Pediatric splenic infarction: Assessment of associated clinical conditions and outcome.

Pediatric splenic infarction (SI) is rare yet clinically significant. Publications regarding this complication are mostly limited to case reports. This is a retrospective study examining SI etiology, clinical presentation, management, and outcomes among children. Twenty-two patients (median age: 7.9 years) were included, mostly with pre-existing hematological diseases. Splenomegaly (72%), thrombocytopenia, and anemia were common. Most of the patients did not receive antithrombotic therapy yet only two patients experienced recurrences. During follow up 36% of patients died, however no fatalities were attributed to thrombotic or bleeding complications.

Excellent response to treatment with hydroxychloroquine in pediatric patients with SLE-related immune thrombocytopenia.

BACKGROUND: Pediatric immune thrombocytopenia (ITP) may precede systemic autoimmune disorders. In adolescent patients with ITP, routine screening for systemic lupus erythematosus (SLE) may be performed by testing for antinuclear antibody (ANA) titer. Hydroxychloroquine (HCQ) is a safe and effective immunomodulatory drug in patients with SLE but rarely used in ITP. We analyzed the platelet count response and safety of HCQ in treating pediatric patients with SLE-related ITP. METHODS: A retrospective study including pediatric patients with ITP and definite or incomplete SLE, who were treated with HCQ during 2010-2021. SLE was defined by ANA titer ≥ 1:160 as measured by immunofluorescence and ≥10 points according to the 2019 EULAR/ACR 2019 classification criteria, while patients with incomplete SLE achieved a score < 10. Complete response (CR) of the platelet count was defined as platelet count > 100 × 109/L; partial response (PR) as platelet count 30-100 × 109/L and exceeding ≥ twice baseline counts. RESULTS: Of the 17 patients included (median age 15.5 years; IQR 3.6), 15 (88.2%) were female, 13 had definite SLE, and four had incomplete SLE. HCQ was initiated at a median of 17 months after ITP diagnosis with a median platelet count of 38 × 109/L (IQR 28). At 8 weeks, 8 (47.1%) patients responded, including 6 (35.3%) achieving CR. After one year, the overall response was 82.4%, with the remaining patients having stable platelet counts requiring no additional ITP therapy. The response was maintained at a median follow-up of 42 months. No adverse effects to HCQ were noted. CONCLUSION: Pediatric patients with SLE-related ITP may benefit from treatment with HCQ.

Elevated International Normalized Ratio and Mortality in Hospitalized Patients Treated with Direct Oral Anticoagulants.

BACKGROUND: Direct oral anticoagulants (DOACs) are associated with a prolongation of the prothrombin time and an increased international normalized ratio (INR). The clinical significance of these changes is unclear. This study aimed to examine the association between an elevated INR on admission and in-hospital death and long-term survival in patients treated with DOACs. METHODS: Data were retrospectively retrieved from records of hospitalized patients at the Sheba Medical Center between November 2008 and July 2023. Patients were selected based on DOAC treatment, coagulation profile, and INR test done within 48 hours of hospitalization. The outcomes were in-hospital mortality and mortality in the year following hospitalization. RESULTS: The study included 11,399 hospitalized patients treated with DOACs. Patients with elevated INR had a 180% higher risk of in-hospital mortality (adjusted odds ratio 2.80; 95% confidence interval, 2.30-3.39) and a 57% increased risk of death during the following year (adjusted hazard ratio 1.57; 95% confidence interval, 1.44-1.71). Similar results were observed in subgroup analyses for each DOAC. CONCLUSIONS: An elevated INR on admission is associated with a higher risk for in-hospital death and increased risk for mortality during the first year following hospitalization in hospitalized patients treated with DOACs. This highlights that elevated INR levels in patients on DOACs should not be dismissed as laboratory variations due to DOAC treatment, as they may serve as a prognostic marker.

Management of surgery in persons with hemophilia A receiving emicizumab prophylaxis: data from a national hemophilia treatment center.

