Related Survival Research Articles

Survival outcomes of endometrial cancer patients with disease involving the lower uterine segment: A meta-analysis.

Lower uterine segment (LUS) involvement is encountered in a small proportion of endometrial cancer patients and is associated with aggressive histological features. Despite the available evidence, there seems to be a lack of consensus concerning its actual impact on disease related survival. The search strategy involved the Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases. Nine studies were included in the present systematic review that recruited 3300 patients. Pooled hazard ratios (HR) were retrieved from Cox-regression analyses to limit the confounding effect of other factors that influence the course of the disease. Nine articles were included in the present meta-analysis that involved 3300 endometrial cancer patients. The meta-analysis revealed a significant difference in progression free survival that was found increased in patients without LUS involvement (HR 1.59, 95% CI 1.22, 2.05, data from 9 studies). Similarly, a significantly smaller overall survival was observed among patients with LUS involvement (HR 1.69, 95% CI, 1.34, 2.13, data from 7 studies). Sensitivity analysis revealed that there were no outliers in either outcome, however, the possibility of data manipulation could not be ruled out entirely. The results of this meta-analysis indicate that lower uterine segment involvement is associated with decreased survival outcomes. It remains unclear if these patients can benefit from adjuvant treatment in the absence of other negative prognostic indicators and this needs to be examined by future studies.

Survivability prognosis of lung cancer patients with comorbidities-a Gaussian Bayesian network model.

Comorbidities are influencing factors that cause lung cancer. An accurate survivability prediction model is required considering these confounding factors (a variety of comorbidities and treatments). The study developed a conditional Gaussian Bayesian network (CGBN) model to predict the related survival time with likelihood under various conditions. The lung cancer patients were collected from the National Health Insurance Research Database in Taiwan. Six major chronic diseases (i.e., pulmonary tuberculosis, COPD, kidney failure, diabetes mellitus, stroke, and liver disease) are investigated. A total of 2875 lung cancer cases with key comorbidities were selected. This study examined three types of lung cancer treatment: surgery, chemotherapy, and targeted therapy. The study outcomes provided the likelihood of survival time occurrences. Survival analysis indicates that diabetes mellitus and liver disease are significantly riskier than the other comorbidities for lung cancer patients. The proposed CGBN model achieved high accuracy as compared to the existing literature. The proposed CGBN model is advantageous for modeling the relationship between numerical and categorical influencing factors and response variables for lung cancer with comorbidities. The proposed model facilitates the flexible and accurate estimation of various lung cancer-related queries.

Real world clinical outcomes from targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer: data from a large cohort at a national cancer institute.

Randomised evidence supports the use of partial breast irradiation (PBI) with targeted intraoperative radiotherapy (TARGIT-IORT) for early stage breast cancer, but prospective data from real-world adoption of this technique is also important. The aim of this study was to determine if the outcome reported in TARGIT-A trial could be replicated in large cohort of early stage breast cancer treated with TARGIT-IORT. This prospective observational study analysed all patients treated with TARGIT-IORT between 2004 and 2021 in a single national cancer institute. TARGIT-IORT during lumpectomy was performed according to the risk-adapted TARGIT-A protocol using the Intrabeam® device. We analysed the completeness of follow up, 5-year in-breast-tumour-recurrence (IBTR), long term local recurrence free survival, distant disease-free survival, overall survival and breast-cancer-related survival, using the Kaplan-Meier method. A covariate analysis was performed to investigate risk factors for IBTR. We also analysed high grade toxicity events. The study included 814 patients and the a median follow up was 72 months. The majority of patients (60.3%) received TARGIT-IORT as PBI modality ("exclusive IORT" group); 39.7% received additional EBRT. There was no significant difference between the 5 years IBTR for the whole study population and the "exclusive IORT" cohort (1.6% (95%CI=1.1-2.1%) and 2.5% (95%CI=1.7%-3.3%) respectively). 5 years overall survival and tumour related survival were >95%. In 21% of patients with recurrence, breast was preserved. Radiotherapy toxicity (CTCAE Grade>2) was very rare (0.9%). This large single institute study found that breast cancer control and survival outcomes with TARGIT-IORT were consistent with TARGIT-A trial results. This "real world" experience confirmed that the randomised evidence showing the value of TARGIT-IORT as partial breast irradiation modality that can be replicated in routine clinical practice.

A longitudinal 5-year study for the prediction of HCC, death and liver decompensation by ARFI elastography.

Numerous studies have evaluated elastography for the staging of liver fibrosis. Fewer studies were performed investigating the prognostic relevance using transient elastography (TE), although with promising results. This study was designed to evaluate the prognostic relevance of ARFI elastography. Patients receiving ARFI elastography in our ultrasound department between 2010 and 2012 were initially screened for an ARFI examination with a clinical follow-up of at least 5 years. The following events were recorded: liver related death, liver unrelated death, HCC, liver decompensation/ variceal bleeding. A total of 335 patients were included in the final analysis with an ARFI examination of the liver and a follow-up of 60 months. Within the observation interval the number of events with corresponding AUROCs (shown with 95% confidence interval) were: overall death (n=49, 0.76 [0.69 - 0.83]), liver related death (n=25, 0.85 [0.77 - 0.93]), liver unrelated death (n=24, 0.66 [0.55 - 0.77]), HCC (n=15, 0.80 [0.72 - 0.87]), liver related complications/variceal bleeding (n=34, 0.87 [0.82 - 0.93]). In the group of patients with ARFI values suggestive of cirrhosis (equal to or above 1.80 m/s; n=110) higher values (<2.5 m/s vs. >= 2.5 m/s) where associated with a significant decline in liver related survival (p=0.007). ARFI elastography seems to have a good diagnostic accuracy for the prediction of liver related death and decompensation. Further it seems to allow a risk stratification in patients with cirrhosis suspicious elastography values.

Recommendations for broadening eligibility criteria in esophagus cancer clinical trials: the mortality disparity of esophagus cancer as a first or second primary malignancy.

Esophagus cancer as a second primary malignancy (esophagus-2) is increasingly common, but its prognosis is poorly understood. This study aims to examine the overall, non-cancer related and cancer-specific survival of patients diagnosed with esophagus-2 compared to the first primary esophagus cancer (esophagus-1). We included primary esophagus cancer patients diagnosed from 1975 to 2019 in the Surveillance, Epidemiology, and End Results program. Esophagus-2 was identified in patients with a previous diagnosis of non-esophageal primary malignancy. Hazard ratios of overall, esophagus cancer-specific and non-cancer related mortality were estimated among patients with esophagus-2 compared to esophagus-1, adjusting for age, gender, tumor stage and other demographic and clinical characteristics. A total of 74,521 and 14,820 patients were identified as esophagus-1 and esophagus-2 respectively. Esophagus-2 patients suffered lower risk of esophagus cancer-specific mortality in initial 5 years but with similar risk thereafter, independent of tumor characteristics and treatment. In the first 5 years after diagnosis, patients with esophagus-2 had similar risk of overall mortality with those with esophagus-1 but increased risk thereafter. As for non-cancer related mortality, esophagus-2 patients had higher risk all along. Esophagus-2 patients should not be entirely excluded from clinical trial and a 3-year exclusion window is suggested. A conservative approach to manage esophagus-2 solely based on malignancy history is not supported but effort should be put into surveillance, prevention and management of the comorbidities and complications for the first malignancy.

Breast cancer orbital metastases: Clinical, histopathological features and disease related survival in a retrospective case series

PurposeTo analyze the clinical, radiological and histopathological features, and long-term follow-up of patients with orbital metastases originating from a primary breast carcinoma. Main outcomes were: demographic characteristics of the population, clinical ophthalmological presentation, histological features, orbital metastasis latency, disease related survival, mortality rate. DesignA retrospective observational case-series. MethodsThe medical records of 10 female patients affected by orbital metastases originating from a primary breast carcinoma referring at our tertiary referral center from 01/2016 to 12/2023, were reviewed. ResultsThe median age was 63 (71.50 - 57.25) years (time of orbital biopsy). The prevalent histotype of orbital metastases of breast cancer was lobular 9.00 (90 %). The median orbital metastasis latency time in months was 9 months (IQR: 11 - 5) (in one case the orbital metastases were the first manifestation of an unknown primary tumor). The median Disease Related Survival (DRS) during the observation period was 17.50 months and the 24 months survival rate 57.14 %. The overall Mortality Rate in our population was 60 %. ConclusionsThe most frequent histotype of breast cancer orbital metastasis is the lobular one. The primary tumor precedes the onset of orbital metastasis in the majority of cases and tends to present with the classic symptoms of a mass occupying and infiltrating space. Orbital metastases are a sign that the disease is at an advanced stage, the mortality rate is high and DRS low.

