Assuta Medical Center

To evaluate 10-year outcomes after laparoscopic sleeve gastrectomy (LSG), focusing on weight loss, quality of life, patient satisfaction, physical activity, and psychosocial factors. A prospective cohort of 300 patients who underwent LSG between January 2013 and July 2014 was evaluated. Inclusion criteria were first-time metabolic bariatric surgery, age ≥18 years, and absence of perioperative complications. Long-term follow-up was achieved for 193 patients (64.3% retention). At baseline, mean BMI was 42.54 ± 5.10 kg/m² and mean age 42.86 ± 10.65 years. Substantial weight loss occurred, with BMI decreasing to 29.15 kg/m² at one year (p < .001). Weight regain began after three years, reaching a mean BMI of 31.89 kg/m² at 10 years, while 51.5% maintained ≥25% excess weight loss. Overall, quality of life improved in 86.1% of patients, with over half reporting excellent outcomes. The greatest improvements occurred in the self-esteem, physical activity, and social engagement domains of the MA-II, with smaller gains in sexual satisfaction and eating behavior. A significant decline in global quality of life (QOL) was observed over time (p < .001). Postoperatively, 59.3% participated in structured physical activity programs, while 40.7% remained sedentary. Psychosocial benefits included enhanced interpersonal relationships (35.6%) and greater social participation, although a minority reported marital strain (8.3%) or reduced overall satisfaction. LSG provides durable weight loss and significant improvements in quality of life across multiple MA-II domains, accompanied by high patient satisfaction (85.6%) and healthier lifestyle behaviors. Nonetheless, partial weight regains, sedentary habits, and variable psychosocial outcomes persist.

To describe the clinical and laboratory findings, disease course, and treatment effectiveness of a large, genetically homogenous group of patients with deficiency of adenosine deaminase 2 (DADA2), and to identify factors associated with disease-related damage. We conducted a retrospective cohort study that included 45 patients with DADA2 vasculitis with long-term follow-up. Information was collected from patients' charts, including demographic information, clinical presentations, laboratory findings, and treatment. The extent of disease-related damage was determined based on the Vasculitis Damage Index. In this large homogenous cohort, we found that a young age at disease onset and periodic illness that included recurrent episodes of fever, myalgia, and abdominal pain were associated with disease-related damage. Patients with severe DADA2 disease responded favorably to tumor necrosis factor inhibitors (TNFi). Early age of onset and the periodic nature of the disease warrant prompt initiation of TNFi treatment to prevent later complications and severe disease progression.

Intraoperative radiotherapy (IORT) offers single-session treatment during breast-conserving surgery (BCS). Outcomes depend heavily on patient selection and tumor characteristics. To assess local recurrence (LR) and prognosis using the 2024 American Society for Radiation Oncology (ASTRO) risk classification in IORT-treated patients. This multicenter retrospective study analyzed 358 IORT cases (356 patients) treated between 2014 and 2018 using the Zeiss INTRABEAM system. Cases were classified per the 2024 ASTRO partial-breast irradiation guidelines. The primary endpoint was local recurrence-free survival (LRFS); secondary endpoints included overall survival (OS) and mastectomy-free survival (MFS). The median age was 66 years (range 48-80); all tumors were invasive with a median tumor size of 10 mm. At a median follow-up of 7.1 years, LR occurred in 14/358 cases (3.9%) at a median of 5.2 years post-diagnosis. Five- and 8-year LRFS were 98.3% and 94.8%, respectively; 5- and 8-year OS were 99.4% and 97.7%; MFS at 8 years was 98.2%. Cases that were classified as "conditionally recommended" or "conditionally not recommended" had significantly higher LR than the "suitable" group (8.5% vs. 2.7%; HR 3.25, 95% CI 1.05-10.08, p = 0.041). Exploratory analysis showed that cases with ≥2 conditional criteria carried a markedly higher risk than those with 0-1 (21.4% vs. 3.2%; Firth-penalized Cox HR 8.26, 95% CI 2.06-26.06, p = 0.005). In appropriately selected patients, IORT achieves local control consistent with contemporary series. The 2024 ASTRO risk classification effectively identifies high-risk cases, supporting its use for risk-adapted candidate selection.

Objectives: This study aims to assess the prevalence of complications and failures associated with impacted canine eruption in a specialized referral center, with the goal of identifying factors that contribute to these outcomes. Methods: This retrospective cohort study included cases of impacted canines treated at the School of Dental Medicine between 2010 and 2020. Clinical and radiographic data were collected and evaluated for failures and complications by two independent clinicians (MK, MG). In addition, specialists in oral and maxillofacial surgery and orthodontics (YM, TS, NS) independently assessed all complications and failures. Results: Among the 214 impacted maxillary canines included, 23 (10.7%) failed to erupt following initial surgical-orthodontic treatment and required re-intervention. Eruption difficulty was attributed to orthodontic factors in 43.5% of cases, surgical factors in 13.0%, and combined factors in the remainder. Following a second procedure, 15 canines erupted successfully, while 8 did not, resulting in an overall failure rate of 3.7%. Treatment failure was significantly associated with both anatomical and procedural factors. Canines with centrally positioned crowns exhibited a significantly higher failure rate than those with buccal or palatal positions (χ2 test, p = 0.025). Failure was also more common when the canine root apex was located in close proximity to a cortical plate. Lateral incisor root resorption was significantly associated with treatment complications (p = 0.030). In the multivariable logistic regression analysis, root resorption remained an independent predictor of treatment failure, increasing the odds of failure approximately fourfold (OR = 0.255, CI = 0.077-0.843, p = 0.025). Timing and surgical technique were also significantly associated with treatment outcome. Surgical exposure performed shortly after diagnosis was linked to an increased risk of treatment complications (p = 0.006). Closed surgical exposure demonstrated a significantly higher failure rate compared with open exposure (Pearson exact test, p = 0.009). Although open exposure was associated with a greater likelihood of successful eruption, it was also significantly associated with increased gingival morbidity (Fisher's test, p = 0.030). Conclusions: Failure of impacted maxillary canine eruption following combined surgical-orthodontic treatment is uncommon but is significantly associated with distinct anatomical and procedural risk factors. Central crown position, cortical plate involvement, lateral incisor root resorption, early surgical exposure, and the use of closed exposure techniques all increase the likelihood of treatment failure and complications. Although open exposure enhances the probability of successful eruption, it may also negatively affect gingival outcomes, underscoring the need for individualized, multidisciplinary treatment planning.

