Rambam Health Care Campus (Hebrew: רמב"ם - הקריה הרפואית לבריאות האדם) commonly called Rambam Hospital, is a hospital in the Bat Galim neighborhood of Haifa, Israel founded in 1938, 10 years before the establishment of the State of Israel.It is the largest medical center in northern Israel and fifth largest in Israel, and is named for the 12th century physician-philosopher Rabbi Moshe Ben-Maimon (Maimonides), known as the Rambam.Rambam Health Care Campus is also an academic teaching hospital affiliated with the Rappaport Faculty of Medicine of the Technion – Israel Institute of Technology, Israel's oldest university..
Abstract Purpose This study aimed to evaluate whether episiotomy reduces obstetric anal sphincter injuries (OASIS) rates in nulliparous women with a second stage of labor lasting ≥ 3 h. Methods This retrospective study focused on nulliparous women at ≥ 36 weeks of gestation with singleton pregnancies who experienced a second stage of labor lasting ≥ 3 h and ultimately achieved spontaneous, non-operative, vaginal delivery between 2014 and 2024. Participants were categorized into two groups based on their episiotomy status. The primary outcome was the occurrence of OASIS, namely third- and fourth-degree perineal lacerations. Results The study included 1164 (58.3%) women who underwent episiotomy and 831 (41.7%) who did not. Women in the episiotomy group were significantly younger (27.79 ± 4.31 vs. 28.47 ± 4.51 years, p < 0.001), had a higher prevalence of hypertensive disorders (7.7% vs. 5.2%, p = 0.029), experienced a slightly longer second stage of labor (3.62 ± 0.4 vs. 3.53 ± 0.4 h, p < 0.001), and delivered newborns with higher birthweight (3366 ± 390 vs. 3284 ± 376 g, p < 0.001). The OASIS rates were comparable between the groups (1.9% vs. 2.2%, p = 0.82), consistent across all subtypes and in a subanalysis of women with a second stage of ≥ 4 h (2.9% vs. 2.5%, p = 0.59). In adjusted multivariable analysis, episiotomy was not associated with OASIS (adjusted OR 0.95, 95% CI 0.48–1.84). Conclusion In nulliparous women with spontaneous vaginal delivery and a prolonged second stage (≥ 3 h), episiotomy was not associated with a reduced risk of OASIS, even when the second stage exceeded 4 h. Our findings support existing guidelines that advocate against routine episiotomy in this population.
The goal of this paper is to examine the pathophysiology, diagnostic challenges, and maternal-fetal implications of postprandial (reactive) hypoglycemia in pregnant women following bariatric surgery. It seeks to explain how altered gastrointestinal anatomy and pregnancy-associated metabolic shifts converge to increase the risk of postprandial glycemic excursions. Furthermore, the review identifies current management strategies and highlights significant gaps in standardized screening and treatment protocols. Observational studies and continuous glucose monitoring (CGM) reports reveal a high prevalence of hypoglycemia in post-bariatric pregnancies, ranging from 50
Small nuclear RNAs (snRNAs) combine with specific proteins to generate small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. U4 snRNA forms a duplex with U6 and, together with U5, contributes to the tri-snRNP spliceosomal complex. Variants in RNU4-2, which encodes U4, have recently been implicated in neurodevelopmental disorders. Here we show that heterozygous inherited and de novo variants in RNU4-2 and in four RNU6 paralogs (RNU6-1, RNU6-2, RNU6-8 and RNU6-9), which encode U6, recur in individuals with nonsyndromic retinitis pigmentosa (RP), a genetic disorder causing progressive blindness. These variants cluster within the three-way junction of the U4/U6 duplex, a site that interacts with tri-snRNP splicing factors also known to cause RP (PRPF3, PRPF8, PRPF31), and seem to affect snRNP biogenesis. Based on our cohort, deleterious variants in RNU4-2 and RNU6 paralogs may explain up to ~1.4% of otherwise undiagnosed RP cases. This study highlights the contribution of noncoding RNA genes to Mendelian disease and reveals pleiotropy in RNU4-2, where distinct variants underlie neurodevelopmental disorder and retinal degeneration.
