Israel Medical Center Research Articles

Thiopurines Maintenance Therapy in Children With Ulcerative Colitis: A Multicenter Retrospective Study.

Thiopurines are an established treatment for pediatric ulcerative colitis (UC). However, data regarding safety and efficacy are lacking. We aimed to determine short and long-term outcome following thiopurines use in children with UC. We conducted a retrospective review of children (2-18 years) with UC treated with thiopurines between January 2008 and January 2019 at 7 medical centers in Israel. The primary outcome was corticosteroid (CS)-free clinical remission at week 52 following thiopurines initiation without the need for rescue therapy (infliximab, calcineurin inhibitors, or colectomy). A total of 133 children were included [median age at diagnosis of 12.4 (interquartile range 11.0-15.8) years, 30 (23%) left-sided colitis, 113 (85%) with moderate or severe disease at diagnosis]. At diagnosis 58 patients (44%) were treated with 5-aminosalicylates and 72 (54%) with CS. Sixty patients (45%) received thiopurines as 1st line maintenance therapy. Seventy-four patients (56%) had CS-free clinical remission at week 52 without rescue therapy. Predictors of clinical remission were not identified. In a sub-analysis among patients with steroid-responsive moderate to severe UC, 59 (55%) patients achieved this outcome. The likelihood of remaining free of rescue therapy among thiopurines-treated patients was 83%, 62%, 45%, and 37% at 1, 2, 3, and 4 years, respectively. More than half of children with UC starting thiopurines without previous or concomitant biologic therapy have CS-free clinical remission at 52 weeks later without the need for rescue therapy. Thiopurines are effective in pediatric UC and could be considered prior to biologics.

Vedolizumab Is Associated with Longer Drug Sustainability Compared to Infliximab in Moderate-to-Severe Ulcerative Colitis: Long-Term Real-World Cohort Data.

Drug sustainability (DS) is a surrogate marker for treatment efficacy. We aimed to compare the DS of two main biologics used to treat moderate-to-severe ulcerative colitis (UC), infliximab (IFX) and vedolizumab (VDZ), in a real-world setting. We conducted a retrospective cohort study at a tertiary medical center in Israel. We included patients treated between 1 December 2017 and 1 May 2021, who were followed for up to 300 weeks. DS was defined as corticosteroid-, surgical-, and hospitalization-free treatment. 217 patients with UC were included. VDZ had a significantly longer median DS of 265.6 weeks compared to IFX's 106.5 weeks (p = 0.001) in treatment-naïve patients, even when adjusting for disease severity (HR 0.55 95 CI 0.3-0.98, p = 0.042). In treatment-experienced patients, DS was comparable between IFX and VDZ (p = 0.593). VDZ showed significantly longer DS in treatment-naïve patients with UC compared to IFX, also when adjusted for disease severity. There was no difference in DS between VDZ and IFX in treatment-experienced patients and patients switching from one drug to another. VDZ may be a suitable first-line treatment for biologic-naïve patients with moderate-to-severe UC.

Chronic kidney disease and outcome of patients with tricuspid regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Although chronic kidney disease (CKD) is common among patients with tricuspid regurgitation (TR), these patients are under-represented in clinical trials examining tricuspid transcatheter interventions, and data regarding their outcome are limited. Methods Consecutive echocardiographic reports linked to clinical data from the largest medical center in Israel (2007–2022) were reviewed. Patients were dichotomized into three groups TR groups (mild, moderate and severe), following by stratification according to renal function. The primary outcome was all-cause mortality. Kaplan Meier, Multivariate Cox regression and interaction analysis models were applied. Results The final study population included 78,461 patients with a mean age of 65 (IQR: 55–78 years), 2,998 (4%) of whom had severe TR. There were 11,443 (15%) patients with at least moderate CKD (estimated glomerular filtration rate [eGFR] < 45 mL/min/1.73 m2), 5573 (7%) with eGFR<30 and 1853 (2%) with eGFR<=15. During a median follow-up period of 4 years (IQR: 1–7 years), 28,228 patients (36%) died. Kaplan-Meier survival analysis demonstrated an increased risk for death with both increasing severity of TR and/or CKD grade (log-rank p<.001 for both;). The association of severe TR with poor survival was consistent among all CKD subgroups (FIGURE). Multivariate Cox analysis with adjustment for age, sex, ejection fraction, estimated pulmonary pressure and eGFR demonstrated that compared to mild TR, patients with severe TR were 56% more likely to die during follow up (95% CI 1.47–1.66, p<.001). Interaction analysis demonstrated that the association of severe TR degree with survival was consistent in all subgroups but dependent on renal function, such that it was more pronounced as renal function declined, with adjusted HR of 1.6 among patients with eGFR<=15 (P for intercation <.001). Conclusions While the association of TR with poor survival is consistent across all CKD groups, it is more pronounced among patients with advanced CKD. When examining data and outcome of tricuspid clinical trials, special emphasis should be given to CKD status.

