Efficacy of a third BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL who failed standard 2-dose vaccination.

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to coronavirus disease 2019 (COVID-19) vaccination. Here, we evaluated the antibody response to a third BNT162b2 mRNA vaccine in patients with CLL/small lymphocytic lymphoma (SLL) who failed to achieve a humoral response after standard 2-dose vaccination regimen. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were measured 3 weeks after administration of the third dose. In 172 patients with CLL, the antibody response rate was 23.8%. Response rate among actively treated patients (12.0%; n = 12/100) was lower compared with treatment-naïve patients (40.0%; n = 16/40; OR = 4.9, 95% CI 1.9-12.9; P < .001) and patients off-therapy (40.6%; n = 13/32; OR = 5.0, 95% CI 1.8-14.1; P < .001), (P < .001). In patients actively treated with Bruton's tyrosine kinase (BTK) inhibitors or venetoclax ± anti-CD20 antibody, response rates were extremely low (15.3%, n = 9/59, and 7.7%, n = 3/39, respectively). Only 1 of the 28 patients (3.6%) treated with anti-CD20 antibodies <12 months prior to vaccination responded. In a multivariate analysis, the independent variables that were associated with response included lack of active therapy (OR = 5.6, 95% CI 2.3-13.8; P < .001) and serum immunoglobulin A levels ≥80 mg/dL (OR = 5.8, 95% CI 2.1-15.9; P < .001). In patients with CLL/SLL who failed to achieve a humoral response after standard 2-dose BNT162b2 mRNA vaccination regimen, close to a quarter responded to the third dose of vaccine. The antibody response rates were lower during active treatment and in patients with a recent exposure (<12 months prior to vaccination) to anti-CD20 therapy. This trial was registered at www.clinicaltrials.gov as #NCT04862806.

Using weight-for-age as a screening tool for metabolic syndrome in apparently healthy adolescents.

BACKGROUND: The increasing prevalence of metabolic syndrome (MetS) among adolescents necessitates a simple and easy-to-use screening tool. This study aimed to develop and validate a simple model based on age, sex, race, and weight-for-age or BMI-for-age to identify adolescents with MetS. METHODS: A cross-sectional study of adolescents (aged 12-18 years) who participated in the American National Health and Nutrition Examination Survey (NHANES) was performed. Participants with pre-existing hypertension, diabetes or dyslipidemia were excluded. Data from 2005-2018 were randomly divided into training (70%) and validation (30%) sets. Anthropometric, demographic data, and MetS criteria were extracted. RESULTS: The training group included 1974 adolescents (52% boys, median age 15 years), and the validation group included 848 adolescents (50% boys, median age 14 years). Both weight- and BMI-for-age demonstrated good discrimination ability in the training group (AUC = 0.897 and 0.902, respectively), with no significant difference between them (p = 0.344). Multivariable models showed similar discrimination ability. Therefore, weight-for-age was chosen and using Youden's index, the 93rd weight-for-age percentile (SDS 1.5) was identified as the optimal cut-off value for MetS. Similar values were observed in the validation group. CONCLUSIONS: Among adolescents aged 12-18 years, weight-for-age percentiles are an easy-to-use primary screening indicator for the presence of MetS. IMPACT: The prevalence of metabolic syndrome in adolescents is increasing. An early detection screening tool is required to prevent related adulthood morbidity. Screening adolescents for metabolic syndrome is challenging. This study suggests the use of weight-for-age as a single criterion for primary screening of adolescents aged 12-18. Using weight-for-age as a single predictor of metabolic syndrome is expected to increase screening rates compared to using BMI-for-age, due to its simplicity.

