Association of MRI-based knee osteoarthritis structural phenotypes with short-term structural progression and subsequent total knee replacement.

BACKGROUND: The failure of disease-modifying osteoarthritis drugs (DMOADs) trials lies mainly in the heterogeneity of the disease, which calls for a more precise population with specific progression and outcomes. This study aimed to determine whether and which MRI-based structural phenotype of knee osteoarthritis (KOA) is associated with short-term structural progression and subsequent total knee replacement (TKR). METHODS: A longitudinal study was conducted among participants with baseline Kellgren-Lawrence grade (KLG) ≥ 2 from the Osteoarthritis Initiative (OAI). The structural phenotypes at baseline were defined as subchondral bone, meniscus/cartilage and inflammatory phenotypes according to the MRI Osteoarthritis Knee Score (MOAKS). The primary outcome was the progression of structural abnormalities within 24 months and multivariable logistic regressions were applied to evaluate the associations. The secondary outcome was the incidence of TKR during 108 months. Cox regressions and Kaplan-Meier survival curves were used for the analysis. RESULTS: A total of 733 participants with KOA were finally included in our study, with 493 (67.3%) having the three main structural phenotypes. For the primary outcome, the subchondral bone phenotype (OR [95% CI]:1.71 [1.02, 2.83], 1.52 [1.06, 2.18], 1.65 [1.11, 2.42], respectively) and the inflammatory phenotype (OR [95% CI]: 1.69 [1.05, 2.74], 1.82 [1.31, 2.52], 2.15 [1.48, 3.14], respectively) were both associated with the short-term progression of joint space narrowing, osteophytes and sclerosis in 24 months, whereas the meniscus/cartilage phenotype was only associated with the progression of osteophytes and sclerosis. For the secondary outcome, the subchondral bone phenotype (HR [95% CI]: 1.71 [1.06-2.78]) and inflammatory phenotype (HR [95%CI]: 2.00 [1.02-2.67]) were associated with shorter time to subsequent TKR, but not the meniscus/cartilage phenotype. Besides, the cumulative effect when the structural phenotype overlapped was confirmed in both outcomes. CONCLUSIONS: The subchondral bone phenotype and inflammatory phenotype were associated with the progression of joint space narrowing, osteophytes and sclerosis in 24 months, along with subsequent TKR in 108 months. Besides, additive effects of overlapped phenotypes were further determined. These phenotypes could serve as valuable screening tools for future clinical trials and provide guidance for risk evaluation.

COVID-19 and sepsis-related excess mortality in the US during the first three years: A national-wide time series study.

The COVID-19 pandemic's global impact has been devastating, causing millions of deaths. Our study investigates excess sepsis-related mortality trends over three years during the pandemic. Using CDC's National Vital Statistics System data from January 2018 to March 2023, we projected sepsis-related deaths during the pandemic using a Poisson log-linear regression model. We compared observed versus predicted deaths and analyzed temporal trends by demographics and regions. Among the 753,160 deaths documented between March 2020 and March 2023, a significant downward trend was noted in sepsis-related mortality rates from March 2022 to March 2023, coinciding with the surge of the Omicron variant. The excess mortality rates were 170.6 per million persons (95% CI: 168.2-172.6), 167.5 per million persons (95% CI: 163.6-170.9), and 73.3 per million persons (95% CI: 69.4-76.6) in the first, second, and third years, respectively. Increased sepsis-related mortality was observed across all age subgroups, with the greatest increase noted in those aged 85 years and above compared to middle- and young-aged decedents. Disparities were also observed across racial/ethnic, sex/gender subgroups, and geographic regions. This study highlights the effectiveness of current policies and prevention measures in response to the long-term circulating of SARS-CoV-2 in the community.

Causal relationship between Brugada syndrome and electrocardiogram traits: A bidirectional Mendelian randomization study.

INTRODUCTION: Observational studies have suggested associations between Brugada syndrome (BrS) and electrocardiograms traits. Nonetheless, the causal relationships remains uncertain in observational studies. This study aims to investigate the causal relationships between BrS phenotypic risk and electrocardiogram traits using Mendelian randomization (MR) analysis and colocalization analysis. METHODS: MR analysis was performed to investigate the causal relationships between BrS phenotype risk and electrocardiogram traits (P wave duration, PR interval, QRS wave duration, ST segment duration, T wave duration, QT interval, heart rate (HR) and heart rate variability). The genetic instruments for BrS (number of cases = 12,821) were obtained from the latest GWAS. GWAS summary data of electrocardiogram traits were obtained from the MRC-IEU and GWAS catalog databases. The causal relationships were obtained through MR methods, and sensitivity analyses (e.g. Cochran's Q test, MR-PRESSO). Furthermore, the causal relationships were evaluated whether they were driven by one linkage disequilibrium using colocalization analysis. RESULTS: We found that there are positive causal relationships between BrS phenotypic risk and P wave duration, PR interval, QRS wave duration and QT interval, respectively (IVWP: ß = 1.238, 95 % CI = 0.857-1.619, P<0.001; IVWPR: ß = 2.199, 95 % CI = 1.358-3.039, P<0.001; IVWQRS: ß = 0.157, 95 % CI = 0.115-0.198, P<0.001; IVWQT: ß = 0.593, 95 % CI = 0.391-0.796, P<0.001), and there is a negative causal relationship between BrS phenotypic risk and heart rate (IVWHR: ß = -0.023, 95 % CI = -0.03 âˆ¼ -0.015, P<0.001). Additionally, there are bidirectional causal relationships between BrS phenotypic risk and P wave duration and PR interval, respectively (IVWP: OR = 1.217, 95 % CI = 1.118-1.325, P<0.001; IVWPR: OR = 1.02, 95 % CI = 1.008-1.032, P = 0.001). Furthermore, colocalization analysis identified that the causal relationships between BrS phenotype risk and P wave duration, PR interval and QRS wave duration were driven by rs6790396, rs6801957 and rs6801957, respectively. CONCLUSIONS: Bidirectional causal relationships were identified between BrS phenotypic risk and P wave duration and PR interval, respectively. There were positive causal relationships between BrS phenotypic risk and QRS wave duration and QT interval, respectively, and there is a negative causal relationship between BrS phenotypic risk and heart rate.

Effects of radial extracorporeal shock wave therapy on flexor spasticity of the upper limb in post-stroke patients: A randomized controlled trial.

OBJECTIVE: This study aimed to assess the efficacy of radial extracorporeal shock wave therapy in treating upper limb spasticity after a stroke. DESIGN: Randomized controlled trial. SETTING: Zhujiang Hospital of Southern Medical University. SUBJECTS: This study included 95 people with stroke. INTERVENTION: The active (n = 47) and sham-placebo (n = 48) radial extracorporeal shockwave therapy groups received three treatment sessions (every third day). MAIN MEASURES: The Modified Ashworth Scale, Hmax/Mmax ratio, root mean square, co-contraction ratio, mechanical parameters of the muscle and temperature were measured at baseline and days 2, 5 and 8. RESULTS: Among the 135 potential participants screened, 100 were enrolled and allocated randomly, with 95 participants ultimately being included in the intent-to-treat analysis dataset. The active group showed significantly better improvements in upper limb spasticity and muscle function than did the sham-placebo group. Greater improvements in the Modified Ashworth Scale were observed in the active group than in the sham-placebo group (difference, -0.45; 95% CI, -0.69 to -0.22; P < 0.001). Moreover, significant differences in root mean square, co-contraction ratio and Hmax/Mmax ratio were observed between the two groups (all P < 0.001). The mechanical parameters of the biceps muscle were significantly better in the active group than in the sham-placebo group (P < 0.001). The active group had a higher temperature than the sham-placebo group, although the difference was not significant (P = 0.070). CONCLUSIONS: This study revealed that the treatment with extracorporeal shockwave therapy can relieve upper limb spasticity in people with stroke.

Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis.

