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Bone health is a key determinant of success in spine surgery, making preoperative assessment of bone quality essential to optimal surgical risk stratification. Magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score offers a novel approach to assess bone health in spine surgery candidates. The ability of MRI to assess bone quality without exposure to ionizing radiation makes it a potentially advantageous alternative to other traditional measures of bone density. VBQ has additionally shown potential to predict adverse outcomes, such as fragility fractures, instrumentation failure, subsidence and proximal junctional kyphosis. Variations of VBQ, such as endplate bone quality, S1 VBQ, and cervical VBQ, provide targeted insights at specific anatomical regions and potentially enhance the predictive accuracy of VBQ. However, clinical application of VBQ is limited by variability in MRI systems, patient-specific factors, and lack of standardized threshold values. This review aims to critically evaluate VBQ scores as an opportunistic, MRI-based assessment of bone health and its potential role in predicting surgical outcomes. While VBQ may provide some valuable insights into bone health, its role in preoperative risk assessment likely remains supplementary and requires further research to establish clinical validity and optimal cutoffs.

Background: There is little data available in infants on the extent to which inhalational anesthetics prolong the effects of neuromuscular blocking agents compared with intravenous agents. Here, we assessed the differences between the neuromuscular blocking effects (duration and recovery time) of a single dose of rocuronium during propofol vs. sevoflurane anesthesia. Methods: The prospective study enrolled 20 infants (4–12 months of age) scheduled for craniosynostosis surgery, randomly assigned to receive general anesthesia maintenance with sevoflurane or propofol. All patients received 0.6 mg/kg rocuronium as a single bolus dose to facilitate tracheal intubation and surgery. Primary study endpoint was the clinical duration of rocuronium, from administration until spontaneous recovery to a train-of-four ratio (TOFR) > 0.90. Secondary endpoints were times for reappearance of the first, second, third, and fourth twitches of the TOF (T1, T2, T3 and T4, respectively) in the two patient groups. Results: There were no differences in the infants’ age (sevoflurane maintenance: 5.8 ± 2.4 months; propofol maintenance: 6.7 ± 3.1 months, p = 0.47) or weight (sevoflurane: 7722 ± 1644 g; propofol: 7433 ± 1782 g, p = 0.71). Rocuronium onset time was 101.0 ± 55.0 s in the sevoflurane group and 83.4 ± 47.9 s in the propofol group (p = 0.46). Total duration of anesthesia was comparable in the sevoflurane (122.0 ± 23.8 min) and propofol (107.7 ± 25.2 min, p = 0.18) groups. Rocuronium recovery to TOFR > 0.9 required 136 min (CI: 123.7–149.5 min) in the sevoflurane group and 61.5 min (CI: 58.0–101.0 min) in the propofol group (p < 0.001). Conclusions: In infants, sevoflurane maintenance enhances the neuromuscular blocking effect of a single, 0.6 mg/kg BW dose of rocuronium as compared to propofol maintenance. After discontinuation of sevoflurane, additional time is necessary to reach the acceptable TOFR >0.9 needed before tracheal extubation. The present study further underscores the importance of objective (quantitative) neuromuscular monitoring in infants to guide intraoperative management and prevent residual neuromuscular block.

Abstract Background and Aims Intestinal ultrasound (IUS) is increasingly used to monitor treatment efficacy in inflammatory bowel disease (IBD) trials. However, standardized definitions for response, remission, and optimal assessment timing remain undefined. An international expert consensus meeting was held to establish IUS endpoints for clinical trials. Methods A panel of 35 international gastroenterologists and radiologists participated in a modified Delphi process, reviewing the literature and developing consensus statements. Agreement was defined as at least 75% consensus. Results Consensus was reached on 150 statements across four domains: general IBD (30 statements), luminal Crohn’s disease (CD) (43), perianal CD (51), and ulcerative colitis (UC) (26). For luminal CD and UC, ultrasound response was defined by: (1) a ≥25% reduction in bowel wall thickness (BWT) from baseline, or (2) multifactorial improvement, combining BWT reduction with ≥1 grade decrease in color Doppler signal (CDS) or another IUS parameter. Assessments were set at weeks 4-8 for the colon and week 12 for the terminal ileum. Ultrasound remission in luminal CD was defined as: (1) BWT normalization (≤3 mm) or (2) normalization of multiple parameters, including BWT, CDS, and all other IUS parameters. Similar remission criteria were proposed for UC, but the sigmoid BWT normal range (3-4 mm) remained uncertain. The bowel ultrasound score (BUSS) for CD and the Milan ultrasound criteria (MUC) for UC were supported as standardized scoring systems for trials. Conclusion This consensus provides standardized IUS definitions to enhance consistency in IBD trials, supporting the integration of IUS in future research.

