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Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644

Introduction: This systematic review and meta-analysis compared the revision rates, complications, and outcomes in anatomic total shoulder arthroplasty (aTSA) and reverse TSA (rTSA) performed for primary glenohumeral osteoarthritis in patients aged over 70 years without a full-thickness rotator cuff tear., Materials and Methods: We performed a systematic literature search identifying comparative studies meeting the above patient criteria and published from January 2010 to May 2022 from 3 databases: MEDLINE, EMBASE, and Cochrane Library. We performed the systematic review in accordance with PRISMA guidelines and the study was prospectively registered on PROSPERO., Results: From the 1798 studies identified from the initial literature search, 4 met our inclusion criteria. Two thousand seven hundred thirty-one shoulder arthroplasties (1472 aTSA and 1259 rTSA) were evaluated with a minimum follow up of 2 years. A statistically significant lower revision rate was observed in rTSA compared to aTSA (odds ratio [OR] 0.50, 95% confidence interval [CI]: 0.30, 0.84, p  < .05). No significant difference was noted between aTSA and rTSA in overall complication rate (OR 0.98, 95% CI 0.34, 2.86, p  = .97) while aTSA displayed a statistically significant improved postoperative Constant-Murley score [aTSA: 80(75; 82), rTSA: 68(66; 76.5), p  < .001]., Conclusion: Higher revision rates were identified following aTSA in our study population, although admittedly this is within retrospective studies. aTSA displayed equal functional results and postoperative complications compared to rTSA in patients over 70 without a full-thickness rotator cuff tear. Given these similar results a shoulder surgeon must carefully consider each patient individually prior to deciding the optimal form of arthroplasty to offer., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Emotional intelligence (EI) is defined as the ability to perceive and manage the emotions of oneself and others. Despite being one of the most highly used psychological terms in popular nomenclature, its understanding in the context of clinicians remains poor. There is a dearth of literature on this topic, and this submission examines the relationship between a clinicians' EI and the key domains of "Good Medical Practice" guidelines from the General Medical Council, United Kingdom. It aims to review and critically analyse the existing literature on EI and Good Medical Practice while attempting to establish a relationship between the two. This submission thus examines the relationship between emotional intelligence and a clinician's on-the-job performance. The findings demonstrate how emotional intelligence can aid the clinician in all aspects of their working life in the context of practising in line with General Medical Council (GMC) guidance. The authors also recommend exploring the possibility of inclusion of EI within a modern medical curriculum, as it may lead to improved practice in clinicians., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Dott et al.)

Purpose: The morbidity and mortality of patients requiring mechanical ventilation for coronavirus disease 2019 (COVID-19) pneumonia is considerable. We studied the use of whole-lung low-dose radiation therapy (LDRT) in this patient cohort., Methods and Materials: Patients admitted to the intensive care unit and requiring mechanical ventilation for COVID-19 pneumonia were included in this randomized double-blind study. Patients were randomized to 1 Gy whole-lung LDRT or sham irradiation (sham-RT). Treatment group allocation was concealed from patients and intensive care unit clinicians, who treated patients according to the current standard of care. Patients were followed for the primary endpoint of ventilator-free days at day 15 postintervention. Secondary endpoints included overall survival, as well as changes in oxygenation and inflammatory markers., Results: Twenty-two patients were randomized to either whole-lung LDRT or sham-RT between November and December 2020. Patients were generally elderly and comorbid, with a median age of 75 years in both arms. No difference in 15-day ventilator-free days was observed between groups (P = 1.00), with a median of 0 days (range, 0-9) in the LDRT arm and 0 days (range, 0-13) in the sham-RT arm. Overall survival at 28 days was identical at 63.6% (95% confidence interval, 40.7%-99.5%) in both arms (P = .69). Apart from a more pronounced reduction in lymphocyte counts after LDRT (P < .01), analyses of secondary endpoints revealed no significant differences between the groups., Conclusions: Whole-lung LDRT failed to improve clinical outcomes in critically ill patients requiring mechanical ventilation for COVID-19 pneumonia., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The treatment of inflammatory arthritis with disease modifying drugs and biological agents had reduced the number of patients needing surgical treatment. Surgical treatment of patients with inflammatory arthritis is challenging not only due to the factors such as bone stock and status of soft tissue but also due to the comorbidities associated with inflammatory arthritis. Multidisciplinary approach to these patients is recommended to deal with the complex poly-articular involvement and systemic physiological impairment especially when planning surgery. This review will cover the key articular and peri-articular pathologies that can affect the elbow in inflammatory arthritis and discuss the treatment strategies available to the orthopaedic surgeon in their management. From surgical point of view, the rheumatoid elbow can be classified into 4 types: 1) classic soft tissue type with increased joint laxity, malalignment and instability; 2) osteoarthritic type with stiffness, hypertrophic joints (hypertrophic) and preserved alignment; 3) nodular type with subcutaneous nodules and enthesopathies but preserved jointly; 4) mutilans with bone and joint destruction. Surgical managements of the articular problem in each of the subtypes are discussed in this review. On the other hand, the seronegative arthritis such as psoarisis, gout and lupus seems to affect the peri-articular tissue of the elbow more than the joint itself and the disease specific management of the peri-articular soft tissue problems, such as enthesopathies and inflammatory nodules, are also outlined., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Delhi Orthopedic Association. All rights reserved.)

