An epidemiological survey of COVID-19 serology and its association with clinical infection among older adults- does antibody titer matter?

BACKGROUND: Older adults are at increased risk of severe SARS-CoV-2 infection. In this study we assessed the response to COVID-19 vaccination and infection rates among nursing homes (NH) and assisted-living care home (ALCH) residents. METHODS: The study was conducted between August 2021 and January 2022, after widespread population vaccination with the third dose of Pfizer-BioNtech mRNA COVID-19 vaccine in Israel. Three groups were addressed: hospitalized older patients; NH and ALCH residents. Demographic data, COVID-19 serology (anti-spike IgG antibodies) and PCR test results were obtained to assess the dynamics of antibody titers and its correlation to infection rates. RESULTS: Two-hundred eighty-five individuals were evaluated; 92 hospitalized patients; 100 ALCH residents and 93 NH residents. In the latter two groups two serology surveys were conducted three months apart. Hospitalized patients were younger than ALCH and NH residents (mean age 80.4 ± 8 versus 82.6 ± 8 and 83.6 ± 5, respectively, p = 0.01), and had more comorbidities (p = 0.003). The degree of decline in the antibody level overtime was similar in ALCH and NH residents. Infection rates were higher among NH residents than ALCH residents [35/91 (38.4%) versus 11/100 (11%), p < 0.001]. Antibody level was lower among those infected [2113 (1271-3512) Au/ml versus 4113 (3364-5029) Au/ml, p < 0.001]. Adjusted analysis showed that NH residence, but not antibody levels, were significantly associated with infection. CONCLUSION: Among older adults, infection rates inversely correlated with antibody level. However, only nursing home residence was significantly associated with infection, suggesting that other factors such as crowding considerably contribute to the risk of infection.

Time from symptom onset may influence C-reactive protein utility in the diagnosis of bacterial infections in the NICU.

BACKGROUND: Taking into account the timing of C-reactive protein (CRP) testing may improve the performance of the test in diagnosing bacterial infections in the neonatal intensive care unit (NICU). We aimed to examine the yield of CRP, relative to time from symptoms onset. METHODS: Enrolled were all NICU patients, for whom CRP was obtained as part of a sepsis workup. The time of symptoms onset and of blood draw was recorded. Patients were classified into bacterial and non-bacterial groups according to the National Healthcare Safety Network (NHSN) guidelines. The performance of CRP, CRP velocity, and CRP obtained before or after 6 hours from symptoms onset, was evaluated by receiver-operating characteristic (ROC) curve. Test characteristics were calculated using formulas based on Bayes' theorem. RESULTS: Of 129 infants enrolled in the study, 21(16%) had a bacterial infection. A single CRP test and CRP velocity performed similarly in diagnosing bacterial infection, with area under ROC curve of 0.75 (95%CI: 0.61-0.89) and 0.77 (95% CI:0.66-0.88), respectively. The optimal cut-off value for a CRP test obtained <= 6 hours from symptoms onset was 1 mg/dL, whereas the optimal cut-off > 6 hours was 1.5 mg/dL. Using the optimal cut-off values increased the pre-test probability of 16%, to a post-test probability of 35-38%. For infants whose birth weight was < 1000 g, CRP performed poorly. CONCLUSIONS: The optimal CRP cut-off used in the diagnosis of bacterial infections in NICU patients varies by the time from symptom onset. A "negative" CRP may support a clinical decision to stop empiric antimicrobial therapy, for infants whose blood cultures remain sterile.

The utility of MALDI-TOF MS for outbreak investigation in the neonatal intensive care unit.