Abstract Recent research suggests higher circulating lymphocyte counts may protect against colorectal cancer (CRC). However, the role of specific lymphocyte subtypes and activation states remain unclear. CD4+ T cells—a highly dynamic lymphocyte subtype—undergo gene expression changes upon activation that are critical to their effector function. Previous studies using bulk tissue have limited our understanding of their role in CRC risk to static associations. We applied Mendelian randomization (MR) and genetic colocalisation to evaluate causal relationships of gene expression on CRC risk across multiple CD4+ T cell subtypes and activation states. Genetic proxies were obtained from single-cell transcriptomic data, allowing us to investigate the causal effect of expression of 1,805 genes across CD4+ T cell activation states on CRC risk (78,473 cases; 107,143 controls). Analyses were stratified by CRC anatomical subsites and sex, with sensitivity analyses assessing whether the observed effect estimates were likely to be CD4+ T cell-specific. We identified 6 genes—FADS2, FHL3, HLA-DRB1, HLA-DRB5, RPL28, and TMEM258—with strong evidence for a causal role in CRC development (FDR-P &lt; 0.05; colocalisation H4 &gt; 0.8). Causal estimates varied by CD4+ T cell subtype, activation state, CRC subsite and sex. However, many of genetic proxies used to instrument gene expression in CD4+ T cells also act as eQTLs in other tissues, highlighting the challenges of using genetic proxies to instrument tissue-specific expression changes. We demonstrate the importance of capturing the dynamic nature of CD4+ T cells in understanding CRC risk, and prioritize genes for further investigation in cancer prevention.

The prognosis of high-grade gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is highly variable and reported median overall survival remains low. There is no established standard of care for patients with higher grade 2 (G2) (Ki-67 ≥ 10% and ≤ 20%) and grade 3 (G3) (Ki-67 ≥ 20% and ≤ 55%) GEP-NETs and most of the current treatment regimens, particularly for G3 NETs, are extrapolated from lower-grade GEP-NET treatments or based on data from small retrospective studies. Robust evidence to support treatment recommendations for high-grade NETs, especially in the first-line (1L) setting, is limited and the optimal treatment sequence has not been clearly defined. This review summarizes the latest literature on sequencing of therapies, identifies patient selection considerations for utilizing peptide receptor radionuclide therapy (PRRT), and offers data-driven expert opinions and clinical practice recommendations in high-grade GEP-NETs. As authors, we recommend that all patients with well-differentiated, higher G2 and G3 NETs are evaluated with [68Ga]Ga-DOTA-peptide positron emission tomography (PET) for baseline somatostatin receptor expression and if positive, a 1L treatment option of PRRT should be considered, especially in clinically stable patients. Somatostatin analog therapy may benefit patients with low-volume, indolent disease, and chemotherapy is usually a better fit for patients in visceral crisis, in need of urgent treatment, or with no access to [68Ga]Ga-DOTA-peptide PET. In complex cases, a robust discussion at a multidisciplinary NET tumor board can be beneficial.

IntroductionAlcohol withdrawal syndrome (AWS) is among the most severe components of alcohol dependence (AD). Severe AWS, especially complicated with seizures and delirium, was a common reason for medical complications and death. The introduction of benzodiazepines decreased but did not eliminate those risks. The definition of AWS evolved in different versions of Diagnostic and Statistical Manual for Mental Disorders (DSM) from having hand tremor plus one or more other symptoms in DSM-III-R to any two or more symptoms in DSM-IV, which was retained in the current version of DSM-5.ObjectivesComparing subgroups of individuals with AUD based on AWS symptoms profile to define phenotypes for investigation of biological underpinnings of AWS phenomenology and treatment response.MethodsTreatment-seeking individuals diagnosed with DSM-IV alcohol dependence (AD; n=473; 35.5% females) were assessed with Psychiatric Research Interview for Substance and Mental Disorders (PRISM), Timeline Follow back (past 90 days) alcohol consumption, Penn Alcohol Craving Scale (PACS), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ9), and General Anxiety Disorder-7 (GAD-7). Latent class analysis was used to classify subjects according to lifetime prevalence of AWS symptoms according to DSM-III-R or DSM-IV/5. Demographic and other clinical variables were compared among clusters by linear model ANOVA and chi-squared test.ResultsFour clusters were identified: subjects with (1) no history of meeting any AWS criteria (n=50); (4) with complete number of AWS symptoms, meeting both DSM definitions (n=259); and two clusters of subjects with smaller number of AWS symptoms: (3) those meeting only DSM-IV/5 criteria (n=94) and (2) those also meeting DSM-III-R criteria (n=70). Compared to cluster 2, the Cluster 3 members had higher frequency of anxiety, insomnia, and restlessness during withdrawal. The clusters also differed in the total number of drinks (p=0.021), average drinks per drinking days (p=0.013), history of anxiety disorder (p=0.006), substance-induced depression (p=0.019), and higher scores of PSQI (p<0.001), PHQ9 (p<0.001), and GAD-7 (p<0.001) with a relative increase in frequency between clusters as follows 1<2<3<4. Group 4 also had the highest percentages of subjects with history of seizure, delirium or hallucinations.ConclusionsDifferent definitions of AWS capture clusters of AD patients with different symptomatology, comorbidity and consumption patterns. Understanding of biological underpinnings behind those differences may guide improvement in personalized treatment selection.Disclosure of InterestNone Declared

