Kaplan-Meier Survival Research Articles

Vessel wall enhancement and high-sensitivity CRP as prognostic markers in intracranial atherosclerotic stroke: A prospective cohort study.

Eccentric vessel wall enhancement (EVWE) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers associated with atherosclerotic disease. We investigated their prognostic value in patients with acute ischemic stroke receiving guideline-adherent medical treatment. In this prospective observational cohort study, patients with acute ischemic stroke attributed to intracranial arterial disease (ICAD) underwent vessel wall MRI and hs-CRP testing. The study included intracranial cases of both large artery atherosclerosis (LAA) and small vessel occlusion (SVO). The primary outcome was subsequent ischemic stroke during the follow-up period. The median follow-up duration was 21 months. Kaplan-Meier survival and Cox regression analysis was used to determine the associations between EVWE, hs-CRP levels, and subsequent ischemic stroke. Among 191 patients, 81 (42.4%) had EVWE. EVWE positivity showed a trend toward a lower risk of subsequent ischemic stroke compared to EVWE negativity (HR 0.32, 95% CI 0.12-0.87; p = 0.061). Hs-CRP levels were not associated with recurrent stroke risk. The combination of EVWE positivity and low hs-CRP levels (<1.25 mg/l) was associated with a favorable outcome, while EVWE negativity and high hs-CRP levels (⩾1.25 mg/l) were associated with an unfavorable outcome (HR 0.143, 95% CI 0.04-0.50; p = 0.031). In this observational study of patients with intracranial atherosclerotic stroke receiving optimal medical therapy, EVWE positivity appeared to be associated with a trend toward lower risk of recurrent stroke, though this relationship requires further validation. The combination of EVWE and hs-CRP status might potentially offer prognostic information, with preliminary data suggesting that EVWE positivity and low hs-CRP levels could be associated with more favorable outcomes in patients receiving guideline-adherent medical treatment. These preliminary findings suggest a possible role for combining imaging and serum inflammatory biomarkers in risk stratification, though larger prospective studies are needed to confirm these associations.

Simultaneous curative resection may improve the long-term survival of patients diagnosed with colorectal liver metastases: A propensity score-matching study.

The benefit of simultaneous curative resection in patients with colorectal liver metastases has been unclear. Adjuvant chemotherapy is still considered an effective and priority treatment for advanced-stage colorectal patients. We retrospectively collected patients with colorectal liver metastases from January 2012 to October 2023 at the Guangxi Medical University Cancer Hospital. The baseline information was compared between a simultaneous curative resection group and a palliative treatment group. Propensity score matching with a 1:1 ratio was applied to develop comparable cohorts of curative resection and palliative treatment resection. Kaplan-Meier survival and Cox regression analyses were performed to determine the impact of curative resection on survival of colorectal liver metastasis patients. Prognostic nomogram and a web-version calculator were developed based on the multivariate Cox regression method. Then, the concordance index (C-index), receiver operating characteristic, calibration plots, and decision curves analysis were applied to evaluate the prognostic performance of the nomogram. A total of 716 patients with colorectal liver metastases were enrolled in the study, of whom 131 patients received curative resection. There was no significant difference in terms of baseline information between the curative resection group and the palliative treatment group after propensity score matching. Multivariable Cox regression analysis showed that curative resection was an independent prognostic factor affecting overall survival (P=.001, hazard ratio=1.95, 95% confidence interval1.30-2.91). Compared with patients who did not receive curative resection, patients who received simultaneous curative resection had a significant improvement in overall survival before and after propensity score matching (P < .0001 and P= .0047, respectively). Overall survival nomogram showed excellent predictive performance with the C-indexes of 0.686 (95% confidence interval 0.556-0.792). The areas under the receiver operating characteristic curves were 0.75 (95% confidence interval 64.43-96.05), 0.75 (67.22-82.58), and 0.76 (66.10-85.98) for predicting 1-, 3-, and 5-year survival, respectively. The calibration plots and decision curves analysis also indicated the good predictability of the predictive nomogram. Finally, subgroup analysis further demonstrated a favorable impact of curative resection on overall survival in colorectal liver metastasis patients after propensity score matching. Simultaneous curative resection may improve the overall survival of patients with colorectal liver metastases and is an independent and effective indicator for predicting overall survival. The nomogram may provide a personalized treatment strategy.