Background: Persons with hemophilia A may require surgical procedures. Real-world data on invasive procedures in persons with hemophilia A receiving emicizumab prophylaxis are limited. Objectives: To evaluate the safety of invasive procedures in persons with hemophilia A receiving emicizumab prophylaxis and their outcomes in a longitudinally followed cohort. Methods: Data from medical records of persons with hemophilia A with and without factor VIII (FVIII) inhibitors longitudinally followed at our tertiary center, who received emicizumab prophylaxis and underwent all types of invasive procedures, were retrieved. Outcomes of interest were bleeding and thrombotic complications. Results: Overall, 35 patients underwent 56 invasive procedures, 18 (32.1%) were major. The median age was 36.3 years (IQR, 8.8-55.9 years); 12 patients (34.3%) were younger than 18 years at the time of procedure; 17 (48.6%) were patients with FVIII inhibitors. Among major procedures, orthopedic surgeries prevailed. All patients who underwent major procedures received factor replacement with either recombinant activated factor VII (patients with inhibitors) or FVIII (patients without inhibitors). Factor concentrates were administered prior to 32 (84.2%) of the minor procedures. Repeated doses were given according to international expert opinion recommendations and patients' condition.There were 7 bleeding events in 6 patients, 5 were major bleeds, including 1 patient who underwent a minor procedure without factor replacement. None of the patients experienced a thrombotic complication. Conclusion: Invasive procedures can be performed safely in patients receiving emicizumab prophylaxis with close surveillance after surgery. Factor concentrates may be advised in selected patients undergoing minor procedures.

Fluctuations in Serum Creatinine Levels During Hospitalization and Long-Term End-Stage Kidney Disease and Mortality.

Importance: Acute kidney injury is associated with poor outcomes, but the clinical implication of reversible serum creatinine level fluctuations during hospitalization not necessarily defined as acute kidney injury is poorly understood. Objective: To investigate the long-term outcomes of patients without previously diagnosed kidney disease who present with decreased kidney function and are subsequently discharged with apparently normal kidney function. Design, Setting, and Participants: A retrospective cohort study was conducted of patients hospitalized in a large tertiary hospital in Israel between September 1, 2007, and July 31, 2022. The study included patients admitted to an internal medicine ward. Patients had not undergone dialysis during the index hospitalization, had at least 3 creatinine tests performed during hospitalization, and had a discharge estimated glomerular filtration rate (eGFR) exceeding 60 mL/min/1.73 m2. Patients with preexisting chronic kidney disease were excluded. Exposure: Glomerular filtration rate was estimated from serum creatinine values using the updated 2022 Chronic Kidney Disease Epidemiology Collaboration formula, and eGFR greater than 60 mL/min/1.73 m2 was regarded as normal. Exposure was defined based on the association between the first and last values determined during hospitalization. Main Outcomes and Measures: All-cause mortality in the year following the index hospitalization and end-stage kidney disease (ESKD) in the 10 years following the index hospitalization. Results: A total of 40 558 patients were included. Median age was 69 (IQR, 56-80) years, with 18 004 women (44%) and 22 554 men (56%). A total of 34 332 patients (85%) were admitted with a normal eGFR and 6226 (15%) with decreased eGFR. Patients with decreased eGFR on presentation had an 18% increased mortality in the year following hospitalization (adjusted hazard ratio [AHR], 1.18; 95% CI, 1.11-1.24) and a 267% increased risk of ESKD in the 10 years following hospitalization (AHR, 3.67; 95% CI, 2.43-5.54), despite having been discharged with apparently normal kidney function. The highest risk was noted in patients who presented to the hospital with an eGFR of 0 to 45 mL/min/1.73 m2. Conclusions and Relevance: The findings of this cohort study suggest that patients who present with decreased kidney function and are discharged without clinically evident residual kidney disease may be at increased long-term risk for ESKD and mortality.

Anticoagulant treatment for pediatric splanchnic vein thrombosis: a systematic review and meta-analysis.

