Comparison of outcomes after total hip arthroplasty in hip fracture versus elective cases in patients over 60 years of age.

Background: Total hip arthroplasty (THA) allows for the replacement of impaired parts of the hip joint with artificial ones. This study aimed to compare the differences in preoperative patient profiles, postoperative complications, and clinical outcomes of two patient groups: those who underwent THA for fractures and those who underwent THA electively for diseases such as osteoarthritis (OA) and avascular necrosis (AVN). Methods: We retrospectively analyzed the data of patients who underwent THA between March 2012 and December 2021. Of 232 patients, 173 patients who met the exclusion and inclusion criteria were included. Patients were divided into two groups (Group 1: 113 patients diagnosed with OA or AVN; Group 2: 60 patients diagnosed with hip fracture). Pre- and postoperative Visual Analogue Scale (VAS), Koval scores, and postoperative modified Harris Hip Score (mHHS) were used to assess clinical outcomes. Demographic data and postoperative complications of the two groups were compared. After surgery, a rehabilitation protocol was initiated. Results: Patients in Group 2 (fracture) had more preoperative comorbidities than those in Group 1 (elective). Follow-up months are 26.22 ± 19.78 (Group 1), and 27.42 ± 17.02 (Group 2) respectively (P > 0.05). There were no statistical differences in the prevalence of postoperative complications between two groups (P > 0.05). Compared with Group 1(elective), Group 2(fracture) showed lower VAS (P < 0.01) at last follow-up, and no difference in Koval score (P = 0.77) and mHHS (P = 0.96) at last follow-up. Conclusion: Considering the characteristics of the two groups and their perioperative multidisciplinary care, THA for hip fractures can provide good clinical results compared to those with elective THA.

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.

APRIL/BAFF upregulation is associated with clonal B-cell expansion in Hunner-type interstitial cystitis.

Hunner-type interstitial cystitis (HIC) is a chronic inflammatory disease of the urinary bladder with an unknown etiology. We conducted comprehensive immunogenomic profiling of bladder specimens obtained by biopsy and cystectomy from 37 patients with HIC. Next-generation RNA sequencing demonstrated abundant plasma cell infiltration with frequent light chain restriction in HIC-affected bladder tissue. Subsequent analysis of the B-cell receptor repertoire revealed spatial and temporal expansion of B-cell clones. The extent of B-cell clonal expansion was significantly correlated with the gene expression levels of TNFSF13 and TNFSF13B, which encode APRIL and BAFF, respectively. These findings indicate that APRIL and BAFF are the key regulators of clonal B-cell expansion in HIC and might serve as therapeutic targets in this debilitating disease. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Optimal tactics for surgical revascularisation in diabetic angiopathy of the lower limbs.

OBJECTIVE: Aim: This study aims to compare the efficacy of conservative treatment methods versus advanced surgical interventions, including revascularising automyelotransplantation and stem cell therapy, in improving vascular patency and the quality of life in patients with diabetic angiopathy. PATIENTS AND METHODS: Materials and Methods: The research analyzed 68 patients with angiopathies under medical supervision from January 2007 to December 2017 at the National Scientific Center of Surgery named after A.N. Syzganov. Participants, aged 4 to 49, were divided into two groups based on angiographic blood flow characteristics: one with accelerated and another with delayed blood flow. A comprehensive participant selection process was implemented to ensure a representative sample. Sensitivity analysis was conducted to validate the findings' robustness. RESULTS: Results: The main group demonstrated notable success in limb salvage, with 90.9% avoiding high limb amputation post-revascularising automyelotransplantation. Moreover, 16.7% of patients experienced healing of trophic ulcers and toe necrosis. The use of stem cells from adipose tissue and fetal tissue progenitor cells showed promising results in reducing pain and increasing pain-free walking distance, alongside the formation of collateral vascular networks. CONCLUSION: Conclusions: The study concludes that advanced surgical interventions and stem cell therapies significantly enhance treatment outcomes in patients with diabetic angiopathy compared to conventional conservative treatments. These findings highlight the potential of personalized and innovative approaches in managing vascular complications associated with diabetes, offering new avenues for reducing disability and improving patient quality of life. Future research should focus on further refining these therapeutic strategies and exploring their integration into clinical practice.

