Short- and Long-Term Mortality of Hospitalized Patients With Autoimmune Rheumatic Diseases and Serious Infections: A National Cohort Study.

OBJECTIVE: Infectious conditions are a significant cause of mortality in autoimmune rheumatic diseases (ARD). Among patients hospitalized with an infection, we compared in-hospital and long-term (3-year) mortality between those with and without ARD. METHODS: This retrospective analysis included members of the largest health maintenance organization in Israel, aged > 18 years at the first episode of infection, who required hospitalization during 2003-2019. We compared in-hospital mortality and the results of a 3-year landmark analysis of those who survived the index hospitalization between patients with ARD, according to disease subgroups, and patients without ARD. Additionally, we compared mortality outcomes among patients with ARD, according to subgroup diagnosis, matched in a 1:3 ratio by age, sex, and ethnicity to patients without ARD. RESULTS: Included were 365,247 patients who were admitted for the first time with the diagnosis of a serious infection. Of these, we identified 9755 with rheumatoid arthritis (RA), 1351 with systemic lupus erythematosus, 2120 with spondyloarthritis (SpA), 584 with systemic sclerosis, and 3214 with vasculitis. In a matched multivariate analysis, the risk for in-hospital mortality was lower among patients with RA (odds ratio [OR] 0.89, 95% CI 0.81-0.97) and SpA (OR 0.77, 95% CI 0.63-0.94). In a similar analysis, the risk of 3-year mortality was lower among patients with RA (hazard ratio [HR] 0.82, 95% CI 0.78-0.86) and vasculitis (HR 0.86, 95% CI 0.80-0.93). CONCLUSION: Among patients hospitalized for an infection, the risk of in-hospital and 3-year mortality was not increased among those with ARD compared to those without ARD.

Fourth dose of BNT162b2 vaccine for patients with autoimmune rheumatic diseases in a nationwide setting.

OBJECTIVE: The effectiveness of COVID-19 vaccinations wanes due to immune evasion by the B.1.1.529 (Omicron) variant and diminished antibody titres over time. We aimed to evaluate the benefit of a fourth vaccination dose in patients with autoimmune rheumatic diseases (ARDs). METHODS: This retrospective analysis included ARD patients aged 18 years or older and members of Clalit Health Services in Israel (which at the time of the study insured 52% of the entire population), and covered the period from 16 January 2022 to 31 March 2022, when the predominant SARS-CoV-2 variant was Omicron. We compared patients without previous COVID-19 infection who had received three doses of the BNT162b2 vaccine (the control group) with those who had received the fourth dose. The primary outcome was COVID-19 infection, which was analysed using multivariate Cox regression in the entire cohort and within ARD subgroups. Secondary outcomes were COVID-19-related hospitalizations and COVID-19-related death. RESULTS: We included 43 748 ARD patients, of whom 27 766 and 15 982 were in the control and fourth vaccination groups, respectively. COVID-19 infection occurred in 6942 (25.0%) of the control group and 1754 (11.0%) of the fourth dose group (P < 0.001). Patients vaccinated with the fourth dose had a lower risk of COVID-19 infection than the entire cohort [Hazard Ratio (HR) 0.54, 95% CI 0.52, 0.58] and throughout every subgroup regardless of the baseline characteristic or medical treatment, except for rituximab. A similar association was observed for risk of COVID-19-related hospitalization (HR 0.36, 95% CI 0.22, 0.61) and of COVID-19-related death (HR 0.41, 95% CI 0.24, 0.71). CONCLUSION: A fourth BNT162b2 vaccination of ARD patients was associated with favourable outcomes compared with three doses among patients with no history of COVID-19 infection.

Perinatal outcomes and long-term infectious morbidity of offspring born to mothers with familial Mediterranean fever.

PURPOSE: To investigate perinatal outcomes and long-term infectious morbidity in children of mothers with familial Mediterranean fever (FMF). METHODS: A population-based cohort study comparing perinatal outcomes and long-term infectious morbidity of offspring of mothers with and without FMF was conducted. All singleton deliveries between the years 1991-2021 in a tertiary medical center were included. The study groups were followed until 18 years of age for long-term infectious morbidity. A Kaplan-Meier survival curve was used to compare the cumulative incidence of long-term infectious morbidity, and generalized estimation equation (GEE) models as well as Cox proportional hazards models were constructed to control for confounders. RESULTS: During the study period, 356,356 deliveries met the inclusion criteria. 411 of them were women with FMF. The mean follow-up period interval was 9.7 years (SD = 6.2) in both study groups. Using GEE models, preterm delivery, cesarean delivery, and low birth weight were independently associated with maternal FMF. The total infectious-related hospitalization rate was significantly higher in offspring born to mothers with FMF compared to the comparison group (Kaplan-Meier survival curve, log-rank p < 0.001). Using a Cox proportional hazards model, controlling for gestational age, maternal age, diabetes mellitus, cesarean delivery, and hypertensive disorders, being born to a mother with FMF was found to be an independent risk factor for long-term infection-related hospitalization of the offspring. CONCLUSION: Maternal FMF was found to be independently associated with long-term infection-related hospitalization of the offspring. This positive correlation may reflect an intra-uterine pro-inflammatory environment which may result in the offspring's long-term susceptibility to infection.