Objective: This study aimed to evaluate the efficacy and safety of solid organ transplantation recipients inoculated with an inactivated COVID-19 vaccine. Methods: We retrospectively analyzed the antibody levels and related adverse events of non-transplantation subjects and solid organ transplant recipients, both pre-transplantation (individuals awaiting organ transplantation) and post-transplantation (individuals who have undergone organ transplantation), who received inactivated COVID-19 vaccines from February 2021 to July 2022. Results: The study included 38 pre-transplantation vaccination group, 129 post-transplantation vaccination group, and 246 non-transplantation group. The antibody titer was assessed monthly within the period of 1-12 months after the last injection. The antibody-positive rate among the three groups were 36.84, 20.30, 61.17% (P < 0.05). The antibody-positive rates among three groups with one, two doses vaccine were not significantly different (P > 0.05), but were significantly different after three doses (P < 0.05). The antibody titers among three groups were significantly different after two doses (P < 0.05). Adverse reactions occurred in six transplant recipients, which were relieved after treatment, and not in the non-transplantation subjects. Conclusion: Inactivated COVID-19 vaccine is safe and effective for solid organ transplantation recipients, at least two doses of which should be completed before organ transplant surgery.

Integrating Radiomics and Neural Networks for Knee Osteoarthritis Incidence Prediction.

OBJECTIVE: Accurately predicting knee osteoarthritis (KOA) is essential for early detection and personalized treatment. We aimed to develop and test a magnetic resonance imaging (MRI)-based joint space (JS) radiomic model (RM) to predict radiographic KOA incidence through neural networks by integrating meniscus and femorotibial cartilage radiomic features. METHODS: In the Osteoarthritis Initiative cohort, participants with knees without radiographic KOA at baseline but at high risk for radiographic KOA were included. Patients' knees developed radiographic KOA, whereas control knees did not over four years. We randomly split the participants into development and test cohorts (8:2) and extracted features from baseline three-dimensional double-echo steady-state sequence MRI. Model performance was evaluated using an area under the receiver operating characteristic curve (AUC), sensitivity, and specificity in both cohorts. Nine resident surgeons performed the reader experiment without/with the JS-RM aid. RESULTS: Our study included 549 knees in the development cohort (275 knees of patients with KOA vs 274 knees of controls) and 137 knees in the test cohort (68 knees of patients with KOA vs 69 knees of controls). In the test cohort, JS-RM had a favorable accuracy for predicting the radiographic KOA incidence with an AUC of 0.931 (95% confidence interval [CI] 0.876-0.963), a sensitivity of 84.4% (95% CI 83.9%-84.9%), and a specificity of 85.6% (95% CI 85.2%-86.0%). The mean specificity and sensitivity of resident surgeons through MRI reading in predicting radiographic KOA incidence were increased from 0.474 (95% CI 0.333-0.614) and 0.586 (95% CI 0.429-0.743) without the assistance of JS-RM to 0.874 (95% CI 0.847-0.901) and 0.812 (95% CI 0.742-0.881) with JS-RM assistance, respectively (P < 0.001). CONCLUSION: JS-RM integrating the features of the meniscus and cartilage showed improved predictive values in radiographic KOA incidence.

The impact of ankle-foot orthoses on mobility of dual-task walking in stroke patients? A cross-sectional two-factor factorial design clinical trial.

ABSTRACTTo assess the impact of ankle-foot orthoses (AFOs) on mobility and gait during dual-task walking in post-stroke survivors. In this cross-sectional, factorial design trial, stroke survivors performed four randomized tasks: (1) dual-task walking with AFOs, (2) single-task walking with AFOs, (3) dual-task walking without AFOs, and (4) single-task walking without AFOs. Primary outcome was the Timed Up and Go (TUG) test, with secondary outcomes including gait metrics, Tinetti scores, and auditory N-back tests. In the results, 48 subjects (38 males and 10 females; 19-65 years) completed the trial. Patients had a greater TUG score with AFOs compared with non-AFOs conditions (95% CI: 7.22-14.41, P < 0.001) in single-task and dual-task conditions. Secondary outcomes showed marked enhancement with AFOs during dual-task walking, with significant interaction effects in gait metrics, balance, and cognitive function (P < 0.05). Although not statistically significant, dual-task effects of TUG and walking speed were more pronounced during dual-task walking. In conclusion, AFOs enhance mobility and gait during both single and dual-task walking in post-stroke survivors.

