Multivariate Cox Hazard Model Research Articles

Prognostic Significance of C-reactive protein or Prealbumin in Pancreatic Ductal Adenocarcinoma.

To clarify the prognostic significance of the C-reactive protein to prealbumin ratio (CRP or PALB) in patients with pancreatic cancer after radical resection. A total of 432 patients with pathologically confirmed pancreatic ductal adenocarcinoma were enrolled in this retrospective study. The predictive capacity of various inflammatory indices was analyzed and compared using the area under the time-dependent receiver operating characteristic curve, including CRP or PALB, CRP-to-albumin ratio, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. The univariate and multivariate Cox hazard models were employed to analyze the effects of CRP or PALB on overall survival (OS) and recurrence-free survival (RFS). The optimal cut-off value for preoperative CRP or PALB was 5.94, which was derived from the receiver operating characteristic curve. In comparison with traditional inflammatory indices, CRP or PALB had the highest area under the time-dependent receiver operating characteristic curve (0.693 for 3-y OS, 0.664 for 3-y RFS, 0.662 for 5-y OS, and 0.670 for 5-y RFS), all with P<0.05. However, when compared with neutrophil-to-lymphocyte ratio, the predictive power of CRP or PALB was not significant for 3-y RFS (P=0.085). Based on the results of the univariate and multivariate survival analyses, patients in the high CRP or PALB group (HCP: CRP or PALB >5.94) exhibited significantly poorer OS and RFS (median OS: 20.0 versus. 38.0mo, P=0.003; median RFS: 10.0 versus. 22.0mo, P<0.001) than those in the low CRP or PALB group (CRP or PALB ≤5.94). The multivariate analysis indicated that the HCP was independently associated with poor OS (hazard ratio (HR): 1.556, 95% confidence interval (CI) [1.089-2.222], P=0.015) and RFS (HR: 1.551, 95% CI [1.135-2.119], P=0.006). The predictive capacity of preoperative CRP or PALB in pancreatic ductal adenocarcinoma patients exceeds that of traditional inflammatory indices. HCP levels are significantly correlated with a poor prognosis.

Survival Impacts of Mitochondrial Status in Esophageal Squamous Cell Carcinoma Patients.

Little is known about the survival impacts of mitochondrial status in esophageal squamous cell carcinoma (ESCC) patients who undergo neoadjuvant chemotherapy (NAC) followed by surgery. In total, 260 pre-NAC samples from ESCC patients were analyzed. Mitochondrial status was estimated employing an objective, immunohistochemistry-based system (Mito-score). Mito-scores were dichotomized according to the median value of our cohort. We also evaluated the immune microenvironment (CD4, CD8, Foxp3, HLA class-1, Ki-67 and programmed death ligand-1) on pre-NAC specimens. Multivariate Cox hazards models were applied to determine independent predictors of poor overall survival (OS). Patients with cT3-4 tumors had higher Mito-scores than those with cT1-2 tumors (p=0.06), and good responders to NAC had significantly higher Mito-scores than poor responders to NAC (p=0.04). CD8 cells and Ki-67 expression were significantly higher in Mito-high than Mito-low tumors (p=0.017 and p<0.001, respectively). Patients with low Mito-scores had significantly poorer OS than those with high Mito-scores (3-year OS: 57.6% vs. 68.2%; p=0.03). A survival difference by Mito-score was evident in cStage III-IV patients (3-year OS: low 50.6% vs. high 66.1%; p=0.006). Multivariable analysis revealed that a low Mito-score (hazard ratio 1.59, 95% confidence interval 1.12-2.24; p=0.009) as well as pT3-4 disease (p<0.001) and pN2-3 disease (p<0.001) were independently associated with poor OS outcomes. A low Mito-score before NAC had a significant survival impact in ESCC patients, especially in those with advanced disease. Mitochondrial status might be associated with tumor aggressiveness and responsiveness to NAC, thereby possibly affecting the survival outcomes of ESCC patients.

The association of temperature extremes, ecosystem resilience, with child mortality: Novel evidence from India.

The present study investigates how ecosystem resilience affects children's health and acts as a protective shield against high temperature exposure. Ecosystem resilience is the ability of an ecosystem to absorb anthropogenic or climatic shocks and recover from those shocks. The study used various data sources to estimate the impact of temperature extremes on child mortality in India. Data on neonatal mortality (NMR) and infant mortality (IMR) were obtained from the National Family Health Survey (NFHS-5) conducted between 2019-2021. Satellite data were used to assess extreme heat and ecosystem resilience. Univariate and bivariate Local Indicator of Spatial Autocorrelation (LISA) analysis were applied to examine the spatial association of high temperature, ecosystem resilience, and NMR, IMR. Further, a multivariate Cox hazard model, taking into account the censored data, was used to estimate mortality risk in high temperatures and non-resilient ecosystems. The spatial regression model reveals a significant association between higher temperatures and higher NMR (β: 1.78) and IMR (β: 1.79). The cox-proportional hazard models show elevated risks for neonatal and infant deaths due to high temperatures and non-resilient ecosystems. The resilience of the ecosystem plays an important role in exerting a positive effect on children's health, though, at its current state, resilience fails to moderate the high temperature impact on mortality. The present study, the first of its kind in India, highlights the exposure to high temperatures leading to neonatal and infant deaths when reliance imparts limited protective effect to offshoot the impact of high temperature on excess mortality.

