Univariate Cox Proportional Hazards Analyses Research Articles

Survival and Success of 3D-Printed Versus Milled Immediate Provisional Full-Arch Restorations: ARetrospective Analysis.

To evaluate and compare the survival rates of 3D-printed and chairside milled resin polymethylmethacrylate (PMMA) immediate temporary provisional full-arch implant restorations using prosthetic survival as the primary outcome. Records of 335 routine patients receiving 443 temporary six-implant retained maxillary or mandibular prosthetic restorations between January 2019 and January 2022 at a private clinic (Dr Sobczak Clinical Centre, Radosc, Poland) were considered for this retrospective analysis. The analysis compared prosthetic and implant failure rates between printed and milled restorations as primary and secondary outcomes, respectively. Patient-related and treatment-related characteristics between groups were compared using the Chi-square test and Mann-Whitney U-test, respectively. Group-specific cumulative prosthetic survival was qualitatively and quantitively compared using Kaplan-Meier, generalized linear mixed models and univariate cox proportional hazard analyses. Prosthetic survival was set into context to implant survival using Chi-square tests. A multivariable cox proportional hazards model with frailty was used to identify confounding factors affecting prosthetic survival. Prosthetic failure rates of milled and printed temporary restorations were 13.01% and 11.25% over the average follow-up period of 307.7 ± 115.5 days, respectively. The corresponding 180-day cumulative prosthetic survival rates were 92.4% and 93%. Hazard ratios for the prosthetic failure of milled and printed restorations did not show a statistical difference (p = 0.794). Implant failure rates in restorations that experienced prosthetic failure (17.31%) were higher compared to restorations without failures (5.63%), with a 3.2 times significantly higher odds of failure for a prosthesis experiencing implant loss (p = 0.003). Gender, presence of teeth at treatment baseline, smoking, and bone augmentation were identified as confounding factors impacting prosthetic survival. Chairside 3D-printed restorations may represent an equivalent treatment modality to established chairside milled restorations for immediate full-arch therapy. Provisional prosthetic survival may impact implant survival and treatment success.

Development of Imaging Complexity Biomarkers for Prediction of Symptomatic Radiation Pneumonitis in Patients with Non-Small Cell Lung Cancer, Focusing on Underlying Lung Disease.

Objectives: We aimed to develop imaging biomarkers to predict radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients undergoing thoracic radiotherapy. We hypothesized that measuring morphometric complexity in the lung using simulation computed tomography may provide objective imaging biomarkers for lung parenchyma integrity, potentially forecasting the risk of RP. Materials and Methods: A retrospective study was performed on medical records of 175 patients diagnosed with NSCLC who had received thoracic radiotherapy. Three indices were utilized to measure the morphometric complexity of the lung parenchyma: box-counting fractal dimension, lacunarity, and minimum spanning tree (MST) fractal dimension. Patients were dichotomized into two groups at median values. Cox proportional hazard models were constructed to estimate the hazard ratios for grade ≥ 2 or grade ≥ 3 RP. Results and Conclusions: We found significant associations between lung parenchymal morphometric complexity and RP incidence. In univariate Cox-proportional hazard analysis, patients with a lower MST fractal dimension had a significantly higher hazard ratio of 2.296 (95% CI: 1.348-3.910) for grade ≥ 2 RP. When adjusted for age, sex, smoking status, category of the underlying lung disease, category of radiotherapy technique, clinical stage, histology, and DLCO, patients with a lower MST fractal dimension showed a significantly higher hazard ratio of 3.292 (95% CI: 1.722-6.294) for grade ≥ 2 RP and 7.952 (95% CI: 1.722 36.733) for grade ≥ 3 RP than those with a higher MST fractal dimension. Patients with lower lacunarity exhibited a significantly lower hazard ratio of 0.091 (95% CI: 0.015-0.573) for grade ≥ 3 RP in the adjusted model. We speculated that the lung tissue integrity is captured by morphometric complexity measures, particularly by the MST fractal dimension. We suggest the MST fractal dimension as an imaging biomarker for predicting the occurrence of symptomatic RP after thoracic radiotherapy.

Pre-transplant metabolic tumor volume predicts recurrence following liver transplantation for colorectal metastasis: A multicenter study.

