Multivariate Cox Proportional Hazards Model Research Articles

Unexpected identification of peak systolic velocity in the radial artery as a risk factor for functional primary patency of radiocephalic fistulas

ObjectiveAs radiocephalic fistula is not necessarily appropriate for all patients with advanced kidney disease, our aim was to investigate the sensitive indicators that affect the functional primary patency of radiocephalic fistulas. MethodsThis prospective observational study included consecutive patients referred to the Second Hospital of Dalian Medical University for initial creation of radiocephalic fistula from July 2017 to December 2019. Preoperative ultrasound parameters, demographic characteristics, serum indicators and comorbidities were recorded. The functionality of radiocephalic fistulas would be assessed every 6 months until March 2023, following their unassisted maturation, unless AVF dysfunction, kidney transplantation, mortality or loss to follow-up occurred. Kaplan–Meier analysis was employed to illustrate differences in functional primary patency of radiocephalic fistulas, while log-rank tests were utilized to compare survival curves. Univariate and multivariable Cox proportional hazard models were performed, yielding hazard ratios and 95% confidence intervals. The significance level was set at 5% for a two-sided test. ResultsThe studies included a total of 182 patients who successfully underwent radiocephalic fistulas with primary unassisted maturation. The mean age of the study population was 58 years, with 66 percent being male. All AVFs were placed on the forearm, with 84% located on the left side.The primary patency rates of eleven parameters exhibited significant differences between groups stratified by cut-off values at different time points. Notably, the group with a peak systolic velocity of the radial artery near the elbow ≤59cm/s demonstrated a higher primary patency rate compared to the >59cm/s group at 2 years (78.4% vs 57.5%, P=0.026).In the univariate Cox proportional hazard models, the P values for gender, the diameter of radial artery near the elbow, the peak systolic velocity of radial artery near the elbow, the diameter of brachial artery near the elbow were less than 0.1. The multivariable Cox proportional hazard model revealed that only the peak systolic velocity of radial artery near the elbow exhibited a significant impact on the functional primary patency of radiocephalic fistula (HR=1.017, 95%CI 1.002–1.031, P=0.021). ConclusionsThe peak systolic velocity of the radial artery near the elbow is a significant risk factor for functional primary patency of radiocephalic fistula. Preoperative evaluation of the peak systolic velocity could allow to identify patients with a lower likelihood of long-term radiocephalic fistula patency, facilitating improved selection of candidates for radiocephalic fistula creation.

The role of sarcopenic obesity for the prediction of prognosis of patients with gastrointestinal cancer.

Sarcopenic obesity (SO) in patients with gastrointestinal cancer is associated with a poor prognosis. We aimed to investigate the prognostic impact of SO in patients with gastrointestinal cancer, as well as the diagnostic cut-off value of SO in patients with gastrointestinal cancer among Chinese population. We conducted a consecutive cohort study. Between January 2017 and January 2019, 289 patients diagnosed with gastrointestinal cancer were included in our study. Skeletal muscle area, total fat area, and subcutaneous fat area were measured by CT scan. All patients were followed up for 5 years. Receiver operating characteristic curves (ROC) were adopted to determine the cut-off values of visceral fat obesity for the prediction of sarcopenia. Based on the cut-off values, patients with sarcopenia combined with visceral fat obesity were divided into the SO group, and the others were divided into the non-sarcopenic obesity (NSO) group. Kaplan-Meier curves and univariate and multivariate Cox proportional hazard models were employed to explore the associations of body composition profiles with 5-year overall survival and disease-specific survival. Obtained from Youden's Index for ROC for the prediction of 5-year survival, skeletal muscle mass index (SMI) ≤40.02 cm2/m2 with VFA ≥ 126.30 cm2 in men and SMI ≤32.05 cm2/m2 with VFA ≥72.42 cm2 in women indicate a risk of poor prognosis in patients diagnosed with gastrointestinal cancer. Patients with SO had poorer 5-year overall survival (OS) than patients with NSO (6.74% vs. 82.84%, p < 0.001), and poorer 5-year DFS (6.74% vs. 81.82%, p < 0.001). In multivariate analysis, we found that the long-term mortality risk was approximately 13-fold higher among patients in the SO group compared to those with no conditions. Preoperative assessment of SO is useful not only for monitoring nutritional status but also for predicting 5-year OS in gastrointestinal cancer patients.