Thoracic Aortic Calcification and Complex Large Aortic Arch Plaque in Patients with Chronic Coronary Syndrome

Aortic arch plaque (AAP) morphology and complexity can serve as markers of atherosclerotic cardiovascular disease. This study investigated 1) the diagnostic value of the thoracic aortic calcification (TAC) score for detecting AAP and large complex AAP and 2) the prognostic significance of TAC in patients with chronic coronary syndrome (CCS). The predictors of AAPs with large (≥ 4 mm in thickness) and complex (ulcerated or protruded) morphologies were evaluated in 412 symptomatic patients with CCS who underwent coronary computed tomography angiography and simultaneous assessment of the aortic arch. Receiver operating curve analysis was performed to determine whether the TAC score can improve the diagnostic value of complex large AAP compared with clinical parameters. Multivariate logistic regression analyses revealed that the TAC score was an independent predictor of complex large AAP (odds ratio, 1.46; P = 0.0074). The area under the curve (AUC) for the base model comprising clinical parameters (age ≥ 70 years + current smoking status + systolic blood pressure) was 0.707 (P = 0.0177). The addition of a TAC score of ≥ 978 Agatston units (AUC, 0.744) significantly improved the AUC (AUC, 0.751, P < 0.001) for patients aged ≥ 70 years (AUC, 0.638). The multivariable Cox hazard model revealed that TAC of ≥ 432.4 (hazard ratio [HR], 4.312; P = 0.01) and large complex AAP are independently associated with the incidence of major adverse cardiovascular events (HR, 3.108; P = 0.011). This study demonstrated that TAC and AAP morphology serve as markers of major adverse cardiovascular events. The combination of advanced age, TAC score, and obstructive CAD exhibited robust diagnostic accuracy in detecting complex large AAP.

Incidence of acute kidney injury and its predictors among neonates admitted at neonatal intensive care unit of, Northwest Ethiopia comprehensive specialized hospitals, 2023

BackgroundAcute kidney injury is an acute and reversible increment in serum creatinine (SCr) levels with a reduction in urine output oliguria, or anuria. Acute kidney injury is a major cause of neonatal morbidity and mortality worldwide; it is a serious problem in low and middle-income countries, particularly in sub-Saharan Africa such as Ethiopia. Moreover, there are few studies in developing countries. This study aimed to investigate the incidence and predictors of acute kidney injury in neonates admitted to the neonatal intensive care unit of some specialized hospitals in the Amhara region of northwestern Ethiopia.MethodsA facility-based retrospective follow-up study was conducted in the Northwest Amhara Region’s comprehensive specialized hospitals with 634 neonates from January 2020 to December 2022. Data were collected by reviewing patient charts using simple random sampling with a pretested checklist, entered using Epi-data 4.6, and analyzed using STATA 14. Median survival time, Kaplan–Meier survival curve, and log-rank test were calculated. Bivariable and multivariable Cox hazard models were used to determine the determinants of acute kidney injury. A hazard ratio with a 95% confidence interval was calculated. Variables with p-values less than 0.05 were considered statistically significant.ResultsThe incidence of Acute Kidney Injury among Neonates admitted to Neonatal Intensive Care Unit was 14.9 per 1000 (95% CI: 12.5–17.7) with the proportion of acute kidney injury (20.19%) (95% CI: 17.23–23.50) neonates with sepsis (AHR: 2.59; 95%CI: 1.21–5.56), neonates with perinatal asphyxia [(AHR: 2.70; 95%CI: 1.29–5.65) were taking gentamicin drugs [(AHR = 1.74; 95%CI: 1.03–2.94], neonates were preterm [(AHR; 1.77: 95%CI: 1.05 -2.98], and neonatal-hyponatremia [(AHR: 2.14; 95%CI: (1.00 -4.9)] and hyperkalemia [(AHR: 2.64; 95 CI: (1.11- 6.2)] were statistically found to be significant predictors of acute kidney injury.ConclusionsThe incidence of acute kidney injury in neonates was high. Premature infants, neonates with sepsis, who suffered perinatal asphyxia, who received gentamicin drugs, whose sodium levels decreased and potassium levels increased were at higher risk of developing acute kidney injury. All concerned agencies should work to prevent acute kidney injury and pay special attention to multifactorial causes. Therefore, strategies need to be developed and/or strengthened to prevent the occurrence of acute kidney injury in infants with sepsis, neonates who suffered perinatal asphyxia, and preterm infants whose sodium levels decreased and potassium levels increased.