Liver transplant (LT) for colorectal cancer liver metastases (CRLM) is increasingly popular, yet the ideal selection criteria remain unknown. Pre-transplant PET metabolic tumor volume (MTV) has been described as predicting recurrence, with a proposed cut-off of MTV ≥70cm3. This approach has not been validated. Patients undergoing LT for CRLM at two academic transplant centers (1/1/2017-12/1/2023) were included. PET-MTV was calculated by a staff radiologist from the most recent PET-scan before LT using the published protocol. Twenty-six patients were included. Median follow-up was 609 days (IQR 320-1069) and from PET to LT was 1.9 months (1.3-2.6). Nearly all (n=24, 92.3%) received living donor transplantation. Absolute recurrence rate was 30.8% (n=8). Actuarial unadjusted 1-, and 2-year RFS were 83% (n=15/18), and 62% (n=8/13); 1- and 2-year OS were 100% (n=18/18), and 85% (n=11/13).The incidence of recurrence-per-year follow-up was 0.35 when MTV ≥70cm3 versus 0.10 if MTV <70cm3 (P<0.001). Median RFS using Kaplan-Meier product-estimate was 0.83 years (95%CI 0.43-1.23) in MTV≥70cm3 versus 4.1 years (95%CI 2.90-5.22) when MTV<70cm3 (P<0.001); this was also associated with improved OS (P=0.003). MTV>70cm3 demonstrated HR=2.42 (95%CI 2.2-62.2, P=0.006) for association with RFS on univariate Cox-proportional hazards analysis, and an Area-Under-the-Curve (AUC)=0.771 (95%CI 0.560-0.981) for predicting recurrence (P=0.030)Nineteen patients (69.2%) had histologically viable tumor, which was associated with recurrence (43% vs. 0%, P=0.039) and reduced RFS (log-rank P=0.019). PET-MTV was associated with presence of histologically-viable tumor (AUC=0.763, 95%CI 0.583-0.944). PET-MTV ≥70cm3 was associated with reduced RFS and OS after LT for CRLM, confirming findings from the Norway group. This is likely due to its' ability to identify residual viable tumors, which are independently associated with recurrence. PET-MTV should be a key selection criterion prior to LT for CRLM.

Adjuvant Trastuzumab Plus Pertuzumab Versus Trastuzumab Alone in Patients Achieving Pathologic Complete Response After Chemotherapy With Trastuzumab and Pertuzumab: A Retrospective Cohort Study

BackgroundFor patients who achieve pathologic complete response (pCR) after neoadjuvant chemotherapy with trastuzumab (T) and pertuzumab (P), the benefit of adding P to T remains uncertain. We compared survival outcomes according to the type of adjuvant anti-HER2 therapy in patients with pCR after chemotherapy with TP. MethodPatients who achieved pCR in both the breast and axilla after neoadjuvant chemotherapy with TP were included. Recurrence-free survival (RFS) and distant recurrence-free survival (DRFS) were evaluated. Univariate and multivariate Cox proportional hazards analyses were used to assess the impact of different adjuvant therapies on RFS and DRFS. ResultsIn total, 386 patients were included, with 69 (17.9%) receiving adjuvant TP and 317 (82.1%) receiving adjuvant T alone. At a median follow-up of 49 months, the 3-year RFS rate was 96.1%. There was no significant difference in the 3-year RFS between groups (94.2% in TP and 95.6% in T), with an adjusted hazard ratio (HR) of 1.15 (95% CI, 0.37-3.55, P = .806). In the clinical node-positive group (n = 294), there was no difference in survival between groups (HR 1.64, 95% CI, 0.58-4.65, P = .35). The multivariate analysis showed no significant predictors of recurrence or distant recurrence, including clinical tumor size, nodal status, ER/PR/HER2 status, and adjuvant radiotherapy receipt. Among 11 patients with brain metastasis after pCR, there was no difference according to the type of adjuvant anti-HER2 therapy. ConclusionsIn patients with pCR who responded to chemotherapy and dual HER2 blockade (TP), the 3-year RFS and brain metastasis-free survival did not differ according to the type of adjuvant anti-HER2 therapy.

The activation of cardiac sympathetic nervous system in the non-culprit lesion is a strong prognostic predictor in patients with acute myocardial infarction

Abstract Background The activation of cardiac sympathetic nervous system is associated with poor prognosis in patients with acute myocardial infarction (AMI). However, it remains to be determined whether regional assessment of cardiac sympathetic nerve activity (CSNA) in the culprit and non-culprit lesion of the cardiac MIBG SPECT imaging could have prognostic value in patients with AMI. Purpose The purpose of this study is to investigate the prognostic impact of regional CSNA in patients with AMI. Methods We prospectively enrolled 122 patients with AMI who visited our emergency department and underwent primary percutaneous coronary intervention. The late heart-to-mediastinum ratio (HMR) and washout rate (WR) was calculated to assess CSNA in the whole heart from planar images of in the cardiac MIBG imaging. The MIBG SPECT image parameters were calculated for each coronary artery, and the average WR in the culprit and non-culprit lesion were evaluated to assess the regional status of CSNA in patients with AMI. Abnormal WR in planar image was defined as 34% or more, as previously reported. The cut-off value of late HMR in planar image, WR in the culprit and non-culprit lesions were determined by ROC analysis. The primary endpoint was major adverse cardiac event (MACE) including all cause death, myocardial infarction, hospitalization for heart failure and target lesion revascularization. Results During a mean follow-up period of 3.1±1.8 years, 25 of 122 patients underwent MACE. The late HMR (p=0.004), WR in planar image (p=0.002), WR in the culprit lesion (p=0.023), and WR in the non-culprit lesion (p&amp;lt;0.001) were significantly associated with MACE at univariate Cox proportional hazard analysis. The increased WR in the non-culprit lesion (defined as 28.3% or more: AUC 0.697 [0.576-0.817]) was significantly independently associated with MACE (hazard ratio: 4.36 [1.45-13.11], p=0.009) even adjusted by late HMR, WR in planar image or WR in the culprit lesion, while decreased HMR, abnormal WR in planar image and increased WR in the culprit lesion showed no significant association with MACE in the multivariate model with WR in the non-culprit lesion. Kaplan-Meier analysis revealed that patients with increased WR in the non-culprit lesion had significantly higher risk for MACE than those without increased WR (45% vs 11% p&amp;lt;0.001). Conclusion(s) The activation of cardiac sympathetic nervous system in the non-culprit lesion is particularly associated with poor prognosis in patients with acute myocardial infarction.MACE risk by WR in non-culprit lesion

