2010 was done in a tertiary care hospital in north India. A total 224 patients divided into two groups, one with HIV-TB and the other with HIV alone, were followedup for a minimum period of 3 months. The diagnosis of TB was categorised as ''definitive" and ''probable". RESULTS: Out of a total of 224 patients, 203 completed followup. Paradoxical TB-IRIS occurred in 5 of 123 (4%) HIV-TB patients while 6 of 80 (7.5%) HIV patients developed ART-associated TB. A reduction in plasma viral load was significantly (P = .016) associated with paradoxical TB-IRIS. No identifiable risk factors were associated with the development of ART-associated TB. CONCLUSION: The consensus case-definitions are useful tools in the diagnosis of TB-associated IRIS. High index of clinical suspicion is required for an early diagnosis.