IMbrave152/SKYSCRAPER-14: a Phase III study of atezolizumab, bevacizumab and tiragolumab in advanced hepatocellular carcinoma.

Atezolizumab plus bevacizumab is a standard of care, first-line therapy for advanced hepatocellular carcinoma (HCC). Myeloid and T regulatory cells are key immunosuppressive cell types within the hepatic tumor microenvironment associated with clinical resistance to atezolizumab and bevacizumab therapy for HCC and overall poor prognosis. Therapeutic targeting of TIGIT, which is highly expressed in these cells, with tiragolumab may overcome the immunosuppressive environment and improve clinical benefit, a hypothesis supported by positive efficacy signals in the Phase Ib/II MORPHEUS-Liver study. This paper describes the rationale and design of IMbrave152/SKYSCRAPER-14, a randomized, double-blind, placebo-controlled Phase III study comparing atezolizumab and bevacizumab with tiragolumab or placebo in patients with HCC and no prior systemic treatment.Clinical Trial Registration: NCT05904886 (ClinicalTrials.gov).

This research study is designed to test a new treatment combination for liver cancer, specifically for patients whose cancer cannot be removed with surgery or has spread. The treatment involves three medications: atezolizumab, bevacizumab and tiragolumab.Atezolizumab and bevacizumab are already used together as a standard treatment for liver cancer. Tiragolumab is designed to block the TIGIT receptor, which is normally involved in holding back the immune cells that would attack the tumor. Because tiragolumab may restore the immune response against the tumor, adding tiragolumab might make the treatment more effective.The study is being done worldwide and includes patients who have not received any previous systemic treatment for their advanced liver cancer. Patients participating in the study will be randomly placed into two groups. One group will receive the new combination of three medications, while the other group will receive the standard treatment of two medications plus a placebo (a treatment with no active ingredient). The main goal is to see if the new combination helps patients live longer and slows the cancer's growth compared with the standard treatment. Safety and how patients feel during the treatment are also important parts of the study.

Medical leadership training varies substantially between UK medical schools: Report of the leadership in undergraduate medical education national survey (LUMENS).

BACKGROUND: Doctors are increasingly expected to demonstrate medical leadership and management (MLM) skills. The Faculty of Medical Leadership and Management (FMLM) has published an indicative undergraduate curriculum to guide the development of MLM content at UK medical schools. METHOD: Students from 30 medical schools were surveyed to determine their understanding of MLM teaching at their school. Timetables for 21 schools were searched for MLM-related keywords. Student-reported teaching and timetabled teaching were coded according to predefined themes. Aggregated demographic and postgraduate performance data were obtained through collaboration with the Medical Student Investigators Collaborative (msico.org). RESULTS: Whilst 88% of medical students see MLM teaching as relevant, only 18% believe it is well integrated into their curriculum. MLM content represented ∼2% of timetabled teaching in each 5-year undergraduate medical course. Most of this teaching was dedicated to teamwork, performance/reflection and communication skills. There was minimal association between how much of a topic students believed they were taught, and how much they were actually taught. We found no association between the volume of MLM teaching and performance in postgraduate examinations, trainee career destinations or fitness to practice referrals. CONCLUSION: Our findings demonstrate limited and variable teaching of MLM content. Delivery was independent of broader teaching and assessment factors.

A Systematic Review of Arthroscopic Versus Open Debridement of the Arthritic Elbow.