Electro-acupuncture for central obesity: a patient-assessor blinded, randomized sham-controlled clinical trial.

BACKGROUND: Central obesity is considered as a significant health threat to individuals. Scientific research has demonstrated that intra-abdominal fat accumulation is associated with higher metabolic and cardiovascular disease risks independent of Body Mass Index (BMI). This study aimed to evaluate the efficacy and safety of electro-acupuncture in treating central obesity compared with sham acupuncture. METHOD: This was a patient-assessor blinded, randomized, sham-controlled clinical trial. One hundred sixty eight participants aged between 18 and 65 years old with BMI ≥ 25 kg/m2 and waist circumference (WC) of men ≥ 90 cm / women ≥ 80 cm were enrolled and allocated to the acupuncture or sham acupuncture group equally. For the acupuncture group, disposable acupuncture needles were inserted into eight body acupoints, including Tianshu (ST-25), Daheng (SP-15), Daimai (GB-26), Qihai (CV-6), Zhongwan (CV-12), Zusanli (ST-36), Fenglong (ST-40), and Sanyinjiao (SP-6) with electrical stimulation. For the control group, Streitberger's non-invasive acupuncture needles were utilized at the same acupoints with identical stimulation modalities. The treatment duration was 8 weeks with 2 sessions per week and the follow-up period was 8 weeks. The primary outcome was the change in WC before and after the treatment. The secondary outcomes were the changes in hip circumference, waist-to-hip circumference ratio, BMI, and body fat percentage during the treatment and follow-up period. RESULTS: The acupuncture group displayed a significant change in WC compared to the sham group both treatment and follow-up period (MD = -1.1 cm, 95% CI = -2.8 to 4.1). Significant change in body fat percentage was recorded for both groups after treatment but no significance was observed during the follow-up period (MD = -0.1%, 95% CI = -1.9 to 2.2). The changes in hip circumference were also significant both treatment and follow-up period for the acupuncture group (MD = -2.0 cm, 95% CI = -3.7 to -1.7). Compared with sham acupuncture, the body weight (MD = -1 kg, 95% CI = -3.3 to 5.3), BMI (MD = -0.5, 95% CI = -0.7 to 1.9) also decreased significantly within and between groups. The incidence of adverse events was similar in the two groups. CONCLUSION: This study provided evidence that electro-acupuncture could be effective in treating central obesity by reducing WC, hip circumference, body weight, BMI, and waist-to-hip circumference ratio. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03815253, Registered 24 Jan 2019.

The association between anterior cruciate ligament degeneration and incident knee osteoarthritis: Data from the osteoarthritis initiative.