Maternal particulate matter exposure and gestational diabetes mellitus: a population–based cohort study

Gestational diabetes mellitus (GDM) prevalence is steadily increasing worldwide, posing a significant threat to the short- and long-term health of both mother and offspring. As particulate matter (PM) air pollution has been reported to affect glucose metabolism, it was suggested that maternal PM exposure may be associated with the development of GDM; however, evidence is limited and inconsistent. To study the association between maternal exposure to PM2.5 and PM10 and the risk of GDM, to identify critical windows of susceptibility and to evaluate effect modification by ethnicity. A retrospective cohort study was conducted including pregnancies of women who delivered at a large tertiary medical center in Israel between the years 2003 and 2015. Residential PM levels were estimated by a hybrid spatiotemporally resolved satellite-based model at 1-km spatial resolution. Multivariable logistic analyses were applied to study the association between maternal PM exposure in different pregnancy periods and GDM risk, while adjusting for background, obstetrical and pregnancy characteristics. Analyses were also stratified by ethnicity (Jewish / Bedouin). The study included 89,150 pregnancies, 3,245 (3.6%) were diagnosed with GDM. First trimester exposure to both PM2.5 (adj. OR per 5 μg/m3 = 1.09; 95%CI: 1.02, 1.17) and PM10 (adj. OR per 10 μg/m3 = 1.11; 95%CI: 1.06, 1.17) was significantly associated with increased risk for GDM. In the stratified analyses, the association with first trimester PM10 exposure was consistent among pregnancies of both Jewish and Bedouin women, while the association with first trimester PM2.5 exposure was significant among pregnancies of Jewish women only (adj. OR per 5 μg/m3 = 1.09; 95%CI: 1.00, 1.19), as well as association with preconception PM10 exposure (adj. OR per 10 μg/m3 = 1.07; 95%CI: 1.01, 1.14). No association was found between second trimester PM exposure and GDM risk. Maternal exposure to both PM2.5 and PM10 during the first trimester of pregnancy is associated with GDM, suggesting the first trimester as a particular window of susceptibility to the effect of PM exposure on GDM risk. The effects found in this study differed by ethnic group, emphasizing the importance of addressing ethnic disparities when assessing environmental impacts on health.

WED-308 - Clinical, demographic, laboratory characteristics and disease progression of autoimmune hepatitis patients, asymptomatic at diagnosis, in a tertiary medical center in Israel

WED-308 - Clinical, demographic, laboratory characteristics and disease progression of autoimmune hepatitis patients, asymptomatic at diagnosis, in a tertiary medical center in Israel