Epicardial pacing outcomes in infants with heart block: Lead and device complications from a multicenter experience

BackgroundInfants with complete heart block (CHB) require epicardial pacemaker (PM) insertion. Prior studies described epicardial pacing outcomes in infants and children, although they were limited by small or heterogeneous populations. ObjectiveThis study aimed to explore patient- and procedure-level associations with device complications in infants with CHB who received a permanent PM. MethodsThis was a multicenter, retrospective cohort study including infants receiving an epicardial PM between 2000 and 2021 for CHB. The primary outcome was time to device-related adverse event: lead failure requiring revision; pocket infection; exit block requiring increased pacing output; or lead-related coronary artery compression. Time-to-event analysis was performed by the Kaplan-Meier method with a multivariable Cox proportional hazards model. ResultsThere were 174 infants who received an epicardial PM (282 bipolar, 39 unipolar leads) for CHB. Median age and weight at PM were 93.5 days and 4.5 kg, respectively. Pacing indication was postoperative CHB in 63% and congenital CHB in 37%. The median follow-up was 2.1 years. The primary outcome occurred in 26 infants at a median time to event of 0.6 year. Age ≤90 days at PM implantation was the most significant risk factor for a device-related adverse event (hazard ratio, 7.02; P < .001), primarily driven by pocket infections. Lead failure occurred in 3% of leads with a 5- and 10-year freedom from failure of 93% and 83%, respectively. ConclusionDevice complications affect 15% of infants receiving a permanent PM for heart block. Age ≤90 days at PM implantation is especially associated with infectious complications. Epicardial lead durability appears similar to previously reported pediatric experiences.

Social Factors Associated with the Risk of Glaucoma Suspect Conversion to Glaucoma: Analysis of the Nationwide All of Us Program

To examine social factors associated with the 5-year risk of glaucoma suspects (GS) converting to open-angle glaucoma (OAG). Retrospective cohort analysis. We screened for participants diagnosed with GS in the All of Us database. Cases that converted to OAG within 5 years of GS diagnosis (the "conversion group") were compared with control cases that did not convert. Demographic, socioeconomic and healthcare utilization data of the cases were extracted and compared between the conversion group and the control group. Multivariable Cox proportional hazards modeling was used to identify potential factors associated with the risk of conversion. Hazard ratios (HRs) of significant factors associated with the risk of conversion. A total of 5274 GS participants were identified, and 786 (15%) cases converted to OAG within 5-year follow-up. The two groups showed significant differences in age, race, gender, employment status, income/education level, history of intra-ocular surgery, and healthcare utilization patterns. In the multivariable model, African American/Black race (HR [95% confidence interval] =1.70 [1.44-2.00]), older age at GS diagnosis (1.17 [1.09-1.25]), male gender (1.30 [1.13-1.50], no history of recreational drug use (1.23 [1.07-1.42]), history of intra-ocular surgery (1.60 [1.02-1.53]) and having more reasons for delayed healthcare access (2.27 [1.23-4.18]) were associated with a greater hazard of conversion, while being employed (0.71 [0.60-0.86]) was associated with a smaller hazard of conversion (P<0.05 for all). Several social factors were associated with the conversion from GS to OAG, which may help to identify patients at higher risk of disease progression. Future studies are needed to examine the basis for these findings and the potential interventions that could address them.

Epidemiology of Diffuse Alveolar Hemorrhage in Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients

Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary toxicity that can arise after hematopoietic cell transplantation (HCT). Risk factors and outcomes are not well understood owing to a sparsity of cases spread across multiple centers. The objectives of this epidemiologic study were to characterize the incidence, outcomes, transplantation-related risk factors and comorbid critical care diagnoses associated with post-HCT DAH. Retrospective analysis was performed in a multicenter cohort of 6995 patients age ≤21 years who underwent allogeneic HCT between 2008 and 2014 identified through the Center for International Blood and Marrow Transplant Research registry and cross-matched with the Virtual Pediatric Systems database to obtain critical care characteristics. A multivariable Cox proportional hazard model was used to determine risk factors for DAH. Logistic regression models were used to determine critical care diagnoses associated with DAH. Survival outcomes were analyzed using both a landmark approach and Cox regression, with DAH as a time-varying covariate. DAH occurred in 81 patients at a median of 54 days post-HCT (interquartile range, 23 to 160 days), with a 1-year post-transplantation cumulative incidence probability of 1.0% (95% confidence interval [CI], .81% to 1.3%) and was noted in 7.6% of all pediatric intensive care unit patients. Risk factors included receipt of transplantation for nonmalignant hematologic disease (reference: malignant hematologic disease; hazard ratio [HR], 1.98; 95% CI, 1.22 to 3.22; P = .006), use of a calcineurin inhibitor (CNI) plus mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis (referent: CNI plus methotrexate; HR, 1.89; 95% CI, 1.07 to 3.34; P = .029), and grade III-IV acute GVHD (HR, 2.67; 95% CI, 1.53-4.66; P < .001). Critical care admitted patients with DAH had significantly higher rates of systemic hypertension, pulmonary hypertension, pericardial disease, renal failure, and bacterial/viral/fungal infections (P < .05) than those without DAH. From the time of DAH, median survival was 2.2 months, and 1-year overall survival was 26% (95% CI, 17% to 36%). Among all HCT recipients, the development of DAH when considered was associated with a 7-fold increase in unadjusted all-cause post-HCT mortality (HR, 6.96; 95% CI, 5.42 to 8.94; P < .001). In a landmark analysis of patients alive at 2 months post-HCT, patients who developed DAH had a 1-year overall survival of 33% (95% CI, 18% to 49%), compared to 82% (95% CI, 81% to 83%) for patients without DAH (P < .001). Although DAH is rare, it is associated with high mortality in the post-HCT setting. Our data suggest that clinicians should have a heightened index of suspicion of DAH in patients with pulmonary symptoms in the context of nonmalignant hematologic indication for HCT, use of CNI + MMF as GVHD prophylaxis, and severe acute GVHD. Further investigations and validation of modifiable risk factors are warranted given poor outcomes.