Predictive Factors for the Development of Gallbladder Necrosis.

Introduction Acute cholecystitis is a common complication of gallstone disease. Likewise, gallbladder necrosis is a complication of cholecystitis associated with higher risks of morbidity and mortality. Identification of risk factors which portend to gallbladder necrosis is key in prioritizing the management of higher-risk patients. This study aimed to identify such factors that predict the development of gallbladder necrosis. Method A retrospective review of all patients undergoing emergency cholecystectomy in a tertiary hospital over a two-year period was performed. Gallbladder necrosis was diagnosed on histopathological examination of operative specimens. Multivariable logistic regression was performed to determine risk factors for gallbladder necrosis. Results A total of 163 patients underwent acute cholecystectomy and 43 (26%) had proven gallbladder necrosis. Multivariable analysis demonstrated that elevated white cell count (WCC) (OR 1.122, 95%CI 1.031-1.221, p=0.007), elevated C-reactive protein (CRP) (OR 1.004, 95%CI 1.001-1.008, p=0.022) and positive smoking status (OR 5.724, 95%CI 1.323-24.754, p=0.020) were independently predictive of gallbladder necrosis. Notably, advancing age, elevated BMI, diabetes mellitus or American Society of Anesthesiologists (ASA) grade were not found to be associated with developing necrosis. Conclusion Patients at risk of gallbladder necrosis include those with higher WCC, CRP, and active smokers. Given the increased potential complications, these risk factors should be identified early in the management of those admitted with gallstone disease to ensure such patients receive aggressive medical therapy alongside timely and guided surgical intervention.

Bronchial washing fluid sequencing is useful in the diagnosis of lung cancer with necrotic tumor.

BACKGROUND: Early-stage lung cancers detected by low-dose computed tomography (CT) often require confirmation through invasive procedures due to the absence of endobronchial lesions. This study assesses the diagnostic utility of bronchial washing fluid (BW) sequencing, a less invasive alternative, aiming to identify patient characteristics most suited for this approach. METHODS: From June 2017 to March 2018, we conducted a prospective cohort study by enrolling patients with incidental lung lesions suspected of early-stage lung cancer at two independent hospitals, and 114 were diagnosed with lung cancer while 50 were diagnosed with benign lesions. BW sequencing was performed using a targeted gene panel, and the clinical characteristics of patients detected with cancer through sequencing were identified. RESULTS: Malignant cells were detected in 33 patients (28.9 %) through BW cytology. By applying specificity-focused mutation criteria, BW sequencing classified 42 patients (36.8 %) as having cancer. Among the cancer patients who were BW sequencing positive and BW cytology negative, 15 patients (75.0 %) showed necrosis on CT. The sensitivity of BW sequencing was particularly enhanced in patients with necrotic tumors, reaching 75 %. CONCLUSIONS: BW sequencing presents a viable, non-invasive diagnostic option for early-stage lung cancer, especially valuable in patients with necrotic lesions. By potentially reducing the reliance on more invasive diagnostic procedures, this method could streamline clinical workflows, decrease patient burden, and improve overall diagnostic efficiency.

Analysis and functional validations of multiple cell death patterns for prognosis in prostate cancer.

Prostate cancer (PCa) has garnered significant attention due to its rising incidence, variable therapeutic outcomes, and the absence of reliable prognostic markers. The significance of different cell death patterns in tumor development underscores their potential as predictors of PCa prognosis. This study utilized The Cancer Genome Atlas (TCGA) datasets to evaluate the prognostic capabilities of 15 cell death patterns and established a Cell Death Index (CDI) signature based on necrosis and cuproptosis-related genes. The predictive efficacy of the CDI signature was validated in our PCa cohort and in two public datasets: Deutsches Krebsforschungszentrum (DKFZ) and Memorial Sloan-Kettering Cancer Center (MSKCC) PCa cohorts. Our comprehensive analysis examined the relationship between CDI signature and clinical characteristics, published prognostic signatures, gene mutations, immune cell infiltration, enrichment pathways, and drug sensitivity in PCa. In vitro and in vivo studies assessed the impact of EDA2R and LOXL2 on PCa progression. The CDI signature exhibited robust predictive performance across three independent validation sets, with 1-, 2-, 3-, 4-, and 5-year area under the curve (AUC) values in the TCGA cohort of 0.866, 0.77, 0.836, 0.776, and 0.787, respectively. Higher CDI scores were correlated with advanced T and N stages, elevated Gleason scores, increased immune cell infiltration, gene mutations, and drug sensitivity. EDA2R inhibited PCa cell proliferation and migration, related to tumor necrosis, while LOXL2 promoted these processes and was associated with cuproptosis. In summary, our study identified a novel CDI signature as an effective indicator for diagnosis, personalized treatment, and prognostic assessment in PCa.

