Search

Background: Anxiety is a prevalent mental health disorder, with debilitating symptoms causing avoidance and decreased quality of life. Balance impairments during standing and walking are common in anxiety. However, understanding of gait control mechanisms in people with trait anxiety, particularly when walking requires increased attention (dual-task), is still limited. This work examined the attentional cost of walking in people with varying levels of trait anxiety. Since people with anxiety are often prone to Space and Motion Discomfort (SMD), this work also evaluated the potential role of SMD in the attentional cost of walking., Methods: Fifty-six participants, aged 18-51, classified as anxious and non-anxious, were asked to walk under single- and two dual-task conditions (cognitive: counting backwards; visuomotor: texting on a mobile phone). Task performance (walking, counting and texting) was measured. Prefrontal cortex (PFC) activation was recorded using functional near infrared spectroscopy (fNIRS) for a subset of participants (n = 29)., Results: Anxious individuals walked slower under dual-task conditions, with smaller increases in PFC activation from single to dual-task conditions in the cognitive task. Dual-task walking was unrelated to SMD., Limitations: sample size was limited, particularly for fNIRS data., Conclusions: To the best of our knowledge, this study is the first to identify anxiety-related deficits in attentional gait control in the general population, including during the everyday task of texting on a mobile phone. Since decrements in dual-task walking are linked to poor health outcomes, results from this work may have functional implications for people with anxiety., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Informal caregivers of cancer patients are known to experience extensive burdens, while this issue remains unresolved in the setting of hematological malignancies. Yet, these diseases are characterized by a prolonged course, numerous relapses and implementation of multi-line therapy, administered in outpatient facilities. The current study aimed to assess the factors contributing to burden and depressive symptoms in informal caregivers of patients with hematological malignancies, while concentrating on the role of medical visits. The study population comprised patients and their caregivers, recruited at the Rambam Hematology Ambulatory Unit. Participants completed validated questionnaires, including the Center for Epidemiologic Studies Depression Scale and Zarit Caregiver Burden Interview. The cohort (n=185) included 115 patients [average age 62.8+14.5 years; 54 males] and 70 caregivers. Among caregivers, 80% reported high psychological burden and 50% reported significant depressive symptoms. The burden was higher if caregivers were females, and if patients were less educated, less healthy and more depressed. The caregiver burden and depressive symptoms were significantly linked and the medical visit frequency predicted the level of both. The caregiver burden fully mediated the link between the independent variables of self-rated health and medical visits, and the dependent variable of caregiver depressive symptoms. Informal caregivers of ambulatory hemato-oncological patients experience high levels of psychological burden and depressive symptoms. This is partly attributed to the medical visit frequency. Hence, a decrease in the number and length of such visits via the implementation of advanced technology could essentially reduce burden and depressive symptoms of caregivers, without compromising patient outcomes., (Copyright © 2024 American Society of Hematology.)

Purpose: To identify factors predicting slow visual recovery following myopic microkeratome assisted in situ keratomileusis (LASIK)., Design: Retrospective study., Methods: This study included consecutive patients who underwent microkeratome-assisted myopic LASIK between January 2005 and December 2019 at Care Vision Laser Center, Tel Aviv, Israel. Patients were divided into three groups according to whether they experienced normal recovery of visual acuity (1 week visit), slow visual recovery (1 month visit) or very slow recovery (>1 month). Normal visual recovery was defined as achieving an efficacy index of 0.9 or greater. Efficacy index was calculated as postoperative uncorrected visual acuity/preoperative best corrected visual acuity. A comparison of baseline and intraoperative parameters was performed., Results: Overall, 10 439 eyes were included. Mean age was 30.8 ± 8.7 years and 47.1% were females. The slower visual recovery groups (slow 11.4%, n = 1191; very slow 8.4%, n = 875) were of older age (p < 0.001), steeper preoperative steep keratometry (p = 0.002) and larger refractive astigmatism (p < 0.001). In binary logistic regression older age (p < 0.001), female gender (p = 0.001), larger astigmatism (p < 0.001) and high myopia (p < 0.001) remained significant predictors of slow visual recovery., Conclusion: Slow visual recovery was observed in 19.8% of patients following myopic LASIK. Older age, female gender, larger astigmatism and high myopia were associated with slow visual recovery. Patients may be advised accordingly., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Newborn screening (NBS) for isovaleric acidemia (IVA) reduces mortality and morbidity; however, it has also resulted in the detection of individuals with an asymptomatic or mild presentation for which early detection via newborn screening has not been proven to alter neurological outcome. We reevaluated biochemical and molecular data for newborns flagged positive for IVA in aim of developing a new screening algorithm to exclude the latter from positive screening. Among 2 794 365 newborns underwent routine newborn screening in Israel, 412 flagged positive for IVA, of which, 371 were false positives on recall sample testing and 41 positive newborns were referred to the clinic. 38/41 have biochemical and molecular confirmation in keeping with IVA. Among the 38 patients, 32% (12/38) were classified as symptomatic while, 68% (26/38) were classified as asymptomatic. 69% of the latter group harbor the known variant associated with mild potentially asymptomatic phenotype, c.932C>T; p. Ala311Val. Among asymptomatic patients, only 46% (12/26) are currently treated. Two novel variants have been detected in the IVD gene: c.487G>A; p. Ala163Thr and c.985A>G; p. Met329Val. Cut-off recalculation, of referred newborns' initial biochemical results, after classifying the referred patients to two binary groups of symptomatic and asymptomatic, resulted in an improved NBS algorithm comprising of C5 >5 μM and C5/C2>0.2 and C5/C3>4 flagging only those likely to have the classic symptomatic phenotype., (© 2024 SSIEM.)

Purpose: To compare laser-assisted in situ keratomileusis (LASIK) outcomes in patients with different corneal curvatures., Methods: This is a retrospective comparative chart review. Patients included in this study underwent wavefront-optimized myopic LASIK between January 2013 and December 2022 at Care-Vision Laser Center, Tel-Aviv, Israel. Patients were divided into 3 groups based on the steepness of the cornea (steep keratometry) (flat: <42 diopters [D], normal: 42-46 D, and steep: >46 D). Case-by-case matching was performed to verify that baseline parameters (age, preoperative visual acuity, and refractive error) were similar between groups. Primary outcome measures were postoperative corrected/uncorrected distance visual acuity, efficacy index, safety index, spherical equivalence, and astigmatism., Results: After matching, 300 eyes were included in each group, which were similar in baseline parameters. There were no significant postoperative differences between flat, normal, and steep corneas regarding safety index (1.01 vs. 1.02 vs. 1.01, P = 0.95), efficacy index (1.03 vs. 1.02 vs. 1.02, P = 0.94), logarithm of the minimum angle of resolution corrected distance visual acuity (0.01 vs. 0.01 vs. 0.01, P = 0.17), logarithm of the minimum angle of resolution uncorrected distance visual acuity (0.02 vs. 0.03 vs. 0.02, P = 0.65), proportion of patients with spherical equivalence within 0.50 D (73.0% vs. 73.7% vs. 69.3%, P = 0.45) or 1.00 D (93.3% vs. 94.7% vs. 91.7%, P = 0.34) of the target, and proportion of patients with astigmatism within 0.50 D (86.7% vs. 82.3% vs. 80.3%, P = 0.11) or 1.00 D (98.7% vs. 98.7% vs. 99.0%, P = 0.91) of the target. Longer term follow-up of a smaller set of patients revealed similar results., Conclusions: No significant differences were found between flat, normal, and steep corneas following wavefront-optimized myopic LASIK. Thus, this procedure may be safely and effectively performed across a wide range of corneal curvatures., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To identify factors predicting slow visual recovery following photorefractive keratectomy (PRK)., Methods: This retrospective study included consecutive patients who underwent PRK between January 2005 and December 2019 at Care Vision Laser Center, Tel Aviv, Israel. Myopic patients were divided into 2 groups according to whether they experienced normal recovery of visual acuity (within 60 days) or slow visual recovery (>60 days). Visual recovery was defined as achieving an efficacy index of 0.9 or greater. Efficacy index was calculated as postoperative uncorrected visual acuity/preoperative best corrected visual acuity. A comparison of baseline and intraoperative parameters was performed. Binary logistic regression was performed to identify potential predictors of slow visual recovery., Results: Overall, 4868 eyes were included. The mean age was 25.9 ± 7.7 years, and 53.9% were male. The slow visual recovery group (39.3%, n = 1911/4868) was older (P < 0.001) and had greater refractive astigmatism (P < 0.001) with a larger proportion of recent contact lens wearers (P = 0.002). The slow recovery group had larger optic zone treatments (P < 0.001), alcohol-assisted PRK (vs. transepithelial PRK) (P < 0.001), and greater maximum ablation depth (P < 0.001). In binary logistic regression, older age (P < 0.001), higher refractive astigmatism (P = 0.01), recent contact lens wear (P = 0.01), greater optic zone treatment (P = 0.001), and alcohol-assisted PRK (P < 0.001) remained significant predictors of slow visual recovery., Conclusions: Slow visual recovery was observed in ∼40% of patients following myopic PRK. Older age, greater refractive astigmatism, recent contact lens wear, greater optic zone treatment, and alcohol-assisted PRK were associated with slow visual recovery., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The zygomatic bone has a great impact on the anterior and lateral projection of the midface as well as the proper position of the globe. Primary alignment of zygomatic fractures is very important as secondary reconstruction is far more challenging. Treatment of misaligned zygoma requires refracturing of the bone to allow for repositioning. Due to the great impact of the zygoma on the projection of the midface, a precise 3D realignment is of great importance. Technology nowadays develops rapidly and allows for superior results in many surgical fields. The use of patient specific surgical guides and fixation plates is becoming more abundant., Methods: Using 3D segmentation and design software, we developed a sequence for using 3D planning and printing both for the refracturing stage, avoiding a coronal approach, and for precise repositioning and fixation of the zygoma in the new position., Results: The method is described as well as a unique advanced 3D analysis, allowing for objectively assessing the results. Two cases are presented, including the design and post operative changes., Discussion: Pre-op, planned and final positions were compared and showed exceptional accuracy allowing for the elimination of human errors which are common in a 3D sensitive procedure such as refracturing of the zygoma. This method can easily be applied to other secondary reconstruction procedures requiring realignment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Krasovsky, Hija, Zeineh, Bilder, Emodi, Rachmiel and Shilo.)

