Generalized gangliosidosis in Malta

The purpose of this paper is to describe the clinical features of four cases of generalized gangliosidosis, two of which in siblings. In two of the cases, and in one of the siblings, B-galactosidase deficiency was demonstrated in blood and urine samples. The point that emerges from these cases is the realization that the clinical distinction between the various ganglioside lipidoses is now no 'longer possible, even in the clinically 'typical' case the resemblance to one or other of the classical Tay-Sachs or Niemann Pick is meaningless without the aid of specialized enzymatic tests. Moreover, the dramatic finding of the cherry-red spots in the retina is now no longer pathognomonic of classical Tay-Sachs disease, as was formerly widely held by clinicians. In every case the exact metabolic defect should be pin-pointed before a definite diagnosis can be made. It therefore becomes mandatory to investigate all patients in this group by special chemical techniques.peer-reviewe

Towards a quality education for all

This document summarises the recommendations being proposed in the NCF and examines the implications of such recommendations. There can only be a meaningful strategy for the implementation of the NCF once the recommendations are debated and the full impact of their implications understood. This process of consultation needs to include all stakeholders in a professionally engaging manner. Moreover, the consultation and implementation strategies need to be based on the full understanding of a change management process. This document will therefore map out the way forward by presenting: • a summary of the recommendations being proposed by the NCF; • implications of these recommendations for implementation; • ideas about the management of change which underpin the consultation and implementation strategies the NCF would like to promote; • a strategy for the consultation process following the publication of the draft NCF; and • a proposed timeline for the implementation process of the NCF, following consultation and agreement with the wider educational community about the way forward.peer-reviewe

Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic

PURPOSE: Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with PATIENTS AND METHODS: Eligible patients whose tumors screened positively for RESULTS: Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with CONCLUSION: GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressiv

Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations

Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with loss. Given the predominance of mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas. Eligible patients whose tumors screened positively for mutations were treated with GSK2256098, 750 mg orally twice daily, until progressive disease. Efficacy was evaluated using two coprimary end points: progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria, where PFS6 was evaluated separately within grade-based subgroups: grade 1 versus 2/3 meningiomas. Per study design, the FAK inhibitor would be considered promising in this patient population if either end point met the corresponding decision criteria for efficacy. Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with mutations were enrolled and treated: 12 grade 1 and 24 grade 2/3 patients. Across all grades, one patient had a partial response and 24 had stable disease as their best response to treatment. In grade 1 patients, the observed PFS6 rate was 83% (10/12 patients; 95% CI, 52 to 98). In grade 2/3 patients, the observed PFS6 rate was 33% (8/24 patients; 95% CI, 16 to 55). The study met the PFS6 efficacy end point both for the grade 1 and the grade 2/3 cohorts. Treatment was well tolerated; seven patients had a maximum grade 3 adverse event that was at least possibly related to treatment with no grade 4 or 5 events. GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive -mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system. Results A total of 3288 patients were included in the analysis, of whom 301 (9 center dot 2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P < 0 center dot 001). There were no significant differences in rates of readmission between these groups (6 center dot 6 versus 8 center dot 0 per cent; P = 0 center dot 499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0 center dot 90, 95 per cent c.i. 0 center dot 55 to 1 center dot 46; P = 0 center dot 659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34 center dot 7 versus 39 center dot 5 per cent; major 3 center dot 3 versus 3 center dot 4 per cent; P = 0 center dot 110). Conclusion Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients