A machine learning-based prediction model for gout in hyperuricemics: a nationwide cohort study.

OBJECTIVE: To develop a machine learning-based prediction model for identifying hyperuricemic participants at risk of developing gout. METHODS: A retrospective nationwide Israeli cohort study used the Clalit Health Insurance database of 473 124 individuals to identify adults 18 years or older with at least two serum urate measurements exceeding 6.8 mg/dl between January 2007 and December 2022. Patients with a prior gout diagnosis or on gout medications were excluded. Patients' demographic characteristics, community and hospital diagnoses, routine medication prescriptions and laboratory results were used to train a risk prediction model. A machine learning model, XGBoost, was developed to predict the risk of gout. Feature selection methods were used to identify relevant variables. The model's performance was evaluated using the receiver operating characteristic area under the curve (ROC AUC) and precision-recall AUC. The primary outcome was the diagnosis of gout among hyperuricemic patients. RESULTS: Among the 301 385 participants with hyperuricemia included in the analysis, 15 055 (5%) were diagnosed with gout. The XGBoost model had a ROC-AUC of 0.781 (95% CI 0.78-0.784) and precision-recall AUC of 0.208 (95% CI 0.195-0.22). The most significant variables associated with gout diagnosis were serum uric acid levels, age, hyperlipidemia, non-steroidal anti-inflammatory drugs and diuretic purchases. A compact model using only these five variables yielded a ROC-AUC of 0.714 (95% CI 0.706-0.723) and a negative predictive value (NPV) of 95%. CONCLUSIONS: The findings of this cohort study suggest that a machine learning-based prediction model had relatively good performance and high NPV for identifying hyperuricemic participants at risk of developing gout.

High prevalence of diffuse idiopathic skeletal hyperostosis (DISH) among obese young patients - A retrospective observational study.

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by ossification of ligaments and entheses, and most commonly affects the spinal column. The prevalence of DISH is increasing with age and is considered uncommon before the age of 50 years, with an estimated prevalence of less than 5 %. DISH is known to be highly associated with metabolic syndrome and obesity. We aim to assess the prevalence of DISH among young (≤50 yr.) patients suffering from severe obesity (BMI of 35 kg/m2 or higher). METHODS: A retrospective analysis assessing chest and spine radiographs (including Computed Tomography, CT) of patients with BMI≥35 visiting the bariatric ambulatory clinic in an academic medical center from 2013 to 2022. Patients included in the analysis were 31-50 years old. Diagnosis of DISH was made according to the Resnick criteria. The prevalence of DISH was calculated. Demographic, clinical and laboratory data were collected and compared between the DISH and non-DISH groups. RESULTS: 183 young (mean age: 40.4; 118 females, 64.2 %) obese (BMI median: 40.6; range 35-73) patients were included in the radiographic review. DISH was diagnosed in 33 patients (18.0 %; 95 % CI: 13.1-24.2 %) which was significantly higher than the expected 10 % (Z = 3.62, p<.001); another 8 patients (4.4 %; 95 % CI: 2.2-8.4 %) were considered as "near DISH" (not fulfilling yet the Resnick criteria) as it represents a pre-disease state. Patients diagnosed with DISH were significantly older than patients without DISH (t = 4.54, p<.001), as the prevalence of DISH increased by age (linear association=14.95, p<.001). There was a statistically significantly higher prevalence of hypertension (χ2 = 8.30, p<.004), smoking (χ2 = 4.69, p<.03) and OSA (χ2 = 6.16, p<.013) in the DISH group as compared to their non-DISH counterparts. CONCLUSION: The prevalence of DISH among obese young patients was 18 %, which is much higher than in the general population. Early-onset DISH should be regarded as a musculoskeletal obesity-related complication.

IgA vasculitis in adults, pediatrics and non-vasculitic IgA nephropathy, retrospective analysis from 2 centers.

Renal involvement represents the major long-term morbidity associated with IgA vasculitis (IgAV). Our aim was to evaluate clinical characteristics and long-term renal outcomes of IgAV in pediatrics and adults comparing to IgA nephropathy (IgAN). Our retrospective study included children and adults with IgAV and IgAN patients, admitted in a 13-year period (2007-2019) to rheumatology clinics and in hospital pediatric and internal medicine departments. We compared frequencies of clinical manifestations, laboratory findings, treatments, long-term outcomes at 1 year follow-up, including all-cause mortality and dialysis until the end of follow-up time. A total of 60 adult IgAV, 60 pediatric IgAV and 45 IgAN patients were evaluated. Adult IgAV patients were significantly older than IgAN patients (53.1 ±â€…17.4 years vs 45.1 ±â€…15.7 years respectively, P = .02) and had significantly higher rates of cardiovascular comorbidities. The risk and time to dialysis were similar among IgAN and adult IgAV groups. Yet, overall mortality at long term follow up was higher in IgAV adult group compared to IgAN. No dialysis or renal transplantation were reported in pediatric IgAV patients. IgAV and IgAN adult patients were comparable regarding risk of end stage renal disease. Of note, high mortality rates were observed among adult IgAV group.

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.

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.

A comparison of the power of breathing sounds signals acquired with a smart stethoscope from a cohort of COVID-19 patients at peak disease, and pre-discharge from the hospital.

Objectives: To characterize the frequencies of breathing sounds signals (BS) in COVID-19 patients at peak disease and pre-discharge from hospitalization using a Smart stethoscope. Methods: Prospective cohort study conducted during the first COVID-19 wave (April-August 2020) in Israel. COVID-19 patients (n = 19) were validated by SARS-Cov-2 PCR test. The healthy control group was composed of 153 volunteers who stated that they were healthy. Power of BS was calculated in the frequency ranges of 0-20, 0-200, and 0-2000 Hz. Results: The power calculated over frequency ranges 0-20, 20-200, and 200-2000 Hz contributed approximately 45%, 45%, and 10% to the total power calculated over the range 0-2000 Hz, respectively. Total power calculated from the right side of the back showed an increase of 45-80% during peak disease compared with the healthy controls (p < 0.05). The power calculated over the back, in the infrasound range, 0-20 Hz, and not in the 20-2000 Hz range, was greater for the healthy controls than for patients. Using all 3 ranges of frequencies for distinguishing peak disease from healthy controls resulted in sensitivity and specificity of 84% and 91%, respectively. Omitting the 0-20 Hz range resulted in sensitivity and specificity of 74% and 67%, respectively. Discussion: The BS power acquired from COVID-19 patients at peak disease was significantly greater than that at pre-discharge from the hospital. The infrasound range had a significant contribution to the total power. Although the source of the infrasound is not presently clear, it may serve as an automated diagnostic tool when more clinical experience is gained with this method.

BNT162b2 mRNA COVID-19 vaccine and booster in patients with autoimmune rheumatic diseases: a national cohort study.

INTRODUCTION: Emerging evidence supports the immunogenic response to mRNA COVID-19 vaccine in patients with autoimmune rheumatic diseases (ARD). However, large-scale data about the association between vaccination, and COVID-19 outcomes in patients with ARD is limited. METHODS: We used data from Clalit Health Services, which covers more than half of the population in Israel. Patients with ARD older than 18 were included between 20 December 2020 and 30 September 2021, when the BNT162b2 mRNA COVID-19 vaccine, and later a third booster dose, were available. The primary outcome was a documented positive SARS-CoV-2 PCR test. We used a Cox regression models with vaccination status as time-dependent covariate and calculated the HR for the study outcome. RESULTS: We included 127 928 patients with ARD, of whom, by the end of the study follow-up, there were 27 350 (21.3%) unvaccinated patients, 31 407 (24.5%) vaccinated patients and 69 171 (54.1%) patients who also received a third booster-dose. We identified 8470 (6.6%) patients with a positive SARS-CoV-2 PCR test during the study period. The HR for SARS-CoV-2 infection among the vaccination group was 0.143 (0.095 to 0.214, p<0.001), and among the booster group was 0.017 (0.009 to 0.035, p<0.001). Similar results were found regardless of the type of ARD group or antirheumatic therapy. CONCLUSION: Our results indicate that both the BNT162b2 mRNA COVID-19 vaccine and the booster are associated with better COVID-19 outcomes in patients with ARD.