A 120-MINUTE SALINE INFUSION TEST FOR THE CONFIRMATION OF PRIMARY ALDOSTERONISM

Objective: Saline infusion test (SIT) for confirmation of primary aldosteronism (PA) traditionally requires two liters of normal saline and is 240 minutes long. Previous studies have raised concerns regarding increased blood pressure (BP) and worsening hypokalemia during and after SIT. Therefore, we aim to evaluate the diagnostic applicability of a shorter, one liter 120-minute-long SIT. Design and method: A cross-sectional study, including all consecutive patients with suspected PA who underwent SIT from 1st January 2015 to 31st December 2022 in a large, tertiary medical center in Israel. Blood samples were drawn for renin and aldosterone at baseline (t = 0), after 2 hours (t = 120 min), and after 4 hours (t = 240 min) of saline infusion. Receiver-operator curve (ROC) analysis was used to evaluate the sensitivity and specificity of various aldosterone cutoff values at t = 120 for the confirmation of PA. Logistic regression was performed to analyze the association of baseline variables and aldosterone levels after 120 minutes and after 240 minutes. Results: The final analysis included 55 patients. ROC analysis with an area under the curve (AUC) of 0.97 (95% CI [0.93, 1.00], P < 0.001) demonstrated 90% specificity and 92% sensitivity for an aldosterone cutoff value of 342 pmol/L at t = 120 to confirm PA. 45% (25/55) of patients did not suppress aldosterone levels after 240 minutes, of them 92% (23/25) did not suppress aldosterone at t = 120 according to the 342 pmol/L cutoff. Univariate analysis showed that male sex, hypokalemia, and elevated systolic BP were all associated with failure to suppress aldosterone levels below the traditional threshold for PA confirmation at t = 240 (i.e. <276 pmol/L), as well as below 342 pmol/L at t = 120. Mean systolic BP (SBP) at t = 0 was 139.9±21.2 mm/Hg and increased to 146.2±14.1 mm/Hg (p = 0.016) during the SIT. Conclusions: We present data showing that an aldosterone cutoff of 342 pmol/l at t = 120 has both high sensitivity and specificity for PA diagnosis confirmation.

Clinical characteristics of SARS-CoV-2 vaccine-related acute appendicitis.

In a large nationwide mass vaccination setting, the SARS-CoV-2 vaccine was recently linked to myocarditis, lymphadenopathy, herpes zoster infection and appendicitis. We aimed to examine the characteristics and management of SARS-CoV-2 vaccine-related acute appendicitis. We performed a retrospective cohort study in a large tertiary medical centre in Israel. All patients presenting with acute appendicitis within 21 days of receiving their SARS-CoV-2 vaccination (PCVAA group) were compared with patients who presented with acute appendicitis not related to the vaccination (N-PCVAA group). We reviewed the records of 421 patients with acute appendicitis from December 2020 to September 2021; 38 (9%) patients presented with acute appendicitis within 21 days of receiving their SARS-CoV-2 vaccination. Patients in the PCVAA group were older than those in the N-PCVAA group (mean 41 ± 19 yr v. 33 ± 15 yr, respectively, p = 0.008), with male predominance. More patients were managed nonsurgically during the pandemic than before the pandemic (24% v. 18%, p = 0.03). With the exception of older age, the clinical characteristics of patients presenting with acute appendicitis within 21 days of receiving the SARS-CoV-2 vaccination did not differ from those of patients who presented with acute appendicitis not related to the vaccination. This finding suggests that vaccine-related acute appendicitis is similar to "classic" acute appendicitis.

Erdafitinib treatment in metastatic urothelial carcinoma: a real-world analysis.

Erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor is a standard post chemotherapy advanced treatment line for metastatic urothelial carcinoma harboring FGFR2/3 genomic alterations. It was approved based on a phase 2 clinical trial, revealing a 40% response rate, and 13.8 months overall survival. These FGFR genomic alterations are uncommon. Thus, real-world data on erdafitinb use is scant. We herein describe erdafitinib treatment outcome in a real world patient cohort. We retrospectively reviewed the data of patients treated with erdafitinib from 9 Israeli medical centers. Twenty-five patients with metastatic urothelial carcinoma (median age 73, 64% male, 80% with visceral metastases) were treated with erdafitinib between January 2020 to October 2022. A clinical benefit (complete response 12%, partial response 32%, stable disease 12%) was seen in 56%. Median progression-free survival was 2.7 months, and median overall survival 6.73 months. Treatment related toxicity ≥ grade 3 occurred in 52%, and 32% discontinued therapy due to adverse events. Erdafitinib therapy is associated with a clinical benefit in the real world setting, and associated with similar toxicity as reported in prospective clinical trials.

Insights from 25years of oncogenetics: one person's perspective.

