Search Results (40)

Background: Patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD) who undergo complete revascularization (CR) have a more favorable prognosis than those who receive incomplete revascularization (IR), as evidenced by recent randomized controlled trials. Despite the absence of a survival benefit associated with CR in these trials, positive outcomes were ascribed to combined endpoints, such as repeat revascularization, myocardial infarction, or ischemia-driven rehospitalization. In light of the significant burden that rehospitalization from STEMI imposes on healthcare systems, we examined the long-term effects of CR on ischemia-driven rehospitalization and cardiovascular (CV) mortality in STEMI patients with MVD. Methods: In our retrospective study, we included patients with STEMI and MVD who underwent successful primary percutaneous coronary intervention (PCI) at the University Medical Centre Ljubljana between 1 January 2009, and 11 April 2011. The combined endpoint was ischemia-driven rehospitalization and CV mortality, with a minimum follow-up period of six years. Results: We included 235 participants who underwent CR (N = 70) or IR (N = 165) at index hospitalization, with a median follow-up time of 7 years (interquartile range 6.0–8.2). The primary endpoint was significantly higher in the IR group than in the CR group (47.3% vs. 32.9%, log-rank p = 0.025), driven by CV mortality (23.6% vs. 12.9%, log-rank p = 0.047), as there was no difference in ischemia-driven rehospitalization rate (log-rank p = 0.206). Ischemia-driven rehospitalization did not influence CV mortality in the CR group (p = 0.49), while it significantly impacted CV mortality in the IR group (p = 0.03). After adjusting for confounders, there were no differences in CV mortality between CR and IR groups (p = 0.622). Predictors of the combined endpoint included age (p = 0.014), diabetes (p = 0.006), chronic kidney disease (CKD) (p = 0.001), cardiogenic shock at presentation (p = 0.003), chronic total occlusion (CTO) (p = 0.046), and ischemia-driven rehospitalization (p = 0.0001). Significant risk factors for the combined endpoint were cardiogenic shock at presentation (p < 0.001), stage 4 kidney failure (p = 0.001), age over 70 years (p = 0.004), female gender (p = 0.008), and residual SYNTAX I score > 5.5 (p = 0.017). Conclusions: Patients with STEMI and MVD who underwent CR had a lower combined endpoint of ischemia-driven rehospitalizations and CV mortality than IR patients, but after adjustments for confounders, the true determinants of the combined endpoint and risk factors for the combined endpoint were independent of the revascularization method. Full article

Background: Liposarcoma (LPS) is one of the most frequent histotypes of soft tissue sarcoma (STS). Eribulin is a cytotoxic agent that has improved overall survival in patients with advanced LPS. Additionally, preclinical and clinical evidence suggests its influence on vascularization and cellular differentiation. Based on these data, we developed this study to investigate non-mitotic effects of eribulin in patients with advanced LPS. Methods: In this prospective monocentric observational study, we included patients with advanced LPS eligible to receive eribulin. An assessment with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and a biopsy were planned before treatment and after four cycles of eribulin. DCE-MRI scans were elaborated to obtain perfusion and permeability maps. Results: From September 2019 to January 2024, 11 patients were enrolled. Among them, 8/11 (73%) had successful pre- and post-treatment assessment. At the time of the analysis, 8/11 (73%) patients had disease progression and 4 (36%) had died, median progression-free survival (mPFS) was 3.3 months, and median overall survival (mOS) was 8.7 months. Among the evaluable patients, DCE-MRI perfusion decreased after eribulin treatment in patients with disease control (partial response or stable disease), while perfusion values increased in patients with progressive disease (PD). No significant change in permeability was found. Post-treatment histological changes were seen nearly in all patients, with decreased cellularity the most common change (50%), followed by vascularization modifications (20%). Conclusions: Eribulin appears to exhibit non-mitotic activity involving both vascularization and cell differentiation in LPS patients. Further studies are needed to better define these effects. Full article

Background/Objectives: Hyponatremia is associated with increased mortality in the general hospital population. We sought to investigate whether hyponatremia affects the long-term survival of patients following a myocardial infarction (MI) in both ST-segment elevation (STEMI) and non-ST elevation (NSTEMI) presentations. Methods: In this study, 862 MI patients who were hospitalized between 2012 and 2017 were retrospectively followed-up within the median time period of 41.9 [28.2–73.5] months. All participants were assigned to a hyponatremic or normonatremic group with hyponatremia defined as a sodium level of less than 135 mEq/L on admission. Results: In the acute phase of an MI, hyponatremia was diagnosed in 31 (3.6%) patients. The patients with hyponatremia were less often male (38.7 vs. 70.4%, p < 0.001), and less frequently had Killip class I (63.3 vs. 80%) but more often had Killip class IV on admission (16.7 vs. 4.2%, p = 0.024) and more often had a history of impaired renal function (32.3 vs. 15.5%, p = 0.013) than those with normonatremia. Hyponatremic patients had higher troponin T levels on admission by 75.1% (p = 0.003), a higher isoenzyme MB of creatine kinase level by 34.4% (p = 0.006), and lower hemoglobin (by 8.5%, p = 0.001) levels as compared to the normonatremia group. Long-term mortality was significantly higher in the patients with hyponatremia versus normonatremia (18 [58.1%] vs. 243 [29.2%], log-rank p < 0.001). This was driven by differences in the NSTEMI population (65 vs. 30.5%, p < 0.001). By a Cox proportional hazard regression analysis, hyponatremia was associated with a higher long-term mortality (hazard ratio [HR] of 2.222, a 95% confidence interval [CI] of 1.309–3.773, and p = 0.003). Conclusions: Hyponatremia rarely identified in acute phase of MI was associated with higher long-term mortality, particularly in the NSTEMI population. Full article

Background/Objectives: The historically most commonly used preoperative radiotherapy regimen for soft tissue sarcomas (STSs) consists of 50 Gray (Gy) delivered in 25 fractions over 5 weeks, achieving excellent local control, but with significant challenges due to prolonged treatment duration and early side effects. Reducing therapy duration while maintaining optimal local and distant control would be highly beneficial for patients. We aimed to investigate the outcome of an ultrahypofractionated radiotherapy (uhRT) regimen which may represent a shorter and more patient-friendly alternative. Methods: This multi-center, open-label, phase 2 clinical trial with a clustered cohort design was conducted within the Swiss Sarcoma Network (SSN). Adult patients (aged ≥ 18 years) with STS of the extremities or superficial trunk and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–3 were included. Participants were assigned to either normofractionated radiotherapy (nRT) at 50 Gy in 25 fractions or uhRT at 25 Gy in 5 fractions. Data were collected prospectively in real-world-time clinical settings. The primary outcome was local recurrence-free survival (LRFS), with overall survival (OS) and wound complications as secondary outcomes. Results: Between March 2020 and October 2023, 138 patients were included in the study; 74 received nRT and 64 received uhRT. The median follow-up times were 2.2 years for uhRT and 3.6 years for nRT. The LRFS rates at 1 year were 97.0% for nRT and 94.8% for uhRT (p = 0.57). The two-year LRFS rates were 91.9% and 94.8%, respectively (p = 0.57). The one- and two-year OS rates were 97.1%/86.3% and 98.2%/88.8%, respectively (p = 0.72). The wound complication rate was comparable between the nRT (12.0%) and uhRT (12.5%) groups (p = 0.99). Conclusions: UhRT for STSs offers an effective and safe alternative to traditional nRT, with comparable early LRFS, OS and wound complication rates. Given the two-year median follow-up, which is critical for evaluating local recurrence, uhRT shows promise as a shorter and more convenient treatment regimen. UhRT may be a safe and effective alternative treatment option to traditional nRT. Full article

Serum albumin and body mass index (BMI, kg/m²) have been associated with outcomes following acute myocardial infarction (AMI). Aiming to assess whether the mortality risk inflicted by hypoalbuminemia (<3.5 g/dL) in this context is influenced by BMI, we conducted a retrospective analysis of AMI survivors hospitalized during 2004–2017. Stratified by admission-time albumin level and BMI, eligible cases were evaluated for all-cause mortality up to 10 years after discharge. A total of 6283 individuals (74.1% males, mean age 64.1 ± 13.1 years, 44.3% with ST-elevation MI) were included. Of them, 22.7% had hypoalbuminemia and 1.2%, 41.0%, and 28.6% were underweight (BMI < 18.5), overweight (BMI 25–30), and obese (BMI ≥ 30), respectively. Over a median of 7.9 (IQR, 4.8–10.0) years of follow-up, 42.5% of patients died. Hypoalbuminemia was independently associated with a heightened mortality risk overall (AdjHR = 1.54, 95%CI 1.42–1.67, p < 0.001), accounted for by the normal weight (AdjHR = 1.73, 95%CI 1.50–1.99, p < 0.001), overweight (AdjHR = 1.55, 95%CI 1.35–1.79, p < 0.001), and class 1 obesity (BMI 30–35) (AdjHR = 1.37, 95%CI 1.12–1.68, p = 0.002) subgroups. Upon interaction analysis, the mortality risk imposed by hypoalbuminemia was most pronounced among individuals with normal BMI. In conclusion, hypoalbuminemia constituted a negative prognostic marker for long-term survival in AMI patients with normal or mildly elevated but not reduced or severely increased BMI. Pending further research, addressing hypoalbuminemia based on BMI range may prove beneficial. Full article

Background. Pericarditis has a heterogeneous clinical spectrum and rate of relapse. Data on aetiology, real-life treatment strategies, and long-term course from contemporary pericarditis cohorts are lacking. Methods. Pericarditis patients referred to the Cardioimmunology Outpatient Clinic at Padua University Hospital in 2001–2020 were retrospectively included. Kaplan–Meier method was used for recurrence-free survival probability estimation. The appropriateness of treatment was assessed based on the European Society of Cardiology guidelines. Results. One-hundred forty-four patients (57% males, mean age 50 years) followed up for 18 months (IQR 7–45) were included; of those, 52% had acute, 35% recurrent, 8% incessant, and 5% chronic pericarditis; 9% had cardiac tamponade at diagnosis. Time to pericardial effusion resolution was 53 days (IQR 16–124); median medical treatment duration was 87 days (IQR 48–148). Treatment was readjusted following the ESC guidelines for nonsteroidal anti-inflammatory drugs in 29% of the cases, steroids in 12%, and colchicine in 25%. Eleven (8%) patients were treated with anti-IL1 agents. Recurrence-free survival probability was 86% at 1st-year follow-up, and 23 patients (16%) had at least one recurrence, with a mean of two relapses per patient. Compared to patients without recurrences, they had a higher frequency of cardiac tamponade (27% vs. 6%, p = 0.006) and left bundle branch block (14% vs. 1%, p = 0.034). Out of the 144 patients, 5 (3%) were diagnosed as having constrictive pericarditis at first evaluation at our clinic, underwent successful pericardiectomy, and are currently alive and asymptomatic. Conclusions. When treated following a guideline-based approach, pericarditis has a favourable evolution. A relevant quote of cases benefits from the treatment readjustment of previously prescribed medical therapy when not in line with ESC recommendations. Cases relapsing despite treatment readjustment should receive anti-IL1 therapies. Full article

Background: Specifically young women are at risk for a poor outcome after ST-elevation myocardial infarction (STEMI). We aimed to investigate sex- and age-specific differences in outcome and associate these results with adherence to a guideline-directed optimal medical therapy (OMT). Methods: Administrative insurance data (≈26 million insured) were screened for patients aged 18–60 years with STEMI. Patient demographics, details on in-hospital treatment, adherence to OMT and its effect on mortality were assessed. Adherence to OMT was analyzed using multistate models and an association of those with death was fitted using multivariable Cox regression models with time-dependent co-variables. Results: Overall, 59,401 patients (19.3% women), median age 52 (interquartile range 48, 56) presented with STEMI. Female sex was associated with a poor outcome early after STEMI (90-day mortality: odds ratio 1.22, 95% confidence interval (CI) 1.12–1.32, p < 0.001). Overall survival was reduced in women compared to same-aged men. The ten-year survival rate was 19.7% (18.1–21.2%) versus 19.6% (18.9–20.4%) in men (p < 0.001). Although long-term drug adherence was low, its intake was associated with a better outcome. Specifically younger women showed a markedly lower mortality when on OMT (hazard ratio (HR) 0.22 (95% CI 0.19–0.26) versus HR 0.31 (95% CI 0.28–0.33) in men, p^int < 0.001). Conclusions: Specifically young women were at risk for a poor outcome in the early phase after STEMI. Although long-term adherence to OMT was low, it was generally associated with a lower mortality, specifically in women. Our findings emphasize on early and long-term preventive measures in all patients after STEMI. Full article

Background: The effect of COVID-19 on treatment outcomes in the literature remains limited and is mostly reported either as predictive survival using prioritization and modeling techniques. We aimed to quantify the effect of COVID-19 on lung cancer survival using real-world data collected at the Jewish General Hospital, Montreal. Methods: This is a retrospective chart review study of patients diagnosed between March 2019 and March 2022. We compared three cohorts: pre-COVID-19, and 1st and 2nd year of the pandemic. Results: 417 patients were diagnosed and treated with lung cancer at our centre: 130 in 2019, 103 in 2020 and 184 in 2021. Although the proportion of advanced/metastatic-stage lung cancer remained the same, there was a significant increase in the late-stage presentation during the pandemic. The proportion of M1c (multiple extrathoracic sites) cases in 2020 and 2021 was 57% and 51%, respectively, compared to 31% in 2019 (p < 0.05). Median survival for early stages of lung cancer was similar in the three cohorts. However, patients diagnosed in the M1c stage had a significantly increased risk of death. The 6-month mortality rate was 53% in 2021 compared to 47% in 2020 and 29% in 2019 (p = 0.004). The median survival in this subgroup of patients decreased significantly from 13 months in 2019 to 6 months in 2020 and 5 months in 2021 (p < 0.001). Conclusions: This study is, to our knowledge, the largest single-institution study in Canada looking at lung cancer survival during the COVID-19 pandemic. Our study looks at overall survival in the advanced/metastatic setting of NSCLC during the COVID-19 pandemic. We have previously reported on treatment pattern changes and increased wait times for NSCLC patients during the pandemic. In this study, we report that the advanced/metastatic subgroup had both an increase in the 6-month mortality rate and worsening overall survival during this same time period. Although there was no statistical difference in the proportion of patients with advanced disease, there was a concerning trend of increased M1c disease in cohorts 2 and 3. The higher M1c disease during the COVID-19 pandemic (cohorts 2 and 3) likely played a crucial role in increasing the 6-month mortality rate and leading to a reduced overall survival of lung cancer patients during the pandemic. These findings are more likely to be better identified with longer follow-up. Full article

Fall armyworm (FAW, Spodoptera frugiperda) is a polyphagous and migratory lepidopteran pest insect in field crops and is notoriously invasive worldwide. In large portions of the Americas, its populations are managed using transgenic maize or cotton varieties producing insecticidal proteins from Bacillus thuringiensis (Bt), primarily Vip3Aa pyramided with Cry Bt proteins. We determined the susceptibility of FAW field populations from locations pressured with such maize hybrids for over five years. We used time–mortality bioassays with F₁ third-instar larvae of six geographically distinct populations collected in maize fields of a tropical agricultural region encompassing four Brazilian states. We maintained the neonate progeny from the field populations on an artificial diet until the third instar, and then determined their survival curves on the foliage of three Vip3Aa/Cry-producing Bt maize hybrids. Death of the mid-size, third-instar FAWs occurred relatively rapidly, with larval mortality rates reaching 98–100% in less than five days regardless of Bt maize hybrid. However, median survival time (ST₅₀) for the larvae differed among the populations, with the lowest and highest ST₅₀ values occurring for PI-Cr (42 h, 1.75 d) and PI-Ur populations (66–90 h, 2.75–3.75 h), respectively. Therefore, the F₁ third-instar larvae of FAW populations were largely susceptible to Vip3Aa/Cry-producing maize foliage, and the most contrasting susceptibility occurred in the insects from Piauí state, Brazil. These results indicate that progeny of FAWs from areas highly pressured with Vip3Aa/Cry Bt maize hybrids are killed on maize foliage producing Vip3Aa and Cry Bt proteins despite field reports of increased leaf damage by the larvae in some locations. This research informs decision making for Bt-crop resistance management by producers, technicians, and researchers in local, regional, and world agriculture. Full article

Background: RT-induced hyalinization/fibrosis was recently evidenced as a significant independent predictor for complete response to neoadjuvant radiotherapy (RT) and survival in patients with soft tissue sarcoma (STS). Purpose: Non-invasive predictive markers of histologic response after neoadjuvant RT of STS are expected. Materials and Methods: From May 2010 to April 2017, patients with a diagnosis of STS who underwent neoadjuvant RT for limb STS were retrieved from a single center prospective clinical imaging database. Tumor Apparent Diffusion Coefficients (ADC) and areas under the time-intensity perfusion curve (AUC) were compared with the histologic necrosis ratio, fibrosis, and cellularity in post-surgical specimens. Results: We retrieved 29 patients. The median ADC value was 134.3 × 10⁻³ mm²/s. ADC values positively correlated with the post-treatment tumor necrosis ratio (p = 0.013). Median ADC values were lower in patients with less than 50% necrosis and higher in those with more than 50% (120.3 × 10⁻³ mm²/s and 202.0 × 10⁻³ mm²/s, respectively (p = 0.020). ADC values higher than 161 × 10⁻³ mm²/s presented a 95% sensitivity and a 55% specificity for the identification of tumors with more than 50% tumor necrosis ratio. Tumor-to-muscle AUC ratios were associated with histologic fibrosis (p = 0.036). Conclusions: ADC and perfusion AUC correlated, respectively, with radiation-induced tumor necrosis and fibrosis. Full article

E-TRAB was a non-interventional, prospective trial investigating the feasibility and predictive value of geriatric assessments (GA) in older STS patients treated with trabectedin as first-line therapy. Primary endpoints were overall survival (OS), quality of life and individual clinical benefit assessed by the patient-reported outcome measures QLQ-C30 and PRO-CTCAE. Further, several GA tools were applied and correlated with clinical outcomes and treatment-related toxicities. The final analyses included 69 patients from 12 German-speaking sites. The median age of patients was 78 years (range: 55 to 88). Baseline data on PROs and GA identified a diverse population of older patients with respect to their global health status, although a large proportion of them suffered from limitations, required geriatric help and had a high risk of morbidity. The Cancer and Age Research Group (CARG) score classified 38%, 29% and 23% of the patients with low, intermediate and high risks for therapy-related side effects, respectively. Median OS was 11.2 months [95%CI: 5.6; 19.4]. The study confirmed that trabectedin as first-line treatment in older patients with STS has an acceptable and manageable safety profile. Potential prognostic factors for clinical outcome and therapy-related toxicity were identified among the GA tools. Long Timed Up and Go (TUG) showed a significant correlation to OS and early death, whereas a high CARG score (>9) was associated with an increase in unplanned hospitalizations and the incidence of toxicities grade ≥ 3. Full article

Granular cell tumors (GCT) represent 0.5% of all soft tissue sarcomas (STS), and when metastatic, they exhibit aggressive behavior and determine limited survival. Metastatic GCTs are relatively chemo-resistant; however, there is growing evidence of the benefit of using pazopanib and other targeted therapies in this histology. This is a review of the role of pazopanib and other targeted therapies in the treatment of GCTs, along with some insights on pathology and molecular biology described in GCTs. From 256 articles found in our search, 10 case-report articles met the inclusion criteria. Pazopanib was the most employed systemic therapy. The median reported time on therapy with pazopanib was seven months. Eight out of ten patients (80%) experienced disease control with pazopanib, while four out of ten (40%) patients achieved an objective RECIST response. Molecular studies suggested that antitumoral effects of pazopanib in GCT might be due to a loss-of-function of ATP6AP1/2 genes which consequently enhance signaling through several molecular pathways, such as SFKs, STAT5a/b, and PDGFR-β. Other reported targeted therapies for malignant GCTs included pazopanib in combination with crizotinib, which showed disease control for four months in one patient, and a PI3K inhibitor which achieved disease control for nine months in another patient. Dasatinib and megestrol were ineffective in two other different patients. Pazopanib has been demonstrated to be active in advanced GCTs and may be considered as a preferable treatment option. Full article

Background: Sarcomas are rare, aggressive cancers which frequently metastasise to the lungs. Following diagnosis, patients typically undergo staging by means of a CT scan of their chest. This often identifies indeterminate pulmonary nodules (IPNs), but the significance of these in high-grade soft tissue sarcoma (STS) is unclear. Identifying whether these are benign or malignant is important for clinical decision making. This study analyses the clinical relevance of IPNs in high-grade STS. Methods: All patients treated at our centre for high-grade soft tissue sarcoma between 2010 and 2020 were identified from a prospective database. CT scans and their reports were reviewed, and survival data were collected from patient records. Results: 389 suitable patients were identified; 34.4% had IPNs on their CT staging scan and 20.1% progressed into lung metastases. Progression was more likely with IPNs ≥ 5 mm in diameter (p = 0.006), multiple IPNs (p = 0.013) or bilateral IPNs (p = 0.022), as well as in patients with primaries ≥ 5 cm (p = 0.014), grade 3 primaries (p = 0.009) or primaries arising deep to the fascia (p = 0.041). The median time to progression was 143 days. IPNs at diagnosis were associated with an increased risk of developing lung metastases and decreased OS in patients with grade 3 STS (p = 0.0019 and p = 0.0016, respectively); this was not observed in grade 2 patients. Conclusions: IPNs at diagnosis are associated with significantly worse OS in patients with grade 3 STS. It is crucial to consider the primary tumour as well as the IPNs when considering the risk of progression. Surveillance CT scans should be carried out within 6 months. Full article

Soft tissue sarcomas (STSs) are a heterogeneous group of malignant mesenchymal tumors with similar histological features and biological behaviors. They are characterized by a low to moderate local recurrence rate and low metastasis, affecting approximately 20% of patients. Although this tumor set is vital in veterinary medicine, no previous unified staging system or mitotic count has been associated with patient prognosis. Therefore, this study proposed a new clinicopathological staging method and evaluated a cut-off value for mitosis related to the survival of dogs affected by STS. This study included 105 dogs affected by STS, treated only with surgery, and a complete follow-up evaluation. The new clinicopathological staging system evaluated tumor size (T), nodal involvement (N), distant metastasis (M), and histological grading criteria (G) to categorize the tumor stage into four groups (stages I, II, III, and IV). The proposed tumor staging system was able to differentiate patients’ prognoses, with dogs with stage IV disease experiencing the lowest survival time and dogs with stage I disease having the highest survival time (p < 0.001). Moreover, we assessed the median mitosis (based on mitotic count) and its association with overall survival. Our study’s median mitosis was 5, and patients with ≤5 mitoses had a higher survival time (p = 0.006). Overall, the proposed staging system and mitotic count seemed promising in the prediction of patient prognosis. Full article

Background: MicroRNAs (miRNA, miR) are small, non-coding RNAs which have become increasingly relevant as diagnostic and prognostic biomarkers. The objective of this study was the investigation of blood-derived miRNAs and their link to long-term all-cause mortality in patients who suffered from non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods: This study was an observational prospective study, which included 109 patients with NSTE-ACS. Analysis of the expression of miR-125a and miR-223 was conducted by polymerase chain reaction (PCR). The follow-up period comprised a median of 7.5 years. Long-term all-cause mortality was considered as the primary endpoint. Adjusted Cox-regression analysis was performed for prediction of events. Results: Increased expression of miR-223 (>7.1) at the time point of the event was related to improved long-term all-cause survival (adjusted (adj.) hazard ratio (HR) = 0.09, 95% confidence interval (95%CI): 0.01–0.75; p = 0.026). The receiver operating characteristic (ROC) analysis provided sufficient c-statistics (area under the curve (AUC) = 0.73, 95%CI: 0.58–0.86; p = 0.034; negative predictive value of 98%) for miR-223 to predict long-term all-cause survival. The Kaplan–Meier time to event analysis showed a separation of the survival curves between the groups at an early stage (log rank p = 0.015). Higher plasma miR-125a levels were found in patients with diabetes mellitus vs. in those without (p = 0.010). Furthermore, increased miR-125a expression was associated with an elevated HbA1c concentration. Conclusions: In this hypothesis-generating study, higher values of miR-223 were related to improved long-term survival in patients after NSTE-ACS. Larger studies are required in order to evaluate whether miR-223 can be used as a suitable predictor for long-term all-cause mortality. Full article