New-onset systemic lupus erythematosus following BNT162b2 mRNA COVID-19 vaccine: a case series and literature review.

Emerging data evaluated the possible link between the Coronavirus 19 (COVID-19) vaccine and acute flares of rheumatic autoimmune diseases. However, the association between the COVID-19 vaccine and the development of de-novo rheumatic autoimmune diseases remained unclear. We report the first case series of three male patients who developed new-onset systemic lupus erythematosus following receiving Pfizer BNT162b2 mRNA vaccination. The clinical characteristics share some similarities with drug-induced lupus. More patients with SLE following COVID-19 may be diagnosed in the future. Additional studies will provide more significant insights into the possible immunogenic influence of the COVID-19 vaccine.

[PREMEDICATION WITH CORTICOSTEROIDS PRIOR TO IV INFLIXIMAB - A COMPARISON BETWEEN INFLAMMATORY BOWEL DISEASE (IBD) AND RHEUMATIC PATIENTS].

INTRODUCTION: Infliximab is a protein with an anti TNF-α activity which is given in an intra-venous manner to treat inflammatory bowel disease and inflammatory joint disease. This treatment may cause infusion reaction events, but this may be prevented using treatment with pre-medication. OBJECTIVES: To assess the incidence of infusion reaction in patients with inflammatory bowel disease and patients with rheumatic disease who are treated with Infliximab, with or without corticosteroid premedication respectively. To determine whether premedication with corticosteroids decreases the incidence of infusion reactions. METHODS: We conducted a retrospective cohort study at the Soroka Medical Center that includes records from 92 patients treated with Infliximab: Group A includes 70 inflammatory joint disease patients who were not treated with hydrocortisone premedication and, group B includes 22 inflammatory bowel disease patients who were treated with hydrocortisone premedication. Incidence and severity of infusion reaction were assessed. RESULTS: The incidence of infusion reactions in the group which did not receive premedication was 26.1% (18/69), while in the group receiving premedication the incidence was 13.6% (3/22). Results are not statistically significant but reflect a trend. Most reactions occurred in the second treatment and most were of medium severity. CONCLUSIONS: The results seem to reflect a positive trend favoring the use of premedication with hydrocortisone before Infliximab infusion, especially given the minor side-effects of this treatment.

Clinical, Epidemiological, and Etiological Changes in Erythema Nodosum.

BACKGROUND: Erythema nodosum (EN) is the most common type of panniculitis, commonly secondary to infectious diseases. OBJECTIVES: To elucidate the causative factors and the clinical presentation of patients with EN (2004-2014) and to compare their data to those reported in a previous study. METHODS: A retrospective study was conducted of all patients diagnosed with EN who were hospitalized at Soroka University Medical Center (2004-2014). The clinical, demographic, and laboratory characteristics of the patients were compared to those in a cohort of patients diagnosed with EN from 1973-1982. RESULTS: The study comprised 45 patients with a diagnosis of EN. The most common symptoms of patients hospitalized with EN were arthritis or arthralgia (27% of patients). Patients with EN, compared to those reported in 1987, has significantly lower rates of fever (18% vs. 62% P < 0.001), streptococcal infection (16% vs. 44%, P = 0.003), and joint involvement (27% vs. 66%, P < 0.001). In addition, fewer patients had idiopathic causes of EN (9% vs. 32%, P = 0.006). CONCLUSIONS: In the past decades, clinical, epidemiological, and etiological changes have occurred in EN patients. The lowering in rate of fever, streptococcal infection, and joint involvement in patients with EN are probably explained by improvements in socioeconomic conditions. The significantly decreasing rate of idiopathic causes of EN is possibly due to the greater diagnostic accuracy of modern medicine. The results of the present study demonstrate the impact of improvements in socioeconomic conditions and access to healthcare on disease presentation.

