Accuracy of TB-PCR using endobronchial ultrasound guided trans-bronchial needle aspiration (EBUS-TBNA) samples in mediastinal granulomatous lymphadenopathy.

INTRODUCTION: Mediastinal granulomatous lymphadenopathies, such as tuberculous lymphadenitis, sarcoidosis, are frequently encountered by respiratory physicians, and their diagnosis is based on histological and microbiological tests. Endobronchial ultrasound-guided Trans bronchial needle aspiration (EBUS-TBNA) is widely used to perform mediastinal lymph node sampling. However, very limited data is available on the yield of polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) using EBUS-TBNA samples in patients with mediastinal granulomatous lymphadenopathy. MATERIALS AND METHODS: A retrospective study using a prospectively collected database was performed from January 1, 2018 to December 31, 2018, to evaluate the efficacy of the TB-PCR test using EBUS-TBNA samples in patients with benign mediastinal lymphadenopathy which included both granulomatous lymphadenopathy and reactive lymphadenopathy. The cohort with reactive lymphadenopathy acted as the control group of the study population. The patients with mediastinal lymphadenopathy who were awaiting EBUS-TBNA either for diagnostic evaluation of primary disease or for staging of a known malignancy were included in the study. The patients were then followed up for 1 year post procedure with clinical and radiological evaluation. RESULTS: Of the 310 patients with mediastinal lymphadenopathy who underwent EBUS-TBNA, 190 cases had a benign pathology with granulomatous lymphadenopathy in 120 and reactive lymphadenopathy in 70 patients. The sensitivity, specificity, the positive predictive value and the negative predictive value of TB-PCR was at 90%, 97.14%, 98.18%, and 85% respectively. The accuracy of TB-PCR is 92.63%. CONCLUSION: TB-PCR using EBUS-TBNA samples is an effective tool for diagnosing mediastinal granulomatous lymphadenopathy. This technique can prevent further invasive interventions like mediastinoscopy in patients whose histological and microbiological tests are non-diagnostic. It should always be performed when tuberculosis is in the differential diagnosis of a patient with mediastinal lymphadenopathy.

Role of medical thoracoscopy in the diagnosis of pleural effusions.

BACKGROUND: Medical thoracoscopy (semi-rigid and rigid thoracoscopy) have revolutionized the management of undiagnosed pleural effusions. Though semi-rigid thoracoscopy has a good diagnostic yield in malignant and tubercular effusions, its role in the management of a complicated pleural effusions is debatable. Hence, rigid thoracoscopy becomes handy in these cases. The present study looked into the role of medical thoracoscopy in the diagnosis of pleural effusions in different conditions. METHODS: This study included all patients who underwent medical thoracoscopy at our center between May-2010 and March-2020. Basic demographics data, type of medical thoracoscopy used, and histopathology details were collected and analyzed. RESULTS: A total of 373 patients were subjected to medical thoracoscopy (202 semi-rigid thoracoscopy and 171 rigid thoracoscopy). Out of whom 246 (66%) were males, the mean age was 51.9 ± 13.2 years. Diagnosis was achieved in 370 patients with a yield of 99.2%. The diagnostic yield in semi-rigid thoracoscopy was 99.5% with lung malignancy being the most common diagnosis (41%; n = 81), followed by tuberculosis (31%; n = 61). The diagnostic yield in rigid thoracoscopy was 100% in our study. Along with high diagnostic yield, complete drainage and lung expansion was seen in 93.5% (160 out of 171 patients) without requiring a second procedure. CONCLUSIONS: Semi-rigid thoracoscopy and rigid thoracoscopy should complement each other in the diagnosis of pleural effusions. Rigid thoracoscopy should be considered as the procedure of choice in a complicated pleural effusion.

Evolution of semi-rigid thoracoscopy.

