Assessing the influence of micelle silymarin on laying hens' performance, egg quality, water loss and blood profile.

Micelle silymarin (MS) is known for its various beneficial properties, including antiswelling, antioxidant, hepatoprotective and antidiabetic effects. The primary goal of this research was to investigate how MS impacts the performance, egg quality, water loss and blood profile of laying hens. 288 Hy-Line brown laying hens, 28 weeks in age, were utilized for this experiment. The hens were randomly allocated into three dietary treatment groups, with each group comprising eight replicates of 12 hens, each housed in individual pens with access to feed and water. Over a 12-week feeding trial, the hens were provided with a basal diet supplemented with different levels of MS: 0%, 0.03% and 0.06%. The results indicated that the inclusion of MS in the hens' diet did not have a significant impact on their performance (p > 0.05). However, Haugh units, egg weight and eggshell strength showed a linear improvement (p < 0.05) throughout the entire trial period with MS supplementation. Furthermore, there was a linear decrease in egg yolk colour and eggshell thickness showed linear improvements (p < 0.05), particularly during Week 8, with MS supplementation. Moreover, layers fed diet supplemented with MS showed a linear increased (p < 0.05) in albumen height and eggshell thickness in Week 12. In addition, egg water loss during Week 12, the third day of incubation, linearly decreased as an effect of the increasing level of the MS in the laying hen's diet (p < 0.05). Regarding blood profile parameters, the study revealed a tendency for alkaline phosphatase to decrease, whereas aspartate aminotransferase and cholesterol levels were linearly decreased (p < 0.05). In summary, increasing the level of MS supplementation in the diet of laying hens appeared to be beneficial in improving egg quality, slight improvement for egg water loss and certain aspects of blood profile parameters, without adversely affecting the hens' growth performance.

Deep learning for the automatic detection and segmentation of parotid gland tumors on MRI.

OBJECTIVES: Parotid gland tumors (PGTs) often occur as incidental findings on magnetic resonance images (MRI) that may be overlooked. This study aimed to construct and validate a deep learning model to automatically identify parotid glands (PGs) with a PGT from normal PGs, and in those with a PGT to segment the tumor. MATERIALS AND METHODS: The nnUNet combined with a PG-specific post-processing procedure was used to develop the deep learning model trained on T1-weighed images (T1WI) in 311 patients (180 PGs with tumors and 442 normal PGs) and fat-suppressed (FS)-T2WI in 257 patients (125 PGs with tumors and 389 normal PGs), for detecting and segmenting PGTs with five-fold cross-validation. Additional validation set separated by time, comprising T1WI in 34 and FS-T2WI in 41 patients, was used to validate the model performance. RESULTS AND CONCLUSION: To identify PGs with tumors from normal PGs, using combined T1WI and FS-T2WI, the deep learning model achieved an accuracy, sensitivity and specificity of 98.2% (497/506), 100% (119/119) and 97.7% (378/387), respectively, in the cross-validation set and 98.5% (67/68), 100% (20/20) and 97.9% (47/48), respectively, in the validation set. For patients with PGTs, automatic segmentation of PGTs on T1WI and FS-T2WI achieved mean dice coefficients of 86.1% and 84.2%, respectively, in the cross-validation set, and of 85.9% and 81.0%, respectively, in the validation set. The proposed deep learning model may assist the detection and segmentation of PGTs and, by acting as a second pair of eyes, ensure that incidentally detected PGTs on MRI are not missed.

An unappreciated cell survival-independent role for BAFF initiating chronic lymphocytic leukemia.