Breast cancer patients enrolled in the Swiss mammography screening program "donna" demonstrate prolonged survival.

We compared the survival rates of women with breast cancer (BC) detected within versus outside the mammography screening program (MSP) "donna". We merged data from the MSP with the data from corresponding cancer registries to categorize BC cases as within MSP (screen-detected and interval carcinomas) and outside the MSP. We analyzed the tumor stage distribution, tumor characteristics and the survival of the women. We further estimated hazard ratios using Cox-regressions to account for different characteristics between groups and corrected the survival rates for lead-time bias. We identified 1057 invasive (ICD-10: C50) and in-situ (D05) BC cases within the MSP and 1501 outside the MSP between 2010 and 2019 in the Swiss cantons of St. Gallen and Grisons. BC within the MSP had a higher share of stage I carcinoma (46.5% vs. 33.0%; p < 0.01), a smaller (mean) tumor size (19.1mm vs. 24.9mm, p < 0.01), and fewer recurrences and metastases in the follow-up period (6.7% vs. 15.6%, p < 0.01). The 10-year survival rates were 91.4% for women within and 72.1% for women outside the MSP (p < 0.05). Survival difference persisted but decreased when women within the same tumor stage were compared. Lead-time corrected hazard ratios for the MSP accounted for age, tumor size and Ki-67 proliferation index were 0.550 (95% CI 0.389, 0.778; p < 0.01) for overall survival and 0.469 (95% CI 0.294, 0.749; p < 0.01) for BC related survival. Women participating in the "donna" MSP had a significantly higher overall and BC related survival rate than women outside the program. Detection of BC at an earlier tumor stage only partially explains the observed differences.

Vairimorpha (Nosema) ceranae can promote Serratia development in honeybee gut: an underrated threat for bees?

The genus Serratia harbors opportunistic pathogenic species, among which Serratia marcescens is pathogenic for honeybees although little studied. Recently, virulent strains of S. marcescens colonizing the Varroa destructor mite's mouth were found vectored into the honeybee body, leading to septicemia and death. Serratia also occurs as an opportunistic pathogen in the honeybee's gut with a low absolute abundance. The Serratia population seems controlled by the host immune system, but its presence may represent a hidden threat, ready to arise when honeybees are weakened by biotic and abiotic stressors. To shed light on the Serratia pathogen, this research aims at studying Serratia's development dynamics in the honeybee body and its interactions with the co-occurring fungal pathogen Vairimorpha ceranae. Firstly, the degree of pathogenicity and the ability to permeate the gut epithelial barrier of three Serratia strains, isolated from honeybees and belonging to different species (S. marcescens, Serratia liquefaciens, and Serratia nematodiphila), were assessed by artificial inoculation of newborn honeybees with different Serratia doses (104, 106, and 108 cells/mL). The absolute abundance of Serratia in the gut and in the hemocoel was assessed in qPCR with primers targeting the luxS gene. Moreover, the absolute abundance of Serratia was assessed in the gut of honeybees infected with V. ceranae at different development stages and supplied with beneficial microorganisms and fumagillin. Our results showed that all tested Serratia strains could pass through the gut epithelial barrier and proliferate in the hemocoel, with S. marcescens being the most pathogenic. Moreover, under cage conditions, Serratia better proliferates when a V. ceranae infection is co-occurring, with a positive and significant correlation. Finally, fumagillin and some of the tested beneficial microorganisms could control both Serratia and Vairimorpha development. Our findings suggest a correlation between the two pathogens under laboratory conditions, a co-occurring infection that should be taken into consideration by researches when testing antimicrobial compounds active against V. ceranae, and the related honeybees survival rate. Moreover, our findings suggest a positive control of Serratia by the environmental microorganism Apilactobacillus kunkeei in a in vivo model, confirming the potential of this specie as beneficial bacteria for honeybees.

Drug Survival of IL-17 and IL-23 Inhibitors for Psoriasis: A Systematic Review and Meta-Analysis.

The most recently approved biologics for moderate-to-severe psoriasis are the interleukin (IL)-17 and IL-23 inhibitors. Drug survival is a frequently used outcome to assess drug performance in practice. An overview of the available drug survival studies regarding IL-17 and IL-23 inhibitors is lacking. Therefore, our objective was to assess the drug survival of IL-17 and IL-23 inhibitors for psoriasis. A search of PubMed, Embase, Cochrane Library and Web of Science was conducted (last search 27 December, 2023). Inclusion criteria were (1) cohort study; (2) patients aged ≥ 18 years with plaque psoriasis; and (3) evaluation of drug survival of at least one of the IL-17 and IL-23 inhibitors. Exclusion criteria were: primary focus on patients with psoriatic arthritis, fewer than ten study subjects and another language than English. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Survival probabilities at monthly intervals were extracted from Kaplan-Meier curves using a semi-automated tool. Data were pooled using a non-parametric random-effects model to retrieve distribution-free summary survival curves. Summary drug survival curves were constructed per biologic for different discontinuation reasons: overall, ineffectiveness and adverse events, and split for the effect modifier biologic naivety. Results were analysed separately for registry/electronic health record data and for pharmacy/claims data. A total of 69 studies aggregating drug survival outcomes of 48,704 patients on secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, and tildrakizumab were included. Summary drug survival estimates of registry/electronic health record studies for overall, ineffectiveness and adverse event related drug survival were high (all point estimates ≥ 0.8 at year 1) for included biologics, with highest estimates for guselkumab and risankizumab. All estimates for drug survival were higher in biologic naive than in experienced patients. Estimates of pharmacy/claims databases were substantially lower than estimates from the primary analyses based on registry/electronic health record data. This meta-analysis showed that the investigated IL-17 and IL-23 inhibitors had high drug survival rates, with highest rates for guselkumab and risankizumab drug survival. We showed that effect modifiers such as biologic naivety, and the source of data used (registry/electronic health record data vs pharmacy/claims databases) is relevant when interpreting drug survival studies.

Aquaporin-9 (AQP9) exerts a role in the early phase of the systemic inflammation of a murine model of endotoxic shock

Septic shock is the most severe complication of sepsis, characterized by a systemic inflammatory response following bacterial infection, leading to multiple organ failure and dramatically high mortality. AQP9 is an aquaglyceroporin/peroxiporin mainly expressed in hepatocytes and neutrophils and recently associated with inflammatory and infectious responses. Here, we evaluated whether AQP9 has a role in mouse systemic inflammation during endotoxic shock. Wild-type ( Aqp9+/+; WT) and Aqp9−/− knockout (KO) male mice were submitted to endotoxic shock by i.p. injection of LPS (40 mg/kg) and the related survival times were followed for 72 h. Nitric oxide (NO) and superoxide anion (O2−) production, and the expression of inducible NO‐synthase (iNOS) and cyclooxigenase‐2 (COX‐2) were measured in liver, kidney, aorta, heart and lung of mice. LPS‐treated KO mice survived significantly longer than WT mice, and 25% of the KO mice fully recovered from LPS treatment. The LPS‐injected KO mice had lower inflammatory NO and O2− productions and reduced iNOS and COX‐2 through impaired NF‐κB p65 activation in liver, kidney, aorta, and heart as compared to LPS‐treated WT mice. Treatment of rodent hepatoma FaO cells with the AQP9 blocker HTS13286 prevented the LPS‐induced increase of NO and O2−. AQP9 seems to have a role in the early acute phase of LPS‐induced endotoxic shock likely involving the NF‐κB pathway, potentially through mediating uptake of extracellular H2O2, and PTP-dependent signaling. Support from Italian Government to GC: “Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale 2017” PRIN2017 grant # 2017J92TM5 and “Fondo Integrativo Speciale per la Ricerca 2020”-FISR 2020 CoVAPin grant # FISR2020IP_04051); Support from University of Bari Aldo Moro to GC: grant “Horizon Europe Seeds 2022-2023” NextgenerationEU Programma MUR-Fondo Promozione e Sviluppo-DM 737/2021-Uniba Euroseeds ID #S10. Support from Regione Puglia to PG: “Research for Innovation (REFIN)”, POR Puglia 2014/2020—Asse X—Azione 10.4, UNIBA132-ID #091C54A8. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord

BackgroundMechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function of microglia remains poorly understood.MethodsSpinal cord tissue stiffness was assessed using atomic force microscopy (AFM) in a mouse model of crush injury. Pharmacological depletion of microglia using PLX5622 was used to explore the effect of microglia on mechanical characterization. Conditional knockout of Fascin-1 in microglia (Fascin-1 CKO) alone or in combination with inhibition of myosin activity was performed to delve into relevant mechanisms of microglia regulating mechanical signal. Immunofluorescence staining was performed to evaluate the related protein levels, inflammatory cells, and neuron survival after SCI. The Basso mouse scale score was calculated to assess functional recovery.ResultsSpinal cord tissue significantly softens after SCI. Microglia depletion or Fascin-1 knockout in microglia limits tissue softening and alters mechanical characterization, which leads to increased tissue pathology and impaired functional recovery. Mechanistically, Fascin-1 inhibits myosin activation to promote microglial migration and control mechanical characterization after SCI.ConclusionsWe reveal that Fascin-1 limits myosin activity to regulate mechanical characterization after SCI, and this mechanical signal should be considered in future approaches for the treatment of CNS diseases.

Abstract 4860: Recommendations for enhancing inclusion and management of esophagus cancer clinical trials: Insights on mortality of esophagus cancer as a second primary malignancy

Abstract Background: Esophagus cancer as a second primary malignancy (esophagus-2) is increasingly common, but its prognosis is poorly understood. This study aims to examine the overall, non-cancer related and cancer-specific survival of patients diagnosed with esophagus-2 compared to the first primary esophagus cancer (esophagus-1). Methods: We included primary esophagus cancer patients diagnosed from 1975 to 2020 in the Surveillance, Epidemiology, and End Results program. Esophagus-2 was identified in patients with a previous diagnosis of non-esophageal primary malignancy. Hazard ratios of overall, esophagus cancer-specific and non-cancer related mortality were estimated among patients with esophagus-2 compared to esophagus-1, adjusting for age, sex, tumor stage and other demographic and clinical characteristics. Results: A total of 74521 and 14820 patients were identified as esophagus-1 and esophagus-2. Esophagus-2 patients suffered lower risk of esophagus cancer-specific mortality in initial 5 years but similar risk thereafter, independent of tumor characteristics and treatment. In the first 5 years after diagnosis, patients with esophagus-2 had similar risk of overall mortality with those with esophagus-1 but increased risk thereafter. As for non-cancer related mortality, esophagus-2 patients had higher risk all along. Conclusion: Patients diagnosed with esophagus-2 face a favorable esophagus cancer-specific survival within the early period after diagnosis. However, patients with esophagus-2 are more liable to die of non-cancer cause. A conservative approach to manage esophagus-2 solely based on malignancy history is not supported but effort should be put into surveillance, prevention and management of the comorbidities and complications for the first malignancy. Citation Format: Haiyu Zhou, Jinhang Leng, Hongrui Qiu, Qizhi Huang, Jinqiang Zhang. Recommendations for enhancing inclusion and management of esophagus cancer clinical trials: Insights on mortality of esophagus cancer as a second primary malignancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4860.

Downregulation of INPP4B is Associated with Poor Prognosis in Epithelial Ovarian Carcinoma.

INPP4B is a tyrosine-specific phosphatase in the human body, which plays an important role in the developing process of carcinogenesis. However, The correlation between INPP4B and epithelial ovarian cancer is rarely explored. In this study, the expression of INPP4B in human epithelial ovarian carcinoma and normal ovaries was detected, to explore the correlation between INPP4B expression and clinicopathological risk factors of epithelial ovarian carcinoma and to clarify its significance in the developing process of and prognosis of epithelial ovarian carcinoma. The expression of INPP4B in various tumors was detected by bioinformatics method, and the expression in epithelial ovarian cancer and normal control group was detected by Elisa. The immunohistochemical method was used in this experiment to analyze the expression of INPP4B in specimens of 100 cases of epithelial ovarian carcinoma and 20 cases of normal ovaries. Analysis of clinicopathological risk factors and related survival analysis was carried out on the expression of INPP4B in 100 cases of epithelial ovarian carcinoma. The results showed that the positive expressed INPP4B protein in epithelial ovarian carcinoma was significantly less, compared with that in normal ovaries (P < 0.05). The expression of INPP4B was significantly associated with many clinicopathologic factors, such as tumor differentiation (P < 0.001), FIGO stage (P < 0.001), lymph node metastasis (P < 0.001) and distant metastasis at recurrence (P=0. 009), but not with age, pathologic type of tumor, serum CA125 at recurrence and chemotherapy sensitivity. In epithelial ovarian carcinoma, there is a downregulation of INPP4B expression, which may be related to poor tumor differentiation, late FIGO stage, lymph node metastasis, distant metastasis at recurrence and insensitivity to chemotherapy. Under-expression of INPP4B, lymph node metastasis, FIGO stage, and distant metastasis at recurrence are factors of poor prognostic. The under-expression level of INPP4B may be involved in the progression of epithelial ovarian carcinoma.

Caffeic acid protects against l-methionine induced reduction in neurogenesis and cognitive impairment in a rat model

l-methionine (L-met) is a substantial non-polar amino acid for normal development. L-met is converted to homocysteine that leads to hyperhomocysteinemia and subsequent excessive homocysteine in serum resulting in stimulating oxidative stress and vascular dementia. Several studies have found that hyperhomocysteine causes neuronal cell damage, which leads to memory impairment. Caffeic acid is a substrate in phenolic compound discovered in plant biosynthesis. Caffeic acid contains biological antioxidant and neuroprotective properties. The neuroprotective reaction of caffeic acid can protect against the brain disruption from hydrogen peroxide produced by oxidative stress. It also enhances GSH and superoxide dismutase activities, which protect against neuron cell loss caused by oxidative stress in the hippocampus. Hence, we investigated the protective role of caffeic acid in hippocampal neurogenesis and cognitive impairment induced by L-met in rats. Six groups of Sprague Dawley rats were assigned including control, L-met (1.7 g/kg/day), caffeic acid (20, 40 mg/kg), and L-met + caffeic acid (20, 40 mg/kg) groups. Spatial and recognition memories were subsequently examined using novel object location (NOL) and novel object recognition (NOR) tests. Moreover, the immunofluorescence technique was performed to detect Ki-67/RECA-1, bromodeoxyuridine (BrdU)/NeuN and p21 markers to represent hippocampal neurogenesis changes. The results revealed decreases in vasculature related cell proliferation and neuronal cell survival. By contrast, cell cycle arrest was increased in the L-met group. These results showed the association of the spatial and recognition memory impairments. However, the deterioration can be restored by co-administration with caffeic acid.

Screening of immune related gene and survival prediction of lung adenocarcinoma patients based on LightGBM model

Lung cancer is one of the malignant tumors with the greatest threat to human health, and studies have shown that some genes play an important regulatory role in the occurrence and development of lung cancer. In this paper, a LightGBM ensemble learning method is proposed to construct a prognostic model based on immune relate gene (IRG) profile data and clinical data to predict the prognostic survival rate of lung adenocarcinoma patients. First, this method used the Limma package for differential gene expression, used CoxPH regression analysis to screen the IRG to prognosis, and then used XGBoost algorithm to score the importance of the IRG features. Finally, the LASSO regression analysis was used to select IRG that could be used to construct a prognostic model, and a total of 17 IRG features were obtained that could be used to construct model. LightGBM was trained according to the IRG screened. The K-means algorithm was used to divide the patients into three groups, and the area under curve (AUC) of receiver operating characteristic (ROC) of the model output showed that the accuracy of the model in predicting the survival rates of the three groups of patients was 96%, 98% and 96%, respectively. The experimental results show that the model proposed in this paper can divide patients with lung adenocarcinoma into three groups [5-year survival rate higher than 65% (group 1), lower than 65% but higher than 30% (group 2) and lower than 30% (group 3)] and can accurately predict the 5-year survival rate of lung adenocarcinoma patients.

Modeling the association of bivariate interval-censored data under the additive hazards model

. Bivariate interval-censored failure time data occurs in many fields such as medical followup studies. In this article, we propose an estimation procedure for the association between two related interval-censored survival times when they follow a copula model jointly and the additive hazards model marginally. A simulation study was conducted for assessing the finite sample performance of the presented method and suggests that it works well in practical situations. The proposed method is applied to the AIDS Clinical Trial Group (ACTG) 181 data that motivated this research.

Transoral Laser Microsurgery and Transoral Robotic Surgery in Aging Patients: A State-of-The-Art Review.

In the present study, the findings related to the epidemiology, clinical presentation, and therapeutic outcomes of elderly patients treated with transoral laser microsurgery (TOLM) and transoral robotic surgery (TORS) for supraglottic laryngeal squamous cell carcinoma (LSCC) have been reviewed. A PubMed, Cochrane Library, and Scopus literature search was conducted according to the PRISMA statements. Critical literature analysis was carried out considering the last advancement in TOLS and TORS, and their related surgical, functional, and survival outcomes. The mean age of patients with supraglottic LSCCs has progressively increased in the past decades. The data on postoperative complications in elderly patients with LSCC are heterogeneous and contradictory. The thought of the age-related high risk of complications was based on open supraglottic laryngectomy (SGL), but not on TOLM and TORS findings, which do not support an age-related increase of most postoperative complications. The only complication that could be associated with age is aspiration. The adequate selection of patients undergoing TOLM or TORS, and the pre- to postoperative evaluation of swallowing function can prevent this risk. The OS of elderly patients treated with TOLM or TORS SGL could be lower compared to younger patients. However, the disease-free survival was not influenced by age, highlighting the role of comorbidities and intercurrent diseases in the presumed lower survival. The survival analysis could definitively consider the physiological age rather than the chronological age to investigate the impact of age on survival outcomes. The current literature supports an important place of TOLM and TORS in managing cT1-T3 supraglottic LSCC. The preoperative geriatric, nutritional, and swallowing evaluations are important for ensuring an adequate selection of patients treated with TORS or TOLM SGL.

Nutritional status and body mass index before hematopoietic stem cell transplantation (HSCT) and associated outcomes: a rapid review.

Hematopoietic stem cell transplantation (HSCT) recipients experience several post-HSCT complications affecting nutritional status, body mass index (BMI), and mortality that can potentially be mitigated by nutritional management. This rapid review examines the relationship between pre-HSCT nutritional status and BMI and post-HSCT survival. Articles were identified from PubMed, Scopus, and Embase. Two researchers independently completed the title, abstract, and full-text review. Inclusion criteria included the following: (1) randomized clinical trials or observational studies; (2) human subjects diagnosed with cancer and undergoing HSCT; (3) reported pre-HSCT nutritional status (e.g., diet recall, nutritional survey, dietitian session) or BMI; and (4) reported treatment related mortality and/or survival. The initial search found 3036 articles, 28 were included in full-text review, and 18 met inclusion criteria. Articles had quasi-experimental (n = 2) and observational (n = 16) study designs. Of the studies, n = 5 reported nutritional intake decreased post-HSCT, and n = 2 reported nutrition intervention (i.e., controlled feeding) post-HSCT improved survival. Four studies reported having a BMI classified as underweight improved survival, while n = 5 reported having a BMI classified as overweightorobese improved survival. Current research exploring the relationship between nutritional status and BMI with HSCT survival is mixed. Further research is needed to determine how nutritional status and BMI are associated withsurvival post-HSCT toinform future intervention work.

YAP1/Piezo1 involve in the dynamic changes of lymphatic vessels in UVR-induced photoaging progress to squamous cell carcinoma

BackgroundUV-induced cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers. The constant alterations of the lymphatic-centered immune microenvironment are essential in transforming from photoaging to cSCC. Studying the mechanism will be beneficial for new targets exploration to the early prediction of cSCC.AimsTo investigate the dynamic changes and mechanism of the lymphatic-centered immune microenvironment in transforming from photoaging to cSCC induced by ultraviolet irradiation (UVR).MethodsTIMER2.0 was used to analyze whether YAP1/VEGFC signaling pathway is involved in lymphangiogenesis in head and neck squamous cell carcinoma (HNSCC). Meanwhile, lymphatic-centered immune microenvironments alterations and the related cumulative survival time were also analyzed. With the accumulated UVR, skin photoaging developed and gradually progressed into actinic keratosis and cSCC on SKH-1 hairless mice. The skin lymphatic-centered immune microenvironment was evaluated at the 0th, 8th, 12th, 16-18th, and 20-24th week of UVR. Skin phenotype was assessed using optical coherence tomography (OCT) and skin image. H&E and Masson’s trichrome staining evaluated epidermis and dermis. The structure of lymphatic vessels (LVs), blood vessels, and different types of T cells were evaluated by immunohistochemistry staining. The expression of Piezo1 whose deletion in adult lymphatics led to substantial valve degeneration, VE-cadherin that maintained the permeability of LVs, and YAP1 were evaluated by immunohistochemistry staining as well. Besides, the drainage function of LVs was assessed by Evans Blue assay in vivo.ResultsThe lymphatic function and immune cell infiltration underwent adaptive changes under continuous UVR. TIMER2.0 analysis indicated that VEGFC genes high expressed in HNSCC. YAP1 gene expression was positive correlated with VEGFC in HNSCC. LV density increased in human cSCC. More LVs in HNSCC were beneficial to prolong the survival time. VEGFC gene overexpression was positive correlated to CD8+T cell infiltration. More CD8A+T cells and CD8B+T cell infiltration in HNSCC extended survival time. When YAP1 gene overexpression and high infiltration of endothelial cells took place simultaneously might prolong the survival time of HNSCC patients. And high infiltration of CD8+T cells prolonged the survival time as well. In animal studies, UVR-induced eight weeks (photoaging) and 16–18 weeks (precancerous) were two turning points. The density of LVs in UV-8w was the least. When photoaged skin developed into AK lesions (UV-16-18w), LV slightly exceeded healthy skin and proliferated sharply in cSCC (UV-20-24w). YAP1 expression was almost consistent with LV but rose after the photoaging stage. The drainage of cSCC mice induced by UVR was better than that of photoaged skin and worse than that of health skin. The dynamic alterations of LVs number, Piezo1 expression, and collagen might be reasons for it. The expression of Piezo1 was in the highest point after 8 weeks of UVR, then gradually descended to the platform. The total T cells increased slowly, but the infiltration of CD4+T cells increased, and CD8+T cells decreased after eight weeks of UVR. The CD8+T cells and CD4+T cells increased sharply in UV-16-18w and UV-20-24w groups.ConclusionThe lymphatic-centered immune microenvironment underwent adaptive changes under continuous UVR via regulating YAP1/VEGFC and Piezo1. During the formation of cSCC, there are two turning points, eight weeks (photoaging) and 16–18 weeks (precancerous). YAP1, Piezo1, LVs, and immune cells constantly changed with the skin state induced by UVR. According to these changes the process of cSCC can be identified in advance and intervene timely.

