Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

9. Chronic knee pain.

Introduction: Chronic knee pain is defined as pain that persists or recurs over 3 months. The most common is degenerative osteoarthritis (OA). This review represents a comprehensive description of the pathology, diagnosis, and treatment of OA of the knee.

Predictors of outcome following an epidural steroid injection for disc-related sciatica: a Delphi consensus study.

Purpose: Trial data shows modest reductions in leg pain, disability and surgery avoidance following epidural steroid injections (ESI) for severe sciatica. Despite their common use, there is no clear evidence about which patients are more likely to benefit from ESI. The aim of this study was to generate consensus on potential predictors of outcome following ESI for disc-related sciatica.

Long COVID exhibits clinically distinct phenotypes at 3-6 months post-SARS-CoV-2 infection: results from the P4O2 consortium.

Background: Four months after SARS-CoV-2 infection, 22%-50% of COVID-19 patients still experience complaints. Long COVID is a heterogeneous disease and finding subtypes could aid in optimising and developing treatment for the individual patient.

Methods: Data were collected from 95 patients in the P4O2 COVID-19 cohort at 3-6 months after infection.

Prevalence and risk factors of gross neurologic deficits in children after severe malaria: a systematic review protocol.

Background: Children exposed to severe malaria may recover with gross neurologic deficits (GND). Several risk factors for GND after cerebral malaria (CM), the deadliest form of severe malaria, have been identified in children. However, there is inconsistency between previously reported and more recent findings.

Long-term effectiveness of a lifestyle intervention for rheumatoid arthritis and osteoarthritis: 1-year follow-up of the 'Plants for Joints' randomised clinical trial.

Objectives: In two randomised controlled trials, the Plants for Joints (PFJ) multidisciplinary lifestyle intervention reduced signs and symptoms of rheumatoid arthritis (RA), or metabolic syndrome-associated hip or knee osteoarthritis (MSOA) compared with usual care. The current study investigated long-term outcomes.

Methods: After completion of two 16-week trials in people with (1) RA or (2) MSOA, control groups switched to the active PFJ intervention.

Cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: 12-month and cost-effectiveness results from the multicenter COCOGEN trial.

Background: Radiofrequency (RF) treatment of the genicular nerves reduces chronic knee pain in patients with osteoarthritis (OA) or persistent postsurgical pain (PPSP) after total knee arthroplasty (TKA). The objective of this study is to compare long-term outcomes of cooled and conventional RF and perform an economic evaluation.

Methods: The COCOGEN trial is a double-blinded, non-inferiority, pilot, randomized controlled trial that compared the effects up to 12 months of cooled and conventional RF in patients with chronic knee pain suffering from OA or PPSP after TKA following a 1:1 randomization rate.

Predictors of outcome in sciatica patients following an epidural steroid injection: the POiSE prospective observational cohort study protocol.

Introduction: Sciatica can be very painful and, in most cases, is due to pressure on a spinal nerve root from a disc herniation with associated inflammation. For some patients, the pain persists, and one management option is a spinal epidural steroid injection (ESI). The aim of an ESI is to relieve leg pain, improve function and reduce the need for surgery.

International Delphi Consensus Study on disposable single-use endoscopy: A path to clinical adoption.

Background/objective: Increasing infectious rate estimates and low microbiological surveillance affect safety of gastrointestinal endoscopy globally. Single use endoscopes and accessories have been claimed to improve safety, but there is lack of data on their indication and sustainability. We aimed to identify a series of best practice recommendations for the use of single use endoscopes and accessories using a modified Delphi.

Endovascular therapy in acute ischemic stroke with poor reperfusion is associated with worse outcomes compared with best medical management: a HERMES substudy.

Background: Functional outcomes in patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO) undergoing endovascular treatment (EVT) with poor reperfusion were compared with patients with AIS-LVO treated with best medical management only.

Methods: Data are from the HERMES collaboration, a patient-level meta-analysis of seven randomized EVT trials. Baseline characteristics and functional outcomes (modified Rankin Scale (mRS) score at 90 days) were compared between patients with poor reperfusion (defined as modified Thrombolysis in Cerebral Infarction Score 0-1 on the final intracranial angiography run as assessed by the central imaging core laboratory) and patients in the control arm with multivariable logistic ordinal logistic regression adjusted for pre-specified baseline variables.

Female athlete health domains: a supplement to the International Olympic Committee consensus statement on methods for recording and reporting epidemiological data on injury and illness in sport.

The IOC made recommendations for recording and reporting epidemiological data on injuries and illness in sports in 2020, but with little, if any, focus on female athletes. Therefore, the aims of this supplement to the IOC consensus statement are to (i) propose a taxonomy for categorisation of female athlete health problems across the lifespan; (ii) make recommendations for data capture to inform consistent recording and reporting of symptoms, injuries, illnesses and other health outcomes in sports injury epidemiology and (iii) make recommendations for specifications when applying the Strengthening the Reporting of Observational Studies in Epidemiology-Sport Injury and Illness Surveillance (STROBE-SIIS) to female athlete health data.In May 2021, five researchers and clinicians with expertise in sports medicine, epidemiology and female athlete health convened to form a consensus working group, which identified key themes.