Prognostic value of right ventricular ejection fraction using three-dimensional echocardiography in patients with ischemic cardiomyopathy and dilated cardiomyopathy

Abstract Background Prognostic value of right ventricular (RV) ejection fraction (EF) using three-dimensional echocardiography (3DE) in a diverse group of patients has been demonstrated in several studies [1-3]. However, little is known about its potential utility in patients with ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM). Purpose To investigate the prognostic value of 3DE-RVEF in ICM and DCM. Methods We retrospectively selected ICM and DCM patients who had undergone 3DE from December 2007 to December 2018. 3DE analysis was performed using 3DE speckle tracking software. The primary end point was a composite of cardiac events, including cardiac death, heart failure hospitalization, myocardial infarction, or ventricular tachyarrhythmia. Results 268 ICM and 127 DCM patients were included in this analysis. During a median of 33 and 51 months of follow-up, 84 and 43 patients reached a primary end point in ICM and DCM, respectively. Univariable analysis showed RVEF was significantly associated with cardiac events in both groups [ICM, hazard ratio (HR): 0.92, 95% confidence interval (CI): 0.90 – 0.94; DCM, HR: 0.91, 95% CI: 0.88 – 0.94, respectively]. In multivariable analysis, RVEF (HR: 0.91, both for p&amp;lt;0.001) was significantly associated with cardiac events, after adjustment for age, chronic kidney disease, New York Heart Association function class (NYHA), Charlson comorbidity index (CCI), E/e', left ventricular (LV) EF or LV global longitudinal strain (GLS) in ICM. In DCM, RVEF (HR: 0.91 – 0.94, all for p&amp;lt;0.001) was significantly associated with outcome, after adjusting clinical factors (age and CCI or NYHA) and echocardiographic parameters (E/e' or LVEF or LVGLS). Kaplan-Meier survival curves, divided into four groups by RVEF ≥ 45% and &amp;lt; 45% and E/e' 14 ≥ and &amp;lt; 14, showed significant risk stratification for both ICM and DCM (Log-rank: p&amp;lt;0.0001, Fig 1). Crude Kaplan-Meyer survival analysis revealed there were no significant survival differences between ICM and DCM (p=0.36). However, ICM had a worse outcome than DCM after adjustment for age, NYHA, CCI, E/e', RVEF, LVEF or LVGLS (p=0.049 and p=0.028, respectively, Fig 2). Conclusions Our study confirmed the independent prognostic value of RVEF in patients with ICM and DCM and provided detailed risk stratification of cardiac events by E/e' and RVEF. In addition, ICM was associated with worse outcome than DCM after adjusting multiple covariates.

Characterization of tumor prognosis and sensitive chemotherapy drugs based on cuproptosis-related gene signature in ovarian cancer

BackgroundCuproptosis is a novel form of cell death, acting on the tricarboxylic acid cycle in mitochondrial respiration and mediated by protein lipoylation. Other cancer cell death processes, such as necroptosis, pyroptosis, and ferroptosis, have been shown to play crucial roles in the therapy and prognosis of ovarian cancer. However, the role of cuproptosis in ovarian cancer remains unclear.MethodsThe expression profiles of 10 cuproptosis-related genes were extracted from GSE140082. Kaplan-Meier survival and Cox proportional hazards regression were used to identify prognostic genes for constructing risk models. Following this, Least Absolute Shrinkage and Selection Operator regression was employed to construct a risk score model. Next, a nomogram was constructed to predict overall survival in ovarian cancer. Ultimately, our analysis compared the two groups across various dimensions, including clinical characteristics, tumor progression, metabolism-related pathways, immune landscape, and drug sensitivity.ResultsMTF1 and LIAS were identified as protective factors in ovarian cancer, with patients in the higher risk group being significantly associated with poorer survival. Furthermore, integrating the risk score with clinical characteristics in the nomogram demonstrated high specificity and sensitivity in predicting survival. A higher propotion of M2 macrophages, follicular helper T cells, and resting mast cells was observed in the high-risk group. Additionally, the IC50 values of Dasatinib, Bortezomib, Parthenolide, and Imatinib were significantly lower in the high-risk group.ConclusionsThe study highlights the prognostic significance of cuproptosis-related genes and provides new insights into developing pharmacological therapeutic strategies targeting cuproptosis for the prevention and treatment of ovarian cancer.

Survival Status of HIV-Hepatitis B Virus Co-Infection with HIV Mono-infected Patients on Antiretroviral Therapy in Mekelle City, North Ethiopia: A Retrospective Cohort Study

Background: HIV/AIDS and hepatitis B virus (HBV) are two serious global health threats that co-occur and are resistant to antiretroviral therapy (ART). Milions of people worldwide lost their lives to acquired immunodeficiency in 2019.Thus, this study was aimed to evaluate the survival status of patients co-infected with HIV and hepatitis B viruses who are on antiretroviral therapy (HART). Methods: A retrospective cohort study design was conducted. Individuals with HIV-HBV co-infected with HIV mono-infected in six health facilities in Mekelle City from January 2009 to February 2018. The total sample size was 466, of which 94 were HBV exposed and 372 were unexposed for HBV on ART clients. Kaplan-Meier survival and Cox proportional hazard models for survival analysis were used. Data was analyzed using STATA version 14. Result: Of the total patients, 300 (64.3%) were females and most age groups were 15-30 years old, 199 (43%). Over 1960 person years of observation time at risk, 23 (24%) HIV-HBV co-infected and 26 (7%) HIV mono-infected died. In the adjusted analysis, HIV-HBV co-infected group had a 2.53 times increased hazard of death (aHR: 2.52; 95% CI: 1.31-4.85) than HIV mono-infected. Conclusion: In this cohort study, mortality is higher in the HIV-HBV co-infected group. Hence, special attention shall be given to HIV-HBV co-infected groups, to significantly reduce mortality, and contribute to alleviating public health burden.