Evaluation of patients with severe pulmonary hypertension and a range of comorbidities prescribed inhaled treprostinil

PurposePatients with pulmonary arterial hypertension (PAH) and additional cardiac or pulmonary comorbidities have a poor prognosis and are frequently excluded from clinical trials. The purpose of this study was to evaluate outcomes of patients with PH secondary to a range of World Symposium on PH (WSPH) groups treated with inhaled treprostinil (iTRE) in a real-world setting. MethodsPatients with PH who were started on treatment with iTRE at Duke University were classified by WSPH Group, and included patients with Group 1, Group 2, Group 3, combined Group 2 & 3 (PH in the setting of left heart failure and chronic lung disease), Group 4, and Group 5 PH. Time to disease worsening, a composite of death, lung transplantation or transition to intravenous prostacyclin, was compared by WSPH Group, and iTRE treatment status using a multivariable Cox proportional hazards model adjusted for age, sex, and REVEAL Lite 2 risk score. Treatment with iTRE was defined as a time-varying covariate. ResultsThe cohort included 270 patients with PH: 30.6% Group 1; 10% Group 2; 32.2% Group 3; 11.1% combined Group 2 & 3; and 15.9% with either Group 4 or 5 PH. At 3-months and 6-months of follow-up, 24.8% and 38.9% of patients respectively were no longer treated with iTRE. Patients who discontinued treatment with iTRE had a significantly higher risk of disease worsening (adjusted HR: 5.02, 95% CI: 3.44 – 7.31). There was no significant difference in disease worsening among WSPH Groups. ConclusionIn a real-world setting, many patients with PH secondary to a range of WSPH Groups tolerated treatment with iTRE. Future studies should phenotype patients with PH based on both comorbidities and therapeutic responsiveness.

Serum S-adenosylhomocysteine, rather than homocysteine, is associated with hepatocellular carcinoma survival: a prospective cohort study

BackgroundEmerging evidence suggested that S-adenosylhomocysteine (SAH) may be a better serum biomarker for cardiovascular disease than homocysteine (Hcy). However, the role of SAH in hepatocellular carcinoma (HCC) prognosis remains unclear. ObjectivesWe aimed to prospectively explore the relationships between serum SAH and related metabolites [Hcy, S-adenosylmethionine (SAM)] with HCC survival, and to evaluate the effect modifications by gene polymorphisms in one-carbon metabolism key enzymes. MethodsWe included 1080 newly diagnosed patients with HCC from the Guangdong Liver Cancer Cohort. Serum SAH, Hcy, and SAM were measured utilizing high-performance liquid chromatography–tandem mass spectrometry. Gene polymorphisms in one-carbon metabolism key enzymes were identified using kompetitive allele-specific polymerase chain reaction. Primary outcomes were liver cancer-specific survival (LCSS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariate Cox proportional hazards models. ResultsAfter a median follow-up of 3.6 y, 601 deaths occurred, with 552 (92%) attributed to HCC. Multivariable analysis revealed that patients in the highest quartile of serum SAH concentrations were significantly associated with worse survival compared with those in the lowest quartile, with HRs of 1.58 (95% CI: 1.19, 2.10; P-trend = 0.002) for LCSS and 1.54 (95% CI: 1.18, 2.02; P-trend = 0.001) for OS. There were no significant interactions between serum SAH concentrations and genetic variants of one-carbon metabolism key enzymes. No significant associations were found between serum Hcy, SAM concentrations, and SAM/SAH ratio with LCSS or OS. ConclusionsHigher serum SAH concentrations, rather than Hcy, were independently associated with worse survival in patients with HCC, regardless of the genetic variants of one-carbon metabolism key enzymes. These findings suggest that SAH may be a novel metabolism-related prognostic biomarker for HCC.

Arthroscopic Bankart Repair for Anterior Glenohumeral Instability in 488 Adolescents Between 2000 and 2020: Risk Factors for Subsequent Recurrent Instability Requiring Revision Stabilization.

