Search

Background/aims: To report the long-term visual outcomes and side effects in patients with small choroidal melanoma (CM) undergoing ruthenium-106 (Ru-106) plaque brachytherapy., Methods: Retrospective, interventional, consecutive series of small CM ≤2.5 mm in height and ≤16 mm in largest basal diameter treated with Ru-106 plaque with a median radiation dose of 100 Gy prescribed to tumour apical height., Results: 310 patients (160 men) with a mean (SD) age of 58.4±14.1 years met the study inclusion criteria. The median follow-up was 57.5 (range 3.4-170.5) months. The mean tumour baseline thickness was 1.9±0.4 (range 0.4-2.5) mm. The mean baseline logarithm of the minimum angle of resolution (logMAR) of best corrected visual acuity (BCVA) was 0.21±0.4 (Snellen equivalent 6/9; range -0.1 to 1.5). Mean final BCVA was ≤0.3 logMAR (Snellen equivalent 6/12) in 161 patients (54.2%), better than 1.0 logMAR (Snellen equivalent 6/60) and <0.3 logMAR in 59 patients (19.9%), and ≥1.0 logMAR in 77 patients (25.9%). Kaplan-Meier estimates of poor final VA (≥1.0 logMAR) were 13.2% at 5 years and 54.5% at 10 years. Early and late complications developed in 20.6% and 42.6% of cases, respectively. Radiation maculopathy was the most frequent late side effect (29% of patients) with Kaplan-Meier rates of 18.2%, 31.7% and 42.1% at 3, 5 and 10 years, respectively. Older age, lipofuscin, proximity to fovea, final tumour elevation and radiation maculopathy predicted visual loss ≥5 Snellen lines., Conclusion: Despite early and late complications in 20.6% and 42.6% of cases, Ru-106 brachytherapy for small CM allows retention of BCVA ≤0.3 logMAR in half of the eyes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Ischemia-reperfusion injury (IRI) is a common pathogenic situation that arises throughout all liver surgeries, including liver transplants. We aimed to compare the preventive effects of valsartan (VST) against valsartan + sacubitril (LCZ696) on hepatic injury caused by IRI. A total of thirty-six male Westar albino rats were split into six groups randomly: sham, IRI, VST + IRI, LCZ696 + IRI, VST, and LCZ696. The medicines were given orally for 10 days in a row. Hepatic tissues and blood were examined through histopathological imaging and immunohistochemical detection of hepatic SMAD-4 protein expression plus serum aminotransferase (ALT, AST) and gamma-glutamyl transferase (GGT) levels. Angiotensin II, aldosterone, and plasma renin activity were evaluated in rat serum. Liver tissue homogenate was utilized to assess reduced glutathione (GSH), myeloperoxidase (MPO), malondialdehyde (MDA), and total nitric oxide (NOx) levels. Pro-inflammatory indicators, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β), moreover with apoptosis indicators, BCL2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and galactine-9 (GAL9) proteins plus caspase-3, were measured in hepatic tissue homogenate. Hepatic endothelin-1 and neprilysin activity were evaluated. Western blot was done for c-Jun N-terminal kinase (JNK-7) plus nuclear factor-kappa B (NF-κβ) expressions. The study revealed that VST and LCZ696 pretreatment showed significant restoration of liver injury, correction of oxidative profile, and inhibition in the angiotensin II receptor-neprilysin pathway. Inflammatory mediators and apoptosis were significantly inhibited. The expression of SMAD-4, JNK-7, and NF-κβ proteins was notably diminished. The improvement in hepatic architecture supports these histopathological results. In conclusion, LCZ696 possesses a potentially significant protective effect against liver IRI superior to VST alone., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite extensive ecotoxicological evidence on the adverse effects of oil pollution on rodents, little is known about how rodents make decisions in oil-polluted environments (i.e., outside of lab settings). We investigated the foraging behavior of Allenby gerbils, Gerbillus andersoni allenbyi (GA), that were presented with feeding trays in a semi-natural environment. The trays contained seeds mixed into one of three types of soils - clean soil, and two different soil samples collected from two well-documented terrestrial oil spill sites in Israel. The oil spill disasters occurred in 1975 and 2014 and the spill sites are located within a few hundred meters of each other, in the 'Avrona Nature Reserve in the Arava hyper-arid region in Israel. Gerbils of both sexes avoided foraging in 2014-polluted soil, but surprisingly, they foraged more in 1975-polluted soil. Our results indicate that for the GA, the 1975-polluted soil is an advantageous substrate to forage on, probably because its texture facilitates more efficient foraging, leading to greater energetic gain, and creating a trade-off between energetic gain and perceived foraging cost due to its pollution. We also proceeded to investigate some physiological consequences of chronic exposure to the 2014-polluted soil in the laboratory. Chronic oil exposure did not lead to mortality or weight loss, but female gerbils exhibited heightened cortisol. We conclude that terrestrial oil pollution may have significant sublethal impacts on animal behavior, even when there is no obvious short-term physiological cost to the exposure., 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 Ltd. All rights reserved.)

Background and Aims: Janus kinase [JAK] inhibitors are used for treating inflammatory bowel diseases [IBD]. We aimed to identify the molecular effects of JAK inhibition in human intestinal mucosa, considering IBD location and phenotype., Methods: Colonic and ileal explants from patients with ulcerative colitis [UC], Crohn's disease [CD], and non-IBD controls [NC] were assessed for levels of phosphorylated signal transducers and activators of transcription [p-STAT] and expression of inflammatory genes in response to an ex vivo JAK inhibitor [tofacitinib]. Cytokine production by lamina propria lymphocytes in response to tofacitinib was assessed. Human intestinal organoids were used to investigate the effects of JAK inhibitors on inducible nitric oxide synthase [iNOS] expression., Results: Explants were collected from 68 patients [UC = 20, CD = 20, NC = 28]. p-STAT1/3/5 inhibition rates varied, being higher in colonic compared to ileal explants. p-STAT1/3 inhibition rates negatively correlated with levels of C-reactive protein [CRP]. While significant alterations in 120 of 255 inflammatory genes were observed in colonic explants, only 30 were observed in ileal NC explants. In colonic explants from UC, significant alterations were observed in five genes, including NOS2. JAK inhibition significantly decreased Th1/Th2/Th17-related cytokine production from lamina propria lymphocytes. Various JAK inhibitors reduced the interferon-γ-induced increase in iNOS expression in organoids., Conclusions: A site-specific anti-inflammatory effect of JAK inhibition by tofacitinib was noted, whereby the colon was more robustly affected than the ileum. The ex vivo response to tofacitinib is individual. JAK inhibition may attenuate inflammation by decreasing iNOS expression. Ex vivo mucosal platforms may be a valuable resource for studying personalized drug effects in patients with IBD., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Dendrites are crucial for receiving information into neurons. Sensory experience affects the structure of these tree-like neurites, which, it is assumed, modifies neuronal function, yet the evidence is scarce, and the mechanisms are unknown. To study whether sensory experience affects dendritic morphology, we use the Caenorhabditis elegans ' arborized nociceptor PVD neurons, under natural mechanical stimulation induced by physical contacts between individuals. We found that mechanosensory signals induced by conspecifics and by glass beads affect the dendritic structure of the PVD. Moreover, developmentally isolated animals show a decrease in their ability to respond to harsh touch. The structural and behavioral plasticity following sensory deprivation are functionally independent of each other and are mediated by an array of evolutionarily conserved mechanosensory amiloride-sensitive epithelial sodium channels (degenerins). Calcium imaging of the PVD neurons in a micromechanical device revealed that controlled mechanical stimulation of the body wall produces similar calcium dynamics in both isolated and crowded animals. Our genetic results, supported by optogenetic, behavioral, and pharmacological evidence, suggest an activity-dependent homeostatic mechanism for dendritic structural plasticity, that in parallel controls escape response to noxious mechanosensory stimuli., Competing Interests: SI, YI, AC, HS, MO, MK, BP No competing interests declared, (© 2025, Inberg et al.)

