Gradual Reduction Using Overhead Traction for Late-Detected Developmental Dysplasia of the Hip: A Report of Three Cases Diagnosed Among Children Over Four Years Old.

Optimal reduction methods for late-detected developmental dysplasia of the hip (DDH) remain debatable. Gradual reduction (GR) using traction is a safer and more reliable option for late-detected DDH than closed reduction or open reduction with or without preliminary traction. GR using overhead traction, one of the current GR methods, has been indicated for children of walking age up to four years of age, whereas the upper age limit of this method has not yet been determined. We present three cases of late-detected DDH whose hips were treated between four and six years of age with this method. Stable reduction without subsequent redislocation was technically accomplished for all patients, albeit the duration of horizontal traction became longer than usual. Clinically significant avascular necrosis (AVN) has developed in children aged ≥5 years, indicating the need for some modifications to the conventional protocol to prevent AVN.

A Real-World Comparison of Clinical Effectiveness in Patients with Rheumatoid Arthritis Treated with Upadacitinib, Tumor Necrosis Factor Inhibitors, and Other Advanced Therapies After Switching from an Initial Tumor Necrosis Factor Inhibitor.

INTRODUCTION: This study compared the clinical effectiveness of switching from tumor necrosis factor inhibitor (TNFi) to upadacitinib (TNFi-UPA), another TNFi (TNFi-TNFi), or an advanced therapy with another mechanism of action (TNFi-other MOA) in patients with rheumatoid arthritis (RA). METHODS: Data were drawn from the Adelphi RA Disease Specific Programme™, a cross-sectional survey administered to rheumatologists and their consulting patients in Germany, France, Italy, Spain, the UK, Japan, Canada, and the USA from May 2021 to January 2022. Patients who switched treatment from an initial TNFi were stratified by subsequent therapy of interest: TNFi-UPA, TNFi-TNFi, or TNFi-other MOA. Physician-reported clinical outcomes including disease activity (with formal DAS28 scoring available for 29% of patients) categorized as remission, low/moderate/high disease activity, as well as pain were recorded at initiation of current treatment and ≥ 6 months from treatment switch. Fatigue and treatment adherence were measured ≥ 6 months from treatment switch. Inverse-probability-weighted regression adjustment compared outcomes by subsequent class of therapy: TNFi-UPA versus TNFi-TNFi, or TNFi-UPA versus TNFi-other MOA. RESULTS: Of 503 patients who switched from their first TNFi, 261 were in TNFi-UPA, 128 in TNFi-TNFi, and 114 in TNFi-other MOA groups. At the time of switch, most patients had moderate/high disease activity (TNFi-UPA: 73%; TNFi-TNFi: 52%; TNFi-other MOA: 60%). After adjustment for differences in characteristics at point of switch, patients in TNFi-UPA group (n = 261) were significantly more likely to achieve physician-reported remission (67.7% vs. 40.3%; p = 0.0015), no pain (55.7% vs. 25.4%; p = 0.0007), and complete adherence (60.0% vs. 34.2%; p = 0.0049) compared with patients in TNFi-TNFi group (n = 121). Similar findings were observed for TNFi-UPA versus TNFi-other MOA groups (n = 111). CONCLUSION: Patients who switched from TNFi to UPA had significantly better clinical outcomes of remission, no pain, and complete adherence than those who cycled TNFi or switched to another MOA.

