Search Results (1,385)

Introduction: Esophagectomy has traditionally been considered mandatory after neoadjuvant therapy for locally advanced esophageal cancer. However, recent evidence has challenged this paradigm and motivated interest in organ-preservation strategies with active surveillance in patients achieving clinical complete response (cCR). Methods: A literature search was performed using PubMed/MEDLINE, ScienceDirect, and Embase databases to identify relevant studies related to non-operative management (NOM) of esophageal cancer. Evidence was synthesized qualitatively with a critical focus on the biological rationale of NOM, diagnostic limitations of response-assessment, oncologic outcomes associated with surveillance strategies and the evolving role of molecular biomarkers. Results: The safety of NOM with active surveillance is tightly linked to the diagnostic accuracy of response assessment. Although structured multimodal response assessment protocols combining endoscopy, endoscopic ultrasound, and PET-CT have shown acceptable performance, residual clinically undetectable disease might persist in some patients. Evidence from the SANO trial has suggested non-inferior short-term survival outcomes of NOM compared with immediate esophagectomy in carefully selected patients with cCR after neoadjuvant chemoradiotherapy treated within specialized centers. Nevertheless, long-term oncologic outcomes remain unknown, and uncertainty persists regarding the broader applicability of this strategy outside specialized multidisciplinary settings. Emerging biomarker-driven approaches including PD-L1 expression, microsatellite instability, and circulating tumor DNA (ctDNA) may further refine response assessment and help identify patients most suitable for organ-preservation strategies. Conclusions: Active surveillance represents a promising alternative to immediate esophagectomy in selected patients with cCR after neoadjuvant therapy. However, further studies with longer follow-up and standardized surveillance protocols are still needed to safely implement this strategy outside trial settings. Full article

Cryptococcosis is associated with negative serum (1→3)-β-D-glucan (BDG) results, but the clinical significance of serum BDG (sBDG) positivity is unclear. We characterized the clinical features of sBDG-positive cryptococcosis in patients with cryptococcal disease. We measured the sBDG levels and classified patients as BDG-positive (>11 pg/mL) or BDG-negative. Clinical characteristics, diagnostic modalities, antifungal treatment, post-treatment BDG level changes, and 90-day cryptococcosis-related mortality were compared. BDG-positive patients showed disseminated cryptococcosis, higher inflammatory marker levels, lower serum albumin levels, higher culture positivity rates, and higher cryptococcal antigen titers than BDG-negative patients. Combination antifungal therapy was administered more frequently in the BDG-positive group; repeat measurements in 15 patients showed a significant decrease in sBDG levels. The 90-day mortality rate was significantly higher in the BDG-positive than in the BDG-negative group (37.5% vs. 3.9%), and overall survival was significantly lower. sBDG levels may be elevated in cases of disseminated or severe disease. Serum BDG positivity may reflect a higher fungal burden, greater disease severity, and poorer short-term outcomes. Full article

The coexistence of cancer and severe aortic stenosis (AS) is increasing as a result of population aging and substantial improvements in cancer survival. Transcatheter aortic valve implantation (TAVI) has transformed the management of AS; however, patients with active malignancy or a history of cancer remain markedly under-represented in pivotal randomized trials. This under-representation has resulted in persistent uncertainty regarding patient selection, risk stratification, and the expected benefit of TAVI in this growing and clinically heterogeneous population. This review provides a comprehensive and contemporary synthesis of the evidence on TAVI in patients with cancer, integrating cardiovascular (CV), oncologic, and geriatric perspectives. Available data on epidemiological overlap, cancer-specific procedural challenges, and short- and long-term outcomes following TAVI are critically examined, with particular emphasis on distinctions between active cancer and cancer survivorship. Key modifiers of risk and benefit—including prior thoracic radiotherapy, competing thrombotic and bleeding risk, immunosuppression, frailty, sarcopenia, and nutritional status—are discussed in detail. Limitations of conventional surgical risk scores in oncology populations are highlighted, underscoring the need for individualized assessment beyond traditional CV metrics. Across registries and meta-analyses, TAVI is associated with high procedural success and comparable short-term outcomes in patients with and without cancer. Excess mortality observed during mid- and long-term follow-up is driven predominantly by non-CV causes related to malignancy rather than valve-related complications. Importantly, patients with cancer in remission demonstrate outcomes similar to those of non-cancer populations, whereas prognosis in active cancer is strongly influenced by disease stage, biology, and competing risks. Overall, cancer diagnosis alone should not preclude consideration of TAVI. Optimal management requires multidisciplinary, goal-oriented decision-making that integrates oncologic prognosis, functional status, and patients’ priorities. As cancer survivorship continues to expand, prospective studies, integrated risk stratification tools, and closer alignment between cardio-oncology and structural heart programs are essential to guide evidence-based and equitable care. Full article

Background: Accurate prognostication in terminal cancer patients receiving best supportive care (BSC) is essential for guiding end-of-life decision-making and avoiding non-beneficial interventions. Several prognostic models have been developed for advanced cancer, including the Palliative Prognostic Index (PPI) and the Objective Prognostic Score (OPS). However, prospective data evaluating their performance specifically in patients managed with BSC are limited. This study evaluated the prognostic performance of PPI and OPS in terminal cancer patients receiving BSC. It also examined whether their combined use provides additional value for short-term mortality risk stratification. Methods: This prospective observational cohort study included hospitalized adult patients with terminal-stage cancer and a documented BSC decision. Terminal-stage cancer was operationally defined as stage IV malignancy with poor performance status and no remaining feasible disease-directed oncological treatment option due to severe clinical deterioration and/or major organ dysfunction. Patients were prospectively enrolled from 12 April 2024 to 13 December 2024 and followed until death. Eligible patients had poor Eastern Cooperative Oncology Group performance status (ECOG 3–4) and had not received oncologic treatment within the preceding month. PPI and OPS were calculated at baseline using predefined criteria. Survival time was defined as the interval between baseline assessment and death. The prognostic performance of the scores for 3-, 4-, and 6-week mortality was evaluated, and survival outcomes were analyzed using standard survival analysis methods. Results: A total of 112 patients were included in the final analysis. The mean age was 62.3 ± 12.3 years; 66 patients (58.9%) were male and 46 (41.1%) were female. The most common primary tumor sites were colon cancer (20.5%), non-small cell lung cancer (17.0%), and gastric cancer (15.2%). Both PPI > 6 and OPS ≥ 3 were associated with higher short-term mortality, although their individual discriminatory performance was modest. The combined OPS–PPI approach showed statistically significant but still modest discrimination at all time points. Although this difference was limited, the combined approach supported the stratification of a clinically relevant subgroup at particularly high risk of imminent death. Patients with both OPS ≥ 3 and PPI > 6 had the poorest survival, with a median overall survival (OS) of 11 days. In multivariable Cox regression analysis, the combined high-risk group remained independently associated with poorer OS (HR 1.53, 95% CI 1.01–2.31; p = 0.046). Conclusions: Although the individual discriminatory performance of PPI and OPS was modest, their combined use may provide additional risk stratification value and may help identify patients at particularly high risk of short-term mortality among terminal cancer patients receiving BSC. These findings should be interpreted as supporting bedside risk stratification rather than indicating a definitive individual-level prediction model. Full article

This study reports, for the first time, changes in the microbiome community associated with anhydrobiosis in two tardigrade species of the genus Paramacrobiotus. To identify bacteria linked to the anhydrobiosis phenomenon and to track microbiome changes under anhydrobiotic stress, next-generation sequencing of bacterial 16S rRNA genes was conducted. Microbiome profiling was performed across various developmental and physiological stages of tardigrades, including: eggs; active adult specimens (both before and after 7, and 120 days of anhydrobiosis, referred to as short- and long-term anhydrobiosis, respectively); specimens in the desiccated tun stage; dead specimens following long-term anhydrobiosis (no dead specimens were observed after short-term anhydrobiosis); and the culture medium. It was shown that the microbiome community varied among stages, with high stage-specificity. Several bacterial genera were identified that may assist the host during anhydrobiosis, potentially through biofilm formation and by supporting stress-protective mechanisms such as heat shock protein expression and trehalose synthesis in eggs and tuns. These findings reveal that microbiota may contribute to anhydrobiotic survival in tardigrades, providing novel insights into host–microbe interactions under extreme environmental stress. Full article