Inhibition of CEACAM1 expression in cytokine-activated neutrophils using JAK inhibitors.

OBJECTIVES: Carcinoembryonic-antigen-related cell-adhesion molecule 1 (CEACAM1) is an adhesion molecule that acts as a coinhibitory receptor in the immune system. We previously demonstrated that CEACAM1 is predominantly expressed on peripheral blood neutrophils in patients with RA. The aim of the present study was to investigate the effects of Janus kinase inhibitors (JAKi) on cytokine-activated human neutrophils and CEACAM1 expression. METHODS: Peripheral blood neutrophils were obtained from healthy subjects. Isolated neutrophils were stimulated with tumor necrosis factor-alpha (TNF-α) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence or absence of JAKi. The expression of CEACAM1 in peripheral blood neutrophils was analyzed by flow cytometry. Protein phosphorylation of signal transducer and activator of transcription (STAT)1, STAT3, and STAT5 was assessed by western blot using phospho-specific antibodies. RESULTS: We found that TNF-α-induced CEACAM1 expression was marginally suppressed after pretreatment with pan-JAK inhibitor, tofacitinib. Moreover, TNF-α induced STAT1 and STAT3 phosphorylation at the late stimulation phase (4 to 16 h). The expressions of CEACAM1 on neutrophils were markedly up-regulated by GM-CSF not by interleukin (IL)-6 stimulation. All JAKi inhibited GM-CSF-induced CEACAM1 expressions on neutrophils, however, the inhibitory effects of baricitinib were larger compared to those of tofacitinib or filgotinib. Moreover, CEACAM1 was marginally upregulated in interferon (IFN)-γ stimulated neutrophils. Similarly, JAKi inhibited IFN-γ-induced CEACAM1 expressions on neutrophils. CONCLUSIONS: We demonstrated that JAKi prevent GM-CSF-induced CEACAM1 expression in neutrophils, and JAKi-induced inhibition depends on their selectivity against JAK isoforms. These findings suggest that JAKi can modulate the expression of CEACAM1 in cytokine-activated neutrophils, thereby limiting their activation.

Femoral head and acetabular necrosis combined with hip subluxation in people with HIV: a case report and literature review.

INTRODUCTION: HIV is widely prevalent in all regions of the world. The use of antiretroviral drugs has dramatically reduced the mortality rate of HIV-related diseases, but correspondingly increased the incidence of chronic complications in HIV-positive people. Related studies have found that the incidence of osteonecrosis of the femoral head is higher in HIV-positive people, but the co-occurrence of femoral head necrosis, acetabular necrosis and hip joint dislocation in HIV-positive patients is rare. METHODS: We report a 50-year-old man with a 15-month history of progressively worsening right hip pain with movement restriction. According to the CT findings of the other hospital, the patient was admitted to the hospital with femoral head necrosis. After the admission, the relevant X-ray, CT and MRI examinations showed that the right femoral head collapsed and deformed, with the surrounding bone sclerosis, bone fragments, loose body of the joint, right hip subluxation, acetabular marginal osteogeny, and local microcystic degeneration. The left femoral head was in good shape, and cystic degeneration can be seen under the articular surface. The patient was finally diagnosed with femoral head necrosis and acetabular necrosis combined with hip subluxation. RESULTS: The pain of the patient was significantly relieved after the operation, and the patient was discharged from the hospital one week after the start of treatment to continue rehabilitation training. During the follow-up one month after the operation, the self-reported pain disappeared completely, and the limitation of activity was significantly improved.

