Search Results (64)

Background/Objectives: The COVID-19 pandemic disrupted global cancer care. This study compared gastric cancer surgical outcomes before and during the pandemic in Turkey. We also aimed to analyze the impact of the pandemic and factors on survival and mortality in gastric cancer patients. Materials and Methods: This retrospective, multicenter cohort study included 324 patients from three tertiary centers in Turkey who underwent gastric cancer surgery between January 2018 and December 2022. Patients were stratified into Pre-COVID-19 (n = 150) and COVID-19 Era (n = 174) groups. Comprehensive demographic, surgical, pathological, and survival data were analyzed. To identify factors independently associated with postoperative mortality, a multivariable logistic regression model was applied. For evaluating predictors of long-term survival, multivariable Cox proportional hazards regression analysis was conducted. Results: The median time from diagnosis to surgery was comparable between groups, while the time from surgery to pathology report was significantly prolonged during the pandemic (p = 0.012). Laparoscopic surgery (p = 0.040) and near-total gastrectomy (p = 0.025) were more frequently performed in the Pre-COVID-19 group. Although survival rates between groups were similar (p = 0.964), follow-up duration was significantly shorter in the COVID-19 Era (p < 0.001). Comparison between survivor and non-survivor groups showed that several variables were significantly associated with mortality, including larger tumor size (p < 0.001), greater number of metastatic lymph nodes (p < 0.001), elevated preoperative CEA (p = 0.001), CA 19-9 (p < 0.001), poor tumor differentiation (p = 0.002), signet ring cell histology (p = 0.003), lymphovascular invasion (p < 0.001), and perineural invasion (p < 0.001). Multivariable logistic regression identified total gastrectomy (OR: 2.14), T4 tumor stage (OR: 2.93), N3 nodal status (OR: 2.87), and lymphovascular invasion (OR: 2.87) as independent predictors of postoperative mortality. Cox regression analysis revealed that combined tumor location (HR: 1.73), total gastrectomy (HR: 1.56), lymphovascular invasion (HR: 2.63), T4 tumor stage (HR: 1.93), N3 nodal status (HR: 1.71), and distant metastasis (HR: 1.74) were independently associated with decreased overall survival. Conclusions: Although gastric cancer surgery continued during the COVID-19 pandemic, some delays in pathology reporting were observed; however, these did not significantly affect the timing of adjuvant therapy or patient outcomes. Importantly, pandemic timing was not identified as an independent risk factor for mortality in multivariable logistic regression analysis, nor for survival in multivariable Cox regression analysis. Instead, tumor burden and aggressiveness—specifically advanced stage, lymphovascular invasion, and total gastrectomy—remained the primary independent determinants of poor prognosis. While pandemic-related workflow delays occurred, institutional adaptability preserved oncologic outcomes. Full article

Background: Gastric signet-ring cell carcinoma (GSRCC) is associated with a poor prognosis, and the effectiveness of neoadjuvant chemotherapy (NAC) in improving survival outcomes remains inconclusive. This study aimed to evaluate the impact of NAC on survival in patients with GSRCC. Methods: This retrospective cohort study included GSRCC patients from two databases: the National Cancer Center (n = 1289) and SEER (n = 1773), all of whom underwent radical surgery between January 2011 and January 2018. The primary endpoint was overall survival (OS) after surgery. Kaplan–Meier survival curves were generated, and multivariate Cox regression analyses were performed to adjust for confounding factors. Additionally, subgroup analyses were conducted to assess the potential survival benefits of NAC in specific patient subsets. Results: NAC use was limited, with 24.6% (436/1773) of patients in the SEER cohort and 22.6% (292/1289) of patients in the NCC cohort receiving NAC. The median follow-up duration was 30 months (range: 8–131 months; IQR: 24–70 months). In the SEER cohort, the 3-year and 5-year survival rates were 47.4% and 41.3%, respectively, whereas in the NCC cohort, they were 82.4% and 73.9%. Multivariate analysis identified race, tumor size, cTNM stage, pT stage, and pN stage as independent predictors of survival in the SEER cohort (all p < 0.05). In the NCC cohort, age, tumor size, and cTNM stage were significant predictors (p < 0.05). NAC did not demonstrate a significant OS benefit in either cohort (SEER: p = 0.653; NCC: p = 0.139). Subgroup analyses focusing on mid/distal tumor locations and cTNM stages II/III indicated a significant trend towards improved survival with NAC (all p < 0.001). Conclusions: NAC showed limited efficacy in unselected GSRCC patients. However, its selective application in patients with mid/distal tumors or locally advanced tumors (cTNM II/III) may offer potential survival benefits. Further studies are needed to explore tailored NAC strategies as a means to improve outcomes in this highly aggressive cancer. Full article

