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.

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.

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.

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.

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.

Delirium in Internal Medicine Departments in a Tertiary Hospital in Israel: Occurrence, Detection Rates, Risk Factors, and Outcomes.

Background: The aim of the study was to assess the occurrence rate of delirium among elderly hospitalized patients in the medicine wards of a large tertiary hospital, to identify risk factors, and to evaluate the diagnostic rate for delirium among the medical teams. Methods: A 3-month prospective study of patients 65 years of age and above in three medicine wards: in two wards patients were examined by trained study team members using the Confusion Assessment Method (CAM), while the third was a control ward where CAM was not administered. The third ward served to control for the effect of the presence of investigators in the other wards as a potential confounding factor. Based on the results of this assessment patients were defined as suffering from subsyndromal delirium, full delirium (these two groups were later combined into an "any symptoms of delirium" group), and no delirium. The rate of diagnosis by the medical team was obtained from the electronic medical records. Results: The full delirium rate was 5.1%, the rate of subsyndromal delirium was 14.6%, and the rate of any symptoms of delirium was 19.6%. Absence of a partner, pain, anemia, hyponatremia, hypocalcemia, and the use of drugs with an anticholinergic burden were factors for any symptoms of delirium as well as for subsyndromal delirium. Subsyndromal delirium and any symptoms of delirium were associated with a reduced chance of being discharged to home and a higher 3-month mortality rate. A diagnosis of delirium was found in only 19.4% of the patients with any symptoms of delirium in the medical records. Conclusions: Delirium is a common problem among elderly hospitalized patients, but it is diagnosed sub-optimally by the medical team. There is a need for further training of the medical teams and implementation of delirium assessment as part of the ward's routine.

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.

Hyperuricemia and gout caused by missense mutation in d-lactate dehydrogenase.

Gout is caused by deposition of monosodium urate crystals in joints when plasma uric acid levels are chronically elevated beyond the saturation threshold, mostly due to renal underexcretion of uric acid. Although molecular pathways of this underexcretion have been elucidated, its etiology remains mostly unknown. We demonstrate that gout can be caused by a mutation in LDHD within the putative catalytic site of the encoded d-lactate dehydrogenase, resulting in augmented blood levels of d-lactate, a stereoisomer of l-lactate, which is normally present in human blood in miniscule amounts. Consequent excessive renal secretion of d-lactate in exchange for uric acid reabsorption culminated in hyperuricemia and gout. We showed that LDHD expression is enriched in tissues with a high metabolic rate and abundant mitochondria and that d-lactate dehydrogenase resides in the mitochondria of cells overexpressing the human LDHD gene. Notably, the p.R370W mutation had no effect on protein localization. In line with the human phenotype, injection of d-lactate into naive mice resulted in hyperuricemia. Thus, hyperuricemia and gout can result from the accumulation of metabolites whose renal excretion is coupled to uric acid reabsorption.

[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.

Pain sensitivity and athletic performance.

BACKGROUND: The objective of the study is to determine whether higher pain thresholds are associated with better performance in long-distance runners. METHODS: Seventy participants, divided into groups of fast and non-fast runners according to peak results in a 10km run. Main Outcome Measures, Cold pressor test. RESULTS: Of the 70 participants, 28 were in the fastest group (less than 39 minutes in a 10km run) and 42 in the non-fast group. The faster group was characterized with older age (34.0±8.5 vs. 29.5±5.7, P=0.01), greater mean weekly running time (5.5 [0-17]) vs. 2 [0-10], P<0.001), and more years of running (10 [1.5-34.0] vs. 7 [0-20, P=0.05]). In a multivariable analysis longer cold pressor time was associated with faster 10Km run (OR 1.01, 95% CI 1.00-1.01). CONCLUSIONS: It seems that higher pain thresholds play an important role in the superior ability of long distance runners.

Withholding Treatment From the Dying Patient: The Influence of Medical School on Students' Attitudes.