Accuracy of ultrasound in diagnosing ankle injuries in emergency care.

Background: Ankle injuries are one of the most common presentations in the ED. Although fractures can be ruled out using the Ottawa Ankle Rules, the specificity is low, which means many patients may still receive unnecessary radiographs. Even once fractures are ruled out, assessment of ankle stability is recommended to rule out ruptures, but the anterior drawer test has only moderate sensitivity and low specificity and should be performed only after swelling has receded.

Safe shortening of antibiotic treatment duration for complicated bacteraemia (SAFE trial): protocol for a randomised, controlled, open-label, non-inferiority trial comparing 4 and 6 weeks of antibiotic treatment.

Introduction: A major knowledge gap in the treatment of complicated bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB.

Walking the line between assessment, improvement and learning: a qualitative study on opportunities and risks of incorporating peer discussion of audit and feedback within quality improvement in general practice.

Objectives: There is a broad call for change towards 'new era' quality systems in healthcare, in which the focus lies on learning and improving. A promising way to establish this in general practice care is to combine audit and feedback with peer group discussion. However, it is not known what different stakeholders think of this type of quality improvement.

Th2 high and mast cell gene signatures are associated with corticosteroid sensitivity in COPD.

Rationale: Severe asthma and chronic obstructive pulmonary disease (COPD) share common pathophysiological traits such as relative corticosteroid insensitivity. We recently published three transcriptome-associated clusters (TACs) using hierarchical analysis of the sputum transcriptome in asthmatics from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort comprising one Th2-high inflammatory signature (TAC1) and two Th2-low signatures (TAC2 and TAC3).

Objective: We examined whether gene expression signatures obtained in asthma can be used to identify the subgroup of patients with COPD with steroid sensitivity.

Development and training of a machine learning algorithm to identify patients at risk for recurrence following an arthroscopic Bankart repair (CLEARER): protocol for a retrospective, multicentre, cohort study.

Introduction: Shoulder instability is a common injury, with a reported incidence of 23.9 per 100 000 person-years. There is still an ongoing debate on the most effective treatment strategy.

Breakthrough infections with the SARS-CoV-2 omicron (B.1.1.529) variant in patients with immune-mediated inflammatory diseases.

Objectives: To compare the cumulative incidence and disease severity of reported SARS-CoV-2 omicron breakthrough infections between patients with immune-mediated inflammatory diseases (IMID) on immunosuppressants and controls, and to investigate determinants for breakthrough infections.

Methods: Data were used from an ongoing national prospective multicentre cohort study on SARS-CoV-2 vaccination responses in patients with IMID in the Netherlands (Target-to-B! (T2B!) study). Patients wih IMID on immunosuppressants and controls (patients with IMID not on immunosuppressants and healthy controls) who completed primary immunisation were included.

Early versus delayed lengthening exercises for acute hamstring injury in male athletes: a randomised controlled clinical trial.

Background: To evaluate the efficacy of early versus delayed introduction of lengthening (ie, eccentric strengthening) exercises in addition to an established rehabilitation programme on return to sport duration for acute hamstring injuries in a randomised controlled superiority trial.

Methods: 90 male participants (age: 18-36 years, median 26 years) with an MRI-confirmed acute hamstring injury were randomised into an early lengthening (at day 1 of rehabilitation) group or a delayed lengthening (after being able to run at 70% of maximal speed) group. Both groups received an established rehabilitation programme.

Effects of a lifestyle intervention programme after 1 year of follow-up among South Asians at high risk of type 2 diabetes: a cluster randomised controlled trial.

Introduction: South Asians are at high risk of type 2 diabetes (T2D). We assessed whether intensive family-based lifestyle intervention leads to significant weight loss, improved glycaemia and blood pressure in adults at elevated risk for T2D.

Methods: This cluster randomised controlled trial (iHealth-T2D) was conducted at 120 locations across India, Pakistan, Sri Lanka and the UK.

Dutch multicentre, prospective follow-up, cohort study comparing the neurological and neuropsychological sequelae of hospitalised non-ICU- and ICU-treated COVID-19 survivors: a study protocol.

Introduction: Owing to the novelty of COVID-19, there are still large knowledge gaps concerning its effect on the brain and the resulting impact on peoples' lives. This large-scale prospective follow-up study investigates COVID-19-associated brain damage, neuropsychological dysfunction and long-term impact on the well-being of patients and their close ones. It is hypothesised that structural brain damage and cognitive dysfunction primarily occur in severely ill patients, as compared with moderately ill patients.

Reducing surgical cancellations: a successful application of Lean Six Sigma in healthcare.

Objective: The COVID-19 pandemic emphasises the need to use healthcare resources efficient and effective to guarantee access to high-quality healthcare in an affordable manner. Surgical cancellations have a negative impact on these. We used the Lean Six Sigma (LSS) methodology to reduce cardiac surgical cancellations in a University Medical Center in the Netherlands, where approximately 20% of cardiac surgeries were being cancelled.