The Bnai Zion Medical Center was established in 1922 as the first Jewish hospital in Haifa, the center offers medical care, education, research and services to the diverse and growing population of northern Israel. In a recent survey in a national newspaper, the Bnai Zion medical center was voted the first hospital in the Haifa region of Israel.
Background:Clinical trial designs evaluating on-demand therapies for hereditary angioedema attacks have evolved in response to changes in treatment guidelines. Sebetralstat, an oral plasma kallikrein inhibitor, was evaluated in 2 randomized, placebo-controlled clinical trials, which instructed early treatment of attacks with no minimum severity requirement. Objective:Characterize the efficacy and safety of sebetralstat by pooling data from phase 2 and 3 trials. Methods:This pooled analysis included participants (phase 2, aged ≥18 years; phase 3, aged ≥12 years) who received ≥1 dose of study drug (phase 2, sebetralstat 600 mg or placebo; phase 3, sebetralstat 300 mg or 600 mg, or placebo). Efficacy outcomes included times to beginning of symptom relief within 12 h, reduction in severity within 12 h, and complete attack resolution within 24 h. P values were not adjusted for multiplicity. Results:377 attacks were treated: 87 with sebetralstat 300 mg; 151 with sebetralstat 600 mg; 139 with placebo. Median (interquartile range) time to treatment was 32.5 min (8.0-94.0). Baseline severity was rated as "Mild" (46.2%), "Moderate" (40.6%), or "Severe"/"Very Severe" (12.7%). Compared with placebo, time to beginning of symptom relief was faster with sebetralstat (300 mg; 600 mg [P = 0.0001; P < 0.0001]), as was reduction in severity (P = 0.0038; P < 0.0001) and complete attack resolution (P = 0.0021; P < 0.0001). Median time to beginning of symptom relief was 1.6 h (0.8-7.0) and 1.8 h (1.0-4.3) with sebetralstat 300 mg and 600 mg, respectively, and 8.3 h (1.5 to >12) with placebo. Sebetralstat had a safety profile comparable to placebo. Conclusion:Across phase 2 and 3 clinical trials, sebetralstat enabled early treatment, provided effective symptom relief versus placebo, and was well tolerated, regardless of attack location or baseline severity. Clinical trial registration:ClinicalTrials.gov Identifier NCT04208412, registered on 2019-07-02; ClinicalTrials.gov Identifier NCT05259917 (KONFIDENT), registered on 2022-02-22.
BACKGROUND:Oral abnormalities resulting from childhood leukemia treatment may significantly impact long-term health outcomes. OBJECTIVES:This prospective study aims to evaluate oral health, to assess oral health-related quality of life (OHRQoL) among leukemia survivors, its impact on general Health Related Quality of Life (HRQoL) and to identify risk factors for oral health impairments. METHODS:Dental examination was proposed to patients included in the LEA cohort (long-term follow-up of childhood/adolescent leukemia survivors) in two pediatric hematology centers. For cavities, Decayed/Missing/Filled/Teeth (DMFT/dmft) index was determined. Quantitative and qualitative saliva analyses were performed. Orthopantomograms were independently reviewed. OHRQoL was assessed using age-adapted questionnaires. Patient characteristics, treatment history, socio-economic status and HRQoL were extracted from LEA database. Statistical analyses were performed using SPSS software. Pearson's Chi2/Fisher's exact test/Student's t-test/Spearman correlation test/Adjusted multivariate logistic regression model were used when appropriate. RESULTS:Eighty-nine patients were included with a mean follow-up from diagnosis of 12.5 ± 0.8 years. Females represented 48% of the cohort, acute lymphoblastic leukemia 76%. A history of leukemia relapse concerned 27% of patients; 45% of the cohort underwent hematopoietic stem cell transplantation (HSCT). Eighty-five patients had ≥1 oral abnormalities (excluding cavities); 53 required treatment intervention. Mean DMFT/dmft index was 2.3 ± 0.4; lower parents' education level was linked with higher index (p = 0.029). Younger age at diagnosis (<6 years old) was associated with enamel defects (p = 0.001). History of relapse was associated with teeth number, morphology and eruption abnormalities (p < 0.05). HSCT was associated with morphology abnormalities (p < 0.05). Among transplanted patients, no significant impact of total body irradiation on oral abnormalities was found as compared to busulfan-based conditioning regimen. In children, altered OHRQoL tend to have a negative impact on body image and physical well-being. CONCLUSION:The high prevalence of oral abnormalities in pediatric leukemia survivors necessitates proactive dental monitoring and early interdisciplinary collaboration between pediatrician and dentists.
Malignant ascites is a devastating complication of several advanced malignancies. Beyond serving as a poor prognostic indicator, the rapid accumulation of ascitic fluid imposes a significant symptom burden that can severely worsen quality of life. Although immunotherapy has revolutionized solid tumor oncology, these approaches have shown only limited benefit in the treatment of malignant ascites. Here, we summarize landmark clinical trials exploring immunotherapy as a potential treatment of malignant ascites. We then conceptualize malignant ascites as a functionally distinct immunologic compartment rather than a passive fluid reservoir, highlighting unique immunologic features that may underlie the challenges in translating immunotherapy to this context. By advancing our collective understanding of this unique immune microenvironment, it may become possible to develop rational combination strategies that provide symptomatic relief and meaningfully improve quality of life for patients with end-stage disease.
PURPOSE:The aim of this study was to compare the time to delivery between early (within 2 h) and late (after 2 h) amniotomy and oxytocin initiation in patients undergoing cervical ripening with a cervical ripening balloon (CRB). METHODS:Secondary analysis of data collected from a previous parallel randomized controlled trial comparing CRB removal after 6 versus 12 h. For our study, the full cohort from the original trial was divided into patients who had amniotomy and oxytocin infusion within 2 h of CRB removal (study group) and patients who hadamniotomy and oxytocin more than 2 h after CRB removal (control group). Inclusion criteria were age > 18 years, ≥ 37 gestational weeks, Bishop score < 5, singleton vertex presentation, intact membranes, and no contraindication for vaginal delivery. Primary outcome for the current study was the time from CRB removal to delivery. Secondary outcomes included the rate of cesarean delivery and adverse maternal and neonatal outcomes. RESULTS:A total of 197 patients were analyzed, 34 in the study group and 163 in the control group. The study and control groups did not differ in baseline characteristics but differences were observed in the treatment characteristics stemming from the division into the two groups for the analysis. Time from CRB removal to delivery was significantly shorter in the study group vs control (9 ± 6.7 vs.17 ± 11.9 h, p < 0.001) respectively. The rate of cesarean deliveries and other maternal and neonatal outcomes were similar in the two groups. CONCLUSION:Our findings suggest that early amniotomy and oxytocin infusion combination in patients undergoing labor induction with a CRB is associated with a shorter duration of labor and similar cesarean deliveries rate. Latent confounding remains possible.