P0787 A large-scale comparison of clinical response to IBD therapies in white and non-white ethnicities

Abstract Background IBD phenotypes differ between non-White (NW) and White (WH) populations. Ethnic differences can influence the effectiveness of non-IBD medications, and IBD therapies differ by IBD phenotype. An unanswered question is whether IBD therapies are equally efficacious, with a similar side effect profile, for all ethnic groups. This multi-centre cohort study sought to compare the effectiveness and adverse events (AEs) of IBD therapies in WH and NW patients. Methods Phenotypic and outcome data were extracted from the UK IBD BioResource, a large-scale IBD database enrolling patients across the UK. Response and AEs to 5-ASAs, thiopurines, anti-TNFs and anti-integrins were assessed. Treatment effectiveness was defined as treatment persistence free of discontinuation or failure, and evaluated using Kaplan-Meier survival and Cox regression analysis. The risk of experiencing any AE (and individual AEs with a given treatment) was assessed using Cox regression analysis. Models were adjusted for sex, smoking status, IBD subtype, disease duration, disease location/extent, disease behaviour (CD), perianal disease (CD), co-morbidities, presence of extra-intestinal manifestations, age at commencing therapy, steroid and concomitant immunomodulator use, and the occurrence of an AE (in treatment response models). Results In total 27,433 patients were included [51.1% females; median age at diagnosis 30 years (IQR 21-43); 94.7% WH, 5.3% NW (71.3% South Asian)]. NW were diagnosed at a younger age, exhibited different disease phenotypes, and were younger at treatment initiation therapy than WH. However, no differences in treatment persistence between WH and NW were identified for all therapies analysed, in either CD or UC (Table 1). NW were at significantly increased risk of AEs when treated with thiopurines [HR 1.16 (95% CI 1.00-1.35), p=0.046] and a similar trend was observed for anti-TNFs [HR 1.25 (95% CI 0.99-1.56), p=0.057]; Table 2]. Specifically, NW were at increased risk of developing leucopenia [HR 1.66 (95% CI 1.10-2.42), p=0.01] and pancreatitis [ p=0.009] with thiopurines, and renal dysfunction with anti-TNFs [HR 2.33 (95% CI 1.11-4.38), p=0.02]. Conclusion This is the first large-scale study focussing on ethnic differences in IBD treatment response. No differences were observed in treatment response, but we have shown that thiopurines are associated with increased risks of leucopenia and pancreatitis, whilst anti-TNFs are associated with a higher risk of renal dysfunction in NW patients. These findings underscore the importance of thorough pre-treatment risk assessment and patient counselling by clinicians, and the need for more diverse patient representation in research.

P0837 Prevalence of the HLA-DQA1*05 phenotype in a cohort of Spanish patients with Inflammatory Bowel Disease, and its association with the response to first anti-TNF therapy in real-world settings

Abstract Background Anti-tumor necrosis factor (anti-TNF) drugs usually represent the first line of biological therapy in inflammatory bowel disease (IBD) patients. The presence of the HLA-DQA1*05 allele has been linked to a higher risk of immunogenicity and the development of anti-drug antibodies. This condition may increase the likelihood of primary treatment failure or loss of response to anti-TNF medications. However, clinical data on this topic are scarce and often contradictory. Methods Prospective, single-center cohort study in bio-naive IBD patients receiving the first anti-TNF medication for IBD activity from 1 January 2020 to 31 December 2023. PCR-SSP using the HLA-Ready Gene Coeliac Disease kit detected the DQA1*05 allele in a saliva sample. The result was positive if the DQA1*05:01:01,03 or DQA1*05:01:01,05,08 alleles were present. Patients were followed from first dose to discontinuation or last visit. The primary endpoint was anti-TNF persistence, considering as treatment failures, IBD patients with primary or secondary loss of response, and anti-TNF discontinuation due to adverse events. An appropriate statistical analysis was performed using survival Kaplan-Meier curves to assess anti-TNF persistence. Results We included 209 patients:108 men (51.7%), mean age 43.5 (17) and time since diagnosis 6.5 (10) years. Ulcerative colitis 39.2% and Crohn´s Disease 60.8%. As the first anti-TNF, 107 patients received adalimumab (51.2%) and 101 infliximab. Baseline demographics for the cohort are summarized in Table 1. At anti-TNF initiation, 29.2% and 58% of patients were on immunosuppressants and systemic steroids, respectively. HLA-DQA1*05 was determined in 205 patients with 38.8% (81) positive, 54.5% (114) negative and 4.8% (10) null results. HLA carriers did not differ according to gender, age or IBD clinical phenotype. A total of 87 patients (41.6%) discontinued treatment during a median follow-up of 22.3 (10-36) months, mostly infliximab 59,3% vs 41% (p=0.009). At 12 and 24 weeks, primary anti-TNF failure was reported in 24 (11.5%) and 34 (16.3%) patients, respectively. Anti-TNF was discontinued in another 23 patients (11%) because of loss of response and in 22 (10.5%) for serious adverse events, mainly infusion reactions (5.7%). The mean persistence of first anti-TNF was similar in allele carriers 36.7 CI95%(31.5-41.9) versus naive 33.8 CI 95%(29.6-38.1) months (Figure 1). Conclusion HLA-DQA1*05 ihaplotype is carried by 40%, of bio-naive Spahish IBD patients, a similar prevalence to that obtained in other western IBD populations. HLA-DQA1*05 carrier status was not associated with IBD clinical phenotypes or persistence on the first anti-TNF treatment. References Spencer EA, Stachelski J, Dervieux T et al. Failure to achieve target drug concentrations during induction and not HLA-DQA1∗05 carriage is associated with antidrug antibody formation in patients with Inflammatory Bowel Disease. Gastroenterology. 2022;162(6):1746-48. Pascual-Oliver A, Casas-Deza D, Cuarán C et al. HLA-DQA1*05 was not associated with primary nonresponse or loss of response to first anti-TNF in real-world Inflammatory Bowel Disease patients. Inflamm Bowel Dis.2024; 3:30 (6):922-929.