Background: Chronic Lymphocytic Leukemia (CLL) is characterized by the expansion of CD19+ CD5+ B cells but its origin remains debated. Mutated CLL may originate from post-germinal center B cells and unmutated CLL from CD5+ mature B cell precursors. Irrespective of precursor types, events initiating CLL remain unknown. The cytokines BAFF and APRIL each play a significant role in CLL cell survival and accumulation, but their involvement in disease initiation remains unclear. Methods: We generated novel CLL models lacking BAFF or APRIL. In vivo experiments were conducted to explore the impact of BAFF or APRIL loss on leukemia initiation, progression, and dissemination. Additionally, RNA-seq and quantitative real-time PCR were performed to unveil the transcriptomic signature influenced by BAFF in CLL. The direct role of BAFF in controlling the expression of tumor-promoting genes was further assessed in patient-derived primary CLL cells ex-vivo. Results: Our findings demonstrate a crucial role for BAFF, but not APRIL, in the initiation and dissemination of CLL cells. In the absence of BAFF or its receptor BAFF-R, the TCL1 transgene only increases CLL cell numbers in the peritoneal cavity, without dissemination into the periphery. While BAFF binding to BAFF-R is dispensable for peritoneal CLL cell survival, it is necessary to activate a tumor-promoting gene program, potentially linked to CLL initiation and progression. This direct role of BAFF in controlling the expression of tumor-promoting genes was confirmed in patient-derived primary CLL cells ex-vivo. Conclusions: Our study, involving both mouse and human CLL cells, suggests that BAFF might initiate CLL through mechanisms independent of cell survival. Combining current CLL therapies with BAFF inhibition could offer a dual benefit by reducing peripheral tumor burden and suppressing transformed CLL cell output.

Trajectories of social isolation and loneliness and the risk of incident type 2 diabetes mellitus across genetic risk score.

AIM: This study aimed to investigate the association of social isolation, loneliness, and their trajectory with the risk of developing type 2 diabetes mellitus (T2DM) across genetic risk. METHODS: We included 439,337 participants (mean age 56.3 ± 8.1 years) enrolled in the UK Biobank study who were followed up until May 31, 2021. Social isolation and loneliness were self-reported and were further categorized into never, transient, incident, and persistent patterns. RESULTS: During a median follow-up of 12.7 years, 15,258 incident T2DM cases were documented. Social isolation (versus no social isolation: hazard ratio (HR) 95 % confidence interval (CI) 1.04 [1.00;1.09]) and loneliness (versus no loneliness: 1.26 [1.19;1.34]) were associated with an increased T2DM risk, independent of the genetic risk for T2DM. The interactions existed between social isolation and loneliness (Pinteraction < 0.05); the increased T2DM risk associated with social isolation was only significant among participants without loneliness. In the longitudinal analysis, only persistent social isolation (versus never social isolation: 1.22 [1.02;1.45]) was associated with an increased T2DM risk, whereas incident loneliness (versus never loneliness: 1.95 [1.40;2.71]) and persistent loneliness (2.00 [1.31;3.04]) were associated with higher T2DM risks. CONCLUSION: Social isolation and loneliness, especially their persistent pattern, were independently associated with an increased incident T2DM risk, irrespective of an individual's genetic risk. Loneliness modified the association between social isolation and incident T2DM.

Radiographic Imaging for the Diagnosis and Treatment of Patients with Skeletal Class III Malocclusion.

Skeletal Class III malocclusion is one type of dentofacial deformity that significantly affects patients' facial aesthetics and oral health. The orthodontic treatment of skeletal Class III malocclusion presents challenges due to uncertainties surrounding mandibular growth patterns and treatment outcomes. In recent years, disease-specific radiographic features have garnered interest from researchers in various fields including orthodontics, for their exceptional performance in enhancing diagnostic precision and treatment effect predictability. The aim of this narrative review is to provide an overview of the valuable radiographic features in the diagnosis and management of skeletal Class III malocclusion. Based on the existing literature, a series of analyses on lateral cephalograms have been concluded to identify the significant variables related to facial type classification, growth prediction, and decision-making for tooth extractions and orthognathic surgery in patients with skeletal Class III malocclusion. Furthermore, we summarize the parameters regarding the inter-maxillary relationship, as well as different anatomical structures including the maxilla, mandible, craniofacial base, and soft tissues from conventional and machine learning statistical models. Several distinct radiographic features for Class III malocclusion have also been preliminarily observed using cone beam computed tomography (CBCT) and magnetic resonance imaging (MRI).

The Impact of Social Determinants of Health on Discharge Disposition Following One- and Two-Level Posterior Interbody Fusion.