Introduction: This study aims to explore the reno-protective effect of Curcumin in focal and segmental glomerulosclerosis (FSGS) in Murine models, a common chronic glomerulopathy that leads to end stage renal disease., Methods: Adult Wistar rats were used in this experiment. One group was treated with intravenous Adriamycin (ADR) injection to induce FSGS similar to that seen in humans and a second group was co-administered ADR and Curcumin (ADR-CUR). Saline treated rats served as controls. Renal injury was assessed by measuring the levels of serum creatinine, blood urea nitrogen (BUN), triglyceride and urinary protein. The homogenates of renal cortex were used to estimate the renal content of the inflammatory marker, tumor necrosis factor-a (TNF-a); oxidative stress marker, Malonaldehyde (MDA); and two anti-oxidants superoxide dismutase (SOD) and reduced glutathione (GSH). In addition, the rat kidneys were harvested by ends of week-8 and week-12 and examined for histological abnormalities., Results: The ADR-treated rats showed biochemical and histological evidence of FSGS, in the form of proteinuria, elevated serum creatinine, BUN and triglycerides, elevated renal TNF-a and MDA, and segmental glomerulosclerosis. The ADR-CUR treated rats showed significant correction of all these variables. Co-administration with Curcumin resulted in improvement of the proteinuria, serum creatinine, BUN and triglyceride. The renal tissue levels of anti-oxidants SOD and GSH increased and that of TNF-a and MDA decreased and the histology revealed reduction in the extent of segmental glomerulosclerosis. The FSGS associated renal damage was notably antagonized by curcumin treatment., Conclusion: Our findings confirm the reno-protective effects of Curcumin as a potential therapeutic agent in protection against the progression of FSGS and indicate that it is mitigated by inhibition of oxidant injury and inflammation and also by promotion of antioxidants. Curcumin ameliorated the ADR-induced FSGS in murine models. It may be a promising compound in the treatment of FSGS in human subjects. More human studies are needed to further elucidate its effects in FSGS., (S. Karger AG, Basel.)

In recent decades, there has been a growing interest in the use of polysaccharides that exhibit biological activity for a wide range of innovative applications. This is due to their nontoxicity, biodegradability, biocompatibility, and therapeutic properties. The diverse properties of polysaccharides derived from marine algae make them a promising strategy for the construction of drug delivery systems (DDSs). Marine algal polysaccharides can be utilized in regenerative medicine and gene delivery to facilitate the controlled release of therapeutic substances, which is a critical stage in the fight against severe diseases. Algal polysaccharide-based nanoparticles, microspheres, hydrogels, patches, and films are among the numerous controllable and sustained anti-inflammatory and anticancer DDSs that can be used due to the biological activities of these algal polymers. This review paper summarizes the advantages and applications of marine algal polysaccharides in DDSs (such as nanoparticles, microspheres, hydrogels, patches and films) as well as recent advances in drug delivery technologies, thereby providing valuable information for future research on drug delivery-based algal polysaccharides., 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 © 2025 Elsevier B.V. All rights reserved.)

Background: On 7 October 2023, an armed conflict erupted between Hamas and Israel, leading to numerous combat casualties., Objectives: To describe computed tomography (CT) findings of combat casualties at a tertiary medical center during the first 3 months of the conflict., Methods: A retrospective observational study was conducted on patients admitted between 7 October 2023 and 7 January 2024. Adults with conflict-related trauma who underwent chest, abdomen, and pelvis (body) trauma protocol CT scans were included., Results: Of 272 patients who underwent body trauma protocol CT, 112 combat-related adults were included, mean age of 27 years and one female. In total, 82 patients (73%) underwent additional scans of the head and neck or extremities. Fractures were observed in 53 patients (47%). Vascular injuries were present in 40 patients (35%). Limb injuries were most common, affecting 37 patients (33%), which prompted a protocol update. Lung injuries were the most common in body CT: 30 patients (27%). Head and neck injuries were seen in 21 patients (18%). Multisystem trauma was present in 24 patients (21%). A total of 83 patients (74%) underwent surgery, mostly orthopedic/soft tissue surgeries (63%); 15 (13%) underwent abdominal surgery, with bowel injuries confirmed in eight cases., Conclusions: CT scans are an important tool in conflict trauma management. Limb injuries were the most frequent, necessitating protocol adjustments. Lung injuries were the most common body injury; 21% of patients had multisystem trauma. Most patients required surgery.

Vitiligo pathogenesis is complex. There is some evidence in support of the neurohormonal pathways involved. Although considered a nonpruritic condition, some patients may experience itching, which can occur ahead of the appearance of the patches. We aimed to assess sensory symptoms in active and stable vitiligo patients and to measure 3 neuropeptide expressions in their lesional skin (neuropeptide Y [NPY], calcitonin gene-related peptide [CGRP], and nerve growth factors [NGF]) to correlate neuropeptide levels and sensory symptoms, with vitiligo activity. This case-control study included 85 patients, aged 18 years and older, analyzed into active or stable vitiligo groups. Patients were screened for itching or other abnormal neurological sensations such as paresthesia and numbness. The Vitiligo Disease Activity Score, Vitiligo Signs of Activity Score, and dermoscopic score were performed to assess disease activity. Three neuropeptides were quantified by enzyme-linked immunosorbent assay in skin biopsies from the edge of vitiligo lesions. A normal control group was also included. Results showed that 24.7% of patients had sensory symptoms: itching (18.8%), paresthesia (2.4%), and numbness (3.5%). The NGF, CGRP, and NPY levels were significantly higher in skin of normal controls compared to stable and active vitiligo patients. They were lowest in active vitiligo skin (p = 0.001, 0.016, and 0.01, respectively). NGF was the most relevant neuropeptide to vitiligo activity and sensory manifestations. In conclusion, almost one-third of the patients with active vitiligo reported sensory symptoms, predominantly itching, thus sensory manifestations may suggest a prodroma of activity and could be included in the screening tools for vitiligo activity. Trial Registration: www.clinicaltrials.gov (NCT05390164)., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diabetic macular edema (DME) is a vision-threatening complication of diabetic retinopathy and causes significant morbidity in patients. Anti-vascular endothelial growth factor (VEGF) agents are the mainstay of treatment for DME, with steroid implants being used for the treatment of anti-VEGF resistant eyes. Over the years, several classification systems have been devised to describe the patterns of DME using optical coherence tomography (OCT). With the advent of effective treatments, it has become imperative that imaging cues are not merely used for classifying the disease but also as biomarkers for prognostication of disease activity and treatment response. In this aspect, newer imaging findings such as hyperreflective dots, photoreceptor integrity, and disorganization of retinal inner layers have been characterized in detail by several authors. Macular perfusion analysis using OCT angiography is the latest in the armamentarium for imaging DME. In this narrative review, we have summarized all relevant literature related to the ultrastructural imaging-based biomarkers of DME and their correlation to treatment., (Copyright © 2024 Indian Journal of Ophthalmology.)

Chronic tendinopathy is a degenerative condition characterized by persistent pain, functional limitations, and tendon thickening, often resulting from repetitive overuse or failed tendon healing. Left untreated, it can progress to tendon rupture, prolonged disability, and impaired quality of life. Management typically includes conservative therapies, such as physical therapy, corticosteroid (CS) injections for short-term relief, and platelet-rich plasma (PRP) as a regenerative therapy with potential long-term benefits. This systematic review and meta-analysis evaluates and compares the effectiveness of PRP and CS injections for chronic tendinopathies regarding pain reduction, functional improvement, and long-term outcomes. A structured search of PubMed, Scopus, Google Scholar, and the Cochrane Library identified randomized controlled trials (RCTs) and comparative studies. Primary outcomes included pain reduction and functional improvement while secondary outcomes assessed heterogeneity and publication bias. PRP and CS injections demonstrated no significant difference in short-term pain reduction. Functional outcomes were comparable in the short term but showed a trend favoring PRP at longer follow-up periods. PRP exhibited a slight advantage in long-term functional recovery, though the results were not statistically significant. Substantial heterogeneity across studies highlights the need for standardized protocols and larger trials to confirm these findings and optimize treatment strategies., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Elnewishy et al.)

