OBJECTIVES:SLE is strongly associated with LN, a major cause of chronic kidney disease (CKD). However, long-term renal and cardiovascular outcomes in patients with SLE who have preserved kidney function and do not develop LN remain poorly characterized. We sought to investigate the development of CKD among newly diagnosed patients with SLE who had preserved kidney function and no evidence of concomitant LN at baseline, compared with matched control individuals. METHODS:A national database study of newly diagnosed patients with SLE between 2015 and 2023. Patients with estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73 m2 at diagnosis were matched to non-SLE controls by age, sex and ethnicity. Patients with LN were excluded. The primary outcome was incident CKD, defined as eGFR ≤ 60 ml/min/1.73 m2 after diagnosis. Secondary outcomes included end-stage kidney disease (ESKD), major adverse cardiovascular events (MACE) and all-cause mortality. RESULTS:We identified 1145 patients with SLE and 91 681 matched controls, with a median follow-up of 5.77 years and similar baseline eGFR (103 vs 104 ml/min/1.73 m2). SLE was associated with a higher risk of CKD (5.2% vs 2.7%; HR 1.96, 95% CI 1.50-2.54), ESKD (HR 3.13, 95% CI 1.38-7.08), MACE (HR 1.63, 95% CI 1.31-2.04) and all-cause mortality (HR 4.52, 95% CI 3.71-5.50). Mean eGFR trajectories were similar between the groups. Diabetes (HR 1.51, 95% CI 1.39-1.64) and hypertension (HR 2.72, 95% CI 2.42-3.07) were the strongest risk factors for CKD and ESKD. CONCLUSION:Patients with SLE and preserved kidney function at diagnosis, without LN, are at increased risk of adverse renal outcomes, cardiovascular events and mortality, highlighting the importance of long-term monitoring and optimization of modifiable CKD risk factors.

Background: SARS-CoV-2 infection, its late complications, and SARS-CoV-2 vaccines are known to cause pericardial effusion. We sought to investigate the influence of the COVID-19 outbreak on trends in pericardiocentesis. Methods: We performed a retrospective population study including all >18 years patients undergoing pericardiocentesis in a single tertiary hospital between January 2018 and April 2022. The effusion characteristics and patient outcomes were compared between patients admitted before and after the COVID-19 outbreak. Results: 92 patients underwent pericardiocentesis cases during the COVID-19 period compared to 65 patients during the pre-COVID-19 period (χ2 = 3.07, p = 0.0796). Only 15% of the post-COVID-19 outbreak cases were related to COVID-19 infection or vaccine. In-hospital mortality was numerically higher during the post-COVID-19 group (7.7% vs. 14.4%), but this difference did not reach statistical significance (p = 0.22). The 90-day mortality was also similar between groups. Conclusions: A numerical, yet statistically insignificant increase in pericardiocentesis was observed following the COVID-19 outbreak. We assume this observation cannot be attributed solely to the virus and vaccines per se. Neglect of other chronic diseases, social distancing, and widespread availability of point-of-care ultrasound may have contributed to this observation.

Background/Objectives: Long-term outcomes in systemic lupus erythematosus (SLE) are largely driven by irreversible organ damage, yet the relative contribution of comorbid conditions remains insufficiently characterized. We aimed to characterize damage accrual and identify comorbidities associated with damage severity and mortality. Methods: A retrospective study of adult patients with SLE followed at a single-center (2014-2023). The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), was used to assess damage at last follow-up. Damage was categorized as none (0), mild-moderate (1-2), or severe (≥3). Demographic, clinical, laboratory, treatment, and comorbidity data were extracted from electronic medical records. Multivariable logistic regression and Cox proportional hazards models were applied to identify factors associated with damage severity and mortality. Results: Among 182 patients (84.1% female; mean follow-up 15.6 ± 11.4 years), 59.5% accrued damage, including 30.8% with severe damage. Damage predominantly involved cardiovascular, ocular, neuropsychiatric, and musculoskeletal domains. It was associated with older age, longer disease duration, hematologic and renal involvement, and corticosteroids and immunosuppressive medications. In multivariable analysis, antiphospholipid syndrome (APS) and hypertension emerged as the dominant independent predictors of damage accrual with an odds ratio of 15.70 (95% CI 4.26-57.89, p < 0.001) and 6.46 (95% CI 2.54-16.40, p < 0.001), respectively. Mortality increased with damage severity (16.1% in SDI ≥ 3, 1.9% in SDI 1-2, none in SDI = 0; p < 0.0001). Damage was also associated with increased hospitalizations. Conclusions: Damage accrual is common and strongly predicts mortality. APS and hypertension emerge as dominant, modifiable drivers, supporting integrated cardiovascular and thrombotic risk management in SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease that can involve the central nervous system (CNS), manifesting as a neuropsychiatric syndrome. Differentiating between neuropsychiatric systemic lupus erythematosus (NPSLE) and infections, such as West Nile encephalitis (WNE), as well as other etiologies, presents a significant diagnostic challenge and complicates the management of these patients. We present two cases of SLE patients with neuropsychiatric symptoms ultimately diagnosed as WNE and conducted a targeted literature review using bibliographic databases. We report two cases of SLE patients who presented with fever, cognitive decline, and rapid neurological deterioration. Both were considered to have NPSLE in the differential process, though later, they were found to have WNE after extensive and long diagnostic workups. Each case required subtle clinical management while awaiting confirmatory results. WNE can mimic CNS lupus, complicating the diagnosis and treatment. These cases emphasize the importance of considering infectious causes, especially in the face of the immunocompromised state of SLE patients, and balancing empirical treatments until definitive results are available. A literature review identified six additional cases of WNE in SLE patients. All cases involved diagnostic and management challenges similar to those in our cases, further underscoring the need to consider infectious etiologies in SLE patients presenting with neuropsychiatric symptoms.