Bile Duct Colonization With Enterococcus sp. Associates With Disease Progression in Primary Sclerosing Cholangitis.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation of the biliary mucosa. Bile ducts in PSC are often colonized with bacteria. Although accumulating evidence demonstrates the importance of microbiota for mucosal immunity, little is known about the impact of bile duct colonization with bacteria on the clinical course of PSC. METHODS: Bile samples were sent to culture during endoscopic retrograde cholangio-pancreatography before the administration of peri-interventional antibiotics. Procedures during overt bacterial cholangitis or with prior antibiotic treatment were excluded. The primary endpoint was defined as a composite clinical endpoint of decompensated cirrhosis and/or liver transplantation or death. RESULTS: A cohort of 189 patients with 591 bile fluid cultures was included. In multivariable Cox regression analysis, the presence of Enterococci (present in 28% of the patients), but not of other bacterial species, conferred risk of disease progression with a hazard ratio of 3.61 (95% confidence interval, 1.6-8.11; P = .002) to reach the composite clinical endpoint. Fungobilia, present in 19.6% of patients, was confirmed to associate with disease progression with a hazard ratio of 3.25 (95% confidence interval, 1.87-5.66; P < .001) to reach the composite clinical endpoint. CONCLUSIONS: The novel association of biliary colonization by Enterococci with disease progression underlines the importance of microbiota-mucosal interplay for the pathogenesis of PSC. These results should stimulate further mechanistic studies on the role of microbiota in PSC and highlight potential new therapeutic targets for a disease without effective treatment options.

MRI can accurately diagnose breast cancer during lactation.

OBJECTIVE: To test the diagnostic performance of breast dynamic contrast-enhanced (DCE) MRI during lactation. MATERIALS AND METHODS: Datasets of 198 lactating patients, including 66 pregnancy-associated breast cancer (PABC) patients and 132 controls, who were scanned by DCE on 1.5-T MRI, were retrospectively evaluated. Six blinded, expert radiologists independently read a single DCE maximal intensity projection (MIP) image for each case and were asked to determine whether malignancy was suspected and the background-parenchymal-enhancement (BPE) grade. Likewise, computer-aided diagnosis CAD MIP images were independently read by the readers. Contrast-to-noise ratio (CNR) analysis was measured and compared among four consecutive acquisitions of DCE subtraction images. RESULTS: For MIP-DCE images, the readers achieved the following means: sensitivity 93.3%, specificity 80.3%, positive-predictive-value 70.4, negative-predictive-value 96.2, and diagnostic accuracy of 84.6%, with a substantial inter-rater agreement (Kappa = 0.673, p value < 0.001). Most false-positive interpretations were attributed to either the MIP presentation, an underlying benign lesion, or an asymmetric appearance due to prior treatments. CAD's derived diagnostic accuracy was similar (p = 0.41). BPE grades were significantly increased in the healthy controls compared to the PABC cohort (p < 0.001). CNR significantly decreased by 11-13% in each of the four post-contrast images (p < 0.001). CONCLUSION: Breast DCE MRI maintains its high efficiency among the lactating population, probably due to a vascular-steal phenomenon, which causes a significant reduction of BPE in cancer cases. Upon validation by prospective, multicenter trials, this study could open up the opportunity for breast MRI to be indicated in the screening and diagnosis of lactating patients, with the aim of facilitating an earlier diagnosis of PABC. KEY POINTS: • A single DCE MIP image was sufficient to reach a mean sensitivity of 93.3% and NPV of 96.2%, to stress the high efficiency of breast MRI during lactation. • Reduction in BPE among PABC patients compared to the lactating controls suggests that several factors, including a possible vascular steal phenomenon, may affect cancer patients. • Reduction in CNR along four consecutive post-contrast acquisitions highlights the differences in breast carcinoma and BPE kinetics and explains the sufficient conspicuity on the first subtracted image.

A new metabolic syndrome prediction model for self-evaluation as a primary screening tool in an apparently MetS-free population.

BACKGROUND: Metabolic syndrome (MetS) is a growing global public health concern associated with increased morbidity and mortality. The study aimed to establish a simple self-evaluated prediction model to identify MetS. METHODS: A cross-sectional study based on the American National Health and Nutrition Examination Survey database was performed. Participants aged ≥20 in the 2009-2018 surveys, with no current pregnancy or major morbidities, were included. The model was built with data from 2009 to 2016 and validated using 2017-2018 data. MetS was defined according to AHA/NHLBI guidelines. Multivariable logistic regression was applied to build a prediction model. The area under the receiver operating characteristic curve (AUC) was used to assess the discrimination ability and the maximal Youden's index was used to identify the optimal cut-off value. RESULTS: The study included 4245 individuals (median age 37, IQR 28-49, 51.8% females) in the training group and 911 individuals (median age 37, IQR 28-52, 52.5% females) in the validation group. Older age, male gender, non-Black race, no postsecondary education, and higher BMI were significantly associated with increased risk of MetS. The final model included age, gender, race, education, and BMI, and showed good discrimination ability (AUC = 0.810, 95% CI 0.793-0.827, sensitivity 80.4%, specificity 66.2%, positive likelihood ratio 2.379, negative likelihood ratio 0.296, PPV 59.6% and NPV 84.5%). CONCLUSION: A new model for self-evaluation may serve as a primary, easy-to-use screening tool to identify MetS in an apparently MetS-free population. A simple application may serve for primary and secondary prevention, thus enabling risk reduction in the development of cardiovascular morbidity and health expenditure.