Candida Bloodstream Infection, a Dire Complication in Hospitalized COVID-19 Patients: Three Cases from a Single Center in Northern Israel.

BACKGROUND: Patients with severe coronavirus disease-2019 (COVID-19) are susceptible to superimposed infections. OBJECTIVES: To describe COVID-19 patients who presented with complications due to Candida bloodstream co-infection (candidemia) and their outcome in a single center in northern Israel (Emek Medical Center) during the second outbreak of COVID-19 in Israel (15 June 2020 to 20 September 2020). METHODS: A retrospective study of COVID-19 patients presenting with candidemia was conducted, including clinical and laboratory data. The incidence of candidemia among hospitalized COVID-19 patients was compared to a historical cohort of non-COVID-19 controls. RESULTS: Three COVID-19 patients complicated with candidemia were documented. All three patients died shortly after the detection of candidemia. Three different Candida sp. were isolated from the blood cultures: C. albicans, C. parapsilosis, and C. glabrata. The incidence of candidemia among COVID-19 patients was 0.679 episodes per 1000 hospital days. CONCLUSIONS: Our small sample suggests a much higher incidence of candidemia among COVID-19 patients compared to a historical cohort of non-COVID-19 controls. All clinicians treating COVID-19 patients in GICU should be aware of this complication.

Diplopia from abducens nerve paresis as a presenting symptom of COVID-19: a case report and review of literature.

Neurological manifestations of novel coronavirus disease 3019 (COVID-19) remain unclear. We report the case of a 44-year-old febrile man who presented with double vision and headache 2 d after initial symptoms of fatigue, generalized muscle weakness, and loss of appetite. He was subsequently diagnosed with COVID-19 and transient abducens nerve paresis. He did not present with any respiratory symptoms or additional specific neurological findings. We recommend that with the rising number of cases across the world, physicians develop a greater index of suspicion for COVID-19 in patients with cranial neuropathies, even in those with mild disease without typical respiratory symptoms.

Severe hypercalcemia in a patient with chronic lymphocytic leukemia and non-small cell lung carcinoma: A case report.

RATIONALE: Hypercalcemia is a common finding in patients with advanced-stage cancers. Paraneoplastic hypercalcemia is commonly associated with dismal prognoses, with survival rates of about 3 months. In this paper, we report on a patient with advanced chronic lymphocytic leukemia and non-small cell lung carcinoma who developed severe hypercalcemia and discuss the diagnosis and treatment of this metabolic complication. PATIENT CONCERNS: A 56-year old male with a 2-year history of Rai stage IV chronic lymphocytic leukemia presented with life-threatening hypercalcemia. Positron emission tomography/computed tomography revealed a suspicious lung lesion. A transbronchial biopsy was performed from the upper left lobe. Due to the small size of the specimen, immunohistochemical markers were performed and revealed positive staining for cytokeratin 7 and negative for TTF-1, napsin A and p 40, which were consistent with non-small cell lung carcinoma. DIAGNOSIS: Humoral hypercalcemia of malignancy was diagnosed. INTERVENTION: The patient was treated with saline infusion, calcitonin, intravenous pamidronate, followed with denosumab. OUTCOMES: The hypercalcemia was successfully treated and the patient's calcium levels returned to normal. Further evaluation revealed a non-small cell lung carcinoma as a second primary malignancy. The patient was treated with venetoclax for his refractory CLL and received chemotherapy and immunotherapy for lung adenocarcinoma. Several days after starting venetoclax, he developed Legionella pneumonia and short time after the second course of chemotherapy, a severe sepsis occurred and he passed away. LESSONS: Coexistence of 2 unrelated malignancies, whichever could be a reason for hypercalcemia of malignancy is a rare event. Severe hypercalcemia, which is possible but rare feature of CLL should be a reason for further prompt evaluation.