OBJECTIVES:To evaluate the impact of SGLT2 inhibitors on the estimated glomerular filtration rate (eGFR) over time in patients with systemic lupus erythematosus (SLE). METHODS:This was a retrospective real-world analysis using the Clalit Health Services SLE registry (CHS-SLE registry), a national cohort of 4354 SLE patients. We conducted a two-step propensity-score matching analysis of SLE patients who initiated SGLT2 inhibitors between 2015 and 2022. The primary outcome was the eGFR at 24 months. We also assessed the event-free probability for SGLT2 inhibitor users versus non-users regarding a rapid decline in eGFR, ≥30 % eGFR decline, new-onset end-stage kidney disease (ESKD), and a composite of these outcomes at 24 months. Additionally, we performed subgroup analyses of eGFR changes stratified by baseline patient characteristics. RESULTS:At baseline, 260 SGLT2 inhibitor users were matched with 413 non-users. The baseline eGFR after matching was similar between the two groups (71.0 vs. 70.0 mL/min/1.73 m², p = 0.7). At 24 months, the eGFR was 71.2 mL/min/1.73 m² (95 % CI 69.1-74.9) in the SGLT2 inhibitor users and 65.4 mL/min/1.73 m² (95 % CI 62.5-68.4) in the non-user group (p < 0.001). The use of SGLT2 inhibitors was associated with a reduced risk of developing a rapid decline in eGFR (HR 0.74, 95 % CI 0.59-0.92, p = 0.01), and a reduced risk of developing the composite outcome (HR 0.72, 95 % CI 0.53-0.97, p = 0.03). CONCLUSIONS:In SLE patients, exposure to SGLT2 inhibitors was associated with improved kidney function and a reduced risk of developing adverse kidney outcomes.

BACKGROUND:Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are two distinct hyperglycemic emergencies with different pathophysiological and clinical profiles. While DKA is more common, HHS carries higher mortality rates. Although low-dose insulin protocols used for DKA are often applied, no optimal, evidence-based strategies specific to HHS have been established. OBJECTIVES:To examine clinical characteristics and the outcomes of HHS and DKA syndromes, and to characterize the factors contributing to a higher mortality rate in HHS. To contribute to the development of effective treatment strategies, with the goal of reducing HHS mortality in future research. METHODS:A retrospective analysis of admissions for HHS and DKA in adult patients between 2015 and 2021 in a large tertiary center. Clinical characteristics and outcomes of patients with HHS vs. DKA were compared. The primary outcome was in-hospital mortality. RESULTS:Total 608 patients were included in the study, 223 (37%) patients in the HHS group and 385 (63%) in the DKA group. Patients in the HHS group were older (77.4 vs. 43.6 years, p < 0.001), had more infection as a trigger (41.7% vs. 20.5%, p < 0.001) and more co-morbidities. In-hospital mortality rate was higher in the HHS group (41.2% vs. 4.7%, p < 0.001), however, matched multivariate analysis showed no significant differences for in-hospital mortality (OR 0.43, 95% CI 0.18-1.02). CONCLUSION:Metabolic abnormalities alone do not appear to explain the worse outcomes observed in HHS compared to DKA. Our findings indicate that baseline comorbidities, age and infection trigger have more significant impact on outcomes than the patients' metabolic status.

