Suicides in National Hormone Pituitary Program Recipients of Cadaver-Derived Human Growth Hormone.

Context: Numerous reports of suicide among individuals who received cadaver-derived human growth hormone (c-hGH) through the National Hormone Pituitary Program (NHPP) raised the alarm for potentially increased suicide risk. Objective: We conducted a study to assess suicide risk in the NHPP cohort and identify contributing factors to facilitate early recognition and intervention. Methods: The study population consisted of patients receiving NHPP c-hGH starting from 1957, and cohort deaths with an ICD code consistent with suicide or possible suicide through 2020 were evaluated. Descriptive data were extracted from medical records. Standardized mortality ratios (SMRs) to compare the observed number of suicide deaths in the cohort to the expected number were calculated using general population suicide rates by sex, age group, and time period. Results: Among 6272 patients there were 1200 all-cause cohort deaths, of which 55 (52 male, 3 female) were attributed to suicide. Of these, 47 were identified by ICD code alone compared to an expected count of 37.8 (SMR = 1.25, 95% CI 0.91-1.66). Among male cohort members, the SMR was 1.33 (95% CI 0.97-1.78). Elevated risk of suicide was detected for cohort members aged 25-34 (SMR = 1.79, 95% CI 1.06-2.83) and during the period from September 19, 1985, to December 31, 1998 (SMR = 1.70, 95% CI 1.02-2.65). Conclusion: Overall, the observed number of suicides among NHPP c-hGH recipients was not significantly higher than expected. However, certain subgroups may be at elevated risk of suicide. Studies are needed to better understand the nature and magnitude of suicide risk among c-hGH recipients to facilitate early intervention to prevent suicide deaths.

Treatments and Severe Outcomes for Patients Diagnosed With MIS-C at Four Children's Hospitals in the United States, March 16, 2020-March 10, 2021.

BACKGROUND: Clinical management of multisystem inflammatory syndrome in children (MIS-C) has varied over time and by medical institution. METHODS: Data on patients with MIS-C were collected from 4 children's hospitals between March 16, 2020 and March 10, 2021. Relationships between MIS-C treatments and patient demographics, clinical characteristics, and outcomes were described. Propensity score matching was utilized to assess the relative risk of outcomes dependent on early treatment with intravenous immunoglobulin (IVIG) or low-dose steroids, controlling for potential confounding variables. RESULTS: Of 233 patients diagnosed with MIS-C, the most commonly administered treatments were steroids (88.4%), aspirin (81.1%), IVIG (77.7%) and anticoagulants (71.2%). Compared with those patients without respiratory features, patients with respiratory features were less likely to receive IVIG and steroids on the same day (combination treatment) (44.1%). Controlling for confounding variables, patients receiving IVIG within 1 day of hospitalization were less likely to have hospital length of stay ≥8 days (RR = 0.53, 95% CI: 0.31-0.88). Patients receiving low-dose steroids within 1 day of hospitalization were less likely to develop ventricular dysfunction (RR = 0.45, 95% CI: 0.26-0.77), have increasingly elevated troponin levels (RR = 0.55, 95% CI: 0.40-0.75) or have hospital length of stay ≥8 days (RR = 0.46, 95% CI: 0.29-0.74). CONCLUSION: Treatments for MIS-C differed by hospital, patient characteristics and illness severity. When IVIG and low-dose steroids were administered in combination or low-dose steroids were administered alone within 1 day of hospitalization, the risk of subsequent severe outcomes was decreased.

A Multicenter Retrospective Cohort Study to Characterize Patients Hospitalized With Multisystem Inflammatory Syndrome in Adults and Coronavirus Disease 2019 in the United States, 2020-2021.