The prognostic and therapeutic value of the tumor microenvironment and immune checkpoints in pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms (Pan-NEN) represent a group of highly heterogeneous cancers, characterized by complex and diverse biological behavior. The objective of this study was to systematically investigate the immunological features of the tumor microenvironment (TME) in Pan-NEN, aiming to identify prognostic biomarkers and explore the therapeutic potential of immunotherapy for Pan-NEN. Tumor and adjacent normal tissues were collected from 56 patients with Pan-NEN. Immunohistochemical analysis was conducted on tumor tissues using a panel of monoclonal antibodies targeting key immune markers. The expression levels of these markers were quantitatively assessed and correlated with clinicopathological features and overall survival. Low expression of CD3, CD8, CD4, CD68, CD163, Foxp3, CD56, CD69, GZMB, HLA-1, HLA-II, PD-1, and PD-L1 were observed in the majority of Pan-NEN patient samples. PD-1 expression was positively correlated with CD4 and Foxp3 expression, while PD-L1 expression was positively correlated with CD68, CD163, and Foxp3 expression; HLA-II expression was positively correlated with GZMB expression. Infiltration of lymphocytes (CD3 + or CD8+) and macrophages (CD68 + or CD163+) and expression of PD-1/PD-L1 were more pronounced in poorly differentiated neuroendocrine carcinoma (Pan-NEC) compared to well-differentiated neuroendocrine tumors (Pan-NET), while CD68 and PD-L1 correlated with advanced disease stage. Conversely, HLA-I antigen expression was commonly downregulated in Pan-NEC. Univariate Cox proportional hazard analysis demonstrated that tumor grade, stage; CD4+, CD68+, and CD163 + cell count; and expression of PD-1 and PD-L1 were significantly associated with poor survival outcomes, while the positive expression of HLA-I was correlated with a more favorable survival prognosis. Furthermore, multivariate Cox proportional hazard analyses revealed that tumor grade, stage, and PD-1 expression are independent prognostic factors. The immunological landscape of Pan-NEN offers potential prognostic value and therapeutic targets. The findings suggest that immunotherapy, particularly targeting the PD-1/PD-L1 pathway, may serve as a promising strategy for the treatment of Pan-NEN, especially for Pan-NEC patients.

Preoperative systemic inflammatory response index as a prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy.

The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged. To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma (dCCA) who underwent pancreatoduodenectomy (PD). This single-center study included 216 patients with dCCA after PD between January 1, 2011, and December 31, 2022. The individuals were categorized into two sets based on their systemic inflammatory response index (SIRI) levels: A low SIRI group (SIRI < 1.5, n = 123) and a high SIRI group (SIRI ≥ 1.5, n = 93). Inflammatory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves. Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival (OS) and recurrence-free survival (RFS). The study included a total of 216 patients, with 58.3% being male and a mean age of 65.6 ± 9.6 years. 123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA. SIRI had an area under the curve value of 0.674 for diagnosing dCCA, showing better performance than other inflammatory biomarkers. Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD, leading to lower OS [hazard ratios (HR) = 1.868, P = 0.006] and RFS (HR = 0.949, P < 0.001). Additionally, survival analysis indicated a significantly better prognosis for patients in the low SIRI group (P < 0.001). It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.

Risk Factors for Glaucoma and Ocular Hypertension and Post-Transplant Complications in Keratoconus: A Multivariable Analysis.