Background: Gastric signet-ring cell carcinoma (GSRCC) is an aggressive gastric cancer subtype with limited evidence supporting the role of neoadjuvant chemotherapy (NAC). This study evaluated the impact of NAC on overall survival (OS) in a large, population-based cohort. Methods: We analyzed data from the SEER database (2011–2018), identifying patients aged 20–80 years with primary gastric tumors (C16.0–C16.9) and signet-ring cell histology who underwent curative-intent gastrectomy. Patients with metastatic disease, non-curative surgery, clinical Stage I, incomplete staging, or unknown survival were excluded. OS was assessed using Kaplan–Meier analysis and multivariable Cox regression. Subgroup analyses evaluated the interaction of NAC with tumor location and clinical stage. Results: A total of 978 patients met inclusion criteria; 436 (44.6%) received NAC. The 3- and 5-year OS rates were 43.9% and 38.3%, respectively. NAC was not associated with improved OS compared to surgery alone (5-year OS: 39.7% vs. 37.2%; log-rank p = 0.34) and was not an independent prognostic factor in multivariable analysis (p = 0.651). Independent predictors of worse OS included larger tumor size, advanced stage, positive nodal status, and Black race (all p < 0.05). Subgroup analysis indicated a survival benefit from NAC in patients with mid or distal gastric tumors (p < 0.001 for interaction). Conclusions: In this SEER-based analysis, NAC did not improve OS in the overall GSRCC population. However, selected subgroups may derive benefit, supporting a personalized approach to neoadjuvant therapy in GSRCC. Full article

Introduction: Prosthesis-patient mismatch (PPM) in surgical aortic valve replacement (SAVR) is known to be a poor prognostic factor. However, the parameters for preventing postoperative PPM in SAVR have not been established. Materials and Methods: Two hundred and five patients (mean age 72.5 ± 7.4 years, 129 males) who underwent SAVR were analyzed. Preoperatively, we determined the recommended prosthesis valve size from the mean aortic valve (AV) diameter derived from the AV annulus area by preoperative three-dimensional transesophageal echocardiography (3D-TEE). We investigated the association between pre- and postoperative changes in annulus diameter and the occurrence of PPM. Results: PPM was present in 6 patients (2.9%). Pre- and postoperative AV annulus diameter change ratio was greater in the group with PPM than in that without PPM (10.4 ± 3.6% vs. 3.0 ± 5.6%, p = 0.002). The use of prosthetic valve rings smaller than the recommended size was higher in the group with PPM than in that without PPM. (83.3% vs. 20.6%, p = 0.002). On multivariate logistic regression analysis, use of a valve smaller than the recommended size was an independent predictor of PPM (odds ratio 19.3, 95% confidence interval 2.14–174.5, p = 0.008). Conclusions: The recommended prosthetic AV size based on preoperative 3D-TEE is useful for determining the optimal prosthetic AV size to prevent PPM after SAVR. Full article