Background Current research is limited in exploring the impact of social determinants of health (SDOH) on the discharge location within elective spine surgery. Further understanding of the influence of SDOH on disposition is necessary to improve outcomes. This study explores how SDOH influence discharge disposition for patients undergoing one- or two-level posterior interbody fusion (TLIF/PLIF). Methods This was a retrospective propensity-matched cohort study. Patients who underwent TLIF/PLIF between 2017 and 2020 at a single academic medical center were identified. The chart review gathered demographics, perioperative characteristics, intra/post-operative complications, discharge disposition, and 90-day outcomes. Discharge dispositions included subacute nursing facility (SNF), home with self-care (HSC), home with health services (HHS), and acute rehab facility (ARF). Demographic, perioperative, and disposition outcomes were analyzed by chi-square analysis and one-way ANOVA based on gender, race, and income quartiles. Results Propensity score matching for significant demographic factors isolated 326 patients. The rate of discharge to SNF was higher in females compared to males (25.00% vs 10.56%; p=0.001). Men were discharged to home at a higher rate than women (75.4% vs 61.95%; p=0.010). LatinX patients had the highest rate of home discharge, followed by Asians, Caucasians, and African Americans (83.33% vs 70.31% vs 66.45% vs 65.90%; p<0.001). The post hoc Tukey test demonstrated statistically significant differences between Asians and all other races in the context of age and BMI. Additionally, patients discharged to SNF showed the highest Charlson comorbidity index (CCI) score, followed by those at ARF, HHS, and HSC (4.36 vs 4.05 vs 2.87 vs 2.37; p<0.001). The estimated median income for the cohort ranged from $52,000 to $250,001, with no significant differences in income seen across comparisons. Conclusion Discharge disposition following one- or two-level TLIF/PLIF shows significant association with gender and race. No association was seen when comparing discharge rates among zip code-level median income quartiles.

Early detection of nasopharyngeal carcinoma: performance of a short contrast-free screening magnetic resonance imaging.

BACKGROUND: Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program. METHODS: EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB. EGB was negative if the biopsy was negative or was not performed. Patients also underwent a screening MRI. Diagnostic performance was based on histologic confirmation of NPC in the initial study or during a follow-up period of at least 2 years. RESULTS: The study prospectively recruited 354 patients for MRI and endoscopy; 40/354 (11.3%) endoscopy-positive patients underwent EGB. Eighteen had NPC (5.1%), and 336 without NPC (94.9%) were followed up for a median of 44.8 months. MRI detected additional NPCs in 3/18 (16.7%) endoscopy-negative and 2/18 (11.1%) EGB-negative patients (stage I/II, n = 4; stage III, n = 1). None of the 24 EGB-negative patients who were MRI-negative had NPC. MRI missed NPC in 2/18 (11.1%), one of which was also endoscopy-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI, endoscopy, and EGB were 88.9%, 91.1%, 34.8%, 99.4%, and 91.0%; 77.8%, 92.3%, 35.0%, 98.7%, and 91.5%; and 66.7%, 92.3%, 31.6%, 98.1%, and 91.0%, respectively. CONCLUSION: A quick contrast-free screening MRI complements endoscopy in NPC screening programs. In EBV-screen-positive patients, MRI enables early detection of NPC that is endoscopically occult or negative on EGB and increases confidence that NPC has not been missed.

Prospective assessment of dynamic changes in frailty and its impact on early clinical outcomes following physician-modified fenestrated-branched endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms.