After arthroscopic Bankart repair (ABR) for anterior glenohumeral instability (GHI), adolescent athletes have higher rates of subsequent recurrent GHI than any other subpopulation. Elucidating which adolescents are at highest risk of postoperative recurrent GHI may optimize surgical decision-making. To identify prognostic factors associated with subsequent recurrent GHI requiring revision stabilization surgery (RSS) after ABR. Case-control study; Level of evidence, 3. The study included patients 12 to 21 years old who had undergone ABR for anterior GHI at a pediatric tertiary care hospital by 1 of 5 sports medicine fellowship-trained surgeons between 2000 and 2020. A multivariate Cox proportional hazards model, with percentage of patients with recurrent GHI undergoing subsequent RSS, was used with a time-to-event outcome analysis. The Cox model effects were expressed as the hazard ratio (HR). All tests were 2-sided, with an alpha of .05. Records of 488 adolescent patients with ABR (78% male; mean age, 16.9 ± 1.98 years) were analyzed. Of these, 86 patients (17.6%) underwent subsequent RSS for recurrent GHI, yielding a cumulative risk of 8.8% at 2 years, 16.5% at 5 years, and 20% at 15 years. RSS occurred at a mean of 2.6 ± 2.1 years after ABR. Risk factors for RSS included >1 preoperative dislocation (2 dislocations: HR = 7.4, P = .0003; ≥3 dislocations: HR = 10.9, P < .0001), presence of a Hill-Sachs lesion (small: HR = 2.5, P = .0114; medium-large: HR = 4.2, P = .0004), younger age (1-year decrease: HR = 1.2, P = .0015), and participation in contact sports (HR = 1.8, P = .01). Adolescents with only 1 preoperative dislocation had a cumulative incidence of RSS (3.2%), which was significantly lower than those with 2 (24.2%) or ≥3 preoperative dislocations (33.5%). The number of dislocations before index ABR was the strongest risk factor for recurrent GHI requiring RSS in adolescents with anterior GHI, with 2 dislocations conferring >7-fold increased risk compared with a single preoperative dislocation. Other significant risk factors included the presence of a Hill-Sachs lesion, younger age, and participation in contact sports.

Discrepancy between estimated glomerular filtration rate by creatinine versus cystatin C in different patient care settings

ObjectiveEstimated glomerular filtration rate (eGFR) calculated by cystatin C (cysC) has been recommended for broader adoption. This study assessed the discrepancy between eGFR calculated by cysC (eGFRcys) and creatinine (eGFRcr) in different patient care settings and explored potential contributing factors to such discrepancies. MethodsThis retrospective study included 2072 patients with paired cysC and creatinine results in different patient care settings. Delta eGFRcr-cys (eGFRcr − eGFRcys) was analyzed in relationship to patient care settings and the Elixhauser Comorbidity index. The 90-day survival in patients with different delta eGFR was assessed by Kaplan-Meier analysis, univariate and multivariate Cox proportional hazard models. In addition, discrepancy between eGFRcys and eGFRcr was analyzed in 50 ambulatory patients with systemic inflammation but normal kidney function. ResultsInpatients had higher cysC (median 1.91 mg/L), lower eGFRcys (median 31 mL/min/1.73 m2), and larger delta eGFRcr-cys (median 18 mL/min/1.73 m2) than outpatients (cysC median 1.53 mg/L, p < 0.0001, eGFRcys median 41 mL/min/1.73 m2, p < 0.0001, delta eGFRcr-cys median 4 mL/min/1.73 m2, p < 0.0001). Higher Elixhauser Comorbidity index correlated with lower eGFRcys and larger delta eGFRcr-cys, with median delta eGFRcr-cys 11 and 6 mL/min/1.73 m2 in patients with a Comorbidity index > 15 and ≤ 15, respectively (p < 0.0001). Increased delta eGFRcr-cys was associated with worse 90-day survival. Patients with systemic inflammation but normal kidney function had lower eGFRcys (median 77.5 mL/min/1.73 m2) than eGFRcr (median 97 mL/min/1.73 m2, p < 0.001), with red blood cell abnormalities as associated factors. ConclusionInflammation and comorbidities are associated with decreased eGFRcys and large discrepancies between eGFRcr and eGFRcys independent of kidney function and are most apparent in inpatients. Creatinine-cysC combined eGFR reduces this discrepancy and should be broadly adopted.

Association between short-term changes in serum magnesium and in-hospital mortality following acute myocardial infarction: a cohort study based on the MIMIC database.