Implications of calcified nodule and adjacent calcification severity for target lesion revascularization after percutaneous coronary intervention: multi-center intravascular ultrasound imaging study

Abstract Background Calcified nodule (CN) is a distinct plaque phenotype, characterized as protruding nodular calcification penetrating lumen surface with the attached thrombus. Recent studies revealed that a risk of repeat revascularization after PCI was substantially elevated in patients with coronary artery disease (CAD) attributable to CN. Furthermore, pathohistological studies have elucidated mechanistic insights into the formulation and progression of CN, suggesting that it is formulated by the fracture of sheet calcification at its adjacent segment. Purpose To elucidate the association of calcified plaque volume at CN and adjacent lesions with TLR risks in CAD patients receiving PCI by using IVUS imaging. Methods This multicenter study analyzed IVUS imaging at culprit segment was conducted in 204 CAD patients attributable to de novo CN receiving PCI. The calc grade was assigned at each 1-mm cross-sectional frame of CN and culprit segment, respectively (no calc=0, 1-89°=1, 90-179°=2, 180-269°=3, 270-360°=4). Calcium Volume Index (CVI) at both CN and adjacent zone were calculated (Figure; Calcification volume index at CN zone = the sum of calcium scores at CN・averaged lesion slices of CN / CN lesion slices, Calcification volume index at adjacent zone = the sum of calcium scores at adjacent zone・averaged lesion slices of adjacent zone / adjacent zone slices). Predictors of TLR were analyzed by multivariate Cox hazard model. Results CN was successfully treated by DES (82%) and DCB (18%). 34% and 8.3% of subjects required rotablator and orbital atherectomy, respectively. Consequently, final lumen area after PCI was 7.2 ± 0.4 mm2. During the 2.8-year observational period (interquartile range: 2.4 to 3.2 years), TLR was required in 63 patients (30.9%) of study population. CVI at CN and adjacent zone were 9.9 ± 0.4 and 7.0 ± 0.7, respectively. On multivariate analysis, hemodialysis, final lumen area, CVI at both CN and adjacent zone predicted TLR (Figure). Recurrent TLR (two or more TLRs) was found in 23.3% patients who suffered from TLR. Of note, even among patients who required TLR, CVIs at both zones were significantly higher in patients with recurrent TLR than those without (Figure). Conclusion CAD subjects caused by CN exhibited a considerably high-risk TLRs. Our findings underscore that calcification severity at both CN and adjacent segment predicted TLR and is associated with repeated TLR.methodsResults

Association between reduced risk of gastrointestinal bleeding related to proton pump inhibitor use and subsequent all-cause death in patients with percutaneous coronary intervention

Abstract Background Gastrointestinal bleeding is the leading cause of post-percutaneous coronary intervention (PCI) bleeding complications which are associated with a high risk for subsequent clinical outcomes. The aim of this study was to estimate association between risk of gastrointestinal bleeding events related to proton pump inhibitor (PPI) use and subsequent clinical outcomes in patients with PCI. Methods The Clinical Deep Data Accumulation System (CLIDAS) is a database for inclusive of patient characteristics, medications, laboratory test, physiological test, cardiac catheterization and PCI treatment, all of which were aggregated from electronic medical records in 7 tertiary hospitals in Japan. Data of 6457 patients who underwent PCI between April 2014 and March 2020 and were then followed for 30 days after the index PCI, were analyzed. These patients were divided into two groups based on use of PPI; the PPI group (n=5285; 82%) and the non-PPI group (n=1172; 18%). Clinical outcomes, defined as gastrointestinal bleeding and all-cause death, were assessed using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) models. Results Among the 6457 PCI patients, 90 (1.7%) in the PPI group and 31 (2.6%) in the non-PPI group experienced gastrointestinal bleeding events. Adjusting for baseline demographics, comorbidities, and anti-thrombotic treatments, the multivariable Cox hazard model suggested a trend towards a lower risk of gastrointestinal bleeding with PPI use (HR, 0.70; 95%CI, 0.46-1.05; p=0.087). The PSM analysis confirmed a significant association between PPI use and a lower risk of gastrointestinal bleeding (HR, 0.13; 95%CI, 0.04-0.43; p=0.001), consistent with IPTW model results (HR, 0.60; 95%CI, 0.38-0.95; p=0.031). Subgroup analysis showed that PPI use was associated with a low risk of all-cause death in patients with acute coronary syndrome (ACS) (HR, 0.58; 95%CI, 0.36-0.93; p=0.024). Causal mediation analysis indicated an indirect effect of PPI on reducing all-cause death through the suppression of gastrointestinal bleeding events. Conclusion These findings suggested that use of PPI against gastrointestinal bleeding complications might reduce the risk of subsequent all-cause death in ACS patients undergoing PCI.

