Cox Regression Research Articles

Expression and functional analyses of TERF2 in esophageal carcinoma

BackgroundEsophageal cancer (ESCA) is a prevalent malignancy with a high incidence of morbidity and mortality, particularly in Asia. Telomeric Repeat-binding Factor 2 (TERF2) is a crucial component of the telomere-binding protein complex that maintains telomere stability. Aberrant TERF2 expression has been implicated in tumorigenesis, however, its specific role in ESCA remains largely unexplored. MethodsThe expression levels of TERF2 were assessed in esophageal squamous cell carcinoma (ESCC) samples using RT-PCR, IHC, and Western blotting (WB). Serum tumor marker concentrations were determined via electrochemiluminescence immunoassay (ECLIA) and chemiluminescent microparticle immunoassay (CMIA). Bioinformatics analyses were employed to elucidate TERF2's function in EC. The impact of TERF2 on ESCC cell proliferation was evaluated through cell counting kit-8 (CCK8) assays and flow cytometry. ResultsTERF2 protein and mRNA expression were elevated in ESCC tissues and correlated with age, sex, cancer stage, tumor grade, lymph node metastasis (LNM), and tumor histology. Univariate Cox regression analysis indicated TERF2 was an independent prognostic factor for overall survival (OS). TERF2 mRNA levels were associated with serum levels of carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and tissue polypeptide antigen (TPA) in patients with ESCC. Immune infiltration and chemokine profiles were linked to TERF2 expression in ESCA. TERF2 is involved in regulating ESCC cell proliferation may through the DDR/P53 signaling way. ConclusionsTERF2 is overexpressed in ESCA and contributes to ESCC cell proliferation may via DDR/TP53 signaling pathway. These results suggest that TERF2 may serve as a potential target for developing treatments and diagnostic biomarker for ESCA.

Plasma fatty acid levels and risk of non-small cell lung cancer: a large-scale prospective cohort study

BackgroundNon-small cell lung cancer (NSCLC) ranks among the most prevalent and lethal malignancies globally. Fatty acids (FAs) play a significant role in diverse physiological and pathological mechanisms, yet their precise involvement in NSCLC remains poorly understood.MethodsThis study utilized a large-scale prospective cohort of 249,132 participants, observed over an average of 12 years, to investigate the relationship between different FAs and NSCLC risk. Analytical approaches included Cox proportional hazards regression, Kaplan–Meier survival analysis, accelerated failure time (AFT) modeling, and restricted cubic spline (RCS) analysis.ResultsDuring the follow-up period, 1,460 participants were diagnosed with NSCLC. Cox regression analysis demonstrated that elevated levels of docosahexaenoic acid (DHA), linoleic acid (LA), and omega-3 were inversely associated with NSCLC risk. Kaplan–Meier curves, along with AFT models, corroborated that elevated concentrations of DHA and LA significantly delayed NSCLC onset. Additionally, RCS analysis uncovered nuanced dose–response relationships between these FAs and NSCLC. Stratified analyses highlighted variability based on smoking status, gender, and body mass index subgroups.ConclusionThe concentration of specific FAs exhibits a significant association with NSCLC risk. These results offer a foundation for devising dietary FA composition adjustments aimed at reducing NSCLC risk.

Estimation of outpatient SARS-CoV-2 reinfection and recurrence rates and associated factors among COVID-19 hospitalized patients over one-year old: a multicenter retrospective cohort study

IntroductionReinfection with SARS-Cov-2 after recovery can occur that most of them don’t require hospitalization. The aim of this study is estimation of out-patient COVID-19 reinfection and recurrence rates and its associated factors among Iranian patients with history of confirmed SARS-Cov-2 infection and hospitalization.MethodsThis study is a retrospective cohort conducted from May 2021 to May 2022 in Iran. The national Medical Care Monitoring Center (MCMC) database, obtained from the Ministry of Health and Medical Education, includes all information about confirmed COVID-19 patients who are hospitalized and diagnosed during the pandemic. Using probability proportional to size sampling from 31 provinces, 1,532 patients over one years of age with a history of hospitalization in the MCMC data are randomly selected. After that, interviews by phone are performed with all of the selected patients using a researcher-made questionnaire about the occurrence of overall reinfection without considering the time of infection occurrence, reinfection occurring at least 90 days after the discharge and recurrence (occurring within 90 days after discharge). Univariate and multivariable Cox regression analyses are performed to assess the factors associated with each index. All of the analyses are performed using Stata software version 16.ResultsIn general, 1,532 phone calls are made, out of which 1,095 individuals are willing to participate in the study (response rate ≃ 71%). After assessing the 1,095 patients with a positive history of COVID-19, the rates of non-hospitalized overall SARS-Cov-2 reinfection, reinfection and recurrence are 122.64, 114.09, and 8.55 per 1,000 person-years, respectively. The age range of 19–64 years (aHR:3.93, 95%CI : 1.24–12.41) and COVID-19-related healthcare worker (aHR: 3.67, 95%CI: 1.77–7.61) are identified as risk factors for reinfection, while having comorbidity, being fully vaccinated, and having a partial pressure of oxygen (PaO2) ≥ 93 mmHg during the initial infection are identified as factors that reduce the risk of non-hospitalized reinfection.ConclusionReinfection due to COVID-19 is possible because of the weakened immune system for various reasons and the mutation of the virus. Vaccination, timely boosters, and adherence to preventive measures can help mitigate this risk.

The Association between Aortic Valve Stenosis and a Subsequent Diagnosis of Depression in Germany

Background/Objectives: Aortic valve stenosis (AS) represents one of the most common valve diseases in the western world. It often leads to severe symptoms that can lead to a restriction of everyday life and thus to psychological stress. Therefore, we aimed to investigate the association between AS and depression in outpatients in Germany. Methods: The IQVIATM Disease Analyzer database was used to identify 14,681 individuals with non-rheumatic AS (ICD-10: I35.0 or I35.2). They were propensity score matched (1:1) based on age, sex, average yearly consultation frequency during the follow-up, and co-diagnoses to 14,681 patients without AS. Cox regression models were used to analyze the association between aortic stenosis and depression. Results: Within the follow-up period of up to 10 years, depression was diagnosed in 20.6% of AS patients compared to 20.0% in the matched cohort (p = 0.351). In the regression analysis, we were not able to discover an association between AS and a subsequent diagnosis of depression (HR: 1.03; 95% CI: 0.96–1.11). This effect was consistent among different age and sex groups. Conclusions: In the broad population of patients treated outside of hospital settings in Germany, AS was not associated with a higher incidence of depression.

Standardized bone marrow assessment, risk variables, and survival in dogs with myelodysplastic syndrome and acute myeloid leukemia.

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are heterogeneous neoplasms of hematopoietic stem cells that are challenging to diagnose, differentiate, and prognosticate. Cytogenetic and mutational analyses are useful in humans but unavailable for dogs, where diagnosis and classification still rely largely on hematologic and morphologic assessment. The objectives of this study were to apply a classification scheme to myeloid neoplasms and to assess outcome in relation to predictor variables. Keyword search of a laboratory database, application of sequential exclusion criteria, and consensus from 3 reviewers yielded 70 cases of myeloid neoplasia with hematology results, and cytologic (11), histologic (14), or both (45) types of marrow specimens. Based on blast percentage and morphology, 42 cases were classified as MDS and 28 as AML. Dogs with MDS had significantly lower body weights, hemoglobin concentrations and blood blasts, and higher red blood cell size variability and platelet numbers than dogs with AML. Estimates of median survival using Kaplan-Meier curves for dogs with MDS and AML were 384 and 6 days, respectively (P < .001). The instantaneous risk of death for dogs with MDS was approximately 5× lower than that of dogs with AML. Significant predictor variables of survival were body weight, white blood cell count, platelet count, and percent blood blasts (P < .05). Hazard ratios (HRs) derived from best-fitting Cox regression models were 1.043, 0.998, and 1.061 for increased neutrophils, decreased platelets, and increased blood blasts, respectively. Findings from this study suggest that hematologic and morphologic variables are useful to predict outcomes in myeloid neoplasia.

Use of chemotherapy and loco-regional therapy in stage IA triple-negative breast cancer and their association with oncologic outcomes: A cancer registry study.

We aimed to evaluate the role of adjuvant chemotherapy and loco-regional therapy for stage IA (pT1, pN0) triple-negative breast cancer (TNBC) in a real-world setting. We identified patients with pT1, pN0 TNBC diagnosed between 2009 and 2021 within the Baden-Württemberg cancer registry (BWCR), Germany. Overall survival (OS) was assessed using Kaplan-Meier statistics and multivariate Cox regression models (adjusted for age, use of chemotherapy, local therapy (breast conserving therapy [breast conserving surgery + radiotherapy] vs. mastectomy), and tumor histologic subtype). A total of 1231 patients with a median follow-up of 45.9 months were identified: 1.0% (12 of 1231) with pT1mi stage, 9.5% (117 of 1231) with pT1a, 23.7% (292 of 1231) with pT1b, and 65.8% (810 of 1231) with pT1c. Multivariate Cox regression analysis revealed no significant influence for the use of chemotherapy on OS in pT1b patients (HR 0.90, 95% CI 0.43-1.90). For pT1c patients with Grade 1-2 tumors, the use of chemotherapy was not significantly associated OS (HR 1.01, 95% CI 0.48-2.11) but breast conserving therapy was associated with improved OS (HR 0.41, 95% CI 0.18-0.93). For pT1c patients with Grade 3 tumors, the use of chemotherapy (HR 0.51, 95% CI 0.33-0.78) as well as breast conserving therapy (HR 0.42, 95% CI 0.23-0.76) was associated with OS. This data suggests that OS in stage IA TNBC is strongly influenced by local therapy rather than the use of chemotherapy, except for pT1c patients with Grade 3 tumors. Larger studies with longer-term follow-up are welcomed to fully inform this discussion.

