Explore the vast range of titles available.

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.

Exertional heat stroke (EHS) is the most complicated and dangerous amongst heat injuries that can lead to irreversible injury and even death. Early diagnosis and treatment are therefore crucial determinants of the patient's prognosis. The following case report depicts a soldier who presented primarily with confusion and behavioral changes during physical exercise and later lost consciousness. He was misdiagnosed by the field physician as suffering from supraventricular tachycardia, was treated as such and only diagnosed as suffering from EHS later in the emergency room. Our main aims are: to highlight the possibility of misdiagnosis of EHS even among trained physicians, to describe the main symptoms of EHS, and to emphasize the importance of early diagnosis and proper treatment.

Background/Objectives: ACE (angiotensin-converting enzyme) is considered a serological marker of sarcoidosis as elevated levels have been reported in 30–80% of patients. However, elevated ACE levels are also encountered in other medical conditions, and the clinical correlation between ACE levels and disease activity in sarcoidosis is disputable as well. To determine the significance of elevated ACE levels in the diagnosis and follow-up of sarcoidosis patients. Methods: All electronic patient records in which an ACE level was recorded in a large tertiary hospital were identified using a computerized algorithm. Medical diagnoses, ACE numerical values, and clinical data were also automatically extracted. Furthermore, all records with a diagnosis of sarcoidosis were manually reviewed for ascertainment of the diagnosis and searched for additional clinical manifestations and treatment responses. Results: A total of 1416 records with a documented ACE level were found in the database, and 146 of the records had a diagnosis of sarcoidosis in the medical record. However, the diagnosis was excluded in 27 of these cases after a manual review of the records. Elevated ACE levels were most commonly encountered among patients with sarcoidosis, non-Hodgkin’s lymphoma, cirrhosis, and interstitial lung disease. Elevated ACE levels had a positive predictive value of 12.76% and a negative predictive value of 94.6% for the diagnosis of sarcoidosis in our cohort, with a sensitivity of 63.5% and a specificity of 59.5%. Among patients with sarcoidosis, ACE levels around the time of diagnosis were higher than ACE levels in remission. However, a paired analysis did not find a statistically significant difference in ACE levels between the two timepoints. A positive correlation between lack of cardiac involvement and elevated ACE levels was found on multivariate analysis. Conclusions: ACE levels are a non-specific serological marker with low specificity and sensitivity for sarcoidosis and a poor positive predictive value, but with a negative predictive value of 94.6%. Furthermore, elevated ACE levels correlated poorly with disease activity in our cohort.

BackgroundThe CHA2DS2-VASC score is used to assess the risk of cerebrovascular accident (CVA) in patients with atrial fibrillation (AF) or atrial flutter (AFL).ObjectivesWe aimed to determine whether this score can determine the risk of CVA during the first year after hospitalization, in patients without known AF/AFL.DesignSingle-center retrospective cohort.PatientsWe included all patients aged ≥ 50 who were hospitalized between January 1, 2008, and December 31, 2018, to the internal medicine departments at the Chaim Sheba Medical Center, Israel. Exclusion criteria included history or new diagnosis of CVA, TIA, and AF/AFL and use of anticoagulation at any time.Main MeasuresPatients were stratified into 3 groups according to their CHA2DS2-VASC score (0–1, 2, or ≥ 3). The primary outcome was hospitalization with CVA/TIA within one year of the index hospitalization.Key ResultsOf the patients, 52,206 were included in the study. CVA/TIA occurred in 0.7%, 1.3%, and 1.7% of patients with a CHA2DS2-VASC score of 0–1, 2, and ≥ 3, respectively. Compared to a CHA2DS2-VASC score of 0–1, the HR for CVA/TIA occurrence for CHA2DS2-VASC scores of 2 and ≥ 3 was 1.77 (CI 1.42, 2.22) and 2.33 (CI 1.9, 2.85), respectively (p < 0.001 for both comparisons). Each additional CHA2DS2-VASC point increased the probability for readmission with CVA/TIA within 1-year by 26% (HR 1.26, CI 1.19, 1.32, p < 0.001). Similar trends were seen in subgroup analyses by gender, age, and renal function.ConclusionsThe CHA2DS2-VASC score is a predictor for CVA/TIA during the first year after hospitalization in patients without AF. High CHA2DS2-VASC scores warrant work-up for occult AF/AFL and other risk factors for CVA/TIA.

ObjectiveTo evaluate the frequency of sacroiliitis in older subjects.Materials and methodsConsecutive MRI examinations of the sacroiliac joints (SIJs) performed for suspected sacroiliitis (2005–2019) in patients ≥ 18 years were retrospectively evaluated for the presence of active/structural lesions and were categorized for the presence/absence of sacroiliitis. Clinical and imaging parameters were compared between subjects with sacroiliitis according to age groups < 40 years, 40–55, and > 55 years. Clinical parameters including inflammatory back pain (IBP) and other spondyloarthritis (SpA) features were retrieved from the medical records.ResultsA total of 431 patients with SIJs MRI were evaluated: median age, 44 [IQR 35–54]; female:male 267(62%):164(38%). Sacroiliitis was diagnosed in 89 (20.6%) subjects—median age, 41 years [IQR 32–54], 52% females— and was equally prevalent among the different age groups: > 40 years old, 23.6%; 40–55, 20%; and > 55 years old, 17%, p = 0.43, with active/structural lesions equally dispersed. Older patients (> 55) started suffering from back pain at an older age and had a longer delay in diagnosis. Gender distribution, the presence of IBP, and other SpA features were no different in patients < 45 and > 55 years of age.ConclusionsThe frequency of sacroiliitis on SIJs-MRI in subjects > 55 years is similar to its frequency in younger subjects and is associated with the same type and magnitude of active and structural MRI lesions. Clinical parameters such as IBP and additional SpA features are similarly prevalent in older and younger subjects suggesting they suffer from the same disease and differing only in age of presentation.

Background Gastrointestinal perforations have been reported in a small number of rheumatoid arthritis (RA) patients treated with Janus kinase (JAK) inhibitors in clinical trials. However, large‐scale postmarketing data repositories are needed to further investigate this potentially rare but serious adverse event. Methods A retrospective, pharmacovigilance study of the FDA adverse event reporting system (July 2014 to September 2023) assessing the reporting of gastrointestinal perforations following JAK inhibitors compared to biological disease‐modifying antirheumatic drugs (bDMARDs) in RA patients. The adjusted reporting odds ratio (adj.ROR) was calculated using a multivariable logistic regression model. Results Of 399,983 RA patients included in the study, 76,446 were treated with JAK inhibitors (tofacitinib, n = 52,365; upadacitinib, n = 21,856; baricitinib, n = 2225) and 323,537 were treated with bDMARDs (TNF inhibitors, rituximab, and abatacept). Overall, 230 cases of gastrointestinal perforation following JAK inhibitors were identified, with a median time of 9 (IQR: 4–22) months from treatment initiation. Compared with bDMARDs, JAK inhibitors were associated with a higher‐than‐expected reporting of gastrointestinal perforations (adj.ROR = 1.98[1.69−2.31]). Increased reporting of gastrointestinal perforations was observed among recipients of JAK inhibitors or bDMARDs who used steroids or non‐steroidal anti‐inflammatory drugs concurrently (adj.ROR = 2.82 [2.41–3.31]). Perforations of both the upper and lower gastrointestinal tract were significantly over‐reported (n = 51, adj.ROR = 1.55 [1.12–2.14], n = 143, adj.ROR = 1.78 [1.46–2.17], respectively). Furthermore, the safety signal was significant across all JAK inhibitors: tofacitinib (n = 125, adj.ROR = 1.52 [1.25–1.85]), upadacitinib (n = 84, adj.ROR = 2.73 [2.17–3.44]), and baricitinib (n = 21, adj.ROR = 5.38 [3.46–8.37]). Conclusion In this global pharmacovigilance study, all JAK inhibitors were associated with increased reporting of gastrointestinal perforations compared with bDMARDs in RA patients. Until more data on IBD patients emerge, careful surveillance and increased clinicians' awareness should also be advocated for this population.