Background: Root resorption consists of complex, multistep processes that involve cell signalling caused by inflammation and stromal cells, which promotes the secretion of receptor activator of nuclear factor κB ligand/ macrophage-colony stimulating factor (RANKL/M-CSF) resulting in a resorptive process., Objective: The aim of this narrative review was to analyse the literature related to root resorption resulting from microbial infection and to comparing it with non-microbial infection., Methods: An electronic literature search was performed using the PubMed database and applying keywords of articles published in English. Eligible papers were reviewed to reveal the descriptions of bone and root resorption processes. The abstracts were searched manually to identify articles about infection-stimulating bone and root resorption., Results: Three main types of root resorption were identified, two associated with primary bacterial infection and one secondary to bacterial infection. These include external inflammatory resorption, internal inflammatory resorption and external cervical (invasive) resorption., Discussion: The magnitude of cytokine involvement that promotes resorption and M-CSF/RANKL production depends on multiple factors, including pathogen virulence, site of infection and host genetic factors that activate the inflammation at the infection site. Two mechanisms activate the resorption mechanisms-the canonical and non-canonical pathways that can activate clastic cells independently of the RANKL/RANK canonical pathways., Conclusions: Two pathways of root resorption co-exist in the body. When resorption is caused by infection, chronic inflammation due to bacterial infection prolongs the secretions of pro-inflammatory cytokines that intensify root and bone resorption. The second pathway is bacterial independent of the non-infection root resorption that is part of the wound healing process, which is limited in time due to its innate ability., (© 2024 The Author(s). International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society.)

Temporal lobe epilepsy in children is often secondary to various low-grade glial and glioneural tumors and rarely secondary to mesial temporal sclerosis. Despite the benign nature, tumor-associated TLE in children often becomes refractory over time. Abundant literature has shown the significant advantage of tumor resection compared to conservative treatment, in achieving seizure control, as well as the rates of antiseizure medication reduction. Despite these advantages, several considerations are to be related to when considering surgery. These include the impact of surgery on linguistic and neurocognitive development, especially at the younger age; the extent of resection and the role of ECoG; and the need for mesial temporal resection. Over recent years, traditional resection has been complemented with newer treatment options such as laser ablation and biological treatment, and these should be taken into account depending on the exact location and the ability to perform extensive resection in eloquent regions. In this overview manuscript, we discuss the various considerations treating tumor-associated pediatric temporal epilepsy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Primary hyperoxaluria type 1 (PH1) is a genetic disorder resulting in overproduction of hepatic oxalate, potentially leading to recurrent kidney stones, nephrocalcinosis, chronic kidney disease, and kidney failure. Lumasiran, the first RNA interference therapeutic approved for infants and young children, is a liver-directed treatment that reduces hepatic oxalate production. Lumasiran demonstrated sustained efficacy with an acceptable safety profile over 12 months in infants and young children (age <6 years) with PH1 in ILLUMINATE-B (clinicaltrials.gov: NCT03905694), an ongoing, Phase 3, multinational, open-label, single-arm study., Methods: Here, we report interim efficacy and safety findings from ILLUMINATE-B following 30 months of lumasiran treatment. Eligible patients had an estimated glomerular filtration rate (eGFR) >45 ml/min/1.73 m 2 if ≥12 months old or normal serum creatinine if <12 months old, and a urinary oxalate to creatinine ratio (UOx:Cr) greater than the upper limit of normal. All 18 patients enrolled in ILLUMINATE-B completed the 6-month primary analysis period, entered an extension period of up to 54 months, and continue to participate in the study., Results: At Month 30, mean percent change from baseline in spot UOx:Cr was -76%, and mean percent change in plasma oxalate was -42%. eGFR remained stable through Month 30. In 14 patients (86%) with nephrocalcinosis at baseline, nephrocalcinosis grade improved at Month 24 in 12; no patient worsened. In the 4 patients without baseline nephrocalcinosis, nephrocalcinosis was absent at Month 24. Kidney stone event rates were ≤0.25 per person-year through Month 30. Mild, transient injection site reactions were the most common lumasiran-related adverse events (17% of patients)., Conclusion: In infants and young children with PH1, long-term lumasiran treatment resulted in sustained reductions in urinary and plasma oxalate that were sustained for 30 months, with an acceptable safety profile. Kidney function remained stable, low kidney stone event rates were observed through Month 30, and nephrocalcinosis grade improvements were observed through Month 24., Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT03905694., Competing Interests: YF: consultancy fees from Alnylam Pharmaceuticals and membership in the safety review committee. WH: principal investigator for Alnylam Pharmaceuticals; travel and accommodation expenses from Alnylam Pharmaceuticals to attend an international investigators’ meeting. HS-L: principal investigator for Alnylam Pharmaceuticals; travel and accommodation expenses from Alnylam Pharmaceuticals to attend international investigators’ meetings. DJS: grants and other from Alnylam Pharmaceuticals and Dicerna Pharmaceuticals, and personal fees from Advicenne. MM: principal investigator for Alnylam Pharmaceuticals; served on advisory board for Novo Nordisk, Inc. ALS-L: consultancy fees from Alnylam Pharmaceuticals and Dicerna Pharmaceuticals, and principal investigator for research funded by OxThera. JH: consultancy fees from Alnylam Pharmaceuticals. RW and JMG: employees of and shareholders in Alnylam Pharmaceuticals; contributed to study design, data analysis, and (in partnership with all other authors) review and revision of the manuscript in accordance with the ethical principles of Good Publication Practice (GPP 2022) guidelines. DM: research funding, consultancy fees, and non-financial support from Alnylam Pharmaceuticals. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Frishberg, Hayes, Shasha-Lavsky, Sas, Michael, Sellier-Leclerc, Hogan, Willey, Gansner and Magen.)

Background: Ventricular tachycardia (VT) is a life-threatening arrhythmia originating from the heart's ventricles. Traditional treatments include antiarrhythmic medications, implantable cardioverter-defibrillators (ICDs), and catheter ablation. Stereotactic body radiation therapy (SBRT) targeting the arrhythmogenic focus in the left ventricle-stereotactic arrhythmia radioablation (STAR)-is an emerging treatment and may offer a potential solution for patients with refractory VT., Objective: We designed an interventional prospective clinical trial in Israel aligned with the STOPSTORM.eu consortium's benchmarks, recommendations, and directives to assess the safety and efficacy of STAR in patients with refractory VT., Methods: Our phase I/II single-institutional trial was approved by the Ministry of Health of Israel for 10 patients, initially assessing safety in the first 3 patients. We included patients with ICDs experiencing symptomatic monomorphic VT after an inadequate response to previous therapies. The primary endpoints were treatment-related serious adverse events and a reduction in VT burden as assessed by ICD interrogation. Secondary outcomes included a reduction in antiarrhythmic medications and changes in quality of life., Results: From August 2023 to August 2024, 3 patients underwent STAR treatment. The prescription dose was a single fraction of 25 Gy. Planning target volumes were 47.8, 49.7, and 91.8 cc, and treatment was successfully delivered with no grade 3 or higher adverse events reported. Over a follow-up period of 12 months for the first patient and 8 months for the second one, no VT events were recorded after treatment. The third patient died from progressive heart failure 3 months after treatment. Left ventricular ejection fraction remained stable, and no significant radiation-induced inflammatory changes were noted., Conclusion: The initial results of this trial suggest that STAR can reduce VT episodes in patients with refractory VT without severe adverse effects. The study highlights the importance of international collaboration and standardization in pioneering new treatments. Further follow-up and additional patient data will be necessary to confirm these findings and evaluate long-term outcomes, including potential adjustments to antiarrhythmic medication regimens., (© 2024. The Author(s).)