In early 1995, I established the oncogenetics service at the Genetics Institute of the Sheba Medical Center in Israel. The purpose of this article is to describe the key points and issues that were raised throughout my personal journey since then: physician and public awareness; ethical and legal issues; guidelines for oncogenetic counseling; the development of oncogenetic testing within the unique Israeli reality of the limited spectrum of BRCA1 and BRCA2 mutations; high-risk vs. population screening; and the definition and implementation of guidelines for surveillance of asymptomatic mutation carriers. Since 1995, oncogenetics has been transformed from a rare oddity to a pivotal player, and it represents a successful example of implementing personalized preventive medicine by identifying and providing care and by offering means for early detection and risk reduction for adults who are genetically predisposed to develop a potentially life-threatening disease-cancer in this case. Lastly, I outline my personal vision for the possible way forward for oncogenetics.

Impact of COVID-19 mandatory lockdown on maternal gestational weight gain and neonatal macrosomia rate at an academic medical center in Israel

Background In an effort to prevent the spread of coronavirus disease 2019 (COVID-19), governments restricted outdoor activities and imposed lockdown quarantine. This change in lifestyle probably affected individuals’ eating habits and physical activity. Objective To examine the effect of lockdown due to the COVID-19 pandemic on maternal antenatal weight gain, neonatal macrosomia, and other maternal and neonatal outcomes of women delivering at an academic medical center in Israel. Method A retrospective, two-period cohort study conducted at a university teaching medical center in Afula, Israel. The study period was between April and September 2020. This period signifies worsening in pandemic situations, during which citizens experienced strict prolonged lockdown measures. The parallel unexposed period (control period) was between April and September 2019. Singleton pregnancies delivered at >24 weeks were eligible. Primary outcome was incidence of macrosomia. Secondary outcomes included gestational weight gain, body mass index (BMI) at delivery, rates of gestational diabetes mellitus (GDM), mode of delivery, postpartum hemorrhage (PPH), and neonatal outcomes reflecting neonatal birth weight and condition at delivery. Results A total of 4,765 women were included, 2,442 in the study group and 2,323 in the control group. The incidence of macrosomia was significantly higher in 2020 (6.2%) than in 2019 (4.9%), (p = .048; OR: 1.29; 95% CI: 1.002– 1.65). Women gained significantly more weight (median 1 kg more), weighed more at delivery (median 1 kg), and had higher BMI at delivery in 2020 compared with those in 2019 (p < .01). The incidence of GDM was 9.5% and 8.5% in the study and control groups respectively (p = .26; OR: 1.12; 95% CI: 0.92–1.37). Greater percentage of women did not perform the glucose challenge test in 2020 (9.9%) compared with those in 2019 (7.5%) (p = .003, OR: 1.36; 95% CI: 1.11–1.67). The incidence of any hypertension related to pregnancy was significantly higher in 2020 compared to 2019 (5.8% vs 4.4% respectively, (p = .042; OR: 1.32; 95% CI: 1.02–1.71). The proportion of women who smoked during pregnancy was also significantly higher in 2020 than in 2019 (5.1% vs 3.7%, respectively, p = .02; OR: 1.40; 95% CI: 1.06–1.86). Delivery mode did not differ, while the incidence of PPH was significantly higher in 2020 than in 2019 (5.6% vs 3.4%, respectively, p = .001; OR: 1.65; 95% CI: 1.25–2.19). Neonatal condition at delivery was comparable. Conclusion COVID-19-related lockdown was associated with the increased rate of macrosomic infants. This indirect effect of the pandemic is probably related to poorer maternal antenatal metabolic health status. Long-term consequences should be further examined.

Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households in Israel (ICoFS): a prospective cohort study

Identifying COVID-19 correlates of protection and immunity thresholds is important for policy makers and vaccine development. We aimed to identify correlates of protection of BNT162b2 (Pfizer-BioNTech) vaccination against COVID-19. In this prospective cohort study, households within a radius of 40 km of the Sheba Medical Center in Israel in which a new SARS-CoV-2 infection (defined as the index case) was detected within the previous 24 h were approached between July 25 and Nov 15, 2021. We included adults (aged >18 years) who had received one or two vaccine doses, had an initial negative SARS-CoV-2 PCR and no previous infection reported, and had a valid IgG and neutralising antibody result. The exposure of interest was baseline immune status, including IgG antibody concentration, neutralising antibody titre, and T-cell activation. The outcomes of interest were PCR-positive SARS-CoV-2 infection between day 2 and day 21 of follow-up and intensity of disease symptoms (self-reported via a telephone questionnaire) among participants who had a confirmed infection. Multivariable logistic and ordered logit ordinal regressions were used for the adjusted analysis. To identify immunological thresholds for clinical protection, we estimated the conditional probability of infection and moderate or severe disease for individuals with pre-exposure IgG and neutralising antibody concentrations above each value observed in the study data. From 16 675 detected index cases in the study region, 5718 household members agreed to participate, 1461 of whom were eligible to be included in our study. 333 (22·8%) of 1461 household members who were not infected with SARS-CoV-2 at baseline were infected within 21 days of follow-up. The baseline (pre-exposure) IgG and neutralising antibodies were higher in participants who remained uninfected than in those who became infected (geometric mean IgG antibody concentration 168·2 binding antibody units [BAU] per mL [95% CI 158·3-178·7] vs 130·5 BAU/mL [118·3-143·8] and geometric mean neutralising antibody titre 197·5 [181·9-214·4] vs 136 ·7 [120·3-155·4]). Increasing IgG and neutralising antibody concentrations were also significantly associated with a reduced probability of increasing disease severity. Odds of infection were significantly reduced each time baseline IgG antibody concentration increased by a factor of ten (odds ratio [OR] 0·43 [95% CI 0·26-0·70]) and each time baseline neutralising antibody titre increased by a factor of two (0·82 [0·74-0·92]). In our cohort, the probability of infection if IgG antibody concentrations were higher than 500 BAU/mL was 11% and the probability of moderate disease severity was 1%; the probability of infection if neutralising antibody titres were above or equal to 1024 was 8% and the probability of moderate disease severity was 2%. T-cell activation rates were not significantly associated with reduced probability of infection (OR 1·04, 95% CI 0·83-1·30). Both IgG and neutralising antibodies are correlates of protection against SARS-CoV-2 infection. Our data suggest that IgG concentrations higher than 500 BAU/mL and neutralising antibody titres of 1024 or more are thresholds for immunological protection from SARS-CoV-2 delta variant infection. Potentially, updated protective thresholds against emerging variants of concern could be calculated, which could support decision makers on administration of new vaccination strategies and on the optimal period between vaccine doses. Israeli Ministry of Health.

Commentary: Post-pandemic lessons learnt regarding triage, mitigation, and management of emergency ocular conditions.

Commentary: Post-pandemic lessons learnt regarding triage, mitigation, and management of emergency ocular conditions.

Abstract P167: Residential Exposure to Greenness and Mortality Following Percutaneous Coronary Intervention

Background: Evidence regarding environmental exposure to green spaces and outcomes in coronary disease patients is lacking. We evaluated the association between residential exposure to greenness and mortality in patients undergoing percutaneous coronary interventions (PCI). Methods: Consecutive patients undergoing PCI at the Rabin Medical Center in Israel between 2004-2014 (n = 12,104) were studied. Clinical data at the time of hospitalization were extracted from medical records. Mortality data (through 2017) were obtained from the Ministry of Health. Patients with incomplete information on residential addresses were excluded. Exposure to greenness was estimated using normalized difference vegetation index (NDVI), a satellite-based index derived from Landsat 30 m spatial resolution imagery, with larger values indicating higher levels of vegetative density. NDVI was estimated within a buffer of 300 m around each patient’s home and as the point value of each 30 m pixel (immediate living environment). Additional residential-based environmental measures were obtained. Cox models assessed the hazard ratios (HRs) for mortality associated with greenness measures. Results: Among 11,262 patients analyzed [median age, 69 (IQR 61-78) y, 24% women], median NDVI-300 was 0.15 (IQR 0.13-0.17) and median NDVI-30 was 0.14 (IQR 0.11-0.17). Patients with higher NDVI-300 were slightly older; NDVI-30 was inversely correlated to ambient air pollution. During a median follow-up of 8.1 (IQR 5.1-10.6) years, 3,217 participants died. After adjustment for sociodemographic and clinical factors, NDVI-30 -but not NDVI-300- was associated with lower mortality (Figure), with an HR of 0.96 (95% CI: 0.92-0.99) per 1 SD increase. Conclusions: In this PCI registry, residential exposure to green spaces in the immediate living environment was associated with lower mortality. Results for the extended area of the living environment were inconclusive. This inconsistency between different spatial resolutions warrants further investigation

