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15 pages, 357 KiB  
Article
Apalutamide Monotherapy in Metastatic Hormone-Sensitive Prostate Cancer: A Viable Alternative to First-Generation Anti-Androgen Agents to Avoid the Flare Phenomenon and an Effective Treatment for Achieving Early PSA Response
by Gaetano Facchini, Andrea D’Arienzo, Antonella Nicastro, Fabiano Flauto, Michela Izzo, Liliana Montella, Filippo Riccardo, Giovanni Maria Fusco, Francesco Trama, Giovanni Di Lauro, Giuseppe Di Costanzo, Anna Giacoma Tucci, Francesca Iasiello, Lorena Di Lorenzo, Salvatore Maddaluno, Carmela Liguori, Rita Assante di Cupillo, Paola Coppola, Angela Minissale, Maria Teresa Di Nardo, Luigi Formisano, Erika Martinelli, Giuliana Ciappina, Salvatore Pisconti, Massimiliano Berretta and Chiara Barracoadd Show full author list remove Hide full author list
Cancers 2025, 17(15), 2573; https://doi.org/10.3390/cancers17152573 - 5 Aug 2025
Viewed by 25
Abstract
Background/Objectives: Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor [...] Read more.
Background/Objectives: Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor initially causes a surge in LH and testosterone, defined as the “flare-up phenomenon”, leading to increased bone pain, spinal cord compression, bladder outlet obstruction and cardiovascular issues. To mitigate this effect, combining a first-generation antiandrogen agent (FGA) with aGnRH is recommended. However, second-generation anti-androgens, such as apalutamide, bind selectively and irreversibly to the androgen receptor (AR), exhibiting a more efficient inhibition of the AR pathway. Methods: This is a descriptive retrospective study of 27 patients (pts) with mHSPC, treated at a single center (“Santa Maria delle Grazie” Hospital in Pozzuoli, ASL Napoli 2 Nord, Italy) between June 2022 and April 2024. Patients received apalutamide monotherapy for 14 days followed by continuous combination with aGnRH plus apalutamide. Serum PSA and testosterone levels were measured at baseline, at day 14 (after 13 days of apalutamide monotherapy), at day 28 (after an additional 15 days of apalutamide plus a aGnRH), and at day 60. Results: PSA levels decreased from a mean of 45.2 (±63.1) ng/mL at baseline to a mean of 12.6 (±23.4) ng/mL at day 14 and to 3.3 ng/mL (±6.0) at day 28 of treatment. After 14 days of apalutamide monotherapy, 21 patients (77.8%) achieved a >50% PSA reduction and 4 (14.8%) a >90% PSA reduction. The number of patients with undetectable PSA was one (3.7%) at day 14, two (7.4%) at day 28, and nine (33.3%) at day 60. The mean serum testosterone levels were 6.56 (±4.46) ng/mL at baseline, 6.58 (±4.42) ng/mL at day 14, and 2.40 (± 3.38) ng/mL at day 28. No significant difference in PSA and testosterone level reduction during treatment emerged between subgroups of patients with low- vs. high-volume disease. Conclusions: Apalutamide alone is a viable option for mitigating the flare-up phenomenon, avoiding first generation anti-androgen therapy, and it can achieve rapid and deep biochemical control. Full article
(This article belongs to the Special Issue Advances in Therapeutic Strategies for Prostate Cancer)
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20 pages, 4719 KiB  
Systematic Review
Levosimendan vs. Dobutamine in Patients with Septic Shock: A Systematic Review and Meta-Analysis with Trial Sequential Analysis
by Edith Elianna Rodríguez, German Alberto Devia Jaramillo, Lissa María Rivera Cuellar, Santiago Eduardo Pérez Herran, David René Rodríguez Lima and Antoine Herpain
J. Clin. Med. 2025, 14(15), 5496; https://doi.org/10.3390/jcm14155496 - 5 Aug 2025
Viewed by 91
Abstract
Introduction: Septic-induced cardiomyopathy (SICM) is a life-threatening condition in patients with septic shock. Persistent hypoperfusion despite adequate volume status and vasopressor use is associated with poor outcomes and is currently managed with inotropes. However, the superiority of available inotropic agents remains unclear. This [...] Read more.