BACKGROUND: The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute coronavirus disease 2019 (COVID-19) and may affect clinical management. METHODS: In this retrospective cohort study, we applied the US Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at 6 academic medical centers from 1 March 2020 to 31 December 2021. Patients MIS-A were matched by age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographic characteristics, presenting symptoms, laboratory and imaging results, treatments administered, and outcomes between cohorts. RESULTS: Through medical record review of 10 223 patients hospitalized with SARS-CoV-2-associated illness, we identified 53 MIS-A cases. Compared with 106 matched patients with COVID-19, those with MIS-A were more likely to be non-Hispanic black and less likely to be non-Hispanic white. They more likely had laboratory-confirmed COVID-19 ≥14 days before hospitalization, more likely had positive in-hospital SARS-CoV-2 serologic testing, and more often presented with gastrointestinal symptoms and chest pain. They were less likely to have underlying medical conditions and to present with cough and dyspnea. On admission, patients with MIS-A had higher neutrophil-to-lymphocyte ratio and higher levels of C-reactive protein, ferritin, procalcitonin, and D-dimer than patients with COVID-19. They also had longer hospitalization and more likely required intensive care admission, invasive mechanical ventilation, and vasopressors. The mortality rate was 6% in both cohorts. CONCLUSIONS: Compared with patients with acute symptomatic COVID-19, adults with MIS-A more often manifest certain symptoms and laboratory findings early during hospitalization. These features may facilitate diagnosis and management.

COVID-19 Vaccine Reactogenicity and Vaccine Attitudes Among Children and Parents/Guardians After Multisystem Inflammatory Syndrome in Children or COVID-19 Hospitalization: September 2021-May 2022.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a multiorgan hyperinflammatory condition following SARS-CoV-2 infection. Data on COVID-19 vaccine adverse events and vaccine attitudes in children with prior MIS-C are limited. We described characteristics associated with COVID-19 vaccination, vaccine adverse events and vaccine attitudes in children with a history of MIS-C or COVID-19 and their parents/guardians. METHODS: We enrolled children previously hospitalized for MIS-C or COVID-19 from 3 academic institutions. We abstracted charts and interviewed children and parents/guardians regarding vaccine adverse events and acceptability. RESULTS: Of 163 vaccine-eligible children enrolled with a history of MIS-C and 70 with history of COVID-19, 51 (31%) and 34 (49%), respectively, received mRNA COVID-19 vaccine a median of 10 (Interquartile Range 6-13) months after hospital discharge. Among 20 children with MIS-C and parents/guardians who provided interviews, local injection site reaction of brief duration (mean 1.8 days) was most commonly reported; no children required medical care within 2 weeks postvaccination. Vaccine survey results of interviewed, vaccinated children and their parents/guardians: of 20 children with MIS-C and 15 children with COVID-19, 17 (85%) and 13 (87%), respectively, listed doctors in the top 3 most trusted sources for vaccine information; 13 (65%) and 9 (60%) discussed vaccination with their doctor. CONCLUSIONS: COVID-19 vaccination was well tolerated in children with prior MIS-C or COVID-19 participating in our investigation. Parents/guardians regarded their children's doctors as a trusted source of information for COVID-19 vaccines, and most vaccinated children's parents/guardians had discussed COVID-19 vaccination for their child with their doctor.

Council of State and Territorial Epidemiologists/CDC Surveillance Case Definition for Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection - United States.

This report summarizes the evidence and rationale supporting the components of the CSTE/CDC MIS-C surveillance case definition and describes the methods used to develop the definition. These methods included convening MIS-C clinical experts (i.e., consultants): regarding identification of MIS-C and its distinction from other pediatric conditions, a review of available literature comparing MIS-C phenotype with that of pediatric COVID-19 and other hyperinflammatory syndromes, and retrospective application of different criteria to data from MIS-C cases previously reported to CDC.

First-line corticosteroids for Kawasaki disease: Pulse versus multiple dose.