Insight into Predictors of Cytoreduction Score Following Cytoreductive Surgery-Hyperthermic Intraperitoneal Chemotherapy for Gastric Peritoneal Carcinomatosis Improves Patient Selection and Prognostic Outcomes.

Peritoneal metastases due to gastric adenocarcinoma (GCPM) carry a dismal prognosis. A promising treatment strategy is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), but clear eligibility criteria for GCPM are lacking. We sought to identify factors associated with overall survival (OS) following CRS-HIPEC for GCPM to help optimize patient selection and clinical outcomes. In this single-center retrospective cohort study, we examined CRS-HIPEC outcomes for patients with GCPM between 2001 and 2021. After analyzing patient demographic, clinicopathologic, and perioperative variables, we applied multivariable Cox hazard models to assess factors associated with OS. We then assessed associations between baseline predictors and prognostically important variables using multivariable logistic regression. We analyzed 55 patients with GCPM who underwent CRS-HIPEC. Median age was 54 years and 42% were female. Median peritoneal carcinomatosis index (PCI) was 8, and 75% of patients achieved a cytoreduction completeness score (CC score) of 0. Median progression-free survival (PFS) was 6.9 months, and median OS was 14.1 months. On adjusted analysis, a CC score > 0 (HR 2.3, p = 0.02) was significantly associated with worse OS. A peritoneal carcinomatosis index greater than 13 (OR 52.6, p = 0.001) and fewer lymph nodes (especially < 18) resected with the primary tumor (OR 0.86, p = 0.042) in the metachronous setting were significantly associated with incomplete macroscopic cytoreduction (CC score > 0). We demonstrated that PCI > 13 and primary lymph nodes harvested < 18 in metachronous tumors are associated with CC score > 0, which in turn portends a worse OS. Although these results warrant prospective validation, they provide insight into improved selection of patients with GCPM for CRS-HIPEC.

The impact of Kirsten rat sarcoma (KRAS) status on local tumor progression after surgical ablation of colorectal liver metastases

BackgroundKirsten rat sarcoma mutation was reported to adversely affect local tumor control after percutaneous ablation of colorectal liver metastasis. Nevertheless, the effect of Kirsten rat sarcoma mutation on surgical ablation has not been investigated in the literature. The aim of this study is to analyze the impact of Kirsten rat sarcoma mutation on local recurrence after surgical ablation of colorectal liver metastasis. MethodsThis was an institutional review board–approved study of patients who underwent surgical ablation of colorectal liver metastasis between 2005 and 2023 at a single center and underwent Kirsten rat sarcoma testing with ≥1 year follow-up. Local recurrence was analyzed using univariate Kaplan–Meier and multivariate Cox hazard models. ResultsA total of 163 patients with 424 lesions fulfilled inclusion criteria. Fifty (30.7%) patients received radiofrequency ablation and 113 (69.3%) patients received microwave ablation. Fifty-seven patients (32.2%) with 177 lesions were found to have a Kirsten rat sarcoma mutation. Patients with Kirsten rat sarcoma mutation had a larger number of tumors, percentage of posteriorly located tumors, and tumor burden score compared with those with wild-type Kirsten rat sarcoma. Nevertheless, there was no difference between the groups regarding local recurrence per lesion (15% vs 17%, respectively, P = not significant). Independent predictors of local recurrence included tumor size, ablation margin, and blood vessel proximity for radiofrequency ablation compared with tumor size and ablation margin for microwave ablation. ConclusionThere was no effect of Kirsten rat sarcoma mutations on local recurrence after surgical radiofrequency ablation or microwave ablation of colorectal liver metastasis in this study. Tumor size and ablation margin remained as independent predictors.

Integrated impact of multiple body composition parameters on overall survival in gastrointestinal or genitourinary cancers: A descriptive cohort study.

