Challenges, experiences, and postoperative outcomes in setting up first successful lung transplant unit in India.

BACKGROUND: Lung transplantation (LT) has emerged as a definitive cure for a plethora of end-stage lung diseases (ESLDs). With improvements in immune-suppression protocols, the posttransplantation survival rates have gone up. AIM: The study reported the initial experience of the India's single largest lung transplant program on clinicopathological profile, procedures, challenges encountered, and outcomes. SETTINGS AND DESIGN: A retrospective analysis was done from data available at three centers of Institute of Heart and Lung Transplant, Gleneagles Global Hospitals across Chennai, Bengaluru, and Mumbai. MATERIALS AND METHODS: A total of 132 patients underwent lung (single or bilateral) or combined heart and lung transplant between April 2017 and March 2020. All the participants had 30 days' follow-up. Postoperative complications, graft rejection, and 30-day mortality were reported. Kaplan-Meier survival analysis and logistic regression analysis were performed. STATISTICAL ANALYSIS USED: Kaplan-Meier survival and binary logistic regression was performed. RESULTS: Interstitial lung diseases, 65.91%, were the most common diagnosis. Bilateral LT (81.3%) was the most common type of LT performed. Grade III primary graft dysfunction was observed in 16 (12.1%). Distal airway stenosis (21.97%) was the most common complication followed by anastomotic stenosis (14.30%). Gram-negative bacterial sepsis (52%) was the leading cause of death. Cumulative probability of survival at 1 month was 0.85 (95% confidence interval [CI] 0.80-0.92), and at 1 year, it was 0.78 (95% CI, 0.72-0.86). CONCLUSION: This study establishes the fact that despite multiple challenges, LT is a viable option for selected patients with ESLDs in India and should encourage early referrals to a transplant center.

Powered instrumentation in obstructing laryngeal tumours.

Traditionally, debulking of obstructing laryngeal tumours has been performed with cold steel instruments or CO2 lasers. With recent technological advances and increased availability of microdebriders, powered instrumentation for debulking laryngeal tumours has become a viable option. We describe the use of the Xomed laryngeal Tricut blade in re-establishing the airways in four patients with obstructing laryngeal tumours. In all cases a tracheostomy was avoided, thus allowing adequate time to stage each patient and tailor surgery to the individual.

Moxifloxacin, ofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis: evaluation of in vitro and pharmacodynamic indices that best predict in vivo efficacy.

Members of the fluoroquinolone class are being actively evaluated for inclusion in tuberculosis chemotherapy regimens, and we sought to determine the best in vitro and pharmacodynamic predictors of in vivo efficacy in mice. MICs for Mycobacterium tuberculosis H37Rv were 0.1 mg/liter (sparfloxacin [SPX]) and 0.5 mg/liter (moxifloxacin [MXF], ciprofloxacin [CIP], and ofloxacin [OFX]). The unbound fraction in the presence of murine serum was concentration dependent for MXF, OFX, SPX, and CIP. In vitro time-kill studies revealed a time-dependent effect, with the CFU reduction on day 7 similar for all four drugs. However, with a J774A.1 murine macrophage tuberculosis infection model, CIP was ineffective at up to 32x MIC. In addition, MXF, OFX, and SPX exhibited less activity than had been seen in the in vitro time-kill study. After demonstrating that the area under the concentration-time curve (AUC) and maximum concentration of drug in plasma were proportional to the dose in vivo, dose fractionation studies with total oral doses of 37.5 to 19,200 mg/kg of body weight (MXF), 225 to 115,200 mg/kg (OFX), 30 to 50,000 mg/kg (SPX), and 38 to 100,000 mg/kg (CIP) were performed with a murine aerosol infection model. MXF was the most efficacious agent (3.0+/-0.2 log10 CFU/lung reduction), followed by SPX (1.4+/-0.1) and OFX (1.5+/-0.1). CIP showed no effect. The ratio of the AUC to the MIC was the pharmacodynamic parameter that best described the in vivo efficacy. In summary, a lack of intracellular killing predicted the lack of in vivo activity of CIP. The in vivo rank order for maximal efficacy of the three active fluoroquinolones was not clearly predicted by the in vitro assays, however.