Background/Objectives: Metastatic prostate cancer remains a major clinical challenge, with limited therapeutic options. Doxycycline, a tetracycline antibiotic with anti-inflammatory properties, has shown potential as an adjunctive therapy. This study aimed to evaluate its efficacy in reducing prostate-specific antigen (PSA) levels and improving quality of life in patients receiving standard treatment for metastatic prostate cancer. Methods: This phase II, double-blind, randomized controlled trial included 45 participants (aged 57–81 years) assigned to doxycycline (100 mg daily) or a placebo for six months. The primary outcome was the percentage change in PSA levels at 3 and 6 months. Secondary outcomes included quality of life (EQ-5D-5L), cognitive function (Mini-Mental State Examination), and glucose levels. Additionally, a structure–activity relationship (SAR) analysis was performed through an extensive bibliographic review to identify pharmacophores responsible for doxycycline’s biological activity, particularly its tetracyclic core. The SAR analysis included tetracyclines and derivatives, androgen-targeting agents, and other pharmacologically relevant molecules used in prostate cancer therapy. Statistical analysis was conducted using multivariate logistic regression. Results: At six months, the doxycycline group showed a median PSA reduction of 60% compared to 10% in the placebo group (p = 0.043). A ≥50% reduction in PSA levels was observed in 71.4% of patients receiving doxycycline versus 20.8% in the placebo group (p = 0.001), with an adjusted relative risk of 10.309 (95% CI: 2.359–45.055, p = 0.002). Quality of life improved, with 7.1% of doxycycline-treated patients reporting poor quality of life compared to 42.9% in the placebo group (p = 0.028). A slight improvement in cognitive function was also noted (p = 0.037). SAR analysis suggested that the tetracyclic ring of doxycycline may play a crucial role in its observed biological effects. Conclusions: Doxycycline demonstrates potential as an adjunctive therapy in metastatic prostate cancer by reducing PSA levels and improving quality of life. The SAR analysis supports the hypothesis that its tetracyclic structure may be responsible for its therapeutic effects. Further large-scale trials are warranted to confirm these findings. Full article

Kaposi’s Sarcoma Herpesvirus (KSHV) is the causative agent of several human diseases. There are few effective treatments available to treat infection and KSHV oncogenesis. Disrupting the KSHV infectious cycle would diminish the viral spread. The KSHV lytic phase and production of new virions require efficient copying and packaging of the KSHV genome. KSHV encodes its own lytic DNA replication machinery, including the processivity factor (PF-8), which presents itself as an attractive target for antiviral development. We characterized PF-8 at the single molecule level using transmission electron microscopy to identify key molecular interactions that mediate viral DNA replication initiation. Our results indicate that PF-8 forms oligomeric ring structures (tetramer, hexamer, and/or dodecamer) similar to the related Epstein–Barr virus processivity factor (BMRF1). Our DNA positional mapping revealed high-frequency binding locations of PF-8 within the lytic origin of replication (OriLyt). A multi-variable analysis of PF-8 DNA-binding activity with three mutant OriLyts provides new insights into the mechanisms that PF-8 associates with viral DNA and complexes to form multi-ring-like structures. Collectively, these data enhance the mechanistic understanding of the molecular interactions (protein–protein and protein-DNA) of an essential KSHV DNA replication protein. Full article

Impaired glucose tolerance (IGT), a prediabetic state, is a known risk factor for coronary artery disease (CAD). Low-attenuation plaque (LAP) lesions are associated with a high risk of coronary events. We aimed to evaluate high-risk plaque characteristics in LAP lesions between patients with IGT and normal glucose tolerance (NGT) in patients suspected for stable CAD. Coronary computed tomography angiography (CCTA) identified LAP lesions and assessed plaque volumes, burdens, and high-risk plaque features. Glycemic tolerance was stratified using oral glucose tolerance tests. Among 148 patients, 202 LAP lesions were identified, with 93 patients classified as NGT and 55 as IGT. Patients with IGT had a significantly higher prevalence of LAP lesions compared with NGT (p = 0.007). LAP volume was higher in IGT (16.46 ± 12.52 mm³) compared with NGT (12.66 ± 9.72 mm³, p = 0.01), but this association did not persist in multivariate analysis. The LAP burden was greater in IGT (10.79 ± 6.84%) than NGT (8.62 ± 5.93%, p = 0.02), and the napkin-ring sign was more frequent in IGT (12%) versus NGT (5%, p = 0.02); these associations remained significant in multivariate analysis. Patients with IGT had a higher LAP burden and higher frequency of napkin-ring signs. These findings may help explain the common occurrence of prediabetes in patients with acute myocardial infarction. Full article