Pleural effusions despite being so common, there is no much literature available regarding definite diagnosis for pleural effusions. Application of Light's criteria changed the approach to pleural effusion and till date remains a very useful step in the diagnosis of pleural effusions. Pleural fluid biochemistry and adenosine deaminase (ADA) enzyme levels play a significant role in the diagnosis of tubercular effusion. Studies have shown that levels of ADA are more often higher in tubercular effusion than in any other cause for it. But ADA levels can also be elevated in other types of parapneumonic effusions (PPEs), especially complicated PPEs. Hence it is difficult to distinguish a tubercular pleural effusion (TPE) from other PPEs based on pleural fluid ADA levels alone. LDH/ADA ratio as an indicator for ruling out tuberculosis was analyzed in few studies with high sensitivity and specificity. The pleural fluid cytology has a varying sensitivity, with a maximum of only 60% and it may increase with subsequent tapping. Closed pleural biopsy using a Cope or Abrams needle has a sensitivity up to 80% in cases of tuberculous effusion and 40%-73% in cases of Malignancies. Semi-rigid thoracoscopy not only allows for visualization of the pleura but also helps in procuring the biopsies under direct visualization from the abnormal looking areas. In cases of primary pleural malignancies like mesothelioma, pleurodesis can also be done in the same setting after taking the biopsy, hence reducing the number of procedures. Limitation of the semi-rigid thoracoscopy is smaller sample size and more superficial sampling of the pleura. Cryobiopsy and Electrocautery guided pleural biopsy using the IT knife are the modifications in the semi-rigid thoracoscopy to overcome the drawback of smaller sample size. While navigation band image guided pleuroscopy helps in better visualization of the vasculature of pleura during the biopsy. Management of pleural effusions has evolved over a period of time. Starting with a single criterion based on pleural fluid proteins to semi-rigid thoracoscopy. The inexhaustible research in this field suggests the desperate need for a gold standard procedure with cost effectiveness in the management of undiagnosed pleural effusions. Semi-rigid thoracoscopy has revolutionized the management of undiagnosed pleural effusions, but it has its own limitations. Various modifications have been proposed and tried to overcome the limitations to make it a cost-effective procedure.

Multidisciplinary team obviates biopsy in most patients with diffuse parenchymal lung diseases-A retrospective study from India.

INTRODUCTION: The inflammation and fibrosis in diffuse parenchymal lung diseases (DPLDs) in varied proportions give rise to different patterns in radiology and histopathology. The radiological pattern on CT of the thorax most often allows us to make a diagnosis with varying levels of confidence, to optimize management. With a multidisciplinary team bringing the strengths of their individual domains of knowledge, clinical, radiological, histopathological, and in many cases rheumatological, the level of confidence in making this diagnosis increases, often to the stage where the diagnosis is most often right, is concordant with the diagnosis achieved at histopathology and therefore obviates the need for lung biopsy which carries its own costs and risks of complications. Our study emphasizes the role of the multidisciplinary team (MDT) in the management of DPLDs at a tertiary care referral center. MATERIALS AND METHODS: Every case of DPLD presenting to our pulmonology department was discussed in an MDT meeting before subjecting them to any diagnostic intervention or therapy. A clinico-radiological diagnosis was made according to the 2002 ATS/ERS guidelines initially. Later an official ATS/ERS/JRS/ALAT statement on idiopathic pulmonary fibrosis and a 2013 ATS/ERS consensus for the classification and diagnosis of idiopathic interstitial pneumonia was used. The concordance in our study was defined as the percentage of histopathological diagnoses that were identical to the clinico-radiological MDT diagnosis prior to the biopsy. RESULTS: A total of 434 patients with DPLDs were evaluated. The MDT suggested biopsy for only 38.7% (168/434) patients since the pattern was very clear in 266 (61.3%) cases. As not all patients consented to undergo the biopsy procedure when recommended, histopathology was obtained in 102 patients. The histological diagnosis was concordant with the initial MDT diagnosis in 80.3% (82/102) of samples. On an individual basis, connective tissue disease-interstitial lung disease and sarcoidosis showed the best concordance (87%). In idiopathic non-specific interstitial pneumonitis (NSIP) cases, the histopathological diagnosis concurred in only 53.3% (8/15), out of which 8 were NSIP, 4 were usual interstitial pneumonia, and 3 were reported as inadequate sampling on histopathology. CONCLUSION: The MDT plays a crucial role in the diagnosis of DPLDs. Not every pattern requires biopsy confirmation. However, an idiopathic non-specific interstitial pneumonitis diagnosis by the MDT should probably be better confirmed by biopsy.