Postnatal Outcomes of Fetuses with Prenatal Diagnosis of 6–9.9 mm Pyelectasis

Pyelectasis, also known as renal pelvic dilatation or hydronephrosis, is frequently found on fetal ultrasound. This study correlated prenatally-detected, moderate pyelectasis with postnatal outcomes. This retrospective, observational study was conducted at a tertiary medical center in Israel. The study group consisted of 54 fetuses with prenatal diagnosis of pyelectasis on ultrasound scan during the second trimester, defined as anteroposterior renal pelvic diameter (APRPD) 6-9.9 mm. Long-term postnatal outcomes and renal-related sequelae were obtained using medical records and telephone-based questionnaires. The control group included 98 cases with APRPD < 6 mm. Results indicate that fetal pyelectasis 6-9.9 mm was more frequent among males (68.5%) than females (51%, p = 0.034). We did not find significant correlations between 6-9.9 mm pyelectasis and other anomalies or chromosomal/genetic disorders. Pyelectasis resolved during the pregnancy in 15/54 (27.8%) cases. There was no change in 17/54 (31.5%) and 22/54 (40.7%) progressed to hydronephrosis Among the study group, 25/54 (46.3%) were diagnosed with neonatal hydronephrosis. There were more cases of renal reflux or renal obstruction in the study group compared to the control group 8/54 (14.8%) vs. 1/98 (1.0%), respectively; p = 0.002. In conclusion, most cases of 6-9.9 mm pyelectasis remained stable or resolved spontaneously during pregnancy. There was a higher rate of postnatal renal reflux and renal obstruction in this group; however, most did not require surgical intervention.

Intercontinental validation of a clinical prediction model for predicting 90-day and 2-year mortality in an Israeli cohort of 2033 patients with a femoral neck fracture aged 65 or above

PurposeMortality prediction in elderly femoral neck fracture patients is valuable in treatment decision-making. A previously developed and internally validated clinical prediction model shows promise in identifying patients at risk of 90-day and 2-year mortality. Validation in an independent cohort is required to assess the generalizability; especially in geographically distinct regions. Therefore we questioned, is the SORG Orthopaedic Research Group (SORG) femoral neck fracture mortality algorithm externally valid in an Israeli cohort to predict 90-day and 2-year mortality?MethodsWe previously developed a prediction model in 2022 for estimating the risk of mortality in femoral neck fracture patients using a multicenter institutional cohort of 2,478 patients from the USA. The model included the following input variables that are available on clinical admission: age, male gender, creatinine level, absolute neutrophil, hemoglobin level, international normalized ratio (INR), congestive heart failure (CHF), displaced fracture, hemiplegia, chronic obstructive pulmonary disease (COPD), history of cerebrovascular accident (CVA) and beta-blocker use. To assess the generalizability, we used an intercontinental institutional cohort from the Sheba Medical Center in Israel (level I trauma center), queried between June 2008 and February 2022. Generalizability of the model was assessed using discrimination, calibration, Brier score, and decision curve analysis.ResultsThe validation cohort included 2,033 patients, aged 65 years or above, that underwent femoral neck fracture surgery. Most patients were female 64.8% (n = 1317), the median age was 81 years (interquartile range = 75–86), and 80.4% (n = 1635) patients sustained a displaced fracture (Garden III/IV). The 90-day mortality was 9.4% (n = 190) and 2-year mortality was 30.0% (n = 610). Despite numerous baseline differences, the model performed acceptably to the validation cohort on discrimination (c-statistic 0.67 for 90-day, 0.67 for 2-year), calibration, Brier score, and decision curve analysis.ConclusionsThe previously developed SORG femoral neck fracture mortality algorithm demonstrated good performance in an independent intercontinental population. Current iteration should not be relied on for patient care, though suggesting potential utility in assessing patients at low risk for 90-day or 2-year mortality. Further studies should evaluate this tool in a prospective setting and evaluate its feasibility and efficacy in clinical practice. The algorithm can be freely accessed: https://sorg-apps.shinyapps.io/hipfracturemortality/.Level of evidenceLevel III, Prognostic study.