The main aim of the present study was to uncover multivariate relationships between sleep quantity and quality using principal component analysis (PCA) in professional female soccer players. A second aim was to examine the extent to which objective sleep quantity and quality variables can discriminate between perceived sleep. Ten objective sleep variables from the multisensory sleep-tracker were analyzed. PCA was conducted on the sleep variables, and meaningful principal components (PCs) were identified (eigenvalue > 2). Two sleep PCs were identified, representing the ‘quantity of sleep’ (quantity PC: eigenvalue = 4.1 and variance explained = 45.1%) and the ‘quality of sleep’ (quality PC: eigenvalue = 2.4 and variance explained = 24.1%). Cluster analysis grouped the players’ sleep into three types: long and efficient, short and efficient, and long and inefficient; however, no association was found between the perceived sleep and the sleep clusters. In conclusion, a combination of both quantity and quality sleep metrics is recommended for sleep monitoring of professional female soccer players. Players should undergo a training process to improve self-assessment of sleep quality recorded from a subjective questionnaire, contrasting the perceived information with the sleep quality recorded objectively during a defined period in order to optimize the validity of their perceptions. The aim is to optimize the validity of their perceptions of sleep quality. Full article

Crown ether is widely used in water purification because of its ring structure and good selective adsorption of specific heavy metals. However, its high cost and difficulty in recycling limit the purification of heavy metals in water. The anisotropic [2,4]-dibenzo-18-crown-6-modified bamboo pulp aerogel (DB18C6/PA) is successfully synthesized by microwave irradiation and directional freezing technology. The physical and chemical properties of DB18C6/PA are analyzed by FTIR, XPS, SEM, TEM, TGA, surface area and porosity analyzers. Single or multivariate systems containing Pb²⁺, Cu²⁺ and Cd²⁺ are used as adsorbents. The effects of the DB18C6 addition amount, pH, initial concentration and adsorption temperature on the adsorption of DB18C6/PA are systematically explored. Pseudo-first-order kinetic models, pseudo-second-order kinetic models and the isothermal adsorption models of Langmuir and Freundlich are used to fit the experimental data. The adsorption selectivity is analyzed from the distribution coefficient and the separation factor, and the adsorption mechanism is discussed. The results show that anisotropic DB18C6/PA has the characteristics of 3D directional channels, high porosity (97.67%), large specific surface area (103.7 m²/g), good thermal stability and regeneration (the number of cycles is greater than 5). The surface has a variety of functional groups, including a hydroxyl group, aldehyde group, ether bond, etc. In the single and multivariate systems of Pb²⁺, Cu²⁺ and Cd²⁺, the adsorption process of DB18C6/PA conforms to the pseudo-second-order kinetic model, and the results conform to the Freundlich adsorption isothermal model (a few of them conformed to the Langmuir adsorption isothermal model), indicating that chemical adsorption and physical adsorption are involved in the adsorption process, and the adsorption process is a spontaneous endothermic process. In the single solution system, the maximum adsorption capacities of Pb²⁺, Cu²⁺ and Cd²⁺ by DB18C6/PA are 129.15, 29.85 and 27.89 mg/g, respectively. The adsorption selectivity of DB18C6/PA on Pb²⁺, Cu²⁺ and Cd²⁺ is in the order of Pb²⁺ >> Cu²⁺ > Cd²⁺. Full article

Background/Objectives: The complications of hypertension depend not only on the mean blood pressure (BP) but also on its variability (BPV). Recent studies suggest that the choroid may serve as an indicator of systemic vascular damage. These studies have been made possible by the increased availability of optical coherence tomography (OCT). The aim of our study was to analyze the relationship between short-term BP variability (STBPV) and choroid–retinal thickness in hypertensive patients. Methods: A total of 98 patients with a mean age of 49 ± 12 years were enrolled in the study. All participants underwent 24 h blood pressure (BP) monitoring to measure 24 h mean systolic (SBP) and diastolic blood pressure (DBP), along with their respective standard deviations (SD), the weighted SD of 24 h SBP and DBP, and the average real variability (ARV) of 24 h SBP and DBP. The choroid–retinal region was assessed using Swept-Source OCT, with choroidal thickness (ChT) and retinal thickness divided into three concentric rings, and their mean choroidal thickness (ChT-or) was calculated. Results: The choroidal thickness of the concentric rings was found to be inversely correlated with all ARV values of the monitored blood pressure means. In particular, a correlation was observed between the ARV of daytime DBP and ChT-or. This correlation remained statistically significant (β = −0.34; p = 0.02) even after adjustment for various confounding factors. The ARV of daytime DBP was the only STBPV index to maintain a significant association, in the multivariate analysis, with the central ring mean thickness (β = −0.314; p = 0.001) and the inner choroidal ring mean thickness (β = −0.262; p = 0.003). Conclusions: Our study demonstrated an independent negative association between short-term BP variability (STBPV), when expressed as ARV of daytime DBP, and choroidal thickness. This finding confirms the value of choroidal thickness as a marker of cardiovascular risk. Full article