Enhanced anticancer efficacy of TRAIL-conjugated and odanacatib-loaded PLGA nanoparticles in TRAIL resistant cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) demonstrates unique characteristics in anticancer therapies as it selectively induces apoptosis in cancer cells. However, most cancer cells are TRAIL-resistant. Odanacatib (ODN), a cathepsin K inhibitor, is considered a novel sensitizer for cancer treatment. Combination therapy between TRAIL and sensitizers is considered a potent platform that improves TRAIL-based anticancer therapies beyond TRAIL monotherapy. Herein, we developed ODN loaded poly(lactic-co-glycolic) nanoparticles conjugated to GST-TRAIL (TRAIL-ODN-PLGA-NPs) to target and treat TRAIL-resistant cancer. TRAIL-ODN-PLGA-NPs demonstrated a significant increase in cellular uptake via death receptors (DR5 and DR4) on surface of cancer cells. TRAIL-ODN-PLGA-NPs exposure destroyed more TRAIL-resistant cells compared to a single treatment with free drugs. The released ODN decreased the Raptor protein, thereby increasing damage to mitochondria by elevating reactive oxygen species (ROS) generation. Additionally, Bim protein stabilization improved TRAIL-resistant cell sensitization to TRAIL-induced apoptosis. The in vivo biodistribution study revealed that TRAIL-ODN-PLGA-NPs demonstrated high location and retention in tumor sites via the intravenous route. Furthermore, TRAIL-ODN-PLGA-NPs significantly inhibited xenograft tumor models of TRAIL-resistant Caki-1 and TRAIL-sensitive MDA-MB-231 cells.The inhibition was associated with apoptosis activation, Raptor protein stabilizing Bim protein downregulation, Bax accumulation, and mitochondrial ROS generation elevation. Additionally, TRAIL-ODN-PLGA-NPs affected the tumor microenvironment by increasing tumor necrosis factor-α and reducing interleukin-6. In conclusion, we evealed that our formulation demonstrated synergistic effects against TRAIL compared with the combination of free drug in vitro and in vivo models. Therefore, TRAIL-ODN-PLGA-NPs may be a novel candidate for TRAIL-induced apoptosis in cancer treatment.

Femoral Neck Shaft Angle Measurement for Differentiating Femoral Head Stress Fracture from Avascular Necrosis.

OBJECTIVE: The study aimed to evaluate whether the measurement of Femoral Neck Shaft Angle (FNSA) can be helpful in differentiating femoral head Stress Fracture (SF) from Avascular Necrosis (AVN). METHODS: From September 2019 to April 2022, sixty-four patients [median age 32.0 years, interquartile range (IQR) 23.0-39.0 years] who underwent both hip radiograph and Magnetic Resonance Imaging (MRI) and diagnosed as femoral head SF or AVN were included in our retrospective study. Patients were divided into as having either femoral head SF (n = 34) or AVN (n = 30). The FNSA was measured in anteroposterior hip radiography. Continuous values were compared using the Mann-Whitney U test. The assessment of the predictive value of FNSA for femoral head SF was performed by Receiver Operating Characteristic (ROC) analysis. RESULTS: The FNSA was significantly higher in patients with SF (median 133.5°, IQR 128.0-136.7°) than those with AVN (median 127.5°, IQR 124.0-132.0°) (p = 0.001). In addition, the FNSA was significantly higher in SF femurs (median 134.8°, IQR 129.2-137.4°) than in contralateral normal femurs (median 127.1°, IQR 124.3-132.5°) in patients with unilateral femoral head SF (n = 30) (p < 0.001). In ROC analysis, the sensitivity, specificity, and Area Under the Curve (AUC) for predicting the femoral head SF were 77.3%, 63.3%, and 0.785 (95% confidence interval: 0.666-0.905), respectively, at a cutoff of 130.2°. CONCLUSION: Increased FNSA was associated with femoral head SF; thus, measurement of FNSA could be helpful for differentiating femoral head SF from AVN.

Augmentation of Autologous Platelet-Rich Plasma in Hip Salvage in Stages I and II of Avascular Necrosis: Randomized Blinded Trial Comparing 3 Surgical Techniques in 82 Patients.