Background: Splenic flexure colon cancer (SFCC) is a relatively rare subtype of colon cancer, and the optimal extent of resection and safety of laparoscopic surgery remain controversial. We conducted a multicenter comparative analysis to evaluate the short- and long-term outcomes of laparoscopic segmental left colectomy (LC) for SFCC using laparoscopic anterior resection (AR) as a comparator. Methods: We retrospectively reviewed patients with stage I–III colon cancer involving the distal transverse to sigmoid colon who underwent laparoscopic surgery at four hospitals between March 2004 and December 2020. SFCC was defined as tumors between the distal transverse and proximal descending colon. Outcomes were compared between the AR group (laparoscopic anterior resection for descending to sigmoid colon cancer) and the LC group (laparoscopic segmental left colectomy for SFCC) using propensity score matching. Results: A total of 1889 patients were included in the AR group and 271 in the LC group. The median follow-up was 60 months. After 2:1 propensity score matching, baseline clinicopathologic characteristics were comparable between groups. Operative time was longer in the LC group. Overall complication rates were similar, except for a higher incidence of postoperative ileus in the LC group, while overall 30-day morbidity did not differ. Five-year disease-free survival and overall survival were comparable, with no significant differences in stage-stratified analyses. Conclusions: Laparoscopic segmental left colectomy for SFCC achieved short- and long-term outcomes comparable to laparoscopic anterior resection for descending and sigmoid colon cancer, supporting it as a safe and oncologically feasible option. Full article

Background: Acute respiratory distress syndrome (ARDS), particularly in COVID-19–related severe respiratory failure, remains a major challenge in intensive care. Flow-controlled ventilation (FCV) may improve gas exchange by enabling precise airway pressure control; however, clinical data on its prolonged use in ARDS are limited. Methods: This single-center retrospective observational study included adult patients with moderate to severe ARDS who underwent FCV during invasive mechanical ventilation. FCV was delivered using the Evone^® ventilator with the Tritube^®. Demographic data, ventilatory settings, and arterial blood gas values were analyzed before and during 48 h of FCV and for 8 h after transition to conventional ventilation. Results: Seven patients with COVID-19–related ARDS were included. Following initiation of FCV, PaO₂ increased within the first 8 h (median increase: +24 mmHg), accompanied by a median 38% improvement in the PaO₂/FiO₂ ratio, which remained above baseline throughout follow-up. Arterial PCO₂ progressively declined, with the most pronounced reduction observed within the first 24 h (median decrease: −14 mmHg; approximately 22%). After transition back to conventional ventilation, mild deterioration in gas exchange parameters was observed; however, none returned to baseline values. All patients died during their ICU stay, mainly due to secondary infections and pulmonary embolism. Conclusions: In advanced COVID-19–related ARDS unresponsive to conventional ventilation, prolonged FCV application was technically feasible under controlled ICU conditions and associated with descriptively observed improvements in gas exchange parameters. However, late initiation of FCV did not translate into survival benefit. Prospective studies are required to define the optimal timing and patient selection for FCV. The present findings primarily support the technical feasibility and short-term physiological effects of FCV rather than clinical efficacy. Full article

Current protocols for generating cortical interneurons from human pluripotent stem cells are hindered by slow differentiation kinetics and poor reproducibility across cell lines. Here, we present a defined small-molecule-based strategy that efficiently directs human-induced neural stem cells (hiNSCs) toward cortical GABAergic interneurons within 14–18 days, which is substantially faster than conventional methods. Short-term dual-SMAD and WNT inhibition rapidly commits hiNSCs to an interneuron progenitor fate, reaching transcriptional states equivalent to those obtained with prolonged protocols. Prolonged activation of Sonic Hedgehog (via SAG) further enhances lineage specification, markedly upregulating NKX2.1, FOXG1, GABA, somatostatin (SST), and parvalbumin (PV) expression, and enriching pathways associated with early functional maturation. Importantly, RNA-sequencing reveals that under identical induction conditions, hiNSCs differentiate more rapidly and homogeneously than human-induced pluripotent stem cells (hiPSCs), which exhibit broader, less lineage-focused transcriptional trajectories. This differentiation strategy is highly reproducible across four genetically distinct hiNSC lines, with minimal off-target populations. Functionally, hiNSC-derived cortical interneurons display robust migratory behavior, produce abundant GABA, and survive transplantation into the adult mouse hippocampus, where they extend processes and form synapse-like structures. These findings establish a rapid, scalable, and robust approach for generating human cortical interneurons, supporting their safety and integration potential as a foundation for future cell replacement strategies in neurological disorders. Full article