Introduction: The rapid advancement of artificial intelligence (AI), particularly in large language models like ChatGPT and Google's Gemini AI, marks a transformative era in technological innovation. This study explores the potential of AI in ophthalmology, focusing on the capabilities of ChatGPT and Gemini AI. While these models hold promise for medical education and clinical support, their integration requires comprehensive evaluation. This research aims to bridge a gap in the literature by comparing Gemini AI and ChatGPT, assessing their performance against ophthalmology residents using a dataset derived from ophthalmology board exams., Methods: A dataset comprising 600 questions across 12 subspecialties was curated from Israeli ophthalmology residency exams, encompassing text and image-based formats. Four AI models - ChatGPT-3.5, ChatGPT-4, Gemini, and Gemini Advanced - underwent testing on this dataset. The study includes a comparative analysis with Israeli ophthalmology residents, employing specific metrics for performance assessment., Results: Gemini Advanced demonstrated superior performance with a 66% accuracy rate. Notably, ChatGPT-4 exhibited improvement at 62%, Gemini at 58%, and ChatGPT-3.5 served as the reference at 46%. Comparative analysis with residents offered insights into AI models' performance relative to human-level medical knowledge. Further analysis delved into yearly performance trends, topic-specific variations, and the impact of images on chatbot accuracy., Conclusion: The study unveils nuanced AI model capabilities in ophthalmology, emphasizing domain-specific variations. The superior performance of Gemini Advanced superior performance indicates significant advancements, while ChatGPT-4's improvement is noteworthy. Both Gemini and ChatGPT-3.5 demonstrated commendable performance. The comparative analysis underscores AI's evolving role as a supplementary tool in medical education. This research contributes vital insights into AI effectiveness in ophthalmology, highlighting areas for refinement. As AI models evolve, targeted improvements can enhance adaptability across subspecialties, making them valuable tools for medical professionals and enriching patient care., Key Messages: What is known AI breakthroughs, like ChatGPT and Google's Gemini AI, are reshaping healthcare. In ophthalmology, AI integration has overhauled clinical workflows, particularly in analyzing images for diseases like diabetic retinopathy and glaucoma. What is new This study presents a pioneering comparison between Gemini AI and ChatGPT, evaluating their performance against ophthalmology residents using a meticulously curated dataset derived from real-world ophthalmology board exams. Notably, Gemini Advanced demonstrates superior performance, showcasing substantial advancements, while the evolution of ChatGPT-4 also merits attention. Both models exhibit commendable capabilities. These findings offer crucial insights into the efficacy of AI in ophthalmology, shedding light on areas ripe for further enhancement and optimization., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Osteosarcoma (OS) mortality stems from lung metastases. Matrix metalloproteinases (MMPs) facilitate metastatic dissemination by degrading extracellular matrix components. Herein we studied the impact of targeted MMP downregulation on OS metastasis. Differential gene expression analysis of human OS cell lines revealed high MMP9 expression in the majority of OS cell lines. Furthermore, 143B, a metastatic OS cell line, exhibited increased MMP1 and MMP9 mRNA levels. Gene set enrichment analysis on metastatic and non-metastatic OS patient specimens indicated epithelial-mesenchymal transition as the most enriched gene set, with MMP9 displaying strong association to genes in this network. Using the same dataset, Kaplan-Meier analysis revealed a correlation between MMP1 expression and dismal patient survival. Hence, we undertook targeted suppression of MMP1 and MMP9 gene expression in OS cell lines. The ability of OS cells to migrate and form colonies was markedly reduced upon MMP1 and MMP9 downregulation, whereas their cell proliferation capacity remained intact. MMP9 downregulation decreased tumor growth and lung metastases area in an orthotopic mouse OS model. Consistently, human OS lung metastasis specimens displayed marked MMP9 protein expression. Our findings highlight the role of MMP1 and MMP9 in OS metastasis, warranting further exploration of simultaneous inhibition of MMPs for future OS therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The Druze are a distinct group known for their close community, traditions, and consanguineous marriages, dating back to the eleventh century. This practice has led to unique genetic variations, impacting both pathology and gene-associated phenotypes. Some Druze clans, particularly those with exceptional long-lived family heads (ELLI), attracted attention. Given that the bulk of these ELLI were men, the d3GHR polymorphism was the first obvious possibility. Among the 73 clan members, 8.2% carried the d3GHR isoform, with nearly 11% being males. There was a significant age-related increase (p = 0.04) in this isoform among males, leading to examination of potential environmental mediators affecting gene regulation among these carriers during life (namely epigenetic). We focused on DNA methylation due to its crucial role in gene regulation, development, and disease progression. We analyzed DNA samples from 14 clan members with different GHR genotypes, finding a significant (p < 0.05) negative correlation between DNA methylation levels and age. Employing a biological age clock, we observed a significant + 4.229 years favoring the d3GHR group over the WT and heterozygous groups. In conclusion, this study highlights the advantage of d3GHR carriers among this unique Druze clan and underscores the importance of genotype-environment interaction in epigenetic regulation and its impact on health., (© 2024. The Author(s).)

Aim: To compare the job crafting strategies nurse mentors use when mentoring students versus during periods of respite and to assess the effectiveness of these strategies in reducing instances of missed nursing care (MNC)., Background: Nurses who serve as mentors may have to train a group of nursing students on top of their routine nursing duties. The corresponding high workloads and limited resources may force them to decide which nursing care to delay or omit (i.e., MNC). The mentors' initiative and the actions they take to address the multiple job requirements which do not align with the organization's resources are referred to as job crafting strategies. Mentors can use these strategies to shape their role as nurses as well as their role as mentors, depending on their motives and personality., Design: A longitudinal study with data collected at two time points., Methods: One hundred nurse mentors completed validated questionnaires assessing job crafting strategies, MNC and work overload while actively mentoring students. Eighty returned for a follow-up during a non-mentoring period three months later. Data analysis included paired t-tests and hierarchical multivariable linear regressions., Results: No significant differences were found in MNC between the two points (1.83 SD 0.6 vs. 1.82 SD 0.75; p=0.942). A decrease in hindering demands was noted during active mentoring compared with respite (2.6 SD 0.97 vs. 2.84 SD 0.96; p=0.038). Enhancing structural job resources was significantly negatively correlated with MNC during active mentoring, while enhancing challenging job demands was positively correlated with MNC during these periods (β=0.48, p=0.18 and β=-0.35, p=0.014, respectively)., Conclusion: Nurse mentors can effectively reduce MNC by focusing on enhancing structural resources and limiting challenging demands during mentoring periods. It is essential for healthcare organizations to support nurse mentors with manageable workloads and necessary resources to maintain high-quality care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Abstract: Ataxia-telangiectasia (A-T) is an autosomal-recessive disorder caused by pathogenic variants (PVs) of the ATM gene, predisposing children to hematological malignancies. We investigated their characteristics and outcomes to generate data-based treatment recommendations. In this multinational, observational study we report 202 patients aged ≤25 years with A-T and hematological malignancies from 25 countries. Ninety-one patients (45%) presented with mature B-cell lymphomas, 82 (41%) with acute lymphoblastic leukemia/lymphoma, 21 (10%) with Hodgkin lymphoma and 8 (4%) with other hematological malignancies. Four-year overall survival and event-free survival (EFS) were 50.8% (95% confidence interval [CI], 43.6-59.1) and 47.9% (95% CI 40.8-56.2), respectively. Cure rates have not significantly improved over the last four decades (P = .76). The major cause of treatment failure was treatment-related mortality (TRM) with a four-year cumulative incidence of 25.9% (95% CI, 19.5-32.4). Germ line ATM PVs were categorized as null or hypomorphic and patients with available genetic data (n = 110) were classified as having absent (n = 81) or residual (n = 29) ATM kinase activity. Four-year EFS was 39.4% (95% CI, 29-53.3) vs 78.7% (95% CI, 63.7-97.2), (P < .001), and TRM rates were 37.6% (95% CI, 26.4-48.7) vs 4.0% (95% CI, 0-11.8), (P = .017), for those with absent and residual ATM kinase activity, respectively. Absence of ATM kinase activity was independently associated with decreased EFS (HR = 0.362, 95% CI, 0.16-0.82; P = .009) and increased TRM (hazard ratio [HR] = 14.11, 95% CI, 1.36-146.31; P = .029). Patients with A-T and leukemia/lymphoma may benefit from deescalated therapy for patients with absent ATM kinase activity and near-standard therapy regimens for those with residual kinase activity., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Food is an important environmental factor in the development of inflammatory bowel diseases, chronic immune-mediated diseases of the gastrointestinal tract. Consequently, there is significant focus on the role that dietary approaches might have in the management of these diseases. The introduction of exclusive enteral nutrition (EEN) as a treatment option for induction of remission in Crohn's disease was a breakthrough in disease pathophysiology understanding and has paved the way for dietary options based on this understanding. This review aims to summarize the current data on the effect of different available diets on disease symptoms and the inflammatory process.