This study aimed to evaluate if combining low muscle mass with additional body composition abnormalities, such as myosteatosis or adiposity, could improve survival prediction accuracy in a large cohort of gastrointestinal and genitourinary malignancies. In total, 2015 patients with surgically-treated gastrointestinal or genitourinary cancer were retrospectively analyzed. Skeletal muscle index, skeletal muscle radiodensity, and visceral/subcutaneous adipose tissue index were determined. The primary outcome was overall survival determined by hospital records. Multivariate Cox hazard models were used to identify independent predictors for poor survival. C-statistics were assessed to quantify the prognostic capability of the models with or without incorporating body composition parameters. Survival curves were significantly demarcated by all 4 measures. Skeletal muscle radiodensity was associated with non-cancer-related deaths but not with cancer-specific survival. The survival outcome of patients with low skeletal muscle index was poor (5-year OS; 65.2%), especially when present in combination with low skeletal muscle radiodensity (5-year overall survival; 50.2%). All examined body composition parameters were independent predictors of lower overall survival. The model for predicting overall survival without incorporating body composition parameters had a c-index of 0.68 but increased to 0.71 with the inclusion of low skeletal muscle index and 0.72 when incorporating both low skeletal muscle index and low skeletal muscle radiodensity/visceral adipose tissue index/subcutaneous adipose tissue index. Patients exhibiting both low skeletal muscle index and other body composition abnormalities, particularly low skeletal muscle radiodensity, had poorer overall survival. Models incorporating multiple body composition prove valuable for mortality prediction in oncology settings.

Low Levels of Natural Killer Cell in Newly Diagnosed Myelodysplastic Syndromes Patients May Confer Poor Prognosis: A Retrospective Cohort Study.

Immune imbalance appears to have a critical role in tumor growth according to emerging research. Peripherallymphocyte subsets are considered to reflect the systemic immune response and clinical prognosis. The prognostic value of lymphocyte subpopulations in myelodysplastic syndrome (MDS) patients remains unclear. A total of 94 MDS patients were enrolled for the study. X-tile software was performed to determine the prognostic significance of various lymphocyte subpopulations, CD3, CD4, CD8, CD4/CD8 ratio, natural killer cell (NK) and CD19. Among them, the appropriate threshold of NK percent could be found only. Patients were divided into the high NK percent group and the low NK percent group. The prognostic significance was determined by univariate and multivariate Cox hazard models. MDS patients with lower NK level had significantly shorter overall survival (OS). Based on univariate analysis, male gender (P = 0.030), lower HB (<10 g/dl, P = 0.029), higher BM blast (>5%, P < 0.0001), higher-risk IPSS-R cytogenetic (P = 0.032) and lower NK percent (P < 0.0001) were significantly associated with shorter OS. Multivariate Cox proportional hazards regression analysis indicated that low NK was also independent adverse prognostic factor for OS in MDS. Decreased NK level predicts poor prognosis independent of the IPSS-R and provide a novel evaluation factor for MDS patients.

Potential Association of Blood Transfusion in Deceased Donors With Outcomes of Liver Transplantation in the United States

BackgroundDonor blood transfusion may potentially affect transplant outcomes through an inflammatory response, recipient sensitization, or transmission of infection. The aim of this study was to evaluate the association of donor blood transfusion with outcomes of liver transplantation (LT). MethodsFrom January 2004 to December 2022, donor blood transfusion information was available for 113,017 adult recipients of LT in the United Network for Organ Sharing database and was classified into 4 levels of transfusion: no-transfusion (N = 68,130), transfusion of 1-5 units (N = 33,629), 6-10 units (N = 8067), and >10 units (N = 5329). Recipient survival analysis was performed by Kaplan–Meier method and multivariable Cox-hazard model. ResultsAmong this cohort, 40.8% of donors (N = 46,261) received blood transfusion during the index hospitalization. Compared to no-blood transfusion donors, blood transfusion donors were younger (median age 37 versus 46 y P < 0.001) and were more brain death donors (94.5% versus 92.1%, P < 0.001). An increased risk of rejection at 6-mo (transfusion 10.3% versus no-transfusion 9.9%, P = 0.055) and 1 y (transfusion 12.5% versus no-transfusion 11.9%, P = 0.0036) post-LT was noted in this cohort. Multivariable Cox-hazard model showed blood transfusion was associated with increased 1-y mortality (transfusion 1.07; 95% CI 1.02-1.12, P = 0.007) and graft failure (transfusion 1.09; 95% CI 1.04-1.13, P < 0.001). ConclusionsDonor blood transfusion was associated with an increased risk of rejection at 6 mo and 1 y among LT recipients and worse post-transplant graft and overall survival. Additional information regarding donor blood transfusion, along with other known factors, may be considered when deciding the optimization of overall immune suppression in LT recipients to decrease the risk of delayed rejection.