Introduction Bipolar disorder (BD) is a chronic illness affecting approximately 2-3% adults worldwide. Mood stabilizers, such as lithium, valproate, carbamazepine, and lamotrigine are mainstays of the treatment. Despite their benefits, mood stabilizers carry a risk of side effects, which can lead to treatment discontinuation and non-adherence rates ranging from 10 to 60% in BD patients (Dols et al. Int Clin Psychopharmacol 2013; 28, 287-296). Dermatologic side effects, also known as cutaneous adverse drug reactions, are particularly distressing, often impacting patients’ self-esteem and social interactions, and contributing to non-compliance. These reactions can range in severity from mild rashes, acneiform eruptions, hair loss and psoriasis to severe, life-threatening conditions like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) (Mitkov et al. Psychosomatics 2014; 55, 1-20).Objectives Despite the well-documented association between mood stabilizers and dermatologic adverse effects (AE), the overall prevalence of these reactions across mood stabilizers remains unclear. This systematic review and meta-analysis aims (1) to estimate the prevalence of dermatologic AE associated with mood stabilizer (lithium, valproate, carbamazepine and lamotrigine) use in patients with BD, and (2) to summarize the available evidence on the onset and timing of these reactions.MethodsWe searched Ovid MEDLINE®, Embase, Cochrane Library, Web of Science, Scopus, and PsycINFO from 1970 onward for studies on dermatologic AEs in BD patients treated with lithium, valproate, carbamazepine, or lamotrigine (CRD42022357268). Study selection, data extraction, and bias risk assessment were performed by two reviewers. Meta-analyses were conducted to estimate the prevalence rates for dermatologic AEs.ResultsThe initial database searches yielded 5,354 studies. 47 articles were deemed relevant and included in this systematic review. Study designs included 16 randomized controlled trials, 10 non-randomized open-label trials, 12 cohort studies, and 9 cross-sectional studies. Lithium was associated with acneiform eruptions in 4.4% (95% CI: 1.0-17.0%), rash in 1.8% (95% CI: 0.7-4.8%), and hair loss in 1.7% (95% CI: 0.4%-6.4%) of patients. For valproate, hair loss was observed in 4.6% of patients (95% CI: 3.0-6.7%) and rash in 2.9% (95% CI: 1.6-5.3%). Carbamazepine was associated with rash in 6.0% of patients (95% CI: 4.4-7.6%), but severe reactions such as SJS and TEN were not reported. Lamotrigine had the highest rash prevalence with 9.2% (95% CI: 7.2-11.8%), while severe reactions were rare (0.04%, 95% CI: 0.00-0.63%).Conclusions Mood stabilizers showed varying levels of dermatologic AEs, but severe reactions were rare. Future studies should explore factors influencing these outcomes, their impact on quality of life and treatment participation, and potential management strategies.Disclosure of InterestNone Declared