Aim: To report local tumour control, metastasis and survival rates of patients with small choroidal melanoma (CM) after treatment with ruthenium-106 (Ru-106) plaque brachytherapy., Methods: Retrospective case series of 353 consecutive eyes with small CM (thickness ≤2.5 mm and largest basal diameter ≤16 mm) treated with Ru-106 brachytherapy at the London Ocular Oncology Service, between October 2004 and May 2019., Results: The final cohort included 310 eyes and tumour recurrence was observed in 52 (17%) eyes. Ocular retention rate was 96%. Metastatic disease and tumour-related death occurred in 18 (5.8%) and 12 (3.9%) patients, respectively. Metastases were diagnosed after a median of 54 (54±35; range 3.6-118) months from initial treatment. Kaplan-Meier estimates for tumour recurrence, melanoma-related metastases and survival were 17% (95% CI 13.3% to 22.9%), 4.8% (95% CI 2.6% to 8.5%) and 98% (95% CI 94.4% to 99.1%) at 5 years and 26% (95% CI 18.3% to 35.3%), 16% (95% CI 8.7% to 27.7%) and 92% (95% CI 84.5% to 95.7%) at 10 years, respectively. On multivariable analysis, factors predictive for tumour recurrence included juxtapapillary location, larger plaque and final tumour thickness, and for metastasis exudative retinal detachment., Conclusion: Small CMs treated with Ru-106 brachytherapy show recurrence and death rates of 17% and 2% at 5 years and 26% and 8% at 10 years. As small CMs have better prognosis than large tumours, early treatment is the key for better survival outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Psoriasis is a common chronic systemic disease affecting the skin, nails, and joints. Nails are commonly associated with a greater severity of the disease. Radiofrequency (RF) is a nonionizing radiation that provides energy originating from electric current to generate heat inside the dermis with anti-inflammatory effects., Objective: To assess the efficacy of nonablative bipolar radiofrequency in treating fingernail psoriasis., Methods: Forty-three affected fingernails were treated with nonablative bipolar RF. Sessions were performed every 2 weeks for 2 months, with a maximum of 5 sessions. The 32-point target nail psoriasis severity index (tNAPSI), ultrasonography, and the physicians' global assessment were used for assessment at baseline, 1 month, and 3 months from the last treatment session., Results: One month after the last RF session, a significant reduction in median tNAPSI score from baseline was recorded (p = .002), with a 58.33% reduction in pit count. The median thickness of subungual hyperkeratosis decreased significantly from baseline (p = .024), and the median score of onycholysis was also significantly reduced (p = .005). Ultrasonography revealed a significant reduction in the median nail matrix, bed thickness, and nail vascularity (p = .020, p < .001, and p = .013, respectively)., Conclusion: Radiofrequency may offer a safe and effective treatment modality for fingernail psoriasis., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

With aging, facial lines on the forehead and glabella are sometimes converted from dynamic to static giving an aged appearance. Polydioxanone sutures are popular now as a management option in correcting deep static wrinkles on the upper face .This work was conducted to assess the synergistic efficacy of combining Botulinum toxin injection with Polydioxanone threads on the upper face static wrinkles. 30 adult patients with static wrinkles on forehead were included in this work. They were randomly distributed to one of two groups; threads insertion either alone or with Botulinum toxin injection. Treatment efficacy was evaluated after 2 months by using a Global Aesthetic Improvement Scale. Our results displayed a statistically significant improvement in forehead wrinkles in group II compared to group I (P=0.001). There was a trend toward improvement that did not reach significance in glabellar wrinkles in group II compared to group I, but this improvement did not reach the statistical significant level (P<0.112). Absorbable polydioxanone threads can be considered as a third line procedure for wrinkle correction beyond Botulinum toxin and soft tissue fillers. Threads alone don't fit all situations but their combination with Botulinum toxin can give a better natural-looking appearance with more patient satisfaction., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This systematic review and meta-analysis compares the effectiveness of single-bundle (SB) and double-bundle (DB) ACL reconstruction techniques in improving knee stability and functional outcomes in patients with ACL injuries. A structured search across PubMed, Scopus, Google Scholar, and the Cochrane Library identified studies comparing SB and DB ACL reconstructions. Ten studies met the inclusion criteria, including randomized controlled trials, prospective, and retrospective studies. The primary outcomes analyzed were the International Knee Documentation Committee (IKDC) subjective score, Lysholm score, Lachman test, and pivot-shift test results. Meta-analytic methods included calculating standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) alongside assessments of heterogeneity using the I² statistic. The meta-analysis showed no significant difference between SB and DB techniques for IKDC subjective scores (SMD: -0.14, 95% CI: -0.68 to 0.39, p = 0.59) or Lysholm scores (SMD: -0.18, 95% CI: -0.39 to 0.02, p = 0.08). Lachman test results also indicated no significant differences between techniques (pooled OR: 1.02, 95% CI: 0.70-1.47, p = 0.92). Pivot-shift test outcomes similarly revealed comparable rotational stability (OR: 1.00, 95% CI: 0.70-1.43, p = 1.00). Moderate heterogeneity was observed across analyses (I² = 37%-43%), reflecting variations in study designs and patient populations. SB and DB ACL reconstruction techniques achieve similar functional outcomes and knee stability, with no significant differences in Lachman test results, pivot-shift outcomes, or patient-reported measures. Further research with standardized methodologies is needed to verify these findings across diverse populations., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Elsenosy et al.)

Medial meniscus root tears (MMRTs) are serious injuries that disrupt knee biomechanics, often accelerating cartilage degeneration and osteoarthritis when left untreated. These injuries are increasingly recognized as a major cause of knee pain and functional limitations, particularly among middle-aged and older adults. This systematic review and meta-analysis aimed to evaluate the outcomes of conservative management compared to surgical intervention for MMRT, focusing on pain relief, functional recovery, and the progression of osteoarthritis. A thorough search of PubMed, Scopus, Google Scholar, and the Cochrane Library identified six studies that directly compared surgical repair, primarily transtibial pull-out repair, with conservative management. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Lysholm score, and the International Knee Documentation Committee (IKDC) subjective score. Surgical intervention showed marked superiority in KOOS scores, with a standardized mean difference (SMD) of 1.42 (95% CI: 0.97 to 1.88, P < 0.00001), reflecting significant improvements in pain, daily function, and quality of life. However, pooled analyses for the Lysholm score (SMD: 0.21, 95% CI: -0.23 to 0.65, P = 0.35) and IKDC score (SMD: 0.12, 95% CI: -0.56 to 0.80, P = 0.73) did not show statistically significant differences between treatments. High heterogeneity (I² > 50%) was noted, likely due to differences in study populations, follow-up periods, and methodologies. These results suggest that surgical repair offers superior pain relief and functional benefits for MMRT compared to conservative management, positioning it as the preferred option for most patients. Nonetheless, conservative management may remain suitable for certain patients, particularly those with contraindications to surgery. Further high-quality, long-term research is essential to confirm these findings and inform clinical decision-making., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Elnewishy et al.)

Introduction: Real-world data on tofacitinib's effectiveness is limited and mainly retrospective or registry-based. We elected to conduct a pragmatic prospective study to assess the efficacy of tofacitinib for moderate to severe ulcerative colitis (UC), aiming to evaluate the ability of intestinal ultrasound (IUS) to discriminate responders vs. non-responders in real-time., Methods: This pragmatic prospective clinical study included consecutive adult patients starting tofacitinib treatment for active moderate to severe UC. Patients were evaluated at baseline and after 8 weeks of tofacitinib (clinical, biomarker, endoscopy, and IUS). The primary outcome was clinical response defined by a decrease in the full Mayo score (fMS) of ≥3 at week 8. Next, we explored ultrasonographic parameters in the sigmoid colon as potential real-time classifiers to differentiate between responders and non-responders at week 8., Results: Overall, 30 adult patients started tofacitinib; the median age was 26.3 years (IQR 22.5-39.8), and 50% were female. Most patients (86.6%) had left-sided or extensive colitis, 96.7% had previously failed biologic therapy, and 60% (18/30) were on oral corticosteroids at the start of tofacitinib. At week 8, clinical response (a decrease in the fMS ≥ 3) and remission (fMS ≤ 2) rates were 40% (12/30) and 20% (6/30), respectively. Biomarker response (FC < 250µg/g) and biomarker normalization (FC ≤ 100µg/g) were achieved in 47.6% (10/21) and 38.1% (8/21) of patients, respectively. Endoscopic healing (endoscopic Mayo sub-score [EMS] ≤ 1) was achieved in 33.3% (10/30) of patients. Sigmoid bowel wall normalization as assessed by IUS (sBWT ≤ 3) was achieved in 18.2% (4/22). The best sBWT cut-off at week 8 to accurately classify endoscopic healing vs. no healing was a sBWT of 3.6 mm (AUC of 0.952 [95% CI: 0.868-1.036], p  < 0.001)., Conclusion: In this real-world pragmatic prospective study, tofacitinib was an effective treatment for moderate to severe UC, and IUS at week 8 accurately discriminated treatment response from non-response.