Background: Though anterior cruciate ligament (ACL) tear has been widely accepted as an important accelerator for knee osteoarthritis (KOA), the role of intrinsic ACL degeneration in developing KOA has not been fully investigated. Purpose: To determine whether ACL degeneration, in the absence of ACL tear, is associated with incident KOA over 4 years. Study design: Cohort study; Level of evidence, 2. Methods: Participants' knees in this nested case-control study were selected from the Osteoarthritis Initiative (OAI) study, with Kellgren-Lawrence grading (Kellgren-Lawrence grading) of 0 or 1 â€‹at baseline (BL). Case knees which had incident KOA (KLG ≥2) over 4 years, were matched 1:1 with control knees by gender, age and radiographic status. ACL signal intensity alteration (0-3 scale) and volume were assessed as compositional feature and morphology of ACL degeneration, using knee MRI at P0 (time of onset of incident KOA), P-1 (1 year prior to P0) and baseline. Conditional logistic regression was applied to analyze the association between measures of ACL degeneration and incident KOA. Results: 337 case knees with incident KOA were matched to 337 control knees. Participants were mostly female (68.5%), with an average age of 59.9 years old. ACL signal intensity alterations at BL, P-1 and P0 were significantly associated with an increased odds of incident KOA respectively (all P for trend ≤0.001). In contrast, ACL volumes were not significantly associated with incident KOA at any time points. Conclusions: ACL signal intensity alteration is associated with increased incident KOA over 4 years, whereas ACL volume is not.The translational potential of this article: This paper focused on ACL signal intensity alteration which could better reflect ACL degeneration rather than ACL tear during the progression of KOA and explored this topic in a nested case-control study. Utilizing MR images from KOA participants, we extracted the imaging features of ACL. In addition, we established a semi-quantitative score for ACL signal intensity alteration and found a significant correlation between it and KOA incidence. Our findings confirmed that the more severe the ACL signal intensity alteration, the stronger relationship with the occurrence of KOA. This suggests that more emphasis should be placed on ACL degeneration rather than ACL integrity in the future.

Osteoporosis and osteoarthritis: a bi-directional Mendelian randomization study.

OBJECTIVE: To investigate the causal relationship between low bone mineral density (BMD) and osteoarthritis (OA) using Mendelian randomization (MR) design. METHODS: Two-sample bi-directional MR analyses were performed using summary-level information on OA traits from UK Biobank and arcOGEN. Sensitivity analyses including MR-Egger, simple median, weighted median, MR pleiotropy residual sum, and outlier approaches were utilized in conjunction with inverse variance weighting (IVW). Gene ontology (GO) enrichment analyses and expression quantitative trait locus (eQTL) colocalization analyses were used to investigate the potential mechanism and shared genes between osteoporosis (OP) and OA. RESULTS: The IVW method revealed that genetically predicted low femoral neck BMD was significantly linked with hip (ß = 0.105, 95% CI: 0.023-0.188) and knee OA (ß = 0.117, 95% CI: 0.049-0.184), but not with other site-specific OA. Genetically predicted low lumber spine BMD was significantly associated with OA at any sites (ß = 0.048, 95% CI: 0.011-0.085), knee OA (ß = 0.101, 95% CI: 0.045-0.156), and hip OA (ß = 0.150, 95% CI: 0.077-0.224). Only hip OA was significantly linked with genetically predicted reduced total bone BMD (ß = 0.092, 95% CI: 0.010-0.174). In the reverse MR analyses, no evidence for a causal effect of OA on BMD was found. GO enrichment analysis and eQTL analysis illustrated that DDN and SMAD-3 were the most prominent co-located genes. CONCLUSIONS: These findings suggested that OP may be causally linked to an increased risk of OA, indicating that measures to raise BMD may be effective in preventing OA. More research is required to determine the underlying processes via which OP causes OA.

Use of patient-derived tumor organoid platform to predict the benefit of postoperative adjuvant chemotherapy for poor responders to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Postoperative adjuvant chemotherapy (AC) for poor responders to neoadjuvant chemoradiotherapy (nCRT) remains debatable among patients with locally advanced rectal cancer (LARC), necessitating biomarkers to accurately predict the benefits of AC. This study aimed to develop a patient-derived tumor organoid (PDTO) platform to predict the benefit of AC in LARC patients showing poor nCRT response. PDTOs were established using irradiated rectal cancer specimens with poor nCRT responses, and their sensitivity to chemotherapy regimens was tested. The half-maximal inhibitory concentration (IC50) value for the PDTO drug test was defined based on the clinical outcomes, and the accuracy of the PDTO prognostic predictions was calculated. Predictive models were developed and validated using the PDTO drug test results. Between October 2018 and December 2021, 86 PDTOs were successfully constructed from 138 specimens (success rate 62.3%). The optimal IC50 cut-off value for the organoid drug test was 39.31 µmol/L, with a sensitivity of 84.75%, a specificity of 85.19%, and an accuracy of 84.88%. Multivariate Cox regression analysis revealed that the PDTO drug test was an independent predictor of prognosis. A nomogram based on the PDTO drug test was developed, showing good prognostic ability in predicting the 2-year and 3-year disease-free survivals (AUC of 0.826 [95% CI, 0.721-0.931] and 0.902 [95% CI, 0.823-0.982], respectively) and overall survivals (AUC of 0.859 [95% CI, 0.745-0.973] and 0.885 [95% CI, 0.792-0.978], respectively). The PDTO drug test can predict the benefit of postoperative AC in poor responders with LARC to nCRT.