The association between short-term changes in serum magnesium level and risk of in-hospital mortality was investigated in patients with acute myocardial infarction (AMI). In this retrospective cohort study, data of 2,716 patients with AMI were extracted from the Medical Information Mart for Intensive Care (MIMIC-III and MIMIC-IV) database for 2001-2012. Univariate and multivariate Cox proportional hazards models were used to explore the association between serum magnesium level and short-term change and in-hospital mortality in patients with AMI. In addition, subgroups according to age, gender, Sequential Organ Failure Assessment (SOFA) score, and Simplified Acute Physiology Score (SAPS-II) were also analysed. In total, 504 (18.6%) patients died in hospital. After adjusting for covariates, all AMI patients with high magnesium levels at ICU admission (HR=1.03, 95%CI: 0.83-1.27) or 48 hours after ICU admission (all p<0.05), or those demonstrating a change in magnesium level within the first 48 hours of ICU stay (all p<0.05) were shown to have a high risk of in-hospital mortality. Moreover, this correlation was retained irrespective of age, gender, SOFA score, and SAPS-II (allp<0.05). Serum magnesium levels at different time points after ICU admission and change in serum magnesium level during the first 48 hours were associated with in-hospital mortality in patients with AMI, indicating that clinical attention should be paid to short-term changes in serum magnesium levels regarding treatment adjustment, which may further reduce the risk of mortality.

Verification of haemoglobin level to prevent worsening of prognosis in heart failure with preserved ejection fraction patients from the PURSUIT-HFpEF registry.

Anaemia has been reported as poor predictor in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to evaluate the impact of changes in haemoglobin (Hb) from discharge to 1year after discharge on the prognosis using a lower cut-off value of Hb than the World Health Organization (WHO) criteria. First, 547 HFpEF cases were divided into two groups, Hb<11.0g/dL (n=218) and Hb≥11.0g/dL (n=329), according to Hb at discharge, and further were divided according to Hb 1year after discharge into Hb<11.0g/dL (G1, n=113), Hb≥11.0g/dL (G2, n=105), Hb<11.0g/dL (G3, n=66), and Hb≥11.0g/dL (G4, n=263), respectively. Major adverse cardiovascular events (MACE) was defined as composite of all-cause death and heart failure readmission after a visit 1year after discharge. The cut-off value of Hb was analysed by the receiver operating characteristics curve that predicts MACE. We examined the incidence rate of MACE between G4 and other subgroups and verified predictors of improving or worsening anaemia and covarying factors with change in Hb. In multivariate Cox proportional hazard model, MACE was significantly higher in G3 with worsening anaemia from Hb≥11.0g/dL to <11.0g/dL than G4 with persistently Hb≥11g/dL (adjusted hazard ratio (HR): 3.14 [95% confidence interval (CI), 1.76-5.60], P<0.001). MACE was not significantly different between G2 with improving anaemia from Hb<11.0g/dL to ≥ 11.0g/dL and G4 (adjusted HR: 1.37 [95% CI, 0.68-2.75], P=0.38). In multivariate logistic regression analysis, independent predictors of improving anaemia were male [odds ratio (OR): 0.45], chronic obstructive pulmonary disease (OR: 10.3), prior heart failure hospitalization (OR: 0.38), and estimated glomerular filtration rate (OR: 1.04). Independent predictors of worsening anaemia were age (OR: 1.07), body mass index (BMI) (OR: 0.86), clinical frailty scale score (OR: 1.29), Hb at discharge (OR: 0.63), and use of angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker (OR: 2.76). In multivariate linear regression analysis, covarying factors with change in Hb were BMI (β=-0.098), serum albumin (β=0.411), and total cholesterol (β=0.179). Change in haemoglobin after discharge using a lower cut-off value than WHO criteria has prognostic impact in patients with HFpEF.

Impact of early bleeding on long-term mortality after left atrial appendage occlusion

BackgroundShort-term antithrombotic therapy is recommended after left atrial appendage occlusion(LAAO) to reduce the risk of device-related thrombosis(DRT). However, patients referred for LAAO have excess bleeding risk. Yet, short-term bleeding events post-LAAO are not well characterized. ObjectiveWe aimed to evaluate the incidence of early bleeding post-LAAO and its association with long-term mortality risk. We also sought to identify predictors of early bleeding. MethodsPatients who underwent LAAO at Mayo Clinic between 2018 and 2023 were included. Early bleeding was defined as bleeding that occurred within three months of discharge. A multivariable Cox proportional hazards model was used to assess the association between early bleeding and death and to estimate the hazard ratio(HR). Multivariable regression analysis was used to identify predictors of early bleeding. ResultsAmong the 592 patients included, 389(66%) were male, and mean age was 75.6 years. Eighty-three patients(14.0%) experienced early bleeding, with the majority having minimal(63.4%) or minor(17.3%) bleeding. At a median follow-up of 14.4 months(IQR 4.2-27.9), early bleeding after LAAO was associated with an increased risk of all-cause mortality (adjustedHR, 2.07; 95%CI, 1.15-3.75; P=0.02). A history of intracranial bleeding, non-paroxysmal atrial fibrillation, CHA2DS2VASc score, and early DRT were independent predictors of early bleeding. Anti-thrombotic therapy on discharge was not associated with early non-procedural bleeding. ConclusionsOne in seven patients experience a non-procedural bleeding event within 90 days after LAAO. Early bleeding after LAAO is associated with a higher all-cause mortality during mid-term follow-up. Further studies are needed to optimize the management of patients undergoing LAAO.