We examined differences between social workers in hospitals versus social workers in community health services regarding levels of professional quality of life (ProQoL), proximity to COVID-19, resilience, perceived social support, and preparedness for the next pandemic during waves 3-5 of the COVID-19 pandemic in Israel (December 2020-December 2021, the main COVID-19 variants were Alpha and Delta). We also examined the moderating role of resilience, social support, preparedness for the next pandemic, and health care service type in the association between proximity to COVID-19 and ProQoL. Participants were 163 social workers from four hospitals and 98 social workers from a major health maintenance organization in the community. Social workers in both settings revealed moderate-high levels of compassion satisfaction and moderate levels of burnout and secondary traumatic stress. The study's model indicated that after controlling for the effects of the covariates, higher levels of self-reported-resilience and greater perceived organizational support were associated with higher compassion satisfaction and lower burnout and secondary traumatic stress. Furthermore, a stronger sense of preparedness for the next pandemic was related to lower levels of burnout. The model indicated that the effects of organizational support, informal social support, and preparedness on compassion satisfaction were dependent on the study group (i.e., working in hospital or community settings). Findings indicate that intervention programs should be implemented to help increase compassion satisfaction and prevent/reduce burnout and secondary traumatic stress among social workers in health care settings during health care crises. Enhancing resilience and preparedness should focus not only on the social workers as individuals but also on the institutions for which they work. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: The diagnosis of Gaucher disease (GD) presents a major challenge due to the high variability and low specificity of its clinical characteristics, along with limited physician awareness of the disease's early symptoms. Early and accurate diagnosis is important to enable effective treatment decisions, prevent unnecessary testing, and facilitate genetic counseling. This study aimed to develop a machine learning (ML) model for GD screening and GD early diagnosis based on real-world clinical data using the Maccabi Healthcare Services electronic database, which contains 20 years of longitudinal data on approximately 2.6 million patients., Study Design and Setting: We screened the Maccabi Healthcare Services database for patients with GD between January 1998 and May 2022. Eligible controls were matched by year of birth, sex, and socioeconomic status in a 1:13 ratio. The data were partitioned into 75% training and 25% test sets and trained to predict GD using features obtained from medical and laboratory records. Model performances were evaluated using the area under the receiver operating characteristic curve and the area under the precision-recall curve., Results: We detected 264 confirmed patients with GD to which we matched 3,429 controls. The best model performance (which included known GD signs and symptoms, previously unknown clinical features, and administrative codes) on the test set had an area under the receiver operating characteristic curve = 0.95 ± 0.03 and area under the precision-recall curve = 0.80 ± 0.08, which yielded a median GD identification of 2.78 years earlier than the clinical diagnosis (25th-75th percentile: 1.29-4.53)., Conclusion: Using an ML approach on real-world data led to excellent discrimination between GD patients and controls, with the ability to detect GD significantly earlier than the time of actual diagnosis. Hence, this approach might be useful as a screening tool for GD and lead to earlier diagnosis and treatment. Furthermore, advanced ML analytics may highlight previously unrecognized features associated with GD, including clinical diagnoses and health-seeking behaviors., Plain Language Summary: Diagnosing Gaucher disease is difficult, which often leads to late or incorrect diagnoses. As a result, patients may undergo unnecessary tests and treatments and experience health deterioration despite medications availability for Gaucher disease. In this study, we used electronic health data to develop machine learning models for early diagnosis of Gaucher disease type 1. Our models, which included known Gaucher disease signs and symptoms, previously unknown clinical features, and administrative codes, were able to significantly outperform other models and expert opinions, detecting type 1 Gaucher disease 3 years on average before actual diagnosis. Our models also revealed new features linked to type 1 Gaucher disease, including specific diagnoses and patterns in patients' healthcare-seeking behaviors. We believe that the tool of machine learning can be valuable for patients with rare diseases., Competing Interests: Declaration of competing interest S. R. V. has received research grants, speaker fees, and travel support from Pfizer, Sanofi Genzyme, and Takeda; A. G. was an employee of Takeda at the time of this study and holds Takeda stock; D. G. was an employee of Takeda at the time of this study and holds Takeda stock/stock options; G. C. and S. G. are employees of MaccabiTech. V. S. is the chief marketing officer of Alike and has received speaker fees from Novartis and Roche; A. T., M. R., O. M., and O. P. have no competing interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Obstetric anal sphincter injury (OASI) is associated with serious morbidity and reduced quality of life. The role of anorectal manometry (ARM) to guide treatment is unclear. We aimed to define the role of ARM and symptom assessment post OASI in predicting anal incontinence at long-term follow-up., Methods: Prospective evaluation of 205 consecutive post-OASI women who underwent baseline ARM and symptom assessment in a tertiary setting was undertaken. 99 were available for long term follow-up (median 6.6 years). Associations between post-OASI ARM testing and short- and long- term anal incontinence were examined in addition to clinical and obstetric factors., Results: 4th degree tears and lower anal resting and squeeze pressures were associated with short-term anal incontinence. Females with anal incontinence at baseline, and females with lower anal resting pressure, were more likely to suffer from long-term fecal incontinence (FI). A best-fit cut-off value of 59 mmHg for baseline anal resting pressure predicted long-term FI, and none of the short-term asymptomatic females with an anal resting pressure of >59mmHg reported FI at long-term follow-up., Conclusions: Symptoms of anal incontinence and ARM in patients post OASI are both useful to predict subsequent long-term FI with a best-fit cut-off of 59mmHg for anal resting pressure. This provides rationale for routine ARM and accurate symptom assessment in all patients after OASI, to identify high risk groups to follow and treat, and it may assist decision-making regarding mode of subsequent obstetric deliveries., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have diverse effects on sodium and water homeostasis. They decrease thirst perception, potentially inhibit arginine vasopressin (AVP) production, and induce natriuresis. We present three cases of AVP deficiency (AVP-D) where GLP-1 RA initiation led to desmopressin dose reduction., Cases: Three patients with AVP-D on stable desmopressin therapy started GLP-1 RAs for type 2 diabetes mellitus or obesity. Following weight loss and decreased thirst, all patients reduced their desmopressin dose while maintaining normal thirst and urine output., Discussion: GLP-1 RAs influence sodium and water homeostasis through various mechanisms. In individuals with intact AVP systems, GLP-1 RAs may directly suppress AVP production and induce natriuresis in the kidney leading to increased water excretion. In AVP-D, with exogenous desmopressin replacing endogenous AVP, the osmotic permeability of collecting ducts is primarily influenced by desmopressin dose. Thus, increased distal fluid delivery may allow for lower desmopressin doses to maintain water balance., Conclusion: Our findings indicate a potential interaction between GLP-1 RAs and desmopressin in AVP-D. Clinicians should reassess desmopressin dosage upon initiating GLP-1 RA therapy., (© 2024. The Author(s).)