Effects of machine perfusion strategies on different donor types in liver transplantation: a systematic review and meta-analysis.

BACKGROUND: The increasing use of extended criteria donors (ECD) sets higher requirements for graft preservation. Machine perfusion (MP) improves orthotopic liver transplantation (OLT) outcomes, but its effects on different donor types remains unclear. The authors' aim was to assess the effects of hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), or normothermic regional perfusion (NRP) versus static cold storage (SCS) on different donor types. MATERIALS AND METHODS: A literature search comparing the efficacy of MP versus SCS in PubMed, Cochrane, and EMBASE database was conducted. A meta-analysis was performed to obtain pooled effects of MP on ECD, donation after circulatory death (DCD), and donor after brainstem death. RESULTS: Thirty nine studies were included (nine randomized controlled trials and 30 cohort studies). Compared with SCS, HMP significantly reduced the risk of non-anastomotic biliary stricture (NAS) [odds ratio (OR) 0.43, 95% confidence interval (CI) 0.26-0.72], major complications (OR 0.55, 95% CI 0.39-0.78), and early allograft dysfunction (EAD) (OR 0.46, 95% CI 0.32-0.65) and improved 1-year graft survival (OR 2.36, 95% CI 1.55-3.62) in ECD-OLT. HMP also reduced primary non-function (PNF) (OR 0.40, 95% CI 0.18-0.92) and acute rejection (OR 0.62, 95% CI 0.40-0.97). NMP only reduced major complications in ECD-OLT (OR 0.56, 95% CI 0.34-0.94), without favorable effects on other complications and survival. NRP lowered the overall risk of NAS (OR 0.27, 95% CI 0.11-0.68), PNF (OR 0.43, 95% CI 0.22-0.85), and EAD (OR 0.58, 95% CI 0.42-0.80) and meanwhile improved 1-year graft survival (OR 2.40, 95% CI 1.65-3.49) in control DCD-OLT. CONCLUSIONS: HMP might currently be considered for marginal livers as it comprehensively improves ECD-OLT outcomes. NMP assists some outcomes in ECD-OLT, but more evidence regarding NMP-ECD is warranted. NRP significantly improves DCD-OLT outcomes and is recommended where longer non-touch periods exist.

A continuous age-specific standardized mortality ratio for estimating the unascertained rates in the early epidemic of COVID-19 in different regions.

The difference in age structure and aging population level was an important factor that caused the difference in COVID-19's case fatality rate (CFR) in various regions. To eliminate the age effect on estimating the CFR of COVID-19, our study applied nonlinear logistic model and maximum likelihood method to fit the age-fatality curves of COVID-19 in different countries and regions. We further computed the standardized mortality ratio from the age-fatality curves of COVID-19 in the above regions and found that the risk of COVID-19 death in Wuhan was of a moderate level, while the non-Hubei region was even lower, compared with other regions. Regarding the disparity of CFRs among different regions in the country, we believed that there might be an unascertained phenomenon in high-endemic regions. Based on age-fatality rate curves, we estimated unascertained rates in cities with severe epidemics such as Wuhan and New York, and it was found that the total unascertained rates in Wuhan and New York were 81.6% and 81.2%, respectively. Meanwhile, we also found that the unascertained rates varied greatly with age.

Evaluating the causal effect of circulating proteome on the risk of osteoarthritis-related traits.