INTRODUCTION: Frailty, a predictor of poor outcomes, has been widely studied as a screening tool in surgical decision-making. However, the impact of frailty on the outcomes after fenestrated-branched endovascular aortic repairs (FBEVARs) is less well established. In addition, the changes in frailty during recovery after FBEVAR are unknown. We aim to assess the impact of frailty on outcomes of high-risk patients undergoing physician-modified FBEVARs for complex abdominal and thoracoabdominal aortic aneurysms, as well as the changes in frailty during follow-up. METHODS: Consecutive patients enrolled in a single-center prospective Physician-Sponsored Investigational Device Exemption protocol (FDA# G200159) were evaluated. In addition to the baseline characteristics, frailty was assessed using the Hopkins Frailty Score (HFS) and frailty index (FI) measured by the Frailty Meter. Sarcopenia was measured by L3 total psoas muscle area (PMA). These measurements were repeated during follow-up. The follow-up HFS and FI were compared with baseline scores using the Wilcoxon signed-rank test, whereas follow-up PMA measurements were compared with the baseline using the paired t test. The association between baseline frailty and morbidity was evaluated by the Wilcoxon rank-sum test. RESULTS: Seventy patients were analyzed in a prospective Physician-Sponsored Investigational Device Exemption study from February 9, 2021, to June 2, 2023. At baseline, HFS identified 54% of patients as not frail, 43% as intermediately frail, and 3% as frail. Technical success of FBEVAR was 94% with one in-hospital mortality. Early major adverse events were seen in 10 (14.3%) patients. No difference in baseline FI was seen between patients with early morbidity and those without. Patients who were not frail per HFS were less likely to experience early morbidity (P = .033), and there was a significantly lower baseline PMA in patients who experienced early morbidity (P = .016). At 1 month, patients experienced a significant increase in HFS and HFS category (P = .001 and P = .01) and a significant decrease in sarcopenia (mean PMA: -96 mm2, P = .005). At 6 months, HFS and HFS category as well as PMA returned toward baseline (P = .42, P = .38, and mean PMA: +4 mm2, P = .6). CONCLUSIONS: Preoperative frailty and sarcopenia were associated with early morbidity after physician-modified FBEVAR. During follow-up, patients became more frail and sarcopenic by 1 month. Recovery from this initial decline was seen by 6 months, suggesting that frailty and sarcopenia are reversible processes rather than a unidirectional phenomenon of continued decline.

Radiologic extranodal extension for nodal staging in nasopharyngeal carcinoma.

PURPOSE: Extranodal extension (ENE) has the potential to add value to the current nodal staging system (N8th) for predicting outcome in nasopharyngeal carcinoma (NPC). This study aimed to incorporate ENE, as well as cervical nodal necrosis (CNN) to the current stage N3 and evaluated their impact on outcome prediction. The findings were validated on an external cohort. METHODS & MATERIALS: Pre-treatment MRI of 750 patients from the internal cohort were retrospectively reviewed. Predictive values of six modified nodal staging systems that incorporated four patterns of ENE and two patterns of CNN to the current stage N3 for disease-free survival (DFS) were compared with that of N8th using multivariate cox-regression and concordance statistics in the internal cohort. Performance of stage N3 for predicting disease recurrence was calculated. An external cohort of 179 patients was used to validate the findings. RESULTS: Incorporation of advanced ENE, which infiltrates into adjacent muscle/skin/salivary glands outperformed the other five modifications for predicting outcomes (p < 0.01) and achieved a significantly higher c-index for 5-year DFS (0.69 vs 0.72) (p < 0.01) when compared with that of N8th staging system. By adding advanced ENE to the current N3 increased the sensitivity for predicting disease recurrence from 22.4 % to 47.1 %. The finding was validated in the external cohort (5-year DFS 0.65 vs. 0.72, p < 0.01; sensitivity of stage N3 increased from 14.0 % to 41.9 % for disease recurrence). CONCLUSION: Results from two centre cohorts confirmed that the radiological advanced ENE should be considered as a criterion for stage N3 disease in NPC.

Radiomics Analysis in Characterization of Salivary Gland Tumors on MRI: A Systematic Review.

Radiomics analysis can potentially characterize salivary gland tumors (SGTs) on magnetic resonance imaging (MRI). The procedures for radiomics analysis were various, and no consistent performances were reported. This review evaluated the methodologies and performances of studies using radiomics analysis to characterize SGTs on MRI. We systematically reviewed studies published until July 2023, which employed radiomics analysis to characterize SGTs on MRI. In total, 14 of 98 studies were eligible. Each study examined 23-334 benign and 8-56 malignant SGTs. Least absolute shrinkage and selection operator (LASSO) was the most common feature selection method (in eight studies). Eleven studies confirmed the stability of selected features using cross-validation or bootstrap. Nine classifiers were used to build models that achieved area under the curves (AUCs) of 0.74 to 1.00 for characterizing benign and malignant SGTs and 0.80 to 0.96 for characterizing pleomorphic adenomas and Warthin's tumors. Performances were validated using cross-validation, internal, and external datasets in four, six, and two studies, respectively. No single feature consistently appeared in the final models across the studies. No standardized procedure was used for radiomics analysis in characterizing SGTs on MRIs, and various models were proposed. The need for a standard procedure for radiomics analysis is emphasized.

MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier.

BACKGROUND & AIMS: MUC13 cell surface mucin is highly expressed on the mucosal surface throughout the intestine, yet its role against bacterial infection is unknown. We investigated how MUC13 impacts Salmonella typhimurium (S Tm) infection and elucidated its mechanisms of action. METHODS: Muc13-/- and wild-type littermate mice were gavaged with 2 isogenic strains of S Tm after pre-conditioning with streptomycin. We assessed clinical parameters, cecal histology, local and systemic bacterial load, and proinflammatory cytokines after infection. Cecal enteroids and epithelial cell lines were used to evaluate the mechanism of MUC13 activity after infection. The interaction between bacterial SiiE and MUC13 was assessed by using siiE-deficient Salmonella. RESULTS: S Tm-infected Muc13-/- mice had increased disease activity, histologic damage, and higher local and systemic bacterial loads. Mechanistically, we found that S Tm binds to MUC13 through its giant SiiE adhesin and that MUC13 acts as a pathogen-binding decoy shed from the epithelial cell surface after pathogen engagement, limiting bacterial invasion. In addition, MUC13 reduces epithelial cell death and intestinal barrier breakdown by enhancing nuclear factor kappa B signaling during infection, independent of its decoy function. CONCLUSIONS: We show for the first time that MUC13 plays a critical role in antimicrobial defense against pathogenic S Tm at the intestinal mucosal surface by both acting as a releasable decoy limiting bacterial invasion and reducing pathogen-induced cell death. This further implicates the cell surface mucin family in mucosal defense from bacterial infection.

Antibiotic susceptibility and clonal distribution of Staphylococcus aureus from pediatric skin and soft tissue infections: 10-year trends in multicenter investigation in China.

Background: Skin and Soft Tissue Infections (SSTIs) Surveillance Network of S. aureus In Pediatrics in China was established in 2009 to routinely report epidemiological changes. We aimed to monitor the present antibiotic sensitivity and molecular characteristics of S. aureus and methicillin-resistant S. aureus (MRSA) from SSTIs in children nationwide and track the changes over the past decade. Methods: Patients diagnosed with SSTIs from the dermatology departments of 22 tertiary pediatric hospitals in seven geographical regions of China were recruited continuously from May 2019 to August 2021. S. aureus was isolated, and its sensitivity to 15 antimicrobials was evaluated using the broth microdilution method. The molecular characteristics of the MRSA isolates were determined through multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. The presence of the Panton-Valentine leukocidin gene (pvl) was determined. Results: The detection rate of S. aureus was 62.57% (1379/2204), among which MRSA accounted for 14.79% (204/1379), significantly higher than the result in previous study in 2009-2011 (2.58%, 44/1075). Compared with previous study, the sensitivity to cephalosporins and fusidic acid decreased to varying degrees, while that to chloramphenicol, ciprofloxacin, clindamycin, erythromycin, gentamicin, penicillin, and tetracycline increased significantly. The sensitivity to mupirocin, trimethoprim/sulfamethoxazole (TRISUL), and rifampicin still maintained at a high level (97.90%, 99.35% and 96.66% respectively). The leading multidrug resistance pattern of MRSA and methicillin-sensitive S. aureus (MSSA) were erythromycin-clindamycin-tetracycline (55.84%; 43/77) and erythromycin-clindamycin-chloramphenicol (27.85%, 44/158) respectively. 12 high-level mupirocin-resistant strains were detected, and notable differences in geographical distribution and seasonal variation were observed. The main types of MRSA were ST121 (46.08%, 94/204), followed by ST59 (19.61%, 40/204). SCCmec V (65.69%, 134/204) and SCCmec IV (31.86%, 65/204) were dominant epidemic types. ST121-V, ST59-IV, and ST22-V were the most prevalent clones nationwide. The detection rate of pvl had increased markedly from 9.09% (4/44) in 2009-2011 to 22.55% (46/204) in 2019-2021 (P<0.05). Conclusion: The antibiotic sensitivity and molecular characteristics of S. aureus from pediatric SSTIs has changed significantly over the past decade. To standardize medical care, provide timely and reasonable clinical treatment, and effectively manage infection control, Chinese pediatric SSTIs guidelines are urgently needed.