PURPOSE: To systematically review the available data with regard to clinical and functional outcomes of arthroscopic and open debridement for elbow arthritis to determine the complication rate with transition to arthroscopic surgery. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta Analyses protocol, a systematic review was performed including studies reporting clinical and functional outcomes following open or arthroscopic debridement of elbow arthritis. The primary outcome measures analyzed were functional outcome (Mayo Elbow Performance Score), range of motion, and complication rate. Data were extracted for the whole group and then compared between the techniques using ranges and forest plots. RESULTS: In total, 39 level IV and 3 level III studies with 1097 elbows were eligible for inclusion; 684 elbows were treated using an open technique and 413 using an arthroscopic technique. Regarding functional outcome scores, mean Mayo Elbow Performance Score improved significantly with comparable magnitude of improvement in both groups (arthroscopic group: range 28-34, open group: range 25-31). Regarding range of motion, mean flexion-extension arc improved significantly in both groups (arthroscopic group: range 8-26°, open group: range 13-49°). The open group had a lower preoperative flexion-extension arc (range 63-96) in comparison with the arthroscopic group (range 84-119). The overall incidence of complications was 5.7% (range 0%-19%) in the arthroscopic group and 6.1% (range 0%-25%) in the open group. The most common complication type was neurologic, with an incidence of 2.1% (range 0%-8%) in the arthroscopic group and 1.9% (range 0%-12%) in the open group. The deep infection rate was 0.7% (range 0%-10%) in the open group with no reported incidence in the arthroscopic group. CONCLUSIONS: This systematic review demonstrated good mid-term functional outcomes following debridement arthroplasty of the arthritic elbow. There was no increase in complications with an arthroscopic technique confirming its safety and efficacy. LEVEL OF EVIDENCE: IV, Systematic Review of Level III and IV articles.

The Analysis of Teaching of Medical Schools (AToMS) survey: an analysis of 47,258 timetabled teaching events in 25 UK medical schools relating to timing, duration, teaching formats, teaching content, and problem-based learning.

BACKGROUND: What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL). METHOD: The Analysis of Teaching of Medical Schools (AToMS) survey used detailed timetables provided by 25 schools with standard 5-year courses. Timetabled teaching events were coded in terms of course year, duration, teaching format, and teaching content. Ten schools used PBL. Teaching times from timetables were validated against two other studies that had assessed GP teaching and lecture, seminar, and tutorial times. RESULTS: A total of 47,258 timetabled teaching events in the academic year 2014/2015 were analysed, including SSCs (student-selected components) and elective studies. A typical UK medical student receives 3960 timetabled hours of teaching during their 5-year course. There was a clear difference between the initial 2 years which mostly contained basic medical science content and the later 3 years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2 years. Medical schools differed in duration, format, and content of teaching. Two main factors underlay most of the variation between schools, Traditional vs PBL teaching and Structured vs Unstructured teaching. A curriculum map comparing medical schools was constructed using those factors. PBL schools differed on a number of measures, having more PBL teaching time, fewer lectures, more GP teaching, less surgery, less formal teaching of basic science, and more sessions with unspecified content. DISCUSSION: UK medical schools differ in both format and content of teaching. PBL and non-PBL schools clearly differ, albeit with substantial variation within groups, and overlap in the middle. The important question of whether differences in teaching matter in terms of outcomes is analysed in a companion study (MedDifs) which examines how teaching differences relate to university infrastructure, entry requirements, student perceptions, and outcomes in Foundation Programme and postgraduate training.

Indications, Outcomes, and Complications of Lateral Ulnar Collateral Ligament Reconstruction of the Elbow for Chronic Posterolateral Rotatory Instability: A Systematic Review.

