Multivariate Cox Regression Analysis Research Articles

A preliminary study of developing an MRI-based model for postoperative recurrence prediction and treatment direction of intrahepatic cholangiocarcinoma.

To establish an MRI-based predictive model for postoperative recurrence in intrahepatic cholangiocarcinoma (iCCA) and further to evaluate the model utility in treatment direction for neoadjuvant and adjuvant therapies. Totally 114 iCCA patients with curative surgery were retrospectively included, including 38 patients in the neoadjuvant treatment, traditional surgery, and adjuvant treatment groups for each. Predictive variables associated with postoperative recurrence were identified using univariate and multivariate Cox regression analyses, and a prognostic model was formulated. Recurrence-free survival (RFS) curves were compared using log-rank test between MRI-predicted high-risk and low-risk iCCAs stratified by the optimal threshold. Tumor multiplicity (hazard ratio (HR) = 1.671 [95%CI 1.036, 2.695], P = 0.035), hemorrhage (HR = 2.391 [95%CI 1.189, 4.810], P = 0.015), peri-tumor diffusion-weighted hyperintensity (HR = 1.723 [95%CI 1.085, 2.734], P = 0.021), and positive regional lymph node (HR = 2.175 [95%CI 1.295, 3.653], P = 0.003) were independently associated with postoperative recurrence; treatment group was not significantly related to recurrence (P > 0.05). Independent variables above were incorporated for the recurrence prediction model, the 1-year and 2-year time-dependent area under the curve values were 0.723 (95%CI 0.631, 0.815) and 0.725 (95%CI 0.634, 0.816), respectively. After risk stratification, the MRI-predicted high-risk iCCA patients had higher cumulative incidences of recurrence and worse RFS than the low-risk patients (P < 0.001 for both). In the MRI-predicted high-risk patients, neoadjuvant therapy was associated with improved all-stage RFS (P = 0.034), and adjuvant therapy was associated with improved RFS after 4months (P = 0.014). The MRI-based iCCA recurrence predictive model may serve as a decision-making tool for both personalized prognostication and therapy selection.

Development and validation of a nomogram for predicting overall survival of head and neck adenoid cystic carcinoma

This study aimed to develop and validate a nomogram using clinical variables to guide personalized treatment strategies for adenoid cystic carcinoma of the head and neck (ACCHN). Data from 1069 patients with ACCHN diagnosed between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were used to construct the nomogram. External validation was performed using an independent cohort of 70 patients from Fujian Cancer Hospital. Multivariate Cox regression analysis was conducted using IBM SPSS version 26.0 and R Software version 4.2.3. The concordance index (C-index) and receiver operating characteristic (ROC) curves were used to assess the predictive accuracy of the nomogram. Age, tumor site, surgery, N stage, M stage, and TNM stage were identified as independent prognostic factors through univariate and multivariate Cox analyses. The nomogram demonstrated superior predictive performance compared to the TNM staging system, effectively stratifying patients into high-risk and low-risk groups. This nomogram offers a valuable tool for predicting overall survival in patients with ACCHN and tailoring individualized treatment approaches.

Brain metastasis burden and management in patients with small cell lung cancer in Canada: a retrospective, population-based cohort study

Patients with small cell lung cancer (SCLC) have historically been characterised by poor overall survival (OS) and high risk for brain metastasis (BM), but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. Our aim was to describe the clinical characteristics and outcomes of patients with SCLC and BM in Ontario, Canada. This population-based, retrospective cohort study included all patients in Ontario, Canada, who were diagnosed with SCLC between April 1, 2010, and March 31, 2018. Data were analysed between June 2, 2022, and December 20, 2023. Patients with second cancer diagnosis were excluded. Patients were identified and data retrieved from the Institute for Clinical Evaluative Sciences (ICES) databases. Kaplan-Meier and multivariable Cox regression analyses were performed to compare OS between patient cohorts stratified by disease stage, BM diagnosis, and intracranial treatment modality. Propensity score-matching based on age, disease stage, time to BM, and receipt of chemotherapy was performed to compare OS between intracranial treatment modalities. 8705 patients were included (male: 4433, female: 4272). Median age at diagnosis was 68 years (interquartile range, IQR, 61-75). Median OS of all patients was 7.46 months (95% confidence interval, CI, 7.23-7.69). 32% (n=2686) of patients developed BM (synchronous, 43.7%; asynchronous, 56.3%) with median OS of 9.76 months (95% CI, 9.36-10.22). 102 (4%), 1654 (62%), and 930 (35%) patients received stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), or no treatment, respectively, for their BM in the first-line setting or after prophylactic cranial irradiation (PCI). In propensity score-matched analyses, OS from time of BM diagnosis was non-inferior between SRS- and WBRT-treated cohorts among patients who did not receive PCI (hazard ratio, HR, 0.68, 95% CI, 0.44-1.06, p=0.091, n=86) and in favour of SRS for those who received PCI prior to BM development (HR, 0.47, 95% CI, 0.31-0.72, p=0.0042, n=112). OS for patients with SCLC remains poor, and many patients present with BM. With careful selection, patients with SCLC and BM may benefit from SRS treatment. Future research should incorporate information on burden of intracranial disease and novel immunotherapies. None.