[Survey of Helicobacter pylori levofloxacin and clarithromycin resistance rates and drug resistance genes in Ningxia, 2020-2022].

Objective: To explore the rate of Helicobacter pylori (Hp) resistance to levofloxacin and clarithromycin and the common mutation patterns of resistance genes in Ningxia, and to assess the concordance between phenotypic resistance and genotypic resistance. Methods: Cross-sectional study. Patients diagnosed with Hp infection in 14 hospitals in Ningxia region from February 2020 to May 2022 were retrospectively selected. Hp strains were isolated from gastric biopsy specimens of Hp-infected patients and subjected to phenotypic drug sensitivity testing and detection of resistance genes to analyze the rate of Hp resistance to levofloxacin and clarithromycin and the common mutation patterns of resistance genes in Ningxia region; and the concordance rate and Kappa concordance test were used to assess the concordance between phenotypic resistance and genotypic resistance. Results: A total of 1 942 Hp strains were isolated and cultured, and among the infections, 1 069 cases (55.0%) were male and 873 cases (45.0%) were female, aged (50.0±12.5) years (15-86 years). The rates of Hp resistance to levofloxacin and clarithromycin in Ningxia were 42.1% (818/1 942) and 40.1% (779/1 942), respectively, and the rate of dual resistance to both was 22.8% (443/1 942). The rate of resistance to levofloxacin and clarithromycin of Hp strains from female patients was higher than in male patients (levofloxacin: 50.4%(440/873) vs 35.4%(378/1 069); clarithromycin: 44.4%(388/873) vs 36.6%(391/1 069), both P<0.001). Among the GyrA gene mutations associated with levofloxacin resistance, the differences in mutation rate of amino acid at positions 87 and 91 were statistically significant in both drug-resistant and sensitive strains(both P<0.001), except for Asn87Thr. Hp strains were statistically significant for levofloxacin (Kappa=0.834, P<0.001) and clarithromycin (Kappa=0.829, P<0.001) had good concordance in resistance at the phenotypic and genotypic levels. Conclusion: The resistance of Hp to levofloxacin and clarithromycin in Ningxia region is severe, and there is good consistency between genotypic and phenotypic resistance.

Clinical outcomes and complications after biportal endoscopic spine surgery: a comprehensive systematic review and meta-analysis of 3673 cases.

PURPOSE: Current literature suggests that biportal spinal endoscopy is safe and effective in treating lumbar spine pathology such as lumbar disc herniation, lumbar stenosis, and degenerative spondylolisthesis. No prior study has investigated the postoperative outcomes or complication profile of the technique as a whole. This study serves as the first comprehensive systematic review and meta-analysis of biportal spinal endoscopy in the lumbar spine. METHODS: A PubMed literature search provided over 100 studies. 42 papers were reviewed and 3673 cases were identified with average follow-up time of 12.5 months. Preoperative diagnoses consisted of acute disc herniation (1098), lumbar stenosis (2432), and degenerative spondylolisthesis (229). Demographics, operative details, complications, and perioperative outcome and satisfaction scores were analyzed. RESULTS: Average age was 61.32 years, 48% male. 2402 decompressions, 1056 discectomies, and 261 transforaminal lumbar Interbody fusions (TLIFs) were performed. Surgery was performed on 4376 lumbar levels, with L4-5 being most common(61.3%). 290 total complications occurred, 2.23% durotomies, 1.29% inadequate decompressions, 3.79% epidural hematomas, and < 1% transient nerve root injuries, infections, and iatrogenic instability. Significant improvement in VAS-Back, VAS-Leg, ODI, and Macnab Scores were seen across the cohort. CONCLUSION: Biportal spinal endoscopy is a novel method to address pathology in the lumbar spine with direct visualization through an endoscopic approach. Complications are comparable to previously published rates. Clinical outcomes demonstrate effectiveness. Prospective studies are required to assess the efficacy of the technique as compared to traditional techniques. This study demonstrates that the technique can be successful in the lumbar spine.