Purpose: Treatment with recombinant human growth hormone (rhGH) increases insulin growth factor-1 (IGF1) levels, therefore, monitoring both IGF1 and growth constitutes an acceptable parameter of therapeutic safety and efficacy. We aimed to investigate the relationship between IGF1 level and body composition in children and adolescents undergoing rhGH therapy for growth hormone deficiency (GHD) and idiopathic short stature (ISS)., Methods: This observational retrospective study included the bioimpedance analysis (BIA) reports (n = 305) of 135 pediatric patients (age 5-18 years), 64 with GHD and 71 with ISS, conducted as part of routine clinic visits. Sociodemographic and clinical data were extracted from medical records. Generalized estimating equations linear models were used to explore the contributing factors for body composition components of fat percentage (FATP), appendicular skeletal muscle mass (ASMM) z-score, and muscle-to-fat ratio (MFR) z-score while adjusting for cumulative doses of rhGH., Results: Subjects with GHD exhibited higher body mass index z-scores (p < 0.001), higher FATP and truncal FATP scores, lower MFR z-score, and higher diastolic blood pressure percentiles than the ISS group (p = 0.010, p = 0.027, p = 0.050, and p = 0.050, respectively). Female sex (p < 0.001) and a GHD diagnosis (p < 0.001), were major contributors to higher FATP scores; female sex (p = 0.049) and ISS diagnosis (p = 0.005) were major contributors to higher MFR z-scores; and female sex (p < 0.001), older age (p < 0.001) and higher insulin-like growth factor 1 z-scores (p = 0.021) were major contributors to higher ASMM z-scores. Socioeconomic position and cumulative rhGH dose were not significant contributors to body composition parameters., Conclusion: Children with GHD, including those undergoing rhGH treatment, may be at risk for increased adiposity and associated metabolic implications. Sex- and age-adjusted IGF1 levels were related to muscle mass but not to adiposity. Hence, rhGH treatment aimed at increasing IGF1 levels may alleviate these effects by promoting muscle growth., Competing Interests: Compliance with ethical standards Conflict of interest The author declares no competing interests. Ethics approval This study protocol was reviewed and approved by the Tel Aviv Sourasky Medical Center review board, approval number (065-18-TLV). Informed parental consent was waived by the institutional review board. Consent to participate Tel Aviv Sourasky Medical Center review board waived informed parental consent., (© 2024. The Author(s).)

Objective: Drug sustainability (DS), a surrogate marker for drug efficacy, is important, especially when aiming for precision medicine. However, it lacks reliable prediction methods., Aims: To develop and externally validate a web-based artificial intelligence(AI)-derived tool for predicting DS of infliximab and vedolizumab in patients with moderate-to-severe Ulcerative Colitis (UC)., Methods: Data from three Israeli centers included infliximab or vedolizumab patients treated for >54 weeks. Sustainability meant no corticosteroids, hospitalizations or surgeries. Machine learning techniques predicted >54-week and overall DS using baseline clinical data., Results: The model was developed using data from 246 patients from Rabin Medical Center and externally validated on 67 patients from Rambam Health Care Campus and Sheba Medical Center. No significant difference in DS was observed across the datasets. Most patients were biologic-naïve and primarily treated with vedolizumab. The model performed well, with an area under the ROC curve of 0.86, and showed good accuracy (65.5 %-76.9 %) across the test sets., Conclusions: The study introduces a novel, AI-based tool for predicting >54-week DS of infliximab and vedolizumab in moderate-to-severe UC, using baseline parameters. This can aid clinical decision-making in the framework of precision medicine, promising to optimize disease management while maintaining physician autonomy., Competing Interests: Conflicts of interest HY- Has received research grants from Pfizer; consulting fees from Abbvie, Janssen, Pfizer, Takeda, and BMS; Speaker fees from Abbvie, Janssen, Pfizer, Takeda, and Bristol Myers Squibb; Data Safety Monitoring Board or Advisory Board fees from Abbvie, Pfizer Takeda and Bristol Myers Squibb. JEO- Has received grant support from Pfizer, consulting fees from Takeda, and speaker fees from Abbvie, Janssen, Pfizer, Takeda, Novartis, and Bristol Myers Squibb. IAB- Has received speaker fees from Abbvie, Janssen, Pfizer, Takeda, and Neopharm. ID- consultation fee or honorarium from: Abbott, Abbvie, Athos, Arena, Altman Research, Cambridge Healthcare, Celltrion, Celgene/BMS, Eli-Lilly, Ferring, Falk Pharma, Food Industries Organization, Gilead, Galapagos, Iterative Scopes, Integra Holdings, Janssen, Neopharm, Pfizer, Rafa laboratories, Roche/Genentech, Sangamo, Sublimity, Sandoz, Takeda, Wildbio. Grants: Altman Research, BMS, Pfizer UK- Research support- Jannsen, Takeda, Medtronic, speaker/advisory fees- Abbvie BMS Celtrion Jannsen Pfizer Takeda Medtronic Roche No specific funding has been received for this study., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Abstract: Spinal muscular atrophy is an incurable inherited disease caused by lower motor neuron death from mutations of the survival motor neuron genes. Intrathecal therapy with the antisense oligonucleotide, nusinersen, has been demonstrated to be beneficial in children with this disease, but the experience in adults, particularly ambulatory patients, is limited. We present a prospective observational case series from a single center using nusinersen therapy where we categorize 6 adult patients with spinal muscular atrophy into 2 functional categories: ambulatory (n = 3) or nonambulatory (n = 3). All received therapy that was administered intrathecally every 4 months. We monitored the course and laboratory data for 1 year and observed for side effects. There was no significant deterioration for 1 year. There was some minor improvement particularly in subjective changes. The benefit seems to decrease after 3 months. No significant complications were observed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The expression pattern of CD27 and CD44 was found to correlate with the differentiation stages of B cell precursors, which were known to be involved in a variety of immunological responses., Aim of the Study: This study aimed to determine the biological significance of CD27 and CD44 expression in patients with B-precursor acute lymphoblastic leukemia (B-ALL), as well as their association with standard prognostic factors and therapeutic response., Patients and Methods: This case-control study included 60 pediatric patients newly diagnosed with B-ALL and 30 pediatric controls. The patient CD27 and CD44 levels were measured using the Beckman Coulter Navios Flow Cytometer., Results: Most malignant cells (91.6 %) expressed CD44, but only 50 % of the patients had CD27 expressed. The positive CD 44 expression was associated with unfavorable prognostic markers, including a decrease., Competing Interests: Conflicts of interest The author(s) declare no potential conflicts of interest, with respect to the research, authorship and/or publication of this article., (Copyright © 2023 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Ziziphus leaf extract (ZEX), chitosan nanoparticles (CS NPs) and Ziziphus leaf extract loaded chitosan nanoparticles (ZEX-CS NPs) were prepared in this study and after chemical analysis and characterization, they were used in wastewater purification. The study also aimed to establish, using an animal model, the feasibility of employing treated water in drinking applications. ZEX-CS NPs were prepared by ionic gelation method. About 25 male Sprague Dawley rats (10 weeks and 170-200 g) were divided into five groups (5 rats/group): group I received tape water; group II received untreated wastewater, group III received ZEX treated wastewater, group IV received CS NPs treated wastewater and group V received ZEX-CS NPs treated wastewater. ZEX-CS NPs have a size of 73 nm, hydrodynamic size of 85.81 nm and zeta potential of -33.68 mV. In addition, ZEX-CS NPs have stronger antioxidant and anti-inflammatory activity with moderate anti-coagulant activity and weaker cytotoxicity than ZEX and CS NPs. Group II showed a significant elevation in the kidney function parameters, oxidative stress and cytokine levels when compared to the other groups, in addition; no significant differences were found in all measured parameters between the rats of group I and V. ZEX-CS NPs were effective in wastewater purification., 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.)

