Lower Survival Research Articles

Prospective evaluation of patients with non-cirrhotic portal hypertension: A single centre study.

Non-cirrhotic portal hypertension (NCPH) is a spectrum of liver diseases, including porto-sinusoidal vascular disorder, with portal hypertension (PH) in the absence of cirrhosis. The natural history and diagnostic approach to NCPH are not well understood. We aimed to evaluate disease progression and outcomes in NCPH. Patients with or at risk for NCPH were enrolled in a single centre prospective study; two groups were formed based on the presence of specific features of PH, such as varices, collaterals, portal hypertensive gastropathy or portal hypertensive bleeding. All participants underwent a baseline liver biopsy. Liver stiffness measurement (LSM), and imaging were repeated every 6-12 months. Fifteen patients without specific features of PH (Group I), and 35 patients with specific features (Group II) were enrolled. The median follow-up time was 50 months. Group II had higher hepatic venous pressure gradients, non-invasive measures of PH and a lower platelet count (PLT) when compared to Group I. Rates of survival and decompensation were similar in both groups. Patients with PLT ≤100 K/mcL had lower survival compared to those with PLT >100 K/mcL. Patients with LSM ≥10 kPa had lower survival and survival without decompensation when compared to patients with LSM <10 kPa. Patients irrespective of specific features of PH had similar survival or survival without decompensation. Patients without specific features are at risk for disease progression and should be monitored closely. Thrombocytopenia and increased LSM are associated with severe forms of liver disease, which are strongly associated with outcomes.

Alleviation of Angiotensin II-Induced Vascular Endothelial Cell Injury through Long Non-coding RNA TUG1 Inhibition.

Hypertension damages endothelial cells, causing vascular remodelling. It is caused by Ang II-induced endothelial cell (EC) destruction. The long noncoding RNA (lncRNAs) are emerging regulators of endothelium homeostasis. Injured endothelium expresses lncRNA taurine-upregulated gene 1 (TUG1), which may mediate endothelial cell damage, proliferation, apoptosis, and autophagy and contribute to cardiovascular disease. However, uncertainty surrounds the function of lncRNA TUG1, on arterial endothelium cell damage. This research aimed to investigate the role and mechanism of lncRNA TUG1 in vascular endothelial cell injury. A microarray analysis of lncRNA human gene expression was used to identify differentially expressed lncRNAs in human umbilical vein endothelial cell (HUVEC) cultures. The viability, apoptosis, and migration of Ang II-treated HUVECs were then evaluated. In order to investigate the role of lncRNA TUG1 in hypertension, qRT-PCR, western blotting, and RNA-FISH were used to examine the expression of TUG1 in SHR mice. Ang II-activated HUVECs and SHR rats' abdominal aortas highly express the lncRNA TUG1. LncRNA TUG1 knockdown in HUVECs could increase cell viability, reduce apoptosis, and produce inflammatory factors. In SHR rat abdominal aortas, lncRNA TUG1 knockdown promoted proliferation and inhibited apoptosis. HE spotting showed that lncRNA TUG1 knockdown improved SHR rats' abdominal aorta shape. lncRNA TUG1 knockdown promotes miR-9- 5p, which inhibits CXCR4 following transcription. The lncRNA TUG1/miR-9-5p/CXCR4 axis and vascular cell injury were also examined. MiR-9-5p silencing or CXCR4 overexpression lowered cell survival, apoptosis, and lncRNA TUG1-induced IL-6 and NO expression. lncRNA TUG1 suppression could reduce Ang II-induced endothelial cell damage by regulating and targeting miR-9-5p to limit CXCR4 expression and open new vascular disease research pathways.

Fenestrated/Branched Endovascular Aortic Repair Patients With Peripheral Artery Disease Have Significantly Lower Long-Term Survival and Higher Incidence of Postoperative Mesenteric Ischemia

Fenestrated/Branched Endovascular Aortic Repair Patients With Peripheral Artery Disease Have Significantly Lower Long-Term Survival and Higher Incidence of Postoperative Mesenteric Ischemia

Alternatives to the Gold Standard: A Systematic Review of Profunda Artery Perforator and Lumbar Artery Perforator Flaps for Breast Reconstruction.

Breast reconstruction with the deep inferior epigastric perforator (DIEP) flap is the current gold-standard autologous option. The profunda artery perforator (PAP) and lumbar artery perforator (LAP) flaps have more recently been described as alternatives for patients who are not candidates for a DIEP flap. The aim of this study was to review the survival and complication rates of PAP and LAP flaps, using the DIEP flap as a benchmark. A literature search was conducted using PubMed, MEDLINE, Embase, BIOSIS, Web of Science, and Cochrane databases. Papers were screened by title and abstract, and full texts reviewed by three independent blinded reviewers. Quality was assessed using MINORS criteria. Sixty-three studies were included, for a total of 745 PAP, 62 stacked PAP, 187 LAP, and 23,748 DIEP flap breast reconstructions. The PAP (98.3%) had comparable success rate to DIEP (98.4%), and the stacked PAP (88.7%) and LAP (92.5%) success rate was significantly lower (P < 0.0001). The PAP and LAP groups both had a low incidence of fat necrosis. However, the revision rate for the LAP group was 16.1% whereas the PAP group was 3.3%. Donor site wound dehiscence rate was 2.9 in the LAP group and 9.1% in the PAP group. Profunda artery perforator and DIEP flaps demonstrate very high rates of overall survival. The LAP flap has a lower survival rate. This review highlights the survival and complication rates of these alternative flaps, which may help clinicians in guiding autologous reconstruction technique when a DIEP flap is unavailable.

Akirin2 enhances antibacterial ability via interacting with 14-3-3ζ in V. splendidus-challenged Apostichopus japonicus

Akirin2 is pivotal for regulating host immunological responses in vertebrates, including antibacterial immunity and inflammation. However, the functional significance of Akirin2 in invertebrates remains largely unexplored. In this study, we cloned the complete cDNA sequence of Akirin2 from A. japonicus (AjAkirin2) and elucidated its immunological mechanism upon pathogen infection. The whole AjAkirin2 cDNA sequence spanned 1014 bp, which comprised a 630 bp open reading frame encoding 209 amino acids, a 230 bp 5'-untranslated region (UTR), and a 154 bp 3'-UTR. Spatial expression analysis displayed constitutive expression of AjAkirin2 in all examined tissues. Both mRNA and protein expression abundance of the AjAkirin2 showed considerably high in coelomocytes of sea cucumbers challenged with Vibrio splendidus or stimulated with lipopolysaccharide. In addition, we found that sea cucumbers with 107 CFU/mL V. splendidus infection had a lower survival rate upon AjAkirin2 knockdown. Mechanistically, the result of GST-pull down and co-IP assays indicated that AjAkirin2 directly interacted with Aj14-3-3ζ. Moreover, we also detected that AjAkirin2 positively regulated Aj14-3-3ζ expression in sea cucumber coelomocytes. Furthermore, the knockdown of AjAkirin2 or Aj14-3-3ζ resulted in increasing intracellular bacteria load and suppressed the expression of key genes of the NF-κB signaling pathway (p65 and p105) and inflammatory cytokines including IL-17, VEGF, and MMP-1. In summary, these results confirmed the critical role of AjAkirin2 in mediating innate immune responses against V. splendidus infection via interaction with Aj14-3-3ζ and thereby exerting antibacterial function.

MiRNAs in radiotherapy resistance of cancer; a comprehensive review.

While intensity-modulated radiation therapy-based comprehensive therapy increases outcomes, cancer patients still have a low five-year survival rate and a high recurrence rate. The primary factor contributing to cancer patients' poor prognoses is radiation resistance. A class of endogenous non-coding RNAs, known as microRNAs (miRNAs), controls various biological processes in eukaryotes. These miRNAs influence tumor cell growth, death, migration, invasion, and metastasis, which controls how human carcinoma develops and spreads. The correlation between the unbalanced expression of miRNAs and the prognosis and sensitivity to radiation therapy is well-established. MiRNAs have a significant impact on the regulation of DNA repair, the epithelial-to-mesenchymal transition (EMT), and stemness in the tumor radiation response. But because radio resistance is a complicated phenomena, further research is required to fully comprehend these mechanisms. Radiation response rates vary depending on the modality used, which includes the method of delivery, radiation dosage, tumor stage and grade, confounding medical co-morbidities, and intrinsic tumor microenvironment. Here, we summarize the possible mechanisms through which miRNAs contribute to human tumors' resistance to radiation.

Factors Associated with Primary Liver Cancer Survival in a Southern Italian Setting in a Changing Epidemiological Scenario

A retrospective observational study utilising cancer incidence data from a population-based registry investigated determinants affecting primary liver cancer survival in a southern Italian region with high hepatitis viral infection rates and obesity prevalence. Among 2687 patients diagnosed between 2006 and 2019 (65.3% male), a flexible hazard-based regression model revealed factors influencing 5-year survival rates. High deprivation levels [HR = 1.41 (95%CI = 1.15–1.76); p &lt; 0.001], poor access to care [HR = 1.99 (95%IC = 1.70–2.35); p &lt; 0.0001], age between 65 and 75 [HR = 1.48 (95%IC = 1.09–2.01); p &lt; 0.05] or &gt;75 [HR = 2.21 (95%CI = 1.62–3.01); p &lt; 0.0001] and residing in non-urban areas [HR = 1.35 (95%CI = 1.08–1.69); p &lt; 0.01] were associated with poorer survival estimates. While deprivation appeared to be a risk factor for primary liver cancer patients residing within the urban area, the geographic distance from specialised treatment centres emerged as a potential determinant of lower survival estimates for residents in the non-urban areas. After balancing the groups of easy and poor access to care using a propensity score approach, poor access to care and a lower socioeconomic status resulted in potentially having a negative impact on primary liver cancer survival, particularly among urban residents. We emphasise the need to interoperate cancer registries with other data sources and to deploy innovative digital solutions to improve cancer prevention.

Winter survival in red clover: experimental evidence for interactions among stresses

BackgroundThere is a lack of knowledge on the combined effects of different stresses on plants, in particular different stresses that occur during winter in temperate climates. Perennial herbaceous plants in temperate regions are exposed to many different stresses during winter, but except for the fact that cold temperatures induce resistance to a number of them, very little is known about their interaction effects. Knowledge about stress interactions is needed in order to predict effects of climate change on both agricultural production and natural ecosystems, and to develop adaptation strategies, e.g., through plant breeding. Here, we conducted a series of experiments under controlled conditions to study the interactions between cold (low positive temperature), clover rot infection (caused by Sclerotinia trifoliorum) and freezing, in red clover (Trifolium pratense) accessions. We also compared our results with winter survival in field experiments and studied associations between stress and shoot growth.ResultsExposure to low positive temperatures (cold acclimation) induced resistance to clover rot. There was a clear negative interaction effect between freezing stress and clover rot infection, resulting in up to 37% lower survival rate compared to what would have been expected from the additive effect of freezing and infection alone. Freezing tolerance could continue to improve during incubation under artificial snow cover at 3 °C in spite of darkness, and we observed compensatory shoot growth following freezing after prolonged incubation. At the accession level, resistance to clover rot was negatively correlated with growth in the field during the previous year at a Norwegian location. It was also negatively correlated with the shoot regrowth of control plants after incubation. Clover rot resistance tests under controlled conditions showed limited correlation with clover rot resistance observed in the field, suggesting that they may reveal variation in more specific resistance mechanisms.ConclusionsWe here demonstrate, for the first time, a strong negative interaction between freezing and infection with a winter pathogen. We also characterize the effects of cold acclimation and incubation in darkness at different temperatures on winter stress tolerance, and present data that support the notion that annual cycles of growth and stress resistance are associated at the genetic level.

Venom Immunotherapy Does Not Affect Survival of Patients with Malignant Tumor in Poland

Background: Allergen immunotherapy (AIT) is a well-established and efficient method of causative treatment for allergic rhinitis, asthma and insect venom allergy. Traditionally, a recent history of malignant neoplasm is regarded as a contraindication to AIT due to concerns that AIT might stimulate tumor growth. However, there are no data confirming that the silencing of the Th2 response affects prognosis in cancer. Objectives: The aim of this study was to investigate frequency of malignant tumors in patients undergoing AIT and the association between AIT and cancer-related mortality. Patients and Methods: A group of 2577 patients with insect venom allergy undergoing AIT in 10 Polish allergology centers was screened in the Polish National Cancer Registry. Data on cancer type, diagnosis time and patients’ survival were collected and compared with the general population. Results: In the study group, 86 cases of malignancies were found in 85 patients (3.3% of the group). The most common were breast (19 cases), lung (9 cases), skin (8 cases), colon and prostate cancers (5 cases each). There were 21 cases diagnosed before AIT, 38 during and 27 after completing AIT. Laplace’s crude incidence rate was 159.5/100,000/year (general population rate: 260/100,000/year). During follow-up, 13 deaths related to cancer were revealed (15% of patients with cancer). Laplace’s cancer mortality rate was 37.3/100,000/year (general population rate: 136.8/100,000/year). Conclusions: Malignancy was found in patients undergoing immunotherapy less often than in the general population. Patients with cancer diagnosed during or after AIT did not show a lower survival rate, which suggests that AIT does not affect the prognosis.

The impact of the OPTN policy change on patients with a durable left ventricular assist device and chronic kidney disease: Analysis of the UNOS database.

The Organ Procurement and Transplantation Network (OPTN) implemented modifications in 2018 to the adult heart transplant allocation system to better stratify the most medically urgent transplant candidates. We evaluated the impact of these changes on patients supported by a durable left ventricular assist device (LVAD) with chronic kidney disease (CKD). To evaluate the impact of the OPTN policy change on patients supported by durable left ventricular assist devices (LVAD) with chronic kidney disease (CKD). We performed an analysis of patients from the United Network of Organ Sharing Database supported by durable LVAD listed for a heart transplant (HT) between October 17, 2016 and September 30, 2021. Patients were divided into two groups: pre- and postpolicy, depending on whether they were listed on or prior to October 17, 2018. Patients who were on dialysis prior to surgery or discharge were excluded from the analysis. Patients with simultaneous heart and kidney transplants were excluded. Patients who were listed for transplant prepolicy change but transplanted postpolicy change were excluded. This cohort was then subdivided into degrees of CKD based on estimated glomerular filtration rate (eGFR), which resulted in 678 patients (23.7%) in Stage 1 (GFR ≥89.499) (Prepolicy: 345, Postpolicy: 333), 1233 (43.1%) in Stage 2 (89.499 > GFR ≥ 59.499) (Prepolicy: 618, Postpolicy: 615), 613 (21.4%) in Stage 3a (59.499 > GFR ≥ 44.499) (Prepolicy: 291, Postpolicy: 322), 294 (10.3%) in Stage 3b (44.499 > GFR ≥ 29.499) (Prepolicy: 143, Postpolicy: 151), 36 (1.3%) in Stage 4 (29.499 > GFR ≥ 15) (Prepolicy: 21, Postpolicy: 15), and 9 (0.3%) in Stage 5 (15 > GFR) (Prepolicy: 4, Postpolicy: 5). The primary outcome was 1-year and 2-year post-HT survival. There were 2863 patients who met the study criteria (1422 prepolicy, 1441 postpolicy). Overall survival, regardless of CKD stage, was lower following the policy change (p < 0.01). There was a similar risk of primary graft failure (PGF) in the pre- and postpolicy period (1.8% vs. 1.2%, p = 0.26). 1-year overall survival was 93% (91, 94) and 89% (87, 91) in the pre- and postpolicy periods, respectively. 2-year overall survival was 89% (88, 91) and 85% (82, 87) in the pre- and postpolicy periods, respectively. For CKD Stages 1, 2, 3a, 3b, 4, and 5, 1 -year survival was 93% (91, 95), 92% (90,93), 89% (86, 91), 89% (86, 93), 80% (68, 94), and 100% (100, 100), respectively. For CKD Stages 1, 2, 3a, 3b, 4, and 5, 2-year survival was 91% (88, 93), 88% (86, 90), 84% (81, 88), 84% (80, 89), 73% (59, 90), and 100% (100, 100), respectively. Patients with CKD 1 and 2 had better survival compared to those with CKD 3 (p < 0.01) and CKD 4 and 5 (p = 0.03) in the pre- and postpolicy periods. Patients with CKD 3 did not have a survival advantage over those with CKD 4 and 5 (p = 0.25). On cox regression analysis, advancing degrees of CKD were associated with an increased risk of mortality. Patients with LVAD support had decreased overall survival after the OPTN policy change. Patients with more advanced CKD had lower survival than patients without advanced CKD, though they were not impacted by the OPTN policy change.

Lower mortality following surgical management for distal femur fractures: A cohort study

Introduction Geriatric distal femur fractures pose a difficult problem for orthopaedic surgeons with an aging population. The present study aims to report mortality rates following distal femur fractures from a geriatric population over 60 years old, with a primary emphasis on determining whether surgical management differentially affects mortality rate as compared to conservative management. Methods Patients over 60 years old with distal femur fractures for patients admitted into the New Territories West Cluster from 2012 to 2020 were identified in this retrospective cohort study. Patient demographics, comorbidities, and management characteristics were examined and analyzed. Kaplan-Meier survival analysis was done to delineate differences in mortality rates between surgical and conservative management. Further analysis was done for patients &gt;80 years old using Kaplan-Meier survival analysis to delineate whether surgical intervention still affects the survival in this narrowed geriatric population. Subsequent multivariate cox regression was done to determine variables with significant effect on mortality in this age group. Results Of 168 patients, the 1-year mortality rate is 21.5%. The cumulative median survival time of the surgical group (5.98 years) versus the conservative group (2.32 years). Survival analysis on patients &gt;80 years old revealed age, management type, ambulatory status, place of residence, dementia, chronic pulmonary disease, or chronic kidney disease had statistically different median time of survival. In these patients, a reduction in death hazard by 47% (CI 0.28–1.01, p = 0.05) was seen in those with surgical management. On the other hand, patients with chronic obstructive pulmonary disease (COPD) and moderate chronic kidney disease (CKD) show an increased death hazard by 2.61 times (CI 1.23–5.53, p = 0.01) and 7.17 times (CI 1.47–34.86, p = 0.02), respectively. Conclusion Compared to conservative management, surgical management resulted in higher cumulative survival in geriatric patients with distal femur fractures. Unfavourable factors that may contribute to a lower cumulative survival includes history of COPD and CKD.

Juvenile survival increases with dispersal distance and varies across years: 15 years of evidence in a prairie perennial.

Juvenile survival is critical to population persistence and evolutionary change. However, the survival of juvenile plants from emergence to reproductive maturity is rarely quantified. This is especially true for long-lived perennials with extended pre-reproductive periods. Furthermore, studies rarely have the replication necessary to account for variation among populations and cohorts. We estimated juvenile survival and its relationship to population size, density of conspecifics, distance to the maternal plant, age, year, and cohort for Echinacea angustifolia, a long-lived herbaceous perennial. In 14 remnant prairie populations over seven sampling years, 2007-2013, we identified 886 seedlings. We then monitored these individuals annually until 2021 (8-15 years). Overall, juvenile mortality was very high; for almost all cohorts fewer than 10% of seedlings survived to age 8 or to year 2021. Only two of the seedlings reached reproductive maturity within the study period. Juvenile survival increased with distance from the maternal plant and varied more among the study years than it did by age or cohort. Juvenile survival did not vary with population size or local density of conspecific neighbors. Our results suggest that low juvenile survival could contribute to projected population declines.

Effect of Cigarette Smoking on Clinical and Molecular Endpoints in COPD Patients

Cigarette smoking is a primary contributor to mortality risks and is associated with various diseases. Among these, COPD represents a significant contributor to global mortality and disability. The objective of this study is to investigate the effect of smoking on a selected battery of variables, with an emphasis on DNA damage. A total of 87 elderly patients diagnosed with COPD, divided into three groups based on their smoking history (current, former, never-smokers), were evaluated using a cross-sectional approach. Clinical features including mortality and inflammatory/oxidative parameters (Lymphocytes/Monocytes, Neutrophils/Lymphocytes, Platelets/Lymphocytes ratio), SII, MDA, 8-Oxo-dG, and IL6 (ELISA assay), as well as DNA damage (comet assay), were investigated. Virus infection, i.e., influenza A virus subtype H1N1, JC polyomavirus (JCPyV), BK polyomavirus (BKPyV), and Torquetenovirus (TTV), was also tested. Current smokers exhibit higher levels of comorbidity (CIRS; p &lt; 0.001), Platelets/Lymphocytes ratio (p &lt; 0.001), systemic immune inflammation (p &lt; 0.05), and DNA damage (p &lt; 0.001). Former smokers also showed higher values for parameters associated with oxidative damage and showed a much lower probability of surviving over 5 years compared to never- and current smokers (p &lt; 0.0017). This study showed a clear interaction between events which are relevant to the oxidative pathway and cigarette smoking. A category of particular interest is represented by former smokers, especially for lower survival, possibly due to the presence of more health problems. Our findings raise also the attention to other parameters which are significantly affected by smoking and are useful to monitor COPD patients starting a program of pulmonary rehabilitation (DNA damage, inflammation parameters, and selected viral infections).

An Annual Symposium on Disparities in Milwaukee, WI, with a 2023 Focus on Older Adults with Cancer.

Cancer-related inequities are prevalent in Wisconsin, with lower survival rates for breast, colorectal, and lung cancer patients from marginalized communities. This manuscript describes the ongoing efforts at the Medical College of Wisconsin and potential pathways of community engagement to promote education and awareness in reducing inequities in cancer care. While some cancer inequities are related to aggressive disease biology, health-related social risks may be addressed through community-academic partnerships via an open dialogue between the community members and academic faculty. To develop potential pathways of community-academic partnerships, an annual Cancer Disparities Symposium concept evolved as a pragmatic and sustainable model in an interactive learning environment. In this manuscript, we describe the programmatic development and execution of the annual Cancer Disparities Symposium, followed by highlights from this year's meeting focused on geriatric oncology as discussed by the speakers.

α5-nAChR/ADAM10 signaling mediates nicotine-related cutaneous melanoma progression via STAT3 activation.

Skin cutaneous melanoma (SKCM) is the skin malignancy with the highest mortality rate, and its morbidity rate is on the rise worldwide. Smoking is an independent marker of poor prognosis in melanoma. The α5-nicotinic acetylcholine receptor (α5-nAChR), one of the receptors for nicotine, is involved in the proliferation, migration and invasion of SKCM cells. Nicotine has been reported to promote the expression of a disintegrin and metalloproteinase 10 (ADAM10), which is the key gene involved in melanoma progression. Here, we explored the link between α5-nAChR and ADAM10 in nicotine-associated cutaneous melanoma. α5-nAChR expression was correlated with ADAM10 expression and lower survival in SKCM. α5-nAChR mediated nicotine-induced ADAM10 expression via STAT3. The α5-nAChR/ADAM10 signaling axis was involved in the stemness and migration of SKCM cells. Furthermore, α5-nAChR expression was associated with ADAM10 expression, EMT marker expression and stemness marker expression in nicotine-related mice homograft tissues. These results suggest the role of the α5-nAChR/ADAM10 signaling pathway in nicotine-induced melanoma progression.

Emergency department involvement in the diagnosis of cancer among older adults: a SEER-Medicare study.

Internationally, 20-50% of cancer is diagnosed through emergency presentation, which is associated with lower survival, poor patient experience, and socioeconomic disparities, but population-based evidence about emergency diagnosis in the U.S. is limited. We estimated Emergency Department (ED) involvement in the diagnosis of cancer in a nationally representative population of older US adults, and associations with sociodemographic, clinical, and tumor characteristics. We analyzed SEER-Medicare data for Medicare beneficiaries (≥66 years old) diagnosed with female breast, colorectal, lung and prostate cancers (2008-2017), defining their earliest cancer-related claim as their index date, and patients who visited the ED 0-30 days before their index date to have "ED involvement" in their diagnosis, with stratification as 0-7 or 8-30 days. We estimated covariate-adjusted associations of patient age, sex, race/ethnicity, marital status, comorbidity score, tumor stage, diagnosis year, rurality, and census tract poverty with ED involvement using modified Poisson regression. Among 614,748 patients, 23% had ED involvement with 18% visiting the ED in the 0-7 days before their index date. This varied greatly by tumor site: breast 8%, colorectal 39%, lung 40%, prostate 7%. In adjusted models, older age, female sex, non-Hispanic Black and Native Hawaiian/Other Pacific Islander race, being unmarried, recent diagnosis year, later-stage disease, comorbidities, and poverty were associated with ED involvement. The ED may be involved in the initial identification of cancer for 1 in 5 patients. Earlier, system-level identification of cancer in non-ED settings should be prioritized, especially among underserved populations.

Long-term outcomes of ventricular tachycardia ablation in patients with ischemic and non-ischemic cardiomyopathy: a propensity-score matched analysis

Abstract Background Catheter ablation (CA) has been shown to be effective in the treatment of ventricular tachycardia (VT). Although some observational data suggest that patients with non-ischemic cardiomyopathy (NCIM) have less favorable clinical outcomes when compared to those with an ischemic etiology (ICM), direct comparisons are scarcely reported. We aimed to compare the outcomes of VT ablation in a propensity score-matched population of ICM or NICM patients. Methods Single-center observational registry including 246 consecutive patients with ischemic (ICM, N=166) and non-ischemic cardiomyopathy (NICM, N=80) who underwent drug-resistant VT ablation from 2012 to 2023. A propensity score (PS) was used to match patients in a 1:1 fashion according to the following variables: age, sex, left ventricular ejection fraction (LVEF), NYHA class, electrical storm (ES) at presentation, and previous endocardial VT ablation. The outcomes of interest were VT-free survival and all-cause mortality. Results The PS yielded two groups of 71 patients each (mean age 63±10 years, 92.3% male, mean LVEF 35±10%, 35.9% with ES at presentation, and 23.2% with previous ablation), well matched for baseline characteristics. Those with NICM were more likely to undergo epicardial or combined VT ablation (43.7% vs. 9.9%, P&amp;lt;0.001). The procedural complication rate was low (4.9%, N=7) and similar between groups (P&amp;gt;0.05). During a median follow-up of 27 (IQR 15–45) months, patients with NICM had a significantly lower VT-free survival (53.5% vs. 69.0%, log-rank P=0.037), although there were no differences regarding all-cause mortality (22.5% vs. 16.9%, log-rank P=0.245) – Figure. Multivariate analysis identified NICM (HR 2.34 [95% CI 1.32–4.14], P=0.004), NYHA class III/ IV (HR 2.11 [95% CI 1.11–4.04], P=0.024), and chronic kidney disease (HR 2.23 [95% CI 1.25–3.96], P=0.006), as independent predictors of VT recurrence. Non-inducibility of any VT immediately after ablation was associated with significantly lower rates of VT recurrence (22.8%/ year vs. 42.4%/ year, log-rank P=0.03). Conclusion NCIM patients are at increased risk of VT recurrence after ablation, although long-term mortality was similar to ICM in a propensity-matched cohort. Non-inducibility of any VT after CA is associated with better outcomes.Figure

Post-ablation atrial arrhythmogenic channels predict atrial fibrillation recurrence - iatrogenic substrate revisited

Abstract Background Fibrosis is a hallmark of atrial fibrillation (AF) arrhythmogenic substrate, and the extent of atrial fibrosis, as determined by late gadolinium enhancement (LGE)-MRI, predicts AF recurrence after ablation. However, ablation fundamentally alters the individual composition of fibrotic tissue, and inhomogeneous ablation lesions may constitute an arrhythmogenic substrate themselves. From ventricular arrhythmias (VA) we know that it is not the extent of scar tissue that determines arrhythmogenicity, but rather the scar-pervading channels of surviving tissue with residual conduction. Purpose To investigate post-ablation arrhythmogenic substrate in terms of atrial scar channels using LGE-MRI. Methods Patients with PVI-only AF ablation were included. All patients received a systematic 12-months follow-up and an LGE-MRI 3 months post-ablation. Scar channels were defined as corridors of borderzone tissue (residual conduction), protected by dense scar. Channels were automatically identified using a software algorithm that has been extensively validated in the ventricle and was now adapted for the atrium. To differentiate healthy tissue, borderzone and dense scar, LGE was quantified based on the signal intensity ratios of each voxel relative to the blood pool. Signal intensity ratio thresholds defining dense scar and borderzone, were then empirically tested to enhance the predictive value of the identified channels. The algorithm was then applied to an independent validation cohort using the empirically determined thresholds. Results 150 patients were included. 10 different combinations of signal intensity ratio thresholds defining borderzone tissue and dense scar were empirically tested regarding the prediction of potentially arrhythmogenic channels in 50 patients (derivation cohort). For each of the threshold combinations, the number of predicted channels was linked to 12-months arrhythmia-free survival using logistic regression. The computed channels best predicted 12-months arrhythmia recurrence, when based on signal intensity ratios of 1.1-1.32 (borderzone) and &amp;gt;1.32 (dense scar). This threshold combination was then validated in an independent cohort of 100 patients. Patients with scar channels had significantly lower arrhythmia-free survival than those without (55% vs. 88%, p=0.016, Fig. 1). The number of detected scar channels was predictive of 12-months arrythmia recurrence (OR 4.9; p=0.012) – independent of other factors like LA diameter, AF type or the extent of native atrial fibrosis (pre-ablation LGE-MRI). Of note, the number of gaps in the PV-encircling lesions was not predictive of AF recurrence. Conclusions LGE-MRI-detected post-ablation scar channels predict recurrent AF after PVI and may be a surrogate of iatrogenic substrate. In light of large-area ablations with PFA and other single-shot devices fueling a trend towards more and more extensive lesions, the concept of iatrogenic arrhythmogenic substrate may have to be reconsidered.

NPTX1 Mediates the Facilitating Effects of Hypoxia-Stimulated Human Adipocytes on Adipose-Derived Stem Cell Activation and Autologous Adipose Graft Survival Rate.

Autologous adipose tissue is an ideal material for soft tissue filling and transplantation; however, high volumes of fat absorption over time lead to a relatively low overall survival percentage. The survival and differentiation of adipose-derived stem cells (ADSCs) in the transplanted microenvironment might improve adipose graft survival. Adipocytes have been reported to affect ADSC activation. However, its underlying mechanisms remain unclear. Human ADSCs were incubated in a culture medium supplemented with hypoxic or normoxic conditioned culture medium (CM) derived from human adipocytes. Neuronal Pentraxin 1 (NPTX1) was overexpressed or knocked down in human adipocytes using an overexpression vector (NPTX1 OE) or small interfering RNA (siRNA) transfection, respectively. ADSC differentiation and paracrine secretion were assessed. Nude mice were implanted with human adipocytesand ADSCs. The adipose tissue was subsequently evaluated by histological analysis. CM from hypoxic-stimulated human adipocytes significantly facilitated the differentiation ability and paracrine levels of ADSCs. NPTX1 was significantly up-regulated in human adipocytes exposed to hypoxic conditions. In vitro, CM derived from hypoxia-stimulated human adipocytes or NPTX1-overexpressing human adipocytes exposed to normoxia promoted ADSC differentiation and paracrine; after silencing NPTX1, the facilitating effects of hypoxia-treated human adipocytes on ADSC activation were eliminated. Similarly, in vivo, the NPTX1 OE + normoxia-CM group saw improved histological morphology and fat integrity, less fibrosis and inflammation, and increased vessel numbers compared with the OE NC + normoxia-CM group; the adipocyte grafts of the si-NC + hypoxia-CM group yielded the most improved histological morphology, fat integrity, and the most vessel numbers. However, these enhancements of ADSC activation and adipose graft survival were partially abolished by NPTX1 knockdown in human adipocytes. NPTX1 might mediate the facilitating effects of hypoxia-stimulated human adipocytes on ADSC activation, thereby improving adipose tissue survival rate after autologous fat transplantation and the effectiveness of autologous fat transplantation through promoting ADSC activation. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

#2900 Appetite changes as a predictor of mortality among end-stage renal disease patients (ESRD) on maintenance hemodialysis: one year survival analysis

Abstract Background and Aims End-stage renal disease (ESRD) has become a major health problem worldwide. Appetite loss is a dominant feature of the disease which plays an important role in protein energy wasting and malnutrition, with subsequent higher rates of mortality. The study aimed to examine appetite changes among patients with ESRD on maintenance hemodialysis and its association with one-year mortality. Method This is a prospective observational study that was conducted at Mansoura Nephrology and Dialysis Unit (MNDU), Mansoura University and Aga Hospital Dialysis Unit over a period of one-year Patients who fulfilled inclusion and exclusion criteria were included. The study was explained to all participants and informed consent was obtained. All demographic, clinical, and laboratory data were collected. Appetite was assessed using the following 4 scores: subjective assessment of appetite, the self-assessment of appetite changes for 30 days, The Visual Analog Scale (VAS), and The Functional Assessment of Anorexia/Cachexia Therapy (FAACT). All patients were followed up for one year to report the mortality events. Results The current study included 162 hemodialysis patients whose age (SD) was 48.72±12.64 years, and males constituted 57.4% of them. Around 44.4% of the cases reported having good appetite using the subjective assessment score, and 13% reported decreased appetite using the self-assessment of appetite score. The median VAS score was 80, and the FAACT score ranged from 7 to 32 with a mean value of 15.85. After one year of observation, death occurred in 24/162 (14.8%). There were statistically significant differences in mean values of three appetite scores among both dead and alive groups with lower values reported in the deceased one [self-assessment of appetite (p=0.019), VAS score (p=0.001), and FACCT (p=&amp;lt;0.001)]. The ROC analysis shows that FACCT &amp; VAS scores were able to determine patients who destinated to mortality with area under curve (AUC) of (0.774 &amp;0.704), at a cut-off point of (14.5%, and 75), with sensitivity of (83.3% &amp;and 66.7%) and specificity of (61.6%, and 53.6%), respectively. Kaplan Meier survival analysis demonstrated that VAS &amp; FACCT scores had a statistically significant effect on median survival time among studied cases. Lower median survival time was detected among cases with decreased appetite by self-assessment tool, VAS score less than 80, and FACCT score less than 15. Kaplan-Meier and hazard curves for the included sample showed lower Median survival time (95% CI) among patients with diminished appetite by the 4 scores: 311.67(265.98-357.36) by self-assessment score (p=0.008), 344.28 (329.57-358.9) days by subjective assessment of appetite (p=0.28), 342.33(330.46-354.19) days by VAS score (p=0.016), and 332.01(314.6-349.43) days by FAACT score (p&amp;lt;0.0001). Cox regression analysis demonstrated that VAS and FACCT scores were statistically significant predictors of median survival time among studied cases (p&amp;lt;0.001, &amp;lt;0.001) and hazard ratio (HR) of (0.968 &amp; 0.734), respectively. Conclusion Diminished appetite is prevalent among hemodialysis patients. Poor appetite is associated with higher mortality. Lower appetite score values can predict mortality among such patients.