Conditional survival estimates for ependymomas reveal the dynamic nature of prognostication

BackgroundTraditional survival analysis is frequently used to assess the prognosis of ependymomas (EPNs); however, it may not provide additional survival insights for patients who have survived for several years. Thus, the conditional survival (CS) pattern of this disease is yet to be further investigated. This study aimed to evaluate the improvement of survival over time using CS analysis and develop a CS-based nomogram model for real-time dynamic survival estimation for EPN patients.MethodsData on patients with EPN were collected from the Surveillance, Epidemiology, and End Results (SEER) database. In order to construct and validate the model effectively, the selected patients were randomly divided at 7:3 ratio. CS is defined as the probability of surviving for a specified time period (y years) after initial diagnosis, given that the patient has survived x years. The CS pattern of EPN patients were explored. Then, the least absolute shrinkage and selection operator (LASSO) regression method with tenfold cross-validation was employed to identify prognostic predictors. Multivariate Cox regression was employed to develop a CS-based nomogram model, and we used this model to quantify EPN patient risk. Finally, the performance of the prediction model was also evaluated and verified.ResultsIn total, 1829 patients diagnosed with EPN were included in the study, with 1280 and 549 patients in the training and validation cohorts, respectively. The CS analysis demonstrated that patients' OS saw gradual improvements over time. With each additional year of survival post-diagnosis, the 10-year survival rate of EPN patients saw an increase, updating from 74% initially to 79%, 82%, 85%, 87%, 89%, 91%, 93%, 96%, and 98% (after surviving for 1–9 years, respectively). The LASSO regression model, which implements tenfold cross-validation, identified 7 significant predictors (age, tumor grade, tumor site, tumor extension, tumor size, surgery and radiotherapy) to develop a CS-based nomogram model. And further risk stratification was conducted based on nomogram model for these patients. Furthermore, this survival prediction model was successfully validated.ConclusionThis study described the CS pattern of EPN patients and highlighted the gradual improvement of survival observed over time for long-term survivors. We also developed the first novel CS-nomogram model that enabled individualized and real-time prognosis prediction. But patients must be counselled that individual circumstances may not always accurately reflect the findings of the nomogram.

The efficacy of mifepristone-misoprostol regimen versus misoprostol-only for medication abortion at 22 + 0/7 to 30 + 0/7weeks' gestation.

This study aimed to compare duration of medication abortion after pretreatment with mifepristone versus misoprostol-only regimens at 22 + 0/7 to 30 + 0/7weeks. This retrospective cohort study included patients admitted for medication abortion from 2014 to 2022. Patients underwent feticide due to genetic or anatomical abnormalities at gestational age of 22 + 0/7 to 30 + 0/7weeks. Excluded from this study were patients admitted at gestational age < 22 + 0/7 or > 30 + 0/7weeks, with multiple gestation, with diagnosis of intrauterine fetal demise before feticide, with contraindication for vaginal delivery, and who were administered a medical regimen other than the mifepristone-misoprostol or misoprostol-only protocol. Information collected included patients' demographics, clinical outcomes, additional procedural interventions, and complications. Data of patients treated with mifepristone-misoprostol versus misoprostol-only were compared. The study group included 46 patients in the mifepristone-misoprostol group and 35 in the misoprostol-only group. Median interval from first dose of misoprostol to fetal expulsion was shorter in the mifepristone-misoprostol group (10.6 vs. 15.3h; p = 0.007) with shorter duration of hospitalization (3.5 ± 1.1 vs. 4.1 ± 1.2days; p = 0.013). Study groups did not differ in terms of complications. Patients in the mifepristone-misoprostol group had a younger gestational age (23.8 ± 1.69 vs. 25.37 ± 2.4weeks; p = 0.002). However, multivariable Cox regression found that mifepristone was independently associated with shorter abortion time (OR 1.7, 95% CI 1.03-2.9, p = 0.03). Medication abortion with mifepristone-misoprostol was associated with shorter time to fetal expulsion at gestational ages 22 + 0/7 to 30 + 0/7weeks, compared with misoprostol-only regimen.

Myocardial contrast echocardiography evaluation of coronary microvascular dysfunction to Predict MACEs in patients with heart failure with preserved ejection fraction follow-up

BackgroundCMD refers to the abnormalities of the tiny arteries and capillaries within the coronary artery system, which result in restricted or abnormal blood flow. CMD is an important mechanism involved in ischemic heart disease and secondary heart failure. CMD can explain left ventricular dysfunction and poor prognosis.The European Association of Cardiovascular Imaging recommends the use of MCE for the assessment of myocardial perfusion. Myocardial contrast echocardiography (MCE) is used to evaluate the accuracy of Coronary microvascular dysfunction (CMD) for predicting major adverse cardiac events (MACEs) in patients with heart failure with preserved ejection fraction (HFpEF) at follow-up.MethodsThe clinical data of 142 patients diagnosed with HFpEF in our hospital from January 2020 to January 2022 were retrospectively summarized and stratified into 77 cases (> 1) in the CMD group and 65 cases (= 1) in the non-CMD group based on the perfusion score index (PSI) of the 17 segments of the left ventricle examined by the admission MCE, and the perfusion parameters were measured at the same time, including the peak plateau intensity (A value), the curve slope of the curve rise (βvalue) and A × β values. At a median follow-up of 27 months till October 2023, MACEs were recorded mainly including heart failure exacerbation, revascularization, cardiac death, etc.ResultsIncreasing age, hypertension, diabetes, and coronary artery disease in the CMD group resulted in decreased left ventricular ejection fraction (LVEF), increased plasma NT-B-type natriuretic peptide (BNP) and left ventricular global longitudinal strain (LVGLS), decreased A-values and A × β-values, and an increased incidence of MACEs (P < 0.05). Univariate and multivariate Cox regression analyses showed that LVGLS (HR = 1.714, 95% CI = 1.289–2.279, P < 0.001) and A × β values (HR = 0.636, 95% CI = 0.417 to 0.969, P = 0.035) were independent predictors of MACEs in patients with HFpEF. The receiver operating characteristic curve (ROC) showed that the area under the curve (AUC) of LVGLS combined with A × β value for diagnosis of MACEs was 0.861 (95% CI = 0.761 ~ 0.961, P < 0.001), which was significantly higher than that of LVGLS or A × β value (P < 0.05). The Kaplan-Meier survival curves showed that the cumulative survival rate in CMD group was significantly lower than non-CMD group (logrank χ2 = 6.626, P = 0.010), with the most significant difference at 20 months of follow-up.ConclusionMCE can evaluate CMD semi-quantitatively and quantitatively, LVGLS combined with A × β value has good performance in predicting the risk of developing MACEs in patients with HFpEF at 3 years of follow-up, and CMD can be used as an important non-invasive indicator for assessing clinical prognosis.

Consumption of milk and other dairy products and incidence of Parkinson's disease: a prospective cohort study in French women.

Previous studies showed positive associations between milk intake and Parkinson's disease (PD) in men but not in women, but few studies were available in women. Due to the long prodromal PD phase, reverse causation represents a major threat to investigations of diet in PD; cohort studies with a long follow-up are needed. We investigated associations between intake of milk and other dairy products with PD incidence in women from the E3N cohort study (1993-2018). PD diagnoses were validated using medical records and drug claim databases. Diet was assessed via a dietary questionnaire. Hazard ratios (HR) were estimated using multivariable Cox regression models. Exposures were lagged by 5y in main analyses and longer lags in sensitivity analyses. We examined the impact of adjustment for premotor symptoms (constipation/depression). During a mean follow-up of 18.8y, 845 of 71,542 women developed PD. Main analyses showed a J-shaped association between total milk intake and PD (P-non linearity = 0.045), with a significant linear positive association among drinkers (HR/1-SD = 1.09, 95% CI = 1.01-1.18, P = 0.024), that was explained in secondary analyses by a different pattern of association for plain milk (alone or with cereals) and milk added to drinks (tea/coffee/chicory). PD incidence increased significantly with plain milk consumption (HR/1-SD = 1.08 [1.02-1.14], P = 0.014). A U-shaped relation was observed for milk added to drinks (P-non linearity = 0.038), with lower PD incidence in women with moderate consumption (HR = 0.77 [0.61-0.97], P = 0.030) and no difference between non-drinkers and those with the highest consumption (HR = 0.98 [0.79-1.21], P = 0.848). Findings were similar in analyses using longer lags and adjusted for constipation/depression. Consumption of other dairy products was not associated with PD. A J-shaped association between total milk intake and PD was explained by a different pattern of association for plain milk intake and milk added to drinks. Reverse causation is unlikely to explain a positive association of plain milk with PD incidence in women. The U-shaped relation for milk added to drinks could be explained by an interaction between milk and coffee/tea/chicory. Further studies are warranted to elucidate the underlying mechanisms.

The effect of study partner characteristics on the reporting of neuropsychiatric symptoms across the neurocognitive spectrum.

We explored the influence of study partner (SP) characteristics on SP-reported neuropsychiatric symptoms (NPS) presence across the neurocognitive spectrum and on the prognostic utility of mild behavioral impairment (MBI). We performed cross-sectional (n = 26,748) and longitudinal (n = 12,794) analyses using participant-SP dyad data from the National Alzheimer's Coordinating Center. Participants were cognitively normal (CN; n = 11,951) or had mild cognitive impairment (MCI; n = 5686) or dementia (n = 9111). SPs rated NPS using the Neuropsychiatric Inventory Questionnaire. We used multivariable logistic regression to model the association between SP characteristics (age, sex, and relationship to participant [spouse, child, and other]) and NPS status (outcome). Cox regressions assessed SP characteristics as moderators of MBI associations with incident dementia or as predictors of incident dementia in MBI + participants only. Among CN persons, younger, female, and spouse SPs reported NPS more frequently. In MCI, younger SPs and those who were spouses or children of participants reported higher NPS odds. For dementia participants, NPS odds were higher in female and spouse SPs. MBI associations with incident dementia were slightly weaker when SPs were older but did not depend on SP sex or relationship to participant. Among MBI + participants with spouse or child SPs, hazard for dementia was higher when compared to MBI + participants with other SPs. SP age, sex, and relationship to participant influence NPS reporting across the neurocognitive spectrum, with potential implications for MBI prognosis. Considering SP characteristics may enhance the accuracy of NPS assessments, which may facilitate therapy planning and prognosis.

Hypertension control and risk of age-associated dementia in people with hiv infection.

Hypertension is a major risk factor for dementia, but sustained blood pressure control is difficult to achieve. We evaluated whether inadequately controlled hypertension may contribute to excess dementia risk among people with HIV. Retrospective cohort study. We studied demographically matched people with and without HIV between 7/1/2013 and 12/31/2021 who were ≥50 years old and had a hypertension diagnosis but no dementia diagnosis. Hypertension control was calculated using a disease management index (DMI) which captured degree and duration above the hypertension treatment goals of systolic blood pressure (SBP) <140 mmHg and diastolic blood pressure (DBP) <90 mmHg. DMI values ranged from 0% to 100% (perfect control); hypertension was considered "inadequately controlled" if DMI<80% (i.e., in control for <80% of the time). Annual, time-updated DMI was calculated for SBP and DBP. Associations of SPB and DPB control with incident dementia were evaluated using extended Cox regression models. The study included 3,099 hypertensive people with HIV (mean age: 58.3 years, 90.2% men) and 66,016 people without HIV. Each year of inadequate SBP control was associated with greater dementia risk in both people with HIV (adjusted hazard ratio [aHR] = 1.26, 0.92-1.64) and people without HIV (aHR = 1.27 (1.21-1.33); p-interaction = 0.85). Similarly, inadequate DBP control was associated with greater dementia risk in both people with HIV (aHR = 1.43, 0.90-1.95) and people without HIV (aHR = 1.71, 1.50-1.93; p-interaction = 0.57). Findings suggest the association of inadequate hypertension control with greater dementia risk is similar by HIV status. Stronger associations of DBP control with dementia merits further investigation.

The correlation between serum bone metabolism indexes and bone disease and survival in newly diagnosed multiple myeloma patients

ABSTRACT Objective Myeloma-related bone disease (MBD) is one of the most common complications of multiple myeloma (MM). This study aims to investigate the correlation between serum bone metabolism indexes (BMIs), the clinical characteristics and prognosis of newly diagnosed MM (NDMM) patients. Methods: The serum BMIs of 148 patients with NDMM in a single hematological disease treatment center from April 2014 to December 2019 were analyzed retrospectively, including type I collagen amino terminal elongation peptide (PINP), β-C-terminal telopeptide of type I collagen (β-CTX) and N-terminal osteocalcin (N-MID). Other clinical indexes were simultaneously collected and the degree of bone damage in patients was evaluated. We explored the effect of serum BMIs on the prognosis and identified independent prognostic factors. Another 77 NDMM patients from April 2018 to February 2021 served as the validation cohort. Results: The area under the curve (AUC) predicted by β-C-terminal telopeptide of type I collagen (β-CTX), type I collagen amino terminal elongation peptide (PINP), and N-terminal osteocalcin (N-MID) for overall survival (OS) were 0.708, 0.613, and 0.538, respectively. Patients with high serum levels had shorter OS (p < .001, p = .004, p = .027, respectively). Cox multivariate analysis indicated that serum β- CTX、lactic dehydrogenase、hemoglobin and the degree of bone injury were independent prognostic factors. A COX regression model was established with a C-index of 0.782 and validated with a C-index of 0.711. Conclusion: The serum BMIs are correlated with the patients’ OS, and β- CTX can be an independent prognostic factor.

Association of the Triglyceride-Glucose Index With Resistant Hypertension and a Nomogram Model Construction.

Resistant hypertension (RH) remains one of the major risk factors for cardiovascular disease. This study aims to investigate the association between the triglyceride-glucose (TyG) index and RH incidence in patients with hypertension and to construct a nomogram for predicting the occurrence of RH. A retrospective cohort study was conducted on 1635 patients initially diagnosed with hypertension at the Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University from August 2019 to August 2021. Patients were followed up for a median of 31 months, with 373 cases (22.81%) developing RH. Least absolute shrinkage and selection operator regression and multivariable Cox regression analysis identified the TyG index as the strongest predictor of RH (hazard ratio, 5.472 [95% CI, 4.028-7.433]; P<0.001). Consistent results were also observed in subgroup analyses across different ages and sexes. In addition to the TyG index, other independent risk factors, including uric acid, age, and the apnea-hypopnea index, were noted. A nomogram model was subsequently developed using these risk factors, and including the TyG index notably enhanced the diagnostic effectiveness of the model in predicting the occurrence of RH. The TyG index appears to be a potential predictor of RH in patients with hypertension, indicating that insulin resistance might be an important factor in the development and progression of RH.

Association of hemoglobin, albumin, lymphocyte, and platelet score with risk of all-cause and cause-specific mortality among cancer survivors: NHANES 1999-2018

BackgroundThe HALP score, comprising hemoglobin, albumin, lymphocyte, and platelet levels, serves as an indicator of both nutritional and inflammatory status. However, its correlation with all-cause and cause-specific mortality among cancer survivors remains unclear. Therefore, this study aims to investigate the relationship between HALP scores and mortality outcomes in this population.MethodWe extracted cohort data spanning ten cycles (1999-2018) from the U.S. National Health and Nutrition Examination Survey (NHANES). Mortality rates, determined using the National Death Index (NDI) as of December 31, 2019, were assessed. Weighted multivariate logistic regression analyzed the association between HALP scores and cancer prevalence. Kaplan-Meier analyses and weighted multivariate-adjusted Cox analyses investigated the link between HALP scores and all-cause and cause-specific mortality in cancer survivors. Restricted cubic spline (RCS) analysis was employed to assess nonlinear relationships. Furthermore, multi-parametric subgroup analyses were conducted to ensure the robustness of the results.ResultsOur study included 41,231 participants, of whom 3,786 were cancer survivors (prevalence: 9.5%). Over a median follow-up of 91 months (range: 51-136), we observed 1,339 deaths, including 397 from cancer, 368 from cardio-cerebrovascular disease, and 105 from respiratory disease. Elevated HALP scores showed a consistent association with reduced cancer incidence (P for trend &amp;lt;0.001). In multivariable-adjusted Cox regression analyses, HALP scores were significantly inversely associated with all-cause mortality, cancer mortality, cardio-cerebrovascular disease mortality, and respiratory disease mortality in cancer survivors (P for trend &amp;lt; 0.05). Nonlinear relationships between HALP scores and all-cause and cause-specific mortality in cancer survivors were evident through RCS regression modeling (P for nonlinearity &amp;lt; 0.01). Kaplan-Meier analyses demonstrated that higher HALP scores were indicative of a poorer prognosis.ConclusionOur findings indicate a notable inverse correlation between HALP scores and both all-cause and cause-specific mortality among cancer survivors.

Ischemic Stroke in Adults With Congenital Heart Disease: Cumulative Incidence and Associated Factors.

