SummaryBackgroundWHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50–70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis.MethodsWe prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda. HIV-infected adults with suspected meningitis (eg, headache, nuchal rigidity, altered mental status) were screened consecutively at Mbarara Regional Referral Hospital. We centrifuged CSF, resuspended the pellet in 2 mL of CSF, and tested 0·5 mL with mycobacteria growth indicator tube culture, 1 mL with Xpert, and cryopreserved 0·5 mL, later tested with Xpert Ultra. We assessed diagnostic performance against uniform clinical case definition or a composite reference standard of any positive CSF tuberculous test.FindingsFrom Feb 27, 2015, to Nov 7, 2016, we prospectively evaluated 129 HIV-infected adults with suspected meningitis for tuberculosis. 23 participants were classified as probable or definite tuberculous meningitis by uniform case definition, excluding Xpert Ultra results. Xpert Ultra sensitivity was 70% (95% CI 47–87; 16 of 23 cases) for probable or definite tuberculous meningitis compared with 43% (23–66; 10/23) for Xpert and 43% (23–66; 10/23) for culture. With composite standard, we detected tuberculous meningitis in 22 (17%) of 129 participants. Xpert Ultra had 95% sensitivity (95% CI 77–99; 21 of 22 cases) for tuberculous meningitis, which was higher than either Xpert (45% [24–68]; 10/22; p=0·0010) or culture (45% [24–68]; 10/22; p=0·0034). Of 21 participants positive by Xpert Ultra, 13 were positive by culture, Xpert, or both, and eight were only positive by Xpert Ultra. Of those eight, three were categorised as probable tuberculous meningitis, three as possible tuberculous meningitis, and two as not tuberculous meningitis. Testing 6 mL or more of CSF was associated with more frequent detection of tuberculosis than with less than 6 mL (26% vs 7%; p=0·014).InterpretationXpert Ultra detected significantly more tuberculous meningitis than did either Xpert or culture. WHO now recommends the use of Xpert Ultra as the initial diagnostic test for suspected tuberculous meningitis.FundingNational Institute of Neurologic Diseases and Stroke, Fogarty International Center, National Institute of Allergy and Infectious Disease, UK Medical Research Council/DfID/Wellcome Trust Global Health Trials, Doris Duke Charitable Foundation.

Biliary tract cancer consists of cholangiocarcinoma (CC) and gallbladder cancer (GBC). When resectable, surgery provides the best chance at long-term survival. Unfortunately, surgery for these tumors is associated with long operative times, high morbidities, and prolonged hospital stays. Minimally invasive surgery has been shown to impact selected outcomes, including length of stay, in other diseases, and robotic surgery may offer additional advantages compared to laparoscopic surgery in treating bile duct cancers. This is a systematic review of robotic surgery for biliary tract cancer. Predetermined selection criteria were used to appraise the literature. The PRISMA guidelines were followed. In total, 20 unique articles with a total of 259 patients with biliary tract cancer undergoing robotic surgery met the inclusion criteria. For CC and GBC, respectively, the weighted average operative time was 401 and 277 min, the estimated blood loss was 348 and 260 mL, the conversion rate to open was 7 and 3.5%, the all-cause morbidity was 52 and 9.7%, the major morbidity was 12 and 4.4%, the perioperative mortality was 1.4 and 0%, the length of stay was 15 and 4.8 days, the positive margin rate was 27 and 9%, and the number of lymph nodes retrieved was 4.2 and 8. Robotic surgery for biliary tract cancer appears non-inferior to open surgery when compared to the published contemporary data. However, the current literature on the topic is of low quality, and future prospective/randomized studies are needed.

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