OBJECTIVES: This study aims to identify circulating proteins that are causally associated with osteoarthritis (OA)-related traits through Mendelian randomisation (MR)-based analytical framework. METHODS: Large-scale two-sample MR was employed to estimate the effects of thousands of plasma proteins on 12 OA-related traits. Additional analyses including Bayesian colocalisation, Steiger filtering analysis, assessment of protein-altering variants and mapping expression quantitative trait loci to protein quantitative trait loci were performed to investigate the reliability of the MR findings; protein-protein interaction, pathway enrichment analysis and evaluation of drug targets were conducted to deepen the understanding and identify potential therapeutic targets of OA. RESULTS: Dozens of circulating proteins were identified to have putatively causal effects on OA-related traits, and a majority of these proteins were either drug targets or considered druggable. CONCLUSIONS: Through MR analysis, we have identified numerous plasma proteins associated with OA-related traits, shedding light on protein-mediated mechanisms and offering promising therapeutic targets for OA.

Excess Deaths of Gastrointestinal, Liver, and Pancreatic Diseases During the COVID-19 Pandemic in the United States.

Objectives: To evaluate excess deaths of gastrointestinal, liver, and pancreatic diseases in the United States during the COVID-19 pandemic. Methods: We retrieved weekly death counts from National Vital Statistics System and fitted them with a quasi-Poisson regression model. Cause-specific excess deaths were calculated by the difference between observed and expected deaths with adjustment for temporal trend and seasonality. Demographic disparities and temporal-spatial patterns were evaluated for different diseases. Results: From March 2020 to September 2022, the increased mortality (measured by excess risks) for Clostridium difficile colitis, gastrointestinal hemorrhage, and acute pancreatitis were 35.9%; 24.8%; and 20.6% higher than the expected. For alcoholic liver disease, fibrosis/cirrhosis, and hepatic failure, the excess risks were 1.4-2.8 times higher among younger inhabitants than older inhabitants. The excess deaths of selected diseases were persistently observed across multiple epidemic waves with fluctuating trends for gastrointestinal hemorrhage and fibrosis/cirrhosis and an increasing trend for C. difficile colitis. Conclusion: The persistently observed excess deaths of digestive diseases highlights the importance for healthcare authorities to develop sustainable strategies in response to the long-term circulating of SARS-CoV-2 in the community.

Effects of vaginal microbiota transfer on the neurodevelopment and microbiome of cesarean-born infants: A blinded randomized controlled trial.

The microbiomes of cesarean-born infants differ from vaginally delivered infants and are associated with increased disease risks. Vaginal microbiota transfer (VMT) to newborns may reverse C-section-related microbiome disturbances. Here, we evaluated the effect of VMT by exposing newborns to maternal vaginal fluids and assessing neurodevelopment, as well as the fecal microbiota and metabolome. Sixty-eight cesarean-delivered infants were randomly assigned a VMT or saline gauze intervention immediately after delivery in a triple-blind manner (ChiCTR2000031326). Adverse events were not significantly different between the two groups. Infant neurodevelopment, as measured by the Ages and Stages Questionnaire (ASQ-3) score at 6 months, was significantly higher with VMT than saline. VMT significantly accelerated gut microbiota maturation and regulated levels of certain fecal metabolites and metabolic functions, including carbohydrate, energy, and amino acid metabolisms, within 42 days after birth. Overall, VMT is likely safe and may partially normalize neurodevelopment and the fecal microbiome in cesarean-delivered infants.

Latest insights in disease-modifying osteoarthritis drugs development.

Osteoarthritis (OA) is a prevalent and severely debilitating disease with an unmet medical need. In order to alleviate OA symptoms or prevent structural progression of OA, new drugs, particularly disease-modifying osteoarthritis drugs (DMOADs), are required. Several drugs have been reported to attenuate cartilage loss or reduce subchondral bone lesions in OA and thus potentially be DMOADs. Most biologics (including interleukin-1 (IL-1) and tumor necrosis factor (TNF) inhibitors), sprifermin, and bisphosphonates failed to yield satisfactory results when treating OA. OA clinical heterogeneity is one of the primary reasons for the failure of these clinical trials, which can require different therapeutic approaches based on different phenotypes. This review describes the latest insights into the development of DMOADs. We summarize in this review the efficacy and safety profiles of various DMOADs targeting cartilage, synovitis, and subchondral bone endotypes in phase 2 and 3 clinical trials. To conclude, we summarize the reasons for clinical trial failures in OA and suggest possible solutions.