Introduction: Septic-induced cardiomyopathy (SICM) is a life-threatening condition in patients with septic shock. Persistent hypoperfusion despite adequate volume status and vasopressor use is associated with poor outcomes and is currently managed with inotropes. However, the superiority of available inotropic agents remains unclear. This meta-analysis aims to determine which inotropic agent may be more effective in this clinical scenario. Methods: A systematic review and meta-analysis were conducted, including data from randomized clinical trials (RCTs) comparing levosimendan and dobutamine in patients with septic shock and persistent hypoperfusion. Summary effect estimates, including odds ratios (ORs), standardized mean differences (SMDs), and 95% confidence intervals (CIs), were calculated using a random-effects model. Trial sequential analysis (TSA) was also performed. Results: Of 244 studies screened, 11 RCTs were included. Levosimendan was associated with a reduction in in-hospital mortality (OR 0.64; 95% CI: 0.47; 0.88) and ICU length of stay (SMD 5.87; 95% CI: –8.37; 20.11) compared with dobutamine. Treatment with levosimendan also resulted in significant reductions in BNP (SMD –1.87; 95% CI: –2.45; −1.2) and serum lactate levels (SMD –1.63; 95% CI: –3.13; −0.12). However, TSA indicated that the current evidence is insufficient to definitively confirm or exclude effects on in-hospital and 28-day mortality. Conclusions: Levosimendan may improve hemodynamics, tissue perfusion, and biomarkers, and may reduce in-hospital mortality and ICU length of stay in patients with SICM compared with dobutamine. However, TSA highlights the need for further studies to inform clinical practice and optimize inotrope selection. Full article
(This article belongs to the Special Issue Sepsis: Current Updates and Perspectives)
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13 pages, 551 KiB  
Article
Classifying Patient Characteristics and Determining a Predictor in Acute Stroke Patients: Application of Latent Class Analysis in Rehabilitation Practice
by Junya Uchida, Moeka Yamada, Hirofumi Nagayama, Kounosuke Tomori, Kohei Ikeda and Keita Yamauchi
J. Clin. Med. 2025, 14(15), 5466; https://doi.org/10.3390/jcm14155466 - 4 Aug 2025
Viewed by 201
Abstract
Background/Objectives: Predicting comprehensive patient characteristics is essential for optimal individualized rehabilitation plans for acute stroke patients. However, current models primarily predict single outcomes. This study aimed to assess the applicability of latent class analysis (LCA) in rehabilitation practice by identifying comprehensive characteristics [...] Read more.
Background/Objectives: Predicting comprehensive patient characteristics is essential for optimal individualized rehabilitation plans for acute stroke patients. However, current models primarily predict single outcomes. This study aimed to assess the applicability of latent class analysis (LCA) in rehabilitation practice by identifying comprehensive characteristics and associated predictors in acute stroke patients. Methods: We conducted a retrospective observational study using the Japan Association of Rehabilitation Database, including 10,270 stroke patients admitted to 37 acute-care hospitals between January 2005 and March 2016. Patients were classified using LCA based on outcomes at discharge, including Functional Independence Measure (FIM), National Institutes of Health Stroke Scale (NIHSS) subscales for upper-extremity function, length of hospitalization, and discharge destination. Predictor variables at admission included age, FIM scores, NIHSS subscales for upper-extremity function, stroke type, and daily rehabilitation volume. Results: 6881 patients were classified into nine distinct classes (class size: 4–29%). Class 1, representing the mildest cases, was noted for independent ambulation and good upper limb function. Class 2 comprised those with the most severe clinical outcome. Other classes exhibited a gradient of severity, commonly encountered in clinical practice. For instance, Class 7 included right-sided paralysis with preserved motor activities of daily living (ADLs) and modified dependence in cognitive functions, such as communication. All predictors at admission were significantly associated with class membership at discharge (p < 0.001). Conclusions: LCA effectively identified unique clinical subgroups among acute stroke patients and demonstrated that key admission variables could predict class membership. This approach offers a promising insight into targeted, personalized rehabilitation practice for acute stroke patients. Full article