IntroductionBipolar disorder (BD) is a chronic illness that can lead to severe functioning impairment, which can disrupt daily life. This study aims to compare overall functioning and clinical presentation associated with early onset (EO) and mid-life onset (MO) BD.ObjectivesThe objective of this study is to be able to predict the cognitive and functional impairment evolution of bipolar disorder based on the onset.MethodsA total of 154 BD patients (81 in euthymia and 51 in a depressive episode) participated in this cross-sectional study. We selected two groups of subjects based on age at onset of the first mood episode (EO: 0-20 years, n=117; MO: 20-40 years, n=37) and compared socio-demographic, clinical variables and functional impairment assessed by the World Health Organization Disability Assessment Schedule (WHODAS 2.0).Results75.2% of the patients with an EO were female, they had higher psychiatric comorbidities prevalence (76.1% vs. 43.2%; p<.001), being personality disorders the most significant (30.2% vs. 5.4%; p=.001), more suicide attempts (51.3% vs. 16.2%; p<.001), mood episodes (mdn=12, iqr=17 vs. mdn=6, iqr=9.5; p=.001), childhood abuse (93.5% vs. 73.9%; p=.014), being verbal (78.0% vs. 52.2%; p=.015) and physical abuse (51.6% vs. 21.7%; p=.009) higher compared to MO. Functionality was also affected, with higher dysfunction percentages in EO (mdn=47, iqr=34.7 vs. mdn=24, iqr=12.5; p<.001) affecting cognition (mdn=8.5, iqr=6 vs. mdn=4, iqr=7; p<.001), self-care (mdn=2, iqr=5 vs. mdn=0, iqr=1; p<.001), daily activities (mdn=12, iqr=13 vs. mdn=4, iqr=10; p<.001) and community participation (mdn=13, iqr=8.7 vs. mdn=8, iqr=7; p<.001).EO depressed patients (n=38; F: 30; M: 8), had more personality disorders (42.1% vs. 0%; p=.010), suicide attempts (60.5% vs. 0%; p<.001), mood episodes (mdn=12, iqr=12 vs. mdn=5.5, iqr=4.7; p=.001), lower overall functionality (mdn=57, iqr=41.5 vs. mdn=35, iqr=38.3; p=.009), cognition (mdn=10, iqr=6.5 vs. mdn=4, iqr=9; p=.023), self-care (mdn=4, iqr=6.2 vs. mdn=0, iqr=3; p=.008), oneself care (mdn=9, iqr =7 vs. mdn=5, iqr=8.5; p=.025), daily activities (mdn=15.5, iqr=14 vs. mdn=11, iqr=12.7; p=.037) and community participation (mdn= 15.5, iqr=8.2 vs. mdn=11.5, iqr=5.7; p=.030).EO euthymic patients (n=59; F: 42; M: 17) had more psychiatric comorbidities (74.6% vs. 33.3%; p=.001), physical abuse history (51.2% vs. 0%; p= .002), and lower functionality (mdn=7, iqr=7 vs. mdn=2, iqr=7; p=.004), cognition (mdn=7.5, iqr=7 vs. mdn=4, iqr=7; p=.033), daily activities (mdn=9, iqr=11 vs. mdn=3, iqr=8.5; p=.005) and community participation (mdn=10, iqr=9 vs. mdn= 7, iqr=7; p=.031).ConclusionsResults suggest that patients with an EO are more associated with severe psychosocial functioning impairment. Future studies are needed to clarify a more severe illness prediction between EO and MO.Disclosure of InterestNone Declared

When long bones fracture, healing occurs spontaneously in about 90% of cases, while the remaining 10% result in non-union, presenting significant clinical challenges. The standard treatment for non-unions is autologous bone grafting, but this approach has limitations, including high complication rates, donor site morbidity, and limited graft availability. An alternative strategy involves using growth factors to promote bone regeneration, with recombinant bone morphogenetic protein-2 (rBMP-2) being the most common. Although effective, rBMP-2 requires supra-physiological doses that cause inflammation, poor bone quality, and severe side effects. Our previous work suggests that genetic delivery of BMP-2 may offer more controlled healing. We aim to develop a more effective therapy for non-unions using adeno-associated viral vectors. By lyophilizing the vector onto a scaffold, we also aim to increase treatment potency, reduce leakage, and improve transduction using cryoprotectant buffers.AAV6-GFP-Luciferase was used to compare the activity of AAV6 stored at −80°C versus lyophilized in cryoprotectant buffer. A rat critical-sized defect model was employed, as described in [1]. For standard storage, AAV was added to the collagen sponge before implantation into a 5mm defect. For lyophilization, AAV was mixed with cryoprotectant, loaded onto the sponge, and lyophilized. Rats were imaged at 7- and 10-days using IVIS. To assess therapeutic relevance, the experiment was repeated with AAV6-BMP2-IL1Ra, implanted into 5mm femoral defects on collagen sponges, with healing monitored by X-ray every 4 weeks (continuing through 12-weeks post-operation).The reporter and therapeutic vectors showed improved transduction efficiency with lyophilization. The reporter vector exhibited higher transgene expression at days 7 and 10. This boost in expression either remained significant through 4 weeks or continued to show better signal at that time, correlating with improved healing seen in the X-rays (Fig. 2).Preliminary data suggest that lyophilization could reduce the therapeutic dose of AAV needed for treating osseous nonunion with a bicistronic vector. Lyophilization offers various benefits: enhanced transduction efficiency, improved stability of the gene product at logistically feasible conditions, and reduced off-target effects due to less AAV leakage from the implantation site. While in vivo experiments with AAV6-BMP2-IL1Ra are ongoing, these findings warrant further investigation into lyophilized AAV therapies for this application.For any figures or tables, please contact the authors directly.