Ocular manifestations (OMs) are recognized extraintestinal complications in inflammatory bowel disease (IBD), but their incidence remains understudied. We aimed to evaluate the incidence and trends of OM in a large population-based cohort of adults with newly diagnosed IBD over the past 2 decades. We conducted a retrospective cohort study including all adult-onset IBD patients between 2005 and 2024 in a large health maintenance organization. Patients with pre-existing OM diagnoses were excluded. The primary outcome was incident OM (uveitis, episcleritis/scleritis, or orbital inflammation) after IBD diagnosis. Annual incidence trends were assessed using the Cochran-Armitage test. Risk factors were analyzed via multivariable Cox regression, stratified by IBD type. Among 15 035 newly diagnosed IBD patients (51.8% Crohn's disease [CD], 48.2% ulcerative colitis [UC]), 349 developed an OM over 119 669 person-years (incidence: 2.9 per 1000 person-years; 95% confidence interval [CI], 2.62-3.24). OM incidence was higher in CD than UC (log-rank P < .001) and remained stable over time (P = .125). The median time to OM was 45 months. In CD, female sex (hazard ratio [HR], 1.62; 95% CI, 1.24-2.13) and systemic corticosteroid use (HR, 1.62; 95% CI, 1.18-2.22) were significant risk factors. In UC, corticosteroids (HR, 2.17; 95% CI, 1.40-3.37) and intestinal surgery (HR, 3.50; 95% CI, 1.69-7.28) were associated with increased OM risk. OMs in adult-onset IBD are infrequent but clinically relevant, particularly among CD patients and those with markers of severe disease. Clinician awareness and early referral remain essential for prompt diagnosis and management.

Abstract Introduction Oral immunotherapy (OIT) induces desensitization in IgE-mediated food allergy, yet the role of myeloid cells in acquisition of tolerance is unclear. CD300 receptors regulate activation of myeloid cells, with CD300f acting as an inhibitory receptor and CD300b as an activating receptor. Their modulation during OIT may reflect effector cell reprogramming and serve as biomarkers of treatment response. Methods Thirty-five patients undergoing OIT were prospectively enrolled. Peripheral blood was collected at baseline and first 3 months of up-dosing; 19 patients completed sampling upon reaching maintenance. CD300b and CD300f expression in eosinophils, monocytes, and neutrophils was analyzed by flow cytometry. Allergen-specific IgE and IgG4 were measured by ImmunoCAP. Associations with clinical parameters were assessed using logistic regression. Results . Baseline CD300b was higher in patients with lower starting doses ( p ≤0.05). CD300f expression was lower in those with atopic dermatitis or multiple food allergies ( p ≤0.03). A significant downregulation of CD300b expression in the surface of eosinophils, monocytes, and neutrophils, was noted early in treatment (p≤0.05). Expression of CD300f was slightly but non-significantly increased. Longitudinally, the expression of CD300f increased on eosinophils, whereas CD300b expression decreased on the surface of monocytes and neutrophils. Specific IgE reduction correlated with downregulation of CD300b expression in monocytes (R =0.51, p =0.02) and higher CD300f expression in eosinophils (R =-0.45, p =0.05). Conclusions Downregulation of CD300b and upregulation of CD300f during OIT suggests myeloid cell reprogramming toward a less inflammatory phenotype. These dynamic changes in expression and their correlation with serologic markers of desensitization, suggest CD300b and CD300f as candidate biomarkers for understanding and monitoring OIT response. Key Message OIT is associated with downregulation of the activating receptor CD300b and upregulation of the inhibitory receptor CD300f on myeloid cells. Myeloid cell reprogramming accompanies OIT, extending immune tolerance beyond adaptive regulatory mechanisms. CD300b and CD300f expression dynamics correlate with clinical dosing and serologic markers of OIT response.

Histiocytic neoplasms are clonal disorders of the monocyte/macrophage lineage defined by mutations activating mitogen-activated protein kinase (MAPK) signaling. Recently, the MEK1/2 inhibitor cobimetinib was FDA-approved for patients with adult histiocytoses. Here, aided by a prospective registry of patients with histiocytoses (NCT03329274), we identify that MEK1/2 mutations which constitutively activate MEK independently of RAF are associated with worse progression-free survival with MEK1/2 inhibition as compared to patients with other MEK1/2 mutational classes. The most common RAF-independent MEK1 mutation (MEK1E102_I103del) drove a lethal histiocytic-like neoplasm in mice, which was sensitive to the ERK1/2 inhibitor ulixertinib. We subsequently treated five MEK1E102_I103del-mutant patients with ulixertinib on prospective protocols, four of whom were refractory to MEK inhibition. Four of five patients experienced objective responses to ulixertinib. These data reveal the impact of oncogenic MEK mutations in vivo, identify patients with likelihood of resistance to MEK inhibition, and nominate ERK inhibition to overcome resistance to MEK inhibition in histiocytoses.