[TREATMENT DILEMMAS IN BEHÇET'S SYNDROME].

Behçet's disease is an inflammatory systemic disorder, characterized by a relapsing and remitting course, it manifests with oral and genital ulcerations, skin lesions, uveitis, vasculitis, central nervous system and gastrointestinal involvement. The main histopathological finding is widespread vasculitis of the arteries and veins. Therapy is variable and depends largely on the severity of the disease and organ involvement. There is common practice to treat with anticoagulation in patients suffering from vessel thrombosis, but there are no control trials to support this tendency. Anticoagulation treatment can cause major bleeding events in patients suffering from aneurysms. In this case report we describe a treatment dilemma in a patient suffering from deep vein thrombosis and pulmonary aneurysms.

Athlete's heart in Israel: fact or fiction.

BACKGROUND: The effects of exercise training on cardiac structure and function have been thoroughly investigated in athletes from sport-developed nations; few data are available on sportsmen from sport-developing countries. OBJECTIVES: To assess the incidence and magnitude of the "athlete heart" phenomenon in an elite group of Israeli cyclists. METHODS: An echocardiography study was performed in 56 cyclists (49 males, mean age 38 +/- 10 years, weekly average training 13.1 +/- 5.9 hours); 96 sedentary subjects served as a control group. RESULTS: There were significant differences in left ventricular end-diastolic diameter (LVEDD) between cyclists and the control group (48 +/- 4.7 mm versus 45 +/- 4.1 mm respectively, P < 0.001), as well as in inter-ventricular septum (IVS) thickness (9.9 +/- 1.2 versus 8.9 +/- 1.2 mm, P < 0.001) and LV mass index (LVMI) (79 +/- 16 versus 68 +/- 13 g/m(2), P < 0.001). In 5% of the cyclists LVEDD exceeded the upper normal limit of 56 mm. In 7% of the cyclists IVS thickness exceeded the upper normal limit of 11 mm. LV hypertrophy defined as LVMI > or = 134 g/m(2) was absent in the entire cyclist group. CONCLUSIONS: Endurance sport activity in well-trained Israeli sportsmen results in a modest increment in LV dimensions and LV mass. LV dilatation and wall thickness above values compatible with primary cardiac disease are rare. These results highlight that in Israeli athletes any abnormal echocardiographic value must be thoroughly investigated and not simply assumed to be a consequence of sport activities.

[Differences in clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in Jewish and Bedouin patients].

BACKGROUND: The aim of this study was to compare clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in the Jewish and Bedouin populations. METHODS: A retrospective analysis was conducted of hospital admissions for diabetic ketoacidosis in adult patients between 2003 and 2010. The clinical and biochemical characteristics and outcomes of diabetic ketoacidosis patients of Jewish origin were compared with those of Bedouin origin. The primary outcome was in-hospital all-cause mortality. RESULTS: The study cohort included 220 consecutive patients for whom the admission diagnosis was diabetic ketoacidosis. The cohort was categorized according to Jewish and Bedouin origin as follows: 177 (80.5%) Jewish and 43 (19.5%) Bedouin patients. The Jewish patients were significantly older than the Bedouin patients (45.8 +/- 18.9 vs. 32.9 +/- 15.3, p < 0.001). The majority of the patients with diabetic ketoacidosis in both the Jewish and Bedouin groups had type 1 diabetes mellitus. No differences were found for in-hospital mortality, 30 days mortality or complication rates in groups of Jewish and Bedouin patients. The Length of hospital stay was significantly Longer in the Jewish compared to the Bedouin groups of patients (median 4 days (IQR 2; 6 days) vs. median 3 days (IQR 2; 4 days) respectively, p = 0.05). CONCLUSIONS: We did not find significant differences in the outcomes between Bedouin and Jewish patients with diabetic ketoacidosis. The Bedouin patients in the present study were younger compared to Jewish patients and the Length of the hospital stay was shorter in the Bedouin compared to the Jewish group. Advanced age, mechanical ventilation and bed-ridden state were independent predictors of 30-day mortality in both ethnic groups.

The effect of pre-match sexual intercourse on football players' performance: a prospective cross over study.