Introduction: Avascular necrosis of the femoral head is common in routine orthopedic clinics. The challenge arises in managing early stages (I and II) without obvious radiological evidence. Authors explore this naïve research area by comparing surgical procedures in early AVN patients. Materials and Methods: A prospective multicentric study was performed from November 2020 to February 2023 on 82 patients treated with surgical decompression and adjuvants, concerning the defined inclusion and exclusion criteria. Radiopacity and intraosseous edema resolution and THA conversion rates were assessed. Hip pain VAS, groin/thigh pain, difficulty in sitting cross-legged incidence, pain-free walking distance, Harris hip scores, 30-s chair test, and complications were noted. Results: Among 82 patients, the mean age was 28.46 years. Male:female ratio of 3.9:1. 8.5% had bilateral affection and 48.78% had a positive family history. 93.90% presented with groin pain and difficulty in sitting cross-legged, restricted hip movements in 85.3%, and thigh pain in 54.87%. Harris hip scored worst in Group 3 followed by Group 2 and Group 1. 63.41% and 36.58% of patients had Grades 1 and 2 AVN, respectively. At 1 week post-operatively, 96.3% and 93.9% of patients were relieved from groin and thigh pain, respectively (p < 0.001); the trend being Group 3 > Group 2 > Group 1. Hip pain VAS followed a similar trend. At 4 weeks, Harris hip scores improved in Group 3 > Group 2 > Group 1. At 6 months, the trend was Group 2 > Group 3 > Group 1. Group 3 had better 30-s chair test results, pain-free walking distance, and longer cross-legged sitting time. Complication rate of 3.6%. 6.09% of patients underwent THA later. Sclerotic patch and marrow edema resolution early in Group 3, i.e., 46 and 31 days respectively, followed by Group 2 and Group 1. Conclusion: In Stages I and II AVN, biplanar core decompression (double) and intraosseous PRP injection is a promising salvage option; patients have better early hip scores (4 weeks), and early groin and thigh pain recovery. Patients treated early have better clinical and radiological recovery.

Efficacy of Autologous Adult Live-Cultured Osteoblast (AALCO) Implantation in Avascular Necrosis of the Femoral Head: A Mid-Term Outcome Analysis.

Introduction: Avascular Necrosis (AVN) of the femoral head, a condition characterized by the interruption of blood supply leading to bone tissue death, presents significant therapeutic challenges. Recent advancements in orthobiologics, including the use of Autologous Adult Live-Cultured Osteoblasts (AALCO), combined with core decompression, offer a novel approach for managing AVN. This study assesses the efficacy of this treatment modality in improving functional outcomes and hindering disease progression. Materials and methods: This retrospective observational study encompassed 30 patients treated between 2020 and 2023 for idiopathic AVN of the femoral head, grades I to III, who had not responded to conservative treatment. Patients were excluded based on specific criteria including age, secondary AVN causes, and certain health conditions. The treatment involved a two-stage surgical procedure under spinal anesthesia with OSSGROW® for AALCO generation. Post-operative care emphasized early mobilization, DVT prevention, and avoidance of NSAIDs. Outcome measures were evaluated using the Visual Analog Scale (VAS) for pain, modified Harris Hip Score, and annual MRI imaging for up to 36 months. Results: Among 26 patients (41 hips) completing the study, statistically significant improvements in pain and hip functionality were documented, alongside positive radiological signs of osteogenesis in the majority of cases. However, four instances required advancement to total hip replacement due to disease progression. Conclusion: The combination of core decompression and AALCO implantation shows promise as an effective treatment for AVN of the femoral head, with notable improvements in functional and radiological outcomes. This study supports the potential of orthobiologic approaches in AVN treatment, warranting further investigation through comprehensive randomized controlled trials.

No small dilemma: small bowel volvulus mimicking acute coronary syndrome.

Acute abdominal pathologies can cause electrocardiogram (ECG) changes mimicking an acute coronary syndrome (ACS), resulting in diagnostic uncertainty and delay. We report a 65-year-old male with multiple risk factors for ACS who presented with four hours of progressive epigastric and chest pain that resolved in the emergency department. ECG findings were concerning for new deeply inverted T-waves with normal troponins, raising concerns for Wellens Syndrome. Emergent heart catheterization was negative but abdominal computed tomography angiography showed occlusion of the superior mesenteric vessels. Subsequent exploratory laparotomy revealed a small bowel volvulus with extensive necrosis, resulting in a 430 cm resection.

Sequential bowel necrosis and large gastric ulcer in a patient with a ruptured femoral artery: A case report.