P726 Fecal calprotectin and quality of life questionnaires are responsive to change in pouch disease activity following antibiotic therapy—results from a prospective clinical trial

Abstract Background Whether fecal calprotectin (FC) and quality of life (QoL) questionnaires reflect change in disease activity in patients with a J-pouch is unknown. Methods Patients with UC following ileal pouch-anal anastomosis developing acute pouchitis were prospectively recruited to a clinical trial at the Rabin Medical Center in Israel, a major referral center for patients with a J-pouch. Consecutive patients with acute pouchitis were diagnosed clinically by the treating physician in a patient with compatible clinical symptoms. Patients were treated with a 2-week course of antibiotics – either metronidazole and ciprofloxacin or metronidazole and doxycycline. Full PDAI, including clinical, endoscopic, and histologic evaluation, was performed at baseline and following 2 weeks of antibiotic therapy. Patients had comprehensive laboratory tests, including fecal calprotectin (FC) measurements at both time points. Patients also filled out QoL questionnaires (short inflammatory bowel disease questionnaire - SIBDQ, inflammatory bowel disease [IBD] disk) at both time points. Outcomes of interest included the responsiveness of FC and QoL questionnaires to change in pouch disease activity according to the PDAI. Paired analyses were performed to compare results between the 2-time points. Results Twenty patients were enrolled in a prospective clinical trial. At enrollment, the median age was 36 years IQR [27-56], females 12 (60%). The median interval from the ileostomy closure was 7 years IQR [2-17]. Median PDAI score: 9 IQR [8-11.5], median FC: 661 ug/g IQR [425-1261], median C-reactive protein: 1.1 mg/dl IQR [0.5-1.8] and median hemoglobin: 13.2 g/dl IQR [12.1-14.1]. Following 14 days of antibiotic treatment, there was a significant decrease in the total PDAI, which decreased from a median of 9 IQR[8-11.5] to 6 IQR[2.5-7],(p=0.007). This difference was mainly related to a significant reduction in both the clinical (p=0.01) and endoscopic subscores (p=0.001) but not the histologic subscore (p=0.1). FC was responsive to this change in PDAI and correlated with the change in endoscopic findings; it decreased significantly between the 2-time points from a median of 661 ug/g IQR[425-1261] to 294 ug/g IQR[113-418] (p=0.02). Both quality of life questionnaires (SIBDQ, IBD disk) improved significantly following antibiotic therapy: The median SIBDQ increased from 44 to 50 (p=0.02), and the median IBD disk score decreased from 59 to 31 (p=0.01) Figure 2 Panel B and C respectively. Conclusion FC is a sensitive and rapidly responsive biomarker of pouch disease activity, and we encourage its use when managing patients with pouchitis. Likewise, the SIBDQ and IBD disk accurately reflect change in QoL associated with change in disease state in patients with a pouch

Ethnic disparity in cervical cancer stage at diagnosis: A retrospective study in an Israeli referral-center.

