Search Results (5,000)

Background/Objectives: The optimal management of bone-only progressive disease (PD) in metastatic breast cancer remains unclear for several reasons. Radiologic diagnosis of bone PD is complicated by the lack of standardized response assessment criteria, unspecific morphologic changes of the bone, and flare-up phenomena. Furthermore, bone-only disease and oligoprogression have been associated with favorable prognosis challenging a change of systemic treatment with the consequence of limited treatment options in the future. Additionally, bone-only metastatic disease is frequently excluded from clinical trials resulting in scarce data. This study aimed to assess the therapeutic management and outcome of bone-only PD in metastatic breast cancer patients in a real-world academic setting. Methods: A retrospective analysis of all breast cancer patients with bone metastases (BMs) and at least one event of radiologic evidence of bone-only PD and/or the occurrence of a skeletal-related event (SRE) who were treated at the Department of Obstetrics and Gynecology of the Medical University of Vienna, Austria, between 1 January 2015 and 14 December 2021 was performed. In cases of multiple bone-only PD events in one patient only the first event was considered for analysis. All cases with PD in organs other than the bone were excluded. The primary outcome of the study was to assess therapeutic measures of bone-only PD. Secondary outcomes were the time from bone-only PD to next bone PD (TTF BD) and overall survival (OS; time from bone-only PD to death). Predictors of TTF BD and OS were assessed as exploratory outcomes. Results: Out of a total of 308 breast cancer patients with BMs, 57 had at least one event of bone-only PD. In 59.3% of bone-only PD cases the systemic treatment was continued with a numerically higher rate if multiple metastatic sites were present (71.4% vs. 46.4%). In most bone-only PD events the bone-targeted agent (BTA) was continued (94.5%), independent of the total number of metastatic sites. In 24.1% radiotherapy (RT) was administered with similar rates between patients with bone-only and multiple metastatic sites. The median TTF BD was 6.3 months. In multivariate analysis no predictor for TTF BD could be identified including change of systemic treatment, RT, previous BTA treatment duration, number of previous treatment lines for the metastatic disease, number of metastatic sites and previous or current SRE. Median OS was 21.8 months. Number of previous treatment lines for the metastatic setting was significantly associated with OS with shorter OS in the more advanced disease stage (p-value = 0.0208). Conclusions: Systemic and BTA treatment were continued in the majority of bone-only PD cases. In 24.1% RT was administered. No association between change of systemic therapy and improved oncologic outcome was found. The study’s results are hypothesis-generating in terms of whether change of systemic treatment should be performed restrictively to avoid limited treatment options in the future. Similarly, radiotherapy did not ameliorate prognosis. Full article

Background/Objectives: Elevated lipoprotein(a) [Lp(a)] is an independent causal risk factor for atherosclerotic cardiovascular disease and may contribute to increased coronary complexity and adverse outcomes after acute myocardial infarction (AMI). Data regarding its prognostic significance in Southeastern Europe remains limited. This study aimed to evaluate the association between elevated Lp(a) levels, coronary artery disease severity, and major adverse cardiovascular events (MACE) at 1 and 6 months after AMI. Methods: This prospective study included 150 consecutive patients with STEMI and NSTEMI enrolled between December 2024 and August 2025. MACE was defined as a composite of overall cardiac death, recurrent myocardial infarction, cerebrovascular insult, heart failure with reduced ejection fraction occurrence, and new revascularization, either PCI or CABG. Results: Patients with elevated Lp(a) had significantly greater coronary disease burden, reflected by higher mean SYNTAX scores (17.3 ± 7.0 vs. 13.8 ± 7.0; p = 0.011) and a greater proportion of intermediate- and high-risk SYNTAX classifications (p = 0.016). Although the number of diseased vessels did not differ significantly, three-vessel disease was more frequent in the elevated Lp(a) group. At 1-month follow-up, overall MACE incidence was numerically higher but not statistically significant between groups. At 6 months, heart failure with reduced ejection fraction was significantly increased in patients with elevated Lp(a) (27.7% vs. 12.2%; p = 0.027). Binary logistic regression demonstrated that elevated Lp(a) independently predicted 6-month MACE (OR 2.768, p = 0.011, 95% CI 1.262–6.072), but not 1-month outcomes. Conclusions: Elevated Lp(a) is associated with increased coronary artery disease severity and higher mid-term MACE risk after AMI. Full article

Background/Objectives: Inpatient clinical deterioration is a major contributor to adverse hospital outcomes, such as unplanned intensive care unit (ICU) admissions and death. Rapid response systems aim to address this challenge by enabling early identification and intervention in at-risk patients. This study evaluated the impact of implementing a mobile intensive care team on clinical outcomes in surgical patients. Methods: A retrospective observational cohort study was conducted in a tertiary care hospital, comparing two consecutive periods: a pre-intervention phase (PRETIM) and a post-intervention phase (TIM). The study included 17,156 adult surgical patients. The TIM consisted of a proactive outreach team composed of one attending intensivist and two resident physicians, focusing on post-ICU monitoring and early identification of clinical deterioration on surgical wards. The primary outcome was in-hospital mortality. Secondary outcomes included ICU readmission and length of stay. Multivariable logistic regression adjusted for age, sex and surgical section was performed, along with subgroup and sensitivity analyses excluding early non-modifiable deaths. Results: Baseline characteristics were comparable between groups. In-hospital mortality decreased significantly following implementation of the TIM (8.0% vs. 5.3%; p < 0.001), corresponding to an absolute risk reduction of 2.7% and a number needed to treat of 37. ICU readmission rates did not differ significantly between groups. Sensitivity analysis excluding early deaths confirmed the mortality reduction. Subgroup analysis demonstrated consistent effects across surgical specialties, with the largest reductions observed in neurosurgery and general surgery. Conclusions: The implementation of a mobile intensive care team was associated with a significant and clinically meaningful reduction in in-hospital mortality among surgical patients. The findings support the role of proactive post-ICU monitoring and early intervention strategies in improving patient outcomes in high-risk hospital populations. Full article

Introduction: Recent research underscores the risks of maintaining a positive calcium balance in hemodialysis (HD) patients. This study aims to evaluate outcomes based on the calcium levels of HD patients, specifically those with hypocalcemia. Methods: In this retrospective cohort study, data from 71,101 HD patients were analyzed and classified into six groups based on calcium levels: severe hypocalcemia (<7.5 mg/dL, n = 1078), moderate hypocalcemia (7.5–7.99 mg/dL, n = 4000), mild hypocalcemia (8.0–8.39 mg/dL, n = 9846), lower-normal calcium (8.4–9.29 mg/dL, n = 38,697), upper-normal calcium (9.3–10.19 mg/dL, n = 14,505), and hypercalcemia (≥10.2 mg/dL, n = 1975). Results: The numbers of deaths, CVE, and fracture at the end point of the follow-up were recorded: 401 (37.2%), 189 (23.2%), and 224 (20.8%) in the severe hypocalcemia group, respectively; 1523 (38.1%), 663 (22.8%), and 802 (20.1%) in the moderate hypocalcemia group, respectively; 3985 (40.5%), 1618 (22.9%), and 2054 (20.9%) in the mild hypocalcemia group, respectively; 17,067 (44.1%), 6948 (24.9%), and 8676 (22.4%) in the lower-normal calcium group, respectively; 6904 (47.6%), 2967 (27.3%), and 3471 (23.9%) in the upper-normal calcium group, respectively; and 1074 (54.4%), 457 (30.0%), and 473 (23.9%) in the hypercalcemia group, respectively. The 5-year patient survival rates for the severe hypocalcemia, moderate hypocalcemia, mild hypocalcemia, lower-normal calcium, upper-normal calcium, and hypercalcemia groups were 73.9%, 70.0%, 68.8%, 66.4%, 66.1%, and 62.8%, respectively. The 5-year cardiovascular event-free survival rates for the severe hypocalcemia, moderate hypocalcemia, mild hypocalcemia, lower-normal calcium, upper-normal calcium, and hypercalcemia groups were 78.2%, 79.0%, 78.2%, 76.2%, 75.3%, and 72.6%, respectively. The hazard ratios (HRs) for the all-cause mortality (HR: 0.94, 95% CI: 0.84–1.05) and cardiovascular events (HR: 0.98, 95% CI: 0.84–1.15) of the severe hypocalcemia group were consistently not higher than those of the lower-normal calcium group even after thorough adjustments were made for various clinical variables. Multivariable Cox regression analyses revealed that the HRs for all-cause mortality and cardiovascular events of the mild hypocalcemia groups were lower than those of the lower-normal calcium group. Serum calcium levels were not associated with increased risk of fracture. Conclusions: Patients with various degrees of hypocalcemia, including severe hypocalcemia, were not associated with increased mortality and cardiovascular event rates. We suggest that symptoms and clinical presentation should be prioritized rather than simply targeting the normalization of calcium levels in hypocalcemia correction. Full article

Infections of chronic wounds are a major healthcare burden worldwide and can lead to poor health outcomes such as amputations of limbs and death. Detecting infections early significantly increases the effectiveness of therapeutic interventions. Screening of volatile organic compounds (VOCs) emitted from wound swab samples can potentially serve as a highly specific indicator of infection. Profiling of VOCs from infected and non-infected wounds was carried out. Swab samples were collected from 26 wounds from 23 patients (n = 20 diabetic patients; n = 3 non-diabetic patients). There were 16 wounds sampled that were clinically determined as infected, and 10 as non-infected. Headspace-solid phase microextraction gas chromatography-mass spectrometry (HS-GC-MS) was used to rapidly sample and detect VOCs from the swabs following a short incubation period. A total of 42 compounds were identified and included for analysis. Infected wounds emitted more diverse VOCs compared to non-infected wounds. Higher numbers of compounds with significantly higher abundances were detected from severely infected wounds compared to less severely infected wounds. Abundances of short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) were found to be the strongest discriminators of infected from non-infected wounds. Further validation is needed, but the results of this pilot study highlight the potential of detecting these compounds as a highly specific and targeted route to predicting or detecting wound infections in the future. Full article

Diabetes complications may increase frailty rates among the elderly, leading to falls, immobility, dependency, hospitalizations, and death. The study aimed to assess any association between frailty status and glycaemic control among older adults with type 2 diabetes mellitus at Kenyatta National Hospital, Kenya. We conducted a cross-sectional study of 430 older individuals aged 60+ years with type 2 diabetes at a specialized diabetes clinic using a modified FRAIL scale. Mean age was 69.1 years; 65.7% were female and 76.2% completed primary school. Frailty prevalence was 3.8%, pre-frailty constituted 24.3%, and robust/non-frail comprised 71.9%. It was associated with age, social status, health knowledge, duration of DM, blood pressure, body mass index, high-density lipoprotein-C, and renal failure. Mean fasting plasma glucose (FPG) was 8.7 mmol/L, with 60% having FPG > 7 mmol/L; mean glycated haemoglobin (HbA1C) was 8.0%, with 41% having HbA1C > 8%. Glycaemic control was correlated with number of medications, blood pressure, and lipidaemia, but not age, sex, or social status. No correlation was found between frailty and glycaemic control: frailty versus FPG (r = 0.038, p = 0.459; χ² = 0.699, p = 0.705) and HbA1C (r = −0.009, p = 0.877; χ² = 0.046, p = 0.977). Low frailty prevalence was noted, with no association to glycaemic control. Our findings provide evidence for conducting frailty assessments in chronic disease care. Full article

Background: There is a high burden of influenza among individuals aged 50–64 years, with the highest rates of influenza infections other than children. The MF59-adjuvanted influenza vaccine (adjuvanted trivalent influenza vaccine [aTIV]/adjuvanted quadrivalent influenza vaccine [aQIV]) is designed to enhance response to vaccination among older adults. Among those aged ≥65 years, adjuvanted vaccine (aTIV/aQIV) has shown to be 14% more effective than standard (TIV/QIV) vaccines. This modeling study aimed to estimate the potential public health impact of aTIV/aQIV over standard influenza vaccines (TIV/QIV) among individuals aged 50–64 years over five influenza seasons. Methods: A static compartmental model was developed based on a Centers for Disease Control and Prevention model. Model inputs included vaccine effectiveness, vaccine coverage, population counts and disease burden estimates. Additional burden averted (symptomatic cases, outpatient visits, hospitalizations, intensive care unit [ICU] admissions, and deaths) was expressed as total incremental cases averted between the vaccines. Sensitivity analyses explored the influence of uncertainties in model input on the results. Results: Across the influenza seasons evaluated, on average each 5% increase in the relative vaccine effectiveness (rVE) of aTIV/aQIV vs. QIV prevented an additional 172,738 symptomatic illnesses, 74,277 outpatient visits, 1832 hospitalizations, 343 ICU admissions, and 105 deaths. This corresponds to an average seasonal incremental burden averted of 15.2%, with a range of 5.9% to 37.2%. Deterministic sensitivity analyses revealed the greatest variability was tied to rVE and burden estimates. Probabilistic sensitivity analyses results were normally distributed. Conclusions: Individuals aged 50–64 years could benefit from use of aTIV/aQIV over TIV/QIV, with an average increase in the number of influenza outcomes prevented of 15.2% per 5% improvement in vaccine effectiveness. Full article

Background/Objectives: Individuals with alcohol use disorder (AUD) and tobacco use disorder (TUD) are at increased risk for severe COVID-19 outcomes. However, real-world evidence on vaccine effectiveness (VE) in these populations remains limited, particularly in low- and middle-income countries. This study aimed to evaluate the effectiveness of three or more COVID-19 vaccine doses against mortality in hospitalized patients with AUD and TUD in Brazil. Methods: This retrospective cohort study used data from the SIVEP Gripe database, a national surveillance system of hospitalized COVID-19 cases in Brazil. The study included adults aged ≥18 years with confirmed SARS-CoV 2 infection between February 2020 and June 2025. The intervention was defined as receipt of three or more vaccine doses (fully vaccinated) versus no doses (unvaccinated). Propensity score matching was performed separately for AUD and TUD cohorts. Vaccine effectiveness was estimated using McNemar’s test for paired samples, and the average treatment effect (ATE) and number needed to vaccinate (NNV) were calculated. Results: Among 2,184,723 hospitalized patients, 12,115 had AUD and 45,679 had TUD. After matching, VE against mortality was 42% (95% CI: 27.5–53.5) in the AUD group and 52.6% (95% CI: 46.5–58.1) in the TUD group, compared to 58.5% and 58.9% in their respective non-exposed counterparts. The ATE was consistent across groups (approximately −0.12), and the NNV to prevent one death was 8 (95% CI: 6–15 for AUD; 7–12 for TUD). Conclusions: Although VE was attenuated in individuals with AUD and TUD compared to the general population, the absolute benefit of vaccination remained substantial. Full article

Climate change will impact the distribution of daily deaths in Austria until the end of the century. This study examines the net effects of fewer cold and more-frequent hot days on daily mortality under different climate and demographic scenarios. Projected district-level mortality data and daily temperatures based on Representative Concentration Pathways (RCP4.5 and RCP8.5) are analyzed to estimate the number of attributable deaths for every fifth year due to heat and cold using district-wise temperature–effect estimates from a previous analysis. While the overall shape of the time course of temperature-attributable deaths depends mostly on the demographic developments (with the highest numbers of daily mortality mid-century), under all climate scenarios investigated, the increase in heat-attributable deaths will be more pronounced than the decrease in cold-attributable deaths. Contrary to common claims, shift in temperatures due to climate change already has a net negative effect on population health in Austria now. Full article

The increase in older adults and active lifestyles has made chondral and osteochondral lesions common in the population, making them one of the central challenges in orthopedics. Although hydrogel-based regenerative medicine offers an encouraging therapeutic option for these lesions, important obstacles still prevent these therapies from reaching the clinic. In view of these factors, we adopted a risk-based approach for this review, in line with the current legislative requirements in clinical translation and clinical trials. We identified the factors that could undermine patient safety or lead to poor outcomes. Then, we outlined solutions to remedy these problems that integrate hydrogel technology, clinical/pharmaceutical/surgical protocols, and post-operative follow-up. Upcoming studies should give priority to the development of hydrogel scaffolds modified to mimic cartilage’s mechanical and physicochemical properties, together with patient-specific features. Other crucial characteristics are host-tissue integration, long-lasting cartilage tissue regeneration, and a positive outcome. In parallel, to scale complex and costly innovations, efforts should focus on a harmonized, simplified legislative landscape, optimized standards, and established follow-up protocols. Getting through this “valley of death” between research and innovation is strategic for reaching the clinics and the largest number of patients. Full article

Cancer poses a serious threat to human life and health, and the number of new cancer and death cases worldwide is substantial, of which breast cancer is the most common among women. p-QM-1h is an organic small molecule with excellent anti-cancer activity, but it has low solubility and requires a high dosage, and it is not a targeted anti-tumor drug. In this study, p-QM-1h was loaded into a nanostructured lipid carrier (NLC) using the thin-film dispersion method to construct p-QM-1h-NLC, and its surface was modified with cetuximab (CTX) to construct CTX-p-QM-1h-NLC, which was tested for activity in 4T1 cells and tumor-bearing mice. The construction of CTX-p-QM-1h-NLC used Miglyol 812N as a liquid lipid, which effectively improved the solubility and encapsulation efficiency of p-QM-1h. Nanoparticles were uniform, well dispersed, and had good stability, and the CTX modification of p-QM-1h-NLC exhibited high connection efficiency and ensured antibody integrity. CTX-p-QM-1h-NLC exhibited effective anti-tumor activity in both 4T1 cells and tumor-bearing mice. The construction of CTX-p-QM-1h-NLC effectively improved the solubility of p-QM-1h, enhanced its therapeutic efficacy and reduced its drug dosage. It also had a certain targeting ability, increasing drug aggregation in tumor tissues. Flow cytometry and Western blot results showed that CTX-p-QM-1h-NLC could effectively inhibit the expression of TrxR and increase the expression of Bax and caspase 3 in vivo, which was consistent with the increase in ROS levels and the induction of apoptosis in 4T1 cells. These results indicated that the construction of CTX-p-QM-1h-NLC is worthy of further investigation. Full article

Background: Past workplace exposure to asbestos in combination with tobacco smoking has increased the risk of lung cancer for some residents in an area within the Friuli Venezia Giulia region, Northeast Italy. In light of studies showing that lung cancer screening (LCS) with low-dose computed tomography (LDCT) can reduce mortality, local stakeholders and decision-makers decided to assess the potential benefits, harms and cost-effectiveness of a single round of LCS with LDCT versus standard care among people aged 55 to 80 who were formerly exposed to asbestos and with at least 10 pack-years of smoking. Methods: An economic model was developed using a decision tree connected to a Markov cohort model. The primary outcome was the incremental cost per additional quality-adjusted life year (QALY). Other outcomes included the number of life years saved, the number of deaths averted and overdiagnosis. Results: Per 10,000 people screened, the intervention led to 395 additional QALYs (95% credible interval: 129 to 831) and incremental total costs of EUR 1,086,345 (95% credible interval: −852,607 to 2,155,826). The incremental cost per QALY gained was EUR 2750. There was a probability of cost-effectiveness of 99.5% relative to a threshold of EUR 25,000. Conclusions: The model estimated that the intervention was cost-effective. The model’s simplifications and limitations should be considered when interpreting the findings in relation to policy-making decisions. Further research could include the costs and benefits of incidental findings and could assess the cost-effectiveness of repeated rounds of screening for the same population. Full article

Background: Myocarditis is an uncommon but recognized adverse event following mRNA COVID-19 vaccination, with risk varying by age, sex, dose number, and vaccine product. Clarifying the magnitude of risk, clinical course, and recovery—relative to myocarditis following SARS-CoV-2 infection—is essential for risk–benefit assessment and public health guidance. Methods: We performed a systematic PubMed and Embase search (January 2020–December 2024) and synthesized cohort, registry, and surveillance data on myocarditis incidence and outcomes following mRNA COVID-19 vaccination. Outcomes included incidence, observed-to-expected (OE) or incidence rate (IRRs) ratios, hospitalization, and short-term recovery. Study selection followed PRISMA 2020 systematic review guidelines. Results: Myocarditis following mRNA COVID-19 vaccination was identified as a rare adverse event, most commonly occurring after the second dose and in younger male individuals. Across multiple cohort and registry-based studies, cases were generally mild and self-limited, with most patients recovering without complication. In contrast, myocarditis following SARS-CoV-2 infection was consistently associated with more severe outcomes, including higher rates of hospitalization and mortality. Conclusions: Vaccine-associated myocarditis is rare, typically mild, and self-limited, with excellent short-term recovery; vaccinated individuals also exhibit lower odds of in-hospital death and intubation. In contrast, infection-associated myocarditis is more frequent and severe. Overall, the benefit–risk profile of mRNA vaccination remains strongly favorable. Full article

Background: POLE-mutated endometrial carcinomas are associated with exceptionally favorable outcomes, forming the basis for treatment de-escalation in early-stage disease. Nevertheless, rare adverse clinical courses have been reported. This study describes an unusual case of late metastatic recurrence in a POLE-mutated tumor and provides a review of similar cases in the literature. Methods: We present a detailed clinical, radiological, pathological, and molecular description of a patient who developed metastatic recurrence 16 years after initial surgery. A systematic literature search was conducted to identify reports of recurrence, progression, or cancer-related death in POLE-mutated endometrial carcinoma, with extraction of recurrence patterns, genomic features, treatment, and outcomes. Results: The patient experienced sequential pulmonary, cerebral, and leptomeningeal metastases despite harboring a canonical POLE hotspot mutation, proficient mismatch repair status, wild-type TP53, no additional known driver mutation beyond PTEN alterations. The literature review identified a small number of similarly adverse cases. Reported recurrences were heterogeneous, though distant and occasionally central nervous system involvement were noted. Conclusions: While POLE-mutated tumors overall retain an excellent prognosis, rare cases may follow an atypical and aggressive course. Improved molecular annotation and integrated risk-stratification models are needed to better identify this minority of higher-risk patients. Full article