Evofosfamide (Evo or TH302) is a hypoxia-activated prodrug which is reduced leading to the release of alkylating agent bromo-isophosphoramide mustard, which has shown safety and signals of efficacy in a prior phase 1 study in recurrent glioblastoma. We performed a dual center single-arm Phase II study to expand on the safety and efficacy of Evo plus bevacizumab in bevacizumab refractory glioblastoma. 33 patients with bevacizumab refractory GBM received Evo 670 mg/m2 in combination with Bevacizumab 10 mg/kg IV every 2 weeks. Assessments included adverse events, response, and survival. Median age of patients was 47 (range 19–76) and 24 (69%) were male. At the time of study entry, 9 (26%) had ongoing corticosteroid use. ECOG performance status was 0 or 1 in 83% of patients. Patients were mostly heavily pretreated with 77% have three or more prior regimens. A total of 12 patients (36%) suffered grade 3–4 drug associated adverse event (AE); no grade 5 AE were reported. Of the 33 evaluable patients, best response was PR in 3 (9%), SD in 14 (43%), and PD in 16 (48%) with responses confirmed by a second reviewer. Median time to progression of disease was 53 days (95% CI 42–113) and Median time to death was 129 days (95% CI 86–199 days). Progression free survival at 4 months (PFS-4) on Evo-Bev was 31%, which was a statistically significant improvement over the historical rate of 3%. The median overall survival of patients receiving Evo-Bevacizumab was 4.6 months (95% CI 2.9–6.6). The progression free survival of patients on Evo-Bevacizumab met the primary endpoint of progression free survival at 4 months of 31%, although the clinical significance of this may be limited. Given the patient population and Phase II design, these clinical outcomes will need further validation.

ObjectivesTobacco is an important risk factor for tuberculosis (TB) infection and TB disease. Identifying tobacco users and providing tobacco cessation services is expected to reduce the burden of TB. We assessed tobacco use among presumptive TB patients attending a tertiary hospital and their willingness to attend tobacco cessation services.MethodsA cross-sectional study was conducted among presumptive TB patients attending a designated microscopy center of a tertiary hospital in South India. All presumptive TB patients aged ≥ 18 years attending the designated microscopy center were interviewed using a semistructured interview schedule. Data on presumptive TB patient's age, sex, tobacco use and forms of tobacco, attempts to quit tobacco since 1 year, and willingness to attend a smoking cessation clinic in tertiary hospital were captured. History of use of tobacco in the past 1 month was considered as “tobacco use.”.ResultsA total of 424 presumptive TB patients aged ≥ 18 years were interviewed. Tobacco use in the past 1 month was reported by 176 (41.5%, 95% confidence interval: 36.9–46.3%) presumptive TB patients. In total, 78 (18%) presumptive TB patients were eventually diagnosed with smear-positive pulmonary TB, of them 63 (80%) were tobacco users. Presumptive TB patients aged ≥ 30 years, male sex, and < 10 years of education were significantly associated with tobacco use. Of 176, a majority of 132 (75%) used some form of smoking. Of a total of 132 smokers, 70 (53%) were willing to avail of tobacco cessation services.ConclusionTobacco use among presumptive TB patients was high. Considering the high willingness to quit among smokers, proven brief interventions to help quit smoking can be tried.

The management of patients with elevated intracranial pressure (ICP) requires a systematic approach. After the failure of tier zero, tier one, and tier two therapies, all potential secondary causes of elevated ICP must be reviewed. Up to 28% of patients with blunt traumatic brain injury (TBI) develop cerebral sinus venous thrombosis (CSVT), among these, patients up to 55% have occlusive thrombi. A literature review revealed a dearth of specific treatment guidelines in this scenario. Here, we present one such case of refractory elevated ICP due to occlusive CSVT secondary to skull fractures. Initial CT venogram (CTV) on admission showed an occlusive CSVT; however, subsequent CTV on the post-trauma day (PTD) 4 and 6 showed non-occlusive thrombi only. The risks of worsening acute TBI-related hemorrhage with systemic anticoagulation versus the benefit of treating an occlusive CSVT are discussed here. In cases of occlusive CSVT with refractory elevated ICP and stable intracranial hemorrhage, the benefit of anticoagulation may outweigh the overall risks of hemorrhage expansion as prolonged uncontrolled ICP elevation is inevitably fatal. In this case, anticoagulation started on PTD 6, led to the resolution of ICP elevation and an excellent outcome for the patient, who was discharged to an acute rehab center, subsequently discharged home with no residual motor deficits, and was able to resume employment. Further prospective trials are necessary to develop guidelines for the management of occlusive CSVT in patients with severe TBI and to determine which patient populations are likely to benefit from early initiation of therapeutic anticoagulation.

No abstract

No abstract