Preoperative Tumor Growth Rate Does Not Predict Overall or Progression-free Survival in Patients With Glioblastoma.

Presurgical tumor volume progression in glioblastoma (GBM) may be a predictor of survival. This study aims to evaluate the potential impact of preoperative tumor growth and other clinical as well as laboratory parameters on overall survival (OS) of GBM patients. We retrospectively analyzed 98 adult patients with GBM who received two magnetic resonance imaging (MRI) scans between 2013 and 2023, before primary surgery and concurrent Stupp chemoradiotherapy. Tumor growth rates were calculated to classify GBM into slower and faster growing categories. Statistical analyses, including Kaplan-Meier and multivariable Cox regression survival analyses, were performed to evaluate the impact of various clinical and treatment-related factors on OS and progression-free survival (PFS). Slower growing tumors had a significantly longer doubling time than faster growing lesions. Univariable analysis showed no significant differences in OS (p=0.12) or PFS (p=0.4) when analyzed according to tumor growth. When stratified by O6-methylguanin-DNA-methyltransferase (MGMT) status, there were still no differences in OS (p=0.14), but in PFS (p=0.009). In the multivariable Cox regression analysis, radiation dose (p=0.02) and the number of adjuvant cycles of temozolomide (TMZ) (p=0.002) were significantly associated with OS. MGMT status (p=0.02) and the number of adjuvant TMZ cycles (p<0.001) were significantly associated with prolonged PFS. Specific volume growth rate (SVGR), patient age, baseline tumor volume, Karnofsky performance status, extent of resection, and total radiation dose were not significantly associated with PFS. SVGR was not significantly associated with OS or PFS. In contrast, MGMT status, radiation dose, and number of adjuvant TMZ cycles were identified as predictors of treatment outcomes. These factors can guide physicians when designing personalized treatment concepts for patients with GBM.

Stereotactic radiotherapy for patients with bone metastases: a selected group with low rate of radiation treatment during the last month of life?

BackgroundComplex high-precision radiotherapy, such as stereotactic body radiotherapy (SBRT), should only be offered to patients with sufficiently long survival. In the context of bone metastases radiotherapy, low rates of treatment close to the end of life, e.g. last 30 days (RT30), may serve as a quality of care indicator. While traditional, pain-relieving short-course regimens have been studied comprehensively, real-world SBRT results are still limited.MethodsRetrospective analysis (2010–2023, n = 1117 episodes) of patients with bone metastases treated with traditional single-fraction (8 Gy × 1) or multi-fraction regimens (often 4 Gy × 5 or 3 Gy × 10) compared to stereotactic single-fraction (12–16 Gy × 1) or multi-fraction regimens.ResultsExcept for gender, almost all baseline variables were uneven distributed. Failure to complete fractionated radiotherapy was uncommon in the stereotactic (4%) and non-stereotactic group (3%), p = 1.0. With regard to RT30, relevant differences emerged (19% for 8-Gy single-fraction versus 0% for stereotactic single-fraction, p = 0.01). The corresponding figures were 11% for multi-fraction non-stereotactic and 2% for multi-fraction stereotactic, p = 0.08. Median overall survival was shortest after 8-Gy single-fraction irradiation (4.2 months) and longest after stereotactic multi-fraction treatment (13.9 months). Neither stereotactic radiotherapy nor multi-fraction treatment improved survival in multivariate Cox regression analysis. Factors significantly associated with longer survival included better performance status, lower LabBM score (5 standard blood test results), stable disease outside of irradiated area(s), metachronous distant metastases, longer time interval from metastatic disease to bone irradiation, and outpatient status.ConclusionThe implementation of SBRT for selected patients has resulted in low rates of non-completion and RT30. Optimal selection criteria remain to be determined, but in current clinical practice we exclude patients with poor performance status, unfavorable blood test results (high LabBM score) and progressive disease sites not amenable to SBRT. Established, guideline-endorsed short-course regimens, especially 8-Gy single-fraction treatment, continue to represent an important palliative approach.