Survival of different caries managements in children with autism and unaffected peers: a retrospective cohort study.

Dental caries is a common oral disease in children with special needs such as those with autism spectrum disorders (ASDs). The aim is to assess whether the type and survival of three caries management, conventional resin restorations (CR), ART technique (ART) and SDF application without caries removal (SDF), in primary teeth carried out at the Pediatric Dentistry Department of San Paolo Hospital (University of Milan) differed between children with ASDs and unaffected peers. Data from a convenience sample of children with and without ASDs, who have received dental care for caries in primary teeth from January 2019 to June 2022, were analysed. Medical history, age, sex, teeth treated, and type of treatment were collected from dental charts. Data on success and minor and major failures of each treatment were also collected. Two survival analysis were performed, one considering both major and minor failures, a second considering only major failures. Cox Proportional Hazards multivariate logistic models were run to assess factors associated with failures. The statistical significance was set at 5% (p< 0.05). In children with autism, the different techniques for approaching caries lesions seem to have the same probability of success. Therefore, the choice of treatment should be patient-oriented rather than lesion-oriented. In unaffected children, the gold standard always seems to be traditional restorative treatment.

Defining and Understanding Diagnostic Delays Among Pancreatic Cancer Patients: A Retrospective Cohort Study

Pancreatic cancer is a lethal cancer of increasing incidence, presenting with several clinically detectable signals allowing for earlier diagnosis. However, there is limited data related to diagnostic process, including prevalence of diagnostic delays and their contributing factors. We aimed to develop a standardized definition of diagnostic delay, evaluate its prevalence, and identify its contributing factors among pancreatic cancer patients. We convened an expert panel who defined "diagnostic delay" among pancreatic cancer patients. We then conducted a retrospective cohort study among pancreatic adenocarcinoma patients consecutively diagnosed from 2007-2019 at a tertiary care Veterans Affairs medical center. We manually reviewed diagnostic delay instances for contributing factors. Secondary analyses, using multivariate logistic regression and Cox proportional hazards models, explored associations between diagnostic delays and cancer outcomes. "Diagnostic delay" was defined as cancer diagnosis made ≥60 days after first clinical presence of predefined red-flag(s). Among 197 pancreatic adenocarcinoma patients, 38.6% experienced a diagnostic delay. Among delay cases, the most common primary contributing factor was related to the patient-provider encounter (44.7% with lack of recognition of objective weight loss). Patients with delays were more likely to be diagnosed at advanced stage disease (adjusted odds ratio (OR) 1.62; 95% confidence interval (CI) 0.79-3.30) and less likely to receive potentially curative treatment (adjusted OR 0.72; 95% CI 0.28-1.84), although these trends did not reach statistical significance. Over one-third of pancreatic cancer patients experienced a diagnostic delay, mostly due to inadequate recognition of red-flag findings. Results can inform targeted interventions to reduce preventable diagnostic delays among pancreatic cancer patients.

Prevalence and Prognostic Significance of Malnutrition in Patients with Type B Aortic Dissection Undergoing Endovascular Repair.

Malnutrition is a poor prognostic factor in a wide range of diseases. Nevertheless, there is a lack of data investigating the association between malnutrition and outcomes of patients with type B aortic dissection (TBAD) undergoing thoracic endovascular aortic repair (TEVAR). Therefore, the aim of the present study was to report the prevalence and clinical impact of malnutrition assessed by the controlling nutritional status (CONUT) score in TBAD patients undergoing TEVAR. The retrospective study indicated that a total of 881 patients diagnosed with TBAD and treated with TEVAR from January 2010 to December 2017 were categorized into subgroups based on their CONUT score (low 5 vs. high 5). To assess the correlation between malnutrition and early and follow-up outcomes of TBAD patients, logistic and Cox regression analysis were utilized, incorporating inverse probability weighting. Malnutrition was present in 20.3% of patients according to the CONUT score. Multivariate logistic regression analysis revealed that pre-operative CONUT score modeled as a continuous variable was an independent risk factor for prolonged intensive care unit stay (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.17; p = 0.015), 30-day death (OR, 1.43; 95% CI, 1.19-1.72; p 0.001), delirium (OR, 1.11; 95% CI, 1.01-1.23; p = 0.035) and acute kidney injury (OR, 1.09; 95% CI, 1.01-1.16; p = 0.027). During a median follow-up of 70.8 (46.1-90.8) months, 102 (11.8%) patients died (high CONUT group: 21.8% vs. low CONUT group: 9.0%; p 0.001). Multivariable Cox proportional-hazards models showed that malnutrition was an independent predictor for follow-up mortality (hazard ratio, 1.68; 95% CI, 1.11-2.53; p = 0.014). Results remained consistent across various sensitivity analyses. Malnutrition assessed by the CONUT score could profoundly affect the early and follow-up prognosis in patients undergoing TEVAR. Routine pre-intervention nutritional evaluation might provide valuable prognostic information.