Purpose: Ibrutinib is an irreversible Bruton's tyrosine kinase inhibitor that disrupts B-cell receptor signalling. It is licensed for treatment of low-grade B-cell malignancies, including chronic lymphocytic leukaemia, mantle cell lymphoma and lymphoplasmacytic lymphoma. A few case reports in the literature suggest that uveitis may be a side effect of ibrutinib treatment. A strong association between ibrutinib and uveitis is yet to be established in significant numbers., Methods: The study is a retrospective case series, reporting cases of uveitis associated with ibrutinib from two tertiary centres in the United Kingdom: Liverpool University Hospitals NHS Foundation Trust and University Hospitals of Leicester NHS Trust., Results: The study reports eight cases presenting over a four year period, with mean age of 66.8 years. Onset of uveitis was between 9 and 48 (median 14) months from commencing ibrutinib, categorising it as a Type D or delayed drug reaction. Cases included unilateral and bilateral; anterior, intermediate, posterior and panuveitis. There was an association with cystoid macular oedema or disc swelling. Severity varied from mild, to severe and vision threatening. Presenting visual acuity ranged from 6/9 to 6/60. In all eight cases, uveitis resolved after ibrutinib cessation. In two cases, reintroducing ibrutinib caused uveitis recurrence., Conclusion: Our case series provides evidence suggestive of a connection between ibrutinib and development of uveitis. Ibrutinib related uveitis appears to be more common than previously recognised. Ibrutinib cessation, if appropriate, appears to be the definitive management. Patients with ibrutinib-related uveitis benefit from multidisciplinary management involving communication between ophthalmologist and haemato-oncologist.

In this study, the nuarimol enantiomers were successfully baseline separated with Rs 1.70 by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The absolute configurations of the nuarimol enantiomers were confirmed as R -(+)-nuarimol and S -(-)-nuarimol. The enantioselective bioactivity assay indicated that R -(+)-nuarimol exhibited greater potency against seven phytopathogenic fungi, with values approximately 1.4-3.5 and 4.5-51.4 times higher than those of rac-nuarimol and S -(-)-nuarimol. The active contribution value of R -enantiomer was 82-98%, showing that R -(+)-nuarimol played a crucial role in bioactivity. Meanwhile, R -(+)-nuarimol exhibited stronger effects in increasing the cell membrane permeability, compromising the cell membrane integrity, and inhibiting ergosterol biosynthesis. Molecular docking analysis showed that R -(+)-nuarimol possessed a stronger binding affinity to sterol 14-α demethylase (CYP51) than S -(-)-nuarimol, with docking energies of -7.42 and -7.36 kcal/mol. This study contributes essential data for screening a high-activity enantiomer of nuarimol and provide guidance for reducing used dosage and increasing the efficiency of nuarimolAQ.

Acute first-time traumatic patellar dislocation is a prevalent knee injury, particularly in adolescents, often managed conservatively with knee bracing. Recently, medial patellofemoral ligament (MPFL) reconstruction has gained popularity for its potential benefits in reducing redislocation rates and enhancing functional outcomes. This systematic review and meta-analysis compared the outcomes of MPFL reconstruction versus knee bracing for managing acute first-time traumatic patellar dislocation. A comprehensive search of PubMed, Scopus, Google Scholar, and the Cochrane Library identified studies published within the last 10 years that directly compared these treatment approaches, with primary outcomes focusing on redislocation rates and functional recovery measured by Kujala scores. A total of six studies, involving 325 patients, were included in the analysis. Results indicated that MPFL reconstruction significantly reduced redislocation rates (OR: 0.17, 95% CI: 0.09 to 0.32, P < 0.00001) and improved functional outcomes (MD in Kujala scores: 8.10, 95% CI: 6.46 to 9.75) compared to knee bracing. Despite notable heterogeneity across studies (I² = 95%), MPFL reconstruction consistently demonstrated superior long-term knee stability and fewer reoperations. These findings suggest that surgical intervention is the preferred treatment for long-term stability; however, further high-quality randomized controlled trials are recommended to confirm these results., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Elnewishy et al.)

Periampullary malignancies are uncommon and encompass a wide variety of tumors. Early and accurate biopsy-proven diagnosis is important because different malignancy subtypes warrant different management and treatment plans. We present a unique and rare case of periampullary lymphoma, initially presenting as acute pancreatitis., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Patients with ulcerative colitis (UC) undergoing proctocolectomy and ileal pouch-anal anastomosis (IPAA) may eventually require biologic therapy. Factors associated with biologic therapy after IPAA have not been previously studied., Methods: All patients with UC after total proctocolectomy and IPAA who were followed at Rabin Medical Center comprehensive pouch clinic and who consented to prospective observational follow-up were included. The primary outcome was the initiation of biologic therapy after IPAA. Cox proportional hazard models were used to evaluate potential associations., Results: Out of 400 patients receiving their care at the pouch clinic, 148 patients consented to prospective observational follow-up and constituted the study cohort. The median age at diagnosis was 21 years and the age at IPAA was 30 years. Median time-to-biologic therapy initiation post-IPAA was 9.2 years, with 34 patients (23%) initiating biologic therapy: Associated factors for initiating biologic therapy post-IPAA were preoperative treatment with biologic therapy and immunomodulatory therapy (hazard ratio [HR] 6.1 and 3.6, respectively, P < .001); Arab descent (HR 5.3, P < .001); heterozygosity of NOD2 variant rs2066845 (HR 5.1, P = .03); past smoking status (HR 2.3, P = .03); 3-stage IPAA (HR 2.3, P = .02); immediate postoperative complications (HR 2.1, P = .033); and pediatric-onset UC (HR 2.1, P = .03). None of the patients undergoing IPAA due to dysplasia (n = 27) required biologic therapy., Conclusions: Several demographic, disease-related, surgery-related, and genetic factors associated with post-IPAA biologic therapy were identified. Physicians treating patients with UC undergoing colectomy should incorporate these factors into their decision-making process. These patients may benefit from closer postoperative follow-up, and earlier initiation of biologic therapy should be considered., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Melasma is an acquired dysfunction of melanogenesis, that poses a major therapeutic challenge and tends to recur after therapy. Several combination therapies are being tested nowadays for the treatment of melasma, with promising results. Metformin, an anti-diabetic medication, seems to inhibit melanogenesis by different mechanisms. In addition, there has been a long-term improvement in melasma after microneedle therapy. To evaluate the potential therapeutic role of topical metformin combined with micro-needling for the treatment of melasma. Eighteen patients with melasma received treatment in split-face manner, right side with micro-needling and topical metformin, while the left side was treated with micro-needling and topical placebo for four sessions at 2-week intervals. Hemi-mMASI score was used for the final evaluation of results. The variability pattern in Hemi-mMASI score between both sides revealed significant reduction in the right side (micro-needling + metformin), as compared to the left side (micro-needling + placebo) (2.39 ± 1.42 vs 4.72 ± 1.27, p = 0.001). The effectiveness of topical metformin in the management of melasma could be significantly improved by pretreatment with micro-needling as a combined therapy, without any apparent side effects., Competing Interests: Declarations Conflict of interest As a corresponding author I hereby state that there is no conflict of interest on behalf of each co-author., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Patients' perspectives on outcomes of clinical trials are critical to the design of meaningful trials. As they are the primary recipients of treatment, it is important to focus on outcomes that are of value to the patients. We planned a study involving patients in defining and prioritizing endpoints for intervention trials for bloodstream infections., Methods: A survey was conducted at Rambam Health Care Campus, targeting hospitalized patients over 18 years old. Participants were asked to score the importance of various outcomes on a scale of 1 to 10, 10 being most important. We calculated the mean and median and dispersion measures per outcome., Results: Seven hundred thirty-two randomly selected patients were approached; 378 were not available due to technical reasons. Of the remaining 354 approached to take the survey, 300 consented and participated in the study. The median age was 51.9 years, with 55.3% female. Death was scored as the most important outcome, whereas the length of hospital stay was the least important., Discussion: Eliciting patient views on outcome importance was challenging but revealed key insights. Patients prioritized death, functional decline, and the development of secondary infections. Nonclinical outcomes, such as microbiological failure, were less clearly understood. Future studies should focus on clinical outcomes and include larger, more diverse patient populations to enhance the relevance of bloodstream infection trials., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Patellar tendon injuries, although less frequent than other knee injuries, can have a profound impact on knee function, often leading to significant disability. Among the various surgical techniques employed to repair these injuries, the suture anchor and transosseous tunnel methods are the most commonly used. This systematic review and meta-analysis compares the biomechanical properties and functional outcomes of these two repair techniques. A thorough search of relevant databases was conducted until June 2024, including studies that directly compared the suture anchor and transosseous tunnel methods for patellar tendon repair. Data extraction and quality assessments were performed independently by two reviewers. The primary outcomes assessed were biomechanical strength and functional recovery, using the International Knee Documentation Committee (IKDC) scores, Lysholm score, and Kujala score. A total of four studies involving 196 participants met the inclusion criteria. Both techniques were found to significantly improve functional outcomes. However, suture anchor repairs were associated with lower complication rates and earlier rehabilitation compared to the transosseous tunnel technique. Despite these differences, the meta-analysis showed no statistically significant difference in postoperative IKDC scores between the two methods. In conclusion, while both the suture anchor and transosseous tunnel techniques are effective for patellar tendon repair, the suture anchor method appears to offer biomechanical advantages, fewer complications, and faster recovery. Further high-quality research is recommended to validate these findings., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Elnewishy et al.)