The Long-Term Results of Proximal Gastrectomy for Proximal Gastric Cancer: A Propensity Score Matching Analysis Based on SEER Database.

Proximal gastrectomy (PG) is one of function-preserving gastrectomy (FPG). In this study, we compared the long-term results of proximal gastric cancer (PGC) patients undergoing proximal gastrectomy and total gastrectomy (TG). Patients diagnosed with PGC and receiving PG or TG between 2004 and 2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was applied to minimize confounding factors. Kaplan-Meier analysis and log-rank test were used to compare overall survival (OS) and cancer-specific survival (CSS) between the PG and TG groups. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting OS. A total of 3916 patients were recruited according to the inclusion and exclusion criteria, with 2614 undergoing PG and 1302 undergoing TG. After 1:1 PSM matching, 912 pairs of data were included for analysis. Before PSM matching, PG group tended to have better OS and CSS outcomes. However, after PSM matching, both surgical approaches showed similar long-term results. PG for PGC yields comparable long-term outcomes to TG and demonstrates safety in terms of oncologic outcomes.

Construction and Validation of a Prognostic Prediction Model for Gastric Mucinous Adenocarcinoma Based on the SEER Database

This study focused on the development and validation of a prognostic model to predict overall survival (OS) in patients with gastric mucinous adenocarcinoma (GMA), utilizing data from the SEER database. A cohort of 537 GMA patients was analyzed to identify factors affecting survival, using both univariate and multivariate Cox regression analyses on demographic and clinicopathological variables. The analysis led to the creation of a nomogram model. Findings revealed that TNM staging and the administration of radiotherapy or chemotherapy were significant factors impacting survival outcomes. Specifically, patients at stages T4, N3, and M1 faced a notably higher mortality risk, while those who received radiotherapy and chemotherapy experienced a significant reduction in mortality risk. The model's performance, as indicated by C-indices of 0.73 in the training set and 0.66 in the validation set, suggests robust predictive capability. The area under the curve (AUC) analysis confirmed high accuracy in predicting 1-year, 3-year, and 5-year survival rates, and calibration curves displayed strong agreement between predicted and actual outcomes. Decision curve analysis (DCA) demonstrated that the model exhibited significant clinical utility across various thresholds. Overall, this study presents a reliable prognostic tool for individualized risk stratification and clinical treatment in GMA patients. Future work should focus on enhancing the model by incorporating molecular biological data to increase its predictive accuracy and applicability.

Construction of a combined prognostic model for pancreatic ductal adenocarcinoma based on deep learning and digital pathology images

BackgroundDeep learning has made significant advancements in the field of digital pathology, and the integration of multiple models has further improved accuracy. In this study, we aimed to construct a combined prognostic model using deep learning-extracted features from digital pathology images of pancreatic ductal adenocarcinoma (PDAC) alongside clinical predictive indicators and to explore its prognostic value.MethodsA retrospective analysis was conducted on 142 postoperative pathologically confirmed PDAC cases. These cases were divided into training (n = 114) and testing sets (n = 28) at an 8:2 ratio. Tumor whole-slide imaging features were extracted and screened to construct a pathological risk model based on a pre-trained deep learning model. Clinical and pathological data from the training set were used to select independent predictive factors for PDAC and establish a clinical risk model using LASSO, univariate, and multivariate Cox regression analyses. Based on the pathological and clinical risk models, a combined model was developed. The Harrell concordance index (C-index) was computed to assess the predictive performance of each model for PDAC survival prognosis.ResultsFor the training and testing sets, the C-index values for the clinical risk model were 0.76 and 0.75, respectively; for the pathological risk model, they were 0.82 and 0.73, respectively; and for the combined model, they were 0.86 and 0.77, respectively. The combined model exhibited appropriate calibration at 1-, 3-, and 5-year time points, as well as a superior area under the curve of the receiver operating characteristic curve and clinical net benefit compared to the single models.ConclusionsIntegrating the pathological and clinical risk models may provide a higher predictive value for survival prognosis.

A Novel Liver Metastasis Score for Patients Undergoing Surgical Resection of Gastroenteropancreatic Neuroendocrine Tumors: A Multi-institutional Study.

Liver metastasis impacts survival in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs); however, current guidelines lack consensus on post-resection surveillance and adjuvant therapy. A comprehensive risk stratification tool is needed to guide personalized management. We aimed to develop and validate a predictive model for liver metastasis risk after surgical resection of GEP-NETs that incorporates pathological factors and adjuvant therapy. Patients with GEP-NETs who underwent surgical resection with curative intent at three major Chinese hospitals (2010-2022) were identified. Univariable and multivariable Cox regression analysis identified independent risk factors of liver metastasis. The liver metastasis score (LMS) was developed using weighted risk factors and validated by tenfold cross-validation. Among the 724 patients included in the analytic cohort, liver metastasis occurred in 66 patients (9.1%) at a median of 36 months; patients with liver metastasis had a worse 5-year overall survival (no liver metastasis 63.6% vs. liver metastasis 95.8%; p<0.001). Independent predictors were Ki-67 index (hazard ratio [HR] 10.36 for Ki-67 3-20%, HR 18.30 for Ki-67 >20%, vs. <3%), vascular invasion (HR 5.03), lymph node metastases (HR 2.24), and lack of adjuvant therapy (HR 3.03). The LMS demonstrated excellent discrimination (C-index 0.888) and stratified patients into low, intermediate, and high-risk relative to 5-year risk of liver metastasis: 2.9%, 20.8%, and 49.7%, respectively (p<0.001). The novel LMS effectively predicted the risk of liver metastasis after surgical resection of GEP-NETs. This validated model can help guide personalized surveillance and adjuvant treatment strategies, potentially improving outcomes for high-risk patients.

Sex differences in cardiovascular outcomes in patients with acute pancreatitis.

The risk of cardiovascular disease increases in patients with acute pancreatitis. However, it remains unknown whether this increase varies between males and females. To assess sex differences in cardiovascular outcomes among acute pancreatitis patients during long-term follow-up. Participants were recruited from the UK-biobank, which is a population-based cohort study consisting of 502 368 individuals aged 40-69 years old. Cardiovascular outcomes were defined as major cardiovascular and cerebrovascular adverse events (MACCE), encompassing all-cause death, myocardial infarction, and stroke. We compared sex difference in MACCE incidence using incidence rate per 1,000 person-years. The association between sex and MACCE risk was assessed using Cox proportional hazards models and win-ratio method, adjusted for demographic, lifestyle, metabolic factors and medication use. A total of 1371 participants with acute pancreatitis were included, 42.5% were male. Over a median follow-up of 13.9 years, 226 MACCE cases occurred. The incidence rate of MACCE for male was 16.44, compared to 9.80 in female. Multivariate Cox regression analysis indicated a higher risk of MACCE in male compared to female (HR 1.80 [95% CI 1.36-2.38]). Adjusted HR for all-cause mortality, myocardial infarction, and stroke were 1.49, 2.75, and 1.67, respectively. The adjusted win ratio by inverse probability of treatment weighting was 0.55 (P <0.001), suggesting a worse outcome in male acute pancreatitis patients. Male experienced more adverse cardiovascular outcomes than female in the long follow-up after acute pancreatitis, suggesting a need for sex-specific management strategies in acute pancreatitis patients.

Predictive value of early-stage postoperative albumin-bilirubin grade on the overall survival of hepatocellular carcinoma patients undergoing resection.