BACKGROUND: Severe bleeding as a result of a major vascular injury is a potentially fatal event commonly observed in the emergency department. Bowel necrosis and gastric ulcers secondary to ischemia are rare due to their rich blood supply. In this case, we present the case of a patient who was treated successfully following rupture of his femoral artery resulting in bowel necrosis and an unusually large gastric ulcer. CASE SUMMARY: A 28-year-old male patient sustained a knife stab wound to the right thigh, causing rupture of his femoral artery and leading to massive bleeding. He underwent cardiopulmonary resuscitation and received a large blood transfusion. Abdominal surgeries confirmed bowel necrosis, and jejunostomy was performed. The necrotic intestine was removed, the remaining intestine was anastomosed, and the right thigh was amputated. After three surgeries, the patient's overall condition gradually improved, and the patient was discharged from the hospital. However, one day after discharge, the patient was admitted again due to dizziness and melena, and a gastroduodenoscopy revealed a giant banded ulcer. After 2 weeks of treatment, the ulcer had decreased in size without bleeding. Six months after the last surgery, enterostomy and reintroduction surgery were completed. The patient was fitted with a right lower limb prosthesis one year after surgery. After 3 years of follow-up, the patient did not complain of discomfort. CONCLUSION: Trauma department physicians need to be aware of the possible serious complications involving the abdomen of trauma patients with massive bleeding.

Berberine HCl and diacerein loaded dual delivery transferosomes: Formulation and optimization using Box-Behnken design.

Introduction: Berberine is a poorly water-soluble alkaloid compound showing significant anti-inflammatory characteristics. It reduces the levels of pro-inflammatory and inflammatory cytokines, including tumour necrosis factor (TNF-α, IFN-γ) and interleukin (IL-23, IL-12, and IL-23). Diacerein significantly reduces the splenomegaly associated with psoriasis. It downregulates the production of TNF-α and IL-12. Method: This study reported the development of transferosomes containing berberine HCl and diacerein using a film hydration method followed by optimization using a Box-Behnken design. Sodium deoxycholate was used as an edge activator. The impact of independent variables (amount of phosphatidylcholine, amount of edge activator, and sonication cycles) on dependent variables (particle size and entrapment efficiency) was examined. The optimized formulation was characterized for polydispersity index, vesicle size, entrapment efficiency, ζ potential, spectral analysis like Fourier transform infrared, thermal analysis, X-ray diffraction, deformability, transmission electron microscopy, antioxidant assay, in-vitro release, and ex-vivo skin permeation studies. Results: The optimized formulation had a particle size of 110.90±2.8 nm with high entrapment efficiency (89.50±1.5 of berberine HCl and 91.23±1.8 of diacerein). Deformability, polydispersity index, ζ potential, and antioxidant activity of the optimized formulation were 2.44, 0.296, -13.3, and 38.36 %, respectively. Optimized transferosomes exhibited 82.093±0.81 % and 85.02±3.81 % release of berberine HCl and diacerein after 24 h of dissolution study. The transdermal flux of optimized formulation was 0.0224 µg cm-2 h-1 (2.24 cm h-1 permeation coefficient) and 0.0462 µg cm-2 h-1 (4.62 cm h-1 permeation coefficient), respectively, for berberine HCl and diacerein. Raman analysis of treated pig skin confirmed that the transferosomes can permeate the skin. No change in the skin condition or irritation was observed in BALB/c mice. Formulation stored at 4 and 25±2 °C / 60±5 % relative humidity was stable for 3 months. Conclusions: Thus, the results demonstrated successful optimization of the transferosomes for the efficient topical delivery of berberine HCl and diacerein in the effective management of psoriasis.

Low level of tumor necrosis factor α in tumor microenvironment maintains self-renewal of glioma stem cells by Vasorin-mediated glycolysis.