Serum tumor necrosis factor-alpha status in hospitalized patients with coronavirus disease-2019 (COVID-19).

Background: Tumor necrosis factor alpha (TNF-α) produces an inflammatory process and plays a critical role against infection and in the control of viral infection. The present study was conducted to determine the status of serum TNF-α in hospitalized patients with coronavirus disease-2019 (COVID-19). Methods: In this cross-sectional study the serum TNF-α level, sex, and age, were determined in patients with COVID-19. The association between variables was determined using the student t-test, analysis of variance (ANOVA) test, multiple logistic regression analysis, and the statistical package for the Social Sciences (SPSS)-18 (p < 0.05). Results: A total of 91 (women 41.75%, and men 58.24%) patients with a mean serum TNF-α level of 9.9 picograms per milliliter (pg/mL) were considered. In all (100%) patients, the TNF-α serum level was more than the normal limit (P=0.95). 95.60% of patients suffered severe COVID-19, with a TNF-a serum level of 10.20 pg/mL (P=0.87). Mean TNF-α serum levels in women and men were 11.37 pg/mL and 8.8 pg/mL, respectively (P= 0.17). In the age group of > 70 years (11.30 pg/mL), serum TNF-α concentration was higher than the other age groups (p>0.05). Conclusion: A significant proportion of women and men patients with COVID-19 in the middle and old age had a high concentration of serum TNF-α which may indicate the severity of the disease. Serum TNF-α level is different in women and men of different ages, so it can contribute to treatment strategies.

TNFα prevents FGF4-mediated rescue of astrocyte dysfunction and reactivity in human ALS models.

Astrocytes play a crucial role in the onset and progression of amyotrophic lateral sclerosis (ALS), a fatal disorder marked by the degeneration of motor neurons (MNs) in the central nervous system. Although astrocytes in ALS are known to be toxic to MNs, the pathological changes leading to their neurotoxic phenotype remain poorly understood. In this study, we generated human astrocytes from induced pluripotent stem cells (iPSCs) carrying the ALS-associated A4V mutation in superoxide dismutase 1 (SOD1) to examine early cellular pathways and network changes. Proteomic analysis revealed that ALS astrocytes are both dysfunctional and reactive compared to control astrocytes. We identified significant alterations in the levels of proteins linked to ALS pathology and the innate immune cGAS-STING pathway. Furthermore, we found that ALS astrocyte reactivity differs from that of control astrocytes treated with tumor necrosis factor alpha (TNFα), a key cytokine in inflammatory reactions. We then evaluated the potential of fibroblast growth factor (FGF) 2, 4, 16, and 18 to reverse ALS astrocyte phenotype. Among these, FGF4 successfully reversed ALS astrocyte dysfunction and reactivity in vitro. When delivered to the spinal cord of the SOD1G93A mouse model of ALS, FGF4 lowered astrocyte reactivity. However, this was not sufficient to protect MNs from cell death. Further analysis indicated that TNFα abrogated the reactivity reduction achieved by FGF4, suggesting that complete rescue of the ALS phenotype by FGF4 is hindered by ongoing complex neuroinflammatory processes in vivo. In summary, our data demonstrate that astrocytes generated from ALS iPSCs are inherently dysfunctional and exhibit an immune reactive phenotype. Effectively targeting astrocyte dysfunction and reactivity in vivo may help mitigate ALS and prevent MN death.

Management of Rarest Type of Talus Fracture: A Case Report.

This is a case of the rarest type of talus fracture in a 28-year-old male who presented with pain in his right ankle and foot following a road traffic accident. He was unable to bear weight or walk after the injury. Imaging studies indicated fractures in the head and neck of the talus, as well as the talar dome, with a fracture line extending into the subtalar joint. The patient underwent open reduction and internal fixation using mini fragment plating and Herbert screw fixation for the osteochondral fragment. Both the intraoperative and postoperative periods were without complications. The patient was placed in plaster of Paris (POP) slab immobilization for four weeks and was advised to avoid weight-bearing while using a walker for eight weeks, after which physiotherapy commenced. Follow-up assessments showed satisfactory fracture union, good range of motion in the ankle, an excellent American Orthopedic Foot and Ankle Society (AOFAS) score, an excellent 17-Italian Foot Function Index (FFI) score, and a good Hawkins score.