Posterior epistaxis: identification of common bleeding sites.

OBJECTIVE: The objective of this study was to determine common bleeding sites in the nasal cavity of patients with posterior epistaxis and thus review our management protocol. STUDY DESIGN: A prospective study was carried out from 1989 to November 2003 in the otolaryngology-head and neck surgery department of a tertiary referral center. This study included patients who presented with posterior epistaxis uncontrolled with standard nasal packing and with no identifiable bleeding point on examination under local anesthesia. METHOD: All patients underwent a formal examination under general anesthesia by the senior author of this article. Findings at examination were documented along with subsequent management and its outcome. RESULTS: Forty-three patients were included in this study. Bleeding points were identified in 36 cases. Seven patients had septal bleeding points (20%). The rest were located on the lateral nasal wall (81%). Of these, 4 were on the lateral wall of inferior meatus, 7 on the lateral surface of inferior turbinate, 8 on the lateral wall of middle meatus, and 10 on the lateral surface of middle turbinate. All were located posteriorly. CONCLUSIONS: We recommend examination under general anesthesia when conservative measures fail to control bleeding, concentrating on the posterior aspect of the lateral nasal wall. In addition, the lateral aspect of the middle and inferior turbinates may contain a groove within which bleeding points may be concealed. The lateral position of most bleeding sites indicates that use of nasal packing can only attempt to indirectly tamponade blood flow and is rarely justified bilaterally. Electrothermocautery can achieve excellent results with minimal complications. Failure to identify a bleeding point, after thorough examination under general anesthesia, does not require further intervention unless complicated by further bleeding.

Isoniazid pharmacokinetics-pharmacodynamics in an aerosol infection model of tuberculosis.

Limited data exist on the pharmacokinetic-pharmacodynamic (PK-PD) parameters of the bactericidal activities of the available antimycobacterial drugs. We report on the PK-PD relationships for isoniazid. Isoniazid exhibited concentration (C)-dependent killing of Mycobacterium tuberculosis H37Rv in vitro, with a maximum reduction of 4 log10 CFU/ml. In these studies, 50% of the maximum effect was achieved at a C/MIC ratio of 0.5, and the maximum effect did not increase with exposure times of up to 21 days. Conversely, isoniazid produced less than a 0.5-log10 CFU/ml reduction in two different intracellular infection models (J774A.1 murine macrophages and whole human blood). In a murine model of aerosol infection, isoniazid therapy for 6 days produced a reduction of 1.4 log10 CFU/lung. Dose fractionation studies demonstrated that the 24-h area under the concentration-time curve/MIC (r2 = 0.83) correlated best with the bactericidal efficacy, followed by the maximum concentration of drug in serum/MIC (r2 = 0.73).

Pharmacokinetics-pharmacodynamics of rifampin in an aerosol infection model of tuberculosis.

Limited information exists on the pharmacokinetic (PK)-pharmacodynamic (PD) relationships of drugs against Mycobacterium tuberculosis. Our aim was to identify the PK-PD parameter that best describes the efficacy of rifampin on the basis of in vitro and PK properties. Consistent with 83.8% protein binding by equilibrium dialysis, the rifampin MIC for M. tuberculosis strain H37Rv rose from 0.1 in a serum-free system to 1.0 mg/ml when it was tested in the presence of 50% serum. In time-kill studies, rifampin exhibited area under the concentration-time curve (AUC)-dependent killing in vitro, with maximal killing seen on all days and with the potency increasing steadily over a 9-day exposure period. MIC and time-kill studies performed with intracellular organisms in a macrophage monolayer model yielded similar results. By use of a murine aerosol infection model with dose ranging and dose fractionation over 6 days, the PD parameter that best correlated with a reduction in bacterial counts was found to be AUC/MIC (r(2) = 0.95), whereas the maximum concentration in serum/MIC (r(2) = 0.86) and the time that the concentration remained above the MIC (r(2) = 0.44) showed lesser degrees of correlation.