ABSTRACT:Circadian rhythms orchestrate immune activation and effector function, yet whether within-day timing influences chimeric antigen receptor (CAR) T-cell therapy outcomes remains unknown. We conducted an international, multicenter retrospective study of 1052 adults with relapsed or refractory large B-cell lymphoma treated with CD19-directed CAR T-cell therapy across 7 centers (2017-2025). The median infusion time was 11:48 am (interquartile range, 11:06 am to 12:45 pm). Each hour later in infusion time was associated with an increased risk of progression, relapse, or death (hazard ratio, 1.11; 95% confidence interval, 1.03-1.20; P = .004) after adjustment for center, product, and key clinical variables. One-year progression-free survival (PFS) was 51.4% for early (before 12:00 noon) infusion vs 35.2% for late (at or after 12:00 noon) infusion, whereas overall survival was similar between groups. The PFS benefit was driven by lower relapse and higher complete response rates in the early infusion group. Although no differences were observed in immune toxicities, late infusion correlated with higher peak inflammatory markers and reduced day 7 CAR T-cell expansion. Together, these findings suggest that the timing of CAR T-cell infusion may influence therapeutic efficacy and support prospective evaluation of circadian-informed delivery strategies.
Background Consolidation durvalumab is standard of care treatment for patients with unresectable, stage III non-small-cell lung cancer without progression after chemoradiotherapy. Additional study is warranted to investigate the long-term efficacy of this regimen in real-world settings. Methods PACIFIC-R (NCT03798535) was an international, observational, cohort study of patients who started durvalumab 10 mg/kg intravenously every 2 weeks within an AstraZeneca-initiated early access program between September 2017 and December 2018. Data were extracted retrospectively from medical records to describe the real-world effectiveness of consolidation durvalumab in patients with unresectable non-small-cell lung cancer without progression after chemoradiotherapy. The primary endpoints were real-world progression-free survival (rwPFS) and overall survival (OS). Results Median age was 65.0 years (range 26-88 years); most patients [747/1153 (64.8%)] were male and current [300/1153 (26.0%)] or former [750/1153 (65.0%)] smokers. Among patients with reported data, most had Eastern Cooperative Oncology Group performance status <2 [743/755 (98.4%)], stage IIIB/C disease [584/1090 (53.6%)], non-squamous histology [746/1137 (65.6%)], and programmed death-ligand 1 expression on ≥1% of tumor cells [572/791 (72.3%)]. Median follow-up (censored patients) was 63.5 months for rwPFS and 67.5 months for OS. Median rwPFS was 24.3 months [95% confidence interval (CI) 20.3-28.4 months]; 5-year rwPFS was 35.2% (95% CI 32.4% to 38.1%). Median OS was 59.0 months (95% CI 52.7-64.3 months); 5-year OS was 49.2% (95% CI 46.2% to 52.2%). Encouraging results were observed across subgroups, including among patients who received durvalumab after either concurrent or sequential chemoradiotherapy [median rwPFS (95% CI): 25.8 months (20.9-31.8 months) versus 23.2 months (16.9-29.5 months); median OS: 63.1 months (57.3-73.5 months) versus 47.1 months (35.3-58.1 months)], and irrespective of programmed death-ligand 1 expression [on ≥1% versus <1% of tumor cells; median rwPFS (95% CI): 25.5 months (19.1-32.8 months) versus 16.3 months (10.9-27.5 months); median OS: 62.4 months (55.0 months-not estimable) versus 43.3 months (31.6-60.7) months]. Conclusions PACIFIC-R provides mature data on OS and rwPFS from a large, real-world cohort, supporting consolidation durvalumab as a standard of care in this setting.