Background: Acute malignant colorectal obstruction requires urgent management, traditionally by emergency resection or stoma formation. Colonic stenting as a bridge to surgery (BTS) has emerged as an alternative, but concerns persist regarding oncologic safety. This systematic review evaluates short-term and long-term outcomes of BTS with self-expanding metal stents (BTS-stent) compared with acute resection (AR). Methods: A systematic review was conducted on multiple databases. PubMed, Cochrane Library, and Google Scholar were searched for studies published between 2015 and 2025 reporting surgical management of obstructive colon cancer. Outcomes included perioperative morbidity and mortality, laparoscopic conversion, stoma formation, stent-related complications, and long-term overall survival (OS) and disease-free survival (DFS). Data were synthesized descriptively with reference to reported comparative effects and prior meta-analyses. Results: Fifteen studies published between 2015 and 2025 were included, encompassing 6999 patients (AR: 4944; BTS-stent: 1739; other BTS: 311). BTS was associated with higher rates of laparoscopic surgery (57% vs. 14%) and primary anastomosis, and significantly reduced stoma formation (27% vs. 60%). Postoperative morbidity and 30-day mortality were lower or comparable in BTS cohorts (4.9% vs. 7.8%). SEMS technical success ranged from 78 to 97%, with perforation rates of 0–15%, representing the main adverse event. Long-term outcomes were comparable between groups. Five-year OS ranged from 46 to 75% (BTS) and 46 to 74% (AR), with similar DFS. Subgroup data suggested possible worse outcomes in T4 tumors and improved results in selected stage III patients. Delayed surgery (>4 weeks) may improve survival, but increases complication risk. Conclusions: BTS with SEMS improves short-term outcomes without compromising long-term survival. Careful selection and avoidance of perforation are essential. Full article

Short-term mortality following the last dose of immune checkpoint inhibitors (ICIs) is an increasingly recognized real-world outcome measure, yet its clinical predictors remain poorly characterized. This multicenter retrospective study included 458 consecutive patients with advanced melanoma, non-small cell lung cancer, or renal cell carcinoma who received ICIs at four tertiary centers in Turkey between 2018 and 2023. The primary endpoint was 30-day mortality after the final ICI dose. Among 458 patients, 71 (15.5%) died within 30 days. Multivariable logistic regression identified ECOG performance status ≥ 2, number of metastatic sites ≥ 3, and log-transformed C-reactive protein-to-albumin ratio (log-CAR) as independent predictors of 30-day mortality in Model 1 (AUC 0.954), while ECOG PS ≥ 2, brain metastasis, metastatic sites ≥ 3, and log-NLR were independent predictors in Model 2 (AUC 0.912). In the lung cancer subgroup, log-CAR and NLR remained independent predictors while ECOG PS did not. Patients who died within 30 days had significantly shorter progression-free survival (1.18 vs. 4.63 months) and overall survival (2.30 vs. 14.39 months) compared with survivors. These findings suggest that routine assessment of inflammatory and nutritional biomarkers alongside tumor burden parameters may help identify patients at high risk of early mortality and inform the timing of supportive care in ICI-treated populations. Full article

Salt tolerance is a key factor limiting coastal vegetation restoration. In backshore areas, foliage is frequently exposed to salt mist and wave splash, which severely constrains plant survival and restoration outcomes. While root salt tolerance under short-term stress has been widely studied, foliar salt tolerance remains poorly understood. Here, using a self-developed experimental apparatus, we investigated the salt tolerance mechanisms of the coastal shrub Volkameria inermis through a long-term (159-day) foliar salt stress experiment (0–3.0% NaCl), followed by a 64-day recovery period. Field suitability was also evaluated at different coastal locations in Quanzhou Bay, Fujian Province. The results show that: (1) trait plasticity (e.g., leaf thickening), resource redirection (e.g., reduced growth rate, and new bud emergence in unstressed parts), and strong recovery capacity together enhance V. inermis adaptation to long-term foliar salt stress; (2) V. inermis exhibits adaptability to salinity ≤2.0% and survival under 3.0% despite severe injury; (3) besides osmotic adjustment, proline accumulation helps alleviate oxidative damage; and (4) field data demonstrated that leaf thickness and leaf water content were significantly associated with distance from the sea and elevation, thereby validating the salt-adaptation strategies observed under controlled conditions. This study provides a novel methodological framework and practical insights for selecting salt-tolerant species in coastal restoration. Full article

Background/Objectives: Acute-on-chronic liver failure (ACLF) is characterized by multiple organ failure and short-term mortality, and hepatic encephalopathy (HE) is its frequent complication. We investigated whether the severity of HE upon admission in patients with alcohol-related ACLF at the intensive care unit (ICU) was associated with short-term mortality. Methods: In total, 100 patients with alcohol-related ACLF and HE admitted in ICU were enrolled in the study. Laboratory biomarkers, total hospital length of stay (LOS), ICU length of stay, acute kidney injury (AKI), Acute Physiology and Chronic Health Evaluation II score, CLIF-C organ failure and Sequential Organ Failure Assessment score were tested in relation to the mortality risk. HE was assessed and divided into groups using the West Haven criteria. Results: Total hospital LOS, 7-day and 28-day mortality were significantly higher in the higher-grade HE group (p = 0.035, p = 0.031, p = 0.002, respectively). CLIF-C OF, SOFA, and APACHE II scores were significantly higher in the higher-grade HE group (p < 0.001). Kaplan–Meier survival analysis demonstrated reduced survival in patients with higher-grade HE (log-rank p < 0.001). In Cox regression analyses, AKI was associated with short-term mortality in both HE groups. Total hospital LOS and ICU length of stay were also associated with mortality, but were interpreted as post-baseline markers of clinical trajectory rather than baseline prognostic predictors. Conclusions: In patients with alcohol-related ACLF and HE, higher-grade HE was associated with poorer short-term survival. AKI and higher CLIF-C OF, SOFA and APACHE II scores were associated with poor outcomes, supporting their clinical relevance for mortality risk stratification in this population. LOS-related findings should be interpreted as markers of clinical trajectory rather than baseline prognostic predictors. Full article

Background/Objectives: Type 2 respiratory failure (T2RF) is associated with significant morbidity and mortality, partly driven by cardiopulmonary interactions and right ventricular (RV) dysfunction. The tricuspid annular plane systolic excursion to systolic pulmonary artery pressure (TAPSE/sPAP) ratio has emerged as a non-invasive marker of RV–pulmonary arterial (RV–PA) coupling; however, its prognostic value in T2RF remains insufficiently explored. This study aimed to evaluate the association between TAPSE/sPAP and short-term clinical outcomes in hospitalized T2RF patients. Methods: In this retrospective cohort study, 182 adult patients hospitalized with T2RF between January 2024 and December 2025 were included. Patients were followed from hospital admission until discharge or death, and survival status was additionally evaluated up to 60 days after admission using hospital electronic medical records and follow-up databases for Kaplan–Meier survival analysis. Complete follow-up data were available for all included patients. Demographic, clinical, laboratory, and transthoracic echocardiographic data were analyzed. Patients were stratified into low and high TAPSE/sPAP groups. The primary outcome was in-hospital mortality; secondary outcomes included 60-day all-cause mortality, non-invasive ventilation (NIV) failure, intensive care unit (ICU) admission, and length of hospital stay. Statistical analyses included receiver operating characteristic (ROC) curves, multivariable logistic regression, calibration assessment, and decision curve analysis. Results: Patients with a low TAPSE/sPAP ratio had significantly higher in-hospital mortality (38.6% vs. 12.8%, p < 0.001), higher rates of NIV failure and ICU admission, and longer hospital stays. TAPSE/sPAP demonstrated the highest predictive performance for mortality (AUC: 0.82, 95% CI: 0.75–0.88), outperforming conventional echocardiographic parameters. In multivariable analysis, TAPSE/sPAP remained an independent predictor of mortality (OR: 1.48 per 0.1 decrease, p < 0.001). The model showed good calibration (Hosmer–Lemeshow p = 0.62), and decision curve analysis confirmed its clinical utility with a higher net benefit across a wide range of threshold probabilities. Conclusions: The TAPSE/sPAP ratio was independently associated with in-hospital mortality and adverse clinical outcomes in patients with T2RF, reflecting impaired RV–PA coupling. As a readily obtainable non-invasive echocardiographic parameter, it demonstrated promising prognostic value for risk stratification in this population. However, given the retrospective single-center design of the study, these findings should be considered hypothesis-generating and require confirmation in prospective multicenter studies before routine clinical implementation can be recommended. Full article