BACKGROUND: The clinical characteristics of splanchnic vein thrombosis (SVT) in pediatric patients and its optimal treatment strategies are unknown. OBJECTIVES: This study aimed to assess the effectiveness and safety of anticoagulant therapy for pediatric SVT. METHODS: MEDLINE and EMBASE databases were searched up to December 2021. We included observational and interventional studies that enrolled pediatric patients with SVT and reported anticoagulant treatment and outcomes, including rates of vessel recanalization, SVT extension, venous thromboembolism (VTE) recurrence, major bleeding, and mortality. Pooled proportions of vessel recanalization were calculated with their 95% CI. RESULTS: A total of 506 pediatric patients (aged 0-18 years) across 17 observational studies were included. The majority of patients had portal vein thrombosis (n = 308, 60.8%) or Budd-Chiari syndrome (n = 175, 34.6%). Most events were triggered by transient provoking factors. Anticoagulation (heparins and vitamin K antagonists) was prescribed in 217 (42.9%) patients, and 148 (29.2%) patients underwent vascular interventions. The overall pooled proportions of vessel recanalization were 55.3% (95% CI, 34.1%-74.7%; I2 = 74.0%) among anticoagulated patients and 29.4% (95% CI, 2.6%-86.6%; I2 = 49.0%) among non-anticoagulated patients. SVT extension, major bleeding, VTE recurrence, and mortality rates were 8.9%, 3.8%, 3.5%, and 10.0%, respectively, in anticoagulated patients and 2.8%, 1.4%, 0%, and 50.3%, respectively, in non-anticoagulated patients. CONCLUSION: In pediatric SVT, anticoagulation appears to be associated with moderate recanalization rates and a low risk of major bleeding. VTE recurrence is low and comparable to that reported in pediatric patients with other types of provoked VTE.

Deep learning for embryo evaluation using time-lapse: a systematic review of diagnostic test accuracy.

OBJECTIVE: This study aimed to investigate the accuracy of convolutional neural network models in the assessment of embryos using time-lapse monitoring. DATA SOURCES: A systematic search was conducted in PubMed and Web of Science databases from January 2016 to December 2022. The search strategy was carried out by using key words and MeSH (Medical Subject Headings) terms. STUDY ELIGIBILITY CRITERIA: Studies were included if they reported the accuracy of convolutional neural network models for embryo evaluation using time-lapse monitoring. The review was registered with PROSPERO (International Prospective Register of Systematic Reviews; identification number CRD42021275916). METHODS: Two reviewer authors independently screened results using the Covidence systematic review software. The full-text articles were reviewed when studies met the inclusion criteria or in any uncertainty. Nonconsensus was resolved by a third reviewer. Risk of bias and applicability were evaluated using the QUADAS-2 tool and the modified Joanna Briggs Institute or JBI checklist. RESULTS: Following a systematic search of the literature, 22 studies were identified as eligible for inclusion. All studies were retrospective. A total of 522,516 images of 222,998 embryos were analyzed. Three main outcomes were evaluated: successful in vitro fertilization, blastocyst stage classification, and blastocyst quality. Most studies reported >80% accuracy, and embryologists were outperformed in some. Ten studies had a high risk of bias, mostly because of patient bias. CONCLUSION: The application of artificial intelligence in time-lapse monitoring has the potential to provide more efficient, accurate, and objective embryo evaluation. Models that examined blastocyst stage classification showed the best predictions. Models that predicted live birth had a low risk of bias, used the largest databases, and had external validation, which heightens their relevance to clinical application. Our systematic review is limited by the high heterogeneity among the included studies. Researchers should share databases and standardize reporting.