The Hyper-Inflammatory Response in Adults with Severe COVID-19 Pneumonia Differs from the Cytokine Storm of Hemophagocytic Syndrome.

BACKGROUND: In this review we described the values of commonly available HScore laboratory markers in patients with coronavirus-19 (COVID-19)-pneumonia associated cytokine storm syndrome (CPN-CSS) and compared results with those of other forms cytokine storm syndrome (O-CSS) to determine a pattern for CPN-CSS. Twelve CPN-CSS studies and six O-CSS studies were included. CPN-CSS typically obtained a single HScore value (e.g., aspartate transaminase > 30 U/L) while failing all other HScore criteria. A typical pattern for CPN-CSS was revealed when compared to O-CSS: lymphopenia vs. pancytopenia and increased vs. decreased fibrinogen. Findings, other than HScore commonly found in CPN-CSS studies, showed elevated lactate dehydrogenase, D-dimer, and C-reactive protein. Although CPN-CSS studies describe severely ill patients, the HScore markers are typically less toxic that O-CSS.

Sodium glucose cotransporter2 inhibitor-possible treatment for patients with diabetes, pulmonary disease and CO2 retention.

Chronic pulmonary diseases such as chronic obstructive pulmonary disease, obstructive sleep apnea and obesity hypoventilation syndrome are common conditions which share decreased pulmonary ventilation and CO2 retention. CO2 is an end-product of metabolism of all body cells. When CO2 accumulates, it is recommended to consider measures to reduce its endogenous production. One such measure relates to the sources of energy ingested as nutrition. It is recommended to increase the intake of dietary lipids and reduce carbohydrates, as the former produces less endogenous CO2 when metabolized. Our hypothesis focuses on a different mechanism for reducing the availability of carbohydrates, especially glucose, as a fuel for body cells metabolism. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a new class of oral anti-hyperglycemic agents. Physiologically, glucose filtered through kidney glomeruli is reabsorbed in the proximal convoluted tubule; SGLT2i inhibit this mechanism. Therefore, glucose is secreted in the urine (glucosuria) and as a result glucose serum level is reduced. If glucose serum level is reduced, less glucose is available for metabolism, less CO2 is endogenously produced, and less CO2 must be expelled from the diseased lungs. It is hypothesized that these agents may be beneficial for patients with diabetes and concomitant pulmonary disease who retain CO2.

Beta-blockers in non-surgical patients with type A aortic dissection.

Type A aortic dissection (TAAD) is a catastrophic condition with 24-48% mortality during the first day, if patients are not surgically treated. Due to old age and associated co-morbidities surgeons may be reluctant to operate and patients are administered medical therapy for the end of reducing systolic blood pressure and heart rate. Beta-blockers (BB) are the "medications of choice". Based on physical and physiological considerations, it was hypothesized that BB may actually exacerbate TAAD.

Rare clinical manifestation of community-acquired pneumonia.

A 71-year-old patient was admitted due to fever and persistent (>48 hours) hiccups. History and physical examination were not instructive. Lab tests were not specific, showing an inflammatory response. Chest film did not demonstrate opacities. The patient was treated with chlorpromazine with no relief. Fever and hiccups persisted, and therefore neck and chest CT was performed revealing a right lower lobe infiltrate, a finding consistent with pneumonia. Antibiotics were initiated and within 48 hours fever and hiccups resolved and patient recovered. Although hiccups are rarely described as a clinical manifestation of community acquired pneumonia, one should consider this diagnosis in a patient with unexplained fever.