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Clinical and Genetic Evaluation of People with or at Risk of Hereditary ATTR Amyloidosis: An Expert Opinion and Consensus on Best Practice in Ireland and the UK.
No full textHereditary transthyretin-mediated amyloidosis (hATTR) is challenging to diagnose early owing to the heterogeneity of clinical presentation, which differs according to the TTR gene variant and its penetrance in each individual. The TTR variants seen most frequently in the UK and Ireland (T80A, V142I and V50M) differ to those commonly occurring in other geographic locations and warrant a specific consideration for diagnosis and genetic testing. In addition, recent availability of treatment for this condition has reinforced the need for a more consistent approach to the management of patients, including access to specialist services, genetic testing and counselling, and clinical investigation for families living in the UK and Ireland. A multidisciplinary panel of experts from the UK and Ireland was convened to identify the current challenges, provide recommendations, and develop a consensus for the diagnosis and screening of people with, or at risk of, hATTR. Over a series of meetings, experts shared their current practices and drafted, refined and approved a consensus statement. This consensus statement provides recommendations for three different groups: (1) people with symptoms raising a possibility of hATTR amyloidosis; (2) people with biopsy-confirmed hATTR amyloidosis; and (3) people without symptoms who may have hATTR amyloidosis (i.e. relatives of people with identified TTR variants). For each group, recommendations are made for the required steps for the diagnosis and follow-up of symptomatic patients, and for guidance on the specialist support for counselling and pre-symptomatic genetic testing of at-risk individuals. This guidance is intended to be practical and based on available evidence. The aim is for regional amyloid specialist centres to provide timely diagnosis, clinical screening, and treatment for individuals and their families with hATTR amyloidosis
Myocardial Fibrosis Predicts Ventricular Arrhythmias and Sudden Death After Cardiac Electronic Device Implantation.
No full textBACKGROUND
Increasing evidence supports a link between myocardial fibrosis (MF) and ventricular arrhythmias.
OBJECTIVES
The purpose of this study was to determine whether presence of myocardial fibrosis on visual assessment (MF) and gray zone fibrosis (GZF) mass predicts sudden cardiac death (SCD) and ventricular fibrillation/sustained ventricular tachycardia after cardiac implantable electronic device (CIED) implantation.
METHODS
In this prospective study, total fibrosis and GZF mass, quantified using cardiovascular magnetic resonance, was assessed in relation to the primary endpoint of SCD and the secondary, arrhythmic endpoint of SCD or ventricular arrhythmias after CIED implantation.
RESULTS
Among 700 patients (age 68.0 ± 12.0 years), 27 (3.85%) experienced a SCD and 121 (17.3%) met the arrhythmic endpoint over median 6.93 years (IQR: 5.82-9.32 years). MF predicted SCD (HR: 26.3; 95% CI: 3.7-3,337; negative predictive value: 100%). In competing risk analyses, MF also predicted the arrhythmic endpoint (subdistribution HR: 19.9; 95% CI: 6.4-61.9; negative predictive value: 98.6%). Compared with no MF, a GZF mass measured with the 5SD method (GZF) >17 g was associated with highest risk of SCD (HR: 44.6; 95% CI: 6.12-5,685) and the arrhythmic endpoint (subdistribution HR: 30.3; 95% CI: 9.6-95.8). Adding GZF mass to MF led to reclassification of 39% for SCD and 50.2% for the arrhythmic endpoint. In contrast, LVEF did not predict either endpoint.
CONCLUSIONS
In CIED recipients, MF excluded patients at risk of SCD and virtually excluded ventricular arrhythmias. Quantified GZF mass added predictive value in relation to SCD and the arrhythmic endpoint
International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome.
No full textBACKGROUND
Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT).
OBJECTIVES
This study sought to characterize HCT outcomes in APDS.
METHODS
Retrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT.
RESULTS
Pre-HCT comorbidities such as lung, gastrointestinal, and liver pathology were common, with hematologic malignancy in 26%. With median follow-up of 2.3 years, 2-year overall and graft failure-free survival probabilities were 86% and 68%, respectively, and did not differ significantly by APDS1 versus APDS2, donor type, or conditioning intensity. The 2-year cumulative incidence of graft failure following first HCT was 17% overall but 42% if mammalian target of rapamycin inhibitor(s) (mTORi) were used in the first year post-HCT, compared with 9% without mTORi. Similarly, 2-year cumulative incidence of unplanned donor cell infusion was overall 28%, but 65% in the context of mTORi receipt and 23% without. Phenotype reversal occurred in 96% of evaluable patients, of whom 17% had mixed chimerism. Vulnerability to renal complications continued post-HCT, adding new insights into potential nonimmunologic roles of phosphoinositide 3-kinase not correctable through HCT.