(This article belongs to the Section Clinical Rehabilitation)
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11 pages, 480 KiB  
Article
A Novel Deep Learning Model for Predicting Colorectal Anastomotic Leakage: A Pioneer Multicenter Transatlantic Study
by Miguel Mascarenhas, Francisco Mendes, Filipa Fonseca, Eduardo Carvalho, Andre Santos, Daniela Cavadas, Guilherme Barbosa, Antonio Pinto da Costa, Miguel Martins, Abdullah Bunaiyan, Maísa Vasconcelos, Marley Ribeiro Feitosa, Shay Willoughby, Shakil Ahmed, Muhammad Ahsan Javed, Nilza Ramião, Guilherme Macedo and Manuel Limbert
J. Clin. Med. 2025, 14(15), 5462; https://doi.org/10.3390/jcm14155462 - 3 Aug 2025
Viewed by 169
Abstract
Background/Objectives: Colorectal anastomotic leak (CAL) is one of the most severe postoperative complications in colorectal surgery, impacting patient morbidity and mortality. Current risk assessment methods rely on clinical and intraoperative factors, but no real-time predictive tool exists. This study aimed to develop [...] Read more.
Background/Objectives: Colorectal anastomotic leak (CAL) is one of the most severe postoperative complications in colorectal surgery, impacting patient morbidity and mortality. Current risk assessment methods rely on clinical and intraoperative factors, but no real-time predictive tool exists. This study aimed to develop an artificial intelligence model based on intraoperative laparoscopic recording of the anastomosis for CAL prediction. Methods: A convolutional neural network (CNN) was trained with annotated frames from colorectal surgery videos across three international high-volume centers (Instituto Português de Oncologia de Lisboa, Hospital das Clínicas de Ribeirão Preto, and Royal Liverpool University Hospital). The dataset included a total of 5356 frames from 26 patients, 2007 with CAL and 3349 showing normal anastomosis. Four CNN architectures (EfficientNetB0, EfficientNetB7, ResNet50, and MobileNetV2) were tested. The models’ performance was evaluated using their sensitivity, specificity, accuracy, and area under the receiver operating characteristic (AUROC) curve. Heatmaps were generated to identify key image regions influencing predictions. Results: The best-performing model achieved an accuracy of 99.6%, AUROC of 99.6%, sensitivity of 99.2%, specificity of 100.0%, PPV of 100.0%, and NPV of 98.9%. The model reliably identified CAL-positive frames and provided visual explanations through heatmaps. Conclusions: To our knowledge, this is the first AI model developed to predict CAL using intraoperative video analysis. Its accuracy suggests the potential to redefine surgical decision-making by providing real-time risk assessment. Further refinement with a larger dataset and diverse surgical techniques could enable intraoperative interventions to prevent CAL before it occurs, marking a paradigm shift in colorectal surgery. Full article
(This article belongs to the Special Issue Updates in Digestive Diseases and Endoscopy)
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12 pages, 1639 KiB  
Article
Neuroanatomical Reflections of Childhood Obesity: Volumetric Analysis of the Pituitary Gland and Olfactory Bulb
by Emel Hatun Aytaç Kaplan, Elif Bulut, Nazlı Gülsüm Akyel, Zümrüt Kocabey Sütçü and Şeyda Doğantan
Children 2025, 12(8), 1009; https://doi.org/10.3390/children12081009 - 31 Jul 2025
Viewed by 189
Abstract
Introduction: Obesity is a rapidly increasing condition that leads to serious health issues. The sense of smell, one of the oldest senses related to energy metabolism, has been increasingly studied in relation to obesity. Objective: This study investigates the impact of childhood obesity [...] Read more.
