Background: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. Methods: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. Findings: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the mRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Other immune-mediated conditions included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. Interpretation: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. Funding: none.

Aims: To estimate the prevalence, incidence, mortality, and risk factors for atrial fibrillation (AF) in 195 countries and territories from 1990 to 2017. Methods and results: Following the methodologies used in the Global Burden of Disease Study 2017, the prevalence, incidence, and mortality of AF were analysed by age, sex, year, socio-demographic index (SDI), and location. The percentage contributions of major risk factors to age-standardized AF deaths were measured by population attributable fractions. In 2017, there were 37.57 million [95% uncertainty interval (UI) 32.55–42.59] prevalent cases and 3.05 million (95% UI 2.61–3.51) incident cases of AF globally, contributing to 287 241 (95% UI 276 355–304 759) deaths. The age-standardized rates of prevalent cases, incident cases, and deaths of AF in 2017 and their temporal trends from 1990 to 2017 varied significantly by SDI quintile and location. High systolic blood pressure was the leading risk factor for AF age-standardized deaths [34.3% (95% UI 27.4–41.5)] in 2017, followed by high body mass index [20.7% (95% UI 11.5–32.2)] and alcohol use [9.4% (95% UI 7.0–12.2)]. Conclusion: Our study has systematically and globally assessed the temporal trends of AF, which remains a major public heath challenge. Although AF mainly occurred in developed countries, the unfavourable trend in countries with lower SDI also deserves particular attention. More effective prevention and treatment strategies aimed at counteracting the increase in AF burden should be established in some countries.

Furosemide-loaded microneedles, comprising PLGA needle tips and a flexible base, were fabricated and characterized in vitro and ex vivo. The microneedles exhibited an initial burst release followed by sustained release of furosemide.

Fever of unknown origin (FUO) poses a diagnostic challenge, and 18-fluorodexoyglucose positron emission tomography with computed tomography (18FDG-PET/CT) may identify the source. We aimed to evaluate the diagnostic yield of 18FDG-PET/CT in the work-up of FUO. The records of patients admitted to Sheba Medical Center between January 2013 and January 2018 who underwent 18FDG-PET/CT for the evaluation of FUO were reviewed. Following examination of available medical test results, 18FDG-PET/CT findings were assessed to determine whether lesions identified proved diagnostic. Of 225 patients who underwent 18FDG-PET/CT for FUO work-up, 128 (57%) met inclusion criteria. Eighty (62.5%) were males; mean age was 59 ± 20.3 (range: 18–93). A final diagnosis was made in 95 (74%) patients. Of the 128 18FDG-PET/CT tests conducted for the workup of FUO, 61 (48%) were true positive, 26 (20%) false positive, 26 (20%) true negative, and 15 (12%) false negative. In a multivariate analysis, weight loss and anemia were independently associated with having a contributary results of 18FDG-PET/CT. The test yielded a sensitivity of 70%, specificity of 37%, positive predictive value of 70%, and negative predictive value of 37%. 18FDG-PET/CT is a valuable tool in the diagnostic workup of FUO. It proved effective in diagnosing almost half the patients, especially in those with anemia and weight loss.

Background: In patients undergoing high‐risk percutaneous coronary intervention, Impella has become an important adjunctive tool to support revascularization. The impact of age on the outcomes of patients undergoing high‐risk percutaneous coronary intervention is limited. The aim of this study is to describe the characteristics and outcomes of patients ≥75 years of age undergoing Impella‐supported high‐risk percutaneous coronary intervention. Methods and Results: Baseline characteristics and outcomes of patients ≥75 years of age versus those of patients <75 years of age in patients enrolled in the cVAD PROTECT III (Catheter‐Based Ventricular Assist Device Prospective, Multi‐Center, Randomized Controlled Trial of the IMPELLA RECOVER LP 2.5 System Versus Intra Aortic Balloon Pump in Patients Undergoing Non Emergent High Risk Percutaneous Coronary Intervention) study (NCT04136392). Major adverse cardiovascular and cerebral events (composite of all‐cause death, nonfatal myocardial infarction, stroke/transient ischemic attack, and repeat revascularization) were assessed at 30 and 90 days and all‐cause death at 1 year. Out of 1237 patients, 493 (39.9%) patients were ≥75 years of age. Patients ≥75 years of age had less diabetes and prior myocardial infarction, more hypertension and dyslipidemia, worse renal function, more severe valvular heart disease, but higher left ventricular ejection fraction ( P <0.05 for all comparisons). Baseline Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery scores were similar between groups. Older patients underwent more left main percutaneous coronary intervention (58% versus 39%; P <0.0001), atherectomy (32% versus 22%; P <0.0001), and femoral access (87% versus 79%, P =0.0003) as compared with younger patients. In‐hospital vascular complications did not differ, but rates of respiratory failure, pericardial tamponade, and cardiogenic shock were higher in older patients. Rates of all‐cause death and major adverse cardiovascular and cerebral events did not differ between groups at 30 and 90 days. Rates of all‐cause death at 1 year were higher in patients ≥75 years (adjusted hazard ratio, 1.99 [95% CI, 1.24–3.18], P =0.004). Conclusions: Impella‐supported high‐risk percutaneous coronary intervention in older patients is feasible with an acceptable safety profile. However, age ≥75 years remained a statistically significant predictor for all‐cause death at 1 year. Registration: URL: https://clinicaltrials.gov ; Unique Identifier: NCT04136392.