Survivorship of Periprosthetic Joint Infection in Unicompartmental Knee Arthroplasty: A Single Healthcare System's 23-Year Experience.

Unicompartmental knee arthroplasty (UKA) is increasingly favored in clinical practice due to its favorable long-term survival rates, positive clinical outcomes, and expedited recovery. Periprosthetic joint infections (PJIs) remain a formidable complication in knee arthroplasty, and guidelines for the management are limited. This study aims to assess the failure rates of débridement, antibiotics, and implant retention (DAIR) in UKAs, providing insights into optimal treatment management and infection-free survival for PJI in this context. Twenty-five patients met the inclusion criteria of PJI, as defined by Musculoskeletal Infection Society criteria, and were retrospectively reviewed from January 2000 to September 2023. Surgical treatment included 17 DAIRs (78%), six one-stage revision procedures (20%), and three two-stage revision procedures (12%). Seventeen patients (78%) had acute hematogenous infections (<3 weeks of symptoms). Kaplan-Meier survivorship analysis was done for reinfection and revision procedures. The overall infection-free survival and all-cause survival regardless of management at 3 years was 60.1% (95% confidence interval [CI], 45.7% to 89.6%) and 55.8% (95% CI, 38.2% to 81.5%), respectively. Both two-stage and one-stage revision procedures had an infection-free survivorship of 100% at 3 years (95% CI, 100% to 100%). DAIR treatment had an infection-free survival at 3 years of 41.6% (95% CI, 22.4% to 77.4%). Nine of 17 patients (53%) undergoing DAIR were unsuccessful and required subsequent second DAIR, one-stage, or two-stage revision procedures. The efficacy of DAIR following PJI in UKA is notably limited, suggesting a need for reevaluation of its role in managing UKA PJIs. Given the absence of established guidelines for PJI management specifically tailored to UKA, there is an urgent and compelling need for future studies to elucidate optimal clinical strategies to allow for the best treatment for patients. Level III, retrospective comparative study.

CYP24A1 DNA Methylation in Colorectal Cancer as Potential Prognostic and Predictive Markers.

The DNA methylation of CYP24A1 can regulate its gene expression and may play a role in the occurrence and progression of colorectal cancer (CRC). However, the association between CYP24A1 DNA methylation and the prognosis of CRC patients has not yet been reported. In this study, differential methylation analysis was conducted in both blood and tissue cohorts, and differential expression analysis was performed in the tissue cohort with in vitro validation. GO and KEGG enrichment analyses were performed on CYP24A1-related genes. A correlation between CYP24A1 promoter methylation and its gene expression was explored. Kaplan-Meier survival and Cox regression analyses were performed to investigate the impact of CYP24A1 DNA methylation on the prognosis of CRC patients. Prognostic risk scores were constructed for survival prediction. Immune infiltration analysis was also conducted. Our results showed that the hypermethylation of cg02712555 in tumor tissues (hazard ratio, 0.48; 95% confidence interval, 0.24-0.94; p = 0.032) and CpG site 41 in peripheral leukocytes (HR, 0.35; 95%CI, 0.14-0.84; p = 0.019) were both associated with decreased overall mortality in CRC patients. Prognostic risk scores showed robust predictive capabilities of these two CpG loci for the prognosis of CRC patients. CYP24A1 hypermethylation was positively correlated with infiltration levels of activated CD4 + T cells, activated CD8 + T cells, activated B cells, activated dendritic cells, and macrophages. Taken together, our findings indicate that the methylation levels of specific CpG sites within the CYP24A1 promoter region in blood leukocytes and tumors are potential prognostic and predictive markers for overall survival in CRC patients.