Association of Social Isolation and Loneliness With Incident Heart Failure in a Population-Based Cohort Study.

BACKGROUND: Social isolation and loneliness have emerged as important risk factors for cardiovascular diseases, particularly during the coronavirus disease pandemic. However, it is unclear whether social isolation and loneliness had independent and joint associations with incident heart failure (HF). OBJECTIVES: This study sought to examine the association of social isolation, loneliness, and their combination with incident HF. METHODS: The UK Biobank study is a population-based cohort study. Social isolation and loneliness were assessed using self-reported questionnaires. HF cases were identified by linking hospital records and death registries. The weighted polygenic risk score associated with HF was calculated. RESULTS: Among the 464,773 participants (mean age: 56.5 ± 8.1 years, 45.3% male), 12,898 incident HF cases were documented during a median follow-up of 12.3 years. Social isolation (most vs least: adjusted HR: 1.17; 95% CI:1.11-1.23) and loneliness (yes vs no: adjusted HR: 1.19; 95% CI: 1.11-1.27) were significantly associated with an increased risk of incident HF. The association between an elevated risk of HF and social isolation was modified by loneliness (Pinteraction = 0.034). A gradient of association between social isolation and the risk of incident HF was found only among individuals without loneliness (Ptrend < 0.001), but not among those with loneliness (Ptrend = 0.829). These associations were independent of the genetic risk of HF. CONCLUSIONS: Social isolation and loneliness were independently associated with a higher likelihood of incident HF regardless of genetic risk. The association between social isolation and incident HF was potentially modified by loneliness status.

Safety and Effectiveness of SB2 (Infliximab Biosimilar) in Adult Patients with Immune-Mediated Inflammatory Diseases: A Post-Marketing Surveillance in Korea.

INTRODUCTION: SB2 is a biosimilar of infliximab (IFX), which is approved for rheumatoid arthritis (RA), ankylosing spondylitis (AS), adult and pediatric Crohn's disease (CD), adult and pediatric ulcerative colitis (UC), psoriatic arthritis (PsA), and plaque psoriasis (PsO). The drug approval process in Korea includes post-marketing surveillance (PMS) studies to re-examine the safety and effectiveness of approved new medications. METHODS: This was a prospective, multi-center, open-label, observational, phase 4 PMS study of IFX-naïve patients or patients switched from reference IFX or another IFX-biosimilar to SB2 in all approved indications. The primary endpoint was to evaluate the safety of SB2 reported as adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was to evaluate the effectiveness measured as investigators' overall effectiveness assessment, categorized as improved, stable, or worsened. Furthermore, disease-specific activity scores were collected for each indication [28-joint Modified Disease Activity Score (DAS28) for RA, Korean Bath Ankylosing Spondylitis Disease Activity Index (KBASDAI), Crohn's Disease Activity Index (CDAI), and Full Mayo Score for UC]. RESULTS: In the safety and effectiveness analysis, 180 and 128 patients were included, respectively. Most patients (83.9%) were IFX-naïve patients and 16.1% were switched patients. RA (48.9%) and AS (31.1%) were the most frequent indications. Overall, 23 (12.8%) patients reported AEs and 14 (7.8%) patients reported ADRs. Serious adverse events (SAEs) were reported by 3 (1.7%) patients. As per investigators' overall effectiveness assessments, SB2 was effective in 94.6% (105/111) of IFX-naïve patients and 82.4% (14/17) of switched patients. In IFX-naïve patients, disease activity scores decreased significantly from baseline to week 30 (week 24 for AS); mean (SD) changes of disease scores for each indication were DAS28 - 1.9 (0.79) for RA, KBASDAI - 3.8 (1.68) for AS, CDAI - 200.4 (112.47) for CD, and Full Mayo Score - 6.6 (2.92) for UC. The persistence rate of SB2 treatments was 88.3% with median treatment duration of 30.1 weeks. CONCLUSION: This PMS study of the IFX-biosimilar SB2 in Korea confirmed the safety and effectiveness of SB2 in major indications.