Survival outcome and prognostic factors in patients with chemotherapy-naive metastatic castration-resistant prostate cancer treated with abiraterone acetate – real-world experience in Vietnam

Introduction and aim. In real life, metastatic castration-resistant prostate cancer patients (mCRPC) had more complex clinical presentation than patients in the COU-AA-302 trial. This study primarily aimed to describe the overall survival of chemotherapy-naive mCRPC treated with abiraterone acetate plus prednisone (AAP). Other relevant outcomes and baseline characteristics of these patients were also evaluated. Material and methods. This retrospective, observational study collected data from chemotherapy-naive mCRPC patients treated with AAP in Vietnam. Kaplan-Meier curves were used to estimate time to treatment failure (TTF), and overall survival (OS). The impact of baseline characteristics on OS was explored using univariate and multivariate Cox proportional hazard models. Results. Data from 65 eligible patients were analyzed. The rate of PSA response was 73.8%, median PSA PFS was 10.5 months (95% CI: 7.4–13.6), median TTF was 15 months (95% CI: 11.1–18.9), and median OS was 24.9 months (95% CI: 18.9–30.9). Shorter OS was significantly associated with a higher Gleason score (≥8), shorter time from ADT start to mCRPC (&lt;12 months), visceral metastases, and &lt;50% PSA decline (p&lt;0.05). Conclusion. Abiraterone acetate plus prednisone is well tolerated and effective for chemotherapy-naive mCRPC patients in clinical practice. Moreover, Gleason score, visceral metastasis, time from ADT start to mCRPC, and PSA response are the independent indicators for predicting the OS of mCRPC patientsin both univariate and multivariate analyses.

Incidence and Survival of Patients With Malignant Primary Spinal Cord Tumors: A Population-Based Analysis

Objective: Epidemiological studies on spinal cord tumors are rare, and studies on primary intramedullary tumors are even rarer. The incidence and survival of patients with primary intramedullary spinal cord tumors have not been well documented. We aimed to study the incidence and survival of patients with primary spinal cord malignant and borderline malignant tumors based on data from the Surveillance, Epidemiology, and End Results (SEER) database and provide information for revealing the epidemiology and exploring the prognosis of patients with primary intramedullary tumors.Methods: Patients in the SEER database with microscopically diagnosed malignant and borderline malignant primary spinal cord tumors from 2000 and 2019 were included in this study. We analyzed the distribution of patients according to the demographic and clinical characteristics. Then, we extracted the incidence rate and 5-year relative survival for the whole cohort and different subgroups of the cohort. Finally, multivariate Cox proportional hazards models were used to analyze the independent prognostic factors associated with overall survival.Results: A total of 5,211 patients with malignant and borderline malignant primary spinal cord tumors were included in this cohort study. Ependymoma, astrocytoma (including oligodendrogliomas and glioblastoma), lymphoma and hemangioblastoma were the most common pathological types. The age-adjusted incidence rates of primary spinal cord ependymoma was 0.18 per 100,000. The incidence rate for females was significantly lower than that for males. The incidence rate was highest in Caucasian. The incidence rate of ependymoma was significantly higher than that of other pathological types. The incidence of astrocytoma was highest among people aged 0–19 years, the incidence of ependymoma was highest among people aged 40–59 years, and the incidence of lymphoma was highest among people aged 60 years or older. The 5-year observed survival and relative survival rates for the whole cohort were 82.80% and 86.00%, respectively. Patients diagnosed with ependymoma had significantly better survival than their counterparts. We also found the impact of surgery and chemotherapy on the prognosis of patients with different tumors varies a lot.Conclusion: We conducted a population-based analysis of malignant and borderline malignant primary spinal cord tumors with the aim of revealing the epidemiology and survival of patients with primary intramedullary spinal cord tumors. Despite some shortcomings, this study provides valuable information to help us better understand the epidemiological characteristics of primary intramedullary spinal cord tumors.

Endoscopic Resections for Barrett's Neoplasia: A Long-Term, Single-Center Follow-Up Study.