Background: The purpose of this study was to investigate the risk factors for glaucoma in patients with keratoconus following keratoplasty and to identify potential factors that could affect post-transplant complications. Methods: A retrospective analysis was conducted on the medical records of 192 keratoconus patients who underwent keratoplasty. Data on treatment history, perioperative information, tissue bank data, postoperative regimens, complications, and infections were collected and analyzed. Statistical analysis was performed to identify risk factors associated with glaucoma and transplant complications. Results: There was a 41.6% incidence of glaucoma (high IOP) (p < 0.001), with the median time to glaucoma development being 314 ± 67 days post-transplant. A significant number of patients required surgical intervention, accounting for 48.05%. Our analysis revealed a 14% graft failure rate. On univariable Cox proportional hazard analysis, the following factors demonstrated statistically significant associations with the risk of glaucoma after transplantation: donor endothelial cell density, the use of a single continuous suture type, and the surgeon (performing the surgery). For many variables, the only factor that remained significant was the surgeon. Among the factors analyzed for risks of failure post-transplantation, significant associations were observed for the donor age, the time from harvest to transplant, and the surgeon. In the multivariable analysis, donor age emerged as a significant predictor of post-transplant complications. Conclusions: Risk factors such as donor endothelial cell density, suture type, surgeon, host and donor size, and host gender were found to increase the risk of developing glaucoma post-keratoplasty. Surgeon type was identified as a significant risk factor, while donor age was predictive of post-transplant complications.

Preoperative liquid biopsy for optimal patient selection in metastatic colorectal cancer

ObjectiveIn this pilot study, we sought to determine if preoperative circulating tumor DNA could be a useful predictor to avoid futile metastasectomy, predict early postoperative recurrence, and determine optimal chemotherapy duration during the management of patients with resectable metastatic colorectal cancer. MethodsPatients from 2021 to 2023 were enrolled prospectively and evaluated with circulating tumor DNA preoperatively and postoperatively for detection of recurrence. Clinicopathologic and treatment factors as well as disease-free survival were compared between those with undetectable versus detectable preoperative circulating tumor DNA. ResultsTwenty-eight patients were evaluated, with a median follow-up time of 24 months. The median preoperative circulating tumor DNA level was 0.16 MTM/mL [0.00, 2.30]. Of the 10 patients (40%) with a preoperative circulating tumor DNA level of zero, 5 patients (50%) recurred between 4 and 18 months postoperatively. Among the 18 patients whose disease recurred, 10 patients (56%) had circulating tumor DNA detected postoperatively. Median change between preoperative and postoperative circulating tumor DNA levels was 0.00 [–0.02, 0.05] in those who did not recur and 0.00 [–7.04, 0.00] in those who recurred. When disease-free survival was evaluated by detectable versus undetectable preoperative circulating tumor DNA levels, there was no difference in disease-free survival estimates (P value = .11). On univariate Cox proportional hazards analysis, the preoperative circulating tumor DNA level, change between preoperative and postoperative circulating tumor DNA levels, and postoperative circulating tumor DNA levels did not influence disease-free survival. However, those with detectable postoperative circulating tumor DNA were 3.96 (95% confidence interval 1.30–12.06) times as likely to recur compared to those with undetectable postoperative circulating tumor DNA. ConclusionNew technologies including use of circulating tumor DNA may help better predict which patients with colorectal liver metastases will undergo futile surgery. Our preliminary findings suggest that postoperative, and not preoperative, circulating tumor DNA is predictive of recurrence following metastasectomy. Use of circulating tumor DNA in guiding operative management should be done in conjunction with high-quality imaging and other serologic markers to determine which patients with colorectal liver metastases are likely to receive durable benefit from operative intervention.

Long-term outcomes of laparoscopic versus open total gastrectomy in patients with advanced gastric cancer after neoadjuvant chemotherapy: a retrospective cohort study

BackgroundThis study was conducted to investigate the long-term outcomes of laparoscopic total gastrectomy (LTG) versus open total gastrectomy (OTG) in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NACT).MethodsPatients with AGC who received NACT before surgery were enrolled in either the LTG or OTG group. Propensity score matching (PSM) (1:2) was performed between the two groups based on the propensity score using a 0.15 calliper width. Three-year overall survival (OS) and disease-free survival (DFS) were compared between these two groups before and after PSM. OS and DFS rates were calculated by the Kaplan‒Meier method, and any differences in survival were evaluated with a log-rank test. Univariate and multivariate Cox proportional hazards analyses were used to estimate the simultaneous effects of prognostic factors on survival and the hazard ratio (HR) between LTG and OTG patients.ResultsA total of 144 patients completed the follow-up, with 24 patients in the LTG group and 120 patients in the OTG group. After a mean follow-up of 64.40 months, there were no significant differences in the 3-year OS or DFS rates between the two groups before (P = 0.453 and P = 0.362, respectively) or after PSM (P = 0.972 and P = 0.884, respectively). Multivariate Cox proportional hazards analysis indicated that ypN stage was an independent risk factor for worse OS (P = 0.013).ConclusionsThis study showed that LTG with D2 lymphadenectomy performed by an experienced surgical team resulted in comparable 3-year OS and DFS compared with OTG in patients with AGC after NACT.Trial registrationThis study is not registered.

