Effectiveness and Safety of Varying Doses of Linezolid With Bedaquiline and Pretomanid in Treatment of Drug-Resistant Pulmonary Tuberculosis: Open-Label, Randomized Clinical Trial.

BACKGROUND: Treatment of drug-resistant tuberculosis with bedaquiline-pretomanid-linezolid regimen has demonstrated good treatment efficacy. Given linezolid's toxicity profile, prudence suggests reconsidering its dose and duration. We determined the effectiveness and safety of structured dose reduction of linezolid with bedaquiline and pretomanid in adults with pre-extensively drug-resistant (pre-XDR) or treatment-intolerant/nonresponsive multidrug-resistant (MDRTI/NR) pulmonary tuberculosis. METHOD: Adults with pre-XDR or MDRTI/NR pulmonary tuberculosis were enrolled in a multicenter, parallel-group, randomized clinical trial in India. Patients were randomized to 26 weeks of bedaquiline, pretomanid, and daily linezolid, at 600 mg for 26 weeks (arm 1); 600 mg for 9 weeks followed by 300 mg for 17 weeks (arm 2); or 600 mg for 13 weeks followed by 300 mg for 13 weeks (arm 3). Study end points included sustained cure, bacteriological failure, toxicity, and death. RESULTS: Of 403 patients enrolled, 255 (63%) were <30 years old, 273 (68%) had prior tuberculosis episodes, and 238 (59%) were malnourished. At the end of treatment, after excluding those with negative baseline cultures, cure was seen in 120 (93%), 117 (94%), and 115 (93%) in arms 1, 2, and 3 respectively. Myelosuppression seen in 85 patients each in arms 1 and 2 and 77 patients in arm 3, not significantly different. Peripheral neuropathy was noticed in 66 patients (30, 17, and 19 in arms 1, 2, and 3) at 10-26 weeks (P = .02). The linezolid dose was reduced because of toxicity in 13, 2, and 4 patients in arms 1, 2, and 3, respectively. CONCLUSIONS: In adults with pre-XDR or MDRTI/NR pulmonary tuberculosis, structured linezolid dose reduction to 300 mg/d is as effective as the standard 600-mg dose but with fewer cases of peripheral neuropathy when given with bedaquiline and pretomanid. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry of India (CTRI/2021/03/032189).

Spontaneous resolution of an inflammatory pseudotumour of the lung subsequent to wedge biopsy.

Spontaneous, complete resolution of inflammatory pseudotumour (IPT) of lungs is exceptionally rare. A 44-year-old male was referred for evaluation for «non resolving pneumonitis¼. He had cough and minimal expectoration for 5 months, chest pain, haemoptysis and fever for a fortnight. Computed tomography of thorax (CT-thorax) confirmed the presence of a homogenous mass with irregular borders in right middle lobe with areas of breakdown and air bronchogram. Transbronchial lung biopsy was suggestive of «plasma cell granuloma¼. Thoracotomy disclosed a hard mass in right middle lobe adherent to lower lobe, chest wall and mediastinum which could not be removed. A wedge biopsy confirmed IPT. Chest radiograph after 4 weeks revealed significant resolution. CT-thorax a year later showed fibrotic scar. Till date, there are only five reports documenting 6 patients with spontaneous resolution of IPT of lungs and in 4 this occurred within 3 months of an invasive diagnostic intervention.

Surgical treatment for tracheobronchial carcinoid tumors: a 16-year experience.

We conducted a 16-year retrospective review of 31 cases of tracheobronchial carcinoid tumors treated in our institution between 1995 and 2011, to determine their characteristic features and outcome of management. There were 12 men and 19 women. The most common presenting symptoms were cough and hemoptysis (71%) with a mean duration of 4 years. Preoperative bronchoscopy confirmed the diagnosis in 80% of patients. Right-sided tumors accounted for 60% of cases. Most tumors arose from the mainstem bronchi. Histologic analysis revealed typical carcinoids in 28 cases and atypical carcinoids in 3. Surgical treatment was mainly radical resection (pneumonectomy in 19 patients). A parenchymal-preserving surgery (sleeve resection of left main bronchus and end-to-end anastomosis) was only possible in 2 cases. Mediastinal lymph nodes were involved in 30% of cases. Most patients had widespread extraluminal extension. Follow-up revealed recurrence in one patient. No deaths were recorded, and complications were mainly atelectasis and air leak. Radical resection remains the mainstay of surgical management of bronchial carcinoids in cases of late presentation with destroyed and bronchiectatic distal pulmonary parenchyma. Parenchymal-preserving surgery should only be carried out when indicated.