Our aim was to evaluate the performance of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), routinely used in the microbiology laboratory for bacterial identification, for bacterial typing in the setting of extended spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-KP) outbreak in the neonatal intensive care unit (NICU). Isolates from a 2011 outbreak in the NICU were retrieved from frozen stocks and analyzed by MALDI-TOF. The MALDI typing was compared with core genome multilocus sequence typing (cg-MLST). MALDI typing divided the 33 outbreak isolates into 2 clones: sequence type (ST)-290 and 405. These results were in complete agreement with cg-MLST results. The differentiation of the outbreak isolates into two clones correlated with the patients' location in the NICU, but also with their place of residence.Conclusion: Here, we show that MALDI-TOF MS, which has been integrated into the microbiology laboratory workflow for microbial species identification, can be secondarily used for epidemiological typing at no added cost. What is Known: • Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is now routinely used in the microbiology laboratory for bacterial identification What is New: • MALDI typing was used for outbreak investigation in the NICU and divided the outbreak isolates into two clones • MALDI-TOF MS may be secondarily used for epidemiological typing at no added cost.

Ibrutinib-associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: An observational study.

BACKGROUND: Invasive fungal diseases (IFD) are life-threatening infections most commonly diagnosed in acute leukaemia patients with prolonged neutropenia and are uncommonly diagnosed in patients with lymphoproliferative diseases. OBJECTIVES: Following the initial report of aspergillosis diagnosed shortly after beginning ibrutinib for chronic lymphocytic leukaemia, a survey was developed to seek additional cases of IFD during ibrutinib treatment. METHODS: Local and international physicians and groups were approached for relevant cases. Patients were included if they met the following criteria: diagnosis of chronic lymphocytic leukaemia/non-Hodgkin lymphoma; proven or probable IFD; and ibrutinib treatment on the date IFD were diagnosed. Clinical and laboratory data were captured using REDCap software. RESULT: Thirty-five patients with IFD were reported from 22 centres in eight countries: 26 (74%) had chronic lymphocytic leukaemia. The median duration of ibrutinib treatment before the onset of IFD was 45 days (range 1-540). Aspergillus species were identified in 22 (63%) of the patients and Cryptococcus species in 9 (26%). Pulmonary involvement occurred in 69% of patients, cranial in 60% and disseminated disease in 60%. A definite diagnosis was made in 21 patients (69%), and the mortality rate was 69%. Data from Israel regarding ibrutinib treated patients were used to evaluate a prevalence of 2.4% IFD. CONCLUSIONS: The prevalence of IFD among chronic lymphocytic leukaemia/non-Hodgkin lymphoma patients treated with ibrutinib appears to be higher than expected. These patients often present with unusual clinical features. Mortality from IFD in this study was high, indicating that additional studies are urgently needed to identify patients at risk for ibrutinib-associated IFD.

High-dose aspirin for Kawasaki disease: outdated myth or effective aid?

OBJECTIVES: To compare the efficacy and safety of intravenous immunoglobulin (IVIG) plus high-dose aspirin (HDA) vs. IVIG plus low-dose aspirin (LDA) for the treatment of Kawasaki disease, with an emphasis on coronary artery outcomes. METHODS: This study was a retrospective, medical record review of paediatric patients with Kawasaki disease comparing 6 centres that routinely used HAD for initial treatment and 2 that used LDA in 2004-2013. Treatment response and adverse events were compared. The primary outcome measure was the occurrence of coronary aneurysm at the subacute or convalescent stage. RESULTS: The cohort included 358 patients, of whom 315 were initially treated with adjunctive HDA and 43 with LDA. There were no demographic differences between the groups. Coronary aneurysms occurred in 10% (20/196) of the HDA group and 4% (1/24) of the LDA group (p=0.34). Equivalence tests indicate it is unlikely that the risk of coronary aneurysm in LDA exceeds HDA by more than 3.5%. There were no significant between-group differences in the need for glucocorticoid pulse therapy or disease recurrence. Coronary ectasia rate and hospitalisation time were significantly greater in the HDA group. Adverse events were similar in the two groups. CONCLUSIONS: We found no significant clinical benefit in using IVIG+HDA in Kawasaki disease compared to IVIG+LDA. The use of adjunctive HDA in this setting should be reconsidered.

