Immunological alterations in tuberculosis associated immune reconstitution inflammatory syndrome in HIV infected patients

The tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) frequently complicates the course of HIV/AIDS and HIV-TB treatment and its immunological mechanisms are poorly understood. Here, we investigated T-cells frequencies, their secreted chemokines and cytokines. In this prospective case-control study, HIV/AIDS and HIV-TB patients during treatment with highly active antiretroviral treatment (HAART) and anti-TB treatment were followed for TB-IRIS development. Age, gender and BMI-matched patients without IRIS constituted as “Controls” (non-IRIS). Activation and proliferation were assessed in CD4 and CD8 cell compartments. CCR4, CCR6 and T-reg cells were also analysed in PBMCs. Cytokines (IL-2, IL-4, IL-10, IFN-γ and TGF-β1) and chemokines (IP-10, MCP-1, MIG and RANTES) were measured in culture supernatants. Of 560 enrolled HIV/AIDS patients, TB-IRIS developed in 50 (8.9%) patients (25-paradoxical and 25-unmasking) at a median interval of 35-days (IQR, 24-78). After ART therapy, CD8+ T-cell proportion decreased in both paradoxical and unmasking-TB-IRIS as compared to non-IRIS. Simultaneously, activation of CD4+ T-cells was observed in unmasking TB-IRIS only. Similarly, CD161+ T-cells, Th17-cells and inflammatory cytokines like IFN-γ, IP-10 and MIG elevated in both TB-IRIS subgroups as compared to non-IRIS.In conclusion, during HAART treatment the dominance of pro-inflammatory cells and cytokines in TB-IRIS patients favours the development of IRIS event. On the other hand, in non-IRIS patients relative increase of anti-inflammatory cells and cytokines prevents the development of IRIS event.

Comparison of resection margins and cosmetic outcome following intraoperative ultrasound-guided excision versus conventional palpation-guided breast conservation surgery in breast cancer: A randomized controlled trial

INTRODUCTION: Use of intraoperative ultrasound (IOUS) has been shown to help achieve satisfactory cosmesis and negative margins in breast conserving surgery (BCS). This study has been done to compare the oncological and cosmetic outcomes following BCS using conventional palpatory method and IOUS. MATERIALS AND METHODS: This is a prospective randomized controlled trial conducted at a tertiary care teaching and research institute in India. Patients with early operable breast cancer willing for BCS were included. Tumors were excised with 1 cm margin. In palpatory group, tumor was palpated and 1 cm margin was taken with a measuring scale while in the second group, IOUS was used to mark the margins. Histopathological evaluation was done to assess margins and cosmesis was assessed by patient, resident doctor, and nurse independently. RESULTS: Sixty patients were included, 32 in the ultrasonography-guided and 28 in palpation-guided wide local excision. The mean age of patients was 48.78 years. In both groups, mean tumor size was 3.18 cm. Margin thickness and positivity was higher in palpatory group (though P > 0.05). Most patients were satisfied with cosmesis. There was no significant difference in complications and specimen volume in both groups. Presence of ductal carcinoma in situ component and expression of Her2neu by tumor cells had a significant impact on margin positivity. CONCLUSIONS: Intraoperative use of ultrasound offers a real-time assessment of margin status and may reduce the margin positivity rate compared to conventional palpation-guided method.

Image guided versus palpation guided core needle biopsy of palpable breast masses: a prospective study.

Background & objectives: Biopsy of palpable breast masses can be performed manually by palpation guidance or under imaging guidance. Based on retrospective studies, image guided biopsy is considered more accurate than palpation guided breast biopsy; however, these techniques have not been compared prospectively. We conducted this prospective study to verify the superiority and determine the size of beneficial effect of image guided biopsy over palpation guided biopsy. Methods: Over a period of 18 months, 36 patients each with palpable breast masses were randomized into palpation guided and image guided breast biopsy arms. Ultrasound was used for image guidance in 33 patients and mammographic (stereotactic) guidance in three patients. All biopsies were performed using 14 gauge automated core biopsy needles. Inconclusive, suspicious or imaging-histologic discordant biopsies were repeated. Results: Malignancy was found in 30 of 36 women in palpation guided biopsy arm and 27 of 36 women in image guided biopsy arm. Palpation guided biopsy had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 46.7, 100, 100, 27.3 per cent, respectively, for diagnosing breast cancer. Nineteen of 36 women (52.8%) required repeat biopsy because of inadequate samples (7 of 19), suspicious findings (2 of 19) or imaging-histologic discordance (10 of 19). On repeat biopsy, malignancy was found in all cases of imaging-histologic discordance. Image guided biopsy had 96.3 per cent sensitivity and 100 per cent specificity. There was no case of inadequate sample or imaging-histologic discordance with image guided biopsy. Interpretation & conclusions: Our results showed that in palpable breast masses, image guided biopsy was superior to palpation guided biopsy in terms of sensitivity, false negative rate and repeat biopsy rates.