Introduction: Obesity is a rapidly increasing condition that leads to serious health issues. The sense of smell, one of the oldest senses related to energy metabolism, has been increasingly studied in relation to obesity. Objective: This study investigates the impact of childhood obesity on the volumes of the olfactory bulb and pituitary gland, exploring the relationship between body mass index and these brain structures. Method: This study included 146 participants aged 6–18 years with different body mass indices between 2021 and 2024 at Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey. Participants were classified into normal weight, obese, and morbidly obese groups, and olfactory bulb and pituitary gland volumes were retrospectively analyzed. MRI scans were performed to exclude intracranial pathologies due to headache complaints, and patients with cranial pathologies were excluded from the study. Results: This study examined the olfactory bulb and pituitary gland volumes among normal weight, obese, and morbidly obese groups aged 6–18 years. In the morbidly obese group, right olfactory bulb area and right olfactory bulb volume were significantly higher compared to the other groups, while left olfactory bulb area was higher in both the obese and morbidly obese groups. Additionally, in the morbidly obese group, pituitary height was significantly lower than the other groups, and pituitary volume was also found to be reduced in morbid obesity. Conclusions: This study demonstrated that childhood obesity is linked to significant changes in the volumes of the olfactory bulb and pituitary gland. In morbidly obese children, an increase in pituitary volume and alterations in olfactory bulb volume suggest possible neuroanatomical adaptations. Full article
(This article belongs to the Section Pediatric Endocrinology & Diabetes)
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12 pages, 537 KiB  
Article
Surgical Versus Conservative Management of Supratentorial ICH: A Single-Center Retrospective Analysis (2017–2023)
by Cosmin Cindea, Samuel Bogdan Todor, Vicentiu Saceleanu, Tamas Kerekes, Victor Tudor, Corina Roman-Filip and Romeo Gabriel Mihaila
J. Clin. Med. 2025, 14(15), 5372; https://doi.org/10.3390/jcm14155372 - 30 Jul 2025
Viewed by 348
Abstract
Background: Intracerebral hemorrhage (ICH) is a severe form of stroke associated with high morbidity and mortality. While neurosurgical evacuation may offer theoretical benefits, its impact on survival and hospital course remains debated. We aimed to compare the outcomes of surgical versus conservative [...] Read more.
Background: Intracerebral hemorrhage (ICH) is a severe form of stroke associated with high morbidity and mortality. While neurosurgical evacuation may offer theoretical benefits, its impact on survival and hospital course remains debated. We aimed to compare the outcomes of surgical versus conservative management in patients with lobar, capsulo-lenticular, and thalamic ICH and to identify factors influencing mortality and the surgical decision. Methods: This single-center, retrospective cohort study included adult patients admitted to the County Clinical Emergency Hospital of Sibiu (2017–2023) with spontaneous supratentorial ICH confirmed via CT (deepest affected structure determining lobar, capsulo-lenticular, or thalamic location). We collected data on demographics, clinical presentation (Glasgow Coma Scale [GCS], anticoagulant use), hematoma characteristics (volume, extension), treatment modality (surgical vs. conservative), and in-hospital outcomes (mortality, length of stay). Statistical analyses included t-tests, χ2, correlation tests, and logistic regression to identify independent predictors of mortality and surgery. Results: A total of 445 patients were analyzed: 144 lobar, 150 capsulo-lenticular, and 151 thalamic. Surgical intervention was more common in patients with larger volumes and lower GCS. Overall, in-hospital mortality varied by location, reaching 13% in the lobar group, 20.7% in the capsulo-lenticular group, and 35.1% in the thalamic group. Within each location, surgical intervention did not significantly reduce overall in-hospital mortality despite the more severe baseline presentation in surgical patients. In lobar ICH specifically, no clear survival advantage emerged, although surgery may still benefit those most severely compromised. For capsulo-lenticular hematomas > 30 mL, surgery was associated with lower mortality (39.4% vs. 61.5%). In patients with large lobar ICH, surgical intervention was associated with mortality rates similar to those seen in less severe, conservatively managed cohorts. Multivariable adjustment confirmed GCS and hematoma volume as independent mortality predictors; age and volume predicted the likelihood of surgical intervention. Conclusions: Despite targeting more severe cases, neurosurgical evacuation did not uniformly lower in-hospital mortality. In lobar ICH, surgical patients with larger hematomas (~48 mL) and lower GCS (~11.6) had mortality rates (~13%) comparable to less