Hepatitis B Virus Revaccination With Standard Versus Pre-S Vaccine in Previously Immunized Patients With Celiac Disease.

OBJECTIVE: Previous studies have suggested that hepatitis B virus (HBV) vaccines may be less immunogenic in individuals with celiac disease (CD). A pre-S vaccine (Sci-B-Vac) has demonstrated superior immunogenicity compared with standard HBV vaccines in several diseases. We compared the short-term immunogenicity of a pre-S vaccine with a HBV vaccine (Engerix B) for repeat vaccination of seronegative, previously immunized patients with CD. METHODS: Participants were 1 to 18-year-old children with CD who despite standard HBV vaccines in infancy had nonprotective hepatitis B surface antibody (HBs-Ab) concentrations (≤10 mIU/mL). Patients were randomized to receive either Engerix B or pre-S vaccine. HBs-Ab concentrations were measured 1 month after the first dose. For those who had not responded after 1 dose, measurement was repeated after the third dose. RESULTS: Children (n = 82) were analyzed (42 pre-S vaccine and 40 Engerix B). Baseline characteristics were similar for both groups, including gluten-free diet status. Both arms showed high response rates following the first injection: 41 (98%) versus 35 (87%) for pre-S vaccine and Engerix B recipients, respectively (P = 0.08). All other patients responded when measured after dose 3. HBs-Ab concentrations (mIU/mL) were higher in the pre-S vaccine group (median 925, interquartile range [IQR] 424-1000) than the Engerix B group (median 363, IQR 106-996, P = 0.005). Twenty (48%) of the pre-S vaccine recipients were "high responders" (>1000 mIU/mL) versus 10 (25%) in Engerix B recipients (P = 0.008). CONCLUSIONS: Both vaccines elicited adequate booster responses in most previously vaccinated patients with CD with nonprotective HBs-Ab concentrations. Pre-S vaccine administration resulted in higher Hbs-Ab concentrations. Our data suggest that a single dose of either vaccine is sufficient to raise titers to protective levels in most patients with CD.

[Effect of a computer application on appropriate use and control of broad spectrum antibiotics].

BACKGROUND: Antibiotics are among the greatest contributions of modern medicine. However, since the onset of the antibiotic age, resistance has emerged, threatening the future usability of these drugs. The complexity of antibiotic prescribing and associated expense has led to the development of infectious disease (ID) expert stewardship programs. PURPOSE: To describe an in-house created computer application, in use since 2005 with which all restricted antimicrobials are ordered and approved by ID physicians before being supplied by the pharmacy. RESULTS: In the nine years since the application was adopted by the entire hospital, 173,436 prescriptions for restricted antibiotics have been ordered through the application, of which 52% were for male patients, 8% for children ≤ 20 years, 31% for adults 21-70 years old and 61% for patients > 70. All prescriptions were reviewed by ID physicians; their response included approval (mean 87%, range 82-92%), rejection (7%, 3-12%), or change (6%, 4-18%). The latter two decisions always involved written and/or oral interaction with the prescribing physicians. The result analysis showed that: by clinical diagnoses, the approval rate ranged from 82% (for central line associated infection) to 94% (for tuberculosis); by class of antimicrobial, the approval rate ranged from 71% (IV ciprofloxacin) to 95% (IV amoxicillin-calvulanate). Overall hospital expenditure on antimicrobials, corrected by 100 admissions and 100 admission days, did not change significantly. CONCLUSIONS: During the nine years of its use, the described computer program has significantly contributed to physician awareness of appropriate antibiotic use, provided tools to assist physicians in their choice of antimicrobial treatment, allowed ID supervision with unprecedented scope and depth and has significantly contributed to cost control.

[Rheumatic fever and Kawasaki disease among children in Israel].