Monocyte to high-density lipoprotein ratio based prognostic nomogram for patients following allogeneic vascular replacement pancreaticoduodenectomy.

Preoperative immune-inflammatory condition influencing the metabolism of malignancies. We sought to investigate the prognostic value of a novel immune-inflammatory metabolic marker, the monocyte-to-high-density lipoprotein ratio (MHR), in patients with locally advanced pancreatic cancer. A retrospective analysis was conducted on the clinical data of 118 patients with locally advanced pancreatic cancer and obstructive jaundice who underwent allogeneic vascular replacement pancreaticoduodenectomy in our hospital from Apr. 2011 to Dec. 2023. To assess the predictive capacity of immune-inflammatory metabolic marker, we utilized the area under the receiver operating characteristic curve (AUC-ROC) and assessed the predictive potential of MHR in forecasting outcomes through both univariate and multivariate Cox proportional hazard analyses. The area under AUC for MHR in predicting 1-year postoperative survival was 0.714, with an optimal cutoff value of 1.184, yielding a sensitivity of 78.9% and specificity of 66.2%. Based on this cutoff value, patients were divided into a low MHR group (MHR ≤1.184, n = 61) and a high MHR group (MHR >1.184, n = 57). The median survival times for the low and high MHR groups were 27.0 months and 12.0 months, respectively (χ2 = 30.575, p < 0.001), and the median DFS were 18.0 months and 8.0 months, respectively (χ2 = 26.330, p < 0.001). Univariate and multivariate analyses indicated that preoperative MHR, preoperative creatinine, operation duration, and TNM stage were independent predictors of postoperative mortality, while preoperative MHR, preoperative creatinine, and TNM stage were independent predictors of postoperative recurrence risk. MHR, as an independent immune-inflammatory metabolic predictor of OS and DFS in patients with advanced PC after pancreaticoduodenectomy. Early monitoring and reduction of MHR may be of great significance in improving prognosis.

Addressing the Neck: An NCDB Study of Clinically Node-Negative Supraglottic Squamous Cell Carcinoma.

Identify the proportion of patients undergoing elective neck dissection (END) in surgically managed supraglottic squamous cell carcinoma (SCCa), assess associations between patient, tumor, and treatment factors with END, and assess associations between neck management and overall survival (OS). Retrospective study. National Cancer Database (NCDB) 2019 Participant User File. Patients with previously untreated, clinically node-negative (cN0) supraglottic SCCa treated with partial laryngectomy were queried from NCDB. Patients without known neck management and who underwent total laryngectomy were excluded. Patient and tumor factors associated with END were evaluated by logistic regression analysis. Univariable Cox proportional hazard analysis was used to examine associations between patient factors and OS, and factors with P < .05 were included on multivariable analysis. A total of 1352 patients met eligibility criteria. Eight hundred eleven (60%) patients had END performed with occult nodal metastasis identified in 177 (22%) patients. END was more likely to be performed at academic centers than nonacademic centers (odds ratio: [1.66], 95% confidence interval [CI]: 1.32-2.09, P < .001). On multivariable analysis, patients who underwent adjuvant radiation had worse OS (hazard ratio [HR]: 1.45, 95% CI: 1.13-3.29, P = .017). END was associated with improved OS overall on univariable analysis (HR: 0.83, 95% CI: 0.69-0.98, P = .026), but not on multivariable analysis. In this NCDB study, 22% of cN0 supraglottic SCCa patients had occult nodal metastatic disease. Despite this, 40% of patients do not receive END at the time of primary resection. Patients who receive END for supraglottic SCCa are more likely to avoid adjuvant radiation without impacting OS.

Brain Radiotherapy Combined with Targeted Therapy for HER2-Positive Breast Cancer Patients with Brain Metastases.

Research on the sequencing of brain radiotherapy and targeted chemotherapy after brain metastasis (BM) in HER2-positive breast cancer patients is limited and inconclusive. This study investigated the efficacy of sequential delivery of radiotherapy and targeted therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with BM. Fifty-seven patients were categorized into two groups: the targeted-radiotherapy group (receiving 2-8 cycles of anti-HER2-targeted therapy followed by radiotherapy after BM) and the radiotherapy-targeted group (undergoing radiotherapy first, followed by regular anti-HER2-targeted therapy). The study endpoints were intracranial progression-free survival (iPFS) and overall survival. Factors associated with intracranial progression and mortality were assessed by univariate and multivariate Cox proportional hazards analysis. Patients in the radiotherapy-targeted group had better iPFS (P < 0.001), while there was no significant difference in overall survival between the two groups (P = 0.145). Multivariate Cox analysis showed that different sequential treatment groups were independent prognostic factors for iPFS. In patients with a modified breast graded prognostic assessment score of 3.5-4.0, the median survival time was 26 months in the radiotherapy-targeted group and 22 months in the targeted-radiotherapy group (P = 0.019). Overall, radiotherapy followed by targeted therapy may improve survival in HER2-positive breast cancer patients with BM, particularly in those with a modified breast graded prognostic assessment score of 3.5-4.0.