Smoking has a thermogenic effect and is associated with low physical performance. Nevertheless, a direct, quantitative effect of acute smoking on exercise heat tolerance has not been reported. Methods: Sixteen healthy young male volunteers, eight cigarette smokers, and eight non-smokers participated in the study. All subjects performed a maximal oxygen consumption test (VO[2max]) and a standardized heat tolerance test (HTT) after at least 12 h without smoking under the following conditions: no nicotine exposure, 10 min after nicotine exposure (2 mg nicotine lozenge), and 10 min after smoking two cigarettes (0.8 mg nicotine in each cigarette, smokers only). Results: There was no significant effect of nicotine exposure on physiological performance and heat tolerance in the non-smokers group. In the smokers group, cigarette smoking, but not nicotine ingestion, resulted with higher heart rate (by 9±9 bpm) at the end of the HTT (p<0.05). Moreover, both smoking and nicotine ingestion increased smokers' rectal temperature at the end of the HTT (by 0.24±0.16°C and 0.21±0.26°C, respectively, p<0.05) and were associated with higher sweat rate during the HTT (by 0.08±0.07 g/h and 0.06±0.08 g/h, respectively, p<0.05). Heart rate variability (HRV) analysis also revealed a higher LF/HF (low frequency/high frequency) ratio after exposure to nicotine and smoking in the smokers group compared with no exposure (2.13±2.57 and 2.48±2.76, respectively, p<0.05), indicating a higher sympathetic tone. Conclusions: According to this preliminary study, cigarette smoking and nicotine ingestion increase the physiological strain during a HTT in smokers. Acute smoking may, therefore, increase heat intolerance and the risk to heat injuries.

Background The common practice in the Israel defense Forces is that exertional heat related injury patients undergo a heat tolerance test 6–8 weeks post event as part of the “return to duty” process. In the case of a positive heat tolerance test the individual is classified as heat intolerant, in some cases however, the thermoregulatory recovery may be longer (several months), and therefore a second heat tolerance test is scheduled 6-8 weeks later. The presented case reports emphasize the possibility of different recovery periods of the thermoregulatory center and the distinction between congenital and acquired physiological heat intolerance. Case description Two young healthy males (A and B) were diagnosed with exertional heat related injury during a pre-recruitment sorting process. Both underwent a heat tolerance test, and were found heat intolerant. During the next months they repeated the test several times. Patient A was finally diagnosed as heat tolerant and patient B was diagnosed as heat intolerant. Conclusion Susceptibility to heat is a significant determinant for active young people such as athletes and soldiers. Both cases emphasize the importance of the heat tolerance test (and repeated test when needed) as a criteria for an exertional heat related injury patient to return to duty/play and to perform intense physical activities. These cases also emphasize the effectiveness and sensitivity of the test in identifying a temporary and a permanent state of heat intolerance.

Early-life exposure to environmental stressors can induce long-term physiological adaptations that extend across generations. This study examines embryonic heat conditioning (EHC) effects on heat stress resilience and paternal transgenerational inheritance in poultry. Fertilized male chicken eggs that underwent EHC (F 0 -EHC) were raised to maturity before breeding with naïve hens to generate F 1 offspring, which were reared under standard conditions. A heat challenge at day 10 post-hatch revealed that both F 0 -EHC chicks and their offspring (F 1 -EHC) exhibited significantly greater thermal resilience compared to controls, as reflected by a lower increase in body temperature. To explore molecular mechanisms underlying EHC we focused on microRNAs (miRs), analyzing CpG-DNA differentially methylated regions near miR genes in the preoptic anterior hypothalamus (PO/AH) of F 1 chicks and identified miR-210a as a key candidate. Both F 0 -EHC chicks and their offspring (F 1 -EHC) displayed increased miR-210a expression at baseline, which was significantly reduced during heat challenge. Intracranial injection of mature miR-210a into naïve chicks confirmed its regulatory role, inducing changes in gene expression in the PO/AH. RNA-Seq analysis identified 57 genes differentially expressed post-injection, including genes involved in chromatin organization, stress responses, and thermogenesis. Overlapping analyses of the RNA-Seq results with RRBS methylation data from F 0 sperm and F 1 PO/AH implicated ARID5B as a potential mediator of epigenetic inheritance to explore its function, we injected ARID5B sense and antisense oligonucleotides into the third ventricle of chicks and found that antisense treatment significantly increased ARID5B and miR-210a expression in the PO/AH without affecting body temperature. Together, these results reveal how embryonic thermal experience shapes hypothalamic gene regulation to promote transgenerational thermotolerance in chickens. Understanding this epigenetic mechanism may inform strategies to enhance resilience and sustainability in poultry exposed to thermal stress.