The ongoing novel coronavirus (2019-nCoV) pandemic is expected to develop into an unprecedented stress test for health care systems worldwide. This brief report, written from a radiation oncology perspective during the developing outbreak of 2019-nCoV in Switzerland, highlights the challenges identified and measures taken in our department to mitigate risks and ensure continued operations during the outbreak., (© 2020 The Authors.)

Background: Wiskott-Aldrich syndrome is a rare, life-threatening, X-linked primary immunodeficiency characterised by microthrombocytopenia, infections, eczema, autoimmunity, and malignant disease. Lentiviral vector-mediated haemopoietic stem/progenitor cell (HSPC) gene therapy is a potentially curative treatment that represents an alternative to allogeneic HSPC transplantation. Here, we report safety and efficacy data from an interim analysis of patients with severe Wiskott-Aldrich syndrome who received lentiviral vector-derived gene therapy., Methods: We did a non-randomised, open-label, phase 1/2 clinical study in paediatric patients with severe Wiskott-Aldrich syndrome, defined by either WAS gene mutation or absent Wiskott-Aldrich syndrome protein (WASP) expression or a Zhu clinical score of 3 or higher. We included patients who had no HLA-identical sibling donor available or, for children younger than 5 years of age, no suitable 10/10 matched unrelated donor or 6/6 unrelated cord blood donor. After treatment with rituximab and a reduced-intensity conditioning regimen of busulfan and fludarabine, patients received one intravenous infusion of autologous CD34+ cells genetically modified with a lentiviral vector encoding for human WAS cDNA. The primary safety endpoints were safety of the conditioning regimen and safety of lentiviral gene transfer into HSPCs. The primary efficacy endpoints were overall survival, sustained engraftment of genetically corrected HSPCs, expression of vector-derived WASP, improved T-cell function, antigen-specific responses to vaccinations, and improved platelet count and mean platelet volume normalisation. This interim analysis was done when the first six patients treated had completed at least 3 years of follow-up. The planned analyses are presented for the intention-to-treat population. This trial is registered with ClinicalTrials.gov (number NCT01515462) and EudraCT (number 2009-017346-32)., Findings: Between April 20, 2010, and Feb 26, 2015, nine patients (all male) were enrolled of whom one was excluded after screening; the age range of the eight treated children was 1·1-12·4 years. At the time of the interim analysis (data cutoff April 29, 2016), median follow-up was 3·6 years (range 0·5-5·6). Overall survival was 100%. Engraftment of genetically corrected HSPCs was successful and sustained in all patients. The fraction of WASP-positive lymphocytes increased from a median of 3·9% (range 1·8-35·6) before gene therapy to 66·7% (55·7-98·6) at 12 months after gene therapy, whereas WASP-positive platelets increased from 19·1% (range 4·1-31·0) to 76·6% (53·1-98·4). Improvement of immune function was shown by normalisation of in-vitro T-cell function and successful discontinuation of immunoglobulin supplementation in seven patients with follow-up longer than 1 year, followed by positive antigen-specific response to vaccination. Severe