The albumin-bilirubin (ALBI) and ΔALBI grades have attracted substantial attention for their ability to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). This retrospective study aimed to evaluate the predictive value of the ALBI grade at different time points for the OS of patients with HCC who underwent surgical resection. The clinical data of patients with HCC who underwent radical resection in our hospital were collected and analyzed. The survival rate was analyzed using the Kaplan-Meier method and log-rank test. The risk factors influencing OS were identified via univariate and multivariate Cox regression analyses. A total of 104 patients with HCC were included in this study. The 1-, 3-, and 5-year OS rates of these patients were 91.3%, 64.0%, and 60.2%, respectively. The OS rates were significantly higher in patients with early-stage postoperative ALBI grade 2 than in those with grade 3 (P < 0.001); however, the preoperative ALBI grade, later-stage postoperative ALBI grade, ΔALBI grade (early stage), or ΔALBI grade (later stage) did not affect the OS rate. Furthermore, resection of ≥3 Couinaud liver segments [hazard ratio (HR) = 4.74; 95% confidence interval (CI), 2.32-9.67; P < 0.001], occurrence of postoperative complications (HR = 2.95; 95% CI, 1.38-6.31; P = 0.005), and early-stage postoperative ALBI grade 3 (HR = 2.50; 95% CI, 1.18-5.31; P = 0.02) were identified as independent risk factors for the OS of patients with HCC. Early-stage postoperative ALBI grade can be used to predict the OS of patients with HCC who have undergone radical hepatectomy. Early-stage postoperative ALBI grade 3, resection of ≥3 Couinaud liver segments, and occurrence of postoperative complications are independent risk factors affecting the OS of these patients.

The combined predictive power of the atherogenic index of plasma and serum glycated albumin for cardiovascular events in postmenopausal patients with acute coronary syndrome after percutaneous coronary intervention

BackgroundGlycated Albumin (GA) and atherogenic index of plasma (AIP) are two important biomarkers that respectively reflect lipid and glucose levels. Previous research has revealed their roles in cardiovascular diseases (CVD) and diabetes. However, their combined predictive ability in forecasting cardiovascular events (CVE) after percutaneous coronary intervention (PCI) among postmenopausal acute coronary syndrome (ACS) patients remains insufficiently studied.MethodsBased on the levels of AIP (AIP-L and AIP-H) and GA (GA-L and GA-H), four groups were used to categorize the patients. The CVE assessed included cardiac death, nonfatal myocardial infarction (MI) and nonfatal stroke. To evaluate the relationship between AIP, GA, and CVE, multivariate Cox regression analyses were performed.Results98 patients (7.5%) experienced CVE during follow-up. AIP and GA were revealed as strong independent predictors of CVE through multivariate analysis (AIP: HR 3.324, 95%CI 1.732–6.365, P = 0.004; GA: HR 1.098, 95% CI 1.023–1.177, P = 0.009). In comparison to those in the initial group (AIP-L and GA-L), the fourth group (AIP-H and GA-H) of patients exhibited the greatest CVE risk (HR 2.929, 95% CI 1.206–5.117, P = 0.018). Derived from the model of baseline risk, the combination of AIP + GA significantly enhanced the AUC, meanwhile combining AIP and GA levels maximized prognostic accuracy in the baseline risk model.ConclusionsThis study found that the combined measurement of AIP and GA significantly enhanced the predictive capability for CVE following PCI in postmenopausal ACS patients. By integrating these two biomarkers, it became possible to more accurately identify high-risk individuals and provided clinicians with new predictive tools for postmenopausal ACS patients in risk assessment and management.

Outcomes for Patients with Metastatic Castration-Resistant Prostate Cancer and Liver Metastasis Receiving [177Lu]Lu-PSMA-617.

It is well known that patients with liver metastasis from metastatic castration-resistant prostate cancer have poor or only transient responses to many forms of systemic therapy. Data on outcomes after treatment with [177Lu]Lu-PSMA-617 (LuPSMA) are scarce. The VISION trial reports a hazard ratio for overall survival (OS) in the subgroup of patients with liver metastasis without disclosing the absolute duration of survival. Using real-world clinical data, we examined this important subgroup of patients, describing prostate-specific antigen (PSA) response and OS. Methods: A single-institution database was assembled to include all patients receiving LuPSMA at Mayo Clinic in Rochester, Minnesota, for whom treatment was initiated between March 2022 and March 2023. Baseline clinicopathologic and imaging characteristics were abstracted. Patients were then categorized by presence or absence of liver metastasis on pretreatment prostate-specific membrane antigen (PSMA) PET. PSA response and OS for the 2 groups (liver metastasis vs. no liver metastasis) were compared using χ2 testing and the Kaplan-Meier method, respectively. A multivariate Cox regression analysis was performed, including established prognostic factors. Finally, those with pretreatment circulating tumor DNA as determined in an 83-gene panel were assessed for the presence of pathogenic and likely pathogenic alterations. These findings were summarized using descriptive statistics and compared between the 2 cohorts using the Fisher exact test. Results: The overall cohort consisted of 273 patients, including 43 (15.75%) with liver metastasis on pretreatment PSMA PET/CT. The median number of cycles received was 3 (range, 1-6) for patients with liver metastasis and 5 (range, 1-6) for those without hepatic involvement. The 50% or greater reduction in PSA from baseline response rate was lower for those with liver metastasis than for those without (30.23% [13/43] vs 49.77% [106/213], P = 0.019). At a median follow-up of 10 mo (interquartile range, 9-13 mo), there was a significant difference in median OS (8.35 mo vs. not reached, P < 0.001). On multivariate analysis, the presence of liver metastasis was independently associated with shorter survival (hazard ratio, 4.06; P < 0.001). Conclusion: Our data suggest that the presence of liver metastasis predicts poorer outcomes in patients receiving LuPSMA treatment. Alternative and combination approaches should be explored to maximize the antitumor activity of radiopharmaceutical therapy in the liver.

Effect of Prone Position Ventilation in Patients with Severe Craniocerebral Injury Complicated with Pulmonary Infection

Objective: To investigate the effects of prone ventilation in patients with severe traumatic brain injury combined with pulmonary infection. Methods: A total of 100 patients with severe traumatic brain injury combined with pulmonary infection in the hospital were randomly divided into a prone ventilation group and a conventional ventilation group, with 50 patients in each group. The Glasgow Coma Scale (GCS) score, APACHE II score, sputum culture results, oxygenation indicators, and prognosis were compared between the two groups. Data were processed using SPSS 25.0 statistical software, and t-tests and chi-square tests were used to compare continuous and categorical variables, respectively. Results: The experimental group showed better oxygenation indicators, a lower positive rate of sputum cultures, and reduced intracranial pressure compared to the control group (all P &lt; 0.05). Multivariate Cox regression analysis indicated that GCS score, APACHE II score, and prone ventilation were independent risk factors affecting patient prognosis (all P &lt; 0.05). Conclusion: Prone ventilation can improve oxygenation, reduce the risk of pulmonary infection, and decrease intracranial pressure in patients with severe traumatic brain injury combined with pulmonary infection, thereby improving patient prognosis. GCS score and APACHE II score can serve as important indicators for prognostic evaluation.

Association of plain water intake with risk of all-cause and cause-specific mortality in individuals with non-alcoholic fatty liver disease or metabolic dysfunction-associated steatotic liver disease

Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD)-related mortality have increased dramatically in past decades. Our study aims to investigate the association between plain water and this prevalent metabolic disease, as water plays a crucial role in regulating metabolic processes. A total of 3,543/3,428 individuals with NAFLD/MASLD were included in this study from National Health and Nutrition Examination Survey (NHANES). Daily plain water intake was recorded, and mortality status was tracked until December 31, 2019. Multivariate Cox regression models and restricted cubic spline (RCS) regression models were used to assess the association between plain water intake and long-term all-cause as well as cause-specific mortality among participants with NAFLD/MASLD. Furthermore, we investigated the relationship between substituting other beverages with plain water intake and the risk of mortality. The multivariate Cox regression analyses revealed a significant association between higher plain water intake and lower all-cause mortality, cerebrovascular diseases mortality, and cancer mortality in both NAFLD or MASLD patients. Dose-response analyses revealed a non-linear trend between plain water intake and mortality among NAFLD/MASLD patients. Additionally, replacing sugar or artificial beverages with plain water was linked to reduced all-cause mortality, cerebrovascular diseases mortality, and cancer mortality in patients with NAFLD/MASLD. Higher plain water intake is independently linked to lower risk of all-cause, cerebrovascular diseases mortality, and cancer mortality in NAFLD/MASLD patients. Increasing plain water intake may be an effective way for these patients to reduce their risk of mortality.