BACKGROUND: Kawasaki disease (KD) can result in severe coronary artery abnormalities (CAAs). Corticosteroids added to initial standard intravenous immunoglobulin (IVIG) treatment may decrease the risk for these complications. Different corticosteroid regimens (single-day high dose pulse vs multiple lower doses) may contribute to the discrepant results of prior studies. METHODS: Using data from the 22nd, 23rd , and 24th Japanese nationwide KD surveys (2011-2016), we identified KD patients who did not have CAAs at first presentation and who were treated with either pulse or multiple-dose corticosteroids as part of their initial treatment. Occurrence of subsequent CAAs and treatment failure were compared between the treatment regimens and adjusted odds ratios were calculated controlling for sex, age group, illness day at first treatment, survey, and recurrent KD. RESULTS: There were 782 KD patients who received pulse corticosteroid treatment and 4,817 who received multiple dose treatment. Patients receiving multiple dose treatment were less likely to develop CAAs (5.5% vs 8.3%, OR 0.64; 95% CI: 0.48-0.85) or treatment failure (21.4% vs 41.6%; OR: 0.38; 95% CI: 0.33-0.45). Adjusted analyses showed similar protective effects of multiple-dose treatment against CAAs (OR: 0.67, 95% CI: 0.51-0.90) and treatment failure (OR: 0.39, 95% CI: 0.33-0.46). CONCLUSIONS: Multiple-dose corticosteroid combination treatment resulted in substantially improved outcomes in KD patients compared to pulse treatment. For patients who may be at elevated risk of treatment failure or CAA, use of multiple-dose corticosteroids in conjunction with IVIG is likely to provide considerable clinical benefit.

Distinguishing Multisystem Inflammatory Syndrome in Children From COVID-19, Kawasaki Disease and Toxic Shock Syndrome.

BACKGROUND: Distinguishing multisystem inflammatory syndrome in children (MIS-C) from coronavirus disease 2019 (COVID-19), Kawasaki disease (KD), and toxic shock syndrome (TSS) can be challenging. Because clinical management of these conditions can vary, timely and accurate diagnosis is essential. METHODS: Data were collected from patients <21 years of age hospitalized with MIS-C, COVID-19, KD, and TSS in 4 major health care institutions. Patient demographics and clinical and laboratory data were compared among the 4 conditions, and a diagnostic scoring tool was developed to assist in clinical diagnosis. RESULTS: A total of 233 patients with MIS-C, 102 with COVID-19, 101 with KD, and 76 with TSS were included in the analysis. Patients with MIS-C had the highest prevalence of decreased cardiac function (38.6%), myocarditis (34.3%), pericardial effusion (38.2%), mitral regurgitation (31.8%) and pleural effusion (34.8%) compared with patients with the other conditions. Patients with MIS-C had increased peak levels of C-reactive protein and decreased platelets and lymphocyte nadir counts compared with patients with COVID-19 and KD and elevated levels of troponin, brain natriuretic peptide and pro-brain natriuretic peptide compared with COVID-19. Diagnostic scores utilizing clinical findings effectively distinguished MIS-C from COVID-19, KD, and TSS, with internal validation showing area under the curve ranging from 0.87 to 0.97. CONCLUSIONS: Compared with COVID-19, KD, and TSS, patients with MIS-C had significantly higher prevalence of cardiac complications, elevated markers of inflammation and cardiac damage, thrombocytopenia, and lymphopenia. Diagnostic scores can be a useful tool for distinguishing MIS-C from COVID-19, KD, and TSS.