SUGT1 is a prognostic biomarker and is associated with immune infiltrates in ovarian cancer

BackgroundOvarian cancer (OC) is a prevalent gynecological malignancy with a relatively dismal prognosis. The SGT1 homolog (SUGT1) protein, which interacts with heat shock protein 90 and is essential for the G1/S and G2/M transitions, was formerly thought to be a cancer promoter, but its precise role in OC remains unknown.MethodsWe conducted a comprehensive bioinformatics analysis of SUGT1 expression in patients with OC compared with their normal controls, including the data from the cancer genome atlas (TCGA), genotype–tissue expression (GTEx) databases, gene ontology (GO) analysis, Kyoto Encylopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), single sample gene set enrichment analysis (ssGSEA). In addition, Kaplan–Meier (KM) analysis, univariate and multivariate Cox analyses were applied to investigate the prognostic role of SUGT1 in ovarian cancer. Furthermore, we validated the expression of SUGT1 in OC and normal tissues through immunohistochemistry.ResultsSUGT1 was significantly overexpressed in OC than in normal tissues. In addition, the GO, KEGG and GSEA analysis revealed that SUGT1 was associated with the functions related to immunoglobulin complex, antigen binding, immunoglobulin receptor binding, among others. Besides, ssGSEA demonstrated a positive correlation between SUGT1 expression and the abundance of T central memory cells, natural killer cells, and T gamma delta cells, although it showed a negative association with activated dendritic cells, cytotoxic cells, T cells, and T helper 1 cells. Subsequently, KM survival analysis revealed that high SUGT1 expression indicated a shorter overall survival, disease specific survival and progression free interval in OC patients. Univariate and multivariate Cox regression revealed that SUGT1 could serve as an independent risk factor for prognosis of patients with OC.ConclusionsAll these results of this study show that SUGT1 is an important molecular component in immune infiltration in OC and may have a new significant prognostic role in OC.

Prospective Evaluation of Clinical Outcomes of the Subchondroplasty Procedure for Treatment of Symptomatic Bone Marrow Lesions of the Knee.

Bone marrow lesions (BMLs) have a strong correlation to patient-reported pain, functional limitations, joint deterioration, and rapid progression to total knee arthroplasty. The Subchondroplasty (SCP) procedure uses AccuFill, a calcium phosphate bone substitute material (BSM), to treat bone defects such as microtrabecular fractures and BML. This observational, prospective, multicenter, cohort study evaluated the effect of the SCP procedure at the 2-year follow-up for 70 patients with knee BML. Under arthroscopic and fluoroscopic guidance, the BML was injected with AccuFill. Patient-reported outcomes, including Visual Analog Scale (VAS) pain, Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and modified Knee Society Score (mKSS) were collected through 24 months postoperatively. Radiographs and magnetic resonance imaging (MRI) were performed at baseline and up to 24 months postoperatively. Patient selection was not limited based on the degree of osteoarthritis (OA) as determined radiologically by the Kellgren-Lawrence (K-L) grade. For a subset of patients, patient-reported outcomes were collected up to 5 years including pain evaluation, patient knee global assessment, and satisfaction with the procedure. Preoperative radiographs indicated moderate to severe OA (K-L grades 2-4) in 65 patients (92.8%). Significant improvements (p < 0.0001) in mean VAS pain, IKDC, mKSS, and KOOS scores were observed compared with baseline. Kaplan-Meier survivorship free from conversion to knee arthroplasty was 76.2% at 2 years. The subset of patients followed for 5 years demonstrated low pain scores and high procedure satisfaction. This study presents statistically significant and clinically meaningful evidence of improvement in clinical outcomes following SCP for BMLs of the knee after 2 years. The survivorship rate from arthroplasty at 2 years was 76.2%. SCP for BMLs can relieve pain with a minimally invasive procedure and may delay the need for knee arthroplasty. REGISTRATION: NCT01621893 (ClinicalTrials.gov). LEVEL OF EVIDENCE: Level II, Prospective Cohort Therapeutic Study.