BACKGROUND: Rheumatic Fever (RF) and Kawasaki Disease (KD) are the two leading causes of childhood acquired heart disease in developed countries. AIM: The objective of this paper is to characterize the epidemiologic changes and estimate the incidence rate of RF and KD among children in Israel in the past two decades. METHODS: Using the Israel National Hospital Discharges Register (NHDR), we investigated the epidemiologic features of RF and KD among children in Israel under 18 years of age, between the years 1996 and 2012. Incidence rates were calculated using the corresponding Central Bureau of Statistics (CBS) data. RESULTS: The average annual incidence rates of RF and KD were, respectively, 2 and 2.03 cases per 100,000 children under 18 years of age. During the study period, the incidence rate of RF declined by over 50%, while the incidence rate of KD increased by more than 40%. The hospitalization rate of RF and KD diagnoses in children showed similar trends. CONCLUSIONS: The incidence rates of RF and KD had undergone significant changes in the past two decades. These changes probably reflect increased awareness of preventing RF and diagnosing KD among health professionals. Due to the high risk of chronic heart disease associated with inadequately treated children, it is important to maintain high awareness among healthcare professionals and provide timely diagnosis of both conditions.

Clinical presentation and outcome of hemodialysis tunneled catheter-related bloodstream infection in older persons.

BACKGROUND: The use of a tunneled catheter as the primary vascular access among old hemodialysis patients is frequent. Catheter-related bloodstream infection (CRBSI) is a common complication, associated with increased mortality. Data regarding the clinical presentation and outcomes of CRBSI among old hemodialysis patients is limited. METHODS: All chronic hemodialysis patients hospitalized between 2010 and 2022 with CRBSI were included. Patients were classified into two groups: old adults (≥ 75) and younger patients. Clinical, microbiological, and outcome data were collected and analyzed. RESULTS: One hundred and fifty-four patients with CRBSI were identified. Fifty-seven were aged ≥ 75 years. Mean age in the older and younger groups was 81.2 ± 5 and 59.7 ± 12.7, respectively. Male gender was predominant (64%). Charlson comorbidity score and Pitt bacteremia score were comparable among both groups. Norton score < 14 was more common among old persons (n = 24, 67% versus n = 21, 31%, p < 0.001), as well as nursing-home residence. Gram-negative pathogens and Staphylococcus aureus were common in both groups. The frequency of inappropriate empirical antimicrobial treatment was higher among older persons. Overall, in-hospital and 90-day mortality was high (age ≥ 75, 36.8%, age < 75, 24.7%, p = 0.14). Age was not significantly associated with mortality after adjustment for low Norton score, residence, and inappropriate antimicrobial therapy as well as resistance patterns of bloodstream isolates [OR = 1.2 (95% CI 0.4-3.3), p = 0.76]. CONCLUSIONS: Clinical characteristics and outcomes of CRBSI were comparable among old and young hemodialysis patients. However, the high mortality rate in this cohort suggests that the use of tunneled catheters as a permanent vascular access should be discouraged in both patient groups.

Clinical significance of microbial infection and adaptation in cystic fibrosis.

A select group of microorganisms inhabit the airways of individuals with cystic fibrosis. Once established within the pulmonary environment in these patients, many of these microbes adapt by altering aspects of their structure and physiology. Some of these microbes and adaptations are associated with more rapid deterioration in lung function and overall clinical status, whereas others appear to have little effect. Here we review current evidence supporting or refuting a role for the different microbes and their adaptations in contributing to poor clinical outcomes in cystic fibrosis.

Chlorhexidine bathing in a tertiary care neonatal intensive care unit: A pilot study.

BACKGROUND: Concerns regarding potential risk of dermal irritation have led to the exclusion of NICU patients from the recommendation regarding the use of 2% chlorhexidine gluconate (CHG) wash for daily skin cleansing to reduce bloodstream infections. Our aim was to assess the safety of 2% CHG bathing in NICU patients. METHODS: The regulator required a stepwise study enrollment to three successive groups: term infants, followed by near-term and pre-term infants. For comparison, we used a cohort of matched controls. A propensity score-adjusted regression model was used to compare the groups. INTERVENTION: Infants were bathed thrice-weekly with 2% CHG-impregnated washcloths. Participant's skin was examined daily. RESULTS: Over a total of 661 days of treatment: 384,129, and 148 days for the term, near-term and pre-term groups, respectively, no skin reactions were observed. The intervention group was generally sicker, however, bloodstream infections were similar between the groups. CONCLUSION: For infants >30 weeks and >3 days old, 2% CHG bathing was safe. Large multicenter studies are urgently needed to establish the effectiveness of this practice in the NICU.