Prognostic value of the left ventricular mass index by magnetic resonance imaging in patients with hypertrophic obstructive cardiomyopathy undergoing septal myectomy

Abstract Research background Traditional risk factors for hypertrophic cardiomyopathy (HCM) have limited ability to predict poor survival outcomes in the medium to long term after surgical septal myectomy (septal myectomy) in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing septal myectomy. Additionally, there is a lack of studies reporting the relationship between left ventricular mass index (LVMI), an index of ventricular remodeling in hypertrophic obstructive cardiomyopathy, and medium to long-term prognostic outcomes after septal myectomy. Research methods: From June 2011 to July 2016, 490 patients with HOCM who completed preoperative cardiac magnetic resonance (CMR) were retrospectively enrolled for mid- to long-term follow-up. The study's primary endpoint included all-cause death. Secondary endpoints included cardiac death and adverse cardiovascular events. Furthermore, CMR measures were applied to study the risk factors for mid- and long-term adverse endpoint events after septal myectomy treatment. Study results: 486 patients with HOCM completed follow-up and were included in the final analysis. Twenty-one patients (4.3%) died during follow-up (median 73.6, maximum 105.6 months), and 66 patients (16.3%) had an adverse cardiovascular event during follow-up. In the Cox proportional risk regression model, the most significant predictor of all-cause mortality after septal myectomy was CMR-LVMI (risk ratio 1.009, 95% confidence interval 1.003-1.015, P=0.018). In receiver operating characteristic (ROC) analysis, LVMI &amp;gt; Cutoffpredicted all-cause death analyzed separately by male and female subgruop(P&amp;lt;0.05). In Cox proportional risk regression models (incorporating age, maximum septal thickness, left atrial diameter, left ventricular end-diastolic dimension, left ventricular ejection fraction, LV outflow tract peak pressure, pulmonary hypertension, LGE positive and LVMI), the most significant predictor after surgical septal resection was LVMI measured by CMR (hazard ratio 1.025, 95% confidence interval 1.009-1.040, P=0.002). From ROC analysis, LVMI &amp;gt;cutoff accurately predicted the occurrence of all-cause mortality analysed separately by male and female (P&amp;lt;0.05). Additionally, K-M survival curve plots suggested that patients with HOCM above the LVMI threshold group had lower all-cause mortality-free survival (Log-rank: P=0.0.025), hear failure related mortality-free survival (Log-rank: P=0.0.014) in the medium to long term after septal myectomy. Conclusions An elevated preoperative left ventricular myocardial mass index suggests adverse ventricular remodeling and is an independent predictor of poor survival outcomes in patients with HOCM in the medium to long term after septal myectomy.ROC analysis of LVMI for all cause deathK-M survival curve devided by LVMI level