Extranodal marginal zone lymphoma (EMZL) is a rare subtype of non-Hodgkin's lymphoma characterized by the malignant transformation of lymphoid tissue at sites affected by chronic inflammation. Pleural marginal zone lymphoma (PMZL) is an infrequent manifestation of this condition. We report a case of PMZL co-occurring with primary lung adenocarcinoma. This case involves an 88-year-old female patient who presented to the emergency department with recurrent pleural effusions and symptoms suggestive of decompensated heart failure. A thoracentesis of the effusion revealed an aspergillus population. Throughout her hospitalization, the patient underwent multiple evaluations for malignancy; however, no conclusive findings emerged. Ultimately, PMZL and poorly differentiated primary adenocarcinoma of the lung were confirmed through random biopsies of the parietal pleura and lung opacities, respectively. The pleural pathology showed a monoclonal population of immunoglobulin G kappa, positive for cluster of differentiation (CD) markers CD20 and CD43. Consequently, she was treated with rituximab for PMZL, with plans to address the adenocarcinoma through stereotactic body radiation therapy (SBRT). Unfortunately, due to deconditioning from multiple hospitalizations and a pulmonary embolism, the patient chose comfort measures and subsequently passed away. Diagnosing PMZL can be challenging due to the absence of identifiable nodules. Reported cases have similarly required extensive investigations to reach a final diagnosis. While a direct correlation between chronic inflammation, frequent infectious pathogens, and the development of PMZL has yet to be established, a known association exists between EMZL and pathogens such as Helicobacter pylori in gastric involvement and Chlamydia psittaci in ocular adnexa. This report highlights the difficulties in obtaining a diagnosis for PMZL and examines the various mechanisms that may have contributed to this unusual finding., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Onatsko et al.)

High intensity (HI) binge drinking has emerged as a high-risk drinking phenotype in young adult drinkers, yet few studies have evaluated clinically meaningful correlates of HI binge drinking among young adults at risk for co-occurring psychopathologies, such as interpersonal trauma-exposed drinkers. The present study compared three groups (i.e., HI binge, standard binge, non-binge drinkers) of interpersonal trauma-exposed college student drinkers (N = 221) on alcohol and interpersonal trauma characteristics. Results of one-way ANOVAs indicated that the HI binge group endorsed significantly greater negative alcohol-related consequences relative to the other two groups. The HI binge group endorsed significantly greater enhancement motives compared to the non-binge group, and no group differences were detected for PTSD and interpersonal trauma characteristics. Individuals who engage in HI binge drinking may experience greater alcohol problems due to their use of alcohol to enhance positive mood. HI binge drinking does not differentiate individuals on the basis of interpersonal trauma experiences or related psychopathology.

Purpose: To evaluate the risk of acute cardiovascular events (CVE), including cardiovascular diseases, cerebrovascular diseases, and all-cause mortality in patients with paracentral acute middle maculopathy (PAMM)., Design: Retrospective cohort study., Methods: We studied 43 individuals with optical coherence tomography-documented PAMM attending Moorfields Eye Hospital between January 2014 and June 2021. We excluded patients with preceding (<2 years) major adverse cardiac events. We stratified patients by age (<50 and ≥50 years) and whether associated with retinal vascular diseases (RVD) or isolated (iPAMM). We assessed risk factors, clinical characteristics, and visual prognosis of the patients. CVE risk was estimated using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards regression., Results: In young patients with iPAMM patients (n = 12), underlying predisposing factors included six (50%) sickle cell disease and five (41.6%) others, including breakthrough bleeding in pregnancy, migraine, genetic cardiomyopathy, amphetamine use; among those with PAMM + RVD (n = 12) one (9%) had a vascular disorder, and four (44.4%) oral contraceptive use. In the older group of 20 patients, 15 (75%) had at least one coronary risk factor. During a median follow-up of 14 months (range 12-54), older subjects with iPAMM had a higher risk of developing CVE than those with PAMM + RVD (P < .001). Notably, iPAMM displayed a significantly earlier peak in peri-PAMM CVE risk compared to PAMM + RVD (median: one month, range 1-40 months vs 36 months, range 12-54 months). Relative to those with PAMM + RVD, risk of CVE was significantly higher in patients with iPAMM, adjusted for age and sex (hazard ratio: 6.37, 95% confidence interval 1.68-24.14, P = .017). No young patients experienced adverse CVE. At baseline, older iPAMM patients mean best corrected visual acuity of 0.7 (0-1.8) logarithm of the minimum angle resolution, which improved significantly to 0.2 (0-1.30) logarithm of the minimum angle resolution at the latest visit (P = .033)., Conclusions: Young individuals with iPAMM have a higher prevalence of predisposing factors compared to those presenting with combined PAMM + RVD. Older patients with iPAMM had a higher risk of CVE than those with PAMM + RVD, especially in the peri-onset timeframe. This suggests the need for a prompt cardiovascular assessment to rule out systemic etiologies and optimize cardiovascular risk factors, in addition to ongoing ophthalmology input., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Neoadjuvant chemotherapy (NACT) improves muscle-invasive bladder cancer (MIBC) survival. However, its efficacy is limited to a group of patients. This study explored CK5/6 and GATA3 for molecular subtyping and their prediction to response in patients with MIBC., Methods: This is a prospective study that includes 50 patients with TCC bladder. All Patients received 4 cycles neoadjuvant gemcitabine/ cisplatin then guided to further treatment according to the response to NACT. Responders (CR & PR) went for CCRTH whereas non-responders (SD & PD) went surgery if resectable or second line chemotherapy if non-resectable. The baseline TUR pathology specimens were examined for histopathological feature and CK5/6 and GATA3 and divided into 4 molecular subgroups., Results: The patients were divided into four molecular subgroups: luminal (n=12/26.7%), basal (n=8/17.8%), double-positive (n=21/26.7%), and double-negative (n=4/8.9%). There was no clinicopathological difference seen among the 4 molecular subgroups. The PFS was higher in patients with GATA3 positive (24 months) than GATA3 negative (17 months). Yet, it did not reach a statistically significant value (P = 0.1605). On the other hand, PFS was not affected by either CK5/6 status or different molecular subgroups. The OS was better in the luminal subgroup than the basal (20.8 months versus 16.16 months respectively, While the double positive showed the highest OS of 26 months(P=0.0352)., Conclusion: GATA3 and CK5/6 IHC can classify MIBCs into four subtypes. These subtypes predicted treatment outcomes, however, were not correlated with the response to NACT. GATA3-positive tumors, luminal and double-positive subtypes tend to have higher OS and PFS. CK5/6 positivity did not impact the treatment outcome.