Trends in Treatments for Multisystem Inflammatory Syndrome in Children (MIS-C), United States, February 2020 - July 2021.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a novel severe postinfectious condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The purpose of this report is to describe nationwide trends in the evolving clinical management of MIS-C. METHODS: Patients with MIS-C were reported from state and local jurisdictions to the Centers for Disease Control and Prevention's (CDC's) MIS-C national surveillance system. Patients' case reports were reviewed to ensure that they met the CDC MIS-C case definition and had sufficient data for analysis. The prevalence of use of treatments for MIS-C, temporal trends in use of these treatments, and frequency of administration of different treatment combinations were analyzed. RESULTS: There were 4470 patients meeting the MIS-C case definition with onset dates from 19 February 2020 to 31 July 2021. The proportion of patients admitted to an intensive care unit (ICU) has declined over time, from 78.7% in April 2020 to 57.5% in June 2021 (P = .001). The most common treatments were intravenous immunoglobulin (IVIG), given to 85.6% of patients; steroids (77.7%), and antiplatelet medications (73.7%); use of each of these treatments has increased over time, particularly in patients not requiring admission to an ICU (all P < .001). Older patients and non-Hispanic Black patients were more likely to receive additional modes of therapy including vasoactive medication, noninvasive respiratory support, anticoagulation medication, and intubation/mechanical ventilation. CONCLUSIONS: IVIG, steroids, and antiplatelet medication have become increasingly utilized as standard treatment for MIS-C patients, while the use of other treatments may be contingent on the type and severity of clinical findings.

Multisystem Inflammatory Syndrome in Children-United States, February 2020-July 2021.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory condition in persons aged <21 years associated with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to describe MIS-C cases reported to Centers for Disease Control and Prevention's (CDC's) national surveillance since the coronavirus disease 2019 (COVID-19) pandemic began. METHODS: We included patients meeting the MIS-C case definition with onset date from 19 February 2020 through 31 July 2021, using CDC's MIS-C case report form, which collects information on demographics, clinical presentation, and laboratory results. Trends over time across 3 MIS-C pandemic waves were assessed using Cochran-Armitage test for categorical and Jonckheere-Terpstra test for continuous variables. RESULTS: Of 4901 reported cases, 4470 met inclusion criteria. Median patient age increased over time (P < .001), with a median of 9 years (interquartile range, 5-13 years) during the most recent (third) wave. Male predominance also increased (62% in third wave, P < .001). A significant (P < .001) increase in severe hematologic and gastrointestinal involvement was observed across the study period. Frequency of several cardiovascular complications (ie, cardiac dysfunction, myocarditis, and shock/vasopressor receipt) and renal failure declined (P < .001). Provision of critical care including mechanical ventilation (P < .001) and extracorporeal membrane oxygenation (ECMO; P = .046) decreased, as did duration of hospitalization and mortality (each P < .001). CONCLUSIONS: Over the first 3 pandemic waves of MIS-C in the United States, cardiovascular complications and clinical outcomes including length of hospitalization, receipt of ECMO, and death decreased over time. These data serve as a baseline for monitoring future trends associated with SARS-CoV-2 B.1.617.2 (Delta) or other variants and increased COVID-19 vaccination among children.

Racial and Ethnic Disparities in Multisystem Inflammatory Syndrome in Children in the United States, March 2020 to February 2021.

BACKGROUND: The incidence of multisystem inflammatory syndrome in children (MIS-C) varies by race and ethnicity. This study assessed whether disparities in MIS-C in the United States by race and ethnicity exceed known disparities in coronavirus disease 2019 (COVID-19) incidence. METHODS: We compared the distribution of race and ethnicity among patients with MIS-C (<21 years of age, termed children) with onset March 2020 to February 2021 to that of children with COVID-19 and in the general population. Analysis was restricted to 369 counties with high completeness of race and ethnicity reporting for MIS-C and COVID-19. For each racial and ethnic group, observed numbers of patients with MIS-C were compared with expected numbers (observed/expected ratio) in children with COVID-19 and in the general population within these counties. RESULTS: Compared with children in the general population, MIS-C was more frequent among Hispanic (139% of expected) and non-Hispanic Black children (183%) and less frequent among non-Hispanic White (64%) and non-Hispanic Asian children (48%). Compared with children with COVID-19, MIS-C was more frequent in non-Hispanic Black children (207% of expected) and less frequent in non-Hispanic White children (68%); however, frequency was not different among Hispanic (102%) and non-Hispanic Asian (74%) children. CONCLUSIONS: Disparities in MIS-C by race and ethnicity exist, even after controlling for COVID-19 disparities and geographic variations. The high proportion of MIS-C among Hispanic children and low proportion among non-Hispanic Asian children align with COVID-19 rates, while the high proportion among non-Hispanic Black children and low proportion among non-Hispanic White children are not explainable by COVID-19 rates.

Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a newly identified and serious health condition associated with SARS-CoV-2 infection. Clinical manifestations vary widely among patients with MIS-C, and the aim of this study was to investigate factors associated with severe outcomes. METHODS: In this retrospective surveillance study, patients who met the US Centers for Disease Control and Prevention (CDC) case definition for MIS-C (younger than 21 years, fever, laboratory evidence of inflammation, admitted to hospital, multisystem [≥2] organ involvement [cardiac, renal, respiratory, haematological, gastrointestinal, dermatological, or neurological], no alternative plausible diagnosis, and either laboratory confirmation of SARS-CoV-2 infection by RT-PCR, serology, or antigen test, or known COVID-19 exposure within 4 weeks before symptom onset) were reported from state and local health departments to the CDC using standard case-report forms. Factors assessed for potential links to severe outcomes included pre-existing patient factors (sex, age, race or ethnicity, obesity, and MIS-C symptom onset date before June 1, 2020) and clinical findings (signs or symptoms and laboratory markers). Logistic regression models, adjusted for all pre-existing factors, were used to estimate odds ratios between potential explanatory factors and the following outcomes: intensive care unit (ICU) admission, shock, decreased cardiac function, myocarditis, and coronary artery abnormalities. FINDINGS: 1080 patients met the CDC case definition for MIS-C and had symptom onset between March 11 and Oct 10, 2020. ICU admission was more likely in patients aged 6-12 years (adjusted odds ratio 1·9 [95% CI 1·4-2·6) and patients aged 13-20 years (2·6 [1·8-3·8]), compared with patients aged 0-5 years, and more likely in non-Hispanic Black patients, compared with non-Hispanic White patients (1·6 [1·0-2·4]). ICU admission was more likely for patients with shortness of breath (1·9 [1·2-2·9]), abdominal pain (1·7 [1·2-2·7]), and patients with increased concentrations of C-reactive protein, troponin, ferritin, D-dimer, brain natriuretic peptide (BNP), N-terminal pro B-type BNP, or interleukin-6, or reduced platelet or lymphocyte counts. We found similar associations for decreased cardiac function, shock, and myocarditis. Coronary artery abnormalities were more common in male patients (1·5 [1·1-2·1]) than in female patients and patients with mucocutaneous lesions (2·2 [1·3-3·5]) or conjunctival injection (2·3 [1·4-3·7]). INTERPRETATION: Identification of important demographic and clinical characteristics could aid in early recognition and prompt management of severe outcomes for patients with MIS-C. FUNDING: None.

Kawasaki Disease With Coronary Artery Lesions Detected at Initial Echocardiography.

Background Detection of coronary artery lesions (CALs) at initial echocardiography can aid in diagnosing Kawasaki disease (KD) and inform primary adjunctive treatments. We aimed to characterize patients with KD with CALs detected at initial echocardiography. Methods and Results We analyzed data from the nationwide Japanese KD survey that contained information on 103 222 population-based patients diagnosed with KD across Japan during 2011 to 2018. Patients with CALs detected at initial echocardiography were assessed by age, day of illness, and number of principal KD signs (≥3). Multivariable logistic regression analysis was performed to evaluate factors independently associated with CAL detection. Overall, 3707 (3.6%) patients had CALs detected at initial echocardiography. Patients aged <12 and ≥60 months were associated with CAL detection (adjusted odds ratio [95% CI], 1.28 [1.18‒1.39] and 1.32 [1.20‒1.45], respectively; reference, 12‒59 months). Patients with delayed hospital visits were increasingly at higher risk for CAL detection (days 7‒8, 1.84 [1.63‒2.08]; days 9-10, 4.30 [3.58-5.15]; and days ≥11, 9.12 [7.63‒10.90]; reference, days 1-4). Patients with 3 or 4 principal KD signs were independently associated with CAL detection (1.75 [1.63‒1.88]). These patients were significantly more likely to be aged <12 months but were not associated with delayed hospital visit. Younger patients visited at earlier days of illness. Conclusions Timely diagnosis could be beneficial for patients with KD. However, even when the hospital visit occurred early in the course of illness, patients with 3 or 4 principal KD signs, especially younger patients, were at higher risk of CAL detection at initial echocardiography.