Chest Wall Hydatid Disease: Surgical management and risk Factors for Recurrence and Mortality

Background Hydatidosis of the thoracic wall differs from other hydatid localizations in its pathophysiology, diagnostic, and therapeutic management. It is a little-studied entity. The objectives of our work were to describe its surgical management and to analyze the factors that may influence recurrence and mortality. Methods A retrospective, descriptive, longitudinal, and multicenter study on four university hospital surgical centers of Tunis, from January 1995 to December 2022 including operated hydatid cysts of the thoracic wall. Overall survival (OS) and cumulative recurrence rates were calculated. Univariate and multivariable Cox regression analyses were performed to identify recurrence and mortality risk factors. Results Forty-nine patients were included. The mean age was 41 ± 17 years [8-76]. The main presenting sign was thoracic parietal swelling (n=22). Chest ultrasound and CT scan showed multivesicular formation in 17 and 33 cases, respectively. Muscle involvement was in the intercostal (n=4), paravertebral (n=13), and pectoralis major (n=3) muscles. Bone involvement was vertebral (n=11), costal (n=12), costo-vertebral (n=21) and sternal (n=2). A posterolateral thoracotomy was performed (n=20). Surgical excision at various levels of the chest wall with spinal stabilization (n=15) was performed. Sixty-three percent of the patients received antiparasitic medical treatment. Recurrence occurred in 37% of cases. Four patients died from hydatidosis-related complications. Factors could be independently associated with recurrence such as male gender, and vertebral involvement. The presence of a visceral hydatid cyst located at a distance from the parietal lesion at the time of diagnosis and the occurrence of postoperative infectious complications could increase mortality. Conclusions Chest wall hydatidosis represents a rare medical condition where surgery remains the preferred treatment modality. However, it carries a substantial burden of morbidity and mortality, influenced by various factors. Further large-scale studies are necessary to gain a deeper understanding of these factors and to optimize management strategies accordingly.

Influence of Right and Left Bundle Branch Block in Patients With Cardiogenic Shock and Cardiac Arrest.

The study investigates the prognostic impact of right bundle branch block (RBBB) and left bundle branch block (LBBB) in patients with cardiogenic shock (CS) compared with no bundle branch block (BBB). In patients with heart failure, existence of RBBB and LBBB has influence on prognosis. Prospective registry-study. ICU of a tertiary academic hospital in Germany. Adult patients with CS. None. Consecutive patients with CS were included. The prognostic impact of RBBB and LBBB on 30-day all-cause mortality was tested within the entire cohort and in the subgroup of CS patients with cardiac arrest at admission. The final study cohort comprised 248 patients. Patients with RBBB showed the highest 30-day all-cause mortality followed by LBBB and no BBB (72.5% vs. 52.9% vs. 50.0%; log-rank p = 0.015). These findings were consistent even after solely including CS patients with cardiac arrest (90.0% vs. 73.3% vs. 62.2%; log-rank p = 0.008). After adjustment for lactate, norepinephrine, troponin I, Acute Physiology Score, Society of Cardiovascular Angiography & Interventions shock stage, and heart rate in a multivariable Cox regression analysis, RBBB still revealed a negative impact on 30-day all-cause mortality (hazard ratio [HR], 1.807; 95% CI, 1.107-2.947; p = 0.018), whereas LBBB was not associated with 30-day all-cause mortality. In this multivariable Cox regression model lactate (HR, 1.065; 95% CI, 1.018-1.115; p = 0.006), troponin I (HR, 1.003; 95% CI, 1.001-1.005; p = 0.001), and Acute Physiology Score (HR, 1.033; 95% CI, 1.001-1.066; p = 0.041) were as well associated with 30-day all-cause mortality. Finally, no association of RBBB was found with the incidence of liver or severe renal failure. Besides the Acute Physiology Score, lactate, and troponin levels, RBBB was associated with an increased 30-day all-cause mortality in consecutive CS patients with and without cardiac arrest, whereas LBBB showed no prognostic impact.

The association between age at natural menopause and risk of asthma among postmenopausal women from the Canadian Longitudinal Study on Aging.

This study aimed to investigate the association between age at natural menopause and incidence of asthma among postmenopausal Canadian women. Women between the ages of 45-85 yr were followed for a 10-yr period. Analysis was restricted to naturally postmenopausal women who are nonsmokers and did not have asthma prior to menopause. Age at natural menopause was examined using the following categories: 40-44, 45-49, 50-54 (reference), and ≥55. Survival analysis was utilized to determine time to onset of asthma. Multivariable Cox regression analysis was performed to assess the relationship between age at natural menopause and asthma after adjusting for covariates. The multivariable Cox regression analysis showed a 30% decreased risk of asthma in women with age at natural menopause of 40-44 yr compared with age at natural menopause of 50-54 yr with a hazard ratio of 0.7 (95% confidence interval: 0.49-0.95). Women with later ages at natural menopause may be at increased risk for asthma.