Low dose mifepristone in medical management of uterine leiomyoma - An experience from a tertiary care hospital from north India.

Background & objectives: Uterine myoma is a common indication for hysterectomy in India. An effective medical treatment option may reduce hysterectomy associated morbidity. This study was undertaken to evaluate efficacy and safety of low dose mifepristone in medical management of myoma and to compare two doses - 10 vs. 25 mg/day. Methods: In this randomized clinical trial, women with symptomatic myoma or myoma>5cm were included. Uterine size >20 wk, fibroids >15 cm were excluded. Pictorial blood loss assessment chart (PBAC) score was used to assess menstrual-blood-loss and visual analog scale (VAS) for other symptoms. Haemogram, liver function test, ultrasound with doppler and endometrial histology was performed. Patients were randomized and were given oral mifepristone as 25 mg/day in group 1 and 10 mg/day in group 2 for 3 months. Patients were followed at 1, 3 and 6 months. Results: Seventy patients in group 1 and 73 in group 2 completed treatment. Mean PBAC score reduced from 253 to 19.8 and from 289.2 to 10.4 at 1 and 3 months in groups 1 and 2, respectively. At 3 months, 67 of 70 (95.7%) patients of group 1 and 66 of 73 (90.4%) of group 2 developed amenorrhoea which reverted after median 34 (range 4-85) days. Mean myoma volume decreased by 35.7 per cent (from 176.8 to 113.7cm3) and 22.5 per cent (from 147.6 to 114.4 cm3) at 3 months in groups 1 and 2, respectively. Side effects seen were leg cramps in 7 of 70 (10%) and 5 of 73 (6.8%) and hot-flushes in 5 of 70 (7.1%) and 5 of 73 (6.8%) in groups 1 and 2, respectively. Repeat endometrial-histopathology did not reveal any complex hyperplasia or atypia in either group. Interpretation & conclusions: Mifepristone (10 and 25 mg) caused symptomatic relief with more than 90 per cent reduction in menstrual blood. Greater myoma size reduction occured with 25 mg dose. Amenorrhoea was developed in 90-95 per cent patients which was reversible. It can be a reasonable choice for management of uterine leiomyoma as it is administered orally, cost-effective and has mild side effects.

Rare manifestations of sarcoidosis in modern era of new diagnostic tools.

Background & objectives: Growing body of literature on sarcoidosis in India has led to an increased awareness of the disease. With the advent of better imaging tools hitherto under-recognized manifestations of sarcoidosis are likely to be better recognized. We sought to study the rare clinical and radiological manifestations (<5%) in patients with sarcoidosis. Methods: Retrospective review of records of 164 patients with histopathologically proven sarcoidosis seen over six years in a tertiary care centre in north India, was done. Results: Fifty four rare manifestations were observed in 164 patients. Acute presentation in the form of Lofgren syndrome was seen in eight (4.9%) and Heerfordt's syndrome in two (1.2%) patients. Musculoskeletal manifestations included chronic sarcoid arthritis in three (1.8%), deforming arthritis and bone erosion in one (0.6%) each. Rare initial presentation with dilated cardiomyopathy in one (0.6%), complete heart block in two (1.2%), bilateral sequential facial nerve palsy in two (1.2%), and pyrexia of unknown origin was seen in one (0.6%) patient. Other rare manifestations included chronic respiratory failure in one (0.6%), dysphagia in one (0.6%), sicca syndrome in five (3%), massive splenomegaly in one (0.6%), portal hypertension in two (1.2%), hypersplenism, gastric sarcoidosis, ninth and tenth cranial nerve palsies, moderate pericardial effusion and nephrocalcinosis in one (0.6%) each, and pulmonary artery hypertension in two (1.2%) patients. Rare radiological manifestations included moderate pleural effusion in two (1.2%), pleural thickening in five (3%), calcification of intrathoracic lymph nodes in four (2.4%), alveolar (nodular) sarcoidosis in three (1.8%), and myocardial uptake of 18F-fluorodeoxyglucose (F-18 FDG) in two (1.2%) patients. Fourteen patients had airways obstruction and behaved typically like seasonal bronchial asthma with excellent response to corticosteroids. Interpretation & conclusions: Increased awareness of rare manifestations will facilitate better management of these patients. With increasing use of modern diagnostic tools, manifestations hitherto considered rare, are likely to be recognized more frequently in the future.

Pyelonephritis presenting with severe acute renal failure.

We describe an unusual case of an 8-yr-old child presenting with low grade fever and acute renal failure. Investigations showed blood urea 246 mg/dl, serum creatinine 6.4 mg/dl, microscopic hematuria and 2+ proteinuria. Renal biopsy was done in view of rapidly worsening kidney function and showed dense lymphoplasmacytic infiltrate and neutrophils with focal areas of interstitial necrosis, confirming acute pyelonephritis. Ultrasonography and MRI demonstrated multiple renal abscesses. He was managed with antimicrobial therapy and hemodialysis.