Haemophilus influenzae activity in a single medical center in Israel in the post-vaccine era.

BACKGROUND: The incidence of invasive disease due to Haemophilus influenzae has decreased since the implementation of vaccination against serotype B. OBJECTIVES: To describe the epidemiological, clinical and microbiological characteristics of patients with H. influenzae meningitis or bacteremia in the vaccine era in Israel. METHODS: We reviewed the medical records of all patients admitted to Shaare Zedek Medical Center between 1997 and 2010 who had blood or cerebrospinal fluid culture positive for H. influenzae. RESULTS: The study group comprised 104 patients - 57 children and 47 adults. Overall, 21 (20%) of the infections were due to serotype b. The children had shorter hospitalizations (6vs. 12 days, P = 0.005) and lower mortality rate (5% vs. 28%, P = 0.003) as compared to the adults. Bacteremic pneumonia was the most common diagnosis in adults (45% vs. 28% in children, P = 0.08) while meningitis was more common in children (17% vs. 3.5%, P = 0.09). There was a seasonal pattern, with infections being more common during the winter and spring. CONCLUSIONS: Invasive H. influenzae disease is uncommon but still exists in both children and adults. The disease course tends to be more severe in adults. Even in the global vaccination era, serotype b constitutes a significant portion of invasive disease.

[Congenital skull base defect causing recurrent bacterial meningitis].

Bacterial meningitis is a life threatening disease. Most patients will experience only one episode throughout life. Children who experience bacterial meningitis more than once, require further immunologic or anatomic evaluation. We report a 9 year old child with five episodes of bacterial meningitis due to a congenital defect of the skull base. A two and a half year old boy first presented to our medical center with pneumococcal meningitis. He was treated with antibiotics and fully recovered. Two months later he presented again with a similar clinical picture. Streptococcus pneumoniae grew in cerebrospinal fluid (CSF) culture. CT scan and later MRI of the brain revealed a defect in the anterior middle fossa floor, with protrusion of brain tissue into the sphenoidal sinus. Corrective surgery was recommended but the parents refused. Three months later, a third episode of pneumococcal meningitis occurred. The child again recovered with antibiotics and this time corrective surgery was performed. Five years later, the boy presented once again with clinical signs and symptoms consistent with bacterial meningitis. CSF culture was positive, but the final identification of the bacteria was conducted by broad spectrum 16S ribosomal RNA PCR (16S rRNA PCR) which revealed a sequence of Neisseria lactamica. CT and MRI showed recurrence of the skull base defect with encephalocele in the sphenoid sinus. The parents again refused neurosurgical intervention. A year later the patient presented with bacterial meningitis. CSF culture obtained after initiation of antibiotics was negative, but actinobacillus was identified in the CSF by 16S rRNA PCR. The patient is scheduled for neurosurgical intervention. In patients with recurrent bacterial meningitis caused by organisms colonizing the oropharynx or nasopharynx, an anatomical defect should be carefully sought and surgically repaired.

The NICU flora: An effective technique to sample surfaces.

