Factor For Survival Research Articles

Radiotherapy for central neurocytoma: A multicentric retrospective study in France

PurposeNeurocytomas represent 0.25 to 0.5% of primary brain tumours and are mainly found in young adults. These tumours have neuronal differentiation. The cornerstone treatment is neurosurgery. The efficacy of other therapies, including radiotherapy, is still unclear. The objective of this study was to evaluate the management of central neurocytomas and the role of radiotherapy. Materials and methodsAll adult patients (age 18 years or older) newly diagnosed with a histologically confirmed neurocytoma between 2006 and 2015 in France were included. ResultsOne hundred and sixteen patients were diagnosed with a central neurocytoma during the study period. All patients underwent surgical resection, and six received adjuvant radiotherapy. Eleven patients received radiotherapy due to progression. After a median follow-up of 68.7 months, local failure occurred in 29 patients. The 5-year local control rate was 73.4%. According to univariate analysis, marker of proliferation Ki67 index greater than 2% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.40–1.57; P=0.027) and subtotal resection (HR: 8.48; CI: 8.01–8.99; P<0.001) were associated with an increase in local failure. Gross total resection was associated with a higher risk of sequelae epilepsy (HR: 3.62; CI: 3.42–3.83; P<0.01) and memory disorders (HR: 1.35; CI: 1.07–1.20; P<0.01). Ten patients (8.6%) died during the follow-up. The 10-year overall survival rate was 89.0%. No prognostic factors for overall survival were found. ConclusionThe analysis showed that patients who underwent subtotal surgical resection, particularly when the tumour had a Ki67 index greater than 2%, had an increased risk of local recurrence. These patients could benefit from adjuvant radiotherapy.

Causes of death analysis and the prognostic model construction in neuroendocrine carcinoma of the cervix: A SEER-based study.

Neuroendocrine carcinoma of the cervix (NECC) is rare but results in poor prognosis. The causes of death (CODs) in NECC patients are rarely reported. Our study aimed to explore the distributions of death causes of NECC patients compared with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) and to develop a validated survival prediction model. Patients diagnosed with NECC, SCC, or ADC were identified from the Surveillance, Epidemiology, and End Results Program database from 1975 to 2019. We analyzed the standardized mortality ratio (SMR) to determine each cause of death for each survival time category. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate Cox regression analyses were used to establish a nomogram model. A total of 358 NECC patients were included in this study, and 270 (75.4%) died during the follow-up period. Patients with NECC had 5.55 times (95% CI, 4.53-6.79, p < 0.0001) higher risk of death compared with patients with SCC and 10.38 times (95% CI, 8.28-13.01, p < 0.0001) higher compared with ADC. Cervical cancer is the main cause of death in NECC. As the diagnosis time increased, the risk of death from all causes and cervix cancer gradually decreased. While after at least 10 years of follow-up time, the highest and most dramatical SMR values were observed for metastasis (SMR, 138.81; 95% CI, 37.82-355.40; p < 0.05) and other cancers as the reason for death has an over 7-fold higher SMR (SMR: 7.07; 95% CI: 2.60-15.40, p < 0.05) more than 5 years after the cancer diagnosis. Race, FIGO stage, and surgery were independent risk factors for the overall survival (OS) of NECC patients. For the predictive nomogram, the C-index was 0.711 (95% CI: 0.697-0.725) and was corrected to 0.709 (95% CI: 0.680, 0.737) by bootstrap 1000 resampling validation. Compared with SCC and ADC, NECC patients have an elevated risk of mortality due to cervical cancer and metastasis. We successfully constructed a prognostic nomogram for patients with NECC. Based on refractoriness and high mortality of NECC, targeted treatment strategies and follow-up plans should be further developed according to the risk of death and distribution characteristics of CODs.

Effect of genetic polymorphisms of interleukin-1 beta on the microscopic portal vein invasion and prognosis of hepatocellular carcinoma.

Several studies have demonstrated a relationship between genetic polymorphisms of interleukin-1 beta (IL-1β) and cancer development; however, their influence on cancer prognosis is unknown. In the present study, we aimed to evaluate the impact of IL-1β single nucleotide polymorphisms on the hematogenous dissemination and prognosis of hepatocellular carcinoma. We conducted a retrospective cohort study including patients with hepatocellular carcinoma who underwent primary liver resection at our hospital between April 2015 and December 2018. The primary endpoints were overall and recurrence-free survival. Secondary endpoints were microscopic portal vein invasion and number of circulating tumor cells. A total of 148 patients were included, 32 with rs16944 A/A genotype. A/A genotype was associated with microscopic portal vein invasion and number of circulating tumor cells (p = .03 and .04). In multivariate analysis, A/A genotype, alpha-fetoprotein level, and number of circulating tumor cells were associated with microscopic portal vein invasion (p = .01, .01, and <.01). A/A genotype, Child-Pugh B, and intraoperative blood loss were independent predictive factors for overall survival (p = .02, <.01, and <.01). Our results indicate that the IL-1β rs16944 A/A genotype is involved in number of circulating tumor cells, microscopic portal vein invasion, and prognosis in HCC.