Purified Astragalus Polysaccharide Combined with Inactivated Vaccine Markedly Prevents Infectious Haematopoietic Necrosis Virus Infection in Rainbow Trout (Oncorhynchus mykiss).

Rainbow trout (Oncorhynchus mykiss) is experiencing a catastrophic pandemic. In recent years, infectious hematopoietic necrosis virus (IHNV) has spread nationwide, resulting in significant mortality. Currently, there are no available treatments or vaccines for IHNV in China. Here, the Astragalus extract was purified and characterized. Then, we developed an inactivated IHNV vaccine with purified Astragalus polysaccharide (P-APS) as an adjuvant. Safety assays showed that IHNV was successfully inactivated. After a serious IHNV challenge, the cumulative mortality rates were 76.0, 38.0, and 22.1% in control, vaccine, and P-APS + vaccine groups, respectively. P-APS + vaccine was effective at reducing head kidney damage and apoptosis after IHNV challenge by histopathological and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses. The P-APS + vaccine group showed better results in enhancing specific antibodies (IgM) and immune enzyme activities (C3, LZM, GOT, and GPT). RNA-seq revealed that many immune-related pathways were significantly enriched. TLR2, TLR7, C3, IFN-γ, IgM, MHC1, MHC2, MX1, and VIG1 were identified as core genes based on RNA-seq and PPI networks. Mechanistic investigations showed that P-APS + vaccine activates the immune pathway by upregulating the expression of these genes. P-ASP+vaccine induced effective innate and adaptive immune responses that were stronger than single vaccines after vaccination and IHNV challenged. Our findings will provide a promising vaccine candidate against IHNV.

Diagnosis and management of brain radiation necrosis.

Brain radiation necrosis (BRN) is a significant and complex side effect of stereotactic radiotherapy (SRT). Differentiating BRN from local tumor recurrence is critical, requiring advanced diagnostic techniques and a multidisciplinary approach. BRN typically manifests months to years post-treatment, presenting with radiological changes on MRI and may produce neurological symptoms. Key risk factors include the volume of irradiated brain tissue, the radiation dose, and prior radiotherapy history. This manuscript reviews the diagnostic process for BRN, emphasizing the importance of assessing baseline risk, clinical evaluation, and advanced imaging modalities. Multimodal imaging enhances diagnostic accuracy and aids in distinguishing BRN from tumor relapse. Therapeutic management varies based on symptoms. Asymptomatic BRN may be monitored with regular imaging, while symptomatic BRN often requires corticosteroids to reduce inflammation. Emerging therapies like bevacizumab have shown promise in clinical trials, with significant radiographic and symptomatic improvement. Surgical intervention may be necessary for histological confirmation and severe, treatment-resistant cases. Ongoing research aims to improve diagnostic accuracy and treatment efficacy, enhancing patient outcomes and quality of life. This review underscores the need for a multidisciplinary approach and continuous advancements to address the challenges posed by BRN in brain tumor patients.

Anti-inflammatory effects of proprotein convertase subtilisin/kexin 9 inhibitor therapy in the early phase of acute myocardial infarction.