Circulating resistin levels and mutation burden of the RETN gene variants predict long-term mortality in a Taiwanese population

Human resistin is a proinflammatory cytokine involving the development and progression of cancer and cardiovascular diseases. However, prediction of long-term outcome using circulating resistin level and its genetic determinants in a population-based study remain to be explored. After genome-wide association study (GWAS), DNA methylation (DNAm) analysis and functional assays of a RETN rs370006313 variant, we tested whether resistin level and its genetic determinants can be used to determine the long-term outcomes of 5678 Taiwan Biobank (TWB) participants. GWAS and DNAm analysis revealed RETN variants, rs3219175, rs370006313, and rs3745368, and DNAm sites, cg21271423 and cg09909011, independently associated with circulating resistin levels. Functional assays showed rs370006313 variant played a key role in affecting RETN promoter activity, whereas genotypes of rs3219175 and rs3745368, but not rs370006313, exhibited genome-wide significant associations with RETN promoter DNAm levels. Using Kaplan-Meier survival and Cox regression analyses, participants with progressively increasing resistin levels had a higher hazard ratio for all-cause mortality and cancer mortality compared to those with lower resistin levels. Participants with all three RETN variants (high mutation burden) also exhibited significantly higher hazard ratios for all-cause mortality and cancer mortality, at 3.99 and 5.55, respectively, compared to those without a high mutation burden. In conclusion, RETN rs370006313 is a functional variant affecting RETN promoter activity. Elevated circulating resistin levels and a high RETN mutation burden predict all-cause and cancer mortality in TWB participants. Both resistin levels and RETN variants may serve as biomarkers of long-term outcomes in the general Taiwanese populations.

Assessment of Treatment Outcomes and Associated Factors Among Pediatric Patients With Burkitt Lymphoma at Kenyatta National Hospital.

In developing countries, the treatment outcomes of Burkitt lymphoma are poor due to the poorly equipped healthcare systems. In addition, there is limited comprehensive data within the African continent, including Kenya, about the outcomes of treatment for this cancer. To assess treatment outcomes and variables associated with an increased risk of death from disease progression or treatment-related toxicities among Burkitt lymphoma pediatric patients at the Kenyatta National Hospital (KNH). A retrospective one-arm cohort study was conducted to examine the treatment outcomes of pediatric patients with Burkitt lymphoma. All eligible Burkitt lymphoma pediatric patients treated between January 1, 2016 and December 31, 2022 were included. The patients were retrospectively monitored from the initial cancer diagnosis until either death or the last follow-up appointment visit in the facility. Data analysis of factors associated with treatment and disease progression-related death was carried out using the SPSS version 29.0 software. Kaplan-Meier survival and Cox regression analyses were employed to determine the survival time and predictors of mortality, respectively. The median age of the patients at diagnosis was 6 years (range: 3-13 years). The majority of patients were diagnosed with Stage IV disease accounting for 46.7% of all patients. Of the 75 patients studied, 24% (18) of them were died. The 5-year overall survival rate was 70%, and most patients had stable disease during the follow-up period. Patients with Stage IV disease who were treated with full-fuse chemotherapy were 19.2 (AHR = 19.2, 95% CI = 5.2-48.5, p < 0.001) and 7.4 times (AHR = 7.4, 95% CI = 2.2-19.9, p = 0.003) more hazard of dying as compared to patients without metastasis and received a combination of radiation and reduced-dose chemotherapy, respectively. However, the age, gender, stage of cancer, histological type of cancer, and co-morbidity were not significant predictors of survival. Because of the retrospective nature of the study design, the data accuracy relied on the proper documentation of medical records in the study setting. The 5-year overall survival rate among pediatric burkitt's lymphoma patients was above average as compared to other African countries. Most patients had reduced tumor size and stable disease during the follow-up period. Metastases and full-fuse chemotherapy were significant predictors of mortality.

Outcomes of surveyed monolithic CAD/CAM zirconia crowns for removable partial denture abutments: A 7-year clinical study

This retrospective clinical study aimed to evaluate the clinical outcomes of surveyed monolithic computer-aided design and computer-aided manufacturing (CAD/CAM) zirconia crowns for abutment teeth in removable partial dentures (RPDs). Patients who received monolithic surveyed zirconia crowns were clinically examined. The crowns were examined according to the modified United States Public Health Service criteria, and Kaplan-Meier survival was determined. The effect of different variables on the survival and success rates was assessed using Cox regression analysis (α = 0.05). A total of 297 crowns of 275 patients were evaluated over a mean period of 7 years. The cumulative survival and success rates were 95.6% and 91.2%, respectively. Complications were in the form of secondary caries (n=12), minor chipping (n=9), and debonding (n=5). A higher number of failures was observed in the mandibular molars (P < 0.05). Surveyed monolithic zirconia crowns demonstrated high survival after 7 years of service. Monolithic zirconia is an excellent alternative to metal ceramic crowns for RPD abutments.

Effectiveness of Total Hip Arthroplasty Combined With Hip Braces for Hip Charcot Arthropathy.