severe, conservative cohorts, indicating that surgical intervention was associated with similar mortality rates despite higher baseline risk. However, these findings do not establish a causal survival benefit and should be interpreted in the context of non-randomized patient selection. For capsulo-lenticular hematomas > 30 mL, surgery was associated with lower observed mortality (39.4% vs. 61.5%). Thalamic ICH remained most lethal, highlighting the difficulty of deep-brain bleeds and frequent ventricular extension. Across locations, hematoma volume and GCS were the primary outcome predictors, indicating the need for timely intervention, better patient selection, and possibly minimally invasive approaches. Future prospective multicenter research is necessary to refine surgical indications and validate these findings. To our knowledge, this investigation represents the largest and most contemporary single-center cohort study of supratentorial intracerebral hemorrhage conducted in Romania. Full article
(This article belongs to the Section Brain Injury)
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16 pages, 957 KiB  
Article
The Influence of Blood Transfusion Indexed to Patient Blood Volume on 5-Year Mortality After Coronary Artery Bypass Grafting—An EuroSCORE II Adjusted Spline Regression Analysis
by Joseph Kletzer, Maximilian Kreibich, Martin Czerny, Tim Berger, Albi Fagu, Laurin Micek, Ulrich Franke, Matthias Eschenhagen, Tau S. Hartikainen, Mirjam Wild and Dalibor Bockelmann
J. Cardiovasc. Dev. Dis. 2025, 12(8), 287; https://doi.org/10.3390/jcdd12080287 - 28 Jul 2025
Viewed by 321
Abstract
Background: While timely blood transfusion is critical for restoring oxygen-carrying capacity after coronary artery bypass grafting (CABG), allogeneic blood product transfusions are independently associated with increased long-term mortality, necessitating a risk-stratified approach to balance oxygen delivery against immunological complications and infection risks. Methods: [...] Read more.
Background: While timely blood transfusion is critical for restoring oxygen-carrying capacity after coronary artery bypass grafting (CABG), allogeneic blood product transfusions are independently associated with increased long-term mortality, necessitating a risk-stratified approach to balance oxygen delivery against immunological complications and infection risks. Methods: We retrospectively analyzed 3376 patients undergoing isolated CABG between 2005 and 2023 at a single tertiary center. Patients who died during their perioperative hospital stay within 30 days were excluded. Transfusion burden was assessed both as the absolute number of blood product units (packed red blood cells, platelet transfusion, fresh frozen plasma) and as a percentage of calculated patient blood volume. The primary outcome was all-cause mortality at 5 years. Flexible Cox regression with penalized smoothing splines, adjusted for EuroSCORE II, was used to model dose–response relationships. Results: From our cohort of 3376 patients, a total of 137 patients (4.05%) received >10 units of packed red blood cells (PRBC) perioperatively. These patients were older (median 71 vs. 68 years, p < 0.001), more often female (29% vs. 15%, p < 0.001), and had higher preoperative risk (EuroSCORE II: 2.53 vs. 1.41, p < 0.001). After 5 years, mortality was 42% in the massive transfusion group versus 10% in controls. Spline regression revealed an exponential increase in mortality with transfused units: 14 units yielded a 1.5-fold higher hazard of death (HR 1.46, 95% CI 1.31–1.64), rising to HR 2.71 (95% CI 2.12–3.47) at 30 units. When transfusion was indexed to blood volume, this relationship became linear and more tightly correlated with mortality, with lower maximum hazard ratios and narrower confidence intervals. Conclusions: Indexing transfusion burden to the percentage of patient blood volume replaced provides a more accurate and clinically actionable predictor of 5-year mortality after CABG than absolute unit counts. Our findings support a shift toward individualized, volume-based transfusion strategies to optimize patient outcomes and resource stewardship in a time of limited availability of blood products. Full article
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11 pages, 469 KiB  
Article
Breastfeeding in Preterm Infants Is Not Compromised by Early Discharge and Home Nasogastric Tube Feeding up to 3 Months Postmenstrual Age: A Prospective Cohort Study
by Rahel Schuler, Alice Louise Kreidler, Markus Waitz, Birgit Kampschulte, Jutta Petzinger, Tina Frodermann, Andreas Hahn and Walter A. Mihatsch
Nutrients 2025, 17(15), 2444; https://doi.org/10.3390/nu17152444 - 26 Jul 2025
Viewed by 404
Abstract
Background/Objectives: Breastmilk offers numerous benefits for the health and development of preterm infants, while prolonged hospitalization may impair neurodevelopment. At our institution, the implementation of enhanced family-centered care (FCC) has enabled earlier discharge of preterm infants. This study aimed to assess the [...] Read more.