Multifaced risk factors and clinical impact of a deep Y descent in patients with heart failure irrespective of RV-PA coupling

BackgroundA deep Y descent in the jugular venous pulse (JVP) is associated with diseases such as a decrease in right ventricular (RV) preload reserve. The present study investigated the relationship between RV-pulmonary arterial (PA) coupling and a deep Y descent, examined risk factors for a deep Y descent and clarified whether a deep Y descent was an independent risk factor for cardiac events irrespective of RV-PA coupling in patients with heart failure (HF). MethodsWe enrolled 350 patients with HF who underwent echocardiography and JVP examination. A deep Y descent was identified by a deeper ‘Y’ descent than ‘X’ descent in the JVP waveform. We defined cardiac events of HF as follows: sudden death, death from HF, the emergent infusion of loop diuretics, or hospitalization for decompensated HF. Results and ConclusionsA deep Y descent and cardiac events were observed in 129 and 83 patients, respectively. The prevalence of a deep Y descent increased with decreases in the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary arterial pressure (SPAP) ratio. Not only the TAPSE/SPAP ratio (odds ratio,0.756 per0.1 mm/mmHg, 95 %confidence interval [CI], 0.660–0.866, p < 0.001), but also age, atrial fibrillation, and the use of beta-blockers were independent factors for a deep Y descent in multivariate logistic model. Multivariate Cox hazard model demonstrated that a deep Y descent was for cardiac events in patients with HF (Hazard ratio,2.682, 95 %CI, 1.599–4.497, p < 0.001) irrespective of the TAPSE/SPAP ratio. The development of therapeutic strategies based on central venous waveform may be needed for patients with HF.

#1375 Association of NT-proBNP and kidney function progression in chronic kidney disease patients without heart failure

Abstract Background and Aims Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) is reported to be associated with higher risk of decline in kidney function. However, little evidence exists about the relationship between NT-proBNP and kidney function progression stratified by estimated glomerular filtration rate (eGFR) in chronic kidney disease (CKD) patients without heart failure. Therefore, we aim to investigate the association of NT-proBNP and CKD progression in different CKD stages for CKD patients without heart failure. Method A multicentric retrospective cohort study recruited 23860 patients diagnosed with CKD from China Renal Data System (CRDS) database. Eligible participants were classified into five groups according to eGFR. CKD progression was defined as a composite of an increase in serum creatinine ≥50% or a decrease in eGFR ≥40% from baseline or a need for kidney replacement therapy. A linear regression model evaluated the relationship between eGFR and NT-proBNP. Cox regression analysis assessed the association between NT-proBNP and CKD progression. We also performed restricted cubic spline (RCS) and threshold effect analysis to investigate non-linear relationships between NT-proBNP and CKD progression. Results In a linear regression model, NT-proBNP was negatively correlated with eGFR in CKD patients. Each decrease of 15 ml/min/1.73 m2 in eGFR was associated with 1.06-fold, 1.50-fold, 1.52-fold, 1.94-fold, 3.37-fold higher levels of log (NT-proBNP) in CKD patients with stage 1-2, 3a, 3b, 4 and 5 respectively. In the multivariable Cox hazard model, elevated NT-proBNP was associated with a greater risk of kidney function progression, particularly among CKD stage 3 patients (stage 3a: HR, 1.42, 95% CI, 1.32-1.53; stage 3b: HR, 1.43, 95% CI, 1.32-1.54), with P-interaction≤0.001. However, the correlation of NT-proBNP and CKD progression had no statistical significance among CKD patients with stages 4-5 after sensitivity analyses. RCS and two-segment Cox regression model showed reversed L-shaped non-linear relationships between NT-proBNP and CKD progression in CKD patients with stages 1-4, with the inflection point at 250 pg/mL, 750 pg/mL, 653 pg/mL, 526 pg/mL, but not in stage 5 (Figure). Conclusion NT-proBNP may be a reliable biomarker to predict CKD progression in stages 1-3 CKD (mainly for stage 3) without heart failure. This helps clinicians predict a decline in kidney function early and set the threshold for therapy. However, the predictive role of NT-proBNP in in advanced CKD patients is insignificant.

Impact of Left Ventricular Unloading on Outcome of Heart Transplant Bridging With Extracorporeal Membrane Oxygenation Support in New Allocation Policy.