Charcot arthropathy is characterized by varying degrees of sensory loss and rapidly progressive joint destruction. Historically, limited studies indicated that Charcot arthropathy of the hip joint may be a contraindication for total hip arthroplasty (THA). Yet, some recent studies have shown that good clinical results and acceptable survival rate. Hence, this study aimed to investigate clinical outcomes, radiographic outcomes, complication rates and survivorship of primary THA in Charcot arthropathy. We retrospectively included 11 patients (11 hips) with Charcot arthropathy who underwent THA between 1998 and 2016. All involved patients were diagnosed as syphilis. All patients had classic radiographic findings of Charcot arthropathy. The hip braces were used in all patients for six weeks after surgery. Outcome measures included VAS, Oxford Hip Score, and UCLA score. Statistical analyses involved t-tests, chi-square tests, and Kaplan-Meier survival analysis. The average follow-up period was 81.73 months. The average VAS, Oxford Hip Score, and UCLA score were improved significantly. There was higher complication rate of 45.5% after THA. Reoperation was carried out in two patients due to dislocation and acetabular component loosening. The Kaplan-Meier survivorship with an end point of reoperation for any reason was 81.8%. THA is proved to be reasonable in improving hip joint function, which is suitable for patients with Charcot hip joint. Although the complication rate is high, we consider that THA combined with hip brace may be a valid treatment choice for Charcot arthropathy with detailed preoperative planning and proper precautions.

Robust and interpretable deep learning system for prognostic stratification of extranodal natural killer/T-cell lymphoma.

Extranodal natural killer/T-cell lymphoma (ENKTCL) is an hematologic malignancy with prognostic heterogeneity. We aimed to develop and validate DeepENKTCL, an interpretable deep learning prediction system for prognosis risk stratification in ENKTCL. A total of 562 patients from four centers were divided into the training cohort, validation cohort and test cohort. DeepENKTCL combined a tumor segmentation model, a PET/CT fusion model, and prognostic prediction models. RadScore and TopoScore were constructed using radiomics and topological features derived from fused images, with SHapley Additive exPlanations (SHAP) analysis enhancing interpretability. The final prognostic models, termed FusionScore, were developed for predicting progression-free survival (PFS) and overall survival (OS). Performance was assessed using area under the receiver operator characteristic curve (AUC), time-dependent C-index, clinical decision curves (DCA), and Kaplan-Meier (KM) curves. The tumor segmentation model accurately delineated the tumor lesions. RadScore (AUC: 0.908 for PFS, 0.922 for OS in validation; 0.822 for PFS, 0.867 for OS in test) and TopoScore (AUC: 0.756 for PFS, 0.805 for OS in validation; 0.689 for PFS, 0.769 for OS in test) both exhibited potential prognostic capability. The time-dependent C-index (0.897 for PFS, 0.928 for OS in validation; 0.894 for PFS, 0.868 for OS in test) and DCA indicated that FusionScore offers significant prognostic performance and superior net clinical benefits compared to existing models. KM survival analysis showed that higher FusionScores correlated with poorer PFS and OS across all cohorts. DeepENKTCL provided a robust and interpretable framework for ENKTCL prognosis, with the potential to improve patient outcomes and guide personalized treatment.

Mid-term Results Following Surgical Hip Dislocation for Residual Pediatric Deformities.

Mid-term results following surgical hip dislocation (SHD) for healed slipped capital femoral epiphysis (SCFE) and Perthes-related deformities are limited. This study aimed to characterize patient-reported outcome measures [including rates of achieving the minimal clinically important difference (MCID) and patient-acceptable symptomatic state (PASS)], report survivorship free from conversion to arthroplasty, and identify risk factors associated with composite failure. Twenty-seven patients (n=13 SCFE, n=14 Perthes) with minimum 2-year follow-up (mean 5.7y) who underwent primary SHD from 2011 to 2021 were retrospectively reviewed. Modified Harris Hip Score (mHHS) and International Hip Outcome Tool-12 (iHOT-12) were collected preoperatively and at the latest follow-up. Composite failure was defined as not meeting any MCID/PASS threshold or conversion to arthroplasty. Continuous variables were analyzed using independent-sample t tests or the Wilcoxon Mann-Whitney test, where appropriate. Categorical variables were analyzed using χ2 or Fisher exact test, as indicated. Kaplan-Meier survivorship was determined. Mean mHHS improved from 56.2 to 77.2 (P=0.003) and from 63.0 to 86.3 (P<0.001), while iHOT-12 improved from 36.1 to 64.7 (P=0.008) and 36.8 to 77.2 (P<0.001) in SCFE and Perthes cohorts, respectively. MCID achievement for mHHS and iHOT-12 were 85.7% and 75.0% among SCFE, compared with 83.3% and 81.8% in Perthes. The proportion meeting PASS for mHHS and iHOT-12 was 30% for both in SCFE, compared with 61.5% and 83.3% in Perthes. 5- and 10-year survivorship free of conversion to arthroplasty was 100% and 80%, as well as 93% and 77% in the SCFE and Perthes cohorts, respectively. At mid-term follow-up, patients undergoing SHD for residual deformities related to chronic SCFE and Perthes demonstrated significant improvements in mHHS and iHOT-12, as well as relatively high rates of meeting MCID. SHD is an effective approach providing pain and functional benefit. Preoperative expectations, though, should be tempered in these cohorts, as some pre-existing damage limits the ability to completely normalize anatomy. Level III, retrospective comparative study.

