, during the peak of the coronavirus disease 2019 (COVID-19) pandemic in Europe, a cluster of children with hyperinflammatory shock with features similar to Kawasaki disease and toxic shock syndrome was reported in England* (1). The patients' signs and symptoms were temporally associated with COVID-19 but presumed to have developed 2-4 weeks after acute COVID-19; all children had serologic evidence of infection with SARS-CoV-2, the virus that causes COVID-19 (1). The clinical signs and symptoms present in this first cluster included fever, rash, conjunctivitis, peripheral edema, gastrointestinal symptoms, shock, and elevated markers of inflammation and cardiac damage (1). On May 14, 2020, CDC published an online Health Advisory that summarized the manifestations of reported multisystem inflammatory syndrome in children (MIS-C), outlined a case definition, † and asked clinicians to report suspected U.S. cases to local and state health departments. As of July 29, a total of 570 U.S. MIS-C patients who met the case definition had been reported to CDC. A total of 203 (35.6%) of the patients had a clinical course consistent with previously published MIS-C reports, characterized predominantly by shock, cardiac dysfunction, abdominal pain, and markedly elevated inflammatory markers, and almost all had positive SARS-CoV-2 test results. The remaining 367 (64.4%) of MIS-C patients had manifestations that appeared to overlap with acute COVID-19 (2-4), had a less severe clinical course, or had features of Kawasaki disease. § Median duration of hospitalization was 6 days; 364 patients (63.9%) required care in an intensive care * https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatricmultisystem-%20inflammatory%20syndrome-20200501.pdf. † The MIS-C case definition included a patient aged <21 years with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem organ involvement (cardiovascular, dermatologic, gastrointestinal, hematologic, neurologic, renal, or respiratory) who tested positive for SARS-CoV-2 or had exposure to COVID-19. https:// www.cdc.gov/mis-c/hcp/. § Kawasaki disease is an acute febrile illness of unknown cause, primarily affecting children, and associated with fever, rash, conjunctivitis, redness in the mouth, cracked lips, and swollen lymph nodes, feet, and hands.

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.

Objective To develop a more comprehensive description of multisystem inflammatory syndrome in children (MIS-C), a novel syndrome linked to SARS-CoV-2, by conducting a systematic analysis of studies from different settings which 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: three studies selected patients diagnosed with Kawasaki disease (KD), two required cardiovascular involvement, and three 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 SARS-CoV-2 RT-PCR tests ranged from 13 to 69% and for serology, from 75 to 100%. MIS-C patients 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.

The presented BCSC outcomes data and performance benchmarks may be used by mammography facilities and individual radiologists to evaluate their own performance for diagnostic mammography as determined by means of periodic comprehensive audits.

HZ incidence has been increasing from 1993-2006. We found no evidence to attribute the increase to the varicella vaccine program.

Purpose Breast cancer risk assessment can inform the use of screening and prevention modalities. We investigated the performance of the Breast Cancer Surveillance Consortium (BCSC) risk model in combination with a polygenic risk score (PRS) comprised of 83 single nucleotide polymorphisms identified from genome wide association studies. Methods We conducted a nested case-control study of 486 cases and 495 matched controls within a screening cohort. The PRS was calculated using a Bayesian approach. The contributions of the PRS and variables in the BCSC model to breast cancer risk were tested using conditional logistic regression. Discriminatory accuracy of the models was compared using the area under the receiver operating characteristic curve (AUROC). Results Increasing quartiles of the PRS were positively associated with breast cancer risk, with OR 2.54 (95% CI 1.69-3.82) for breast cancer in the highest versus lowest quartile. In a multivariable model, the PRS, family history, and breast density remained strong risk factors. The AUROC of the PRS was 0.60 (95% CI 0.57-0.64), and an Asian-specific PRS had AUROC 0.64 (95% CI 0.53-0.74). A combined model including the BCSC risk factors and PRS had better discrimination than the BCSC model (AUROC 0.65 versus 0.62, p = 0.01). The BCSC-PRS model classified 18% of cases as high-risk (5-year risk ≥ 3%), compared with 7% using the BCSC model. Conclusion The PRS improved discrimination of the BCSC risk model and classified more cases as high-risk. Impact Further consideration of the PRS's role in decision-making around screening and prevention strategies is merited.

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OBJECTIVE. Patients in the intensive care unit are at increased risk of developing acute calculous and acalculous cholecystitis. Diagnosis based on clinical and sonographic findings is difficult in the presence of severe intercurrent disease. We did a study to evaluate the efficacy of percutaneous cholecystostomy as a diagnostic and therapeutic maneuver in 82 patients in the intensive care unit who had persistent unexplained sepsis. SUBJECTS AND METHODS. Eighty-two patients with unexplained sepsis underwent percutaneous cholecystostomy after a complete clinical, laboratory, and radiologic search showed no source of sepsis outside the gallbladder. All patients were febrile, 65 had an increased WBC count, and 37 were receiving vasopressors. Sonographic abnormalities included a distended gallbladder (71 patients), sludge (63 patients), gallstones (26 patients), wall thickening (34 patients), pericholecystic fluid (25 patients), and Murphy's sign (19 patients). RESULTS. Sonographic findings were not helpful in predicting response to percutaneous