Discriminating between benign and malignant salivary gland tumors using diffusion-weighted imaging and intravoxel incoherent motion at 3 Tesla.

PURPOSE: The purpose of this study was to retrospectively evaluate the diagnostic performances of diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) for discriminating between benign and malignant salivary gland tumors (SGTs). MATERIALS AND METHODS: Sixty-seven patients with 71 SGTs who underwent MRI examination at 3 Tesla were included. There were 34 men and 37 women with a mean age of 57 ± 17 (SD) years (age range: 20-90 years). SGTs included 21 malignant tumors (MTs) and 50 benign SGTs (33 pleomorphic adenomas [PAs] and 17 Warthin's tumors [WTs]). For each SGT, DWI and IVIM parameters, mean, skewness, and kurtosis of apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion volume fraction (f) were calculated and further compared between SGTs using univariable analysis. Areas under the curves (AUC) of receiver operating characteristic of significant parameters were compared using the Delong test. RESULTS: Significant differences in ADCmean, Dmean and D*mean were found between SGTs (P < 0.001). The highest AUC values were obtained for ADCmean (0.949) for identifying PAs and D*mean (0.985) for identifying WTs and skewness and kurtosis did not outperform mean. To discriminate benign from malignant SGTs with thresholds set to maximize Youden index, IVIM and DWI produced accuracies of 85.9% (61/71; 95% CI: 75.6-93.0) and 77.5% (55/71; 95% CI: 66.0-86.5) but misdiagnosed MTs as benign in 28.6% (6/21) and 61.9% (13/21) of SGTs, respectively. After maximizing specificity to 100% for benign SGTs, the accuracies of IVIM and DWI decreased to 76.1% (54/71; 95% CI: 64.5-85.4) and 64.8% (46/71; 95% CI: 52.5-75.8) but no MTs were misdiagnosed as benign. IVIM and DWI correctly diagnosed 66.0% (33/50) and 50.0% (25/50) of benign SGTs and 46.5% (33/71) and 35.2% (25/71) of all SGTs, respectively. CONCLUSION: IVIM is more accurate than DWI for discriminating between benign and malignant SGTs because of its advantage in detecting WTs. Thresholds set by maximizing specificity for benign SGTs may be advantageous in a clinical setting.

Social isolation, loneliness and subsequent risk of major adverse cardiovascular events among individuals with type 2 diabetes mellitus.

Background: Individuals with type 2 diabetes mellitus (T2DM) are more vulnerable to social disconnection compared with the general population; however, there are few relevant studies investigating this issue. Aims: To investigate whether social isolation or loneliness may be associated with subsequent risk of developing major adverse cardiovascular events, whether these associations vary according to fatal and non-fatal outcomes and how behavioural, psychological and physiological factors mediate these associations. Methods: This longitudinal analysis included data from 19 360 individuals with T2DM at baseline (2006-2010) from the UK Biobank. Social isolation and loneliness were measured using self-report questionnaires. The study outcomes included the first events of myocardial infarction (MI) or stroke (n=2273) and all-cause (n=2820) or cardiovascular disease-related mortality through linked hospital data or death registries. Results: Over a median follow-up of 12.4 years (interquartile range (IQR): 11.6-13.3 years), participants who were more socially isolated (most social isolation vs least social isolation) experienced increased risks for all-cause (hazard ratio (HR) : 1.33, 95% confidence interval (CI): 1.19 to 1.47) and cardiovascular disease (HR: 1.36, 95% CI: 1.17 to 1.59) mortality but not first MI or stroke. Loneliness (yes vs no) was associated with a greater risk for a composite of incident MI or stroke (HR: 1.37, 95% CI: 1.19 to 1.57) but not mortality. Social isolation was associated with fatal MI and stroke, whereas loneliness was associated with non-fatal MI and stroke. The significant associations of social isolation and loneliness with outcomes were mainly mediated by behavioural factors (mediating proportion: 17.8%-28.2% and 17.6%-17.8%, respectively). Conclusions: Among individuals with T2DM, social isolation and loneliness are associated with a greater risk of developing major adverse cardiovascular events, with differences in both risks stratified according to fatal and non-fatal events and underlying mediating factors.