infections fell from 2·38 (95% CI 1·44-3·72) per patient-year of observation (PYO) in the year before gene therapy to 0·31 (0·04-1·11) per PYO in the second year after gene therapy and 0·17 (0·00-0·93) per PYO in the third year after gene therapy. Before gene therapy, platelet counts were lower than 20 × 10 9 per L in seven of eight patients. At the last follow-up visit, the platelet count had increased to 20-50 × 10 9 per L in one patient, 50-100 × 10 9 per L in five patients, and more than 100 × 10 9 per L in two patients, which resulted in independence from platelet transfusions and absence of severe bleeding events. 27 serious adverse events in six patients occurred after gene therapy, 23 (85%) of which were infectious (pyrexia [five events in three patients], device-related infections, including one case of sepsis [four events in three patients], and gastroenteritis, including one case due to rotavirus [three events in two patients]); these occurred mainly in the first 6 months of follow-up. No adverse reactions to the investigational drug product and no abnormal clonal proliferation or leukaemia were reported after gene therapy., Interpretation: Data from this study show that gene therapy provides a valuable treatment option for patients with severe Wiskott-Aldrich syndrome, particularly for those who do not have a suitable HSPC donor available., Funding: Italian Telethon Foundation, GlaxoSmithKline, and Orchard Therapeutics., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aims: To evaluate, in a randomized, open-label study, the non-inferiority of a bioequivalent fixed-dose combination of glimepiride and atorvastatin vs. separately co-administered tablets in people with Type 2 diabetes mellitus., Methods: Participants with HbA1c ≥ 53 to < 80 mmol/mol (≥ 7.0 to < 9.5%), average fasting blood glucose > 7.0 mmol/l, who were on metformin for ≥ 3 months, were randomized to combination (n = 215) or co-administered glimepiride and atorvastatin (n = 212) once daily for 20 weeks. Up-titration of glimepiride (1-4 mg) and atorvastatin (10-20 mg) were based on average fasting blood glucose and LDL cholesterol, respectively. Co-primary endpoints were change from baseline to week 20 in HbA1c and LDL cholesterol., Results: Non-inferiority was demonstrated for both co-primary endpoints: the upper limits of 95% CIs for differences (combination-reference) were less than the prespecified margins of 3.3 mmol/mol (0.3%) for change from baseline in HbA1c [difference 0.1 mmol/mol (95% CI -1.6, 1.9); 0.01% (95% CI -0.15, 0.17)] and 6% for percentage change from baseline in LDL cholesterol [difference 0.87% (95% CI -2.47, 4.21)]. Similar proportions of participants on combination and reference had treatment-emergent adverse events (64 vs. 61%). More participants on combination had hypoglycaemia (21 vs. 13%); most events were considered by the treating physician to be unrelated to study drug., Conclusions: The combination was non-inferior to separately co-administered tablets and the safety profile was consistent with the known profiles of glimepiride and atorvastatin. The observed increase in hypoglycaemia on the combination cannot be explained, but may be attributable to non-systematic collectiof glucose readings and may have been influenced by reporting bias in this open-label trial., (© 2015 Diabetes UK.)