Association between intracellular adenosine triphosphate content of CD4+ T lymphocytes and mortality in sepsis patients: A prospective observational study.

This study aimed to link intracellular adenosine triphosphate content in CD4+ T lymphocytes (CD4+ iATP) with sepsis patient mortality, seeking a new predictive biomarker for outcomes and enhanced management. 61 sepsis patients admitted to the Intensive Care Unit between October 2021 and November 2022 were enrolled. iATP levels were gauged using whole blood CD4+ T cells stimulated with mitogen PHA-L. Based on CD4+ iATP levels (<132.24 and ≥132.24 ng/mL), patients were categorized into two groups. The primary endpoint was all-cause mortality. To identify factors associated with mortality, both univariate and multivariate Cox proportional hazard analyses were conducted. Of the patients, 40 had high CD4+ iATP levels (≥132.24 ng/mL) and 21 had low levels (<132.24 ng/mL). In a 28-day follow-up, 21 (34.4%) patients perished. Adjusting for confounders like SOFA score, APACHE II score, lactic acid, and albumin, those with low CD4+ iATP had three- to fivefold higher mortality risk compared to high CD4+ iATP patients (61.9% vs. 20.0%; hazard ratio [95% confidence interval], Model 1: 4.515 [1.276-15.974], p = .019, Model 2: 3.512 [1.197-10.306], p = .022). CD4+ iATP correlated positively with white blood cell and neutrophil counts but not with lymphocytes, CD3, and CD4 counts. Low CD4+ iATP levels were associated with a higher risk of mortality in sepsis patients. Measurement of CD4+ iATP may serve as a useful tool for identifying patients at a higher risk of mortality and could potentially provide a basis for clinical treatment. Further research is warranted to fully elucidate the underlying mechanisms of this association.

Myelofibrosis prognostic models validated in an underserved minority population: A retrospective analysis.

e18529 Background: Contemporary prognostic models for myelofibrosis (MF) risk stratify patients using a heterogeneous composition of clinical and genetic factors. Little is known regarding how these scores perform in underserved populations. Our study assesses how well current models stratify risk at an inner-city tertiary care center which carries unique challenges including increased diversity, later disease presentation, and less access to healthcare resources. Methods: We retrospectively reviewed 88 MF patients referred to our center in the Bronx, NY between 2000 and 2023. Clinical and genetic data were used to calculate prognostic scoring for DIPSS, DIPSS plus, MIPSS70, MIPSSV2, and GIPSS. Overall survival (OS) was calculated from the time of diagnosis and non-deceased patients were censored at last follow-up. Patients with missing clinical or genetic data were excluded from individual analysis. Models were assessed via univariate and multivariate cox proportional hazards analysis followed by concordance analysis. Results: Mean age of the cohort was 66 years (range 29-88) with median survival of 7.7 years. Ethnicities included non-hispanic white (NHW) [30 (34.1%)], NH black [23 (26.1%)], NH asian [6 (6.8%)], and hispanics of all races [22 (25%)] (unknown n=7). DIPSS (n= 88, HR 1.77, CI 1.22 - 2.41, p-value = 0.0001), DIPSS plus (n=83, HR 1.54, 1.15-2.07, p = 0.0033), MIPSS70V2 (n=68, HR 2.06, CI 1.23 - 3.61, p = 0.0088), and GIPSS (n=69, HR 2.73, CI 1.24 - 3.78, p = 0.0063) were significantly associated with OS based on univariate analyses. Both DIPSS and GIPSS were significant even upon adjustment for each other (p=.009 and p=.043 respectively). MIPSS70 (n=73, HR 1.87, CI .93 - 3.88, p = 0.0842) did not meet significance. In terms of predictive accuracy based on C-index scores, DIPSS and GIPSS combined analysis scored highest (0.773), followed by GIPSS (.7226), DIPSS (0.719), MIPSSV2 (0.717), DIPSS Plus (0.6495), then MIPSS70 (0.6414). Conclusions: Our study shows that GIPSS, DIPSS, DIPSS plus, MIPSSV2 all function as valid prognostic models in the inner-city setting and that integrating both clinical and genetic models may have higher predictive value than either individual model alone. Additionally, GIPSS predicted superior survival outcomes to what was observed in our cohort for higher risk categories, prompting the need for further investigation. [Table: see text]

Genomic analysis of recurrent early stage and de novo metastatic colorectal cancer among veterans.