Identification of pyroptosis-associated miRNAs in the immunoscape and prognosis of hepatocellular carcinoma

BackgroundHepatocellular carcinoma is one of the most prevalent types of liver malignancy and poses a severe threat to global health. Despite recent improvements in therapeutic approaches, treatment options for patients with advanced or recurrent HCC are still limited.Materials and methodsOur study analyzed miRNA differential expression using data from hepatocellular carcinoma patients in the Cancer Genome Atlas. Pyroptosis-related genes were identified from gene cards. Differential expression of miRNAs was analyzed using DESeq2 and visualized using ggplot2 and pheatmap. A prognostic risk model for pyroptosis-associated miRNAs was constructed using LASSO regression and validated by principal component analysis, Kaplan-Meier survival and ROC curve analysis. We also performed gene and pathway enrichment analysis. Immune cell infiltration and function in HCC were assessed using single-sample genomic enrichment analysis, and correlations with immune cells and function were explored. Also, CCK-8 assay as well as migration and invasion assays were performed after knockdown of miR-6844.ResultsWe have established and validated a prognostic risk model based on ten DEmiRNAs, which is important for the survival of HCC patients. Significant changes in immune cell infiltration and immune function were also found in high-risk patients. It also demonstrated that knockdown of miR-6844 inhibited HCC cell proliferation, migration and invasion, highlighting its role in HCC progression.ConclusionOur study reveals the implications of pyroptosis-associated differential miRNAs on the prognosis of patients with hepatocellular carcinoma and provides a foundation for novel HCC therapies, especially immunotherapy.

Identification of diagnostic biomarkers in prostate cancer-related fatigue by construction of predictive models and experimental validation.

Cancer-related fatigue (CRF) is a prominent cancer-related complication occurring in Prostate cancer (PCa) patients, profoundly affecting prognosis. The lack of diagnostic criteria and biomarkers hampers the management of CRF. The CRF-related data and PCa single-cell data were retrieved from the GEO database and clinical data was downloaded from the TCGA database. The univariate logistic/Cox regression analysis were used to construct the prediction models. The predictive value of models was analyzed using the ROC curve and Kaplan-Meier survival. The hub genes were screened by an intersection analysis of DEGs. The mice model of PCa and PCa-related fatigue were established, and fatigue-like behaviors of mice were detected. The expression of selected hub genes was validated by RT-PCR and IHC analysis. The diagnosis and risk models showed great predictive value both in the training and validation dataset. Five genes (Baiap2l2, Cacng4, Sytl2, Sec31b and Ms4a1) that enriched the CXCL signaling were identified as hub genes. Among all hub genes, the MS4A1 expression is the most significant in PCa-related fatigue mice. We identified MS4A1 as a promising biomarker for the diagnosis of PCa-related fatigue. Our findings would lay a foundation for revealing the pathogenesis and developing therapies for PCa-related fatigue.

Outcomes of primary and revision total knee arthroplasty with constrained condylar knee prosthesis: A retrospective review

Background The constrained condylar knee (CCK) implants are becoming more frequently used but the long-term outcomes are inadequately reported. A retrospective review of complex primary and revision total knee arthroplasty (TKA) with use of Legacy Constrained Condylar Knee prosthesis (LCCK; Zimmer) was performed to evaluate the functional and radiological outcomes, identify complications, and ascertain prosthesis survival. Methods A cohort of 54 primary TKA and 37 revision TKA cases were performed between December 2002 and March 2021 using the second-generation CCK prosthesis. The cases without using the constrained insert were excluded. Functional outcome comparison includes flexion and extension range of movement (ROM), Knee Society knee score (KSKS), function score (KSFS) and complications. Radiological outcome comparison includes tibiofemoral angle, hip-knee-ankle (HKA) angle and prosthesis components alignment. Survival analysis was performed using revision surgery for any reason as censoring criteria. Results The mean follow-up duration was 4.8 years (1.0–9.9 years) in primary TKA group and 6.2 years (1.0–18.6 years) in revision TKA group. The mean KSKS improved from 40.5 to 86.6 in primary TKA group and from 58.8 to 79.6 in revision TKA group. The mean KSFS improved from 41.8 to 58.9 in primary TKA group and from 34.1 to 58.2 in revision TKA group. The overall complication rate was 7.5% in primary TKA group and 35.1% in revision TKA group. Aseptic loosening was found in 6 cases and periprosthetic joint infection was found in 5 cases. Kaplan-Meier survivorship analysis estimated the overall mean survival was 17.9 years and 10-year survival rate was 93%. Conclusions Complex primary and revision TKA with use of LCCK prosthesis yielded significant reproducible improvement of clinical outcomes. The failure rate was low in primary TKA but relatively higher in revision cases.