Comprehensive Analysis of Prognostic Alternative Splicing Signatures in Tumor Immune Infiltration in Bladder Cancer.

Bladder cancer exhibits substantial heterogeneity encompassing genetic expressions and histological features. This heterogeneity is predominantly attributed to alternative splicing (AS) and AS-regulated splicing factors (SFs), which, in turn, influence bladder cancer development, progression, and response to treatment. This study aimed to explore the immune landscape of aberrant AS in bladder cancer and establish the prognostic signatures for survival prediction. Bladder cancer-related RNA-Seq, transcriptome, and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA). Gene set enrichment analysis (GSEA) was used to identify significantly enriched pathways of cancer-related AS events. The underlying interactions among differentially expressed genes (DEGs) and cancer-related AS events were assessed by a protein-protein interaction network. Univariate and multivariate Cox regression analyses were performed to identify crucial prognostic DEGs that co-occurred with cancer-related AS events (DEGAS) for overall survival. The area under the curve (AUC) of receiver operating characteristic (ROC) curves was used to assess the efficiency of the prognostic signatures. The CIBERSORT algorithm was used to explore the abundance of immune infiltrating cells. A total of 3755 cancer-related AS events and 3110 DEGs in bladder cancer were identified. Among them, 379 DEGs co-occurred with cancer-related AS events (DEGAS), of which 102 DEGAS were associated with 14 dysregulated SFs. GSEA and KEGG analysis showed that cancer-related AS events were predominantly enriched in pathways related to immunity, tumorigenesis, and treatment difficulties of bladder cancer. Multivariate Cox regression analysis identified 8 DEGAS (CABP1, KCNN2, TNFRSF13B, PCDH7, SNRPA1, APOLD1, CX3CL1, and DENND5A) significantly associated with OS, and they were further integrated into the prediction model with good AUCs at 3-year, 5-year and 7-year ROC curves (all>0.7). Immune infiltration analysis revealed the significant enrichment of three immune cell types (B cells naïve, dendritic cells resting, and dendritic cell activated) in high-risk bladder cancer patients. This study not only unveiled comprehensive prognostic signatures of AS events in bladder cancer but also established a robust prognostic model based on survival-related DEGAS. These aberrant AS events, dysregulated SFs, and the identified 8 DEGAS may have significant clinical potential as therapeutic targets for bladder cancer.

A multidimensional analysis of the impact of obesity on immune checkpoint inhibitor therapy efficacy

BackgroundObesity is a well-known risk factor for developing malignant tumors and promoting tumor cell growth and spread. However, recent studies have shown that obese cancer patients, who typically have a worse prognosis than nonobese cancer patients, show a significant improvement in survival after receiving immune checkpoint inhibitor (ICI) therapy. This phenomenon is known as the “obesity paradox”. However, this phenomenon is influenced by tumor type and sex. Therefore, this study aimed to explore the impact of obesity on immunotherapy efficacy from multiple perspectives, aiming to verify this paradox and provide new scientific evidence on the effect of obesity on ICI efficacy.MethodsThis retrospective study evaluated the data of patients who received ICI therapy between June 2019 and August 2023. Automatic segmentation of skeletal muscle, subcutaneous fat, and visceral fat was performed using Slice-O-Matic software, and the corresponding skeletal muscle index (SMI), subcutaneous fat index (SFI) and visceral fat index (VFI) were calculated. The neutrophil-to-lymphocyte ratio (NLR) was determined by dividing the neutrophil count by the lymphocyte count. Univariate and multivariate Cox regression analyses were used to evaluate the correlation between body mass index (BMI), body composition parameters, and the NLR with overall survival (OS) and progression-free survival (PFS) in obese patients receiving ICI therapy.ResultsWe analyzed 219 patients with a median age of 60 years (IQR 53–69 years; 155 men and 64 women). Obese patients, particularly those with visceral fat accumulation, exhibited extended OS after ICI therapy (log­rank P = 0.027). Cox multivariate analysis revealed that the NLR (HR = 1.036; 95% CI: 0.996 to 1.078; P = 0.002) was independently associated with OS. Patients with a high NLR had worse OS than those with a low NLR.ConclusionsThis study corroborates the veracity of the "obesity paradox" under specific conditions and identifies NLR as an independent prognostic factor, with elevated NLR indicative of a poor prognosis.