Toxic Shock Syndrome in Patients Younger than 21 Years of Age, United States, 2006-2018.

We examined the incidence of toxic shock syndrome in the United States during 2006-2018 among persons <21 years old with commercial or Medicaid-insurance using administrative data. There were 1008 commercially-insured and 481 Medicaid-insured toxic shock syndrome cases. The annual rate was 1 per 100,000 and stable over time. Rates were even lower in children <5 years old and stable over time.

Kawasaki Disease and Kawasaki Disease Shock Syndrome Hospitalization Rates in the United States, 2006-2018.

BACKGROUND: Kawasaki disease (KD) is a febrile illness of unknown etiology. Patients with Kawasaki disease shock syndrome (KDSS) may present with clinical signs of poor perfusion and systolic hypotension in addition to typical KD features. The United States Centers for Disease Control and Prevention analyzes and interprets large hospitalization databases as a mechanism for conducting national KD surveillance. METHODS: The Kids' Inpatient Database (KID), the National (Nationwide) Inpatient Sample (NIS), and the IBM MarketScan Commercial (MSC) and MarketScan Medicaid (MSM) databases were analyzed to determine KD-associated hospitalization rates and trends from 2006 to the most recent year of available data. KD and potential KDSS hospitalizations were defined using International Classification of Disease-Clinical Modification codes. RESULTS: For the most recent year, the KD-associated hospitalization rates for children <5 years of age were 19.8 (95% CI: 17.2-22.3, KID: 2016), 19.6 (95% CI: 16.8-22.4, NIS: 2017), 19.3 (MSC: 2018), and 18.4 (MSM: 2018) per 100,000. There was no indication of an increase in KD rates over the time period. Rates of potential KDSS among children <18 years of age, ranging from 0.0 to 0.7 per 100,000, increased; coding indicated potential KDSS for approximately 2.8%-5.3% of KD hospitalizations. CONCLUSIONS: Analyses of these large, national databases produced consistent KD-associated hospitalization rates, with no increase over time detected; however, the percentage of KD hospitalizations with potential KDSS increased. Given reports of increasing incidence elsewhere and the recent identification of a novel virus-associated syndrome with possible Kawasaki-like features, continued national surveillance is important to detect changes in disease epidemiology.

Multisystem Inflammatory Syndrome in Children Associated with Severe Acute Respiratory Syndrome Coronavirus 2: A Systematic Review.

OBJECTIVE: To develop a more comprehensive description of multisystem inflammatory syndrome in children (MIS-C), a novel syndrome linked to severe acute respiratory syndrome coronavirus 2, by conducting a systematic analysis of studies from different settings that used various inclusion criteria. STUDY DESIGN: MIS-C studies were identified by searching PubMed and Embase as well as preprint repositories and article references to identify studies of MIS-C cases published from April 25, 2020, through June 29, 2020. MIS-C study metadata were assessed and information on case demographics, clinical symptoms, laboratory measurements, treatments, and outcomes were summarized and contrasted between studies. RESULTS: Eight studies were identified representing a total of 440 MIS-C cases. Inclusion criteria varied by study: 3 studies selected patients diagnosed with Kawasaki disease, 2 required cardiovascular involvement, and 3 had broader multisystem inclusion criteria. Median age of patients by study ranged from 7.3 to 10 years, and 59% of patients were male. Across all studies, the proportion of patients with positive results for severe acute respiratory syndrome coronavirus 2 reverse transcriptase-polymerase chain reaction tests ranged from 13% to 69% and for serology, from 75% to 100%. Patients with MIS-C had high prevalence of gastrointestinal (87%), dermatologic/mucocutaneous (73%), and cardiovascular (71%) symptoms. Prevalence of cardiovascular, neurologic, and respiratory system involvement significantly differed by study inclusion criteria. All studies reported elevated C-reactive protein, interleukin-6, and fibrinogen levels for at least 75% of patients in each study. CONCLUSIONS: This systematic review of MIS-C studies assists with understanding this newly identified syndrome and may be useful in developing a refined, universal case definition of MIS-C.