When more patients with congenital heart disease reach adult age, increased incidence of long-term complications, including ischemic stroke, are expected. The aim of this study was to analyze cumulative incidence of ischemic stroke, associated factors, and case fatality in adult congenital heart disease. The study is based on Swedish national registers on congenital heart disease and stroke. Patients with congenital heart disease were followed between 2001 and 2018 for first-ever ischemic stroke events (ischemic stroke due to patent foramen ovale excluded). Factors possibly associated with ischemic stroke were analyzed using Cox regression models. Out of 8914 adult patients with congenital heart disease, 108 suffered ischemic stroke over a mean period of 7.6±4.7 years. The mean age at ischemic stroke was 53.8 years, and the cumulative incidence was 0.15% at 1 year, 0.5% at 5 years, and 1.5% at 10 years. In multivariable analysis, age (hazard ratio [HR], 1.04 [95% CI, 1.03-1.06]), diabetes (HR, 2.9 [95% CI, 1.3-6.4]), ejection fraction <50% (HR, 1.9 [95% CI, 1.1-3.4]), atrial septal defect (HR, 3.0 [95% CI, 1.03-8.5]), and aortic valve lesions (HR, 4.8 [95% CI, 1.6-14.1]) were associated with increased risk. Among those with ischemic stroke, approximately half were on antithrombotic treatment (anticoagulants or antiplatelets) before admission. Case fatality was 6.5%. The cumulative incidence of ischemic stroke was 1.5% after 10 years. In adult congenital heart disease, the type of heart lesion, diabetes, ejection fraction <50%, and age were important factors associated with ischemic stroke. Despite a relatively young age, mortality is a significant threat. At time of the ischemic stroke event, approximately half of the patients were on antithrombotic treatment.

SNAI1: a key modulator of survival in lung squamous cell carcinoma and its association with metastasis

BackgroundSnail family zinc finger 1 (SNAI1) has been implicated in cancer progression and prognosis across various malignancies. This study aims to elucidate the prognostic significance of SNAI1 expression in Lung Squamous Cell Carcinoma (LUSC) using data from The Cancer Genome Atlas (TCGA) database.MethodsSNAI1 expression levels in LUSC patients were stratified using X-tile software to establish optimal cut-off values. Kaplan-Meier survival analysis was performed to assess the impact of SNAI1 expression on overall survival (OS). Univariate and multivariate Cox regression analyses were conducted to evaluate the prognostic value of SNAI1, considering clinical parameters such as age, clinical stage, and TNM classification. Additionally, we explored the interaction between SNAI1 expression and metastatic status, and performed Gene Set Enrichment Analysis (GSEA) to investigate associated cellular pathways. Correlations between SNAI1 and immune checkpoint molecules were also examined.ResultsKaplan-Meier analysis revealed significant differences in OS among high, medium, and low SNAI1 expression groups (p < 0.001), with median survival times of 1.6, 3.0, and 5.8 years, respectively. Dichotomizing patients into high and low SNAI1 expression groups confirmed that high SNAI1 expression was associated with significantly poorer OS (p < 0.001). SNAI1 remained an independent prognostic factor in multivariate analysis. High SNAI1 expression correlated with poorer survival outcomes regardless of metastatic status, and the combination of high SNAI1 expression and metastasis resulted in the poorest survival. GSEA identified significant associations between SNAI1 and inflammatory, immune response pathways. Positive correlations were observed between SNAI1 and key immune checkpoint molecules, suggesting an interplay with immune checkpoint mechanisms.ConclusionsHigh SNAI1 expression is a robust prognostic indicator of poor survival in LUSC, independent of other clinical factors. Its association with immune checkpoint molecules highlights its potential as a therapeutic target. These findings underscore the prognostic and therapeutic relevance of SNAI1 in LUSC and possibly other cancers. Further research is warranted to explore targeted therapies against SNAI1.

Prognostic Significance of Human Papillomavirus Genotypes in Oropharyngeal Squamous Cell Carcinoma.

The prognostic significance of human papillomavirus (HPV) genotypes in oropharyngeal squamous cell carcinoma (OPSCC) has garnered considerable attention due to the increasing reliance on HPV status for clinical decision-making. This study aimed to compare the survival outcomes associated with different HPV genotypes in patients with OPSCC relative to HPV-negative tumors, providing insights into the potential implications for treatment de-intensification strategies. Patients diagnosed with invasive OPSCC were included from the National Cancer Database (NCDB). Patients were stratified based on HPV status and genotype, with HPV-negative tumors serving as the reference group. Multivariable Cox regression analysis was performed to assess the independent prognostic value of different HPV genotypes. Th majority of patient were classified as HPV-positive (N = 17,358, 70.0%), with HPV 16 being the most common genotype (N = 15410/17358, 88.8%) compared with other high-risk (N = 1217/17,358, 7.0%) and low-risk (N = 731/17,358, 4.2%) HPV genotypes. A significantly lower risk of death was measured for all HPV-positive compared with HPV-negative tumors (HPV 16: adjusted HR 0.51; 95% CI: 0.49-0.54; other high-risk HPV: adjusted HR 0.56; 95% CI: 0.49-0.63; low-risk HPV: adjusted HR 0.59; 95% CI: 0.50-0.68; p < 0.001). This study highlights the significant prognostic value of HPV genotypes in OPSCC, underscoring the superior survival outcomes of HPV-positive tumors across all genotypes compared with HPV-negative tumors. Detailed HPV subtype analysis can inform better treatment decisions and support de-intensification strategies for patients with low-risk genotypes. 3 Laryngoscope, 2024.