BACKGROUND: Self-renewal of glioma stem cells (GSCs) is responsible for glioblastoma (GBM) therapy-resistant and recurrence. Tumor necrosis factor α (TNFα) and TNF signaling pathway display an antitumor activity in preclinical models and in tumor patients. However, TNFα exhibits no significance for glioma clinical prognosis based on Glioma Genome Atlas database. This study aimed to explore whether TNFα of tumor microenvironment maintains self-renewal of GSCs and promotes worse prognosis in glioma patient. METHODS: Spatial transcriptomics, immunoblotting, sphere formation assay, extreme limiting dilution, and gene expression analysis were used to determine the role of TNFα on GSC's self-renewal. Mass spectrometry, RNA-sequencing detection, bioinformatic analyses, qRT-RNA, immunofluorescence, immunohistochemistry, single cell RNA sequencing, in vitro and in vivo models were used to uncover the mechanism of TNFα-induced GSC self-renewal. RESULTS: Low level of TNFα displays a promoting effect on GSC self-renewal and worse glioma prognosis. Mechanistically, Vasorin (VASN) mediated TNFα-induced self-renewal by potentiating glycolysis. Lactate produced by glycolysis inhibits the TNFα secretion of tumor-associated macrophages (TAMs) and maintains TNFα in a low level. CONCLUSIONS: TNFα-induced GSC self-renewal mediated by VASN provides a possible explanation for the failures of endogenous TNFα effect on GBM. Combination of targeting VASN and TNFα anti-tumor effect may be an effective approach for treating GBM.

Outcomes of cobalt-chrome 3D-printed total talus replacement with and without combined total ankle replacement.

BACKGROUND: Collapse of the talus and peri-talar arthritis pose treatment challenges due to the anatomy and location of the talus as a keystone of the foot and ankle. Custom 3D-printed total talus replacement (TTR) and combined total ankle total talus replacement (TATTR) have emerged as treatment options for these pathologies. However, the safety and efficacy of these implants is unknown due to the limited number of cases and short follow-up durations. METHODS: This was a retrospective study to assess surgical outcomes of patients who underwent a TTR and TATTR with or without subtalar fusion. Patient demographics, intraoperative parameters, device related surgical and non-surgical events, imaging and clinical evaluations, and patient reported outcome (PRO) measures were compiled. RESULTS: A total of 38 patients received a custom 3D-printed implant with mean follow-up time of 22.1 (range: 12-45) months. In this cohort, 7 (18.4 %) required secondary surgery and 3 (7.9 %) required implant removal. Multivariate logistic regression revealed that patient diagnosis of depression was a significant predictor of secondary surgery with an OR 17.50 (p = 0.037). Significant postoperative improvements were observed in the talocalcaneal height (p = 0.005) and talar declination angle (p = 0.013) for the TATTR group. VAS and PROMIS pain interference (PI) scores demonstrated an initial significant improvement in pain, but this improvement did not maintain significance at most recent follow-up. However, there was a significant increase in the PROMIS physical function (PF) scores (p = 0.037) at most recent follow-up. CONCLUSION: These results demonstrate that TTR and TATTR provide significant improvement in post-operative radiographic foot and ankle alignment and physical function at the two-year timepoint. PRO findings suggest that patients are more active after surgery. Surgeons considering proceeding with either of these procedures should counsel patients about pain and functional outcomes as well as realistic expectations in patients with depression. LEVEL OF EVIDENCE: Level 3.

Nano-emulsion based on Santolina chamaecyparissus essential oil potentiates the cytotoxic and apoptotic effects of Doxorubicin: an in vitro study.

AIM: This study was aimed at investigating the cytotoxic effect of a novel combination of doxorubicin (DOX) and nano-formulation of Santolina chamaecyparissus L. essential oil (SCEO-NANO) on hepatic (HepG2) and colon (HT29) cancer cell lines. METHODS: A nano-emulsion was prepared by high-pressure homogenisation, then analysed by zetasizer and Fourier transform infrared spectroscopy. HepG2 and HT29 cells were used in in vitro tests for apoptosis detection. RESULTS: Formulated droplet size increased in DOX@SCEO-NANO/DOX to 11.54 ± 0.02 with uniform distribution (PDI = 0.13 ± 0.01), when compared with SCEO-NANO (size: 8.91 ± 0.02 nm; PDI = 0.1 ± 0.02). In both cells, DOX@SCEO-NANO/DOX led to a considerable reduction in colony formation. Compared to DOX, apoprotein proteins were overexpressed in HepG2 cells, showing increases of 8.66-fold for caspase-3 and 4.24-fold for the Bax/Bcl-2 ratio. In HT29 cells, ROS-dependent necrosis and apoptosis were seen. Comparing DOX@SCEO-NANO/DOX versus DOX, greater levels of caspase-3 and the Bax/Bcl-2 ratio were observed. CONCLUSION: The DOX@SCEO-NANO/DOX formulation showed potential for targeted eradication of colon adenocarcinoma and hepatocellular carcinoma cells.

