Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies

We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE-158 (NCT02628067; phase 2) and KEYNOTE-028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, and no prior immunotherapy. Programmed death ligand 1 (PD-L1)-positive tumors were required for eligibility in KEYNOTE-028 only. Patients received pembrolizumab 200 mg every three weeks (KEYNOTE-158) or 10 mg/kg every two weeks (KEYNOTE-028) for ≤2 years. Primary efficacy endpoint was objective response rate (ORR) by RECIST v1.1. Response assessed by independent central review is reported. KEYNOTE-158 enrolled 104 patients and KEYNOTE-028 enrolled 24 patients. Median (range) follow-up was 7.5 months (0.6-34.3) in KEYNOTE-158 and 5.7 months (0.6-55.4) in KEYNOTE-028. In KEYNOTE-158, ORR was 5.8% (6/104; 95% CI, 2.1%-12.1%); median duration of response (DOR) was not reached (NR) (range, 6.2-26.6+ months). Median (95% CI) OS and PFS were 7.4 (5.5-9.6) and 2.0 (1.9-2.1) months. Among PD-L1-expressers (n = 61) and PD-L1-nonexpressers (n = 34), respectively, ORR was 6.6% (4/61) and 2.9% (1/34). In KEYNOTE-028, ORR was 13.0% (3/23; 95% CI, 2.8%-33.6%); median DOR was NR (range, 21.5-53.2+ months). Median (95% CI) OS and PFS were 5.7 (3.1-9.8) and 1.8 (1.4-3.1) months. Grade 3 to 5 treatment-related adverse events occurred in 13.5% of patients in KEYNOTE-158 (no grade 4; grade 5 renal failure, n = 1) and 16.7% in KEYNOTE-028 (no grade 4/5). In summary, pembrolizumab provides durable antitumor activity in 6% to 13% of patients with advanced BTC, regardless of PD-L1 expression, and has manageable toxicity.     

Toewebs as a source of Gram-negative bacilli

The prevalence of Gram-negative bacilli on the toewebs was 8% in normal students, 24% in hospital outpatients with suspected Tinea pedis, 41% in industrial workers wearing protective clothing and 58% in coal miners. Prevalence was greatest in those exposed to wet working conditions. In miners, the presence of Gram-negative bacilli was related to symptoms of itching/soreness and cracking/fissuring, and was negatively related to malodour, but this latter trend was reversed in outpatients and in industrial workers. The feet are a source of many 'enteric' and 'environmental' bacilli and could contribute to infection elsewhere than in the toewebs themselves.     

Brain abscess in the 1980s

Brain abscess was reviewed in 24 patients admitted to University Hospital, Nottingham over a period of 3 years. Chronic ear infection was the most common predisposing factor, but in 11 patients the focus of infection remained unknown. CT scanning, carried out in all patients, was negative in one patient with clinical signs of meningitis. Polymicrobial and anaerobic infections were common. Actinomyces species were isolated in mixed culture from seven patients; in five the abscess was located in the cerebellum. Therapy was most often a combination of surgical drainage and antimicrobial therapy with beta-lactam agents and metronidazole. Evidence suggests that cefotaxime may offer a suitable alternative to chloramphenicol and benzylpenicillin in the treatment of brain abscess.     

Aggressive behaviour in elderly people with dementia: A review

The progressive degeneration of the brain seen in dementia is often accompanied by behavioural disturbances. Aggressive behaviour is one of the most serious of these disturbances and is a common cause for psychiatric referral, admission to hospital and drug treatment. In this article, we discuss the conceptual issues associated with defining aggressive behaviour in cognitively impaired patients. We then review the aetiology, epidemiology, methods of assessment, and management of aggressive behaviour in elderly people with dementia.     

Aggressive behaviour in elderly psychiatric inpatients.

We describe the types of aggressive behaviour and determine their prevalence in a sample of hospitalized elderly psychiatric patients. Data were obtained by nurse ratings of aggressive behaviour using the recently developed Rating Scale for Aggressive Behaviour in the Elderly; 90 patients were rated over a 3-d period. Nearly half the sample were at least mildly aggressive; the frequencies of some specific types of aggressive behaviour were high. In contrast, the frequency of injuries and the use of restraints and medication for aggressive behaviour were low. Some correlates of the aggressive behaviour were also analysed.