The Yield of Routine Tissue Sampling in Pediatric Gastrointestinal Endoscopy.

OBJECTIVES: Societies' guidelines suggest routine tissue sampling in all children undergoing esophagogastroduodenoscopy and ileocolonoscopy, even in the absence of visible endoscopy abnormalities. We aimed to determine the agreement between endoscopic and histopathological findings in pediatric endoscopy and to assess the yield of routine biopsies from all sites. METHODS: Since January 2019, our endoscopy institute protocol has included routine biopsies sampling from the esophagus, stomach, duodenum, ileum, and colon in all diagnostic procedures. Agreement between tests was done using the kappa coefficient ( κ ). The study included all endoscopies performed during 2019. RESULTS: In total, 541 diagnostic endoscopies were done during the study period with 434 (80%) esophagogastroduodenoscopy and 107 (20%) were ileocolonoscopy. Compared to histology, endoscopic findings performance were: esophagus-sensitivity 33%, specificity 98%; stomach-sensitivity 60%, specificity 89%; duodenum-sensitivity 50%, specificity 97%; duodenal bulb-sensitivity 47%, specificity 89%; terminal ileum-sensitivity 82%, specificity 100%; colon-sensitivity 84%, specificity 96%. Assessment of concordance between endoscopic and histopathologic findings reveals an overall low level of agreement in esophagogastroduodenoscopy ( κ of 0.39, 0.51, 0.53, and 0.24 for the esophagus, stomach, duodenal second part, and bulb, respectively), and good agreement in ileocolonoscopy ( κ of 0.88 and 0.81 for the ileum and colon, respectively). CONCLUSIONS: Endoscopy findings are highly specific for histologic pathology, whereas the absence of findings correlates poorly with histologic findings. Ileocolonoscopy shows better agreement than esophagogastroduodenoscopy. Our data support routine tissue sampling in pediatric endoscopy.

Trends in Biochemical Parameters, Healthcare Resource and Medication Use in the 5 Years Preceding IBD Diagnosis: A Health Maintenance Organization Cohort Study.

BACKGROUND: Few data describing pre-diagnosis changes in patients with inflammatory bowel disease (IBD) exist. We aimed to determine if there is a pattern of change in use of health resources, medications and laboratory results in the years preceding diagnosis. METHODS: This retrospective study used electronic medical records of Maccabi Health Services (MHS). Patients with IBD ≥ 16 years of age and minimum of 5-years follow-up were identified by entry into the MHS IBD registry and included in the analysis. Demographic, clinical, medication and laboratory data were collected. Generalized estimating equation model was applied to study trends and compare between years. RESULTS: This study included 5643 patients with IBD. Of these, 3039 (53.8%) had Crohn's disease (CD), 2322 (41.1%) had ulcerative colitis (UC) and 282 (5%) had indeterminate colitis (IC). Laboratory parameters including white blood cells, platelets and C-reactive protein showed significant increases while haemoglobin and mean cell volume showed significant decreases in mean values in the 2 years prior to diagnosis with stable values prior to that (p < 0.0001). Parameters such as creatinine, total protein and albumin showed significant, progressive decreases in mean values starting 5 years prior to diagnosis (p < 0.0001). Patients with CD had distinct laboratory trends when compared with patients with UC. CONCLUSIONS: Changes in laboratory parameters, healthcare service and medication use occur during the 5-year period before IBD diagnosis. These data can have future clinical applicability by developing a composite score and referral algorithm introducing red flags into primary care visits and appropriate referral for specialist care.

Increased fracture risk among children diagnosed with attention- deficit/hyperactivity disorder: a large matched cohort study.