Spatial attention bias reflects tendency to direct attention to specific side in space. This bias reflects asymmetric dopamine (DA) signaling in the striatum. Administration of DA agonists reduces spatial bias, yet the underlying mechanism is not yet clear. To address this, the current study tested whether methylphenidate (MPH; an indirect DA agonist) reduces orienting bias by modulating fronto-striatal connectivity. 54 adults with consistent bias completed the greyscales task which detects subtle biases during fMRI scanning under MPH (20 mg) or placebo, in a double-blind design. As hypothesized, MPH reduced bias by increasing orienting towards non-preferred hemispace, regardless of whether the initial bias was left or right. MPH-induced increases were found in activation of the medial superior frontal gyrus (mSFG: F[1;53] = 4.632, cluster-defining threshold of P < 0.05, minimal cluster size = 0, p&#95;FWE = 0.036, η2 = 0.08) and its functional connectivity with the caudate (left caudate: F[1;53] = 12.664, p&#95;FWE = 0.001, η2 = 0.192; right caudate: F[1;53] = 11.069, p&#95;FWE = 0.002, η2 = 0.172), when orienting towards the non-preferred hemispace. MPH also reduced mSFG activation and fronto-striatal connectivity for the preferred hemispace. Results suggest modulation of frontal excitability due to increased caudate-mSFG functional connectivity. This mechanism may underlie the positive effect of dopaminergic agonists on abnormal patterns of directing attention in space., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The Tigertriever is a novel, radially adjustable stentriever that addresses limitations in traditional mechanical thrombectomy devices by providing enhanced user control over clot integration. This provides the ability to adapt to patient-specific factors such as varying vessel sizes and clot compositions and may be particularly crucial for ensuring efficacy and safety in distal locations. This consensus paper synthesizes the clinical techniques from a consortium of experienced international operators. It outlines the current data on the Tigertriever, discusses the new operator-controlled capabilities, and provides a recommended approach for both proximal and distal mechanical thrombectomy, emphasizing the "FLEX" approach (Fast Controlled Expansion with Relaxation) for optimal integration and reduced clot disruption., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

To gather national level data on Israeli neonatal HSV (NHSV) infection and to evaluate the distinct clinical characteristics of NHSV and neonatal enteroviral meningitis (NEM). Israeli NHSV patients, hospitalized between January 2015 and April 2022 in 22 medical centers were assessed, together with NEM patients, hospitalized at Sheba Medical Center during the same period. NHSV demographic and clinical characteristics were documented and compared to those of NEM. Eighty-five NHSV (73% males) and 130 NEM (62% males) patients were included. The incidence of NHSV was 5.9/100 000 live births, the common phenotype and HSV type were SEM (53%) and HSV1 (91%), respectively. Horizontal transmission was suspected in 50% cases (of which 67% underwent a Jewish ritual circumcision with direct wound sucking, 33% had relatives with highly suspicious herpetic lesions). Compared with NEM, NHSV tends to present with rash (14% vs. 60%, p-value < 0.01) and seizures (0% vs. 6%, p-value 0.02), while fever, irritability and poor feeding appear more frequently in NEM (94% vs. 18%, p-value < 0.01; 37% vs. 1%, p-value < 0.01; 25% vs. 1%, p-value < 0.01 respectively). Of NEM patients, 28% were treated with acyclovir. Our results mark a decrease in the incidence rate of NHSV in Israel and a prominent mode of horizontal infection acquisition. We underscore the unique localized phenotype of NHSV, in contrast to enterovirus, which tends to cause a systemic disease with constitutional symptoms. These findings should be considered when evaluating the need for comprehensive empirical treatment for HSV in the context of neonatal fever, or according to a certain clinical presentation., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Standard cardiopulmonary exercise testing (CPET) produces a rich dataset but its current analysis is often limited to a few derived variables such as maximal or peak oxygen uptake (V̇O 2 ). We tested whether breath-by-breath CPET data could be used to determine sample entropy (SampEn) in 81 healthy children and adolescents (age 7-18 years old, equal sex distribution). To overcome challenges of the relatively small time-series CPET data size and its nonstationarity, we developed a Python algorithm for short-duration physiological signals. Comparing pre- and post-ventilatory threshold (VT 1 ) CPET phases, we found: (1) SampEn decreased by 9.46% for V̇O 2 and 5.01% for V̇CO 2 (p < 0.05), in the younger, early-pubertal participants; and (2) HR SampEn fell substantially by 70.8% in the younger and 77.5% in the older participants (p < 0.001). Across all ages, females exhibited greater HR SampEn than males during both pre- and post VT 1 CPET phases by 14.10% and 23.79%, respectively, p < 0.01. In females, late-pubertal had 17.6% lower HR SampEn compared to early-pubertal participants (p < 0.05). Breath-by-breath gas exchange and HR data from CPET are amenable to SampEn analysis that leads to novel insight into physiological responses to work intensity, and sex and maturational effects., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Hyperleukocytosis in pediatric acute myeloid leukemia (AML) is associated with severe complications and an inferior outcome. We report results on patients with hyperleukocytosis included in the NOPHO-DBH AML 2012 study. We recommended immediate initiation of full-dose chemotherapy (etoposide monotherapy for 5 days as part of the first course), avoiding leukapheresis and prephase chemotherapy. Of 714 patients included in the NOPHO-DBH AML 2012 study, 122 (17.1%) had hyperleukocytosis, and 111 were treated according to the recommendations with etoposide upfront without preceding leukapheresis or prephase chemotherapy. The first dose was applied the same day as the AML diagnosis or the day after in 94%. Etoposide was administered via peripheral veins in 37% of patients without major complications. After initiation of etoposide the white blood cell counts on days 2-5 were 69%, 36%, 17% and 8%, respectively, of the pre-treatment level. On day 3, 81% of patients had a white blood cell count <100 x109/L. Five-year event-free and overall survival rates for all patients with hyperleukocytosis were 52.9% (95% confidence interval [95% CI]: 44.4-63.0) and 74.1% (95% CI: 66.4-82.6), compared to 64.9% (95% CI: 60.9-69.1) and 78.9% (95% CI: 75.4-82.4) for patients without hyperleukocytosis (P<0.001 for event-free survival, P=0.1 overall survival). Six-week early mortality was 4.1% for all patients with hyperleukocytosis (2.7% for the 111 patients treated with etoposide upfront). We conclude that management of hyperleukocytosis in pediatric AML with immediate etoposide monotherapy without leukapheresis or prephase chemotherapy is feasible, safe and effective. The reduction in white blood cell count during the first days is comparable to the reported results of leukapheresis, and outcomes seem at least equivalent to therapies including leukapheresis. Based on our results, we advocate abandoning leukapheresis for hyperleukocytosis in pediatric AML. Instead, it is crucial to start induction chemotherapy as early as possible.

The rise in ESBL-producing and carbapenem-resistant Gram-negative bacterial infections is alarming. Aminoglycosides remain attractive for treating urinary tract infections (UTIs). However, aminoglycosides-associated acute kidney injury (AKI) raises concerns, especially in patients with underlying renal impairment. We conducted a retrospective cohort study to evaluate the risk of AKI in patients with UTI empirically treated with amikacin. Among 395 patients (median age 41.9 years [IQR 28.3-67.1], 342 [86.6%] female), 162 (41.0%) received amikacin and 233 (59.0%) were empirically treated with other antibiotics. AKI incidence was low (5.6%) and not associated with amikacin exposure (OR 0.56, 95% CI 0.22-1.43, p  = 0.23), even in those with pre-existing renal impairment or AKI on admission. The clinical outcomes (including cure by the third day, AKI, maximal creatinine, length of stay, mortality, and readmission) did not differ between the groups. Once-daily amikacin may offer a safe UTI treatment option amid increasing multi-drug resistance.

The interplay between endogenous testosterone (Te) and prostate cancer (PCa) has long been recognized, with androgen deprivation therapy (ADT) being a cornerstone of advanced and metastatic PCa management. However, the association between Te levels and PCa risk remains complex and not fully understood. This review delves into the complex relationship between adult-onset hypogonadism (AOH) and PCa, shedding light on the complexities surrounding PCa risk and disease aggressiveness. Despite the significant prevalence of PCa among men, particularly as they age, and the emergence of AOH as a prevalent health concern, data regarding their association remains heterogeneous and inconsistently documented. While some studies suggest a potential correlation between low Te levels and decreased PCa detection rates, others indicate a higher risk of aggressive pathological features, primarily observed in prostatectomy cohorts. It's noteworthy that there's evidence indicating hypogonadal men might face an increased risk of reclassification during active surveillance (AS) of low-risk disease. This is supported by the observation of elevated rates of disease upgrading in historical cohorts of low-risk prostatectomies. These contradictory findings are poorly reflected in treatment guidelines. Further research is imperative to comprehensively understand the clinical and associative correlations between AOH and PCa risk and biology, thereby informing more effective management strategies in the future.

