Radiological manifestations of splenic tuberculosis: a 23-patient case series from India

Background & Objective: Splenic tuberculosis (TB) is a less common but important manifestation of abdominal TB, especially in India and other developing countries. Its prevalence is increasing with the epidemic of HIV-TB co-infection and subsequent rise in extrapulmonary TB. The range of radiological manifestations of splenic TB is poorly described. Here, we review the ultrasonographic and computed tomographic (CT) images of 23 cases from two large tertiary care centers in India. Methods: Radiographic images, ultrasonographic in all cases and CT in selected cases, were retrospectively analyzed in a series of 23 patients presenting to two large tertiary care centers in India, with suspected TB and with splenomegaly on physical examination. Images were assessed at baseline and when available following anti-tuberculosis therapy. Results: The ultrasound and CT findings included, in order of most common: single or multiple hypoechoic focal lesions, splenic abscess, calcifications (on CT), and isolated splenomegaly. Five of the six patients with findings of isolated splenomegaly on ultrasound were found to have lesions on CT. Interpretation & Conclusion: Ultrasonography of the spleen is an affordable, non-invasive imaging modality, which can be helpful in diagnosis of splenic TB and assessment of therapeutic response. Proper use of this imaging modality in splenic TB should help avoid unnecessary CT imaging or invasive procedures. However, this technique is operator-dependent, and, when extensive intraabdominal involvement is suspected, or the diagnosis is unclear, CT may be necessary

DOTS at a tertiary care center in Northern India: successes, challenges and the next steps in tuberculosis control

Background and Objectives: The past decade has seen a rapid expansion of directly observed treatment, short-course (DOTS) centers throughout India, under the guidance of the Revised National Tuberculosis Control Programme (RNTCP). While expansion has been rapid and extensive, few reports exist detailing individual DOTS centers' experiences, their challenges, and their successes. We present a brief report on the status of a DOTS center being run at a large tertiary care center in northern India for almost four years (2001-2005). Methods: The DOTS center followed RNTCP guidelines for the evaluation and treatment of suspected TB cases. A register carrying detailed information of all patients seen at the DOTS center was kept by the senior clinician. Data from this register were extracted and analyzed for descriptive measures. Results: A total of 1490 patients were evaluated. Of the 768 patients with cough, 27 per cent (211) were found to be sputum positive for acid-fast bacilli (AFB). Among patients who were initiated on anti-tuberculosis medications, cure was achieved in 92 per cent (71 of 77) of new sputum smear positive patients; treatment completion was achieved in 91 per cent (91 of 100) of extrapulmonary TB (EPTB) and 75 per cent (46 of 61) of sputum-negative pulmonary TB patients. Overall treatment success was achieved in 86 per cent (229 of 266). Interpretation and Conclusion: Treatment results were in keeping with the RNTCP guidelines. Tertiary care centers appear to be excellent place for education of medical students and operational research. The latter is much needed, as HIV-TB co-infection, multi-drug resistant TB, and EPTB continue to be major public health threats even in the era of DOTS

Persistently high HIV seroprevalence among adult tuberculosis patients at a tertiary care centre in Delhi

Background & Objective: This study was designed to estimate HIV seroprevalence among tuberculosis patients presenting to tertiary care centre in Delhi. Methods: Cross-sectional prevalence study among all patients presenting to the inpatient and outpatient departments of All India Institute of Medical Sciences (AIIMS), New Delhi, and receiving anti-tuberculosis treatment from May 2003 to April 2005. Results: Of the 448 patients who presented to the TB clinic during the study period, 23 (5.1%) were previously tested HIV-positive. An additional 21 patients (4.6%) refused testing, and 30 (6.7%) were lost to follow up. Of the remaining 374 patients who consented to testing, 31 (8.3%) were found to be HIV-positive. Risk factors for HIV seropositivity included high-risk sexual behaviours (48% in HIV-TB co-infected vs. 6% in TB infected patients, P<0.001) and history of blood transfusion (23% vs. 5%; P=0.002). Interpretation & Conclusion: Previous studies from the same hospital published in 2000 and 2003 reported HIV seroprevalence among TB patients to be 0.4 and 9.4 per cent respectively. The current study documents a persistently high seropositivity among TB patients. These results emphasize the acute need for improved detection and treatment for HIV among TB patients in northern India

Poor follow-up rates at a self-pay northern Indian tertiary AIDS clinic

<p>Abstract</p> <p>Background</p> <p>In many developing countries, out-of-pocket payment remains a primary mechanism by which patients infected with HIV access treatment. In India, this has been changing as the National AIDS Control Organization (NACO) has been rolling out free antiretroviral therapy throughout the country since 2004. The vast majority of patients, however, remain without access to free medicines.</p> <p>Methods</p> <p>A retrospective chart review was performed on data obtained from a registry of ninety-three (93) patients attending a self-pay clinic at the All India Institute of Medical Sciences in Delhi, India. Multivariable Cox proportional hazard and logistic regression models were explored to assess the relationship between lost-to-follow-up status and the predictor variables: age, sex, household income, baseline CD4 count, and distance from clinic.</p> <p>Results</p> <p>Lost-to-follow-up rates were very high; 68% (63/93) were lost-to-follow-up till the time of chart review, including 59% (55/93) who were lost within one year. In both regression models, younger age, low baseline CD4 counts, and low income level were significantly associated with increased risk of lost-to-follow-up. Additionally, there was a significant interaction between income and CD4 counts. The patients with both low CD4 counts and low income level were more likely to be lost-to-follow-up than would be predicted by each covariable alone.</p> <p>Conclusion</p> <p>In this small cohort of AIDS patients attending a self-pay antiretroviral clinic at a large tertiary care center in Delhi, India, follow-up rates were quite poor. Poorer patients tended to present to clinic with more depressed CD4 counts and were less likely to be retained in care. These findings indicate that greater strides must be taken to improve the recruitment and retention of poor patients. The expansion of free antiretrovirals is one step among many necessary to achieve this objective.</p

Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma: CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results

PURPOSE CheckMate 032 is an open-label, multicohort study that includes patients with unresectable locally advanced or metastatic urothelial carcinoma (mUC) treated with nivolumab 3 mg/kg monotherapy every 2 weeks (NIVO3), nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO3+IPI1), or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO1+IPI3). We report on the expanded NIVO1+IPI3 cohort and extended follow-up for the NIVO3 and NIVO3+IPI1 cohorts. METHODS Patients with platinum-pretreated mUC were enrolled in this phase I/II multicenter study to receive NIVO3, NIVO3+IPI1, or NIVO1+IPI3 until disease progression or unacceptable toxicity. Primary end point was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including duration of response. RESULTS Seventy-eight patients were treated with NIVO3 (minimum follow-up, 37.7 months), 104 with NIVO3+IPI1 (minimum follow-up, 38.8 months), and 92 with NIVO1+IPI3 (minimum follow-up, 7.9 months). Objective response rate was 25.6%, 26.9%, and 38.0% in the NIVO3, NIVO3+IPI1, and NIVO1+IPI3 arms, respectively. Median duration of response was more than 22 months in all arms. Grade 3 or 4 treatment-related adverse events occurred in 21 (26.9%), 32 (30.8%), and 36 (39.1%) patients treated with NIVO3, NIVO3+IPI1, and NIVO1+IPI3, respectively. Grade 5 treatment-related pneumonitis occurred in one patient each in the NIVO3 and NIVO3+IPI1 arms. CONCLUSION With longer follow-up, NIVO3 demonstrated sustained antitumor activity alone and in combination with ipilimumab. NIVO1+IPI3 provided the greatest antitumor activity of all regimens, with a manageable safety profile. This result not only supports additional study of NIVO1+IPI3 in mUC, but demonstrates the potential benefit of immunotherapy combinations in this disease

Theoretical study of peculiarities of unstable longitudinal shear crack growth in sub-Rayleigh and supershear regimes

In the paper we present the results of the theoretical study of some fundamental aspects of mode II crack propagation in conventional sub-Rayleigh regime and transition to intersonic regime. It is shown that development of a sub-Rayleigh shear crack is determined in many respects by elastic vortex traveling ahead of the crack tip at a shear wave velocity. Formation of such a vortex helps to better understand the well-known phenomenon of acceleration of a shear crack towards the longitudinal wave velocity. Simulation results have shown that due to self-similarity of shear crack propagation the conditions of sub-Rayleigh to intersonic transition depend on dimensionless material and crack parameters. Two key dimensionless parameters are proposed

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

The IASLC/ITMIG thymic epithelial tumors staging project: Proposals for the T component for the forthcoming (8th) edition of the TNM classification of malignant tumors

Despite longstanding recognition of thymic epithelial neoplasms, there is no official American Joint Committee on Cancer/ Union for International Cancer Control stage classification. This article summarizes proposals for classification of the T component of stage classification for use in the 8th edition of the tumor, node, metastasis classification for malignant tumors. This represents the output of the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group Staging and Prognostics Factor Committee, which assembled and analyzed a worldwide database of 10,808 patients with thymic malignancies from 105 sites. The committee proposes division of the T component into four categories, representing levels of invasion. T1 includes tumors localized to the thymus and anterior mediastinal fat, regardless of capsular invasion, up to and including infiltration through the mediastinal pleura. Invasion of the pericardium is designated as T2. T3 includes tumors with direct involvement of a group of mediastinal structures either singly or in combination: lung, brachiocephalic vein, superior vena cava, chest wall, and phrenic nerve. Invasion of more central structures constitutes T4: aorta and arch vessels, intrapericardial pulmonary artery, myocardium, trachea, and esophagus. Size did not emerge as a useful descriptor for stage classification. This classification of T categories, combined with a classification of N and M categories, provides a basis for a robust tumor, node, metastasis classification system for the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control stage classification

Tuberculin skin test among pulmonary sarcoidosis patients with and without tuberculosis: its utility for the screening of the two conditions in tuberculosis-endemic regions

Background: Sarcoidosis is an increasingly important condition in developing countries, including those with a high prevalence of tuberculosis. The tuberculin skin test (TST) is one test used in distinguishing these two granulomatous conditions. It has been shown that a negative TST is highly sensitive for sarcoidosis. This retrospective study set out to assess the converse: the role of a positive test in the assessing the likelihood that a patient with sarcoidosis might also have tuberculosis. Methods: A retrospective chart review of 141 patients with biopsy-proved sarcoidosis, among whom there were 16 biopsy-proven sarcoidosis and tuberculosis patients and 125 sarcoidosis-only patients. The receiver operating curve was constructed by calculating the sensitivity and specificity of various levels of induration of the tuberculin skin test for the diagnosis of comorbid tuberculosis. Results: The area under the curve of the ROC did not differ from 0.5, meaning that the TST was not useful as a graded measure. This was largely due to its poor sensitivity. However, a level of greater than or equal to 10 mm induration, though insensitive, had a specificity of 97.6% for the diagnosis of tuberculosis among this population of sarcoidosis patients. Conclusions: The tuberculin skin test in sarcoid patients has a high specificity but a poor sensitivity for tuberculosis. As such, while a negative TST in the general population is a sensitive test for sarcoidosis, a positive TST among sarcoidosis patients is a specific test for indicating tuberculosis. A positive TST in a patient suspected to suffer from sarcoidosis should therefore be an absolute indication for a thorough work-up for tuberculosis

Unsafe medical injections and HIV transmission in India

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