Wolfson Medical Center

The aim of this study was to investigate the association of gestational weight gain with carotid artery intima-media thickness (IMT) during late pregnancy, and the association with metabolic parameters, pregnancy outcome and placental histological assessment. Pregnant patients admitted with signs of labor were prospectively recruited and categorized into two groups: Group 1 included women with excessive weight gain during pregnancy; Group 2 included women with gestational weight gain within recommended range. IMT of the carotid arteries was measured sonographically. Placental histopathology was assessed by an experienced pathologist. The study group included 59 women, 32 in group 1 and 27 in group 2. Mean carotid artery IMT was thicker in group 1 compared with group 2 (0.7 vs. 0.6 mm, P=0.028). Metabolic parameters including blood glucose and insulin resistance, using the homeostasis model assessment-insulin resistance (HOMA-IR) were also significantly higher in women with excessive weight gain during pregnancy as compared with group 2 (P=0.026 and P=0.045, respectively). Gestational age at delivery was similar in the two groups, while birthweight and the rate of macrosomia were significantly higher in group 1 than in group 2 (P=0.033 and P=0.014, respectively). Placental lesions consistent with fetal thrombo-occlusive disease were more prevalent in group 1 than in group 2. Excessive weight gain during pregnancy is associated with increased IMT of the carotid arteries that correlate with abnormal metabolic parameters, adverse pregnancy outcome and abnormal placental findings.

The prevalence of autoimmune diseases (AIDs) in Ethiopian patients with type 1 diabetes (T1D) is mainly unknown. This study aimed to determine the co-occurrence of AIDs in T1D Ethiopian patients and to compare their prevalence to non-Ethiopian Israeli patients. A retrospective cohort analysis of 12,759 T1D patients, of whom 672 (5.3%) were of Ethiopian descent, aged ≥ 18 years, registered in the Clalit Health Services database was conducted. The AID cases were identified by ICD-10 codes from 2000 to 2023. Additionally, data on thyroid peroxidase antibody (TPO) and tissue transglutaminase (TTG) antibodies were extracted and analyzed. The mean age of the entire cohort was 30.4 ± 18.9 years, 54% were male, and the mean follow-up was 10.9 ± 6.1 years. An additional AID was diagnosed among 14% of the Ethiopian and 26% of the non-Ethiopian populations (p < 0.001), respectively. Although the prevalence of coexisting autoimmune conditions was approximately half in the Ethiopian group, the relative distribution pattern of common and less common AIDs remained similar to that observed in the non-Ethiopian population. The prevalence of AIDs in Ethiopians is lower than in non-Ethiopian patients with T1D, indicating the existence of ethnic differences in susceptibility to AIDs. Nevertheless, the low screening rates highlight the need for greater vigilance and adherence to guidelines by medical staff.

To investigate the accuracy of slit lamp measurement of toric Intraocular lens (IOL) axis compared with photography and software measurement of the same IOL. The medical charts of 102 eyes of 86 patients who underwent cataract surgery with toric IOL implantation in Ein-Tal eye center, Israel, were retrospectively reviewed. Preoperative data includes demographics, biometry, and calculated IOL. Post-operative data includes visual acuity, refraction, and the IOL axis as measured at the slit lamp and using the Goniotrans eye photograph software. The difference between the two measurements was calculated. The mean absolute difference between the slit lamp and the photography measurement was 2.13 ± 1.9o (range 0.0-9.0o). In the against the rule (ATR) cases (n = 50) 48% were counterclockwise (CCW), 32% were clockwise (CW) and in 20% there was no difference, the average absolute deviation was 0.4 ± 1.8o CCW, range 0.5-7.0o. In the with the rule (WTR) cases (n = 40), 52% were CCW, 23% were CW and in 25% there was no difference, the average absolute deviation was 1.0 ± 2.0o CCW, range 0.5-9.0o. In the oblique cases (n = 12) 58% were CW, 25% were CCW and in 17% there was no difference, the average absolute deviation was 0.37 ± 1.9 o CW, range 0.5-5.5o. Average discrepancy between the slit lamp and photography measurement was small, but in an individual case it was found to be as high as 9.0o. It can be significant when rotation of toric IOL is needed. When photography is not available slit lamp measurements should be used as is.

Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced non-small cell lung cancer (NSCLC). The influence of statin use, chemotherapy, PD-L1 expression, and sex on immunotherapy outcomes remains incompletely defined in real-world settings. We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with immunotherapy-based regimens. Patients were stratified by statin exposure, chemotherapy use, PD-L1 expression (<1% vs. ≥1%), and sex. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier estimates and log-rank tests. Statin use was not associated with a significant OS benefit, while a numerical improvement in PFS was observed in selected subgroups. Among immunotherapy-treated patients, OS did not differ significantly by chemotherapy or statin use (median range, 19-27 months), whereas PFS differed significantly, with the longest PFS observed in patients receiving immunotherapy plus statins (26 months; p = 0.046). PD-L1 expression was the strongest determinant of outcomes, with PD-L1 ≥ 1% tumors demonstrating markedly longer OS and PFS compared with PD-L1 < 1% disease (OS up to 31 vs. 16 months; PFS up to 21 vs. 12 months; p < 0.001). No significant differences in OS or PFS were observed by sex or statin exposure (OS, 23-27 months; PFS, 14-19 months). In this real-world cohort, PD-L1 expression remained the primary predictor of survival outcomes following immunotherapy. Statin use was associated with modest PFS improvements but no consistent OS benefit, while sex did not significantly influence outcomes. These findings support continued reliance on established biomarkers and warrant prospective evaluation of statins as potential adjuncts to immunotherapy.

Abstract Background Tasty&amp;Healthy (T&amp;H) is a whole food diet shown to induce clinical and biological remission in Crohn’s disease (CD)(1). It eliminates processed foods, gluten, red meat, and dairy (except plain yogurt); no formula or mandatory components are needed. Here we aimed to evaluate whether T&amp;H diet maintenance treatment induces radiologic and endoscopic remission while gradually reintroducing gluten and dairy. Methods Patients, aged 4–37 years, achieving deep remission (MINI index&amp;lt;8 and wPCDAI&amp;lt;12.5/CDAI&amp;lt;150) in the previous TASTI-MM (T&amp;H vs. EEN) and TASTI-E (T&amp;H vs. regular diet) induction RCTs, were enrolled in this open-label maintenance trial and completed 24 weeks on the diet. Gluten and dairy were reintroduced monthly; &amp;gt;30% increase in fecal calprotectin prompted re-elimination of the specific ingredient. Intestinal Ultrasound with Segmental Activity Scoring (IUS-SAS) was performed at weeks 0, 8 and 24 and, in a subset who consented, video capsule-endoscopy (VCE) or ileocolonoscopy at week 24. Results Forty-three patients were enrolled: age 16±5.8 years, 33 children/adolescents; 91% not receiving any therapy besides T&amp;H. Clinical remission at 24 weeks was maintained in 37/43 (86%) participants; 53% successfully re-introduced gluten and dairy. All IUS parameters improved from baseline to weeks 8 and 24 ( including the maximal bowel score (IBUS-SAS 44.9 [IQR 2.1-64.9], 14 [0-48.5], 13.6 [0-34,6]; p = 0.0068) and in the terminal ileum (43 [IQR 0-64.8], 14 [0- 47.5], 5 [0-31], respectively; p = 0.0069). Among 29 patients with paired IUS assessments at baseline and week 24, 86% showed improvement or normalization of the ileal IBUS-SAS score, and 83% (24/29) demonstrated improvement in both the maximal and panenteric cumulative scores. Of the 23 patients who underwent VCE/ileocolonoscopy, 14 (61%) exhibited complete endoscopic healing or had only a few aphthous ulcers. Conclusion The T&amp;H diet, combined with structured, calprotectin-guided reintroduction of gluten and dairy, maintained clinical remission and improved radiological and endoscopic inflammation in patients up to 24 weeks. Reference: 1. Aharoni-Frutkoff Y, Plotkin L, Pollak D, et al. Whole Food Diet Induces Remission in Children and Young Adults With Mild to Moderate Crohn’s Disease and Is More Tolerable Than Exclusive Enteral Nutrition: A Randomized Controlled Trial. Gastroenterology 2025. Conflict of interest: Plotkin, Luba: No conflict of interest Aharoni-Frutkoff, Yonat: No conflict of interest Shavit, Zivia: No conflict of interest Ms. Focht, Gili: No conflict of interest Livovsky, Jessica: No conflict of interest Lev Zion, Raffi: No conflict of interest Ledder, Oren: No conflict of interest Cytter- Kuint, Ruth: No conflict of interest Zharkov, Elena: No conflict of interest Broide, Efrat: No conflict of interest Assa, Amit: No conflict of interest Sigall-Boneh, Rotem: No conflict of interest Weiss, Batia: No conflict of interest Slae, Mordechai: No conflict of interest Dotan, Iris: No conflict of interest Godny, Lihi: No conflict of interest Kierkuś, Jarosław: No conflict of interest Griffiths, Anne: No conflict of interest Naftali, Timna: No conflict of interest Aloi, Marina: No conflict of interest Yerushalmy-Feler, Anat: No conflict of interest Schwerd, Tobias: No conflict of interest Reifen, Ram: No conflict of interest Turner, Dan: No conflict of interest