Spinal metastases may present in a myriad of ways, most commonly back pain with or without neurology. We report an unusual presentation of isolated atypical chest pain preceding metastatic cord compression, secondary to penile carcinoma. Spinal metastasis from penile carcinoma is rare with few cases reported. This unusual presentation highlights the need for a heightened level of clinical suspicion for spinal metastases as a possible cause for chest pain in any patients with a history of carcinoma. The case is discussed with reference to the literature.

Background: Angiogram negative sub-arachnoid haemorrhage (SAH) is generally considered to have a more benign course than SAH of known cause. There is also variability from centre to centre as to what proportion of angiogram negative SAH patients undergo repeat Digital Subtraction Angiography (DSA). We performed a retrospective study looking at the last four years' of SAH patients at our institution in order to ascertain the clinical course, the nature and results of repeat imaging., Methods: Retrospective analysis of clinical records and imaging of all patients presenting to our institution with non-traumatic SAH between April 2008 and February 2012 was performed. Results were analysed for presenting grades, blood distribution, complications, outcomes, repeat imaging modalities and findings., Results: 459 patients with proven non-traumatic SAH of which 50 (11%) had no vascular cause identified on their initial angiogram were identified. The blood distribution was perimesencephalic in 17, non-perimesencephalic in 23, and 10 patients were computed tomography (CT) Negative with a positive lumbar puncture. Eight (16%) patients were complicated by hydrocephalus and 2 (4%) were complicated by vasospasm. Eight patients (16%) underwent repeat cranial DSA with a high suspicion in a multi-disciplinary team setting. None of the repeat angiograms showed an underlying aetiology for the SAH. 76% of patients had a Glasgow Outcome Score of 5 at 6 months. There were no rebleeds., Conclusions: While generally more benign, angiogram negative subarachnoid haemorrhage can have a complicated clinical course. In our experience repeat DSA should be reserved for cases in which there is significant suspicion of occult vascular lesion. However, evidence-based guidelines are needed to aid the development of management protocols for angiogram-negative SAH and ensuring optimal patient outcomes., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Botulinum neurotoxin type A has gained widespread use for treatment of a host of neuromuscular conditions. However, the potential effect of this toxin has on the histological and biochemical properties of skeletal muscle remains largely unexplored. The purpose of this study was to characterize the myosin heavy chain (MHC) distribution of adult rat skeletal muscle treated with botulinum neurotoxin type. Varying doses of the toxin were injected into the triceps surae muscle group of one hind limb. Force production was assessed periodically to access the functional deficit incurred. After 10 weeks, animals were sacrificed, muscles removed, and MHC composition determined. Body weight, muscle weight and force of the injected leg were significantly reduced in all groups, while loss of muscle weight and force in the contralateral leg was variable. In the injected plantaris and gastrocnemius muscles, type I MHC increased approximately 100%, while type IIa/x decreased approximately 50%. In the contralateral gastrocnemius, types I and IIa/x MHC increased approximately 100%, while type IIb decreased approximately 45%. These data suggest that botulinum neurotoxin causes shifts in MHC composition in injected and contralateral muscles that are contrary to those seen with denervation and similar to those seen with aging.

Objective: To define a safe and effective dose of Dysport for treating hip adductor spasticity., Methods: Patients with definite or probable multiple sclerosis, and disabling spasticity affecting the hip adductor muscles of both legs, were randomised to one of four treatment groups. Dysport (500, 1000, or 1500 Units), or placebo was administered by intramuscular injection to these muscles. Patients were assessed at entry, and 2, 4 (primary analysis time-point), 8, and 12 weeks post-treatment., Results: A total of 74 patients were recruited. Treatment groups were generally well matched at entry. The primary efficacy variables-passive hip abduction and distance between the knees-improved for all groups. The improvement in distance between the knees for the 1500 Unit group was significantly greater than placebo (p = 0.02). Spasm frequency was reduced in all groups, but muscle tone was reduced in the Dysport groups only. Pain was reduced in all groups, but improvements in hygiene scores were evident only in the 1000 Unit and 1500 Unit groups. Duration of benefit was significantly longer than placebo for all Dysport groups (p<0.05). Adverse events were reported by 32/58 (55%) Dysport patients, and by 10/16 (63%) placebo patients. Compared with the two lower dose groups, twice as many adverse events were reported by the 1500 Unit group (2.7/patient). The incidence of muscle weakness was higher for the 1500 Unit group (36%) than for placebo (6%). The response to treatment was considered positive by two thirds of the patients in the 500 Unit group, and by about half the patients in the other groups., Conclusion: Dysport reduced the degree of hip adductor spasticity associated with multiple sclerosis, and this benefit was evident despite the concomitant use of oral antispasticity medication and analgesics. Although evidence for a dose response effect was not statistically significant, there was a clear trend towards greater efficacy and duration of effect with higher doses of Dysport. Dysport treatment was well tolerated, with no major side effects seen at doses up to 1500 Units. The optimal dose for hip adductor spasticity seems to be 500-1000 Units, divided between both legs.

This review addresses the currently available information that describes the identification of high risk patients undergoing surgery and how they may be treated to improve their outcome. It is clear from this data that high risk patients have a mortality rate of around 30% and that the major cause of death is due to multiple organ failure (MOF) which occurs days or in some cases weeks after the operation. The hypothesis for the onset of MOF is presented and it relates to the breakdown in gut patency which can allow the translocation of initiating inflammatory mediators which sets the MOF cascade in action. Current treatment strategies based on preclinical and clinical data to prevent MOF are discussed which includes the use of catecholamines such as dobutamine and dopexamine (Dopacard). It is concluded that the high risk surgical patient is not well defined and that the most rigorously tested criteria are those developed by Shoemaker. These criteria relate far more to the patients physiological status than the surgery that they are undergoing. The treatment of these patients is far more successful if intervention starts prior to surgery with fluids and vasoactive drugs such as Dopacard where the mortality rate has been shown to be reduced by 75%.