The new heart allocation policy places veno-arterial extracorporeal membrane oxygenation (VA-ECMO)-supported heart transplant (HT) candidates at the highest priority status. Despite increasing evidence supporting left ventricular (LV) unloading during VA-ECMO, the effect of LV unloading on transplant outcomes following bridging to HT with VA-ECMO remains unknown. From October 18, 2018 to March 21, 2023, 624 patients on VA-ECMO at the time of HT were identified in the United Network for Organ Sharing database and were divided into 2 groups: VA-ECMO alone (N=384) versus VA-ECMO with LV unloading (N=240). Subanalysis was performed in the LV unloading group: Impella (N=106) versus intra-aortic balloon pump (N=134). Recipient age was younger in the VA-ECMO alone group (48 versus 53 years, P=0.018), as was donor age (VA-ECMO alone, 29 years versus LV unloading, 32 years, P=0.041). One-year survival was comparable between groups (VA-ECMO alone, 88.0±1.8% versus LV unloading, 90.4±2.1%; P=0.92). Multivariable Cox hazard model showed LV unloading was not associated with posttransplant mortality after HT (hazard ratio, 0.92; P=0.70). Different LV unloading methods had similar 1-year survival (intra-aortic balloon pump, 89.2±3.0% versus Impella, 92.4±2.8%; P=0.65). Posttransplant survival was comparable between different Impella versions (Impella 2.5, versus Impella CP, versus Impella 5.0, versus Impella 5.5). Under the current allocation policy, LV unloading did not impact waitlist outcome and posttransplant survival in patients bridged to HT with VA-ECMO, nor did mode of LV unloading. This highlights the importance of a tailored approach in HT candidates on VA-ECMO, where routine LV unloading may not be universally necessary.

High PPP4C expression predicts poor prognosis in diffuse large B-cell lymphoma

The significance of Protein phosphatase 4 catalytic subunit (PPP4C) in diffuse large B-cell lymphoma (DLBCL) prognosis is not well understood. This work aimed to investigate the expression of PPP4C in DLBCL, investigate the correlation between PPP4C expression and clinicopathological parameters, and assess the prognostic significance of PPP4C. The mRNA expression of PPP4C was investigated using data from TCGA and GEO. To further analyze PPP4C expression, immunohistochemistry was performed on tissue microarray samples. Correlation analysis between clinicopathological parameters and PPP4C expression was conducted using Pearson's chi-square test or Fisher's exact test. Univariate and multivariate Cox hazard models were utilized to determine the prognostic significance of clinicopathological features and PPP4C expression. Additionally, survival analysis was performed using Kaplan–Meier survival curves. In both TCGA and GEO datasets, we identified higher mRNA levels of PPP4C in tumor tissues compared to normal tissues. Upon analysis of various clinicopathological features of DLBCL, we observed a correlation between high PPP4C expression and ECOG score (P = 0.003). Furthermore, according to a Kaplan–Meier survival analysis, patients with DLBCL who exhibit high levels of PPP4C had worse overall survival (P = 0.001) and progression-free survival (P = 0.002). PPP4C was shown to be an independent predictive factor for OS and PFS in DLBCL by univariate and multivariate analysis (P = 0.011 and P = 0.040). This study's findings indicate that high expression of PPP4C is linked to a poor prognosis for DLBCL and may function as an independent prognostic factors.

The monocyte-to-high-density lipoprotein-cholesterol ratio at diagnosis is associated with cerebrovascular accident during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

In this study, the association between the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) at diagnosis and poor outcomes of atherosclerosis-related antineutrophil cytoplasmic antibody-associated vasculitis (AAV) during follow-up in patients with AAV was investigated. This retrospective study included 138 patients diagnosed with AAV. Their comprehensive medical records were meticulously reviewed. All-cause mortality, cerebrovascular accident (CVA), and acute coronary syndrome (ACS) were evaluated as atherosclerosis-related poor outcomes of AAV. MHR was obtained by dividing monocyte counts (/mm3) by high-density lipoprotein cholesterol (mg/dL) levels. The median age of the 138 patients was 58.3 years with 44 being male (31.9%). Among the 138 patients, 11 (8.0%) died, and 11 (8.0%) and 9 (6.5%) had CVA, and ACS, respectively. MHR at diagnosis was significantly correlated with the Birmingham vasculitis activity score, erythrocyte sedimentation rate, and C-reactive protein at diagnosis. Among the three poor outcomes of AAV, only CVA during follow-up was significantly associated with MHR at diagnosis, and thus, only CVA was considered an atherosclerosis-related poor outcome of AAV. In the multivariable Cox hazards model analysis, MHR (hazard ratio [HR] 1.195) and serum albumin (HR 0.203) at diagnosis were independently associated with CVA during follow-up. Additionally, patients with MHR at diagnosis ≥3.0 exhibited a significantly higher risk for CVA and lower cumulative CVA-free survival rate than those with MHR at diagnosis <3.0. This study is the first to demonstrate clinical implications of MHR suggesting that MHR at diagnosis is significantly and independently associated with CVA during follow-up in patients with AAV.

Effects of simultaneous pancreas and kidney transplantation in Japanese individuals with type 1 diabetes and end-stage kidney disease.