Association between Thrombin Generation and Clinical Characteristics in COVID-19 Patients.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) disease is associated with coagulopathy and an increased risk of thrombosis. An association between thrombin generation (TG) capacity, disease severity, and outcomes has not been well described. METHODS: We assessed the correlation of TG with sequential organ failure assessment (SOFA) and sepsis-induced coagulopathy (SIC) scores and clinical outcomes by analysis of plasma samples obtained from hospitalized COVID-19 patients. RESULTS: 32 patients (68.8% male), whose median age was 69 years, were assessed, of whom only 3 patients did not receive anticoagulant therapy. D-dimers were uniformly increased. During hospitalization, 2 patients suffered thrombosis, 3 experienced bleeding, and 12 died. TG parameters from anticoagulated COVID-19 patients did not significantly differ from the values obtained from non-anticoagulated healthy controls. Patients who received higher than prophylactic doses of anticoagulant therapy had increased lag time (p = 0.003), lower endogenous thrombin potential (ETP) (p = 0.037), and a reduced peak height (p = 0.006). ETP correlated with the SIC score (p = 0.038). None of the TG parameters correlated with the SOFA score or were associated with mortality. CONCLUSION: TG was not associated with disease severity among patients hospitalized with COVID-19. However, a correlation between ETP and the SIC score was noted and deserves attention.

Efficacy and Safety of Third Dose of the COVID-19 Vaccine among Solid Organ Transplant Recipients: A Systemic Review and Meta-Analysis.

Solid organ transplant recipients were demonstrated to have reduced antibody response to the first and second doses of the COVID-19 mRNA vaccine. This review evaluated published data on the efficacy and safety of the third dose among solid organ transplant recipients. We performed a systematic search of PubMed, EMBASE, and Web of Science to retrieve studies evaluating the efficacy of the third dose of anti-SARS-CoV-2 vaccines in adult solid organ transplant recipients. Serologic response after the third vaccine was pooled using inverse variance and generalized linear mixed and random-effects models. Seven studies met our inclusion criteria. A total of 853 patients received the third dose. Except for one randomized controlled trial, all studies were retrospective in design. Following the third COVID-19 vaccine dose, antibody response occurred in 6.4-69.2% of patients. The pooled proportion of antibody response rate after the third vaccine was 50.3% (95% confidence interval (CI): 37.1-63.5, I2 = 90%). Five papers reported the safety profile. No severe adverse events were observed after the third vaccine dose. In conclusion, a third dose of the SARS-CoV-2 mRNA vaccine in solid organ transplant recipients is associated with improved immunogenicity and appears to be safe. Nevertheless, a significant portion of patients remain seronegative.

Obesity as a mortality risk factor in the medical ward: a case control study.

BACKGROUND: Research regarding the association between severe obesity and in-hospital mortality is inconsistent. We evaluated the impact of body mass index (BMI) levels on mortality in the medical wards. The analysis was performed separately before and during the COVID-19 pandemic. METHODS: We retrospectively retrieved data of adult patients admitted to the medical wards at the Mount Sinai Health System in New York City. The study was conducted between January 1, 2011, to March 23, 2021. Patients were divided into two sub-cohorts: pre-COVID-19 and during-COVID-19. Patients were then clustered into groups based on BMI ranges. A multivariate logistic regression analysis compared the mortality rate among the BMI groups, before and during the pandemic. RESULTS: Overall, 179,288 patients were admitted to the medical wards and had a recorded BMI measurement. 149,098 were admitted before the COVID-19 pandemic and 30,190 during the pandemic. Pre-pandemic, multivariate analysis showed a "J curve" between BMI and mortality. Severe obesity (BMI > 40) had an aOR of 0.8 (95% CI:0.7-1.0, p = 0.018) compared to the normal BMI group. In contrast, during the pandemic, the analysis showed a "U curve" between BMI and mortality. Severe obesity had an aOR of 1.7 (95% CI:1.3-2.4, p < 0.001) compared to the normal BMI group. CONCLUSIONS: Medical ward patients with severe obesity have a lower risk for mortality compared to patients with normal BMI. However, this does not apply during COVID-19, where obesity was a leading risk factor for mortality in the medical wards. It is important for the internal medicine physician to understand the intricacies of the association between obesity and medical ward mortality.

Differences in obstetric healthcare utilization and delivery complications before and after the COVID-19 pandemic - a retrospective study.