To analyse the risk of fractures among children with attention-deficit/hyperactivity disorder (ADHD) compared with matched children without ADHD; and to evaluate the impact of pharmacological treatment. This registry-based cohort study included 31,330 children diagnosed with ADHD and a comparison group of 62,660 children matched by age, sex, population sector and socioeconomic status. Demographic and clinical information was extracted from the electronic database of Meuhedet, a health maintenance organization. Fracture events between 2-18 years of age were identified by coded diagnoses. The overall fracture incidence rate was 334 per 10,000 patient-years (PY) in the ADHD group and 284 per 10,000 PY in the comparison group (p < 0.001). Among boys, the fracture incidence rates were 388 per 10,000 PY and 327 per 10,000 PY (p < 0.001), for the respective groups. Among girls, the rates were lower in both groups compared to boys, but higher in the ADHD compared to the matched group (246 vs 203 per 10,000 PY, p < 0.001). Among the children with ADHD, the hazard ratios (HR) to have a fracture were similar in boys (1.18, 95%CI 1.15-1.22, p < 0.001) and girls (1.22, 95%CI 1.16-1.28, p < 0.001). Children with ADHD were also at increased risk for two and three fractures; the hazard ratios (HRs) were 1.32 (95%CI 1.26-1.38, p < 0.001) and 1.35 (95%CI 1.24-1.46, p < 0.001), respectively. In a multivariable model of the children with ADHD, pharmacological treatment was associated with reduced fracture risk (HR 0.90, 95%CI 0.82-0.98, p < 0.001) after adjustment for sex, resident socioeconomic status and population sector.   Conclusion: Children with ADHD had greater fracture risk than a matched group without ADHD. Pharmacological treatment for ADHD may decrease this risk. What is Known: • Children with attention-deficit/hyperactivity disorder (ADHD) may be more prone to injuries and fractures than children without ADHD. What is New: • Children with ADHD were 1.2 times more likely to have a fracture than children with similar characteristics, without ADHD. The increased risk for fractures was even greater for two and three fractures (hazard ratios 1.32 and 1.35, respectively). • Our study suggests a positive effect of pharmacological treatment for ADHD in reducing fracture risk.

Routine statins use is associated with less adverse outcome in patients above 70 years of age admitted to hospital with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to multiorgan insufficiency and death, particularly among the older adults. Statins have been suggested as potentially protective drugs due to their pleotropic effects, but the actual benefit of statin use among the older population in this setting is not clear. This study aimed to evaluate the association between preadmission statin use and the presentation and clinical outcomes of hospitalized COVID-19 patients older than 70 years of age. METHODS: A historical cohort study of all patients above 70 years of age who were hospitalized with COVID-19 infection in a large academic hospital between March and August 2020 was performed. The association between preadmission statin use and patients' presentation and adverse outcome was studied. Adverse outcome was defined as any of the following: shock, invasive or non-invasive ventilation, organ insufficiency, myocardial infarction, cerebrovascular accident, in-hospital or 30-day post-admission mortality, hospital stay longer than the median length of stay of all COVID-19 patients, referral to nursing home or rehabilitation center. RESULTS: Seventy-two (44%) of the 163 studied patients (median age 82 years, 45% males) had been preadmission treated with statins. The statin-treated patients (STP) had a higher prevalence of diabetes (40% vs 24%, p = 0.028) and cardiovascular disease (58% vs. 34%, p = 0.002). Seventy two percent of the STP had adverse outcome, compared to 86% of the non-STP (p = 0.033). After adjustment for potential confounders, prior statin use was associated with decreased risk for an adverse outcome (odds ratio = 0.4, 95% confidence interval 0.18-0.92, p = 0.03). CONCLUSIONS: The preadmission use of statins was associated with a lower risk of adverse outcome in older adults hospitalized with COVID-19. Continuation of statin treatment might be implemented for risk reduction of adverse outcomes in the older population in the era of new SARS-CoV-2 variants and less effective vaccines.

Growth hormone treatment and the risk of adolescent scoliosis: A large matched cohort study.