OBJECTIVE: Environmental surface sampling in healthcare settings is not routinely recommended. There are several methods for environmental surface sampling, however the yield of these methods is not well defined. The aim of the present study is to compare two methods of environmental surface sampling, to characterize the neonatal intensive care unit (NICU) flora, compare it with rates of infection and colonization and correlate it with the workload. DESIGN AND SETTING: First, the yield of the swab and the gauze-pad methods were compared. Then, longitudinal surveillance of environmental surface sampling was performed over 6 months,once weekly, from pre-specified locations in the NICU. Samples were streaked onto selective media and bacterial colonies were identified using matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF). RESULTS: The number of colonies isolated using the gauze pad method was significantly higher compared with the swab method. Overall, 87 bacterial species of 30 different bacterial genera were identified on the NICU environmental surfaces. Of these, 18% species were potential pathogens, and the other represent skin and environmental flora. In 20% of clinical cultures and in 60% of colonization cultures, the pathogen was isolated from the infant's environment as well. The number of bacteria in environmental cultures was negatively correlated with nurse/patient ratio in the day prior to the culture. CONCLUSION: The gauze pad method for environmental sampling is robust and readily available. The NICU flora is very diverse and is closely related with the infants' flora, therefore it may serve as a reservoir for potential pathogens.

Identifying factors affecting latent tuberculosis treatment acceptance among healthcare workers: a retrospective analysis in a tertiary care centre.

OBJECTIVE: Official guidelines recommend tuberculosis (TB) screening programmes for all healthcare workers (HCWs), along with offering treatment when latent TB infection (LTBI) is diagnosed. However, adherence to treatment among HCWs is lower compared with non-HCWs. The aim of the present study was to examine the rate of LTBI treatment acceptance among HCWs and to characterise the factors associated with non-acceptance. DESIGN AND SETTING: This was a retrospective cohort study. All HCWs diagnosed with LTBI, who had tuberculin skin test (TST) conversion during their work, between 2000 and 2015, in a single tertiary academic medical centre, and who consented to answer a questionnaire, were enrolled. RESULTS: Overall, 147 of 219 (67%) with TST conversion agreed to participate. Acceptance rate for LTBI treatment was only 16%. The overall completion rate among those who accepted treatment was 87%. HCWs' recall of discussing the importance of LTBI treatment with their caregiver had the strongest association with LTBI treatment acceptance: 23 of 52 HCWs (44%) who recalled this discussion accepted treatment (adjusted OR=10.2, 95% CI: 2.2 to 47.6, p=0.003). Knowing the risk of developing TB was associated with 3.7 increased odds to accept treatment (95% CI: 1.2 to 11.8, p=0.02). CONCLUSIONS: LTBI acceptance rate was very low among our HCWs. Focusing on educating HCWs is potentially the key step towards an increased rate of LTBI treatment acceptance.

Characterizing the differences between multisystem inflammatory syndrome in children and Kawasaki disease.

To characterize the new SARS-Co-V-2 related multisystem inflammatory syndrome in children (MIS-C) among Israeli children and to compare it with Kawasaki disease (KD). We compared, in two medical centers, the clinical and laboratory characteristics of MIS-C, KD and an intermediate group, which met the case definitions of both conditions. MIS-C patients were older, were more likely to be hypotensive, to have significant gastrointestinal symptoms, lymphopenia and thrombocytopenia and to have non-coronary abnormal findings in their echocardiogram. Lymphopenia was an independent predictor of MIS-C. Most of our MIS-C patients responded promptly to corticosteroid therapy. KD incidence in both centers was similar in 2019 and 2020. Although there is clinical overlap between KD and MIS-C, these are separate entities. Lymphopenia clearly differentiates between these entities. MIS-C patients may benefit from corticosteroids as first-line therapy.

Interaction Tolerance Detection Test for Understanding the Killing Efficacy of Directional Antibiotic Combinations.