e15593 Background: The Veterans Health Administration (VHA) diagnoses approximately 4,000 cases of colon cancer each year and conducts Next Generation Sequencing (NGS) on recurrent and metastatic cases. The molecular profile of cancers resected for cure that recur is poorly characterized and holds promise to clarify both the risk and mechanisms of recurrence. We sought to characterize these genetic differences. Methods: A national database from the VHA consisting of colon cancer patients was analyzed for those with recurrent disease who have received NGS testing from 2015-2021. Data was analyzed by stage and presence of DNA mismatch repair (MMR) (MLH1, MSH2, PMS2, MSH6) and DNA damage repair (DDR) abnormalities (BRCA1, BRCA2, ATM, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D) in addition to receipt of chemotherapy and overall survival with univariate and multivariate cox proportional hazards analyses and multivariate logistic regression analyses. Chi squared analyses were also performed comparing presence of DNA abnormalities between early recurrent and stage IV cancers. Results: From309,318 cases with colon cancer codes, we identified 2,366 colon cancer patients who had NGS and had recurrent or de novo metastatic disease. 1,072 patients had initial staging annotated (I n = 89, II n = 194, III n = 320 , IV n = 453). The average age was 69.41 years; 70.5% white, 21.5% Black and 7.8% other. Among all patients, DNA MMR abnormalities (n = 117) were associated with better overall survival, after controlling for age and race (HR 0.6, 95% CI 0.42-0.85, p &lt; 0.005). Among recurrent early stage (I-III) and stage IV patients, MMR (n = 55 and n = 21, respectively) is associated with improved survival in multivariable models (HR 0.39, 95% CI 0.33-0.46, p &lt; 0.001) . Among the 4 DNA MMR genes, MSH2 mutations had the strongest association with survival (univariate HR 0.31, 0.15-0.62, p &lt; 0.001). Among patients with MMR abnormalities, those who received either only capecitabine or only fluorouracil (without irinotecan or oxaliplatin) had worse overall survival (HR 2.6, 1.34 -5.04, p &lt; 0.005). This effect was more pronounced in early stage recurrent patients versus patients with de novo metastatic disease (HR 5.1, 1.87 – 13.9, p &lt; 0.001). Finally, we also found that early stage patients with recurrent disease are more likely to have MMR abnormalities compared to de novo metastatic (8.8% vs 4.6%, p &lt; 0.01) and confirmed this finding after controlling for race and age. (OR 2.13, p &lt; 0.005). Conclusions: Among Veteranswith colon cancer, resected recurrent colon cancer is more likely to have DNA MMR abnormalities than de novo metastatic disease. Veterans with recurrent and or metastatic disease with DNA MMR have better outcomes regardless of stage at diagnosis. These findings suggest different pathogenesis for those with recurrent disease after curative resection, and for those with de novo metastatic disease.

Clinical outcomes of upfront combination therapy for portopulmonary hypertension

BackgroundLimited data exists on upfront combination therapy for portopulmonary hypertension. We evaluated the clinical efficacy, long-term outcomes, and safety of upfront combination therapy in patients with portopulmonary hypertension. MethodsWe performed a retrospective, single-center cohort study involving a final analysis of 33 consecutive patients diagnosed with portopulmonary hypertension who were taking pulmonary arterial hypertension-specific medication. We compared hemodynamic parameters, risk profiles, composite clinical worsening events, and safety between monotherapy (n = 23) and upfront combination therapy (n = 10). ResultsTwenty-seven patients (82 %) were classified into the Child–Pugh A stage. The change ratios of pulmonary vascular resistance (−32 % vs. −57 %, P = 0.006) were significantly better with upfront combination therapy. Upfront combination therapy also showed significant improvement in risk profiles. Kaplan–Meier analysis showed that the composite event-free rate was significantly lower in patients who received upfront combination therapy than in those who received monotherapy (P = 0.016), although no statistical differences were observed in all-cause death. In the univariate Cox proportional hazards analysis, upfront combination therapy was a factor for decreasing composite clinical worsening outcomes (hazard ratio 0.190, 95 % confidence interval 0.042–0.854; P = 0.030). No significant hepatic impairments were observed over 2 years of follow-up in the upfront combination group. ConclusionsIn patients with portopulmonary hypertension, upfront combination therapy significantly improved symptoms and short-term hemodynamics, and reduced long-term clinical worsening events without serious adverse effects. This study's findings suggest that patients with portopulmonary hypertension presenting with mild hepatic impairment benefit from upfront combination therapy.

Geriatric nutritional risk index and controller nutritional status score before metastatic first-line chemotherapy predict survival in patients over 70 years of age with metastatic bladder cancer.