This study examined the anti-inflammatory and endothelial function-enhancing effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor therapy in the early phase after acute myocardial infarction (AMI) by assessing changes in tumor necrosis factor-α (TNF-α) levels and the L-arginine/asymmetric-dimethylarginine (ADMA) ratio. This retrospective, single-center cohort study included patients who underwent successful timely primary percutaneous coronary intervention (PCI) for first-onset AMI between September 2017 and March 2018. The PCSK9 inhibitor group comprised patients who received 75 mg alirocumab up to 7 days after AMI, while the standard therapy group comprised patients who did not. We evaluated the change in TNF-α levels and the L-arginine/ADMA ratio at the time of hospital admission and prior to discharge. PCSK9 inhibitor therapy in the early phase after AMI suppressed TNF-α levels (standard therapy group, 1.64 ± 2.14 pg/mL vs. PCSK9 inhibitor group, 0.26 ± 0.33 pg/mL; p = 0.033) and increased the L-arginine/ADMA ratio (standard therapy group, - 13.0 ± 39.7 vs. PCSK9 inhibitor group, 23.2 ± 39.7; p = 0.042). Upon multiple regression analysis adjusted for sex, age, and peak creatine kinase levels, PCSK9 inhibitor therapy was associated with TNF-α suppression (p = 0.025; ß = - 0.235, 95% confidence interval [CI], - 0.436 to - 0.033). The L-arginine/ADMA ratio was also analyzed using multiple regression, adjusted for sex, age, peak creatine kinase levels, and smoking, showing a significant improvement in the ratio (p = 0.018; ß = 41.913, 95% CI, 10.337-73.491). Moreover, a weak negative correlation was suggested between the change in TNF-α levels and the change in L-arginine/ADMA ratio (r = - 0.393, p = 0.058). PCSK9 inhibitor therapy in the early phase after AMI suppresses TNF-α levels and improves the L-arginine/ADMA ratio, potentially indicating anti-inflammatory and endothelial function-enhancing effects.

Massive enteric necrosis caused by histiocytic sarcoma embolism: a case report.

BACKGROUND: Histiocytic sarcoma (HS) is a rare disease characterized by the presence of neoplastic histiocytes. We herein report an unusual case of HS that caused massive tumor embolism-related transmural necrosis of the small intestine. CASE PRESENTATION: A 64-year-old man presented with multiple nodules in the lungs, bone, mediastinum, and subcutaneous tissues that were incidentally detected on preoperative computed tomography for early transverse colon cancer. Approximately two months later, the patient presented with signs of peritoneal irritation suggestive of small intestinal necrosis. Emergency surgery was performed and the necrotic small intestine was resected. Pathological examination revealed small bowel necrosis due to multifocal HS embolism. The postoperative course was uneventful. The patient was unsuccessfully treated with chemotherapy for HS and died 122 days postoperatively. CONCLUSIONS: HS can cause massive enteric necrosis due to tumor embolism. Clinicians should be aware of this rare presentation of HS.

Incidence rate of recurrent cardiovascular events in patients with radiographic axial spondyloarthritis and the effect of tumor necrosis factor inhibitors.

BACKGROUND: Patients with radiographic axial spondyloarthritis (r-axSpA) are at increased risk of incident cardiovascular events. Tumor necrosis factor inhibitors (TNFi) have shown a protective effect against incident cardiovacular events. However, the incidence of recurrent cardiovascular events in patients with r-axSpA with a history of cardiovascular events, and the effect of TNFi on recurrent cardiovascular events remain unclear. We aimed to assess the incidence rate of recurrent cardiovascular events in patients with r-axSpA with a history of cardiovascular events and evaluate the effect of TNFi on the risk of recurrent cardiovascular events. METHODS: This nationwide cohort study used data from the Korean National Claims Database. Data of patients with r-axSpA who had a history of cardiovascular events after being diagnosed with r-axSpA were extracted from the database. The outcome of interest was the recurrence of cardiovascular events (myocardial infarction or stroke). Patients were followed from the index date (date of the first cardiovascular event) to the date of cardiovascular event recurrence, the last date with claims data, or December 31, 2021, whichever occured first. The incidence rate of recurrent cardiovascular events was calculated. An inverse probability weighted Cox model was used to assess the effect of TNFi exposure on the risk of recurrent cardiovascular events. RESULTS: This study included 413 patients (TNFi non-exposure, n = 338; TNFi exposure, n = 75). The incidence rate of recurrent cardiovascular events was 32 (95% confidence interval [CI] 22-42) per 1,000 person-years (TNFi non-exposure, 36 [95% CI 24-48] per 1,000 person-years; TNFi exposure, 19 [95% CI 2-35] per 1,000 person-years). In the inverse probability weighted Cox model, TNFi exposure was significantly associated with a lower risk of recurrent cardiovascular events (hazard ratio 0.33, 95% CI 0.12-0.94). CONCLUSIONS: The incidence rate of recurrent cardiovascular events in patients with r-axSpA is substantial. TNFi exposure was associated with a lower risk of recurrent cardiovascular events.