Early B lymphocyte subsets in blood predict prognosis in sepsis

BackgroundB lymphocytes play a key role in immunosuppression. This study investigated the prognostic value of B cell subsets in sepsis.MethodsFlow cytometry was used to assess peripheral B cell subsets from patients with sepsis on the first and seventh days following admission, as well as 111 healthy controls. The patients were divided into survivors and non-survivors, based on 28-day prognosis.ResultsThe analysis showed abnormal distribution and selective depletion of B cells and its subsets in the early stages of sepsis. On day 1, compared with survivors, non-survivors showed significant decreases in the proportion and absolute count of transitional (Tr) B cells, reductions in the proportion of CD5+ B cells, and increases in the proportion of double-negative (DN) B cells. On day 7, the proportions and absolute counts of Tr and CD5+ B cells significantly decreased whereas the proportion of DN B cells significantly increased in non-survivors. Ninety-four survivors and 15 non-survivors were included in our paired-sample rank-sum test. Compared to day 1, only the survivors showed significant increases in absolute B, Tr B, and CD5+ B cell counts by day 7. Multivariate Cox regression analysis showed that the proportion of DN B cells on day 1 (hazard ratio = 1.092 [95% confidence interval: 1.035–1.152], P = 0.001) was a risk factor for mortality, and Kaplan–Meier survival curve analysis showed that patients with proportions of DN B cells &amp;gt; 11.81% on day 1 had poorer prognoses. Receiver operating characteristic curve analysis showed that B cell subset parameters could predict mortality (area under the receiver operating characteristic curve [AUC], 0.741) and enhanced the prognostic value of the Acute Physiology and Chronic Health Evaluation II score (AUC, 0.840).ConclusionOur study revealed that deficiencies of B, Tr B, and CD5+ B cells, as well as a persistent increase in the proportion of DN B cells, were associated with poor prognosis—and that B cell subsets showed predictive value to mortality. These results provide new insights into the roles of B cell subsets in sepsis, as well as ways to better manage its progression and predict its course.

Long-term outcomes in rapamycin on renal allograft function: a 30-year follow-up from a single-center experience

ObjectivesTo evaluate long-term renal graft prognosis and the role of rapamycin from a single-center in China over a 30-year follow-up.MethodsThis study enrolled a total of 654 patients who underwent kidney transplantation between 1989 and 2020. The basic characteristics of the included patients were collected. Graft survival was described and compared using Kaplan-Meier curves (K-M curves). Both continuous and categorical variables were included in a multivariate Cox proportional-hazards model. Patients were divided into rapamycin-based quadruple immunosuppression regimen group (rapa group, n = 41) and conventional tacrolimus-based triple immunosuppression regimen group (control group, n = 218). The indication biopsy results of the two groups were further reviewed to compare the incidence of rejection, acute rejection, and banff score.ResultsThe overall 5, 10, 15, 20-year graft survival rate of our center is 87.5%, 62.4%, 46.4% and 20.9%, respectively. The median survival time after surgery is 14 years. Multiple Cox regression analysis identified BMI (p = 0.035), dialysis type (p < 0.001), immunosuppressants (p < 0.01), urine albumen (p < 0.001), globulin (p = 0.041), and blood glucose (p = 0.002) as risk factors. The 20-year, 10-year and 5-year AUC is 0.78, 0.75 and 0.75. The combination of FK506 and rapamycin was further suggested by the model to effectively improve the graft prognosis (p < 0.01, HR = 0.763). The K-M curve showed that the long-term survival rate of renal grafts in the rapa group was significantly better than that in the conventional group (p < 0.001). In addition, indication biopsy records revealed a lower possibility of immune rejection in the rapa group than that in the conventional group (p < 0.001). Banff score indicated that rapa group had less vascular inflammation in the transplanted kidney.ConclusionsIn this study, a 30-year follow-up was performed in a single center, and a total graft 20-year survival rate of 20.9% was reported. The prognostic model and subgroup analysis suggested that FK506 combined with rapamycin could effectively improve the prognosis of renal transplantation, which could be explained by reduced acute rejection and less vascular inflammation.