Several prognostic factors have been identified in patients with metastatic bladder cancer (BC). As it is known, older adult patients are prone to nutritional deficiency. The knowledge about nutrition and impact on survival in older patients with metastatic bladder cancer is missing. It is necessary to specifically examine this population. Because timely interventions can make a positive impact on this patients population. This retrospective study aimed to evaluate the prognostic effect of the Geriatric Nutritional Risk Index (GNRI), Controller Nutritional Status (CONUT) score and Prognostic Nutritional Index (PNI) before first-line chemotherapy in the metastatic stage in patients with metastatic bladder cancer over 70. Patients over 70 with pathologically confirmed denovo metastatic or recurrent metastatic bladder cancer were included in the study. Patients with infections diagnosed at the time of diagnosis, autoimmune diseases or history of steroid use were excluded. Since our population consists of a specific age group with a specific cancer, we found a new cut-off value by performing ROC analysis to ensure optimal sensitivity and specificity in terms of progression. Low GNRI value was related with poor nutritional status. Low PNI value was related with poor nutritional status and high CONUT score was related with poor nutritional status. Factors predicting overall survival (OS) and Progression-Free Survival (PFS) were assessed using both univariate and multivariate Cox proportional hazards analyses. 106 patients were included in the study and the average age was 75.5 years. In the GNRI-Low group, PFS was significantly shorter than that in the GNRI-High group [HR (95% CI) = 57.1 (12.8-255.5), (p < 0.001)]. Among those with a low-CONUT score, PFS was found to be longer than that in the high-CONUT group [HR (95% CI) = 1.7 (1.0-3.0), (p = 0.039)]. The median PFS of the PNI-Low group wasn't significantly shorter than that of the PNI-High group [HR (95% CI) = 1.8 (0.5-6.2), (p = 0.359)]. Our study suggests that the GNRI and CONUT scores are useful for predicting survival in patients over 70 years of age with BC.

Metabolomic Analysis of Human Cirrhosis and Hepatocellular Carcinoma: A Pilot Study

BackgroundMolecular changes in HCC development are largely unknown. As the liver plays a fundamental role in the body’s metabolism, metabolic changes are to be expected.AimsWe aimed to identify metabolomic changes in HCC in comparison to liver cirrhosis (LC) patients, which could potentially serve as novel biomarkers for HCC diagnosis and prognosis.MethodsMetabolite expression from 38 HCC from the SORAMIC trial and 32 LC patients were analyzed by mass spectrometry. Metabolites with significant differences between LC and HCC at baseline were analyzed regarding expression over follow-up. In addition, association with overall survival was tested using univariate Cox proportional-hazard analysis.Results41 metabolites showed differential expression between LC and HCC patients. 14 metabolites demonstrated significant changes in HCC patients during follow-up. Campesterol, lysophosphatidylcholine, octadecenoic and octadecadienoic acid, and furoylglycine showed a differential expression in the local ablation vs. palliative care group. High expression of eight metabolites (octadecenoic acid, 2-hydroxybutyrate, myo-inositol, isocitrate, erythronic acid, creatinine, pseudouridine, and erythrol) were associated with poor overall survival. The association between poor OS and octadecenoic acid and creatinine remained statistically significant even after adjusting for tumor burden and LC severity.ConclusionOur findings give promising insides into the metabolic changes during HCC carcinogenesis and provide candidate biomarkers for future studies. Campesterol and furoylglycine in particular were identified as possible biomarkers for HCC progression. Moreover, eight metabolites were detected as predictors for poor overall survival.Graphical

The therapeutic effect of radiotherapy combined with systemic therapy compared to radiotherapy alone in patients with simple brain metastasis after first-line treatment of limited-stage small cell lung cancer: a retrospective study

PurposeWe aimed to compare the therapeutic effect of radiotherapy (RT) plus systemic therapy (ST) with RT alone in patients with simple brain metastasis (BM) after first-line treatment of limited-stage small cell lung cancer (LS-SCLC).MethodsThe patients were treated at a single center from January 2011 to January 2022. BM only without metastases to other organs was defined as simple BM. The eligible patients were divided into RT alone (monotherapy arm) and RT plus ST (combined therapy arm). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of extracranial progression. After 1:1 propensity score matching analysis, two groups were compared for extracranial progression-free survival (ePFS), PFS, overall survival (OS), and intracranial PFS (iPFS).Results133 patients were identified and 100 were analyzed (monotherapy arm: n = 50, combined therapy arm: n = 50). The ePFS of the combined therapy was significantly longer than that of the monotherapy, with a median ePFS of 13.2 months (95% CI, 6.6–19.8) in combined therapy and 8.2 months (95% CI, 5.7–10.7) in monotherapy (P = 0.04). There were no statistically significant differences in PFS (P = 0.057), OS (P = 0.309), or iPFS (P = 0.448). Multifactorial analysis showed that combined therapy was independently associated with better ePFS compared with monotherapy (HR = 0.617, P = 0.034); more than 5 BMs were associated with worse ePFS compared with 1–5 BMs (HR = 1.808, P = 0.012).ConclusionsCompared with RT alone, combined therapy improves ePFS in patients with simple BM after first-line treatment of LS-SCLC. Combined therapy and 1–5 BMs reduce the risk of extracranial recurrence.