OBJECTIVE:The aim of this study was to compare differences in clinical response, drug survival, and adverse event rates between anakinra and canakinumab in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. METHODS:This multicenter international study includes patients with VEXAS from France, Israel, and Italy treated with interleukin-1 inhibition. Global response (GR) was defined as the absence of inflammatory symptoms and ≥50% decrease in steroid dose and C-reactive protein. Multiple regression analysis was performed to identify associated variables. Drug survival was analyzed using Kaplan-Meier plots and log-rank test, with Cox regression models for associated factors. RESULTS:We included 47 male patients with VEXAS; 44 received anakinra and 9 received canakinumab, with 6 patients using both at different time points. GR at 1 month was 34% for anakinra and 100% for canakinumab (P < 0.001) and 22% and 78% at 3 months, respectively (P = 0.001). Treatment with canakinumab was associated with a higher odds ratio (OR) of achieving GR at 3 months (OR 28.8, 95% confidence interval 3.0-273.9; P = 0.004) in a multivariable analysis. Median drug survival was 54 (interquartile range [IQR] 30-56) months for canakinumab at 300 mg/month compared with 7 (IQR 4-8) months for canakinumab 150 mg/month and 1 (IQR 1-2.5) months for anakinra (P = 0.01). Injection-site reactions were only recorded for the anakinra group (47 vs 0%; P = 0.006), whereas infections were more frequent in the anakinra group (31% and 11%; P = 0.3). CONCLUSION:Canakinumab demonstrated superior clinical response and drug survival with fewer adverse events compared with anakinra. Monthly canakinumab 300 mg may be considered as an effective steroid-sparing therapeutic option for patients with VEXAS.

Rheumatic paraneoplastic syndromes are rare and generally occur no longer than two years before diagnosis of the associated malignancy. Therefore, it can be an essential clue to occult malignancy. A healthy 18-year-old female with no underlying diseases was referred to the rheumatology clinic due to morning stiffness in her hands and a new rash on her fingers. Her labs showed a positive ANA, anti-double strand DNA antibody, anti-RNP, and anti-ribosomal P. Nine months after the diagnosis with SLE, the patient presented with elevated levels of lactate dehydrogenase. A total-body computed tomography scan revealed a solid mass in the pelvis. The pathological findings corresponded to a dysgerminoma tumor. Following surgical tumor removal and chemotherapy, the patient went into remission with both SLE and her oncology conditions, with no relapse of her lupus symptoms in a one-year follow-up. This case underscores the importance of considering malignancy in unexplained lupus symptoms, a crucial point for all physicians to be aware of. We identified 13 cases of paraneoplastic SLE in a literature review. In most cases, SLE is resolved after the tumor has been treated.

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.

Background: Diabetic ketoacidosis (DKA) is an acute metabolic, life-threatening complication of diabetes mellitus with a mortality rate that now stand at less than 1%. Although mortality is coupled with the etiology of DKA, literature on the influence of DKA etiology on patient outcome is scarce. Objectives: To study different triggers for DKA and their effect on outcomes. Methods: We conducted a retrospective study that include 385 DKA patients from 2004 to 2017. The study compared demographics, clinical presentation, and mortality rates by different precipitating factors. Results: Patients with DKA due to infections had a higher risk to develop in-hospital mortality after controlling for age and sex (odds ratio 4.40, 95% confidence interval 1.35-14.30), had a higher Charlson Comorbidity Index score, a higher risk of being mechanical ventilated (14% vs. 3%, P< 0.01), and a longer duration of hospitalization (5 days vs. 3 days, P < 0.001). Conclusions: It is crucial to find the triggers that precipitate DKA and start the treatment as early as possible in addition to the metabolic aspect of the treatment especially when the trigger is an infectious disease. IMAJ 2024; 26: 342-345

BACKGROUND:ARDS is a heterogeneous syndrome with distinct clinical phenotypes. Here we investigate whether the presence or absence of large pulmonary ultrasonographic consolidations can categorize COVID-19 ARDS patients requiring mechanical ventilation into distinct clinical phenotypes.METHODS:This is a retrospective study performed in a tertiary-level intensive care unit in Israel between April and September 2020. Data collected included lung ultrasound (LUS) findings, respiratory parameters, and treatment interventions. The primary outcome was a composite of three ARDS interventions: prone positioning, high PEEP, or a high dose of inhaled nitric oxide.RESULTS:A total of 128 LUS scans were conducted among 23 patients. The mean age was 65 and about two-thirds were males. 81 scans identified large consolidation and were classified as "C-type", and 47 scans showed multiple B-lines with no or small consolidation and were classified as "B-type". The presence of a "C-type" study had 2.5 times increased chance of receiving the composite primary outcome of advanced ARDS interventions despite similar SOFA scores, Pao2/FiO2 ratio, and markers of disease severity (OR = 2.49, %95CI 1.40-4.44).CONCLUSION:The presence of a "C-type" profile with LUS consolidation potentially represents a distinct COVID-19 ARDS subphenotype that is more likely to require aggressive ARDS interventions. Further studies are required to validate this phenotype in a larger cohort and determine causality, diagnostic, and treatment responses.