To compare stage and survival of cervical cancer between Jewish and Arab women in a tertiary medical center in Israel. Retrospective study of consecutive women diagnosed with cervical cancer in a single institution between 2010 and 2021. We compared Jewish and Arab patients using univariate, multivariable, and survival curves analysis. Overall, 207 Jewish women and 45 Arab women were included with a median follow up of 20 months (interquartile range 7-46 months). The groups did not differ in median body mass index, mean age at diagnosis, or menopausal status. Arab women had higher parity. Arab women were at a higher risk to be diagnosed with advanced stage disease (≥2b) (84.4% vs. 57% Arab and Jewish women, respectively, P< 0.001). In a multivariable regression analysis, Arab descent was found to be the only independent factor associated with advanced stage disease (odds ratio 3.95, 95% confidence interval 1.54-10.10). Overall survival and stage-specific survival were not different between the ethnic groups. Advanced stage at diagnosis was more prevalent in Arab women compared with Jewish women with cervical cancer, whereas stage-specific survival was similar. Further studies addressing possible contributing factors to inequality should be undertaken to find corrective measures.

Clinical impact of exome sequencing in the setting of a general pediatric ward for hospitalized children with suspected genetic disorders.

Background: Genetic conditions contribute a significant portion of disease etiologies in children admitted to general pediatric wards worldwide. While exome sequencing (ES) has improved clinical diagnosis and management over a variety of pediatric subspecialties, it is not yet routinely used by general pediatric hospitalists. We aim to investigate the impact of exome sequencing in sequencing-naive children suspected of having monogenic disorders while receiving inpatient care. Methods: We prospectively employed exome sequencing in children admitted to the general pediatric inpatient service at a large tertiary medical center in Israel. Genetic analysis was triggered by general and/or subspecialist pediatricians who were part of the primary inpatient team. We determined the diagnostic yield among children who were referred for exome sequencing and observed the effects of genetic diagnosis on medical care. Results: A total of fifty probands were evaluated and exome sequenced during the study period. The most common phenotypes included were neurodevelopmental (56%), gastrointestinal (34%), and congenital cardiac anomalies (24%). A molecular diagnosis was reached in 38% of patients. Among seven patients (37%), the molecular genetic diagnosis influenced subsequent clinical management already during admission or shortly following discharge. Conclusion: We identified a significant fraction of genetic etiologies among undiagnosed children admitted to the general pediatric ward. Our results support that early application of exome sequencing may be maximized by pediatric hospitalists' high index of suspicion for an underlying genetic etiology, prompting an in-house genetic evaluation. This framework should include a multidisciplinary co-management approach of the primary care team working alongside with subspecialties, geneticists and bioinformaticians.

Acute Kidney Injury and Hair-Straightening Products: A Case Series

Keratin-based hair straightening treatment is a popular hair styling method. The majority of these products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe AKI following use of hair-straightening treatment occurring in Israel over the past several years. Case series. We retrospectively identified 26 patients from 14 medical centers in Israel who developed severe AKI and reported prior treatment with hair-straightening products between 2019 and 2022. The 26 patients described had a median age of 28.5 years (range, 14-58) and developed severe AKI following hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients developed a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies that demonstrated intra-tubular calcium oxalate deposition in six and microcalcification in tubular cells in one. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in four cases. Three patients required temporary dialysis. Retrospective uncontrolled study, small number of kidney biopsies. This study describes cases of acute kidney injury with prior exposure to hair straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential under-recognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.

Military Clinical Strategist to International Health Investor.

Virtual reality (VR) is emerging as a groundbreaking tool in the treatment of congenital heart diseases. This innovative technology offers a transformative approach by creating immersive, interactive, and personalized environments for both patients and healthcare professionals. In the pediatric cardiology institute in Safra Children's hospital in Sheba Medical Center in Israel, VR is being utilized for patient education, pre-operative planning, and intraoperative guidance. Patients can explore 3D visualizations of their own hearts, gaining a better understanding of their condition and proposed treatments. Surgeons and medical teams benefit from VR simulations that enhance their surgical planning and decision-making processes observing complex cases and evaluating printed models. Furthermore, Augmented reality AR can be employed in the operating room for observing the rib cage and reviewing the patient anatomy. The 3D visualization program is led by the Engineering in Medicine (EiM) tech-lab which cooperates with different specialties in the hospital including plastic surgery, ENT, ObGyn and more. The most critical topic addressed by the lab, cooperating with engineers from the Israeli Institute of technology deals with registration of the holographic image on the real patient body allowing intra-operative guidance. (Presented at the 2008th Meeting, September 27, 2023).