BACKGROUND: Current research suggests that pre-competition sexual intercourse does not influence athletes' performance. Yet, high quality studies in this field are scarce. METHODS: We aimed to investigate whether sexual activity negatively influences physiological performance. We conducted a prospective cross over study, which enrolled active players from the first team of a football club in the Israeli Football Premier League during the 2018-19 season. We gathered participants' physiological performance using GPS driven data per match. In addition, we assessed sexual activity the night before using telephone interviews at the end of every match. We used a linear mixed models methodology, accounting for each player as a cluster. RESULTS: We enrolled 14 participants who participated in 88 football matches. The mean age was 29.7 (±3.8) years and the majority were in permanent relationships for longer than 6 months (78.6%). We identified sexual intercourses the night before the match in 9 (10.2%) cases. The average speed during the match was slower when participants had pre-match intercourse (6.5 vs. 6.0 Km/h, P=0.02). The results remained consistent when using linear mixed models analysis adjusted for age, for previous belief that a pre-match sexual intercourse may affect match performance and for player as a cluster (P=0.02, 95% C.I -0.85- -0.07). Other parameters were not associated with pre-match intercourse. CONCLUSIONS: To the best of our knowledge, this study is the first to show that sexual intercourse the night before a football match may have a negative influence on players' performance.

SARS-CoV-2 infection among patients with autoimmune rheumatic diseases; comparison between the Delta and Omicron waves in Israel.

OBJECTIVE: The Omicron variant of the coronavirus SARS-CoV-2 (COVID-19) had milder clinical impacts than prior variants. This study aimed to describe the impact of COVID-19 on Autoimmune Rheumatic Disease (ARD) patients during the Delta and Omicron variants waves. METHODS: We used data from Clalit Health Services (CHS), the largest health service in Israel. ARD patients diagnosed with COVID-19 between July 1, 2021, to December 1, 2021, were included in the Delta group. Patients diagnosed between December 2, 2021, to March 31, 2022, were included in the Omicron group based on the predominance of COVID-19 in Israel. The study outcomes were COVID-19-related hospitalization or death. RESULTS: The final study cohort included 8443 actively treated ARD patients diagnosed with COVID-19. 1204 patients were positive during the predefined Delta variant period, and 7249 were positive during the predefined Omicron variant period). Compared to the Delta group, the Omicron group showed a lower rate of COVID-19-related hospitalization (3.9% vs. 1.3% for the Delta Vs. Omicron accordingly, p<0.001) and COVID-19-related death (3.2% vs. 1.1% for the Delta Vs. Omicron accordingly, p<0.001). After applying multivariable regression models, the Omicron group showed a lower risk for COVID-19-related hospitalization (Relative risk 0.4, 95% CI 0.27-0.59) and COVID-19-related mortality (RR 0.48, 95% CI 0.31-0.75). CONCLUSION: ARD patients infected with the COVID-19 Omicron variant had a lower risk of developing COVID-19-related adverse outcomes compared to the Delta variant.

Diabetic ketoacidosis: clinical characteristics, precipitating factors and outcomes of care.

BACKGROUND: Diabetic ketoacidosis (DKA) is a common and serious complication of diabetes mellitus (DM). OBJECTIVES: To evaluate the clinical characteristics, hospital management and outcomes of patients with DKA. METHODS: We performed a retrospective cohort study of patients hospitalized with DKA during the period 1 January 2003 to 1 January 2010. Three groups were compared: patients with mild DKA, with moderate DKA, and with severe DKA. The primary outcome was in-hospital all-cause mortality. The secondary outcomes were 30 days all-cause mortality, length of hospital stay, and complication rate. RESULTS: The study population comprised 220 patients with DKA. In the mild (78 patients) and moderate (116 patients) groups there was a higher proportion of patients with type 1 DM (75.6%, 79.3%) compared with 57.7% in the severe group (26 patients, P = 0.08). HbA1c levels prior to admission were high in all three groups, without significant difference (10.9 +/- 2.2, 10.7 +/- 1.9, and 10.6 +/- 2.4 respectively, P = 0.9). In all groups the most frequent precipitating factors were related to insulin therapy and infections. The patients with severe DKA had more electrolyte abnormalities (hypokalemia, hypomagnesemia, hypophosphatemia) compared with the mild and moderate forms of the disease. While 72.7% of the entire cohort was hospitalized in the general medical ward, 80.8% of those with severe DKA were admitted to the intensive care unit. The in-hospital mortality rate for the entire cohort was 4.1%, comparable with previous data from experienced centers. Advanced age, mechanical ventilation and bedridden state were independent predictors associated with 30 day mortality: hazard ratio (HR) 1.1, 95% confidence interval (CI) 1.02-1.11; HR 6.8, 95% CI 2.03-23.1; and HR 3.8, 95% CI 1.13-12.7, respectively. CONCLUSIONS: Patients with DKA in our study were generally poorly controlled prior to their admission, as reflected by high HbA1c levels. Type 2 DM is frequently associated with DKA including the severe form of the disease. The most common precipitating factors for the development of DKA were related to insulin therapy and infections. Advanced age, mechanical ventilation and bedridden state wer independent predictors of 30 day mortality.