AIM: We aimed to evaluate the risk of developing adolescent scoliosis among recipients of recombinant human growth hormone (rhGH). METHODS: This registry-based cohort study included 1314 individuals who initiated rhGH treatment since 2013, treated during 10-18 years of age for at least 6 months. This group was matched to a comparison group of 6570 individuals not treated with rhGH. Demographic and clinical information was extracted from the electronic database. The results are presented using hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: During a median follow-up of 4.2 years, 59 (4.5%) rhGH recipients and 141 individuals (2.1%) from the comparison group were diagnosed with adolescent scoliosis. The age at diagnosis did not differ between the groups (14.7 versus 14.3 years, p = 0.095). Patients treated with rhGH were more likely diagnosed with scoliosis (HR 2.12, 95% CI 1.55-2.88, p < 0.001). Among males, the risk was about three times greater in the treated versus the comparison group (HR 3.15, 95% CI 2.12-4.68, p < 0.001), while in females the risk was not increased (HR 1.12, 95% CI 0.72-2.04, p = 0.469). CONCLUSIONS: Recombinant human growth hormone treatment was associated with an increased risk to be diagnosed with adolescent scoliosis in males. Scoliosis development should be monitored appropriately in rhGH recipients.

Left atrium volume and ventricular volume ratio algorithm as indication of pulmonary hypertension etiology.

BACKGROUND: Pressure overload of the right heart (pulmonary hypertension [PH]) can be an acute or a chronic process with various pathophysiologic changes affecting the dimensions of the heart chambers. The automatic four-chamber volumetric analysis tool is now available to measure the volume of the cardiac chambers in patients undergoing a computed tomography pulmonary angiogram (CTPA). PURPOSE: To characterize the volumetric changes that occurred in response to increased systolic pulmonary arterial pressures (sPAP) in acute events, such as acute pulmonary embolism (APE), compared with other etiologies. MATERIAL AND METHODS: Consecutive patients who underwent CTPA and echocardiography within 24 h between 2011 and 2015 were included. Differences in cardiac chamber volumes were investigated in correlation to the patients' sPAP. RESULTS: The final cohort of 961 patients included 221 (23%) patients diagnosed with APE. The right (RV) to left (LV) ventricular volume ratio (VVR) was higher, while the left atrial (LA) volume index was smaller (P < 0.001) in the patients with APE. A decision tree for the prediction of APE showed that an RV to left VVR >2.8 was characteristic of APE, whereas an LA volume index >37.5 mL/m² was more compatible with PH due to other etiologies (P < 0.001). CONCLUSION: The combination of VVR and LA volume index may help in differentiating between APE and chronic PH. CTPA-based volumetric information may be used to help clarify the underlying etiology of the dyspnea.

Quality of life after radio frequency ablation turbinate reduction (RFATR) among patients with rhinitis medicamentosa & withdrawal from decongestant topical spray abuse.

OBJECTIVE: Radiofrequency ablation (RFA) reliefs nasal obstruction and improves quality of life (QoL) in patients suffering from inferior turbinate hypertrophy (ITH). A substantial benefit was noted among patients suffering from Rhinitis Medicamentosa (RM), enabling ending decongestant spray abuse. Our aim was to establish the benefit from RFA with respect to QoL in patients suffering from ITH, due to the presence of RM. STUDY DESIGN: Prospective cohort study. METHODS: Prospective Cohort study, including patients suffering from ITH undergoing RFA between 9.2017 and 9.2019 in Tel Aviv Medical Center. The cohort was divided to RM and non-RM (including allergic, non-allergic) patients. The differences between the groups were compared before and after RFA, and included patients' complaints, clinical findings and QoL questionnaires (SNOT-22 & NOSE). In the RM group, the ability to wean from decongestants was also described. RESULTS: Our data demonstrated subjective QoL improvement following RFA (88.9 %, N = 90). All RM patients withdrawaled from nasal decongestant spray. NOSE questionnaire demonstrated a significant improvement in QoL after RFA in the RM group (PV = 0.025). SNOT-22 did not demonstrate significant difference in QoL between RM and the reference group (PV = 0.1). Rates of MCID>8.3 were high, without significant difference between the groups (PV = 0.2). CONCLUSION: RFA demonstrated effectiveness in achieving of withdrawal from decongestant spray in RM patients and may be a possible definitive treatment option for this group. The nasal obstruction component in SNOT-22 questionnaire & NOSE questionnaire showed improved QoL in comparison to controls. High QoL after RFA was established in our entire cohort.

Fast vs. Regular Track for Lung and Pancreatic Cancer Diagnosis-Time from Initial Finding to Final Diagnosis and Patient Survival.