Background and Objectives: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are both well-established and effective treatments for dysplasia and early cancer in Barrett's esophagus (BE). This study aims to compare the short- and long-term outcomes associated with these procedures in treating Barrett's neoplasia. Materials and Methods: This single-center retrospective cohort study included 95 patients, either EMR (n = 67) or ESD (n = 28), treated for Barrett's neoplasia at Sahlgrenska University Hospital between 2004 and 2019. The primary outcome was the complete (en-bloc) R0 resection rate. Secondary outcomes included the curative resection rate, additional endoscopic resections, adverse events, and overall survival. Results: The complete R0 resection rate was 62.5% for ESD compared to 16% for EMR (p < 0.001). The curative resection rate for ESD was 54% versus 16% for EMR (p < 0.001). During the follow-up, 22 out of 50 patients in the EMR group required additional endoscopic resections (AERs) compared to 3 out of 21 patients in the ESD group (p = 0.028). There were few adverse events associated with both EMR and ESD. In both the stratified Kaplan-Meier survival analysis (Log-rank test, Chi-square = 2.190, df = 1, p = 0.139) and the multivariate Cox proportional hazards model (hazard ratio of 0.988; 95% CI: 0.459 to 2.127; p = 0.975), the treatment group (EMR vs. ESD) did not significantly impact the survival outcomes. Conclusions: Both EMR and ESD are effective and safe treatments for BE neoplasia with few adverse events. ESD resulted in higher curative resection rates with fewer AERs, indicating its potential as a primary treatment modality. However, the survival analysis showed no difference between the methods, highlighting their comparable long-term outcomes.

APOE epsilon variants and composite risk of dementia, disability, and death in the health and retirement study

AbstractBackgroundClinical trials in older adults are increasingly focused on functional outcomes, and the composite outcome of dementia, disability, and death is gaining pivotal importance. Genetic variation, particularly the APOE epsilon(ε) variants, may modify responses to new treatments. Although APOE ε4 is known to influence these outcomes separately, the magnitude of its effect on this composite outcome remains unknown. We tested the hypothesis that APOE ε4 increases, whereas APOE ε2 decreases, the risk of a composite outcome of dementia, disability, and death.MethodsWe evaluated clinical and genomic data from the Health and Retirement Study collected from 1992 to 2020. We used variants rs429358 and rs7412 to determine APOE genotypes, modeled dominantly (carriers/noncarriers). We conducted survival analysis, using multivariable Cox proportional hazards models with a composite endpoint of dementia, disability, and death. Our primary analysis evaluated participants with genetic data and no previous dementia or disability. In secondary analyses, we focused on persons aged &gt; = 75 years without heart disease or stroke, a subpopulation increasingly important in clinical trials of older adults.ResultsWe included 14,527 participants in the primary analysis. Over a median of 18 (Interquartile Range [IQR] 12–24) years, 6711 (46%) participants developed the composite outcome. In Cox analyses, APOE ε4 associated with higher risk (HR:1.15, 95%CI:1.09–1.22) of the composite outcome, whereas APOE ε2 associated with lower risk (HR:0.92, 95%CI:0.86–0.99). In the secondary analysis, we included 3174 participants. Over a median of 7 (IQR 4–11) years, 1326 participants (42%) developed the composite outcome. In Cox analyses, APOE ε4 associated with higher risk (HR:1.25, 95%CI:1.10–1.41) of the composite outcome, whereas APOE ε2 associated with lower risk (HR:0.84, 95%CI:0.71–0.98).ConclusionsAPOE ε variants are linked to the risk of dementia, disability, and death in older adults. By examining these variants in clinical trials, we can better elucidate how they might alter the effectiveness of tested interventions. Importantly, this genetic information could help identify participants who may have greater absolute benefit from such interventions.

MGMT promoter methylation in prognosis of patients with newly diagnosed IDH1 wildtype Glioblastoma

The objective of this study was to analyse the prognosis values of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation on the overall survival in patients with newly diagnosed isocitrate dehydrogenase 1 (IDH1) wild-type glioblastoma multiforme (GBM). A retrospective observational study was conducted on 108 IDH1 wild-type glioblastoma patients who underwent tumour resection at neurosurgical centres, including Hanoi Medical University Hospital and Viet Duc University Hospital, from October 2017 to December 2021. The MGMT status was assessed using methylation-specific Polymerase Chain Reaction (MSP). Multivariable Cox proportional hazards models and Kaplan-Meier survival analysis were performed. Of 108 patients, 79.6% had methylated MGMT. The median overall survival of patients with IDH1 wild-type GBM was 8.47 months (95%Confidence Interval (CI) =6.93-11.07). Patients with Methylated MGMT had a lower mortality risk (Hazard Ratio (HR) =0.63, 95%CI=0.41-0.98) than those without Methylated MGMT. Patients aged &lt;55 HR=0.55, CI=0.35-0.85)&gt;=55 years old. Having tumours on both sides of the hemisphere was associated with a higher risk of mortality (HR=3.18, 95%CI=1.68-6.00) compared to patients with tumours on the right side of the hemisphere. To conclude, our data underline the impact of the MGMT promoter methylation status in the treatment response of IDH1-wildtype GBM. In addition, age, tumour size and hemisphere were also significant prognostic factors in the overall survival of patients.