The effect of systemic iron status on osteoarthritis: A mendelian randomization study.

Objective: To assess the causal effect of systemic iron status by using four biomarkers (serum iron; transferrin saturation; ferritin; total iron-binding capacity) on knee osteoarthritis (OA), hip OA, total knee replacement, and total hip replacement using 2-sample Mendelian randomization (MR) design. Methods: Three instrument sets were used to construct the genetic instruments for the iron status: Liberal instruments (variants associated with one of the iron biomarkers), sensitivity instruments (liberal instruments exclude variants associated with potential confounders), and conservative instruments (variants associated with all four iron biomarkers). Summary-level data for four OA phenotypes, including knee OA, hip OA, total knee replacement, and total hip replacement were obtained from the largest genome-wide meta-analysis with 826,690 individuals. Inverse-variance weighted based on the random-effect model as the main approach was conducted. Weighted median, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier methods were used as sensitivity MR approaches. Results: Based on liberal instruments, genetically predicted serum iron and transferrin saturation were significantly associated with hip OA and total hip replacement, but not with knee OA and total knee replacement. Statistical evidence of heterogeneity across the MR estimates indicated that mutation rs1800562 was the SNP significantly associated with hip OA in serum iron (odds ratio, OR = 1.48), transferrin saturation (OR = 1.57), ferritin (OR = 2.24), and total-iron binding capacity (OR = 0.79), and hip replacement in serum iron (OR = 1.45), transferrin saturation (OR = 1.25), ferritin (OR = 1.37), and total-iron binding capacity (OR = 0.80). Conclusion: Our study suggests that high iron status might be a causal factor of hip OA and total hip replacement where rs1800562 is the main contributor.

Quantitatively Measured Infrapatellar Fat Pad Signal Intensity Alteration is Associated with Joint Effusion-synovitis in Knee Osteoarthritis.

OBJECTIVE: The objective of this study is to investigate whether quantitatively measured infrapatellar fat pad (IPFP) signal intensity alteration is associated with joint effusion-synovitis in people with knee osteoarthritis (OA) over two years. METHODS: Among 255 knee OA patients, IPFP signal intensity alteration represented by four measurement parameters [standard deviation of IPFP signal intensity (IPFP sDev), upper quartile value of IPFP high signal intensity region (IPFP UQ (H)), ratio of IPFP high signal intensity region volume to whole IPFP volume (IPFP percentage (H)), and clustering factor of IPFP high signal intensity (IPFP clustering factor (H))] was measured quantitatively at baseline and two-year follow-up using magnetic resonance imaging (MRI). Effusion-synovitis of the suprapatellar pouch and other cavities were measured both quantitatively and semi-quantitatively as effusion-synovitis volume and effusion-synovitis score at baseline and two-year follow-up using MRI. Mixed effects models assessed the associations between IPFP signal intensity alteration and effusion-synovitis over two years. RESULTS: In multivariable analyses, all four parameters of IPFP signal intensity alteration were positively associated with total effusion-synovitis volume and effusion-synovitis volumes of the suprapatellar pouch and of other cavities over two years (all P＜0.05). They were also associated with the semi-quantitative measure of effusion-synovitis except for IPFP percentage (H) with effusion-synovitis in other cavities. CONCLUSION: Quantitatively measured IPFP signal intensity alteration is positively associated with joint effusion-synovitis in people with knee OA, suggesting that IPFP signal intensity alteration may contribute to effusion-synovitis and a coexistent pattern of these two imaging biomarkers could exist in knee OA patients.