BACKGROUND: Health systems around the world have begun implementing unique tracks to expedite diagnosis and improve survival of patients with suspected cancers. This study aimed to compare characteristics and survival between patients diagnosed by way of fast and regular diagnostic tracks. METHODS: A historical cohort study of patients (age ≥ 18) diagnosed with lung or pancreatic cancers between 09/2017 and 03/2020 on a fast diagnostic track and treated in a tertiary hospital versus a random sample of patients with the same cancer types who began treatment in the hospital over the same period of time after being diagnosed utilizing the regular track in the community. RESULTS: The study included 336 patients (108 fast-track diagnostics, 228 regular track diagnostics). Advanced stages III-IV at diagnosis were more likely in the fast-track group (94.4% vs. 81.1%, p = 0.001). The median time from initial cancer suspicion to diagnosis was 21 days (IQR 14-37) for the fast-track vs. 31 days (IQR 18-51) for the regular track (p < 0.001). During the follow-up period, 56 patients from the fast-track and 131 patients from the regular track died. No significant difference was found in the median survival time between the fast and regular tracks, whether from the onset of symptoms, diagnosis, or treatment initiation. CONCLUSION: Patients referred to the fast-track were more likely to be diagnosed at a further advanced stage of their cancer. The fast-track shortened the time until diagnosis and treatment but no difference was found in median survival between the tracks, perhaps due to late referral and high fatality rates.

Exploring Popular Social Media Networks for Patients With Inflammatory Bowel Diseases: Insights for Better Care.

GOAL: The aim was to assess topics of interest and concerns among patients with inflammatory bowel diseases (IBD) who are active online. BACKGROUND: Social media (SM) networks are a major communication tool for patients with IBD and health care professionals. PATIENTS AND METHODS: We performed an anonymized investigation of SM networks for IBD patients; I-a thematic analysis of patients' posts, II-an online survey advertised through Facebook and other popular SM networks throughout November 2019. RESULTS: Analyzing 2133 posts (2014 to 2019) revealed 18 topics of interest. The online survey was completed by 534 respondents [63%-Crohn's disease, 56%-female, median age-38 years (interquartile range: 28.7 to 51.0)]. Most respondents (70%) were followed in referral centers, and 45% were receiving biological therapy. Respondents reported high satisfaction with IBD care and health care provider professionalism. The top 5 topics of interest were diet, lifestyle, complementary and alternative medicine, diagnostic test interpretation, and specialist referrals and reviews. Cluster analysis demonstrated that gender, income, and education level were associated with specific interest and concerns. CONCLUSION: Patients' activity on SM is independent of their satisfaction with formal IBD care and rather reflects an ongoing need for information and support. These needs may be addressed both in clinical settings and through online tools.

Characteristics of Second-Line Investigations of Middle-Aged Athletes Who Failed Preparticipation Examinations.

OBJECTIVE: The role of exercise testing during preparticipation examinations (PPEs) of middle-aged athletes is uncertain. This study examined the characteristics of disqualifications after an initial PPE that includes an exercise test in competitive athletes older than 30 years. We investigated disqualification rates and reasons, second-line investigations performed, and final decisions regarding competitive sports participation. DESIGN: Chart review. SETTING: Sports medicine clinic. PARTICIPANTS: Athletes aged >30 years that performed an exercise test as part of their annual PPE at our sports medicine clinic (n = 866). INDEPENDENT VARIABLES: Age, sex, height, weight, sport type, cardiovascular risk factors, and abnormal PPE findings. MAIN OUTCOME MEASURES: Additional investigations performed, approval/disqualification regarding competitive sports participation. RESULTS: The initial disqualification rate of athletes was 9.8%. Three (3.6%) athletes were disqualified following questionnaire and physical examination, 19 (22.4%) because of resting electrocardiogram findings, and 65 (76.5%) following the exercise test. After additional work-up, only 5 athletes (0.4%) were ultimately found ineligible for competitive sports. From those, only 2 athletes (0.2%) were disqualified because of exercise test findings, which were episodes of supraventricular tachycardia and not ischemia-related. CONCLUSIONS: The addition of an exercise test to the PPE of middle-aged athletes is of limited value. If exercise testing of older athletes is performed, arrhythmias are probably of higher significance than ST-T changes.

Pediatric obesity and body weight following the COVID-19 pandemic.

