Survival Expectancy Research Articles

89 Frailty in Renal Transplantation: Retrospective Cohort Study to Examine the Impact of the New 2019 Kidney Offering Scheme on Older Transplant Recipients

Abstract Background In 2019, a new kidney offering scheme was launched in the United Kingdom, aiming to better match estimated patient survival and graft life expectancy. The impact of the scheme on older patients undergoing kidney transplantation (KT) is unknown. Aim This study aims to compare outcomes of elderly KT recipients before and after the introduction of the 2019 kidney offering scheme. Method A retrospective cohort study of two groups of elderly patients who underwent KT was undertaken. Group 1 included patients transplanted between 01/09/2017 and 31/08/2019 as part of the “2006 allocation scheme”. Group 2 included patients transplanted between 01/09/2019 and 31/08/2021 as part of the “2019 offering scheme”. An elderly patient was defined as any person over 60 years of age at the time of KT. Univariate binary logistic regression analysis was performed to determine odds ratios (OR) and 95% confidence intervals. Results There were 107 elderly deceased donor KT recipients; 62 from Group 1 and 45 from Group 2. The median age at transplantation was 68 years (62-71) and 67 years (64-73), respectively. Univariate analysis showed that level four HLA mismatch (OR 4.667 95%CI 1.640-13.275, p = 0.004) and a requirement for re-intervention (OR 6.496 95%CI 1.306-32.216, p = 0.022) were significantly more likely in the 2019 offering scheme. One year graft survival worsened on introduction of the 2019 offering scheme (85% vs 80%). Conclusions The introduction of the 2019 offering scheme has led to less favourable HLA matches, increased need for reintervention, and a lower one-year graft survival in elderly KT recipients.

A Soft Voting Ensemble Classifier to Improve Survival Rate Predictions of Cardiovascular Heart Failure Patients

Cardiovascular disease is one of the deadliest diseases, claiming around 17 million lives worldwide each year. According to data from the World Health Organization (WHO), more than four out of five deaths from cardiovascular disease are caused by heart attacks and strokes, and one-third of these deaths occur prematurely in people under the age of 70. Machine learning approaches can be used to detect the disease. This research aims to improve the prediction model of cardiovascular heart failure patient survival using C4.5, KNN, Logistic Regression algorithms, and the ensemble learning method of Voting Classifier. Based on the testing results, each model showed a significant increase in accuracy in the 70:30 ratio. Logistic Regression and C4.5 achieved the same accuracy, 89.47%, KNN obtained 91.23%, and Voting Classifier experienced a considerable improvement, reaching 94.74%. In testing with ratios of 90:10, 80:20, and 70:30, KNN demonstrated high accuracy but had significant overfitting, with a difference of 7-9% between training and testing accuracy scores in the 90:10 and 80:20 ratios. On the other hand, Voting Classifier showed stable performance in the 70:30 ratio, with an accuracy difference between training and testing scores below 1%. The conclusion of this research is that the Voting Classifier can assist the performance improvement of algorithms for classifying the survival expectancy of cardiovascular heart failure patients into 'Survived' or 'Deceased', compared to Logistic Regression, KNN, and C4.5.

Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

Novel Scoring Formula to Predict Survival in Patients of Primary Tongue Cancer Belonging to Tobacco Chewing Population.

Worldwide and in India head and neck malignancies are a major contributor to cancer mortality and morbidity. Tonguecancer predominates oral cavity cancers worldwide but in India it comes next to buccal mucosa. OPD patients after completing treatment tend to ask about the prognosis of their disease where they want an objective answer to "How long will I live?" His scoring system is intended to answer this question and guide patients for adjuvant therapy. This study enrolled all patients between 20 and 85years old with a history of tobacco chewing at least for the last 1year before diagnosis. Patients should have primary tongue cancer amenable to surgical resection. For survival calculation, date of diagnosis was taken as reference time. Using Kaplan-Meier survival analysis, clinicopathological factors significantly associated with survival were ascertained. Then using logit regression, a scoring system predicting patient survival in years based on clinicopathological risk factors was formulated and internal validation was done. A total 241 were enrolled and there were 69 cancer-related deaths. T stage, N stage, LVSI, and DOI were found to be significantly associated with cancer-related survival in tongue cancer patients. Another factor affecting survival was defaulting adjuvant radiation therapy. Using these variables, a survival predicting score was developed. On internal validation and regression, the score was found 80% accurate with error limits ± 6months. It is a concise comprehensive score applicable on Indian population with history of tobacco chewing. It will not only help clinicians to tell patients about their survival expectancy but also help to counsel them for adjuvant therapy. However, external validation and if required recalibration incorporating other factors need to be done for this score.

Association of cardiovascular disease with health-related quality of life among older women with early-stage breast cancer undergoing adjuvant endocrine therapy

IntroductionDue to the improved overall survival and life expectancy of older women with breast cancer, cardiovascular disease (CVD) arose as the primary cause of non-cancer-related deaths in this population. Therefore, assessing the health-related quality of life (HRQoL) of breast cancer patients with comorbid CVD is becoming increasingly vital. Our study aimed to evaluate the association between comorbid CVD and HRQoL among older women with early-stage breast cancer who are receiving adjuvant endocrine therapy (AET) in the United States. Materials and MethodsWe conducted a retrospective cohort study using the 2006–2017 Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data. We identified female patients over the age of 65 who were diagnosed with stage I-III hormone receptor-positive breast cancer and treated with AET. HRQoL was assessed by the physical and mental component summary (PCS & MCS) in the health survey. CVD was defined as a history of acute myocardial infarction (AMI), congestive heart failure (CHF), angina, stroke, or other heart-related conditions. We performed multivariate linear regression models while controlling for covariates. ResultsAmong 3,904 older women, a history of CHF [β = −1.97, p = 0.025], stroke [β = −3.00, p < 0.010], or other heart-related condition [β = −1.10, p = 0.046] was significantly associated with lower PCS. However, no significant differences in PCS scores were found between women with a history of AMI or angina and those without these conditions. Having a history of CHF [β = −1.72, p = 0.033] or stroke [β = −1.48, p = 0.038] was significantly associated with lower MCS, whereas a history of angina, AMI, or other heart conditions was not associated with significant differences in MCS. Our study did not observe any significant differences in PCS and MCS between the two types AETs. DiscussionThe study found that older women with early-stage breast cancer who were being treated with AETs had a lower HRQoL if they had a history of CHF or stroke. These comorbidities were identified as strong predictors for decreased HRQoL. The findings highlight the significance of managing cardiovascular diseases in such patients for better HRQoL while they receive AET treatment.

Cardiac Interventions in Patients With Active, Advanced Solid and HematologicMalignancies: JACC: CardioOncology State-of-the-Art Review.

Invasive cardiac interventions are recommended to treat ST-segment elevation myocardial infarction, non-ST-segment elevation acute coronary syndromes, multivessel coronary disease, severe symptomatic aortic stenosis, and cardiomyopathy. These recommendations are based on randomized controlled trials that historically included few individuals with active, advanced malignancies. Advanced malignancies represent a significant competing risk for mortality, and there is limited evidence to inform the risks and benefits of invasive cardiac interventions in affected patients. We review the benefit conferred by invasive cardiac interventions; the periprocedural considerations; the contemporary survival expectations of patients across several types of active, advanced malignancy; and the literature on cardiovascular interventions in these populations. Our objective is to develop a rational framework to guide clinical recommendations on the use of invasive cardiac interventions in patients with active, advanced cancer.

On the Relationship of Natural and Modified Radioresistance with Mast Cell Reactivity

This study was caused by accumulation of the data concerning: 1) relationship between the general reactivity of the body and radioresistance; 2) essential role of mast cells in the formation of radiobiological effects; 3) significant individual features of body radioresistance. Purpose of the study was to identify the relationship of radioresistance indicators with the state of body reactivity, manifested by constitutionally determined features of connective tissue mast cells. Natural radioresistance and modifying effect of hypoxia, hyperoxia and indralin radioprotector were considered. The study was performed on 369 white male rats weighing 215–240 g. To determine the individual characteristics of radioresistance, total and cranio-caudal irradiation of animals was performed. As a hypoxic test, hypoxic gas mixture with 8% oxygen content was used. The criteria of radioresistance were 5- and 30-day survival, weight loss, early transient disability. Index of reactivity of skin mast cells was considered as the diagnostic sign. Relationship features between the level of mast cell reactivity and radioresistance indicators were revealed. It has been shown that the minimum level of natural radioresistance is typical for animals with a high index of mast cell response to hypoxia. The modifying effect of hypoxia during irradiation was manifested in all animals. Also, the highest level of modified radioresistance was observed in rats with average values of the mast cell reactivity index. At the same time, When indralin was used, its radioprotective effect was most pronounced in the group of animals with the maximum reaction of mast cells. The radiomodifying effect of oxygen is mostly expressed in rats with the maximum values of the mast cell reactivity index and is characterized by a decrease in 5-day survival and average life expectancy. The relationship between the characteristics of mast cells and radioresistance can serve as a basis for the development of methods for predicting individual natural and modified radioresistance.

Evaluation of renal markers in systemic autoimmune diseases.

Renal involvement is a common occurrence in subjects with systemic autoimmune diseases. The renal manifestation and its severity depend on the underlying condition and may reversely complicate the clinical course of autoimmune diseases. Renal function markers have been widely used in the assessment of normal functioning of kidneys including glomerular filtration rate and concentrating and diluting capacity of the kidney. An increase or decrease in the values of these markers may indicate kidney dysfunction. In this study, a number of critical renal markers were examined in seropositive autoimmune diseases including systemic lupus erythematosus (SLE), connective tissue disorder (CTD), and rheumatoid arthritis (RA). The data from three cohorts of subjects enrolled in renal markers and autoimmune antibody testing between January 2015 to August 2019 were retrospectively studied. The prevalence of renal markers that were out of the reference range and their average levels in female and male subgroups across SLE, CTD, and RA cohorts were compared and analyzed. The levels of renal markers are significantly affected by the presence of autoantibodies, in particular eGFR, cystatin C, and albumin. Autoantibodies were also more frequent in subjects with severe renal function damage. Close follow-up of both renal markers and autoantibodies may potentially assist in the early diagnosis of kidney diseases and improve the survival and life expectancy of autoimmune patients.

CTLA-4 and PD-1 blocking agents affects longitudinal and radial strain in preclinical models, increases systemic SDF-1, cardiac fibronectin, S-100 calgranulin, galectine-3 and NLRP-3/MyD-88 pathways

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ricerca Corrente, Ministero della Salute. Background Immune checkpoint inhibitors (ICIs) have significantly changed the oncology clinic in recent years, improving survival expectations in cancer patients. ICI therapy have a broad spectrum of side effects from endocrinopathies to cardiovascular diseases. In this study, pro-inflammatory and pro-fibrotic effects of short-term ICIs therapy in preclinical models were analyzed. Methods Firstly, in a human in vitro model, human cardiomyocytes co-cultured with hPBMC were exposed to ICIs (with CTLA-4 or PD-1 blocking agents, at 200 nM) for 72h. After treatment, production of DAMPs and 12 cytokines were analyzed in the supernatant through colorimetric and enzymatic assays. C57/Bl6 mice were treated with CTLA-4 or PD-1 blocking agents (15 mg/kg) for 10 days. Before (T0), after three days (T3) and after treatments (T10), ejection fraction, fractional shortening, radial and longitudinal strain were calculated by using bidimensional echocardiography (Vevo 2100,Fujfilm). Fibrosis, necrosis, hypertrophy and vascular NF-kB expression were analyzed through Immunohistochemistry. Myocardial expression of DAMPs (S100- Calgranulin, Fibronectin and Galectine-3), MyD88, NLRP3 and twelve cytokines have been analyzed. Systemic levels of SDF-1, IL-1β and IL-6 were analyzed before, during and after ICIs therapy. Results Radial and longitudinal strain were decreased after 10 days of ICIs therapy. Histological analysis of NF-kB expression shows that short-term anti-CTLA-4 or anti-PD-1 treatment increased vascular and myocardial inflammation. No myocardial hypertrophy was seen with the exception of the pembrolizumab group. Myocardial fibrosis and expression of galectin-3, pro-collagen 1-α and MMP-9 were increased after treatment with all ICIs. Both anti-CTLA-4 or anti-PD-1 treatments increased the expression of DAMPs, NLRP3 inflammasome and MyD88 and induced both in vitro and in vivo the secretion of IL-1β, TNF-α and IL-6. Systemic levels of SDF-1, IL-1β and IL-6 were increased during and after treatment with ICIs. Conclusions Short therapy with PD-1 and CTLA-4 blocking agents increases vascular expression of NF-kB, systemic SDF-1, IL-1β, IL-6 levels and myocardial NLRP3, MyD88 and DAMPs expression in preclinical models. A pro-inflammatory cytokine storm was induced in myocardial tissues and in cultured cardiac cells after ICIs therapy. The overall picture of the study suggests new putative biomarkers of ICIs-mediated systemic and myocardial damages potentially useful in clinical cardioncology.

Comparative efficacy of zanubrutinib (ZANU) versus rituximab (RTX) in relapsed marginal zone lymphoma (MZL): Matching-adjusted indirect comparison (MAIC).

e19526 Background: ZANU is a Bruton tyrosine kinase inhibitor that has been evaluated for relapsed/refractory MZL in two phase 2, single-arm (MAGNOLIA, n=66, NCT03846427; BGB-3111-AU-003, n=20, NCT02343120). At 28 and 35 months of study follow-up in MAGNOLIA and BGB-3111-AU-003, respectively, median progression-free survival (PFS) and overall survival (OS) were not reached. Here, we conducted an unanchored MAIC to estimate relative treatment effects of ZANU vs RTX, a commonly used treatment for patients with relapsed MZL. Note the comparison was restricted to the relapsed population because RTX refractory patients would not be retreated with RTX. Methods: The MAIC was performed using pooled individual patient-level data from MAGNOLIA and BGB-3111-AU-003. Study level-data of RTX in relapsed patients were used from CHRONOS-3 (Özcan et al., Ann Oncol 2021) which was identified as the most suitable comparator study via a systematic literature review. A logistic propensity score model was used to estimate weights for patients in ZANU trials such that their weighted mean baseline characteristics matched those of CHRONOS-3. The following characteristics were identified as key prognostic factors and included in the base case propensity score model: prior lines of therapy, MZL subtype, relapse after prior therapy, and age. Sensitivity analyses incorporating additional characteristics were not possible owing to a lack of reporting from CHRONOS-3, but the impact of each covariate in the base model was explored via a leave-one-out analysis. Comparisons were conducted for OS, PFS, and objective response rate (ORR) by independent review committee using weighted statistical models, with relative treatment effects presented as hazard ratios (HRs), odds ratios (ORs), and 95% CIs. Results: After applying weights estimated from the base case propensity score model, the effective sample size (ESS) for ZANU was 39. ZANU reduced the risk of progression (HR 0.29; 95% CI 0.13–0.65) and had a higher probability of response (OR 5.09; 95% CI: 1.84–14.08) when compared with RTX (Table). OS was comparable for ZANU and RTX, which is consistent with the survival expectancy for indolent lymphomas. The leave-one-out analysis showed that removing any of the characteristics from the propensity score model yielded comparable results. Conclusions: MAIC results suggest ZANU is associated with improved PFS and ORR compared with RTX in relapsed MZL. [Table: see text]

Evaluating the effect of upper-body morbidity on quality of life following primary breast cancer treatment: a systematic review and meta-analysis.

Improvements in breast cancer management continue to increase survival and life expectancy after treatment. Yet the adverse effects of treatment may persist long term, threatening physical, psychological, and social wellbeing, leading to impaired quality of life (QOL). Upper-body morbidity (UBM) such as pain, lymphoedema, restricted shoulder range of motion (ROM), and impaired function are widely reported after breast cancer treatment, but evidence demonstrating its impact on QOL is inconsistent. Therefore, the aim of the study was to conduct a systematic review and meta-analysis evaluating the effect of UBM on QOL following primary breast cancer treatment. The study was prospectively registered on PROSPERO (CRD42020203445). CINAHL, Embase, Emcare, PsycInfo, PubMed/Medline, and SPORTDiscus databases were searched for studies reporting QOL in individuals with and without UBM following primary breast cancer treatment. Primary analysis determined the standardised mean difference (SMD) in physical, psychological, and social wellbeing scores between UBM + /UBM - groups. Secondary analyses identified differences in QOL scores between groups, according to questionnaire. Fifty-eight studies were included, with 39 conducive to meta-analysis. Types of UBM included pain, lymphoedema, restricted shoulder ROM, impaired upper-body function, and upper-body symptoms. UBM + groups reported poorer physical (SMD = - 0.99; 95%CI = - 1.26, - 0.71; p < 0.00001), psychological (SMD = - 0.43; 95%CI = - 0.60, - 0.27; p < 0.00001), and social wellbeing (SMD = - 0.62; 95%CI = - 0.83, - 0.40; p < 0.00001) than UBM - groups. Secondary analyses according to questionnaire showed that UBM + groups rated their QOL poorer or at equal to, UBM - groups across all domains. Findings demonstrate the significant, negative impact of UBM on QOL, pervading physical, psychological, and social domains. Efforts to assess and minimise the multidimensional impact of UBM are warranted to mitigate impaired QOL after breast cancer.

P128 CTLA–4 AND PD–1 BLOCKING AGENTS AFFECTS LONGITUDINAL AND RADIAL STRAIN IN PRECLINICAL MODELS, INCREASES SYSTEMIC CXCL12, CARDIAC FIBRONECTIN EDA, S–100 CALGRANULIN, GALECTINE–3 AND NLRP–3/MYD–88/CHEMOKINE PATHWAYS

Abstract Background Immune checkpoint inhibitors (ICIs) have significantly changed the oncology clinic in recent years, improving survival expectations in cancer patients. ICI therapy have a broad spectrum of side effects from endocrinopathies to cardiovascular diseases. In this study, pro–inflammatory and pro–fibrotic effects of short–term ICIs therapy in preclinical models were analyzed. Methods Firstly, in a human in vitro model, human cardiomyocytes co–cultured with hPBMC were exposed to ICIs (with CTLA–4 or PD–1 blocking agents, at 200 nM) for 72h. After treatment, production of DAMPs and 12 cytokines were analyzed in the supernatant through colorimetric and enzymatic assays. C57/Bl6 mice were treated with CTLA–4 or PD–1 blocking agents (15 mg/kg) for 10 days. Before (T0), after three days (T3) and after treatments (T10), ejection fraction, fractional shortening, radial and longitudinal strain were calculated by using bidimensional echocardiography (Vevo 2100,Fujfilm). Fibrosis, necrosis, hypertrophy and vascular NF–kB expression were analyzed through Immunohistochemistry. Myocardial expression of DAMPs (S100– Calgranulin, Fibronectin and Galectine–3), MyD88, NLRP3 and twelve cytokines have been analyzed. Systemic levels of SDF–1, IL–1β and IL–6 were analyzed before, during and after ICIs therapy. Results Radial and longitudinal strain were decreased after 10 days of ICIs therapy. Histological analysis of NF–kB expression shows that short–term anti–CTLA–4 or anti–PD–1 treatment increased vascular and myocardial inflammation. No myocardial hypertrophy was seen with the exception of the pembrolizumab group. Myocardial fibrosis and expression of galectin–3, pro–collagen 1–α and MMP–9 were increased after treatment with all ICIs. Both anti–CTLA–4 or anti–PD–1 treatments increased the expression of DAMPs, NLRP3 inflammasome and MyD88 and induced both in vitro and in vivo the secretion of IL–1β, TNF–α and IL–6. Systemic levels of SDF–1, IL–1β and IL–6 were increased during and after treatment with ICIs. Conclusions Short therapy with PD–1 and CTLA–4 blocking agents increases vascular expression of NF–kB, systemic SDF–1, IL–1β, IL–6 levels and myocardial NLRP3, MyD88 and DAMPs expression in preclinical models. A pro–inflammatory cytokine storm was induced in myocardial tissues and in cultured cardiac cells after ICIs therapy.

Revisiting the question of endolymphatic therapy

Lymphotropic therapy was the first step in the development of endolymphatic therapy. Lymphotropic therapy was carried out by creating a subcutaneous depot of a contrast agent or injecting the drug directly into the lymph node. The next step was the introduction of the drug into the lymphatic system by a single puncture of the peripheral lymphatic vessel. After G. V. Bondar put his idea into action by making a special tool, it became possible to do long-term endolymphatic infusion.&#x0D; Lymphatic catheterization is performed in a clean operating room. Catheterization of the thigh lymphatic vessels is the most common technique. A network of superficial lymphatic vessels extends from the medial edge of the sartorius muscle into the subcutaneous fat, reaching the lower superficial inguinal lymph nodes. The deep lymphatic vessels of the thigh are adjacent to the femoral vein. The use of a longitudinal or longitudinal-oblique skin incision is preferable. The benefits of this access are that lymphatic vessels can be catheterized more than once during chemotherapy and wounds heal faster because the skin is cut along the fibers instead of across them.&#x0D; When comparing endolymphatic and intravenous methods of administration of platinum group chemotherapy drugs in combination with fluorouracil or methotrexate in 289 patients with T3N0-1 M0-1 ovarian cancer, the vast majority of whom had serous adenocarcinomas (85.62±2.77 and 84.93±3.17), a significantly higher frequency of complete and partial regressions was registered (59.63±3.87%) with the endolymphatic technique than with intravenous administration (32.03±4.14%).&#x0D; Endolymphatic chemotherapy with fluorouracil 700–800 m g/m daily for 5 days in combination with intravenous administration of doxorubicin 40 mg/m in the treatment of patients with advanced, inoperable gastric cancer (n=33) increased overall efficacy to 39.4%±8.5% when compared to patients (n=32) who received the same drugs intravenously (12.5%±5.84%). The compared groups had significantly different median survival (35 and 19 weeks) and life expectancy (41.3±4.4 and 23.8±3.4 weeks).&#x0D; The endolymphatic administration of cytostatics, which demonstrates less toxicity compared to the intravenous one, has the right to exist and the potential to further develop improved techniques of administration.

Volatile Markers for Cancer in Exhaled Breath-Could They Be the Signature of the Gut Microbiota?

It has been shown that the gut microbiota plays a central role in human health and disease. A wide range of volatile metabolites present in exhaled breath have been linked with gut microbiota and proposed as a non-invasive marker for monitoring pathological conditions. The aim of this study was to examine the possible correlation between volatile organic compounds (VOCs) in exhaled breath and the fecal microbiome by multivariate statistical analysis in gastric cancer patients (n = 16) and healthy controls (n = 33). Shotgun metagenomic sequencing was used to characterize the fecal microbiota. Breath-VOC profiles in the same participants were identified by an untargeted gas chromatography-mass spectrometry (GC-MS) technique. A multivariate statistical approach involving a canonical correlation analysis (CCA) and sparse principal component analysis identified the significant relationship between the breath VOCs and fecal microbiota. This relation was found to differ between gastric cancer patients and healthy controls. In 16 cancer cases, 14 distinct metabolites identified from the breath belonging to hydrocarbons, alcohols, aromatics, ketones, ethers, and organosulfur compounds were highly correlated with 33 fecal bacterial taxa (correlation of 0.891, p-value 0.045), whereas in 33 healthy controls, 7 volatile metabolites belonging to alcohols, aldehydes, esters, phenols, and benzamide derivatives correlated with 17 bacterial taxa (correlation of 0.871, p-value 0.0007). This study suggested that the correlation between fecal microbiota and breath VOCs was effective in identifying exhaled volatile metabolites and the functional effects of microbiome, thus helping to understand cancer-related changes and improving the survival and life expectancy in gastric cancer patients.

Survival Outcomes in Advanced Non-Small Cell Lung Cancer in a Cancer Center in Medellin - Colombia

Introduction: survival outcomes of Non-Small Cell Lung Cancer (NSCLC) reported in the literature may not apply to patients in a real-life scenario in Colombia. This study aims to describe these in a cohort of patients with NSCLC treated at Clínica de Oncología Astorga, in Medellín, Colombia. Methods: this is an observational study with survival analysis. Patients with advanced NSCLC established from January 1/2019 treated at the Institution were included. Medical records were analyzed retrospectively. Kaplan Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). To compare the survival distributions log-rank test was performed. Results: fifty-two patients were included. Median age was 70.1 years (IQR:64.6-77.2). Adenocarcinoma in 57.7%. First-line treatment was chemotherapy (48.1%), immunotherapy (40.4%), and anti-ALK/EGFR tyrosine-kinase inhibitors (TKI) (9.6%). One patient was enrolled in a clinical trial. Median PFS and OS for the entire cohort were 6.0 months (95%CI:4.8-7.1) and 11 months (95%CI:6.7-15.3), respectively. Median OS for performance-status (PS) 1-2 was 14.5 months (95%CI:7.3-21.7) and 4.7 months (95%CI:2.7-6.7) for PS 2-4 (P=0.002). Median PFS for chemotherapy, immunotherapy, and TKI were 3.3 months (95%CI:0.8-5.8), 9.9 months (95%CI:4.6-15.2), and not reached, respectively (P&lt;0.001). Median OS for chemotherapy, immunotherapy, and TKI were 6.0 months (95%CI:1.9-10.0), 9.9 months (95%CI:8.1-11.8), and not reached, respectively (P=0.080). Conclusion: clinical outcomes in Real-World-Setting in advanced NSCLC in Colombia, a Low-Middle-Income-Country, can better inform patients and providers in regards to setting-specific survival expectations. Advanced disease with poor PS and lack of access to state-of-art therapy are challenges yet to be addressed.

Comprehensive analysis reveals TSEN54 as a robust prognosis biomarker and promising immune-related therapeutic target for hepatocellular carcinoma.

Hepatocellular carcinoma represents the most common primary malignancy of all liver cancer types and its prognosis is usually unsatisfactory. TSEN54 encodes a protein constituting a subunit of the tRNA splicing endonuclease heterotetramer. Previous researches concentrated on the contribution of TSEN54 in pontocerebellar hypoplasia, but no studies have yet reported its role in HCC. TIMER, HCCDB, GEPIA, HPA, UALCAN, MEXPRESS, SMART, TargetScan, RNAinter, miRNet, starBase, Kaplan-Meier Plotter, cBioPortal, LinkedOmics, GSEA, TISCH, TISIDB, GeneMANIA, PDB, GSCALite were applied in this research. We identified the upregulation of TSEN54 expression in HCC and related it to multiple clinicopathological features. Hypomethylation of TSEN54 was closely associated with its high expression. HCC sufferers who held high TSEN54 expression typically had shorter survival expectations. Enrichment analysis showed the involvement of TSEN54 in the cell cycle and metabolic processes. Afterward, we observed that TSEN54 expression level had a positive relationship to the infiltration level of multiple immune cells and the expression of several chemokines. We additionally identified that TSEN54 was related to the expression level of several immune checkpoints and TSEN54 was linked to several m6A-related regulators. TSEN54 is a prognostic marker of HCC. TSEN54 could become a prospective candidate for HCC diagnosis and therapy.

Immune-related pulmonary toxicities of checkpoint inhibitors in non-small cell lung cancer: Diagnosis, mechanism, and treatment strategies.

Immune checkpoint inhibitors (ICI) therapy based on programmed cell death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) has changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC) and improved the survival expectancy of patients. However, it also leads to immune-related adverse events (iRAEs), which result in multiple organ damage. Among them, the most common one with the highest mortality in NSCLC patients treated with ICI is checkpoint inhibitor pneumonitis (CIP). The respiratory signs of CIP are highly coincident and overlap with those in primary lung cancer, which causes difficulties in detecting, diagnosing, managing, and treating. In clinical management, patients with serious CIP should receive immunosuppressive treatment and even discontinue immunotherapy, which impairs the clinical benefits of ICIs and potentially results in tumor recrudesce. Therefore, accurate diagnosis, detailedly dissecting the pathogenesis, and developing reasonable treatment strategies for CIP are essential to prolong patient survival and expand the application of ICI. Herein, we first summarized the diagnosis strategies of CIP in NSCLC, including the classical radiology examination and the rising serological test, pathology test, and artificial intelligence aids. Then, we dissected the potential pathogenic mechanisms of CIP, including disordered T cell subsets, the increase of autoantibodies, cross-antigens reactivity, and the potential role of other immune cells. Moreover, we explored therapeutic approaches beyond first-line steroid therapy and future direction based on targeted signaling pathways. Finally, we discussed the current impediments, future trends, and challenges in fighting ICI-related pneumonitis.

Sex-biased expression of selected chromosome x-linked microRNAs with potent regulatory effect on the inflammatory response in children with cystic fibrosis: A preliminary pilot investigation.

Previous studies have reported sex disparity in cystic fibrosis (CF) disease, with females experiencing more pulmonary exacerbations and frequent microbial infections resulting in shorter survival expectancy. This concerns both pubertal and prepubertal females, which is in support to the prominent role of gene dosage rather than the hormonal status. The underlying mechanisms are still poorly understood. The X chromosome codes for a large number of micro-RNAs (miRNAs) that play a crucial role in the post-transcriptional regulation of several genes involved in various biological processes, including inflammation. However, their level of expression in CF males and females has not been sufficiently explored. In this study, we compared in male and female CF patients the expression of selected X-linked miRNAs involved in inflammatory processes. Cytokine and chemokine profiles were also evaluated at both protein and transcript levels and cross-analyzed with the miRNA expression levels. We observed increased expression of miR-223-3p, miR-106a-5p, miR-221-3p and miR-502-5p in CF patients compared to healthy controls. Interestingly, the overexpression of miR-221-3p was found to be significantly higher in CF girls than in CF boys and this correlates positively with IL-1β. Moreover, we found a trend toward lower expression in CF girls than in CF boys of suppressor of cytokine signaling 1 (SOCS1) and the ubiquitin-editing enzyme PDLIM2, two mRNA targets of miR-221-3p that are known to inhibit the NF-κB pathway. Collectively, this clinical study highlights a sex-bias in X-linked miR-221-3p expression in blood cells and its potential contribution to sustaining a higher inflammatory response in CF girls.

Efficiency and effectiveness of intensive multidisciplinary follow-up of patients with stroke/TIA or myocardial infarction compared to usual monitoring: protocol of a pragmatic randomised clinical trial. DiVa (Dijon vascular) study

IntroductionThe ongoing ageing population is associated with an increase in the number of patients suffering a stroke, transient ischaemic attack (TIA) or myocardial infarction (MI). In these patients, implementing secondary...

876 Significant Survival Improvements for Patients with Melanoma Brain Metastases: Can We Reach Cure in the Current Era?

INTRODUCTION: New therapies for melanoma have been associated with increasing survival expectations, as opposed to the dismal outcomes of only a decade ago. METHODS: We reviewed 171 melanoma patients with BM receiving stereotactic radiosurgery (SRS) who were followed with point-of-care data collection between 2012-2020. Clinical, molecular and imaging data were collected, including systemic treatment and radiosurgical parameters. RESULTS: Mean age was 63 ± 15 years, 39% were female and 29% had BRAF-mutated tumors. Median overall survival after radiosurgery was 15.7 months (95% Confidence Interval: 11.4-27.7) and 25 months in patients managed since 2015. Thirty-two patients survived 5 years from their initial SRS. BRAF mutation-targeted therapies showed a survival advantage in comparison to chemotherapy (p = 0.009), but not to immunotherapy (p = 0.09). In a multivariable analysis, both immunotherapy and the number of metastases at 1st SRS were predictors of long-term survival (5 years) from initial SRS (p = 0.023 and p = 0.018, respectively). Five patients (16%) of the long-term survivors required no active treatment for 5 years. CONCLUSIONS: Long-term survival in patients with melanoma BM is achievable in the current era of SRS combined with immunotherapies. For those alive 5 years after first SRS, 16% had been also off systemic or local brain therapy for over 5 years. Given late recurrences of melanoma, caution is warranted, however prolonged survival off active treatment in a subset of our patients raises the potential for cure.