Evaluation of a DNA vaccine with self-designed CpG sequences against J genotype IHNV infection in rainbow trout (Oncorhynchus mykiss).

Rainbow trout suffer from infectious hematopoietic necrosis virus (IHNV) outbreaks, which lead to massive mortality and huge economic loss worldwide. The approved commercial vaccine is used for the prevention of IHN in Canada. Given that Chinese domestic J-genotype isolates are different from North American IHNV isolates, the development of an effective DNA vaccine against Chinese J-genotype isolates is urgent. In this study, we developed a DNA vaccine encoding glycoprotein based on our previously isolated IHNV GS21 strain and self-designed CpG sequences were supplemented as molecular adjuvants. The vaccinated rainbow trout were significantly protected against IHNV with approximately a relative percent survival (RPS) of 94.74% compared to the unvaccinated group. Moreover, the specific antibody of IgM and neutralizing antibody (NAb) was significantly provoked after the vaccination. Particularly, the antiviral immune response was rapidly evoked in the early stage of vaccination including the up-regulation of Mx-1, IFN-Ⅰ, and IFN-γ. The IHNV load in vaccinated fish was apparently lower than that in the unvaccinated group. Furthermore, the integration of exogenous genes into the host chromosome and the spread of antimicrobial-resistant genes were not found. These results suggested that our vaccine enhances robust immune responses and evokes considerable protection against IHNV with limited genetically modified risk, which is an effective and promising vaccine candidate for further prevention of IHNV outbreaks.

Serum TNFα and IL-17A levels may predict increased depressive symptoms: findings from the Shika Study cohort project in Japan.

BACKGROUND: Low-grade systemic inflammation may be a key player in the immune activation that has been reported for mental health deterioration. We hypothesised that elevated serum levels of inflammatory cytokines increase neuroinflammation and exacerbate depressive symptoms. METHODS: The participants were part of a cohort study for whom data was available for both 2015 and 2019. In 2015, blood samples were collected from 232 participants. Their depressive symptoms were assessed both 2015 and 2019 using the Centre for Epidemiologic Studies Depression Scale (CES-D) (n = 33). The multiplex immunoassay system (Luminex® 200) was used to measure the serum concentrations of IL-6, IL-10, IL-12, IL-17A and TNFα. Data were analysed using linear models with the level of significance considered to be p < 0.05. RESULTS: After controlling for age, BMI, smoking and alcohol consumption, in 2015 the serum concentrations of IL-17A and TNFα in 2015 were significantly positively associated with the CES-D scores of women (standardised ß (B) = .027, p < 0.01 and B = 0.26, p < 0.01, respectively). The serum concentrations of IL-17A and TNFα of men were significantly positively associated with the CES-D scores of 2019 (B = 0.62, p = 0.02 and B = 0.59, p = 0.02, respectively). CONCLUSIONS: In this cross-sectional study, we found a significant positive correlation between the depressive symptoms and serum TNFα and IL-17A levels of women. In addition, our longitudinal findings suggest the possibility that TNFα and IL-17A could elevate the depressive symptoms of men.

Fatal outcome of postpolypectomy syndrome: A case report.

Postpolypectomy syndrome (PPS), also known as postpolypectomy coagulation syndrome or transmural burn syndrome, is a rare complication following colonic polypectomy characterized by abdominal pain, fever, and leukocytosis. Herein, we present a case of a patient in his 70s who developed abdominal pain and fever after a polypectomy. He was diagnosed with PPS, which rapidly progressed to septic shock necessitating left hemicolectomy. Pathological findings confirmed intestinal necrosis and severe electrocoagulation injury. Despite surgical intervention, the patient succum to multiple complications. While usually mild, approximately 0.07% of PPS cases require hospitalization due to localized peritonitis from electrocautery. Conservative management is effective, though severe complications are rare. Despite its generally favorable prognosis, our case highlights rapid progression to fatal septic shock postsurgery. Recognition of PPS is crucial, particularly in patients with abdominal pain postpolypectomy, as it can lead to life-threatening outcomes.