Combination treatments are commonly prescribed for enhancing drug efficacy, as well as for preventing the evolution of resistance. The interaction between drugs is typically evaluated near the MIC, using growth rate as a measure of treatment efficacy. However, for infections in which the killing activity of the treatment is important, measurements far above the MIC are needed. In this regime, the killing rate often becomes weakly concentration dependent, and a different metric is needed to characterize drug interactions. We evaluate the interaction metric on killing using an easy visual assay, the interaction tolerance detection test (iTDtest), that estimates the survival of bacteria under antibiotic combinations. We identify antibiotic combinations that enable the eradication of tolerant bacteria. Furthermore, the visualization of the antibiotic interactions reveals directional drug interactions and enables predicting high-order combination outcomes, therefore facilitating the determination of optimal treatments. IMPORTANCE The killing efficacy of antibiotic combinations is rarely measured in the clinical setting. However, in cases where the treatment is required to kill the infecting organism and not merely arrest its growth, the information on the killing efficacy is important, especially when tolerant strains are implicated. Here, we report on an easy method for the determination of the killing efficacy of antibiotic combinations which enabled to reveal combinations effective against tolerant bacteria. The results could be generally used to guide antimicrobial therapy in life-threatening infections.

Effect of tolerance on the evolution of antibiotic resistance under drug combinations.

Drug combinations are widely used in clinical practice to prevent the evolution of resistance. However, little is known about the effect of tolerance, a different mode of survival, on the efficacy of drug combinations for preventing the evolution of resistance. In this work, we monitored Staphylococcus aureus strains evolving in patients under treatment. We detected the rapid emergence of tolerance mutations, followed by the emergence of resistance, despite the combination treatment. Evolution experiments on the clinical strains in vitro revealed a new way by which tolerance promotes the evolution of resistance under combination treatments. Further experiments under different antibiotic classes reveal the generality of the effect. We conclude that tolerance is an important factor to consider in designing combination treatments that prevent the evolution of resistance.

Multisystem Inflammatory Syndrome in Children Associated With Severe Acute Respiratory Syndrome Coronavirus-2 in an 8-Week-Old Infant.

We describe an 8-week-old infant with severe gastrointestinal symptoms, significant hypoalbuminemia, and mild carditis following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infant's symptoms, including their temporal appearance, were consistent with multisystem inflammatory syndrome in children (MIS-C). A unique finding on colonic histology which may shed light on the pathogenesis of MIS-C was identified. The patient improved significantly following several anti-inflammatory treatments. The lag between the presentation of MIS-C and initial SARS-CoV-2 exposure, which may often be asymptomatic, together with the young age of our patient, makes this a challenging diagnosis. Clinicians should be aware of this entity, even in the neonatal and infantile age groups, to facilitate timely identification and treatment.

Mode of delivery and offspring adiposity in late adolescence: The modifying role of maternal pre-pregnancy body size.

OBJECTIVE: To study the association between mode of delivery and offspring BMI in late adolescence in a large cohort that predated the obesity epidemic, and assess the role of maternal pre-pregnancy BMI (ppBMI) in this association. STUDY DESIGN: We conducted a historical prospective study in the setting of the Jerusalem Perinatal Study (JPS), a population-based cohort that includes all 17,003 births to residents of West Jerusalem, between 1974 and 1976. Offspring's BMI at age 17 was obtained upon army recruitment and was available for 11,001 of cohort participants. The associations were examined using logistic regressions, adjusting for socio-demographic characteristics and for proxies for indication for C-Section birth. Analyses were then stratified by quartiles of ppBMI. RESULTS: C-Section was associated with offspring overweight/obesity, with adjusted OR of 1.44 (95%CI:1.14-1.82). Significant interaction of ppBMI with mode of delivery was observed, such that the associations of C-Section with overweight/obesity were limited to the upper quartile of ppBMI (adjusted OR = 1.70, 95%CI:1.18-2.43). Restricting the analyses to singleton first births and excluding pregnancies complicated with toxemia and gestational diabetes yielded similar findings. CONCLUSIONS: C-Section was positively associated with being overweight/obese at age 17. Importantly, ppBMI modified this association, with a significant association between C-Section and overweight/obesity evident only among offspring born to mothers in the highest ppBMI quartile. In light of the growing rates of obesity in women of reproductive age, these results should be considered in patient-doctor shared decisions related to selection of mode of delivery, in the absence of a clear medical indication.