The accurate diagnosis and classification of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are challenging due to the overlapping pathological and molecular features of myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). We investigated the genomic landscape in different MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 97), atypical chronic myeloid leukemia (aCML; n = 8), MDS/MPN-unclassified (MDS/MPN-U; n = 44), and MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 12). Our study indicated that MDS/MPN is characterized by mutations commonly identified in myeloid neoplasms, with TET2 (52%) being the most frequently mutated gene, followed by ASXL1 (38.7%), SRSF2 (34.7%), and JAK2 (19.7%), among others. However, the distribution of recurrent mutations differs across the MDS/MPN subtypes. We confirmed that specific gene combinations correlate with specific MDS/MPN subtypes (e.g., TET2/SRSF2 in CMML, ASXL1/SETBP1 in aCML, and SF3B1/JAK2 in MDS/MPN-RS-T), with MDS/MPN-U being the most heterogeneous. Furthermore, we found that older age (≥65 years) and mutations in RUNX1 and TP53 were associated with poorer clinical outcomes in CMML (p < 0.05) by multivariate analysis. In MDS/MPN-U, CBL mutations (p < 0.05) were the sole negative prognostic factors identified in our study by multivariate analysis (p < 0.05). Overall, our study provides genetic insights into various MDS/MPN subtypes, which may aid in diagnosis and clinical decision-making for patients with MDS/MPN. Full article

Currently there are several precipitation reconstructions for northern Mexico; however, there is a lack of temperature reconstructions to understand past climate change, the impact on ecosystems and societies, etc. The central region of Chihuahua is located in a transition zone between the Sierra Madre Occidental and the Great Northern Plain, characterized by extreme temperatures and marked seasonal variability. The objectives of this study were (1) to generate a climatic association between variables from reanalysis models and the earlywood series for the center of Chihuahua, (2) to generate a reconstruction of mean temperature, (3) to determine extreme events, and (4) to identify the influence of ocean–atmosphere phenomena. Chronologies were downloaded from the International Tree-Ring Data Bank and climate information from the NLDAS-2 and ClimateNA reanalysis models. The response function was performed using climate models and regional dendrochronological series. A reconstruction of mean temperature was generated, and extreme periods were identified. The representativeness of the reconstruction was evaluated through spatial correlation, and low-frequency events were determined through multitaper spectral analysis and wavelet analysis. The influence of ocean–atmosphere phenomena on temperature reconstruction was analyzed using Pearson correlation, and the influence of ENSO was examined through wavelet coherence analysis. Highly significant correlations were found for maximum, minimum, and mean temperature, as well as for precipitation and relative humidity, before and after the growth year. However, the seasonal period with the highest correlation was found from May to June for mean temperature, which was used to generate the reconstruction from 1775 to 2022. The most extreme periods were 1775, 1801, 1805, 1860, 1892–1894, 1951, 1953–1954, and 2011–2012. Spectral analysis showed significant frequencies of 56.53 and 2.09 years, and wavelet analysis from 0 to 2 years from 1970 to 1980, from 8 to 11 years from 1890 to 1910, and from 30 to 70 years from 1860 to 2022. A significant association was found with the Multivariate ENSO Index phenomenon (r = 0.40; p = 0.009) and Pacific Decadal Oscillation (r = −0.38; p = 0.000). Regarding the ENSO phenomenon, an antiphase association of r = −0.34; p = 0.000 was found, with significant periods of 1 to 4 years from 1770 to 1800, 1845 to 1850, and 1860 to 1900, with periods of 6 to 10 years from 1875 to 1920, and from 6 to 8 years from 1990 to 2000. This study allowed a reconstruction of mean temperature through reanalysis data, as well as a historical characterization of temperature for central Chihuahua beyond the observed records. Full article