Post-transplant complications, patient, and graft survival in pediatric and adolescent kidney transplant recipients at a tropical tertiary care center across two immunosuppression eras.

BACKGROUND: We report pediatric PAKT patient and graft outcomes at a large tropical tertiary center spanning two transplant eras. METHODS: In this retrospective cohort study, all children ≤18 years who underwent kidney transplantation at our center between 1991 and 2016 were included. Data pertaining to their baseline characteristics, post-transplant events, and outcome were retrieved from transplant records and compared between transplant eras (1991-2005 and 2006-2016). RESULTS: A total of 139 children (mean age 15.2 ± 2.9 years) underwent PAKT during this period. The incidence of UTIs, CMV disease, BKVN, invasive fungal infections, new-onset diabetes after transplant, leucopenia, and recurrent NKD was higher in the 2006-2016 era (P < .001 for all), while 1-year cumulative BPAR was comparable (P = .100). Five-year graft and patient survival in the two eras were 89.9% and 94.2% (P = .365) and 92.1% and 95.3% (P = .739), respectively. Incidence of CMV disease, BKVN, graft loss, and death was lower in the calcineurin withdrawal group. Non-adherence accounted for 36% of graft loss; infections caused 43.7% of deaths. On multivariate Cox proportional hazards analysis, independent predictors for graft loss were UTIs and blood transfusion naïve status and for death were serious infections and glomerular NKD. CONCLUSIONS: PAKT in India has excellent long-term graft outcomes, though patient outcomes remain suboptimal owing to a high burden of infections. Current immunosuppression protocols need to be re-examined to balance infection risk, graft, and patient survival.

Myroides odoratimimus urinary tract infection.

Myroides species formerly known as Flavobacterium odoratum, a rare clinical isolate often considered as nonpathogenic. Myroides odoratimimus commonly found in the environment and frequently isolated from the immunocompromised patients. The incidence of urinary tract infection (UTI) caused by Myroides species is a rare phenomenon. We describe a rare case of UTI caused by Myroides odoratimimus in an elderly patient.

Spectrum of biopsy proven renal disease in South Asian children: Two decades at a tropical tertiary care centre.

AIM: We report findings from a large single centre paediatric renal biopsy cohort in South Asia. METHODS: We analyzed all renal biopsies performed on children aged ≤18 years between 1996 and 2015 at our centre. The clinical characteristics and histological diagnosis pertaining to each case, distribution of renal diseases in children with various clinical presentations, and changes in the pattern of kidney disease during the study period were analyzed. RESULTS: A total of 1740 paediatric kidney biopsies were performed during the study period. The mean age was 12.8 ± 4.9 years (8 months to 18 years) and the male: female ratio was 1.5:1. The most common indication for renal biopsy was nephrotic syndrome (63.2%) followed by acute nephritic syndrome (13%). Minimal change disease was the most common cause of nephrotic syndrome while endocapillary proliferative glomerulonephritis (65.7% infection related), remained the commonest cause of acute nephritic syndrome. IgA nephropathy was the commonest cause of chronic kidney disease. Contrary to trends in European paediatric cohorts, the frequency of lupus nephritis increased over the two decades of the study, while that of endocapillary proliferative glomerulonephritis did not show any appreciable decline. CONCLUSION: This study provides the largest data on biopsy proven renal disease in children from South Asia published till date and highlights important differences in the spectrum and trends of kidney disease compared to data from other regions.

A possible simplification for the estimation of area under the curve (AUC0₋12) of enteric-coated mycophenolate sodium in renal transplant patients receiving tacrolimus.