Importance: Itching is common in geriatric populations and is frequently linked to dermatological or systemic conditions. Itching engages specific brain regions that are implicated in the pathogenesis of frontotemporal lobar degeneration spectrum disorders (FTLD-SD). Thus, itching of undetermined origin (IUO) may indicate the presence of a neurodegenerative process., Objective: To compare the frequency of itching in FTLD-SD and Alzheimer disease (AD) and to determine the neuroanatomical underpinnings of IUO., Design, Setting, and Participants: This case-control study evaluated data and brain magnetic resonance images (MRIs) for participants with FTLD-SD or AD. Participants of a research study on FTLD-SD at the University of California, San Francisco, Memory and Aging Center were evaluated from May 1, 2002, to December 31, 2021. The exposure group underwent structural brain MRI within 6 months of initial diagnosis. Research visit summaries were reviewed to validate qualitative details and accurately identify itching with undetermined origin (IUO)., Exposures: Symptoms suggestive of FTLD-SD or AD., Main Outcomes and Measures: Frequency of itching in FTLD-SD and AD and neuroanatomic correlates., Results: A total of 2091 research visit summaries were reviewed for 1112 patients exhibiting symptoms indicative of FTLD-SD or AD. From 795 records where itching or a related phrase was endorsed, 137 had IUO. A total of 454 participants were included in the study: 137 in the itching group (mean [SD] age, 62.7 [9.9] years; 74 [54%] females and 63 males [46%]) and 317 in the nonitching group (mean [SD] age, 60.7 [10.8] years; 154 [49%] females and 163 males [51%]). Groups were similar in age, sex, and disease severity. More frequent itching was found in FTLD-SD (95/248 patients [38%], of which 44 [46%] had behavioral variant frontotemporal dementia [bvFTD]) compared with the AD group (14/77 patients [18%]; P = .001). The odds of itching were 2.4 (95% CI, 1.48-3.97) times higher for FTLD-SD compared with all other cases of dementia. Compared with healthy controls, the group with IUO exhibited greater gray matter atrophy bilaterally in the amygdala, insula, precentral gyrus, and cingulum, as well as in the right frontal superior gyrus and thalamus. Among patients with bvFTD and itching vs bvFTD without itching, itching was associated with right-lateralized gray matter atrophy affecting the insula, thalamus, superior frontal gyrus, and cingulum., Conclusions and Relevance: Among individuals with IUO, FTLD-SD was disproportionately represented compared with AD. In FTLD-SD, dysfunction in the right anterior insula and its connected regions, including the right precentral gyrus, cingulum, and bilateral amygdala, contribute to dysregulation of the itching-scratching networks, resulting in uncontrollable itching or skin picking. Awareness among physicians about the relationship between neurodegeneration and itching may help in the management of itch in older individuals. Further studies are needed to determine the best treatments for these symptoms in patients with neurodegenerative disorders.

Objective: The number of pediatric trauma patients requiring surgical interventions has been steadily decreasing allowing for a judicious approach to immediately available resources. This study aimed to derive and validate a prediction rule that reliably identifies injured children who are at very low risk for requiring emergency surgery upon emergency department (ED) arrival., Methods: A retrospective cohort study of data included in the Israeli National Trauma Registry from January 1, 2011, through December 31, 2020, was conducted. We included children aged 0-14 years who presented to EDs from the scene of injury and were hospitalized. We excluded patients transferred between facilities or with isolated burns. The primary outcome was emergency operative intervention (EOI) performed within one hour of ED arrival. We tested mechanism, GCS, heart rate, and blood pressure as candidate predictors. We then randomized patients to two cohorts, derived and internally validated a prediction rule., Results: During the study period, 83,859 children met enrollment criteria. The median age was 6 years (IQR 2-10) and 56,867 (67.8 %) were male; 75,450 (90.0 %) sustained blunt trauma. One hundred sixty-nine (0.20 %) children underwent EOI. In the derivation and validation cohorts, 34,138 (81.4 %) and 34,271 (81.7 %) patients, were classified as low risk based on blunt trauma mechanism, normal GCS (15), and low-risk heart rate (according to age). Of those, 8 (0.02 %) and 13 (0.04 %) required an EOI, respectively. In the validation cohort, the prediction rule for EOI had a sensitivity of 84 % (95 % CI 75-91), a specificity of 82 % (95 % CI 81-82), and a negative predictive value of 99.96 % (95 % CI 99.94-99.98). Among children with an Injury Severity Score>15, the sensitivity was 87 % (95 % CI 77-94), the specificity of 57 % (95 % CI 54-59), and the negative predictive value was 98.97 % (95 % CI 98.13-99.44)., Conclusions: A limited set of physiologic parameters, readily available at hospital admission can effectively identify injured children at very low risk for emergent surgery. For these children, immediate deployment of surgical resources may not be necessary., Competing Interests: Declaration of competing interest Yulia GIMELRAIKH, Danny EPSTEIN, Irina RADOMISLENSKY, Ari M. LIPSKY, Adi GIVON, Ron BERANT, Baruch BERZON, Danny BEN-ELI, Moran BODAS, and Nir SAMUEL declare that they have no conflict of interest. Aeyal RAZ reports receiving consultant fees and research support from Medtronic and consultant fees from Neuroindex (none related to this work). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Circulating tumor DNA (ctDNA) is emerging as a potential biomarker in early-stage urothelial cancer, but its utility in metastatic disease remains unknown. In the phase 3 KEYNOTE-361 study, pembrolizumab with and without chemotherapy was compared with chemotherapy alone in patients with metastatic urothelial cancer. The study did not meet prespecified efficacy thresholds for statistical significance. To identify potential biomarkers of response, we retrospectively evaluated the association of pre- and posttreatment ctDNA with clinical outcomes in a subset of patients who received pembrolizumab (n = 130) or chemotherapy (n = 130) in KEYNOTE-361. Baseline ctDNA was associated with best overall response (BOR; P = 0.009), progression-free survival (P < 0.001) and overall survival (OS; P < 0.001) for pembrolizumab but not for chemotherapy (all; P > 0.05). Chemotherapy induced larger ctDNA decreases from baseline to treatment cycle 2 than pembrolizumab; however, change with pembrolizumab (n = 87) was more associated with BOR (P = 4.39 × 10 -5 ) and OS (P = 7.07 × 10 -5 ) than chemotherapy (n = 102; BOR: P = 1.01 × 10 -4 ; OS: P = 0.018). Tumor tissue-informed versions of ctDNA change metrics were most associated with clinical outcomes but did not show a statistically significant independent value for explaining OS beyond radiographic change by RECIST v.1.1 when jointly modeled (pembrolizumab P = 0.364; chemotherapy P = 0.823). These results suggest distinct patterns in early ctDNA changes with immunotherapy and chemotherapy and differences in their association with long-term outcomes, which provide preliminary insights into the utility of liquid biopsies for treatment monitoring in metastatic urothelial cancer. Clinical trial registration: NCT02853305 ., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates, and The Authors.)