BACKGROUND: The SARS-CoV-19 pandemic and its associated lockdowns affected children's lifestyle dramatically. The effect of such changes on children's weight and obesity status is unknown. The aim of this study was to compare body weight and obesity rates in children from before the pandemic to 6 months after the major periods of lockdowns in Israel. METHODS: We used data from medical records of pediatric emergency department visits, where weight is routinely measured, to compare weight and obesity prevalence in the fourth quartile of 2020 (n = 2468) as compared with the fourth quartiles of 2018-2019 (n = 5300). Weight was transformed to age- and sex-specific standard-deviation-scores (SDS) for analysis. RESULTS: Weight-SDS increased by a mean of 0.07 during the first 6 months of the pandemic, yet this was only significant in preschoolers. Obesity rates also increased in this age group only, by 37%, from 8.1% to 11.1% (p = 0.01). CONCLUSIONS: Weight-SDS and obesity prevalence increased during the SARS-CoV-19 pandemic, yet only in younger children. Additional studies from other populations are needed.

Early Indolent Course of Crohn's Disease in Newly Diagnosed Patients Is Not Rare and Possibly Predictable.

BACKGROUND & AIMS: The early stages of Crohn's disease (CD) course are heterogeneous, and it is a challenge to predict the course of disease in patients with new diagnosis. METHODS: We performed an observational longitudinal study of 156 adults (79 male; median age, 27.7 years; 57 treatment naïve) with newly diagnosed CD (within 6 months of enrollment), referred from medical centers and community clinics in Israel from 2013 through 2017. Study participants each received semi-annual scheduled evaluations. Indolent disease was defined as a disease course without need for strict interventions to control complicated course of CD (hospitalization or surgery, or decision to start steroid, immunomodulator, or biologic therapy). Cox regression and receiver operating characteristic analyses were used to identify factors associated with early indolent or complicated course of CD. We validated our findings in an independent cohort of patients with CD from a separate medical center in Israel in 2018. RESULTS: Over a median follow-up period of 17.2 months (interquartile range, 8.8-23.8 months), 52 patients (33.3%) had an indolent course of CD, 29 (18.5%) required hospitalizations, and 75 (48%) were recommended to start steroid, immunomodulator, or biologic therapies. The median time to first intervention was 3.4 months (95% CI, 2.4-4.4). We developed a model based on clinical factors that identified 4 factors associated with complicated course in treatment-naïve patients: body mass index <25 kg/m2 (hazard ratio [HR], 2.45; 95% CI, 1.07-5.43; P = .033), serum level of vitamin B12 <350 pg/mL (HR, 2.78; 95% CI, 1.21-6.41; P = .016), white blood cells ≥7 × 103/µL (HR, 2.419; 95% CI, 1.026-5.703; P = .044), and serum level of ALT ≥25 IU/L (HR, 2.680; 95% CI, 1.186-6.058; P = .018). This model discriminated between patients with vs without a complicated course of disease with 90% and 89% accuracy at 6 and 12 months after diagnosis, respectively. A validation cohort demonstrated a discriminatory ability of 79% at 3 months after diagnosis, and a nomogram was constructed. CONCLUSIONS: In an observational longitudinal study of 156 patients with newly diagnosed CD, we found that one third have an early indolent course of disease. We identified factors that can be measured at diagnosis to identify patients at risk for an early complicated course-these might be used in patient management and selection of treatment.

Daratumumab for relapsed AL amyloidosis-When cumulative real-world data precedes clinical trials: A multisite study and systematic literature review.

OBJECTIVES: Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab treatment in RRAL in real-world setting. METHODS: A retrospective multisite study of RRAL patients treated with daratumumab alone and in combinations. RESULTS: Forty-nine patients, diagnosed between 1.1.2008 and 1.2.2018 were included; 27% also had multiple myeloma (MM). Revised Mayo score was ≥ 3 in 67%. Hematologic overall response rate was 81%, 64% achieved very good partial response (VGPR) or better. Concurrent active MM was associated with lower rates of VGPR (OR 0.19, 95% CI 0.04-0.81; P = .03) in a multi-variate analysis. Cardiac and renal responses were 74% and 73%, respectively. Median progression-free survival (PFS) was 28.4 months and median overall survival (OS) was not reached; 2-year PFS and OS were 68.6 ± 7.5% and 90.4 ± 4.6%, respectively. Hematologic response correlated with prolonged PFS and OS. Daratumumab was safe and well tolerated, no patients discontinued therapy due to toxicity. Our data was aligned with outcomes from a systematic literature review, which identified 10 case series (n = 517) and 2 clinical trials (n = 62) meeting prespecified criteria. CONCLUSIONS: Our data support favorable safety tolerability and efficacy of daratumumab among non-selective RRAL patients in a real-world setting.