TNF reduces osteogenic cell fate in PDL cells at transcriptional and functional levels without alteration of periodontal proliferative capacity.

AIMS: To investigate the effect of tumor necrosis factor (TNF) on the growth of human periodontal ligament (PDL) cells, their osteogenic differentiation and modulation of their matrix secretion in vitro. METHODS: The influence of 10 ng/ml TNF on proliferation and metabolic activity of PDL cells was analyzed by cell counting (DAPI [4',6-diamidino-2-phenylindole] staining) and the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. In addition, cells were cultured under control conditions and osteogenic conditions (media containing 10 mM ß-glycerophosphate). Quantitative expression analysis of genes encoding the osteogenic markers alkaline phosphatase (ALP), collagen type I alpha 1 chain (COL1A1), osteoprotegerin (OPG), and osteopontin (OPN) was performed after 7 and 14 days of cultivation. Calcium deposits were stained with alizarin red. RESULTS: Our studies showed that 10 ng/ml TNF did not affect the survival and metabolic activity of PDL cells. Quantitative expression analysis revealed that long-term cultures with TNF impaired osteogenic cell fate at early and late developmental stages. Furthermore, TNF significantly reduced matrix secretion in PDL cells. CONCLUSION: The present data confirm TNF as a regulatory factor of proinflammatory remodeling that influences the differentiation behavior but not the metabolism and cell proliferation of the periodontium. Therefore, TNF represents an interesting target for the regulation of orthodontic remodeling processes in the periodontium.

Evaluating the incidence and risk factors for developing acute tubular necrosis after percutaneous coronary intervention in the management of coronary artery dissection.

BACKGROUND: Coronary artery dissection is managed primarily conservatively with serial imaging or percutaneous coronary intervention (PCI). Exposure to contrast in either modality could potentially result in acute tubular necrosis (ATN). However, no data compares ATN incidence in these management strategies. This study compares the incidence of ATN and associated mortality of PCI and conservative management of coronary artery dissection. METHODS: A retrospective analysis was performed using data from the National Inpatient Sample database, including patients with coronary artery dissection between 2016 through 2020. We analyzed the incidence of ATN and associated mortality of PCI and conservative management of coronary artery dissection. RESULTS: We found that the odds of developing ATN were 22% lower in patients managed with PCI than those managed conservatively. There was no difference in the in-hospital mortality or hospital length of stay between the two groups but the mortality rate in patients with ATN was double that of those who did not develop ATN in both PCI and conservatively managed groups. CONCLUSIONS: The higher incidents of ATN in patients with coronary dissection being managed with conservative measures compared to PCI suggest that the use of CTA may be harmful. Additionally, persons who developed ATN may have higher mortality. Therefore, more studies in the management of coronary artery dissection need to be done which would allow further steps to be taken to reduce this harm.

Orthodontic extrusion with fixed appliances for treatment of intrusive luxation injuries: A prospective study of 28 permanent maxillary incisors.

BACKGROUND: Limited evidence exists on the treatment options of tooth repositioning after intrusive luxation. AIM: The study aimed to investigate the outcomes and complications of orthodontic extrusion in treating intruded maxillary permanent incisors. DESIGN: A prospective study was conducted involving 28 intruded maxillary permanent incisors treated with orthodontic extrusion, compared with a retrospective control group of 29 teeth that underwent spontaneous re-eruption. The success rate of tooth repositioning, as well as pulp condition, periodontal healing, and root development were assessed and compared. RESULTS: The success rate of orthodontic extrusion was 96.4%, excluding one tooth that was ankylosed before treatment. There were no significant differences in pulp condition between the orthodontic extrusion and control groups for teeth with immature root development. Teeth with mature root development in the orthodontic group, however, showed a significantly higher rate of pulp necrosis (100%, p < .05). Periodontal healing outcomes were similar across both groups, regardless of the maturity of root development. The root length continued increasing during orthodontic extrusion treatment. CONCLUSIONS: Orthodontic extrusion treatment could effectively reposition moderately to severely intrusive permanent incisors, without increasing the risk of complications compared with spontaneous re-eruption.