The effect of exercise cessation on non-articular tenderness measures and quality of life in well-trained athletes.

BACKGROUND: The term chronic multi-symptom illness (CMI) refers to a spectrum of pain disorders, such as fibromyalgia and chronic fatigue syndrome, that are characterized by unexplained chronic pain, fatigue, and cognitive and mood complaints OBJECTIVES: To examine the hypothesis that exercise cessation is associated with symptoms similar to CMI in well-trained amateur athletes. METHODS: The study, conducted in running and triathlon clubs in Israel, involved 26 asymptomatic healthy athletes who regularly exercise 6.75 +/- 3.65 hours a week. All athletes were instructed to refrain from physical activity for 7 days. All underwent a complete physical exam, rheumatological assessment including non-articular tenderness threshold (using dolorimeter) and tender points. In addition they completed the SF-36 quality of life questionnaire. Assessments were conducted before exercise cessation and 7 days later. RESULTS: Seven days after sports deprivation all subjects were significantly more tender by all tender measures (P < 0.001) (dolorimeter thresholds and tender point count). There was also a significant reduction in the scores for physical role function (P < 0.001), emotional role function (P < 0.001) and summary subscales of the SF-36 questionnaire after exercise cessation. CONCLUSIONS: Exercise deprivation is associated with change in non-articular tenderness threshold and reduction in quality of life scores. This may be associated with the development of chronic multi-symptom illness.

[Toxic hepatitis due to the use of Ruta herbal medicine].

In recent years, the use of herbal medicine by the general population is increasing. There are many known side effects resulting from these treatments. Despite the known side effects, physicians tend to neglect the anamnesis details regarding this issue and research budgets of these drugs are relatively low compared with conventional medicine, thus causing a lack of updated information. In this case report, we present an example of toxic hepatitis due to use of Ruta herbal medicine, an unfamiliar side effect of the common herbal medicine Ruta.

A rare complication of infective endocarditis: left main coronary artery embolization resulting in sudden death.

Whilst systemic septic embolization is a common complication of infective endocarditis, a second, less frequently reported, complication is the embolization of vegetative material to the coronary arteries that rarely results in acute myocardial infarction and sudden death. The case is presented of an acute cardiac death in a patient with aortic valve endocarditis, caused by acute occlusion of the left main coronary artery with vegetative material.

[Sudden cardiac death in young athletes--causes, prevention and treatment].

The sudden death of a young athlete is a tragic event which affects teammates, the local community and the medical community. In this review the authors present the main causes of sudden cardiac death and compare between pre-participation medical evaluation recommendations in the United States, Europe and Israel. Finally, the authors present the new approaches of promoting the use of Automated External Defibrillators (AEDs).

Soccer heading and subclinical neuropsychiatric symptomatology in professional soccer players.

OBJECTIVES: To evaluate the association between postconcussive symptomatology and heading in professional soccer players, overcoming the bias of self-reported exposure, we evaluated several clinical neuropsychiatric symptoms using questionnaires after a thorough objective follow-up of players' heading exposure throughout an entire season. METHODS: We collected heading data for all Israeli Premier League players for an entire season using a web-based platform for performance analysis, which enabled us to quantify the exact number of headers per player. Players filled out questionnaires regarding postconcussion symptoms, depression, anxiety, and sleep disorders. We tested the association between the number of headers and each outcome using a negative binomial regression corrected for the hours played. RESULTS: A total of 159 players were included, of whom 79 were considered in the high heading exposure group (49%), defined as more than median number of headings (1.34 per game hour). Among players without any past head injury, those with higher heading exposure were less likely to have postconcussion symptoms compared with players with low heading exposure (relative risk [RR] per heading per hour 0.94, 95% confidence interval [CI] 0.912-0.963). Players with high heading exposure had fewer depression symptoms (RR 0.98, 95% CI 0.961-0.997), anxiety (RR 0.98, 95% CI 0.958-0.997), and sleep disorders (RR 0.98, 95% CI 0.961-0.996). CONCLUSION: Professional soccer players with high heading rate do not display higher postconcussive symptomatology severity. Symptoms among players with low heading exposure might be explained by low resilience, possibly associated with an inferior heading technique. Alternatively, it can reflect heading-avoidant behavior.