Twin discordance: a study of volumetric fetal brain MRI and neurodevelopmental outcome.

OBJECTIVE: This study employed magnetic resonance imaging (MRI) to compare brain volumes of discordant twins and examined their neurodevelopment after birth by using a validated exam. STUDY DESIGN: A prospective historical cohort study of discordant dichorionic diamniotic (DCDA) or monochorionic diamniotic (MCDA) twin fetuses, who undergone an MRI scan to evaluate growth restriction in the discordant twin (weight < 10th centile) during 6 years period, at a single tertiary center. Twenty-seven twin pairs were included in the volumetric study and 17 pairs were included in the neurodevelopmental outcome examination. The volumes of the supratentorial brain region, both hemispheres, eyes, and the cerebellum were measured by 3D MRI semi-automated volume measurements. Volumes were plotted on normal growth curves and discordance was compared between weight at birth and brain structure volumes. Neurodevelopmental outcome was evaluated using the VABS-II questionnaire at a mean age of 4.9 years. RESULTS: The volume of major brain structures was significantly larger in the appropriate-for-gestational-age twins (AGA) compared to the small-for-gestational-age (SGA) co-twins (p < 0.001). The birth weight discordance was 32.3% (24.9-48.6) and was significantly greater (p < 0.001) than the discordance of the prenatal supratentorial brain (13.6% [5.6-18]), cerebellum volume (21.7% [9.5-30.8]). Further neurodevelopmental outcome evaluation found no significant difference between the AGA twin and the SGA twin. CONCLUSION: In discordant twins, the smaller twin showed a "brain-preserving effect," which in our study was not associated with a worse neurodevelopmental outcome. The use of MRI in such cases may aid in decision-making and parental consultation. KEY POINTS: • Weight discordance at birth was significantly greater compared to intrauterine brain volume discordance measured by 3D MRI. • Small-for-gestational-age (SGA) fetuses preserve brain development. • In highly discordant twins, there was no long-term difference in neurodevelopmental outcome at a mean age of 4.9 years.

Anti-tissue transglutaminase titers are associated with endoscopic findings and severity of mucosal damage in children with celiac disease.

We aimed to assess the correlation between clinical findings, serology, endoscopic findings, and histology in children diagnosed with celiac disease. Medical records of children diagnosed with celiac disease (2010-2017) at the Schneider Children's Hospital were reviewed retrospectively. Correlation between serologic measures anti-tissue transglutaminase (anti-tTG)/anti-endomysial antibodies (EMA) and other variables including mucosal damage, endoscopic findings (scalloping of duodenal folds), and clinical findings (abdominal pain, diarrhea, and anemia) was assessed. Out of 686 patients, 432 patients fulfilled the inclusion criteria (females 262, 61%; median age 6.0; interquartile range 4.0-9.0 years). Distribution of histopathology findings was Marsh IIIa 4%, Marsh IIIb 25%, and Marsh IIIc 71% with 313 (73%) patients having anti-tTG titer of ≥ 10 times the upper normal limit. Anti-tTG titer (but not EMA) positively correlated with Marsh grades, scalloping of duodenal folds and anemia. Anti-tTG ≥ 10 times the upper normal limit was associated with Marsh IIIc changes with an adjusted odds ratio of 4.5 (95% confidence interval, 1.7-12.1). Diarrhea and abdominal pain were not associated with serologic, endoscopic, or histologic markers of disease severity.Conclusion: Anti-tTG titers correlated with macroscopic and microscopic mucosal damage, with anemia but not with diarrhea or abdominal pain in children with celiac disease. What is Known: • Tissue transglutaminase antibody titers were shown to correlate with the degree of mucosal damage in patients with celiac disease. • There is a limited evidence regarding the association of celiac serologies with endoscopic and clinical measures. What is New: • Higher titers of tissue transglutaminase but not anti-endomysial antibodies are associated with more severe histologic and endoscopic damage and with the presence of anemia. • Symptoms do not correlate with the severity of mucosal damage such as scalloping of duodenal folds and histopathology changes according to Marsh classification or with serologic markers.