PURPOSE: To determine motives and attitudes towards life-sustaining treatments (LSTs) by clinical and preclinical medical students. METHODS: This was a scenario-based questionnaire that presented patients with a limited life expectancy. The survey was distributed among 455 medical students in preclinical and clinical years. Students were asked to rate their willingness to perform LSTs and rank the motives for doing so. The effect of medical education was then investigated after adjustment for age, gender, religion, religiosity, country of origin, and marital status. RESULTS: Preclinical students had a significantly higher willingness to perform LSTs in all cases. This was observed in all treatments offered in cases of a metastatic oncologic patient and an otherwise healthy man after a traumatic brain injury (TBI). In the case of an elderly woman on long-term care, preclinical students had higher willingness to supply vasopressors but not perform an intubation, feed with a nasogastric tube, or treat with a continuous positive air-pressure ventilator. Both preclinical and clinical students had high willingness to perform resuscitation on a twelve-year-old boy with a TBI. Differences in motivation factors were also seen. DISCUSSION: Preclinical students had a greater willingness to treat compared to clinical students in all cases and with most medical treatments offered. This is attributed mainly to changes along the medical curriculum. Changes in reasons for supplying LSTs were also documented.

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.

Ethical issues in medical cannabis use.

The increasing use of medical cannabis (MC) in the past decade raises several ethical considerations for the clinician. Regulatory issues stem from a gap between MC registration and certification in each country. Professional issues derive from the lack of sufficient knowledge of MC characteristics and the intersection between the physician, the patient and commercial interests. Finally, there are medical and psychological implications which are related to the use of MC regimens. We will discuss these issues in the light of the current era, in which policy has rapidly shifted toward legalization of cannabis, which influences the decisions of both clinicians and patients.

Effectiveness of Inferior Vena Cava Filters without Anticoagulation Therapy for Prophylaxis of Recurrent Pulmonary Embolism.

OBJECTIVE: The optimal treatment of deep vein thrombosis (DVT) is anticoagulation therapy. Inferior vena cava filter (IVC) placement is another option for the prevention of pulmonary embolism (PE) in patients with deep vein thrombosis. This is used mostly in patients with a contraindication to anticoagulant therapy. The purpose of the present study was to compare the two options. METHODS: A retrospective cohort study of two groups of patients with DVT: patients who received an IVC filter and did not receive anticoagulation due to contraindications; and patients with DVT and similar burden of comorbidity treated with anticoagulation without IVC insertion. To adjust for a potential misbalance in baseline characteristics between the two groups, we performed matching for age, gender, and Charlson's index, which is used to compute the burden of comorbid conditions. The primary outcome was an occurrence of a PE. RESULTS: We studied 1,742 patients hospitalized with the diagnosis of DVT in our hospital;93 patients from this population received IVC filters. Charlson's score index was significantly higher in the IVC filter group compared with the anticoagulation group. After matching of the groups of patients according to Charlson's score index there were no significant differences in primary outcomes. CONCLUSION: Inferior vena cava filter without anticoagulation may be an alternative option for prevention of PE in patients with contraindications to anticoagulant therapy.

Intermuscular adipose tissue and thigh muscle area dynamics during an 18-month randomized weight loss trial.

It remains unclear whether intermuscular adipose tissue (IMAT) has any metabolic influence or whether it is merely a marker of abnormalities, as well as what are the effects of specific lifestyle strategies for weight loss on the dynamics of both IMAT and thigh muscle area (TMA). We followed the trajectory of IMAT and TMA during 18-mo lifestyle intervention among 278 sedentary participants with abdominal obesity, using magnetic resonance imaging. We measured the resting metabolic rate (RMR) by an indirect calorimeter. Among 273 eligible participants (47.8 ± 9.3 yr of age), the mean IMAT was 9.6 ± 4.6 cm(2) Baseline IMAT levels were directly correlated with waist circumference, abdominal subdepots, C-reactive protein, and leptin and inversely correlated with baseline TMA and creatinine (P < 0.05 for all). After 18 mo (86.3% adherence), both IMAT (-1.6%) and TMA (-3.3%) significantly decreased (P < 0.01 vs. baseline). The changes in both IMAT and TMA were similar across the lifestyle intervention groups and directly corresponded with moderate weight loss (P < 0.001). IMAT change did not remain independently associated with decreased abdominal subdepots or improved cardiometabolic parameters after adjustments for age, sex, and 18-mo weight loss. In similar models, 18-mo TMA loss remained associated with decreased RMR, decreased activity, and with increased fasting glucose levels and IMAT (P < 0.05 for all). Unlike other fat depots, IMAT may not represent a unique or specific adipose tissue, instead largely reflecting body weight change per se. Moderate weight loss induced a significant decrease in thigh muscle area, suggesting the importance of resistance training to accompany weight loss programs.

[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.