Prognostic Significance of 18F-FDG PET/CT and Tumor Metabolic Changes in Patients With Pancreatic Ductal Adenocarcinoma.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is reportedly associated with the malignant potential of cancer. This study aimed to evaluate the association between FDG accumulation and tumor metabolism in pancreatic ductal adenocarcinoma (PDAC). A prognostic analysis of data from 131 patients with PDAC who underwent FDG-PET/CT before curative-intent pancreatic surgery was performed. Capillary electrophoresis-mass spectrometry (CE-MS) was used to analyze the metabolome of tumor and non-neoplastic pancreas from 80 patients. These patients were divided into two groups: low SUVmax group (SUVmax <6.09) and high SUVmax group (SUVmax ≥6.09). Carbohydrate antigen 19-9 (CA19-9), maximum standardized uptake value (SUVmax) of PET, N stage, and postoperative chemotherapy were identified as significant prognostic factors by univariate analysis. SUVmax emerged as an independent prognostic factor for overall survival [hazard ratio (HR)=1.88, p<0.05] and disease-free survival (HR=2.01, p<0.05) in multivariate analysis. Metabolic analyses confirmed that 43 metabolites significantly differed depending on the accumulation of SUV in tumors. Metabolites involved in the removal of reactive oxygen species (e.g., hypotaurine, glutathione, Met), treatment resistance (UDP-N-acetylglucosamine), and proliferation (e.g., choline, leucine, isoleucine) were increased in the high SUVmax group. FDG accumulation is an important independent prognostic factor reflecting tumor activity associated with metabolic changes in cancer cells.

Recurrence pattern and its risk factors in patients with resected pancreatic ductal adenocarcinoma – A retrospective analysis of 272 patients

BackgroundThe aim of this study was to investigate the patterns of recurrence and their associated risk factors in patients who underwent resection for pancreatic carcinoma. MethodsThis retrospective study included 272 patients, who underwent Ro/R1-resection of PDAC from 2005 to 2020 at the University Hospital Erlangen. Risk factors for different recurrence patterns and the prognostic value of recurrence pattern on the overall survival after recurrence were evaluated. Results61 % of the patients experienced recurrence, mostly within the first 12 postoperative months (62 %) and in the form of metastases (87 %). The median overall survival from recurrence was 9.2 months. The preoperative absence of diabetes and the presence of lymph node metastasis were independent risk factors for recurrence and a preoperative CA19-9 exceeding 97 U/ml for early recurrence. Additionally, lymph node metastases were associated with a higher risk of metastatic recurrence. Early recurrence, but not the site of recurrence, was identified as an independent prognostic factor for worse overall survival from recurrence. ConclusionThe occurrence of recurrence and especially of early and metastatic recurrence are associated with a worse overall survival. Patients lacking preoperative diabetes, having high preoperative CA19-9 values and lymph node metastases are particularly at risk for (early) recurrence.

Neoadjuvant-Based Triple Therapy for Hepatocellular Carcinoma with Type I/II Portal Vein Tumor Thrombosis.

Hepatectomy could provide better survival benefit for hepatocellular carcinoma (HCC) with type I/II portal vein tumor thrombosis (PVTT). However, the postoperative recurrence remains high. We discussed whether neoadjuvant therapy could reduce HCC recurrence for these patients. One hundred and thirty-eight resectable HCC with type I-II PVTT were retrospectively included. The neoadjuvant therapy regimens included tyrosine kinase inhibitor (TKI), programmed death 1(PD-1) antibodies and transarterial chemoembolization (TACE). Short-term and long-term outcomes were compared. Propensity score matching (PSM) was performed to minimize the influence of potential confounders. Thirty-three patients underwent neoadjuvant therapy and 105 patients underwent surgery alone. In the neoadjuvant group, 7 (21.2%) patients achieved stable disease, 13 (39.4%) achieved partial response and 13 (39.4%) achieved complete response based on the modified Response Evaluation Criteria in Solid Tumors criterion. By PSM, the neoadjuvant therapy resulted in less microvascular invasion (24.1% vs 50.0%, P=0.021), satellite nodule (6.9% vs 24.1%, P=0.036) and less patients with alpha-fetoprotein>20(ng/mL) (37.9% vs 69.0%, P=0.006). The neoadjuvant therapy reduced tumor recurrence and prolonged survival. Multivariate analysis found that neoadjuvant therapy was an independent protective factor for overall survival and recurrence free survival. Neoadjuvant treatment presents a promising treatment option for HCC patients with type I/II PVTT.