Background and Purpose: The extent of resection is the most important prognostic factor in patients with glioblastoma. However, the factors influencing the decision to perform a biopsy instead of maximal resection have not been clearly established. The aim of this study was to analyze the factors associated with the intention to achieve maximal resection in glioblastoma patients. Methods: A retrospective single-center case-series analysis of patients with a new diagnosis of glioblastoma was performed. Patients were distributed into two groups: the biopsy (B) and complete resection (CR) groups. To identify factors associated with the decision to perform a B or CR, uni- and multivariate binary logistic regression analyses were performed. Cox regression analysis was also performed in the B and CR groups. Results: Ninety-nine patients with a new diagnosis of glioblastoma were included. Sixty-eight patients (68.7%) were treated with CR. Ring-enhancement and edema volume on presurgical magnetic resonance imaging were both associated with CR. Corpus callosum involvement and proximity to the internal capsule were identified as factors associated with the decision to perform a biopsy. In the multivariate analysis, edema volume (OR = 1.031; p = 0.002) and proximity to the internal capsule (OR = 0.104; p = 0.001) maintained significance and were considered independent factors. In the survival analysis, only corpus callosum involvement (HR = 2.055; p = 0.035) and MGMT status (HR = 0.484; p = 0.027) presented statistical significance in the CR group. Conclusions: The volume of edema and proximity to the internal capsule were identified as independent factors associated with the surgical decision. The radiological evaluation and not the clinical situation of the patient influences the decision to perform a biopsy or CR. Full article

1,4-dihydropyridines (1,4-DHPs) are widely recognized as highly effective L-type calcium channel blockers with significant therapeutic benefits in the treatment of cardiovascular disorders. 1,4-DHPs can also target T-type calcium channels, making them promising drug candidates for neurological conditions. When exposed to light, all 1,4-DHPs tend to easily degrade, leading to an oxidation product derived from the aromatization of the dihydropyridine ring. Herein, the elaboration of a quantitative structure–property relationships (QSPR) model was carried out by correlating the light sensitivity of structurally different 1,4-DHPs with theoretical molecular descriptors. Photodegradation experiments were performed by exposing the drugs to a Xenon lamp following the ICH rules. The degradation was monitored by spectrophotometry, and experimental data were elaborated by Multivariate Curve Resolution (MCR) methodologies to assess the kinetic rates. The results were confirmed by the HPLC-DAD method. PaDEL-Descriptor software was used to calculate molecular descriptors and fingerprints related to the chemical structures. Seventeen of the 1875 molecular descriptors were selected and correlated to the photodegradation rate by means of the Ordinary Least Squares (OLS) algorithm. The chemometric model is useful to predict the photosensitivity of other 1,4-DHP derivatives with a very low relative error percentage of 5.03% and represents an effective tool to design new analogs characterized by higher photostability. Full article

To optimize mitral valve repair outcomes, it is crucial to comprehend the predictors of functional mitral valve stenosis (FMS), to enhance preoperative assessments, and to adapt intraoperative treatment strategies. This study aimed to identify FMS risk factors, contributing valuable insights for refining surgical techniques. Among 228 selected patients, 215 underwent postoperative echocardiography follow-ups, and 36 met the FMS criteria based on a mean trans-mitral pressure gradient of >5 mmHg. Patients with FMS exhibited higher pulmonary systolic arterial pressure and increased late mortality during the follow-up. Univariable logistic regression analysis identified several risk factors for FMS, including end-stage renal disease, anterior leaflet lesion, concomitant aortic valve replacement, smaller ring size, ring type, and neochordae implantation. Conversely, resection alone and resection combined with neochordae implantation had protective effects against FMS. Multivariable logistic regression analysis revealed that smaller ring sizes and patch repair independently predicted FMS. When focusing on degenerative mitral regurgitation, the neochordae implantation without resection in leaflet repair, emerged as an independent predictor of FMS. Surgeons should weigh the substantial impact of surgical procedures on postoperative trans-mitral pressure gradients, emphasizing preoperative evaluation and techniques such as precise ring size assessment and effective leaflet management. Full article