BACKGROUND: Posterolateral rotatory instability (PLRI) of the elbow can lead to pain, recurrent dislocations, and, in the worst-case scenario, disability. PURPOSE: To report the indications, outcomes, and complication rates of lateral ulnar collateral ligament (LUCL) reconstruction for chronic PLRI of the elbow. STUDY DESIGN: Systematic review. METHODS: This systematic review was registered with PROSPERO and performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The review entailed 17 studies that included 168 patients with isolated LUCL reconstruction for chronic PLRI. Patients with concurrent medial collateral ligament reconstruction were excluded. The primary outcome measures were patient characteristics, indication for surgery, surgical technique, functional outcomes, and complications. RESULTS: Chronic PLRI commonly occurred after a previous traumatic injury (n = 168). Of these, there were 119 simple instabilities (no fracture) and 33 complex instabilities (associated fracture). In 11 patients, PLRI was iatrogenic. The cause was unknown in 5 patients. Grafts used were autograft (n = 102; 61%), allograft (n = 18; 11%), synthetic graft (n = 15; 9%), and unknown (n = 33; 20%). The most common surgical technique was a docking procedure or a modification of this (n = 145; 86%). Other techniques included suture anchors (n = 18; 11%), nonanatomic (n = 1; 0.6%), and unknown (n = 4; 2%). There were 45 complications reported in 37 patients (22%). The most frequent complication was recurrent instability (21/138; 15%). No other major complications were reported. The rate of recurrent instability was significantly higher in revision reconstructions (6/15 elbows; 40%) compared with primary reconstructions (15/123 elbows; 12.2%) (P = .005). The mean Mayo Elbow Performance Score and abbreviated Disabilities of the Arm, Shoulder and Hand score were 87.5 (range, 40-100) and 18.8 (range, 0-77), respectively. Of the patients in whom range of motion was measured, 134 of 144 patients (93%) regained a functional range (30L-130L). CONCLUSION: LUCL reconstruction for chronic PLRI proved a reliable method of reconstruction, save for the moderate rate of recurrent instability, which was highest in revision reconstructions.

Do medical students studying in the United Kingdom have an adequate factual knowledge of basic life support?

BACKGROUND: Healthcare professionals have a duty to maintain basic life support (BLS) skills. This study aims to evaluate medical students' factual knowledge of BLS and the training they receive. METHODS: A cross-sectional, closed-response questionnaire was distributed to the first- and fourth-year students studying at institutions in the United Kingdom. The paper questionnaire sought to quantify respondent's previous BLS training, factual knowledge of the BLS algorithm using five multiple choice questions (MCQs), and valuate their desire for further BLS training. Students received 1 point for each correctly identified answer to the 5 MCQ's. RESULTS: A total of 3,732 complete responses were received from 21 medical schools. Eighty percent (n=2,999) of students completed a BLS course as part of their undergraduate medical studies. There was a significant difference (P<0.001) in the percentage of the fourth-year students selecting the correct answer in all the MCQ's compared to the first-year students except in identifying the correct depth of compressions required during CPR (P=0.095). Overall 10.3% (95% CI 9.9% to 10.7%) of respondents correctly identified the answer to 5 MCQ's on BLS 9% of the first-year students (n=194) and 12% of the fourth-year students (n=190). On an institutional level the proportion of students answering all MCQ's correctly ranged from 2% to 54% at different universities. Eighty-one percent of students (n=3,031) wished for more BLS training in their curriculum. CONCLUSION: Factual knowledge of BLS is poor among medical students in the UK. There is a disparity in standards of knowledge across institutions and respondents indicating that they would like more training.

Femoral Shaft Fracture during Bungee Jump: A Case Report and Literature Review.

Bungee jumping is a recreational sport that is accepted to carry a level of risk. We present the case of a femoral fracture sustained during bungee jumping and examine the published literature on bungee jumping-related injuries. A previously well 31-year old female performed a 200ft bungee jump from a crane. The apparatus was performed as expected and documented on the bystander video footage. As the bungee-cord became taut for the second time, there was an audible crack with accompanying scream. A closed, neurovascularly-intact injury was sustained to her right thigh. Radiographs revealed a comminuted mid-diaphyseal spiral femoral fracture, which was treated with intra-medullary nail fixation the following day. Following loss of position with proximal fragment flexion, the intramedullary nail was revised with open reduction and cerclage wiring 6 weeks later. Progression to clinical and radiological union was uneventful. Fatalities in bungee jumping are generally secondary to trauma as a result of equipment malfunction, user error, or related to pre-existing co-morbidity2. As no records are kept on bungee jumping injuries in the UK, reliable statistics are not available regarding the relative risks of this sport. We conclude that incidence of bungee jumping injuries is likely to remain low, but consider that improved recording of bungee jumping-related injury data will allow providers to give customers a realistic quantification of risk before engaging in this sport.