Background: Short-term mortality stratification in sepsis remains clinically challenging, particularly because outcome is influenced by acute inflammation, coagulation abnormalities, organ dysfunction, and baseline comorbidity burden. This study evaluated the clinical performance of the BIO-S and BIO-SC composite bioscores for 28-day mortality stratification in adults with sepsis and septic shock. Methods: We conducted a prospective observational monocentric cohort study including 572 adult patients admitted between January 2022 and December 2024. BIO-S integrated procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), International Normalized Ratio (INR), and Sequential Organ Failure Assessment (SOFA) score, while BIO-SC extended this model by adding the Charlson Comorbidity Index (CCI). Prognostic performance was assessed using receiver operating characteristic (ROC) curve analysis, DeLong comparisons, bootstrap validation, calibration analysis, Kaplan–Meier survival curves, and Cox proportional hazards models. Results: The cohort included 418 patients with sepsis and 154 patients with septic shock. Overall 28-day mortality was 31.5% and was significantly higher in septic shock than in sepsis, 77.9% versus 14.4%, p < 0.001. BIO-S and BIO-SC showed strong discriminatory ability for 28-day mortality, with areas under the curve (AUCs) of 0.889 and 0.897, respectively. BIO-SC had the highest AUC, although the difference between BIO-SC and BIO-S was not statistically significant by the DeLong test, p = 0.328. At the optimal thresholds, BIO-S showed 97.8% sensitivity and 69.4% specificity, while BIO-SC showed 89.4% sensitivity and 77.8% specificity. Both bioscores stratified observed mortality across predefined risk categories and remained significantly associated with 28-day mortality in adjusted Cox models. Conclusions: BIO-S and BIO-SC showed clinically relevant performance for 28-day mortality stratification in adults with sepsis and septic shock. BIO-SC provided a numerically higher AUC and slightly better calibration, suggesting that comorbidity burden may improve prognostic characterization, although further independent multicenter validation is needed before broader clinical implementation. Full article

The brown frog (Rana dybowskii) is an important cold-temperate amphibian species in northeastern China, with considerable ecological and resource value. Because its survival, metabolism, and reproduction are highly sensitive to environmental temperature, elucidating the molecular mechanism’s underlying temperature response is of great significance for understanding environmental adaptation and reproductive regulation in amphibians. In this study, R. dybowskii was used as the experimental model, and a multi-tissue transcriptomic analysis was conducted on the brain, liver, spleen, ovary, oviduct, and testis from both females and males under 2 °C and 12 °C conditions to characterize tissue- and sex-specific responses to temperature variation. The results showed that the global transcriptomic landscape of R. dybowskii was primarily driven by tissue type, whereas temperature effects were mainly manifested within individual tissues. The liver, brain, and spleen exhibited pronounced temperature responsiveness in both sexes, with the liver mainly showing metabolic reprogramming-related functional changes. Intersection analysis further revealed that temperature-responsive genes included not only conserved modules shared across tissues but also a large number of tissue-specific genes. Reproductive tissues displayed more pronounced functional divergence: the ovary showed relatively limited transcriptional changes and remained comparatively stable; the oviduct underwent marked transcriptional remodeling, with upregulated genes mainly involved in glycosylation and macromolecule processing, whereas downregulated genes were primarily associated with ribosomes, translation, and RNA splicing; the testis was likewise highly sensitive to temperature changes, with upregulated genes mainly enriched in amino acid metabolism, mitochondrial function, and DNA repair, while downregulated genes were mainly related to cellular structure and intercellular junctions. Collectively, these findings indicate that the molecular adaptation of R. dybowskii to temperature variation is characterized by strong tissue specificity and sex-biased responses in reproductive tissues. This study provides a transcriptomic basis for elucidating the molecular responses to short-term temperature variation is important for understanding environmental sensitivity and reproductive regulation in amphibians. Full article