Compartment-specific cellular membrane protein turnover is not well understood. We show that FBXO10, the interchangeable component of the cullin-RING-ligase 1 complex, undergoes lipid modification with geranylgeranyl isoprenoid at cysteine953, facilitating its dynamic trafficking to the outer mitochondrial membrane (OMM). FBXO10 polypeptide lacks a canonical mitochondrial targeting sequence (MTS); instead, its geranylgeranylation at C953 and interaction with two cytosolic factors, cytosolic factor-like δ subunit of type 6 phosphodiesterase (PDE6δ; a prenyl-group-binding protein) and heat shock protein 90 (HSP90; a chaperone), orchestrate specific OMM targeting of prenyl-FBXO10. The FBXO10(C953S) mutant redistributes away from the OMM, impairs mitochondrial ATP production and membrane potential, and increases fragmentation. Phosphoglycerate mutase-5 (PGAM5) was identified as a potential substrate of FBXO10 at the OMM using comparative quantitative proteomics of enriched mitochondria. FBXO10 loss or expression of prenylation-deficient FBXO10(C953S) inhibited PGAM5 degradation, disrupted mitochondrial homeostasis, and impaired myogenic differentiation of human induced pluripotent stem cells (iPSCs) and murine myoblasts. Our studies identify a mechanism for FBXO10-mediated regulation of selective mitochondrial proteostasis potentially amenable to therapeutic intervention., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Noninvasive magnetic resonance imaging (MRI) of the relayed nuclear Overhauser effect (rNOE) constitutes a promising approach for gaining biological insights into various pathologies, including brain cancer, kidney injury, ischemic stroke, and liver disease. However, rNOE imaging is time-consuming and prone to biases stemming from the water T1 and the semisolid magnetization transfer (MT) contrasts. Here, we developed a rapid rNOE quantification approach, combining magnetic resonance fingerprinting (MRF) acquisition with deep-learning-based reconstruction. The method was systematically validated using tissue-mimicking phantoms, wild-type mice ( n  = 7), and healthy human volunteers ( n  = 5). In vitro rNOE parameter maps generated by MRF were highly correlated with ground truth (r > 0.98, p  < 0.001). Simultaneous mapping of the rNOE and the semisolid MT exchange parameters in mice and humans were in agreement with previously reported literature values. Whole-brain 3D parameter mapping in humans took less than 5 min (282 s for acquisition and less than 2 s for reconstruction). With its demonstrated ability to rapidly extract quantitative molecular maps, deep rNOE-MRF can potentially serve as a valuable tool for the characterization and detection of molecular abnormalities in vivo ., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

New azo Schiff base disperse dyes based on a chromene moiety were synthesized by reacting (2-amino-7-hydroxy-4-(4-methoxyphenyl)-4 H-chromene-3 carbonitrile) and(2-amino-4-(3,4-dimethoxyphenyl)-7-hydroxy-4 H-chromene-3-carbonitrile), with vanillin and ninhydrin, producing new chromene Schiff base derivatives, which in turn were coupled with 2-chloro-4-nitroaniline diazonium salt to give new 4 azo disperse dyes (1-4). The structures of the prepared dyes were confirmed using elemental analysis, 1 HNMR spectroscopy, mass spectrometry, and IR. The synthesized dyes were applied to polyester and nylon fabrics using different dyeing techniques: high temperature- high pressure, and ultrasonic dyeing methods. The highest K/S values for all investigated dyes were achieved usinga high temperature-high pressure dyeing technique. Also, the color reflectance of all synthesized dyes with different dyeing shades (1%, 2%, and 3%) was obtained. The fastness properties of the dyed samples using the investigated dyes showed good color fastness toward light, washing, rubbing, and perspiration fastness. The presence of a chromene moiety and Schiff base in the investigated dyes promotes a higher antimicrobial activity on nylon and polyester fabrics against all tested bacteria (E. coli gram-negative and Staphylococcus aureus gram-positive) and two fungi, Aspergillus Niger and Candida albicans., (© 2024. The Author(s).)

Background: Neonatal sepsis remains a primary cause of morbidity and mortality among newborns. Rapid and accurate diagnosis poses a significant challenge-the non-specific clinical presentation of neonatal sepsis relies heavily on various laboratory indices for early detection and subsequent management. One such indicator under investigation is the mean platelet volume (MPV), which may serve as a predictive marker. This study aims to evaluate the association between the MPV and late-onset sepsis in preterm infants., Methods: This retrospective study included 63 newborns born at Sheba Medical Center from 2016 to 2020 with late-onset sepsis as evidenced by positive blood cultures, and 63 newborns in the control group. We analysed blood count data at three intervals: preinfection, intrainfection and postinfection. Electronic medical records provided supplemental data. Each septic neonate was paired with a non-septic control., Results: Our results revealed a significant elevation of MPV in septic newborns compared with non-septic controls during the days prior to the infection (9.323 and 8.876, respectively, p=0.043) and persisted up to 2 weeks postinfection (9.39 vs 8.714, p=0.025).The MPV and the MPV-to-total platelet (PLT) count ratio exhibited significant predictive capabilities in receiver operating characteristics analysis (-0.60 and -0.57, respectively)., Conclusions: High MPV in combination with PLT decrement might be predictive for the diagnosis of late-onset sepsis. Future studies should be conducted in order to better understand the underlying pathophysiology and the potential clinical applications of these findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

More than 1200 civilians and military were killed in cities and villages by the Hamas attack on October 7th, 2023. The bodies and body-parts had to be identified and released for burial. This report outlines the challenges and mode of operation of the massive disaster victim identification (DVI) efforts. Bodies were delivered to a central mortuary. Each body was coded and undressed for external inspection and documentation of physical elements. Digital fingerprints were recorded and blood or toenails sampled for DNA. Odontology exams were performed by dentists describing dentition, aided by computerized tomography (CT). Whole-body CT was performed in cases the bodies were disfigured or burned from the second week. Simultaneously, families of missing civilians provided physical elements to the police to extract the DNA for antemortem documentation. The police took the responsibility over the reconciliation, which was based on comparison of the ante-mortem and post-mortem fingerprints, aided by DNA profile matching, odontology examination, clinical and/or radiological findings performed by forensic practitioners. Secondary identification elements were used assure the families regarding the identification. Precise scientific identification a was a priority, even if it slowed the rate of bodies release. Families were allowed to view their relative either at the mortuary or before burial. The DVI process required cooperation between several governmental agencies and police. To maximize the effectiveness, a synchronized approach should be adopted, specifying communication channels between the partners and dividing the responsibilities. The DVI should be led by a single, experienced authority to ensure interdisciplinary teamwork. This catastrophe required personal resilience of the teams for rapid and efficient functioning and communication between the partners., 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: The management of early breast cancer (BC) has witnessed an uprise in the use of neoadjuvant therapy and a remarkable reshaping of the systemic therapy postneoadjuvant treatment in the last few years, with the evolution of many controversial clinical situations that require consensus., Methods: During the 14th Breast-Gynecological and Immuno-Oncology International Cancer Conference held in Egypt in 2022, a panel of 44 BC experts from 13 countries voted on statements concerning debatable challenges in the neo/adjuvant treatment setting. The recommendations were subsequently updated based on the most recent data emerging. A modified Delphi approach was used to develop this consensus. A consensus was achieved when ≥75% of voters selected an answer., Results and Conclusions: The consensus recommendations addressed different escalation and de-escalation strategies in the setting of neoadjuvant therapy for early BC. The recommendations recapitulate the available clinical evidence and expert opinion to individualize patient management and optimize therapy outcomes. Consensus was reached in 63% of the statements (52/83), and the rationale behind each statement was clarified., (© 2024 American Cancer Society.)