Radiological follow-up of osteonecrosis lesions in children and adolescents with Hodgkin lymphoma.

Osteonecrosis (ON) is a common complication of glucocorticoid-based Hodgkin lymphoma (HL) treatment, but the natural evolution and prognosis of ON lesions remain poorly understood. We describe the radiological evolution of ON lesions identified in a Nordic population-based cohort of paediatric HL patients. Magnetic resonance images of suspected ON lesions were centrally reviewed to confirm ON diagnosis and grade the ON lesions according to the Niinimäki classification. The study included 202 ON lesions in 46 patients, of which 77 were joint lesions. Follow-up images were available for 146/202 lesions, with a mean follow-up time of 28 months. During follow-up, 71% of the lesions remained stable, 26% improved or resolved, and 3% progressed. A higher ON grade at diagnosis was associated with a lower likelihood of spontaneous resolution. The likelihood for resolution of ON decreased by 50% for each year of added patient age, when adjusted for sex, ON location, and symptoms. Hip ON showed less spontaneous improvement compared with other joints, and the risk for surgery was 13-fold in hip ON. Grades 3-4 joint ON has the potential to either progress or resolve, warranting follow-up in patients with severe symptoms. Research on secondary prevention should be directed at grade 3-4 joint ON.

Pregnancy and Infant Outcomes After Prenatal Exposure to Golimumab in Denmark, Finland, and Sweden 2006-2019.

PURPOSE: To present the main findings of a post-authorization safety study assessing pregnancy and infant outcomes after prenatal golimumab exposure in a real-world setting. METHODS: This observational population-based cohort study included data from pregnancies ending in 2006-2018 (Finland) or 2019 (Denmark, Sweden). Infants born to women with rheumatic diseases or ulcerative colitis diagnoses were identified. Based on prescription fills from 90 days prior to pregnancy until delivery, infants were assigned to one of the four drug-exposure cohorts: golimumab, other anti-TNF biologics, other biologics, and nonbiologic systemic therapy, and the general population. Prevalence of adverse pregnancy outcomes, mortality, diagnoses of major congenital anomalies (MCA), and inpatient infections in the infants' first year of life were assessed. Odds ratios and 95% CIs were calculated for MCA and infection. RESULTS: Among 134 infants in the golimumab cohort, none were stillborn or died in the first year of life. MCA were diagnosed in 4.5% of the infants in the golimumab cohort, versus 6.8%, 10.9%, 5.5%, and 4.6% in the other anti-TNF biologics, other biologics, nonbiologic systemic therapy and general population cohorts, respectively. Inpatient infections were diagnosed in 11% of golimumab-exposed infants, compared with 9%-11% of infants in the other cohorts. Unadjusted and selected adjusted comparisons showed no association between prenatal golimumab exposure and MCA or infection compared with the other exposure cohorts or general population. CONCLUSIONS: The number of infants with prenatal golimumab exposure was low, but results are reassuringly consistent with the evidence available for other anti-TNF biologics. Continued monitoring is needed.

Postoperative Intimal Hyperplasia: Review from My Research.

Postoperative intimal hyperplasia is the major cause of the vein graft occlusion. It is very important to establish an animal model for the start of research. After my vascular surgery residency in Japan, I started my research work on postoperative intimal hyperplasia at the University of Wisconsin-Madison. My research showed that endothelial injury and monocyte infiltration is the key for postoperative intimal hyperplasia, which is very similar to Ross' pathogenesis of atherosclerosis as an inflammatory disease. Focusing on postoperative intimal hyperplasia as an inflammatory disease, especially on tumor necrosis factor-α, FR-167653 (tumor necrosis factor-α suppressive agent, inhibitor of p 38 mitogen-activated protein kinase; Fujisawa Pharmaceutical Co., Ltd., Japan) is found to suppress postoperative intimal hyperplasia in a rat model by reducing serum monocyte chemoattractant protein-1 levels. However, FR-167653 is not commercially available today. Because endothelial injury is the first step of postoperative intimal hyperplasia, I investigated whether the free radical scavenger, edaravone (Radicut, Mitsubishi Tanabe Pharma Co., Japan), which alleviates the endothelial injury in vitro , can also suppress postoperative intimal hyperplasia. Moreover, the free radical scavenger edaravone (Radicut®, Mitsubishi Tanabe Pharma Co.) is also found to suppress postoperative intimal hyperplasia, by alleviating endothelial injury. In clinical settings, it is very important to detect postoperative intimal hyperplasia before its establishment. Hepatocyte growth factor is not only a hepatic growth factor but also a vascular endothelial growth factor. Recently, serum hepatocyte growth factor level was found to be a candidate biomarker for postoperative intimal hyperplasia in our rat model.