Enteric-coated mycophenolate sodium (EC-MPS) is widely used in renal transplantation. With a delayed absorption profile, it has not been possible to develop limited sampling strategies to estimate area under the curve (mycophenolic acid [MPA] AUC0₋12), which have limited time points and are completed in 2 hours. We developed and validated simplified strategies to estimate MPA AUC0₋12 in an Indian renal transplant population prescribed EC-MPS together with prednisolone and tacrolimus. Intensive pharmacokinetic sampling (17 samples each) was performed in 18 patients to measure MPA AUC0₋12. The profiles at 1 month were used to develop the simplified strategies and those at 5.5 months used for validation. We followed two approaches. In one, the AUC was calculated using the trapezoidal rule with fewer time points followed by an extrapolation. In the second approach, by stepwise multiple regression analysis, models with different time points were identified and linear regression analysis performed. Using the trapezoidal rule, two equations were developed with six time points and sampling to 6 or 8 hours (8hrAUC[0₋12exp]) after the EC-MPS dose. On validation, the 8hrAUC(0₋12exp) compared with total measured AUC0₋12 had a coefficient of correlation (r²) of 0.872 with a bias and precision (95% confidence interval) of 0.54% (-6.07-7.15) and 9.73% (5.37-14.09), respectively. Second, limited sampling strategies were developed with four, five, six, seven, and eight time points and completion within 2 hours, 4 hours, 6 hours, and 8 hours after the EC-MPS dose. On validation, six, seven, and eight time point equations, all with sampling to 8 hours, had an acceptable r with the total measured MPA AUC0₋12 (0.817-0.927). In the six, seven, and eight time points, the bias (95% confidence interval) was 3.00% (-4.59 to 10.59), 0.29% (-5.4 to 5.97), and -0.72% (-5.34 to 3.89) and the precision (95% confidence interval) was 10.59% (5.06-16.13), 8.33% (4.55-12.1), and 6.92% (3.94-9.90), respectively. Of the eight simplified approaches, inclusion of seven or eight time points improved the accuracy of the predicted AUC compared with the actual and can be advocated based on the priority of the user.

Can mycophenolic acid dose requirement during the first transplant help predict dosing for the second transplant?

We describe the pharmacokinetic profile of mycophenolic acid (MPA) in a patient receiving Mycophenolate mofetil (MMF) during her first and second renal transplantations. The MMF dose required to achieve a therapeutic range of MPA-AUC(0)(-)(12)(h) early following the second transplantation was 10 times greater than that required late following the first transplantation. Her MMF requirement then declined and continued to decrease even beyond 1 year. Intra-individual variability in MPA profiles precluded the ability to predict MMF dosing for the second transplant based on that during the first. Therapeutic drug monitoring of MMF should be continued beyond 1 year of transplantation.

A reliable limited sampling strategy for the estimation of mycophenolic acid area under the concentration time curve in adult renal transplant patients in the stable posttransplant period.

In renal transplant patients, there is an established relationship between mycophenolate area under the curve and clinical outcome. The authors have developed and validated a limited sampling strategy to estimate mycophenolic acid area under the curve to 12 hours (MPA AUC0-12) in a stable renal transplant Indian population prescribed a formulation of mycophenolate mofetil (Mofilet) along with prednisolone and tacrolimus. Intensive pharmacokinetic sampling was performed in 29 patients to measure mycophenolate concentration from trough to 12 hours postdose. Subsets of different timed concentrations against total measured 12-hour area under the curve were analyzed by linear regression. Three models were identified and linear regression analysis done. After all subset regression analysis, three, four, and five time point limited sampling strategies (LSS) were developed having correlation coefficients above 0.92. Validation of the models was performed using the jackknife method and their predictive performances were tested. After validation, the correlation coefficients for all three models were above 0.901. The five-point LSS had the best predictive performance with a bias (95% confidence interval) of 0.67% (-3.45 to 4.79) and mean precision 7.73%. In all patients except one, the five-point LSS estimation for total area under the curve was within +/- 20% of the total measured AUC0-12. Trough concentration had a significant correlation with AUC0-12 (r = 0.69). However, if dosing in routine clinical practice was adjusted based only on trough concentration, 41% of our patients would require a different dose compared with monitoring using AUC0-12. The five-point LSS uses half-hourly samples from trough to 1.5 hour postdose with an additional sample at 3 hours. Ninety-three percent of our patients had a Cmax within 1.5 hour and inclusion of all the time points up to1.5 hour gave a better estimate of AUC0-12. This model simplifies area under the curve measurement with high precision in stable adult renal transplant patients.