A multivariate retrospective analysis of high-grade gliomas: Survival and prognostic factors.

High-grade gliomas (HGGs) are highly malignant, aggressive, and have a high incidence and mortality rate. The aim of this study was to investigate survival outcomes and prognostic factors in patients with HGGs. In this retrospective study, a total of 159 patients with histologically confirmed HGGs were included. The recruitment period was from January 2011 to December 2019. We evaluated patient demographic data, tumor characteristics, treatment methods, immunocytochemistry results, overall survival (OS) time, and progression-free survival (PFS) time using Kaplan-<>Meier survival analysis with log-rank testing. Additionally, we employed Cox regression analysis to identify independent factors associated with survival outcomes. Kaplan-Meier survival analysis revealed that the 1-, 2-, and 5-years OS rates were 81.8%, 50.3%, and 12.6%, respectively. Similarly, the 1-, 2-, and 5-years PFS rates were 50.9%, 22.4%, and 3.1%, respectively. The median OS duration was 35.0 months. The univariate analysis indicated that postoperative pathological classification, grade, and age were significantly associated with patient outcomes (p < 0.01). Among the patients, 147 received concurrent chemoradiotherapy, while 12 did not. The immunohistochemical markers of ki-67, MGMT, IDH1R132H, and p53 demonstrated statistically significant differences in their prognostic impact (p = 0.001, p = 0.020, p = 0.003, and p = 0.021, respectively). In conclusion, we found that grades, age, pathological classification, ki-67, MGMT, and IDH1R132H expression were statistically significantly associated with PFS (p < 0.01, p = 0.004, p = 0.003, p = 0.001, p = 0.036, and p = 0.028). Additionally, immunohistochemical expressions of TRIB3 and AURKA were significantly higher in patients with shorter survival (p = 0.015 and p = 0.023). Tumor grade and the use of concurrent chemoradiotherapy after surgery were independent prognostic factors that significantly influenced patient survival. Additionally, tumor grade and MGMT expression were found to be independent factors affecting progression-free survival (PFS). Notably, the expression of TRIB3 and AURKA was higher in patients with poor survival outcomes.

Long-term survivors in 976 supratentorial glioblastoma, IDH-wildtype patients.

Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype is the most aggressive glioma with poor outcomes. The authors explored survival rates and factors associated with long-term survival in patients harboring a glioblastoma, IDH-wildtype. In an observational, retrospective, single-center study, the authors examined the medical records of 976 adults newly diagnosed with supratentorial glioblastomas, IDH-wildtype between January 2000 and January 2021. They analyzed clinical-, imaging-, and treatment-related factors associated with 2-year and 5-year survival. The median overall survival was 11.2 months (12.2 months for patients included after 2005 and the introduction of standard combined chemoradiotherapy). The median progression-free survival was 9.4 months (10.0 months for patients included after 2005). Overall, 17.6% of patients reached a 2-year overall survival, while 2.2% of patients reached a 5-year overall survival. Furthermore, 6.6% of patients survived 2 years without progression, while 1.1% of patients survived 5 years without progression. Two factors that were consistently associated with 2-year and 5-year survival were first-line oncological treatment with standard combined chemoradiotherapy and methylated O6-methylguanine-DNA methyltransferase promoter. Other factors that were significantly associated with 2-year or 5-year survival were age at diagnosis ≤ 60 years, headaches or signs of raised intracranial pressure at diagnosis, cortical contact of contrast enhancement, no contrast enhancement crossing the midline on initial imaging, total or subtotal tumor resection, and a second line of oncological treatment at recurrence. Within 21 cases of 5-year survival, 18 were confirmed to be glioblastomas, IDH-wildtype, and 7 of the 5-year survivors (38.9%) had additional genetic alterations: 3 cases had an FGFR mutation or fusion, 3 cases had a PIK3CA mutation, 1 case had a PTPN11 mutation, and 1 case had a PMS2 mutation in the context of constitutional mismatch repair deficiency syndrome. Five-year overall survival in patients with glioblastoma, IDH-wildtype is extremely low. Predictors of a longer survival are mostly treatment factors, emphasizing the importance of a complete oncological treatment plan, when achievable. Glioblastoma, IDH-wildtype 5-year survivors could be screened for actionable targets in case of recurrence.