Corticosteroids Added to Initial Intravenous Immunoglobulin Treatment for the Prevention of Coronary Artery Abnormalities in High-Risk Patients With Kawasaki Disease.

BACKGROUND Randomized controlled trials previously provided different conclusions about the superiority of adding corticosteroids to initial intravenous immunoglobulin treatment for the prevention of coronary artery abnormalities in patients with Kawasaki disease (KD). To further assess this issue, we analyzed large-scale data from nationwide KD surveys in Japan, where combination treatment (corticosteroids added to initial standard intravenous immunoglobulin treatment) has become commonly used for patients at high risk for KD. METHODS AND RESULTS Standard intravenous immunoglobulin treatment and combination treatment were compared using data from time periods with and without combination treatment. Outcome measures were coronary artery abnormalities and initial intravenous immunoglobulin treatment failure. Hospitals where ≥20% of patients received combination treatment were identified, and treatment and control groups were selected via matching by age, sex, illness day at initial treatment, and KD recurrence. Matched group selection and subsequent analyses were conducted 1000 times to minimize sampling bias and potential confounders (bootstrapping). From 115 hospitals, 1593 patients with KD in the treatment group and 1593 controls were selected for each of the 1000 sample iterations. The median proportion of patients who developed coronary artery abnormalities among the treatment group and controls were 4.6% (95% CI, 3.8%-5.8%) and 8.8% (95% CI, 7.5%-10.0%), respectively: an estimated risk ratio of 0.53 (0.41-0.67). A median of 14.1% (95% CI, 12.4%-15.9%) of the patients in the treatment group and 21.7% (95% CI, 19.8%-23.4%) in the controls had treatment failure: an estimated risk ratio of 0.65 (0.56-0.75). CONCLUSIONS Combination treatment reduced coronary artery abnormality risk by an estimated 47% and treatment failure by 35%. Multiple-dose corticosteroids may provide benefit in selected patients at high risk for KD.

Outcomes in Kawasaki disease patients with coronary artery abnormalities at admission.

BACKGROUND: Previous studies demonstrated that coronary artery lesions (CALs) resulting from Kawasaki disease (KD) can improve over time. However, limited information is available on sub-acute outcomes of CALs detected at admission during KD illness. METHODS: The nationwide Japanese KD survey contained substantial information on KD patients with CALs detected at admission and who received standard IVIG treatment within 10 days of disease onset. Coronary outcomes were evaluated by changes in CALs from admission to the first assessment at 30 days from disease onset in three categories: improved, unchanged, and progressed. Ordinal logistic regression analysis was performed to evaluate factors associated with the outcomes. RESULTS: Of 2024 patients with CALs detected at admission, improved, unchanged, and progressed outcomes were found in 1548 (76.5%), 390 (19.3%), and 86 (4.2%), respectively. Over 80% of patients with coronary artery (CA) dilatations had improved outcome. Independent factors associated with worse outcomes were larger-size CALs (adjusted ORs [95% CIs]: CA aneurysm = 5.13 [3.65-7.22] and giant CA aneurysms = 7.49 [3.56-15.72] compared with CA dilatation, respectively), age ≥ 60 months (1.45 [1.08-1.94] compared with 12-59 months), recurrent KD (1.57 [1.07-2.29]), parental history of KD (2.23 [1.02-4.85]), and delayed admission (8-10 days from disease onset: 1.76 [1.21-2.57] compared with 1-4 days). CONCLUSIONS: KD patients with larger CALs, ≥60 months old, and with recurrent status or parental history may require more rigorous treatment. In addition, delayed admission may result in worse coronary outcome, indicating that prompt diagnosis and treatment are required.