This single-center observational cohort study aimed to assess the potential benefits of simultaneous pancreas and kidney transplantation (SPK) in terms of mortality and kidney graft outcomes in Japanese individuals with type 1 diabetes (T1D) and end-stage kidney disease (ESKD). We first compared all-cause mortality rates between 78 SPK recipients and 108 non-transplanted individuals with T1D and ESKD. To mitigate the bias stemming from immortal time before receiving SPK, we utilized Cox regression models treating SPK as a time-dependent covariate. Next, we compared all-cause mortality rates and kidney graft loss rates between 65 SPK recipients and 58 kidney transplantation alone (KTA) recipients. Multivariate Cox hazard models and Fine and Gray competing-risk models were employed. SPK recipients experienced significantly lower all-cause mortality rates than non-transplanted individuals, even after accounting for immortal time bias (p = 0.015 by log-rank test, hazard ratio [HR] = 0.334, p = 0.025). When comparing SPK and KTA recipients, no statistically significant difference was observed in mortality rates (HR = 0.627, p = 0.588 by Cox model; HR = 0.385, p = 0.412 by Fine and Gray model) or kidney graft loss rates (HR = 0.612, p = 0.436 by Cox model; HR = 0.639, p = 0.376 by Fine and Gray model). Dysglycemia-associated mortality were observed in non-transplanted individuals and KTA recipients, but not in SPK recipients. These findings highlight the potential life-saving impact of SPK compared with intensive insulin therapy and dialysis. Additionally, this study suggests that both SPK and KTA may offer comparable outcomes. These findings have significant implications for clinical decision-making in the context of organ transplantation for individuals with T1D and ESKD.

Clinical Impact of In-Stent Calcification in Coronary Arteries: Optical Coherence Tomography Study

In-stent restenosis with neoatherosclerosis has been known as the predictor of target lesion revascularization (TLR) after percutaneous coronary intervention (PCI). However, impact of in-stent calcification (ISC) alone on clinical outcomes remains unknown since neoatherosclerosis by optical coherence tomography (OCT) includes both in-stent lipid and calcification. We aimed to assess an effect of ISC on clinical outcomes and clinical differences among different types of ISC. We included 126 lesions that underwent OCT-guided PCI and divided those into the ISC group (n=38) and the non-ISC group (n=88) according to the presence of ISC. The cumulative incidence of clinically-driven TLR (CD-TLR) was compared between the ISC and non-ISC groups. Impact of in-stent calcified nodule and nodular calcification on CD-TLR was evaluated in the Cox hazard model. The incidence of CD-TLR was significantly higher in the ISC group than in the non-ISC group (p=0.004). In the multivariate Cox hazard model, ISC was significantly associated with CD-TLR [hazard ratio (HR): 3.58; 95% confidence interval (CI): 1.33-9.65; p=0.01]. In-stent calcified nodule/nodular calcification and in-stent nodular calcification alone were also the factors significantly associated with CD-TLR (HR: 3.34; 95%CI: 1.15-9.65; p=0.03 and HR: 5.21; 95%CI: 1.82-14.91; p=0.002, respectively). ISC without in-stent calcified nodule/nodular calcification, which was defined as in-stent smooth calcification, was not associated with CD-TLR. In conclusion, ISC was associated with the higher rate of CD-TLR. Types of calcifications that led to the high rate of CD-TLR were in-stent calcified nodule/nodular calcification and in-stent nodular calcification alone but not in-stent smooth calcification. In-stent calcified nodule and nodular calcification should be paid more attention.

Low-Attenuation Coronary Plaque Volume and Cardiovascular Events in Patients with Distinct Metabolic Phenotypes with or without Diabetes.

Diabetes mellitus (DM) plays a key role in the pathophysiology of metabolic syndrome (MetS). This study aimed to investigate the association among DM, low-attenuation plaque (LAP) volume, and cardiovascular outcomes across metabolic phenotypes in patients with suspected coronary artery disease (CAD) who underwent coronary computed tomography angiography (CCTA). We included 530 patients who underwent CCTA. MetS was defined as the presence of a visceral adipose tissue area 100 in patients with DM (n = 58) or two or more MetS components excluding DM (n = 114). The remaining patients were categorised as non-MetS patients with DM (n = 52) or without DM (n = 306). A CCTA-based high-risk plaque was defined as a LAP volume of 4%. The primary endpoint was the presence of a major cardiovascular event (MACE), which was defined as a composite of cardiovascular death, acute coronary syndrome, and coronary revascularization. The incidence of MACE was the highest in the non-MetS with DM group, followed hierarchically by the MetS with DM, MetS without DM, and non-MetS without DM groups. In the multivariable Cox hazard model analysis, DM as a predictor was associated with MACE independent of LAP volume 4% (hazard ratio, 2.68; 95% confidence interval, 1.16-6.18; p = 0.02), although MetS did not function as an independent predictor. A LAP volume 4% functioned as a predictor of MACE, independent of each metabolic phenotype or DM. This study demonstrated that DM, rather than MetS, is a predictor of coronary events independent of high-risk plaque volume in patients who underwent CCTA.