Background: The incidence of various types of vasculitis conditions over time, specifically during coronavirus disease 2019 (COVID-19), is unknown. Objectives: We aimed to assess recent trends in vasculitides and the effect of the COVID-19 pandemic on these trends. Design: We conducted a retrospective analysis of Israel’s largest Health Maintenance Organization, which covers over 4.7 million patients and represents 55% of the country. Methods: We calculated the age- and sex-adjusted incidence of giant cell arteritis (GCA), Takayasu, ANCA-associated vasculitis (AAV), IgA vasculitis, cryoglobulinemia, and Behcet’s disease (BD) during 2007–2021. We analyzed associations of COVID-19 with the incidence of each of the examined conditions. Results: During 2007–2021, the adjusted annual incidence decreased from 7.9 (95% confidence interval (CI) 3.5–17.9) to 1.5 (95% CI 0.7–3.6) per 100,000 for GCA, from 5.2 (95% CI 2.7–11.1) to 1.5 (95% CI 0.7–3.3) per million for IgA vasculitis, and from 6.3 (95% CI 3.0–13.5) to 1.0 (0.5–2.5) per 100,000 for BD. The relative risks for these conditions decreased: 0.92 (95% CI 0.91–0.93), 0.93 (95% CI 0.89–0.98), and 0.90 (95% CI 0.85–0.94), respectively. The incidences of Takayasu, AAV, and cryoglobulinemia remained unchanged. The COVID-19 pandemic was not associated with changes in the incidence of any examined vasculitides. Conclusion: The incidences of GCA, IgA vasculitis, and BD decreased substantially in Israel during 15 years and were unaffected by the COVID-19 pandemic. Future studies should focus on possible environmental contributions to these findings.

AIMS:To assess the clinical features and outcomes of patients diagnosed with DKA who were hospitalized for conditions outside of internal medicine. METHODS:Retrospective analysis of admissions for DKA in adult patients between 2005 and 2022 at a tertiary hospital in Israel. Patients with DKA were stratified into medical vs non-medical groups, the primary outcome was in-hospital mortality. RESULTS:429 patients were included in the study, 385 patients (89.7 %) were treated by an internal medicine team, while 44 patients (10.3 %) were hospitalized with surgical or obstetrical conditions. Patients in the non-internal medicine group were older (52 ± 18.9 vs 43.6 ± 20.4, p < 0.005) and had higher rates of diabetes complications such as chronic ischemic heart disease (20.5 % vs. 4.2 %, p < 0.0001) and chronic kidney disease (50 % vs. 3.4 %, p < 0.001). Glucose level on presentation was lower for non-internal medicine patients (398 ± 221 mg/dL vs 551 ± 180 mg/dL) and outcomes of mechanical ventilation and length of hospitalization were more severe (29.5 % vs. 6 %, p < 0.001 and 8.0 vs. 3.0, p < 0.001). Multivariate analysis demonstrated that composite outcome of in-hospital mortality, ICU admission and longer hospitalization was more likely in the non-internal medicine group (OR 3.99, CI 1.89-8.4, p < 0.001). CONCLUSION:DKA is a universal pathology that concerns various medical fields. It is essential for every clinician to be familiar with this condition. Patients diagnosed with DKA who were hospitalized for conditions outside of internal medicine may be at high risk and may present with lower glycemic levels. Future research is needed to characterize the unique features of subgroups of patients with DKA.

Vacuoles, E1 enzyme, X-linked, auto inflammatory, somatic (VEXAS) syndrome is an inflammatory disorder caused by somatic UBA1 variants and is characterized by late-onset systemic autoimmune inflammation and blood abnormalities. Glucocorticoids ameliorate symptoms effectively. However, other treatment options have limited efficacy and a transient effect. Herein, we describe a case of a 69-year-old male patient with VEXAS syndrome with skin, lung and hematologic involvement. He was treated with glucocorticoids and after the failure with anti IL-1 he began treatment with azacitidine with excellent hematological and clinical response. Azacitidine may be a suitable option for treating VEXAS syndrome, especially due to the relationship between inflammatory symptoms and response to azacitidine.

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.