Zika Virus infection and Guillain-Barré syndrome in Northeastern Mexico: A case-control study.

BACKGROUND: Beginning August 2017, we conducted a prospective case-control investigation in Monterrey, Mexico to assess the association between Zika virus (ZIKV) and Guillain-Barré syndrome (GBS). METHODS: For each of 50 GBS case-patients, we enrolled 2-3 afebrile controls (141 controls in total) matched by sex, age group, and presentation to same hospital within 7 days. RESULTS: PCR results for ZIKV in blood and/or urine were available on all subjects; serum ZIKV IgM antibody for 52% of case-patients and 80% of controls. Subjects were asked about antecedent illness in the two months prior to neurological onset (for case-patients) or interview (for controls). Laboratory evidence of ZIKV infection alone (PCR+ or IgM+) was not significantly different between case-patients and controls (OR: 1.26, 95% CI: 0.45-3.54) but antecedent symptomatic ZIKV infection [a typical ZIKV symptom (rash, joint pain, or conjunctivitis) plus laboratory evidence of ZIKV infection] was higher among case-patients (OR: 12.45, 95% CI: 1.45-106.64). GBS case-patients with laboratory evidence of ZIKV infection were significantly more likely to have had typical ZIKV symptoms than controls with laboratory evidence of ZIKV infection (OR: 17.5, 95% CI: 3.2-96.6). This association remained significant even when only GBS case-patients who were afebrile for 5 days before onset were included in the analysis, (OR 9.57 (95% CI: 1.07 to 85.35). CONCLUSIONS: During ZIKV epidemics, this study indicates that increases in GBS will occur primarily among those with antecedent symptomatic ZIKV.

Platelet Count Variation and Risk for Coronary Artery Abnormalities in Kawasaki Disease.

BACKGROUND: Platelet count is considered as a biomarker for the development of coronary artery abnormalities (CAAs) among Kawasaki disease (KD) patients. However, previous studies have reported inconsistent results. We addressed the controversial association of platelet count with CAAs using a large-scale dataset. METHODS: A retrospective cohort study was conducted using KD survey data from Japan (2015-2016; n = 25,448). Classifying patients by intravenous immunoglobulin (IVIG) responsiveness, we described the trends in platelet count using the lowest and highest values along with the specific illness days. Multivariate logistic regression analysis was performed to evaluate the association between platelet count and CAAs, adjusting for relevant factors. RESULTS: Platelet counts rapidly decreased from admission, reached the lowest count at 6-7 days, and peaked after 10 days. Platelet counts in IVIG non-responders decreased with a lower minimum value than IVIG responders, but subsequently rebounded toward a higher maximum. Compared with patients with normal platelet counts (150-450 × 10/L), patients with abnormally high platelet counts (>450 × 10/L) were more likely to have CAAs at admission (adjusted odds ratio: IVIG responders, 1.50 [95% confidence interval 1.20-1.87] and non-responders, 1.46 [1.01-2.12]). By contrast, IVIG non-responding patients whose counts were below normal (<150 × 10/L) after hospitalization were at higher risk for developing CAAs (2.27 [1.44-3.58]). CONCLUSIONS: Platelet count varied widely by illness day and was confounded by IVIG responsiveness, which might have contributed to previous inconsistent findings. KD patients with abnormally high platelet counts at admission or abnormally low counts after hospitalization were at higher risk for CAAs.