CONCLUSIONS
Graft failure, graft instability, and poor graft function requiring unplanned donor cell infusion were major barriers to successful HCT. Post-HCT mTORi use may confer an advantage to residual host cells, promoting graft instability. Longer-term post-HCT follow-up of more patients is needed to elucidate the kinetics of immune reconstitution and donor chimerism, establish approaches that reduce graft instability, and assess the completeness of phenotype reversal over time
EULAR points to consider for minimal reporting requirements in synovial tissue research in rheumatology.
No full textBACKGROUND
Synovial tissue research has become widely developed in several rheumatology centres, however, large discrepancies exist in the way synovial tissue is handled and, more specifically, how data pertaining to biopsy procedure, quality check and experimental results are reported in the literature. This heterogeneity hampers the progress of research in this rapidly expanding field. In that context, under the umbrella of European Alliance of Associations for Rheumatology, we aimed at proposing points to consider (PtC) for minimal reporting requirements in synovial tissue research.
METHODS
Twenty-five members from 10 countries across Europe and USA met virtually to define the key areas needing evaluation and formulating the research questions to inform a systematic literature review (SLR). The results were presented during a second virtual meeting where PtC were formulated and agreed.
RESULTS
Study design, biopsy procedures, tissue handling, tissue quality control and tissue outcomes (imaging, DNA/RNA analysis and disaggregation) were identified as important aspects for the quality of synovial tissue research. The SLR interrogated four databases, retrieved 7654 abstracts and included 26 manuscripts. Three OPs and nine PtC were formulated covering the following areas: description of biopsy procedure, overarching clinical design, patient characteristics, tissue handling and processing, quality control, histopathology, transcriptomic analyses and single-cell technologies.
CONCLUSIONS
These PtC provide guidance on how research involving synovial tissue should be reported to ensure a better evaluation of results by readers, reviewers and the broader scientific community. We anticipate that these PtC will enable the field to progress in a robust and transparent manner over the coming years
Brachial arterial access for PCI: an analysis of the British Cardiovascular Intervention Society database.
No full textCemiplimab in advanced cutaneous squamous cell carcinoma: UK experience from the Named Patient Scheme.
No full textShorter Treatment for Nonsevere Tuberculosis in African and Indian Children.
No full textBACKGROUND
Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen.
METHODS
We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment.
RESULTS
From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberculosis at baseline. A total of 95 participants (8%) had an adverse event of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, all but 2 of which occurred within the first 8 weeks, when the treatments were the same in the two groups).
CONCLUSIONS
Four months of antituberculosis treatment was noninferior to 6 months of treatment in children with drug-susceptible, nonsevere, smear-negative tuberculosis. (Funded by the U.K. Medical Research Council and others; SHINE ISRCTN number, ISRCTN63579542.)
Pityriasis rubra pilaris-like eruption following administration of the BNT163b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine.
No full textWe describe a case of a pityriasis rubra pilaris (PRP)-like eruption occurring following administration of the Pfizer-Biontech mRNA COVID-19 vaccine, with worsening of the condition following the second dose. To our knowledge, this is the first reported case of a PRP-like eruption as a cutaneous adverse event of the Pfizer-Biontech mRNA COVID-19 vaccine
Cross reactivity of spike glycoprotein induced antibody against Delta and Omicron variants before and after third SARS-CoV-2 vaccine dose in healthy and immunocompromised individuals.
No full textApplying a COVID Virtual Ward model, assessing patient outcomes and staff workload.
No full textA COVID virtual ward (CVW) is recommended by NHS England, but 'usual care' outcomes have not been reported. A retrospective study of all adults with COVID-19 attending Queen Elizabeth Hospital Birmingham between 01/06/2020-31/01/2021, assessed against CVW criteria and followed for 28 days. Of 2301 COVID-19 patients, 571(25%) would have met CVW criteria. Of these, 325(57%) were discharged after review and 246(43%) admitted. Of admitted patients who met CVW criteria, 81% required hospital-supported therapies; 11% died. Of the 325 discharged, 13% re-presented, 9% with COVID-related symptoms, 2% required intensive care admission, and one died (0.3%). In this comparison, discharging patients without a CVW did not lead to more re-presentations, re-admissions, ITU escalations or deaths compared to published outcomes for hospitals with a CVW