PURPOSE: To investigate the effect of the COVID-19 pandemic on healthcare utilization related to labor and delivery and to assess the effect of the COVID-19 pandemic on intra-partum and delivery complications. METHODS: This retrospective study was performed at a university-affiliated, tertiary medical center. It included women admitted to the delivery room from 1 March 2020 to 23 July 2020 during the first wave of the COVID-19 pandemic. They were compared against women who were admitted to the delivery room during the same time period in 2019. The outcomes of 2701 deliveries during the pre-pandemic period were compared to those of 2668 deliveries during the pandemic period. Main outcomes were pregnancy and delivery outcomes. RESULTS: The mean number of emergency department visits before admission for delivery was higher in the pre-pandemic period than in the pandemic period (2.3 ± 1.5 and 2.1 ± 1.3 visits, respectively; p < .01). There were no significant differences in other intra- and postpartum complications. The incidence of a prolonged third stage of labor was higher in the pre-pandemic than in the pandemic period (225 (10%) and 182 (8.1%), respectively; p = .03). The mean duration of post-partum maternal hospitalization was longer in the pre-pandemic than in the pandemic period (3.6 ± 0.9 and 3.4 ± 1.0 days, respectively; p < .01). Neonatal outcomes were comparable for Apgar scores, birth weight, and newborn intensive care unit admission for both periods; however, the mean duration of neonatal hospitalization was longer in the pre-pandemic than in the pandemic period (3.5 ± 3.2 and 3.2 ± 1.1 days, respectively; p < .01). CONCLUSIONS: In our study population, in the presence of public and accessible obstetric medicine, the first wave of the COVID-19 pandemic did not affect pregnancy or early delivery outcomes.

The Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Patients Hospitalized with Acute Pulmonary Embolism.

Early risk stratification is essential for determining the appropriate therapeutic management approach of pulmonary embolism (PE). This study aimed to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients hospitalized with acute pulmonary embolism by investigating its association with mortality in a large-scale population diagnosed and hospitalized with acute PE. We retrieved all consecutive patients hospitalized in an internal medicine department or an intensive care unit in a tertiary medical center from December 2007 to April 2021 with a discharge diagnosis of pulmonary embolism. A total of 2072 patients were included. Patients with above-median NLR (i.e., 5.12) had a higher 30-day mortality risk (adjusted odds ratio (aOR), 2.82; 95% confidence interval (CI) 2.14-3.70) and higher one-year mortality risk (aOR, 2.51; 95% CI 2.04-3.08). Similar trends were demonstrated in a sub-analysis of patients without cancer and hemodynamically stable (i.e., systolic blood pressure over 90 mmHg). Furthermore, the median hospital length of stay in patients with an elevated NLR was higher, and so was the in-hospital mortality rate. Elevated NLR in acute PE is associated with a worse short-term and long-term prognosis and with a longer duration of hospitalization.

The association between obesity and peak antibody titer response in COVID-19 infection.

OBJECTIVE: Obesity is associated with severe coronavirus disease 2019 (COVID-19) infection. Disease severity is associated with a higher COVID-19 antibody titer. The COVID-19 antibody titer response of patients with obesity versus patients without obesity was compared. METHODS: The data of individuals tested for COVID-19 serology at the Mount Sinai Health System in New York City between March 1, 2020, and December 14, 2021, were retrospectively retrieved. The primary outcome was peak antibody titer, assessed as a binary variable (1:2,880, which was the highest detected titer, versus lower than 1:2,880). In patients with a positive serology test, peak titer rates were compared between BMI groups (<18.5, 18.5 to 25, 25 to 30, 30 to 40, and ≥40 kg/m2 ). A multivariable logistic regression model was used to analyze the independent association between different BMI groups and peak titer. RESULTS: Overall, 39,342 individuals underwent serology testing and had BMI measurements. A positive serology test was present in 12,314 patients. Peak titer rates were associated with obesity (BMI < 18.5 [34.5%], 18.5 to 25 [29.2%], 25 to 30 [37.7%], 30 to 40 [44.7%], ≥40 [52.0%]; p < 0.001). In a multivariable analysis, severe obesity had the highest adjusted odds ratio for peak titer (95% CI: 2.1-3.0). CONCLUSION: COVID-19 neutralizing antibody titer is associated with obesity. This has implications on the understanding of the role of obesity in COVID-19 severity.

Folate Levels in Patients Hospitalized with Coronavirus Disease 2019.

We aimed to investigate the prevalence of decreased folate levels in patients hospitalized with Coronavirus Disease 2019 (COVID-19) and evaluate their outcome and the prognostic signifi-cance associated with its different levels. In this retrospective cohort study, data were obtained from the electronic medical records at the Sheba Medical Center. Folic acid levels were available in 333 out of 1020 consecutive patients diagnosed with COVID-19 infection hospitalized from January 2020 to November 2020. Thirty-eight (11.4%) of the 333 patients comprising the present study population had low folate levels. No significant difference was found in the incidence of acute kidney injury, hypoxemia, invasive ventilation, length of hospital stay, and mortality be-tween patients with decreased and normal-range folate levels. When sub-dividing the study population according to quartiles of folate levels, similar findings were observed. In conclusion, decreased serum folate levels are common among hospitalized patients with COVID-19, but there was no association between serum folate levels and clinical outcomes. Due to the important role of folate in cell metabolism and the potential pathologic impact when deficient, a follow-up of folate levels or possible supplementation should be encouraged in hospitalized COVID-19 patients. Fur-ther studies are required to assess the prevalence and consequences of folate deficiency in COVID-19 patients.

Myocardial injury in hospitalized patients with COVID-19 infection-Risk factors and outcomes.

Myocardial injury in hospitalized patients is associated with poor prognosis. This study aimed to evaluate risk factors for myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) and its prognostic value. We retrieved all consecutive patients who were hospitalized in internal medicine departments in a tertiary medical center from February 9th, 2020 to August 28th with a diagnosis of COVID-19. A total of 559 adult patients were hospitalized in the Sheba Medical Center with a diagnosis of COVID-19, 320 (57.24%) of whom were tested for troponin levels within 24-hours of admission, and 91 (28.44%) had elevated levels. Predictors for elevated troponin levels were age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.06), female sex (OR, 3.03; 95% CI 1.54-6.25), low systolic blood pressure (OR, 5.91; 95% CI 2.42-14.44) and increased creatinine level (OR, 2.88; 95% CI 1.44-5.73). The risk for death (hazard ratio [HR] 4.32, 95% CI 2.08-8.99) and a composite outcome of invasive ventilation support and death (HR 1.96, 95% CI 1.15-3.37) was significantly higher among patients who had elevated troponin levels. In conclusion, in hospitalized patients with COVID-19, elevated troponin levels are associated with poor prognosis. Hence, troponin levels may be used as an additional tool for risk stratification and a decision guide in patients hospitalized with COVID-19.

Risk factors and mortality in patients with pneumonia and elevated troponin levels.

Pneumonia in hospitalized patients is associated with myocardial injury. In this study, we evaluated risk factors for myocardial injury in hospitalized patients with pneumonia and its prognostic value. We retrieved all patients who were hospitalized in internal medicine departments in a tertiary medical center between 2008 and 2019 with a diagnosis of pneumonia. From 2008 to 2019 a total of 20,683 adult patients were hospitalized in internal medicine wards in the Sheba Medical Center with a diagnosis of pneumonia, 8195 were tested for troponin levels, and 3207 had elevated levels. Risk factors for elevated troponin levels were age, prior diagnosis of ischemic heart disease, and elevated creatinine level upon admission. The in-hospital mortality and 1-year mortality rate were higher among patients who had elevated troponin levels when using a propensity score-based matched analysis. In conclusion, in hospitalized patients with pneumonia elevated troponin levels have a major impact on prognosis. Hence, troponin levels may be used as another tool of risk stratification for patients hospitalized with pneumonia.

Clinical and public health management of conjunctivitis in the Israel Defense Forces.

Acute conjunctivitis is a common diagnosis in the general population, and is especially prevalent among military personnel. Conjunctivitis patients are often contagious, and outbreaks of this infectious condition can cause significant morbidity and may jeopardize military readiness. Early recognition and effective management can prevent additional cases in military units. In this article we review the clinical guidelines and public health policy of the Israel Defense Forces for the management of this important medical condition.