Effectiveness of surgical fixation for lateral compression type one (LC-1) fragility fractures of the pelvis: a systematic review

Objectives: To undertake a systematic review of the evidence base for the effectiveness of surgical fixation of lateral compression (LC-1) fragility fractures of the pelvis compared to non-surgical approaches. Searches: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and two international trials registers were searched up to January 2017 (Medline to February 2019) for studies of internal or external fixation of fragility fractures of the pelvis. Participants: Patients with lateral compression pelvic fractures (LC-1 fractures), sustained as the result of a low energy mechanism, defined as a fall from standing height or less. Interventions: Surgery using either external or internal fixation devices. Conservative non-surgical treatment was the defined comparator. Outcome measures: Outcomes of interest were patient mobility and function, pain, quality of life, fracture union, mortality, hospital length of stay and complications (additional operative procedures, number and type of adverse events and serious adverse events). Quality assessment and synthesis: The Joanna Briggs Institute Checklist for Case Series was used to assess the included studies. Results were presented in a narrative synthesis. Results: Of 3421 records identified, four retrospective case series met the inclusion criteria. Fixation types were not consistent between studies or within studies and most patients had more than one type of pelvic fixation. Where reported, mobility and function improved post-surgery, and a reduction in pain was recorded. Length of hospital stay ranged from four days to 54 days for surgical fixation of any type. Reported complications and adverse outcomes included: infections, implant loosening, pneumonia and thrombosis. Use of analgesia was not reported, Conclusions: There is insufficient evidence to support guidance on the most effective treatment for patients who fail to mobilise after sustaining an LC-1 fragility fracture. Registration: PROSPERO registration number: CRD4201705587

Risk factors for inferior shoulder subluxation in patients with stroke

© 2010 Maney Publishing. Objective: Shoulder subluxation is reported in up to 81% of stroke patients. It presents considerable challenges to those involved in rehabilitation. Extensive research has focused on treatment strategies used to reduce subluxation. A better understanding of the risk factors of shoulder subluxation would enable clinicians to provide effective management of this debilitating complication. Methods: A systematic online search was conducted of MEDLINE, EMBASE, CINAHL, AMED and PEDro databases using appropriate keywords. The search was supplemented by citation tracking from the retrieved papers and manual searches of relevant journals. The search was limited to articles in the English language. All primary studies fulfilling the review's inclusion criteria were included. Four reviewers extracted the data and independently appraised the methodological quality of the selected studies. Discrepancies were resolved following discussions. Results: Of the 36 abstracts identified, eight articles met the inclusion criteria. Complete loss of motor function/severity of arm paralysis, apparent absence of supraspinatus contraction, sensory impairment, loss of proprioception and hemorrhagic type of stroke were identified as potential risk factors. Downward tilting of scapula did not emerge as a risk factor as previously suggested. Conclusion: Despite methodological flaws such as small sample size and the use of insensitive outcome measures, complete loss of motor function in the affected arm has been recognized as a significant risk factor for post-stroke subluxation. The best way to prevent subluxation is to encourage task-specific functional activities to increase voluntary motor control around the shoulder and to advise strengthening exercises to re-establish strength of rotator cuff muscles

Lateral compression type 1 fracture fixation in the elderly (L1FE): study protocol for a randomised controlled trial (with internal pilot) comparing the effects of INFIX surgery and non-surgical management for treating patients with lateral compression type 1 (LC-1) fragility fractures.

BACKGROUND: Lateral compression type1 (LC-1) fragility fractures are a common, painful injury in older adults resulting in reduced mobility. The incidence of these fractures is increasing with the growing older adult population. The current standard of care is non-surgical management; however, patients with this injury are at risk of long-term immobility and related complications. INFIX is a pelvic fixation device used in younger patients with high-energy fractures. The device is fitted via a percutaneous technique with no external pin sites and has good purchase even in osteoporotic bone. It therefore has the potential to be well tolerated in patients with LC-1 fragility fractures. INFIX could improve patients' ability to mobilise and reduce the risk of immobility-related complications. However, there is a risk of complications related to surgery, and robust evidence is required on patient outcomes. This study will investigate the clinical and cost-effectiveness of surgical fixation with INFIX compared to non-surgical management of LC-1 fragility fractures in older adults. METHODS: A multi-centre randomised controlled trial of 600 patients allocated 1:1 to non-surgical management or INFIX surgery. The study will have a 12-month internal pilot to assess recruitment and trial feasibility. The primary outcome will be the patient quality of life over 6 months, measured by the patient-reported EQ-5D-5L. The secondary outcomes will include physical function, mental health, pain, delirium, imaging assessment, resource use, and complications. DISCUSSION: The L1FE study aims to compare the clinical and cost-effectiveness of surgical and non-surgical management of people aged 60 years and older with LC-1 fragility fractures. The trial is sufficiently powered and rigorously designed to inform future clinical and patient decision-making and allocation of NHS resources. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Registry ISRCTN16478561. Registered on 8 April 2019

Lateral compression type-1 fracture fixation in the elderly (L1FE). Study Protocol for a randomised controlled trial (with internal pilot) comparing the effects of INFIX surgery and non-surgical management for treating patients with Lateral Compression type-1 (LC-1) fragility fractures

Background: Lateral compression type-1 (LC-1) fragility fractures are a common, painful injury in older adults resulting in reduced mobility. The incidence of these fractures is increasing with the growing older adult population. Current standard of care is non-surgical management, however patients with this injury are at risk of long term immobility and the related complications. INFIX is a pelvic fixation device used in younger patients with high energy fractures. The device is fitted via a percutaneous technique with no external pin sites and has good purchase even in osteoporotic bone. It therefore has the potential to be well tolerated in patients with LC-1 fragility fractures. INFIX could improve patients’ ability to mobilise and reduce the risk of immobility related complications. However, there is a risk of complications related to surgery and robust evidence is required on patient outcomes. This study will investigate the clinical and cost effectiveness of surgical fixation with INFIX compared to non-surgical management of LC-1 fragility fractures in older adults. Methods: A multi-centre randomised controlled trial of 600 patients allocated 1:1 to non-surgical management or INFIX surgery. The study will have a 12-month internal pilot to assess recruitment and trial feasibility. The primary outcome will be patient quality of life over 6 months, measured by the patient reported EQ-5D-5L. Secondary outcomes will include physical function, mental health, pain, delirium, imaging assessment, resource use and complications. Discussion: The L1FE study aims to compare the clinical and cost effectiveness of surgical and non-surgical management of people aged 60 years and older with LC-1 fragility fractures. The trial is sufficiently powered and rigorously designed to inform future clinical and patient decision making and allocation of NHS resources. Trial Registration: Trial Identifier: ISRCTN16478561. Registry Name: International Standard Randomised Controlled Trial Number Registry. Registered: 8th April 201

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease