Search Results (353)

Prognostic scores that help allocate resources and time to the most critical patients could have potentially improved the response to the SARS-CoV-2 pandemic. We assessed the performance of five risk scores in predicting death or transfer to the intensive care unit (ICU) or sub-intensive care unit (SICU) in hospitalised patients with SARS-CoV-2 infection, with the three aims of retrospectively analysing the effectiveness of these tools, identifying frail patients at risk of death or complications due to infection, and applying these tools in the event of future pandemics. A retrospective observational study was conducted by evaluating data from patients hospitalised with SARS-CoV-2 infection. Among 134 patients considered, 119 were enrolled. All patients were adults, with a mean age of 64 years, and were hospitalised in the Infectious Diseases Division. We compared the five scores using receiver operating characteristic curves and calculation of the areas under the curve (AUCs) to determine their predictive performance. Four of the five scores demonstrated a high accuracy in predicting mortality among COVID-19-positive patients, with AUCs between 0.749 and 0.885. However, only two of the five scores showed good performance in predicting transfer to the ICU or SICU, with AUCs ranging from 0.740 to 0.802. The 4C Mortality Score and COVID-GRAM presented the highest performance for both outcomes. These two scores are easy to apply and low cost. They could still be used in clinical practice as predictive tools for frail and elderly patients with SARS-CoV-2 infection, as well as in the event of future pandemics. Full article

Background/Objectives: Lung cancer remains a major cause of cancer-related mortality, with regional differences in incidence and patient characteristics. This study aimed to verify and quantify a perceived dramatic increase in lung cancer cases at a Romanian center, identify distinct patient phenotypes using unsupervised machine learning, and characterize contributing factors, including demographic shifts, changes in the healthcare system, and geographic patterns. Methods: A comprehensive retrospective analysis of 4206 lung cancer patients admitted between 2013 and 2024 was conducted, with detailed molecular characterization of 398 patients from 2023 to 2024. Temporal trends were analyzed using statistical methods, while k-means clustering on 761 clinical features identified patient phenotypes. The geographic distribution, smoking patterns, respiratory comorbidities, and demographic factors were systematically characterized across the identified clusters. Results: We confirmed an 80.5% increase in lung cancer admissions between pre-pandemic (2013–2020) and post-pandemic (2022–2024) periods, exceeding the 51.1% increase in total hospital admissions and aligning with national Romanian trends. Five distinct patient clusters emerged: elderly never-smokers (28.9%) with the highest metastatic rates (44.3%), heavy-smoking males (27.4%), active smokers with comprehensive molecular testing (31.7%), young mixed-gender cohort (7.3%) with balanced demographics, and extreme heavy smokers (4.8%) concentrated in rural areas (52.6%) with severe comorbidity burden. Clusters demonstrated significant differences in age (p < 0.001), smoking intensity (p < 0.001), geographic distribution (p < 0.001), as well as molecular characteristics. COPD prevalence was exceptionally high (44.8–78.9%) across clusters, while COVID-19 history remained low (3.4–8.3%), suggesting a limited direct association between the pandemic and cancer. Conclusions: This study presents the first comprehensive machine learning-based stratification of lung cancer patients in Romania, confirming genuine epidemiological increases beyond healthcare system artifacts. The identification of five clinically meaningful phenotypes—particularly rural extreme smokers and age-stratified never-smokers—demonstrates the value of unsupervised clustering for regional healthcare planning. These findings establish frameworks for targeted screening programs, personalized treatment approaches, and resource allocation strategies tailored to specific high-risk populations while highlighting the potential of artificial intelligence in identifying actionable clinical patterns for the implementation of precision medicine. Full article

Understanding how hospital length of stay (LoS) evolves with successive SARS-CoV-2 variants is central to the multiscale modeling and forecasting of COVID-19 and other respiratory virus dynamics. Using records from 1249 COVID-19 patients admitted to Chungbuk National University Hospital (2021–2023), we quantified LoS across three distinct variant phases (Pre-Delta, Delta, and Omicron) and three age groups (0–39, 40–64, and 65+ years). A gamma-distributed multi-state model—capturing transitions between semi-critical and critical wards—incorporated variant phase and age as log-linear covariates. Parameters were estimated via maximum likelihood with 95% confidence intervals derived from bootstrap resampling, and Monte Carlo iterations yielded detailed LoS distributions. Omicron-phase stays were 5–8 days, shorter than the 10–14 days observed in earlier phases, reflecting improved treatment protocols and reduced virulence. Younger adults typically stayed 3–5 days, whereas older cohorts required 8–12 days, with prolonged admissions (over 30 days) clustering in the oldest group. These time-dependent transition probabilities can be integrated with real-time bed-availability alert systems, highlighting the need for variant-specific ward/ICU resource planning and underscoring the importance of targeted management for elderly patients during current and future pandemics. Full article

Background: Elderly patients with chronic lower respiratory diseases (CLRDs) demonstrate an increased susceptibility to complications arising from influenza. Influenza vaccination remains the most effective strategy against influenza-related diseases among elderly CLRD patients. This study aimed to evaluate the influenza vaccination status of older CLRD patients and the factors affecting influenza vaccination. Methods: Using population-based health registries, we analyzed the longitudinal uptake of influenza vaccination among elderly patients with CLRDs in Ningbo from the 2018/19 season to the 2022/23 season. A multivariate logistic regression analysis was performed to identify behavioral determinants influencing influenza vaccination among elderly CLRD patients under Ningbo’s post-pandemic free vaccination policy. Results: An average of 487,309 older patients with CLRDs were included in our analysis for each season. The influenza vaccination rate increased from 3.59% in 2018/19 to 43.32% in the 2022/23 influenza season. There was a significant increase in the proportion of timely influenza vaccinations prior to November 15, rising from 3.01% before the COVID-19 pandemic to 33.90% during the pandemic period. The multivariate logistic regression analysis indicated that both the COVID-19 pandemic and free vaccination policy significantly promoted influenza vaccine uptake. Older CLRD patients with comorbidities such as diabetes, hypertension, or cancer exhibited higher influenza vaccination coverage, whereas those who have experienced acute cardiovascular events showed a lower vaccination rate. Additionally, a prior vaccination history significantly influenced uptake. Conclusions: Despite the significant improvement in vaccination rates, coverage among elderly patients with CLRDs remains below the WHO target. Addressing this gap requires integrated interventions that combine expanding the population eligible for free vaccinations, community mobilization efforts, and effective communication regarding cardiovascular safety to mitigate vaccine hesitancy within high-risk groups. Full article

Elderly individuals infected with SARS-CoV-2 are at higher risk of developing cytokine storms and severe outcomes, yet specific biomarkers remain unclear. In this study, we investigated the alteration of primary bile acid metabolism in elderly patients with severe COVID-19 using untargeted metabolomics (n = 31), followed by targeted metabolomics to compare patients with disease progression (n = 16) to those without (n = 48). Significant reductions in chenodeoxycholic acid (CDCA) and glycochenodeoxycholic acid (GCDCA) levels were identified in severe cases, with GCDCA levels at admission correlating strongly with peak inflammatory markers. In vitro, CDCA, GCDCA, and their receptors, Farnesoid X Receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5), effectively inhibited the inflammatory response induced by SARS-CoV-2. NOD-like receptor pathway, activated by SARS-CoV-2, may modulate inflammatory cytokines under the treatment of CDCA, GCDCA, and TGR5. CDCA and GCDCA levels at admission predicted disease progression, suggesting their potential as biomarkers for severe COVID-19 in the elderly and highlighting their regulatory role in inflammation, pointing to new therapeutic avenues. Full article

Background: Prolongation of the QT interval is directly related to the risk of ventricular arrhythmias and sudden cardiac death. Age, comorbidities, and treatment schemes have been shown to influence its prolongation and may also significantly affect the course of SARS-CoV-2 infection. Fluoroquinolones, widely used during the COVID-19 pandemic, are known for their ability to prolong the QT interval. Risk of ventricular arrhythmias has also been reported in patients with infectious diseases, and this risk may have been associated with high levels of interleukin-6 (IL-6). Purpose: The aim of this study is to evaluate the effect of levofloxacin on the corrected QT interval in patients with COVID-19, as well as to identify sociodemographic, clinical, and biochemical parameters associated with QTc interval prolongation among patients with COVID-19. Patients and Methods: The medical records of 93 patients hospitalized for COVID-19 were retrospectively analyzed, focusing on the presence of comorbidities and treatment with levofloxacin. Selected sociodemographic, clinical, and biochemical parameters were then statistically analyzed, with emphasis on their effect on the corrected QTc interval. The QTc interval was calculated according to the Bazett formula. Results: Levofloxacin use was not significantly associated with QTc interval. Statistical analysis identified creatinine, heart failure and atrial fibrillation as significant predictors of QTc interval prolongation. The trends towards QTc interval prolongation observed with hypokalaemia and hypertension suggest that these factors may also contribute to QTc interval variability and should be taken into account when assessing arrhythmia risk. Conclusions: Our retrospective study indicates that QTc prolongation results from the interplay of multiple factors. Full article

Background/Objectives: During the COVID-19 pandemic, several antivirals were approved or repurposed, but their safety profiles have not been fully compared. Pharmacovigilance data help clarify how these drugs perform in real-world use. Methods: This study performed a comparative pharmacovigilance analysis of eight antivirals used or tested during the COVID-19 pandemic, based on individual case safety reports (ICSRs) retrieved from the EudraVigilance database, reported up to 9 February 2025 and extracted from the official platform on 12 February 2025. Adverse reactions were assessed by system organ class (SOC), demographic patterns, and seriousness, and disproportionality analysis (reporting odds ratio (ROR)) was conducted to identify potential safety signals. Results: A total of 64,776 ICSRs were analyzed. Among approved antivirals, nirmatrelvir/ritonavir (NTV/r) accounted for 13.4% (n = 8693) of reports, while remdesivir (RDV) represented 6.3% (n = 4105). Repurposed antivirals such as ribavirin and lopinavir/ritonavir dominated the dataset, together making up over 80% (n = 51,978) of all reports. RDV was associated with a high proportion of serious adverse events (84%, n = 3448), and showed consistent ROR signals in hepatobiliary, renal, cardiac, and general disorders, with values exceeding 2 in several comparisons. NTV/r displayed a milder overall profile, but with positive RORs for psychiatric disorders, gastrointestinal disorders, and product-related issues. The most affected SOCs across all drugs included general disorders (31.6%, n = 20,493), gastrointestinal (19.5%, n = 12,625), nervous system (17.8%, n = 11,511), and investigations (20.4%, n = 13,219). Demographic analysis showed that most events occurred in adults aged 18–64, with RDV more often reported in elderly patients and NTV/r more frequently associated with reports from female patients and non-healthcare reporters. Conclusions: This study highlights distinct pharmacovigilance profiles of COVID-19 antivirals and supports the role of real-world data in guiding safer therapeutic choices. Full article

The introduction of COVID-19 vaccinations has significantly altered the course of the pandemic by markedly reducing the number of severe infection cases, hospitalizations, and deaths due to COVID-19. Elderly individuals constitute a particularly vulnerable group at risk of severe disease progression, which is often related to decreased immune system effectiveness and comorbidities. Severe infection outcomes in vaccinated individuals, though substantially rarer than in the unimmunized population, can still lead to death due to underlying health conditions. This analysis aims to describe the population of elderly individuals who, despite being vaccinated, died from interstitial pneumonia complicating SARS-CoV-2 infection. Data on the infection course and co-existing diseases were obtained from the database of the Józef Struś Multispecialty City Hospital in Poznań, which was converted into a dedicated facility during the pandemic. The inclusion criteria for the analysis were being over 60 years of age on the day of hospital admission, confirmed pneumonia in radiological examination, COVID-19 infection confirmed by PCR test, and an adverse disease course resulting in death. Patients admitted to the hospital from 1 June 2021 to 31 December 2021 were analyzed. Out of all hospitalizations, only 18 individuals met the inclusion criteria. Given the small number of patients, the authors employed descriptive methods to illustrate the clinical states of the individual patients, presenting SARS-CoV-2 infection in the context of co-existing diseases that significantly affect prognosis. The qualitative analysis employed highlights the complex and multidimensional courses of severely ill COVID-19 patients more emphatically. Full article

Studies on the burden of COVID-19 cases in Colombia have focused on specific populations and short timeframes. A retrospective observational study was conducted on adult patients aged 18 diagnosed with COVID-19 who received inpatient and/or outpatient medical care at a large health maintenance organization, to evaluate the burden of COVID-19 cases in Colombia (from March 2020 to January 2023) and associations with demographic and clinical characteristics. COVID-19 cases were identified with ICD-10 codes and confirmed by a laboratory test. The statistical analysis focused on descriptors of the frequency of events. A multivariate regression model was used to identify factors associated with severe conditions and death. Of the 953,661 cases detected, most cases (~79%) were mild or moderate (handled as outpatients). There were 20.1% (N = 191,260) severe cases and 0.9% (N = 8841) critical cases. Most COVID patients were unvaccinated (94.6%) and had, on average, one comorbidity. Hypertension (19.1%), immunocompromised condition (23.8%), mental health conditions (15%), obesity (10.8%), and cancer (11.2%) were the common prevalent comorbidities. The presence of comorbidity increased the risk of severe or critical COVID-19. COVID-19 cases were associated with the lack of vaccination and comorbidities. Effective vaccination strategies are needed to reduce the burden of COVID-19 in Colombia and, considering budgetary constraints, it is advisable to prioritize the elderly or populations with underlying conditions. Full article

Background: Elderly patients infected with SARS-CoV-2 are at higher risk of developing cytokine storm and severe outcomes; however, specific immunological and proteomic biomarkers for early prediction remain unclear in this vulnerable group. Methods: We enrolled 182 elderly COVID-19 patients from the Chinese PLA General Hospital between November 2022 and April 2023, categorizing them based on progression to respiratory failure requiring mechanical ventilation (defined as severe progression). Olink proteomic analysis was performed on admission serum from 40 propensity score-matched samples, with differentially expressed proteins (DEPs) validated by cytometric bead array (CBA) in 178 patients. To predict severe progression, a model was developed using a 70% training set and validated on a 30% validation set. LASSO regression screened features followed by logistic regression and receiver operating characteristic (ROC) analysis to optimize the model by incrementally incorporating features ranked by random forest importance. Results: Elderly patients progressing to severe COVID-19 exhibited early immune dysregulation, including neutrophilia, lymphopenia, monocytopenia, elevated procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), as well as coagulation dysfunction and multi-organ injury. Proteomics identified a set of biomarkers, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and revealed disruptions in signaling pathways, including the mTOR and VEGF signaling pathways. The optimal predictive model, which incorporated PCT, IL-6, monocyte percentage, lymphocyte count, and TRAIL, achieved an area under curve (AUC) of 0.870 (0.729–1.000) during validation. TRAIL levels negatively correlated with fibrinogen (p < 0.05). Conclusions: Elderly COVID-19 patients with severe progression demonstrate early immune dysregulation, hyperinflammation, coagulation dysfunction, and multi-organ injury. The model we proposed effectively predicts disease progression in elderly COVID-19 patients, providing potential biomarkers for early clinical risk stratification in this vulnerable population. Full article

Background/Objectives: Chronic lower respiratory tract inflammation can result from exposure to bacterial particles, leading to the activation of the NLRP3 inflammasome pathway. These effects may cause irreversible respiratory damage, contributing to persistent lung injury and chronic obstructive pulmonary disease (COPD), as observed in long COVID or bacterial pneumonia in older adults’ patients. Given its profound impact, the NLRP3 inflammasome has emerged as a key therapeutic target for mitigating aberrant inflammatory responses. Methods: In this study, we investigated the anti-inflammatory effects of Kum Akha black rice, a functional food, on the attenuation of NLRP3 inflammasome pathway using lipopolysaccharide-induced A549 lung epithelial cells and a C57BL/6NJcl mouse model. The anthocyanin-rich fraction from Kum Akha black rice germ and bran extract (KA1-P1) was obtained using a solvent-partitioned extraction technique. Results: KA1-P1 exhibited a high anthocyanin content (74.63 ± 1.66 mg/g extract) as determined by the pH differential method. The HPLC analysis revealed cyanidin-3-O-glucoside (C3G: 45.58 ± 0.48 mg/g extract) and peonidin-3-O-glucoside (P3G: 6.92 ± 0.29 mg/g extract) as its anthocyanin’s active compounds. Additionally, KA1-P1 demonstrated strong antioxidant activity, as assessed by DPPH and ABTS assays. KA1-P1 (12.5–100 μg/mL) possessed inhibitory effects on LPS + ATP-induced A549 lung cells inflammation through the significant suppressions of NLRP3, IL-6, IL-1β, and IL-18 mRNA levels and the inhibition of cytokine secretions in a dose-dependent manner (p < 0.05). Mechanistic analysis revealed that KA1-P1 downregulated key proteins in the NLRP3 inflammasome pathway (NLRP3, ASC, pro-caspase-1, and cleaved-caspase-1). Furthermore, in vivo studies demonstrated that KA1-P1 significantly diminished LPS-induced lower respiratory inflammation in C57BL/6NJcl mice, as evidenced by the reduced bronchoalveolar lavage fluid and blood levels of inflammatory cytokines (IL-6, IL-1β, and IL-18) and diminished histopathological inflammatory lung lesions. Conclusions: Overall, our findings suggest that the anti-inflammatory properties of KA1-P1 may support its application as a functional supplement or promote the consumption of pigmented rice among the elderly to mitigate chronic lower respiratory tract inflammation mediated by the NLRP3 inflammasome pathway. Full article

Background: Squamoid eccrine ductal carcinoma (SEDC) is an exceedingly rare and aggressive cutaneous adnexal malignancy, with fewer than 100 reported cases. Its histopathologic overlap with squamous cell carcinoma (SCC) frequently leads to misdiagnosis, delaying appropriate management. Unlike SCC, SEDC exhibits biphasic differentiation, deep infiltration, and a high rate of perineural invasion, contributing to significant morbidity and poor long-term outcomes. Given the absence of standardized treatment protocols, managing SEDC remains a challenge. Case Presentation: We report an unusual case of an 80-year-old female presenting with progressive numbness, nasal deviation, and a subcutaneous indurated lesion in the left nasofacial region. The early neurological symptoms were an atypical feature, suggesting perineural invasion (PNI) before visible tumor progression. Initial histopathologic evaluation was inconclusive, raising suspicion of SCC, necessitating immunohistochemical analysis, which confirmed ductal differentiation, leading to the final diagnosis of SEDC. The patient underwent radical resection with intraoperative margin assessment (Mohs micrographic surgery; MMS) followed by adjuvant radiotherapy (62 Gy/31 fractions) due to high-risk features, including perineural and perivascular invasion. Despite initial disease control, a local recurrence involving the left orbit and nasal bone occurred 20 months postoperatively, demonstrating the aggressive nature of SEDC despite clear surgical margins and adjuvant therapy. Due to disease progression and refusal of further surgery, only palliative care was provided. During follow-up, the patient contracted COVID-19, further complicating her clinical status and contributing to her demise. While COVID-19 was not directly linked to SEDC progression, its impact on patient management was significant. Conclusions: This case underscores the diagnostic and therapeutic challenges of SEDC, emphasizing the need for early suspicion, extensive histopathologic assessment, and aggressive multimodal treatment. The importance of multidisciplinary management—particularly in elderly and immunocompromised patients—and long-term surveillance due to high recurrence risk and PNI is crucial. Full article

An exhausted antiviral immune response is observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-SARS-CoV-2 syndrome, also termed long COVID. In this study, potential mechanisms behind this exhaustion were investigated. First, the viral load of Epstein–Barr virus (EBV), human adenovirus (HAdV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV6), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was determined in sputum samples (n = 29) derived from ME/CFS patients (n = 13), healthy controls (n = 10), elderly healthy controls (n = 4), and immunosuppressed controls (n = 2). Secondly, autoantibodies (autoAbs) to type I interferon (IFN-I) in sputum were analyzed to possibly explain impaired viral immunity. We found that ME/CFS patients released EBV at a significantly higher level compared to controls (p = 0.0256). HHV6 was present in ~50% of all participants at the same level. HAdV was detected in two cases with immunosuppression and severe ME/CFS, respectively. HCMV and SARS-CoV-2 were found only in immunosuppressed controls. Notably, anti-IFN-I autoAbs in ME/CFS and controls did not differ, except in a severe ME/CFS case showing an increased level. We conclude that ME/CFS patients, compared to controls, have a significantly higher load of EBV. IFN-I autoAbs cannot explain IFN-I dysfunction, with the possible exception of severe cases, also reported in severe SARS-CoV-2. We forward that additional mechanisms, such as the viral evasion of IFN-I effect via the degradation of IFN-receptors, may be present in ME/CFS, which demands further studies. Full article

Background: Elderly patients with COVID-19 often exhibit a complex interplay between hypercoagulability and coagulopathy, key factors in determining the risk of severe complications and mortality. This study aimed to analyze coagulation and inflammatory markers to identify critical predictors of adverse outcomes in this vulnerable population. Material and Methods: The retrospective study was conducted on a sample of 1429 elderly patients (≥60 years) diagnosed with COVID-19, hospitalized in “Sf. Ap. Andrei” St. Apostle Andrew’s County Emergency Hospital in various wards between March 2020 and August 2022. Data were collected from medical records and included inflammatory markers (C-reactive protein, procalcitonin, ESR) and coagulation markers (prothrombin time, INR, fibrinogen, D-dimer). The SPSS 2.0 statistical software was used to conduct the study. Results:Coagulation markers: Prothrombin activity averaged 74.22%, below normal levels, indicating a heightened bleeding risk, while fibrinogen levels were significantly elevated (mean: 531.69 mg/dL), reflecting hypercoagulability. Prolonged prothrombin time (mean: 17.28 s) and elevated INR (International normalized ratio) (mean: 1.51) were associated with increased mortality, emphasizing their role in risk stratification. Elevated D-dimer levels (mean: 2.75 mg/L) further highlighted thromboembolic risks. Inflammatory markers: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) showed marked elevations (mean CRP: 92.09 mg/L, mean ESR: 58.47 mm/h), correlating with heightened systemic inflammation and poor outcomes. Bacterial infections: Elevated procalcitonin (mean: 1.98 ng/mL) suggested secondary bacterial infections, particularly in mechanically ventilated patients, significantly worsening prognosis. Conclusions: The duality of hypercoagulability and coagulopathy in elderly COVID-19 patients underscores the importance of consistently monitoring coagulation markers such as prothrombin time, INR, D-dimer, and fibrinogen. Simultaneously, elevated inflammatory markers and secondary bacterial infections require prompt therapeutic interventions. This study highlights the critical need for personalized management strategies to mitigate complications and reduce mortality in this high-risk population. Full article

Background and Objectives: This study aims to evaluate neurosurgery consultations for elderly patients during and following the COVID-19 pandemic. Materials and Methods: This study included patients aged 65 and older who were hospitalized in non-neurosurgery departments at Istinye University Gaziosmanpasa Medical Park Hospital and were referred for neurosurgery consultations between 1 April 2020 and 31 May 2024. Patients in the intensive care unit and emergency department were excluded. The period from 1 April 2020 to 30 April 2022 was defined as the pandemic period, and from 1 May 2022 to 31 May 2024 as the post-pandemic period. Results: A total of 123 patients were included in this study, with 57 from the pandemic period and 66 from the post-pandemic period. The average age during the pandemic period was 73.45 years (range: 65–93), compared to 71.09 years (range: 65–94) in the post-pandemic period. During the pandemic, 26.3% of patients were recommended for physical therapy and rehabilitation, 24.6% were advised to undergo surgery, 19.3% received neurology consultations, and 17.5% received medical treatment. In the post-pandemic period, 37.9% were recommended for surgery, 16.7% for neurology, 13.6% for physical therapy and rehabilitation, and 7.6% for medical treatment. Overall, 56.4% of patients accepted surgery. Conclusions: Despite the high prevalence of comorbidities in geriatric patients, appropriate neurosurgical referrals significantly improve treatment success, enhance quality of life and mobility, and reduce mortality. We therefore recommend earlier and more attentive referrals to neurosurgery for elderly patients with relevant symptoms to facilitate timely and effective interventions. Full article