Analysis of Factors Influencing Overall Survival and Prognosis of AML Patients Over 50 Years Old

To explore the overall survival and prognostic factors of patients over 50 years old with acute myeloid leukemia (AML). The clinical data of 222 AML patients aged over 50 years in our hospital from January 2016 and June 2021 were retrospectively analyzed. Kaplan-Meier method was used to evaluate the overall survival (OS) rate, and Cox regression model to evaluate the prognostic factors. The 1-year and 3-year OS rates of all patients were 46.8% and 28.8%, respectively. The recurrence rate of patients who achieved remission during follow-up time was 57%. Both univariate and multivariate analysis showed that advanced age, MLL family fusion gene, PHF6 gene mutation, TP53 gene mutation, intolerance to standard chemotherapy, incomplete remission, complex karyotype, +mar karyotype and inv(3) karyotype were significantly correlated with prognosis (all P <0.05). Negative fusion gene and positive AML- ETO fusion gene had no obvious survival advantage in this population. In patients with complete remission, there was no significant survival advantage in those who achieved minimal residual disease negative. AML patients aged over 50 years have a poor outcome and high recurrence rate. The prognosis is affected by multiple factors and has its own characteristics.

Radiotherapy and chemoradiotherapy for postoperative recurrence in patients with esophageal squamous cell carcinoma.

The optimal treatment for esophageal squamous cell carcinoma (ESCC) patients with postoperative recurrence remains controversial. We aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on postoperative recurrence in ESCC patients. Recurrence ESCC patients who received salvage RT and CRT from January 2015 to January 2019 were retrospectively reviewed. Post-recurrence survival (PRS) and prognostic factors were evaluated by Kaplan-Meier and Cox proportional hazards models, respectively. Subgroup analyses were performed based on pathological lymph node (LN) status (negative/positive) to evaluate the differences in salvage treatments and toxic reaction. A total of 170 patients were enrolled, with a median age of 60 years (range 43-77). No significant difference was found in the median PRS between the salvage RT and CRT groups (p > 0.05). Multivariate analysis revealed that TNM stage III and IV, macroscopic medullary type, and distant metastasis recurrence pattern were independent prognostic factors (all p < 0.05) for PRS. Salvage treatment was not associated with PRS (p = 0.897). However, in patients with negative LN, CRT was associated with prolonged survival (p = 0.043) and had no significant differences in toxic reactions compared to RT (p = 0.924). In addition, RT showed better prognoses (p = 0.020) and lower toxic reactions (p = 0.030) than CRT in patients with positive LNs. Based on prognosis and toxic reactions, ESCC recurrence patients with negative LNs could benefit from CRT, but RT should be recommended for patients with positive LNs.

Survival improvements in esophageal and gastric cancers in the Nordic countries favor younger patients.

Esophageal cancer (EC) and gastric cancer (GC) are fatal cancers with a relatively late age of onset. Age is a negative risk factor for survival in many cancers and our aim was to analyze age-specific survival in EC and GC using the recently updated NORDCAN database. NORDCAN data originate from the Danish, Finnish, Norwegian, and Swedish nationwide cancer registries covering years 1972 through 2021 inviting for comparison of 50-year survival trends between the countries. Relative 1- and 5-year survival and 5/1-year conditional survival (i.e., survival in those who were alive in Year 1 to survive additional 4 years) were analyzed. Survival in EC showed large gains for patients below age 80 years, 5-year survival in Norwegian men reaching 30% and in women over 30% but for 80-89 year old survival remained at 10%. In contrast, hardly any gain was seen among the 80-89 year patients for 1-year survival and small gains in 5 year and 5/1-year survival. Survival gaps between age-groups increased over time. For GC there was also a clear age-related negative survival gradient but the survival gaps between the age groups did not widen over time; Norwegian male and female 5-year survival for 80-89 year old was about 20%. The age-specific survival difference in GC arose in Year 1 and did not essentially increase in 5-year survival. While there were differences in survival improvements between the countries, poor survival of the 80-89 year old patients was shared by all of them. To conclude, survival has improved steadily in younger GC and EC patients in most Nordic countries. While the 80-89 year old population accounts for nearly a quarter of all patients and their poor survival depressed overall survival, which can therefore be increased further by improving diagnostics, treatment and care of elderly EC and GC patients.

Efficacy of Immune Checkpoint Inhibitors in Postoperative Recurrence of Wild-type EGFR Non-Small Cell Lung Cancer.

Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC), but specific outcomes of ICIs treatment among patients with postoperative recurrence of NSCLC remain unclear. The objective of the study was to compare the efficacy of ICIs and chemotherapy with conventional chemotherapy only in patients with postoperative recurrence of epidermal growth factor receptor (EGFR) wild-type NSCLC. A retrospective analysis was performed on patients who underwent anatomical lung resection at the Nagoya University Hospital and were treated for postoperative recurrence of wild-type EGFR NSCLC. This study evaluated the prognosis for postoperative recurrence, including ICIs treatment and other clinicopathological factors. Of the 83 patients included in the analysis, 20 patients underwent chemotherapy and 63 patients underwent chemotherapy combined with ICIs. The combination of ICIs and chemotherapy significantly prolonged survival after recurrence (median survival: 33.1 months vs. 22.0 months, p=0.01). In the ICIs group, no significant differences in survival were detected between patients with different programmed death ligand 1 (PD-L1) status (Tumor Proportion Scores: <1%, 1%-49%, ≥50%, p=0.27). Multivariate analysis revealed that postoperative distant recurrence was a significant poor prognostic factor for survival after recurrence (HR=1.85, 95% CI=1.06-3.25, p=0.03), and combining ICIs with chemotherapy significantly improved survival after recurrence (HR=0.43, 95% CI=0.24-0.78, p<0.01). Combination of ICIs with chemotherapy significantly prolonged survival of postoperative recurrence with wild-type EGFR NSCLC regardless of PD-L1 status.

Momelotinib: Mechanism of action, clinical, and translational science.

Myelofibrosis is a chronic myeloproliferative disorder characterized by bone marrow fibrosis, splenomegaly, anemia, and constitutional symptoms, with a median survival of ≈6 years from diagnosis. While currently approved Janus kinase (JAK) inhibitors (ruxolitinib, fedratinib) improve splenomegaly and symptoms, most can exacerbate myelofibrosis-related anemia, a negative prognostic factor for survival. Momelotinib is a novel JAK1/JAK2/activin A receptor type 1 (ACVR1) inhibitor approved in the US, European Union, and the UK and is the first JAK inhibitor indicated specifically for patients with myelofibrosis with anemia. Momelotinib not only addresses the splenomegaly and symptoms associated with myelofibrosis by suppressing the hyperactive JAK-STAT (signal transducer and activator of transcription) pathway but also improves anemia and reduces transfusion dependency through ACVR1 inhibition. The recommended dose of momelotinib is 200 mg orally once daily, which was established after review of safety, efficacy, pharmacokinetic, and pharmacodynamic data. Momelotinib is metabolized primarily by CYP3A4 and excreted as metabolites in feces and urine. Steady-state maximum concentration is 479 ng/mL (CV%, 61%), with a mean AUCtau of 3288 ng.h/mL (CV%, 60%); its major metabolite, M21, is active (≈40% of pharmacological activity of parent), with a metabolite-to-parent AUC ratio of 1.4-2.1. This review describes momelotinib's mechanism of action, detailing how the JAK-STAT pathway is involved in myelofibrosis pathogenesis and ACVR1 inhibition decreases hepcidin, leading to improved erythropoiesis. Additionally, it summarizes the pivotal studies and data that informed the recommended dosage and risk/benefit assessment.

Noninvasive evaluation of the glymphatic system in diffuse gliomas using diffusion tensor image analysis along the perivascular space.

The aim of this study was to noninvasively explore the glymphatic system (GS) in glioma and its association with glioma characteristics and prognosis by using diffusion tensor image analysis along the perivascular space (ALPS). In the period from April 2015 to November 2021, all patients with pathologically confirmed unihemispheric glioma who had not undergone surgery, chemotherapy, radiotherapy, or stereotactic biopsy; who did not have severe brain deformation; who had undergone preoperative conventional and advanced whole-brain diffusion-weighted imaging; and whose data were available and uncompromised were included in this study. Age- and sex-matched healthy controls (HCs) who had undergone diffusion-weighted imaging were also included. The ALPS index was calculated based on diffusivity maps, allowing noninvasive analysis of the GS. The contralateral ALPS index was measured in all glioma patients, and the ipsilateral ALPS index was measured in glioma patients without severe deformation of the ipsilateral hemisphere. The ALPS index was compared between glioma patients and HCs according to tumor grade, IDH genotype, tumor and edema volume, and tumor location. The association between the bilateral ALPS index of gliomas and tumor characteristics was further analyzed. Survival analysis was conducted using Kaplan-Meier survival curves with the log-rank test and univariable and multivariable Cox regressions. Ninety-one patients with unihemispheric glioma (33 female, mean age 46 ± 13 years) and 59 age- and sex-matched HCs were included in this study. The ipsilateral ALPS index decreased in the glioma group versus the HC group, regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.048), whereas the contralateral ALPS index decreased in gliomas with a high grade, IDH wildtype, larger edema volume, different tumor volumes and locations (p ≤ 0.009). The ipsilateral versus contralateral ALPS index was lower regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.044). Univariable linear regression revealed age (β = -0.004, p = 0.026), tumor grade (β = -0.114, p = 0.011), and IDH genotype (β = 0.120, p = 0.008) were associated with the ipsilateral ALPS index in glioma. Age (β = -0.005, p < 0.001), tumor grade (β = -0.144, p < 0.001), IDH genotype (β = 0.154, p < 0.001), tumor volume (β = -0.002, p = 0.001), and peritumoral edema volume (β = -0.002, p < 0.001) were correlated with the contralateral ALPS index in glioma. Multivariable linear regression revealed that tumor grade (β = -0.125, p = 0.005) was independently associated with the ipsilateral ALPS index. Age (β = -0.003, p = 0.022), IDH status (β = 0.132, p = 0.001), and tumor volume (β = -0.002, p < 0.001) were independently associated with the contralateral ALPS index. Kaplan-Meier analysis showed different survival times between low and high contralateral ALPS groups (log-rank = 10.574, p = 0.001). Univariable Cox regression analysis demonstrated that the lower contralateral ALPS index was related to a shorter survival time (HR 0.095, p = 0.005). Multivariable Cox regression analysis revealed IDH status as the only independent factor for survival (HR 0.138, p < 0.001). GS function was impaired in glioma and correlated with tumor characteristics, and worse contralateral GS function was associated with a shorter survival time.

Diet and exercise in relation to lower extremity artery disease.

Adherence to the Mediterranean diet (MeD) has been associated with a reduced incidence of peripheral arterial disease (PAD)/lower extremity arterial disease (LEAD) in observational trials and in a randomized trial. In secondary prevention, a lower hazard ratio for composite major adverse cardiovascular events has been associated with better adherence to MeD in a relatively small, randomized trial. This has not been confirmed in a sub-analysis of a large interventional trial of dual antithrombotic treatment. The effects of vegetarian, vegan or low carbohydrate/ketogenic diets on the incidence and outcomes of PAD/LEAD are not known. While abdominal obesity is associated with diabetes mellitus and PAD/LEAD, the lowest incidence of PAD/LEAD has been found in subjects with a body mass index 25-29.9 kg/m2. Malnutrition is a negative prognostic factor for survival of patients with chronic limb threatening ischemia. Physical activity (PA) is an acute stressor, but habitual recreational PA results in beneficial adaptations and improved health. In observational studies, lower levels of exercise and lower physical fitness have been associated with more prevalent PAD/LEAD. In contrast to coronary artery disease, that shows a reverse J-shaped relationship between long-term endurance exercise and coronary atherosclerosis, such a relationship is not known for PAD/LEAD. A general recommendation for maintaining cardiovascular health is performing regular moderate-intensity exercise with some vigorous-intensity aerobic PA, and resistance exercise at least twice a week. Combinations of healthy behaviors are more effective in preventing PAD/LEAD than a single behavioral component. In treatment of PAD/LEAD causing intermittent claudication, supervised walking training is recommended among measures of first-line treatment, while unsupervised walking training should be considered as an alternative.

A Retrospective Study of Pediatric Patients With Low- or Intermediate-Risk Acute Myeloid Leukemia Who Underwent Allogeneic Hematopoietic Cell Transplantation for the AML-05 Study Conducted by the Japanese Pediatric Leukemia/Lymphoma Study Group

The AML-05 study aimed to examine the efficacy and safety of a therapeutic strategy based on risk stratification for low-, intermediate-, or high-risk acute myeloid leukemia (AML) pediatric patients. Allogeneic hematopoietic cell transplantation (allo-HCT) was not indicated for low- or intermediate-risk AML patients in first complete remission. The present retrospective study for the AML-05 study aimed to identify prognostic factors for survival and to determine optimal allo-HCT according to multivariate analysis on overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR), and cumulative incidence of nonrelapse mortality for and between low- and intermediate-risk AML group patients in the AML-05 study who had undergone allo-HCT after its completion and relapse. The unique patient numbers (UPNs) of the AML-05 study were matched with the Transplant Registry Unified Management Program (TRUMP)-registered numbers, and the tied data on the AML-05 study's UPNs and the TRUMP-registered numbers were analyzed. The primary endpoint was 3-yr OS. Among 443 AML patients in the AML-05 study, 79 (32 low-risk AML and 47 intermediate-risk AML) were analyzed. The following statistically favorable prognostic factors were identified by multivariate analysis on the low- and intermediate-risk AML groups, respectively: UCB (OS—hazard ratio [HR], 0.105; 95% CI, 0.011 to 0.941; P = .004 and EFS—HR, 0.065, 95% CI, 0.007 to 0.577, P = .014) and late relapse (OS—HR, 0.212; 95% CI, 0.072 to 0.626; P = .005 and EFS—HR, 0.236; 95% CI, 0.088 to 0.630; P = .004). Three-year OS, 3-yr EFS, and 3-yr CIR were significantly different between the low- and intermediate-risk AML groups. UCB may be a safe and beneficial donor source for low-risk AML patients, while late relapse was a favorable prognostic factor for intermediate-risk AML patients. Intermediate-risk AML patients with late relapse and low-risk AML patients may benefit from allo-HCT after relapse.

Reirradiation in head and neck squamous cell carcinoma; prognostic indicators, oncologic and functional outcomes

ObjectivesPatients with recurrent squamous cell carcinoma of the head and neck (HNSCC) have a poor prognosis and limited therapeutic alternatives. While reirradiation is feasible, it is usually associated with high treatment toxicity and is not yet considered the standard of care. Based on current NCCN guidelines, in the context of very advanced head and neck cancer (recurrent and/or persistent disease), surgical intervention is explored initially with/without adjuvants while unresectable disease is approached with radiation and/or systemic therapies. Specific and reliable prognostic indicators for both -oncologic and functional outcomes- have yet to be defined for this population. MethodsRetrospective chart review of 54 patients treated with reirradiation at a tertiary academic institution between January of 1998 and January of 2024. Only patients with non-metastatic recurrent, and second primary HNSCC were included in the series. Demographics, staging, radiation dose and technique, additional therapy, histopathologic variables, EORTC toxicity, pre- and post-treatment PEG/tracheotomy dependency and oncologic outcomes were retrieved. ResultsThe study cohort consisted of 54 patients (37 males, 17 females) with HNSCC, averaging 62.7 years in age. Initial tumors were locally advanced in over 42 % of cases, with 58 % being node-negative. The head and cutaneous regions (24.5 %) and tongue (20.8 %) were the most common tumor sites. Primary surgical resection and adjuvant radiation were performed in 47.2 % of cases, and concurrent chemotherapy was used in 40.7 %. Reirradiation was mainly for local or regional recurrence (88.9 %), often following salvage surgery (68.5 %), with a mean dose of 5623 Gy over 52.5 fractions. Positive surgical margins were present in 29.4 % of cases, and extracapsular spread in 59.5 %. No significant differences were found between the salvage surgery and definitive reirradiation groups except for tumor site (P = 0.022). Median follow-up was 52.6 months, with 27 deaths reported. Lymphovascular invasion was significantly correlated with overall survival (P = 0.017), while initial tumor T-stage and neck disease involvement were linked to local-regional control (P = 0.030 and P = 0.033, respectively). Reirradiation increased tracheotomy and PEG-tube dependency by 20 % (P = 0.011) and 23 % (P = 0.003), respectively. ConclusionsReirradiation is a feasible therapeutic alternative in recurrent head and neck SCC. Oncologic outcomes observed in this series compare favorably to most published reports. Complete response and perineural invasion were independent prognostic factors for survival and locoregional control. While no mortality directly associated with treatment was observed in this series, reirradiation had a significant impact in functional outcomes in terms of increased risk of tracheotomy and peg tube dependency. Further studies are required to define the role of this treatment in head and neck cancer.

Expression of the αVβ3 integrin affects prostate cancer sEV cargo and density and promotes sEV pro-tumorigenic activity in vivo through a GPI-anchored receptor, NgR2.

It is known that small extracellular vesicles (sEVs) are released from cancer cells and contribute to cancer progression via crosstalk with recipient cells. We have previously reported that sEVs expressing the αVβ3 integrin, a protein upregulated in aggressive neuroendocrine prostate cancer (NEPrCa), contribute to neuroendocrine differentiation (NED) in recipient cells. Here, we examine the impact of αVβ3 expression on sEV protein content, density and function. sEVs used in this study were isolated by iodixanol density gradients and characterized by nanoparticle tracking analysis, immunoblotting and single vesicle analysis. Our proteomic profile of sEVs containing αVβ3 shows downregulation of typical effectors involved in apoptosis and necrosis and an upregulation of tumour cell survival factors compared to control sEVs. We also show that the expression of αVβ3 in sEVs causes a distinct reposition of EV markers (Alix, CD81, CD9) to a low-density sEV subpopulation. This low-density reposition is independent of extracellular matrix (ECM) protein interactions with sEVs. This sEV subset contains αVβ3 and an αVβ3 downstream effector, NgR2, a novel marker for NEPrCa. We show that sEVs containing αVβ3 are loaded with higher amounts of NgR2 as compared to sEVs that do not express αVβ3. Mechanistically, we demonstrate that sEVs containing NgR2 do not affect the sEV marker profile, but when injected in vivo intratumorally, they promote tumour growth and induce NED. We show that sEVs expressing NgR2 increase the activation of focal adhesion kinase (FAK), a known promoter of cancer cell proliferation, in recipient cells. We also show that NgR2 mimics the effect of sEVs containing αVβ3 since it displays increased growth of NgR2 transfectants in vivo, as compared to control cells. Overall, our results describe the changes that occur in cargo, density and functions of cancer cell-derived sEVs containing the αVβ3 integrin and its effector, NgR2, without affecting the sEV tetraspanin profiles.

Neurotrophic Factors in Cannabis-induced Psychosis: An Update.

Cannabis is the most widely used illicit substance. Numerous scientific evidence confirm the strong association between cannabis and psychosis. Exposure to cannabis can induce the development of psychosis and schizophrenia in vulnerable individuals. However, the neurobiological processes underlying this relationship are unknown. Neurotrophins are a class of proteins that serve as survival factors for central nervous system (CNS) neurons. In particular, Nerve Growth Factor (NGF) plays an important role in the survival and function of cholinergic neurons while Brain Derived Neurotrophic Factor (BDNF) is involved in synaptic plasticity and the maintenance of midbrain dopaminergic and cholinergic neurons. Glial Cell Derived Neurotrophic Factor (GDNF) promotes the survival of midbrain dopaminergic neurons and Neuregulin 1 (NrG- 1) contributes to glutamatergic signals regulating the N-methyl-D-aspartate (NMDA). They have a remarkable influence on the neurons involved in the Δ-9-THC (tethra-hydro-cannabinol) action, such as dopaminergic and glutamatergic neurons, and can play dual roles: first, in neuronal survival and death, and, second, in activity-dependent plasticity. In this brief update, reviewing in a narrative way the relevant literature, we will focus on the effects of cannabis on this class of proteins, which may be implicated, at least in part, in the mechanism of the psychostimulant-induced neurotoxicity and psychosis. Since altered levels of neurotrophins may participate in the pathogenesis of psychotic disorders which are common in drug users, one possible hypothesis is that repeated cannabis exposure can cause psychosis by interfering with neurotrophins synthesis and utilization by CNS neurons.

Prognostic value of electrical bioimpedance measured with a portable and wireless device in acute heart failure

Introduction and objectivesThe current evaluation of acute heart failure (HF) does not allow an adequate prediction of its evolution. The electrical bioimpedance (BI) allows knowing the state of blood volume, until now only with fixed equipment. We have developed and validated a portable and wireless device to measure BI at the ankle (IVOL). The objective of the study is to know the long-term prognostic value of the point measurement of BI with IVOL in patients with acute HF. MethodsA prospective cohort study of unselected patients admitted for acute HF in a tertiary hospital. The association between BI and different clinical, analytical and echocardiographic variables on admission and clinical evolution were analyzed. Results76 patients were included (mean age 66.1 years, 71.1% men, 68.4% hypertensive, 34.2% diabetic, mean NT-ProBNP: 7,103 pg/ml). Of these, 52.6% with non-preserved left ventricular ejection fraction (LVEF) (<50%) and 56.6% with right ventricular (RV) dysfunction. 26.3% died during a mean follow-up of 35.8 months. Survival in patients with BI ≤ 21,8 Ω was lower, globally and in the subgroups of patients without preserved LVEF and with RV dysfunction, p < 0.008). In the multivariate analysis, a BI ≥ 21.8 Ω was an independent survival factor (HR 0.242, 95% CI:0.86−0.681, p = 0.007). ConclusionsBI values ​​measured with IVOL may be an independent predictor of long-term mortality in patients hospitalized for acute HF. This prognostic value is maintained in patients without preserved LVEF function and with RV dysfunction.