BackgroundAlthough lobectomy is considered the standard surgical treatment for stage I non-small cell lung cancer (NSCLC). Recently, anatomical segmentectomy may represent an acceptable oncologic option for these patients. The study aims to compare perioperative and long-term outcomes between anatomical segmentectomy and lobectomy for stage I NSCLC using propensity score matching (PSM) in a single thoracic surgery centre.MethodsWe retrospectively analyzed 60 patients with stage I NSCLC who underwent pulmonary resection between 2017–2024. After 1:1 PSM, 50 patients (25 per group) were included. All patients underwent radical lymphadenectomy with ≥3 mediastinal stations dissected. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Secondary endpoints included recurrence patterns, perioperative outcomes, and oncological adequacy.ResultsAfter matching, baseline characteristics were well-balanced except for diffusing capacity for carbon monoxide (DLCO) (74.0% vs. 81.5%, P=0.01). All patients achieved R0 resection with comparable lymph node yields (17.3 vs. 16.8 nodes, P=0.32). Segmentectomy was associated with worse DFS [hazard ratio (HR) 2.06, 95% confidence interval (CI): 1.12–3.80, P=0.02] but similar OS (HR 0.70, 95% CI: 0.12–4.07, P=0.69). Overall mortality was 16% (4 deaths per group). Recurrence occurred in 10% of patients (12% segmentectomy vs. 8% lobectomy, P=0.64); however, given the low number of events (n=5), these comparisons should be interpreted with caution. Median follow-up was 24 months.ConclusionsDespite higher recurrence risk, anatomical segmentectomy with radical lymphadenectomy achieved equivalent OS to lobectomy for selected stage I NSCLC ≤2 cm. The relatively small sample size (n=50) limits statistical power, and these findings should be considered exploratory and hypothesis-generating. This parenchyma-sparing approach represents a valuable option in experienced centers, preserving pulmonary function while maintaining oncological adequacy. Careful patient selection and meticulous surgical technique remain paramount for optimal outcomes.

The accurate removal of intronic sequences from pre-mRNA by the spliceosome is essential for correct gene expression, with small nuclear RNAs (snRNAs) such as U4 playing structural and regulatory roles in catalyzing this. De novo variants in the highly constrained critical region including the T-loop region of RNU4-2 have been linked to ReNU syndrome, a neurodevelopmental disorder, but the broader mutational spectrum remains uncharacterized. Here, we show that, in a cohort of unresolved cases with neurodevelopmental disorder, monoallelic and biallelic RNU4-2 variants were identified in 16 affected individuals, expanding the genetic basis beyond the critical region: 12 with de novo T-loop variants and 4 from two families with compound heterozygous variants in non-critical regions (stem II, the k-turn, and the Sm-binding site). Previously reported functional mapping by saturation genome editing confirmed that most of the variant positions in this study are highly functionally constrained. Clinically, individuals with biallelic variants exhibited developmental delay and intellectual disability that were similar to but milder than those with monoallelic variants, notably lacking extracerebral organ involvement. These results suggest that pathogenic RNU4-2 variants act in both dominant and recessive manners, and that non-critical regions may also harbor disease-causing variants. More broadly, this study underscores the diagnostic importance of non-coding RNA genes in neurodevelopmental disorders and demonstrates the need to distinguish pathogenic variants from benign ones, together with their inheritance patterns.

a:2:{s:4:"lang";s:2:"en";s:7:"content";s:1235:"<h3></h3> MINORE (NCT04998812) is a prospective Phase IV, open-label study measuring ocrelizumab placental transfer, infant B-cell levels and detailed maternal and infant clinical outcomes, humoral immunity and safety. Thirty-five women were enrolled, 32 of whom received ocrelizumab within 6 months before last menstrual period (LMP) (3–6 months before LMP, n=18; and 0–3 months before LMP, n=14), and three women received ocrelizumab in the first trimester. The primary endpoint was the proportion of infants with B-cell levels below the lower limit of normal (LLN), measured at week 6 (W6) of life. All 35 pregnancies resulted in full-term live births. Ocrelizumab was undetectable in most infants, both in the umbilical cord blood at birth (94.3%, 33/35) and serum at W6 of life (97.0%, 32/33). All infant B-cell levels were above the age-specific LLN at W6 (100%, 34/34). Rates and types of adverse events (AEs) in mothers were in line with expected AEs during pregnancy, delivery, postpartum and infancy. Results of this study indicate that pregnancy planning is compatible with ocrelizumab treatment and support treatment decisions by clinicians and women with MS. ruth.dobson{at}qmul.ac.uk ";}