Cyclooxygenase-2 (COX-2)-dependent mechanisms mediate sleep responses to microbial and thermal stimuli.

Prostaglandins (PGs) play a crucial role in sleep regulation, yet the broader physiological context that leads to the activation of the prostaglandin-mediated sleep-promoting system remains elusive. In this study, we explored sleep-inducing mechanisms potentially involving PGs, including microbial, immune and thermal stimuli as well as homeostatic sleep responses induced by short-term sleep deprivation using cyclooxygenase-2 knockout (COX-2 KO) mice and their wild-type littermates (WT). Systemic administration of 0.4 µg lipopolysaccharide (LPS) induced increased non-rapid-eye movement sleep (NREMS) and fever in WT animals, these effects were completely absent in COX-2 KO mice. This finding underscores the essential role of COX-2-dependent prostaglandins in mediating sleep and febrile responses to LPS. In contrast, the sleep and fever responses induced by the pro-inflammatory cytokine tumor necrosis factor α, a proinflammatory cytokine which activates COX-2, were preserved in COX-2 KO animals, indicating that these effects are independent of COX-2-related signaling. Additionally, we examined the impact of ambient temperature on sleep. The sleep-promoting effects of moderate warm ambient temperature were suppressed in COX-2 KO animals, resulting in significantly reduced NREMS at ambient temperatures of 30 °C and 35 °C compared to WT mice. However, rapid-eye-movement sleep responses to moderately cold or warm temperatures did not differ between the two genotypes. Furthermore, 6 h of sleep deprivation induced rebound increases in sleep with no significant differences observed between COX-2 KO and WT mice. This suggests that while COX-2-derived prostaglandins are crucial for the somnogenic effects of increased ambient temperature, the homeostatic responses to sleep loss are COX-2-independent. Overall, the results highlight the critical role of COX-2-derived prostaglandins as mediators of the sleep-wake and thermoregulatory responses to various physiological challenges, including microbial, immune, and thermal stimuli. These findings emphasize the interconnected regulation of body temperature and sleep, with peripheral mechanisms emerging as key players in these integrative processes.

Comprehensive analysis of risk factors for flap necrosis in free flap reconstruction of postoperative tissue defects in oral and maxillofacial tumors.

Free flap reconstruction for postoperative tissue defects in oral and maxillofacial tumors is a critical component of reconstructive surgery. Identifying risk factors for flap necrosis is essential for improving surgical outcomes and patient quality of life. A retrospective study was conducted on patients who underwent free flap reconstruction between January 2020 and December 2023. Patients were included if they had comprehensive medical records and at least a six-month follow-up. We excluded those with a history of flap necrosis, uncontrolled systemic diseases, non-adherence to postoperative care, or concurrent malignancy treatments. Data on demographics, comorbidities, flap characteristics, and operative details were collected and analyzed using univariate analysis and logistic regression tests. Univariate analysis did not find a significant correlation between flap necrosis and factors such as hyperlipidemia, lymph node metastasis, or flap type. However, diabetes mellitus, oral infections, and albumin levels below 35 g/L were significantly associated with flap necrosis. Multivariate logistic regression showed diabetes mellitus increased the odds of flap necrosis by approximately ninefold, and oral infection increased it by over tenfold. Diabetes mellitus, oral infection, and low albumin levels are significant risk factors for flap necrosis in free flap reconstruction after oral and maxillofacial surgery. Prompt identification and management of these factors are crucial to mitigate the risk of flap necrosis.