Background: Similarly to wild poliovirus, vaccine-derived poliovirus (VDPV) strains can cause acute flaccid paralysis, posing a considerable challenge to public health and the eradication of poliovirus. VDPV outbreaks, particularly VDPV type 2 (VDPV2), are increasing worldwide, including in high-income countries with high vaccine coverage. We aimed to conduct a comprehensive analysis of the molecular epidemiology of a widespread VDPV2 outbreak in Israel in 2022-23 using conventional polio identification techniques and whole-genome sequencing., Methods: In this genomic epidemiology study, we monitored and identified poliovirus type 2 (PV2) through the surveillance of stool samples from individuals with acute flaccid paralysis and related contacts, as well as environmental surveillance of sewage samples. Environmental surveillance involved 15 routine surveillance sites and an additional 30 sites dedicated to monitoring this outbreak, covering approximately 70% of Israel's population between April 1, 2022, and June 30, 2023. Additionally, we performed phylogenetic and mutation analyses using whole-genome, next-generation sequencing of PV2 isolates to identify recombination events, characterise VDPV2 lineages according to the capsid region, and establish the geographical distribution and linkage of PV2 isolates., Findings: We detected 256 genetically linked samples from environmental surveillance, as well as one case of acute flaccid paralysis and four positive contacts associated with the Sabin type 2 oral vaccine strain. Most affected locations showed a high-density population of Jewish Ultra-Orthodox communities. Through high-resolution genomic characterisation and phylogenetic analysis of 202 representative sequences with complete capsid coverage, including isolates from both environmental surveillance and the case of acute flaccid paralysis, a conclusive linkage was established among all detections, confirming them to be part of a single VDPV2 outbreak. This strategy enabled the characterisation of three distinct lineages and established connections between different locations in Israel, including linking the case of acute flaccid paralysis and nearby environmental surveillance detections from the northern region with detections in the geographically distant central region., Interpretation: This study highlights the role of environmental surveillance in the early detection and monitoring of poliovirus circulation, enabling a prompt public health response involving enhanced surveillance and a catch-up campaign with inactivated polio vaccine. Whole-genome sequencing offered valuable insights into the origins of the outbreak, linkage across detections, and the geographical distribution of the virus, with higher resolution than would have been possible with the standard analysis of the VP1 gene alone., Funding: None., Competing Interests: Declaration of interests LMS reports consulting for a novel OPV working group and attending related meetings. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This systematic review synthesized evidence from randomized controlled trials (RCTs) on the effects of integrated behavioral interventions for adults with alcohol use disorder (AUD)., Methods: A comprehensive search of three databases was conducted in 2022, utilizing terms related to alcohol/substance use disorders and integrated interventions. The sample included adults aged ≥18 years at low, moderate, or high risk for AUD, and had at least two other mental health conditions. Only RCTs were included and screened using Covidence. The quality of the study was evaluated using Cochrane risk of bias tool., Results: Across all 11 studies, the total AUD participants were 1543 aged 18 or older. Integrated intervention led to significant reductions in heavy drinking compared to usual care or other interventions. Measures included percent days of alcohol use, grams of alcohol consumed, and increased days of abstinence. Three studies compared integrated treatments with Twelve-Step Facilitation, indicating a better abstinence rate among participants in the integrated group at the end of treatment. Comparisons between delivery modes demonstrated more significant reductions in alcohol consumption with interventionists. Integrated interventions were also compared with various other treatments, including brief intervention, telephone and individual counseling, and psychological education. Participants in the integrated group showed greater improvement in alcohol consumption and depression compared to those in the standalone intervention group., Conclusions: Integrated behavioral interventions effectively reduce alcohol consumption, decrease heavy drinking and promote alcohol abstinence. However, there is limited evidence to determine whether these interventions are more effective than usual care for individuals with AUD., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Natural language processing (NLP) and large language models (LLMs) have emerged as powerful tools in healthcare, offering advanced methods for analysing unstructured clinical texts. This systematic review aims to evaluate the current applications of NLP and LLMs in rheumatology, focusing on their potential to improve disease detection, diagnosis and patient management., Methods: We screened seven databases. We included original research articles that evaluated the performance of NLP models in rheumatology. Data extraction and risk of bias assessment were performed independently by two reviewers, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to evaluate the risk of bias., Results: Of 1491 articles initially identified, 35 studies met the inclusion criteria. These studies utilized various data types, including electronic medical records and clinical notes, and employed models like Bidirectional Encoder Representations from Transformers and Generative Pre-trained Transformers. High accuracy was observed in detecting conditions such as RA, SpAs and gout. The use of NLP also showed promise in managing diseases and predicting flares., Conclusion: NLP showed significant potential in enhancing rheumatology by improving diagnostic accuracy and personalizing patient care. While applications in detecting diseases like RA and gout are well developed, further research is needed to extend these technologies to rarer and more complex clinical conditions. Overcoming current limitations through targeted research is essential for fully realizing NLP's potential in clinical practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Plane warts, when multiple and recurrent, present a therapeutic challenge acting as a source of reinfection, causing frustration and affecting a patient's quality of life. For large numbers of lesions in cosmetically significant sites, topical treatment is preferred to avoid potential sequelae., Objectives: To evaluate and compare the efficacy and tolerability of tazarotene 0.1% gel vs. imiquimod 5% cream for the treatment of plane warts., Methods: In a parallel three-arm randomized controlled trial, 60 patients were randomized to imiquimod, tazarotene or placebo groups. Patients applied the corresponding treatment once daily at night for a maximum of 12 weeks. Primary outcomes were the percentage of respondents with complete clearance in the three studied groups, and the type and frequency of side-effects in each group., Results: Both active treatments resulted in significant improvement compared with baseline and the placebo group (P = 0.001). The imiquimod 5% treated group showed complete clearance in 50% (10/20) of patients, partial response in 15% (3/20), and no response in 35% (7/20). Tazarotene 0.1% gel showed complete clearance in 40% (8/20) of patients, partial response in 40% (8/20), and no response in 20% (4/20). No significant difference was detected between the imiquimod and tazarotene groups (P = 0.19)., Conclusions: Compared with imiquimod, tazarotene 0.1% gel for the treatment of plane warts seems to offer an equivalent treatment response, it maintained efficacy without recurrence and had a safer profile regarding dyspigmentation with an advantageous cheaper cost., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear., Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis., Results: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability (GDD/ID), infantile intractable seizures, absent speech, autistic features, dystonia, and increased lethality. De novo monoallelic variants result in moderate-to-severe GDD/ID, absent speech, and autistic features, while seizures and dystonia were less frequently observed. Dysmorphic facial features and brain abnormalities, including hypoplastic corpus callosum, parenchymal volume loss/atrophy, are common findings in both groups. We reveal that in the nucleolus, ACTL6B plays a crucial role in ribosome biogenesis, in particular in pre-rRNA processing., Conclusion: This study provides a comprehensive characterization of the clinical spectrum of both autosomal recessive and dominant forms of ACTL6B-associated disorders. It offers a comparative analysis of their respective phenotypes provides a plausible molecular explanation and suggests their inclusion within the expanding category of 'ribosomopathies'., (Copyright © 2024. Published by Elsevier Inc.)

It is controversial whether people with vasovagal syncope (VVS) have abnormal autonomic responses at baseline and whether specific diagnostic manoeuvres have a diagnostic value. We investigated whether the pupillary light reflex and cardiac autonomic tests can be used to identify autonomic dysfunction in volunteers with a medical history of VVS. The study groups included 128 healthy volunteers, of whom 31 reported a history of typical VVS. The right pupil was evaluated using an automated, commercial infra-red pupillometer under strict conditions. In addition to miosis and mydriasis kinetics, pupil diameters were measured. Heart rate variability at rest and heart rate changes to standing were quantified with high-resolution electrocardiography and designated software. The demographic and clinical characteristics of both groups were statistically similar. Average constriction velocity (ACV) was significantly higher in VVS patients following a univariate analysis (3.83 ± 0.59 vs. 3.56 ± 0.73 mm/s, p = 0.042) and after correcting for potential confounders (p = 0.049). All other pupillometric and heart rate indices were comparable between groups. Patients with a history of VVS depict pupillary parasympathetic overactivity in response to light stimuli, manifested as increased ACV. The prognostic implications of this finding and the significance of using this simple clinical tool to identify patients who are at risk for developing frequent episodes of VVS or physical injuries following a syncope merits further study., (© 2024 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)