On October 7, 2023, a war erupted in Israel following a mass terror attack including mass shootings, violent events, civilian abductions, and numerous fatalities, ranking as the third most deadliest terror attack. This cross-sectional, population-based study evaluated the impact on the mental health and utilization of mental health services in the Arab and Jewish populations. Conducted through a virtual platform, the study compared demographic factors, exposure to war-related events, anxiety, and post-traumatic stress symptoms among 517 participants in a representative sample of the adult population in Israel (79.1% Jewish, 20.9% Arab). Jews reported higher exposure to war-related events, but a majority expressed a lack of interest in mental help. In contrast, more Arabs desired mental help but faced barriers like stigma and scarce resources. Arabs showed a greater preference for group therapy and medical treatment. Trust in official bodies was consistently higher among Jews. Both populations exhibited similar levels (12-15.4%) of probable post-traumatic stress disorder (PTSD). This study equips clinicians, researchers and policymakers with real-time insights into improving mental health support for the culturally diverse needs of Jewish and Arab communities following exposure to mass trauma., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Fetal cardiotocography is the most common method to assess fetal well-being during labor. Nevertheless, its predictive ability for acidemia is limited, both in low-risk and high-risk pregnancies (Nelson et al. in N Engl J Med 334: 613-9, 1996; Rinciples P et al. in Health and Human Development Workshop Report on Electronic Fetal Monitoring : Update on Definitions. no. 2007, 510-515, 2008), especially in high-risk pregnancies, such as those complicated by growth restriction. In this study we aim examine the association between deceleration and acceleration areas and other measure of fetal heart rate in intrapartum fetal monitoring and neonatal arterial cord blood pH in pregnancies complicated by growth restriction., Materials and Methods: A retrospective cohort study of 100 deliveries complicated by growth restriction, delivered during 2018, was conducted. Known major fetal anomalies, non-vertex presentation and elective cesarean deliveries were excluded. Total deceleration and acceleration areas were calculated as the sum of the areas within the deceleration and acceleration, respectively., Results: In deliveries complicated by growth restriction, cord blood pH is significantly associated with total deceleration area (p = 0.05) and correlates with cumulative duration of the decelerations (Spearman's rank -0.363, p < 0.05), and total acceleration area (-0.358, p < 0.05). By comparing the cord blood pH in deliveries with a total deceleration area that was above and below the median total deceleration area, we demonstrated a significant difference between the categories., Conclusions: Cord blood pH significantly correlates with total deceleration area and other fetal monitoring characteristics in neonates with growth restriction. Future studies using real-time, machine-learning based techniques of fetal heart rate monitoring, may provide population specific threshold values that will support bedside clinical decision making and perhaps achieve better outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the last decade, artificial intelligence (AI) has significantly impacted ophthalmology, particularly in managing corneal diseases, a major reversible cause of blindness. This review explores AI's transformative role in the corneal subspecialty, which has adopted advanced technology for superior clinical judgment, early diagnosis, and personalized therapy. While AI's role in anterior segment diseases is less documented compared to glaucoma and retinal pathologies, this review highlights its integration into corneal diagnostics through imaging techniques like slit-lamp biomicroscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal biomicroscopy. AI has been pivotal in refining decision-making and prognosis for conditions such as keratoconus, infectious keratitis, and dystrophies. Multi-disease deep learning neural networks (MDDNs) have shown diagnostic ability in classifying corneal diseases using AS-OCT images, achieving notable metrics like an AUC of 0.910. AI's progress over two decades has significantly improved the accuracy of diagnosing conditions like keratoconus and microbial keratitis. For instance, AI has achieved a 90.7% accuracy rate in classifying bacterial and fungal keratitis and an AUC of 0.910 in differentiating various corneal diseases. Convolutional neural networks (CNNs) have enhanced the analysis of color-coded corneal maps, yielding up to 99.3% diagnostic accuracy for keratoconus. Deep learning algorithms have also shown robust performance in detecting fungal hyphae on in vivo confocal microscopy, with precise quantification of hyphal density. AI models combining tomography scans and visual acuity have demonstrated up to 97% accuracy in keratoconus staging according to the Amsler-Krumeich classification. However, the review acknowledges the limitations of current AI models, including their reliance on binary classification, which may not capture the complexity of real-world clinical presentations with multiple coexisting disorders. Challenges also include dependency on data quality, diverse imaging protocols, and integrating multimodal images for a generalized AI diagnosis. The need for interpretability in AI models is emphasized to foster trust and applicability in clinical settings. Looking ahead, AI has the potential to unravel the intricate mechanisms behind corneal pathologies, reduce healthcare's carbon footprint, and revolutionize diagnostic and management paradigms. Ethical and regulatory considerations will accompany AI's clinical adoption, marking an era where AI not only assists but augments ophthalmic care., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: Short inter-pregnancy interval (IPI) of <18 months following a live birth, has been associated with adverse pregnancy outcome. This study aimed to evaluate whether a short IPI following a medically treated missed abortion (MA) poses similar perinatal risks in a subsequent pregnancy., Study Design: The retrospective analysis included patients with history of an MA at up to 10 weeks of gestation, treated with misoprostol (pgE1) only, and with a documented subsequent live pregnancy (2010-2022). 1110 Patients were allocated into two groups: IPI ≤18 months and IPI >18 months. The primary outcome was the risk for a spontaneous preterm birth (PTB) <37 weeks of gestation in the consecutive pregnancy. Secondary outcomes included maternal and neonatal adverse outcomes. Statistical analysis was performed using the Statistical Program for Social Sciences for Windows version 26 (SPSS Inc, Chicago, IL)., Results: The cohort included 1,110 patients: 430 (38.74 %) patients with IPI <18 months and 680 (61.26 %) patients with IPI >18 months. The characteristics of the two groups were not significantly different. The rates of spontaneous PTB <37 and <34 weeks of gestation were significantly higher in the short vs. long IPI cohort (16.28 % vs. 7.06 % and 6.74 % vs. 5.0 %, respectively, p < 0.05). These patients also had a higher risk for Cesarean delivery (31.63 % vs. 23.34 %, p = 0.005) and postpartum hemorrhage (4.42 % vs. 2.06 %, p = 0.029) compared to patients with IPI >18 months. The observed differences remained statistically significant even after adjusting for potential confounding variables using multiple regression analysis. No other significant differences in neonatal or maternal outcomes were noted., Conclusion: Short IPI (≤18 months) following a medical treatment MA may be associated with an increased risk of PTB, Cesarean delivery and PPH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Society guidelines on colorectal dysplasia screening, surveillance, and endoscopic management in inflammatory bowel disease (IBD) are complex, and physician adherence to them is suboptimal. We aimed to evaluate the use of ChatGPT, a large language model, in generating accurate guideline-based recommendations for colorectal dysplasia screening, surveillance, and endoscopic management in IBD in line with European Crohn's and Colitis Organization (ECCO) guidelines., Methods: 30 clinical scenarios in the form of free text were prepared and presented to three separate sessions of ChatGPT and to eight gastroenterologists (four IBD specialists and four non-IBD gastroenterologists). Two additional IBD specialists subsequently assessed all responses provided by ChatGPT and the eight gastroenterologists, judging their accuracy according to ECCO guidelines., Results: ChatGPT had a mean correct response rate of 87.8%. Among the eight gastroenterologists, the mean correct response rates were 85.8% for IBD experts and 89.2% for non-IBD experts. No statistically significant differences in accuracy were observed between ChatGPT and all gastroenterologists ( P =0.95), or between ChatGPT and the IBD experts and non-IBD expert gastroenterologists, respectively ( P =0.82)., Conclusions: This study highlights the potential of language models in enhancing guideline adherence regarding colorectal dysplasia in IBD. Further investigation of additional resources and prospective evaluation in real-world settings are warranted., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose: To investigate whether reducing the volume of intravenous iodinated contrast material injected during brain computed tomography (CT) provides reliable and accurate imaging without compromising diagnostic accuracy., Methods: This prospective study enrolled patients undergoing enhanced brain CT at a single tertiary hospital. Subjects who agreed to participate received a reduced dose of 60 ml contrast. The images were compared to an age and gender-matched control group who received the conventional 80 cc dose. Neuroradiologists assessed image quality and interpretation using a 5-point Likert scale with six specific domains. Based on ICC, inter-rater reliability was high at 0.873. Multiple linear regression predicted overall diagnostic accuracy based on contrast dose, age, and gender. Visual Grading Characteristics (VGC) analysis was also performed to quantify regional brain enhancement differences between the two contrast groups., Results: The study included 47 patients in the 60 cc group and 55 in the 80 cc control group. The results showed the 80 cc group had significantly higher enhancement ratings compared to 60 cc for all six structures assessed. The differences between groups ranged from -0.241 to -0.433 (p < 0.001) on the 5-point scale.The VGC analysis confirmed significantly greater brain parenchymal enhancement in the 80 cc group compared to the 60 cc group., Conclusion: The findings indicate that reducing the intravenous iodinated contrast material volume during brain CT from 80 cc to 60 cc leads to a statistically significant reduction in image quality and diagnostic accuracy. Further research with larger cohorts is needed to confirm these findings and assess the clinical impact of these differences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This case report describes a 2-month-old girl with acute megakaryoblastic leukemia (AMKL) harboring the t(1;22)(p13;q13) translocation, resulting in the RBM15::MRTFA fusion gene. She presented with massive hepatosplenomegaly and liver fibrosis and achieved complete remission with chemotherapy; the liver fibrosis resolved within 2.5 months. After 12 years of follow-up, the patient remained in good health, without relapse. Reviewing the literature on eight additional similar cases of liver fibrosis, this subtype of AMKL predominantly affects female patients below 3 months of age, with a median onset at 6 weeks. High rates of severe complications were observed, with five of nine patients dying within 10 weeks of diagnosis. The authors hypothesized that the proliferation of abnormal megakaryoblasts within the liver leads to the release of profibrotic cytokines, such as TGF-β1, which induces liver fibrosis similar to that observed in transient abnormal myelopoiesis in Down syndrome. Careful monitoring of liver functions and reduced-intensity chemotherapy are recommended for this very young patient population. Nonetheless, long-term survival can be achieved with aggressive supportive care and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Arad-Cohen, Attias, Zohar and Messinger.)

Competing Interests: Financial disclosures/conflicts of interest: None reported.

The herpes simplex viruses consist of the strains, HSV-1 and HSV-2, which are prevalent worldwide and lack a definitive cure. We aimed to explore the specific characteristics of HSV 1 and 2 infections, such as differences between gender assigned at birth, age at infection, site of infection, comorbidities, and effect of pregnancy, through a data analysis. Between 2011 and 2018, the Israeli Central Virology Laboratory diagnosed 9189 samples using multiplexed real-time PCR. In addition, we extracted all of the medical data for 287 females hospitalized at the Sheba Medical Center with HSV-1 (161) or HSV-2 (126) genital infections. HSV-2 was almost absent in the orofacial samples from both genders, while in other lesion sites, HSV-2 was significantly more abundant in females than in males ( p < 0.05,). HSV-2 was initially detected at puberty. In the hospitalized females' malignancies, both HSV-1 and HSV-2 were found with a non-significant difference. Simultaneously, pregnancies were more common in females who were HSV-2-positive compared with those who were HSV-1-positive (27.8% vs. 12.4%, respectively, p < 0.01). Primary infections occur more with HSV-1 than with HSV-2 (15.6% vs. 3.2%, respectively). Our findings demonstrate that genital HSV-2 infection episodes are more frequent during pregnancy, suggesting that pregnancy may serve as a risk factor for HSV-2 reactivation or infection.

Background: Osteoporosis prevalence is increased in Crohn's disease (CD). Its pathogenesis in these patients is incompletely understood., Objectives: To identify factors associated with decreased bone mineral density (BMD) status in CD patients on a time-line course., Methods: A retrospective study was performed that followed CD patients who underwent at least two bone mineral density scans (DEXAs). Follow-up began one year prior to the first DEXA test and lasted at least one year after a second test. Possible correlations between baseline and follow-up variables and changes in BMD status were examined. Change in BMD was defined as a transition from one bone density category to another (normal vs. osteopenia vs. osteoporosis). Binary variables were assessed using the Cochrane-Armitage test. Categorical variables were assessed using the chi-squared test. A multivariate analysis was performed., Results: The study included 141 patients. At baseline, 33 patients (23.4%) had normal BMD, 75 (53.2%) had osteopenia, and 33 (23.4%) had osteoporosis. Patients with low BMD had a lower baseline BMI compared to those with normal BMD ( p < 0.0001). After a median follow-up of 48 months (IQR 29-71), BMD status worsened in 19 (13.5%) patients, whereas in 95 (67.3%) and 27 (19.1%) patients, BMD remained unchanged or improved, respectively. On the multivariate analysis, elevated median CRP throughout follow-up (OR = 0.8, 95% CI: 0.68-0.93) and low baseline BMI (OR = 0.9, 95% CI: 0.83-0.98) were associated with a lack of BMD status improvement., Conclusions: Persistently elevated CRP and low BMI are associated with a lack of improvement in BMD. These findings underscore the importance of effective inflammation control and nutritional support to maintain and improve bone health.

Background: Septic cardiomyopathy (SCM) with diastolic dysfunction carries a poor prognosis, and the mechanisms underlying the development of diastolic dysfunction remain unclear. Matrix metalloproteinase-8 (MMP-8) is released from neutrophils and degrades collagen I. MMP-8 levels correlate with SCM severity., Objectives: We scrutinized, for the first time, the direct impact of MMP-8 on cardiac systolic and diastolic functions., Methods: Isolated rat hearts were perfused with Krebs-Henseleit solution in a Langendorff setup with computer-controlled filling pressures of both ventricles at isovolumetric regime. The end-diastolic pressure (EDP) varied periodically between 3 and 20 mmHg. After baseline recordings, MMP-8 (100 µg/ml) was added to the perfusion. Short-axis views of both ventricles were continuously acquired by echocardiography., Results: MMP-8 perfusion resulted in progressive decline in peak systolic pressures (Psys) in both ventricles, but without significant changes in their end-systolic pressure-area relationships (ESPARs). Counterintuitively, conspicuous leftward shifts of the end-diastolic pressure-area relationships (EDPARs) were observed in both ventricles. The LV end-diastolic area (EDA) decreased by 32.8±5.7%, (p=0.008), at EDP of 10.5±0.4 mmHg, when LV Psys dropped by 20%. The decline of Psys was primarily due to the decrease in EDA and restoring the baseline EDA by increasing EDP recovered 81.33 ± 5.87% of the pressure drops., Conclusion: Collagen I generates tensile (eccentric) stress, and its degradation by MMP-8 causes EDPVR leftward shift, resulting in diastolic and systolic dysfunctions. The diastolic dysfunction explains the clinically observed fluid unresponsiveness, while the decrease in EDV diminishes the systolic functions. MMP-8 can explain the development of SCM with diastolic dysfunction.

Introduction: Titanium dental implants, traditionally used for tooth replacement, face certain biological and aesthetic limitations. Recently, zirconia has become a notable alternative, valued for its aesthetics and biocompatibility. This study evaluated the efficacy of two-piece zirconia dental implants, particularly their impact on inflammatory cytokines and their survival rate over one year., Methods: This study was a single-center, prospective trial and included adults aged 18 and above. 2021-2022, nine two-piece tissue-level zirconia implants were placed in eight patients. Following a three-month osseointegration phase, crowns were cemented. Over a year, we assessed Plaque and Gingival indices, Pocket Depth, and tissue color and texture. Peri-apical radiographs measured bone levels, and IL-1β in peri-implant crevicular fluid (PICF) was quantified using ELISA., Results: Eight subjects (ages 31-63) participated. One implant failed after six months, resulting in a one-year survival rate of 88.8%. Plaque and Gingival indices rose, but peri-implant soft tissue remained stable in color and texture. At 12 months, average bone loss was minimal and insignificant compared to the baseline. IL-1β levels were similar to those at contralateral teeth, with no correlation between IL-1β, Pocket Depth, and Bleeding on Probing., Conclusion: Two-piece zirconia implants emerged as a viable tooth replacement option, with an 88.8% one-year survival rate. They maintained stable soft tissue and bone levels, indicating their potential as effective dental restoratives., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

During embryogenesis, the vertebrae begin development during the 6th week of gestation via two lateral chondrification centers per segment. It was assumed that when disruptions occur in the process of somitogenesis during membranous vertebral body formation, chondrification and ossification will follow the anomalous membranous vertebral body scaffolding, resulting in an anomalous vertebral formation, such as a hemivertebra. Another hypothesis is that hemivertebra may result from anomalous distribution of intersegmental arteries of the vertebral column. There is no description in the medical literature of "excess linear calcifications" of part of the fetal vertebra, characterized by the presence of linear calcifications in the vertebrae of a developing fetus. In the first two trimesters of pregnancy, the fetal vertebrae usually show three calcified points in an axial section: the vertebral body and two transverse processes. Premature linear vertebral calcification was defined as an anterior or posterior echogenic connection between two of the points (Fig. 1). In this study, we describe seven cases of premature fetal linear vertebral calcification., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose: Treatment options are limited for patients with previously treated metastatic colorectal cancer (mCRC). In the LEAP-017 study, we evaluate whether lenvatinib in combination with pembrolizumab improves outcomes compared with standard of care (SOC) in previously treated mismatch repair proficient or not microsatellite instability high (pMMR or not MSI-H) mCRC., Methods: In this international, multicenter, randomized, controlled, open-label, phase III study, eligible patients age 18 years and older with unresectable, pMMR or not MSI-H mCRC, that had progressed on or after, or could not tolerate, standard treatment, were randomly assigned 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 400 mg intravenously once every 6 weeks or investigator's choice of regorafenib or trifluridine/tipiracil (SOC). Randomization was stratified by presence or absence of liver metastases. The primary end point was overall survival (OS). LEAP-017 is registered at ClinicalTrials.gov (NCT04776148), and has completed recruitment., Results: Between April 8, 2021, and December 21, 2021, 480 patients were randomly assigned to lenvatinib plus pembrolizumab (n = 241) or SOC (n = 239). At final analysis (median follow-up of 18.6 months [IQR, 3.9]), median OS with lenvatinib plus pembrolizumab versus SOC was 9.8 versus 9.3 months (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P = .0379; prespecified threshold P = .0214). Grade ≥3 treatment-related adverse events occurred in 58.4% (lenvatinib plus pembrolizumab) versus 42.1% (SOC) of patients. Two participants died due to treatment-related adverse events, both in the lenvatinib plus pembrolizumab arm., Conclusion: In patients with pMMR or not MSI-H mCRC that had progressed on previous therapy, there was no statistically significant improvement in OS after lenvatinib plus pembrolizumab treatment versus SOC. No new safety signals were observed.