Background/Objectives: Breastmilk offers numerous benefits for the health and development of preterm infants, while prolonged hospitalization may impair neurodevelopment. At our institution, the implementation of enhanced family-centered care (FCC) has enabled earlier discharge of preterm infants. This study aimed to assess the impact of early discharge on breastfeeding and breastmilk provision. Methods: This analysis is based on data from a prospective single-center longitudinal cohort study conducted from October 2020 to November 2023, involving six consecutive cohorts (one baseline and five intervention cohorts; n = 184). FCC was progressively enhanced across cohorts. The primary outcome of the main study was postmenstrual age (PMA) at discharge. In this secondary analysis, breastfeeding and breastmilk provision were assessed at four time points: 4 weeks postnatal age, at discharge, 4 weeks post-discharge, and at 3 months PMA. Results: From baseline to intervention cohort 5, the PMA at discharge declined significantly from 37.8 ± 2.1 to 35.7 ± 0.91 weeks (p = 0.03), while the percentage of infants necessitating home nasogastric tube feeding increased from 6.3% to 66.7% (p < 0.01). The proportion of breastmilk of daily feeding volume remained unchanged at 4 weeks postnatal age (0.66 ± 0.42 vs. 0.9 ± 0.28) and at discharge (0.6 ± 0.45 vs. 0.79 ± 0.36). At 4 weeks post-discharge, 65.8% vs. 62.5% of the infants were on partial or exclusive breastmilk (p = 0.91) feeding. Similarly, the percentage of exclusively breastfed infants at 4 weeks post-discharge (23.7% vs. 19.8%) and at 3 months PMA (20% vs. 28.6%) did not differ significantly between baseline and intervention cohort 5. Conclusions: Early discharge did not reduce breastmilk supply or exclusive breastfeeding. However, the persistently low rate of exclusive breastfeeding post-discharge highlights the need for additional support strategies during and after hospitalization. Full article
(This article belongs to the Section Pediatric Nutrition)
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14 pages, 1112 KiB  
Article
Neo-Adjuvant Chemotherapy in Gastric Adenocarcinoma: Impact on Surgical and Oncological Outcomes in a Western Referral Center
by Claudio Fiorillo, Beatrice Biffoni, Ludovica Di Cesare, Fausto Rosa, Sergio Alfieri, Lodovica Langellotti, Roberta Menghi, Vincenzo Tondolo and Giuseppe Quero
Cancers 2025, 17(15), 2465; https://doi.org/10.3390/cancers17152465 - 25 Jul 2025
Viewed by 255
Abstract
Background/Objectives: Neo-adjuvant chemotherapy (NACT) is increasingly utilized in Western countries for the treatment of gastric cancer (GC). While its oncologic benefits are well established, its impact on surgical safety and long-term outcomes remain a matter of debate. This study evaluates the real-world [...] Read more.
Background/Objectives: Neo-adjuvant chemotherapy (NACT) is increasingly utilized in Western countries for the treatment of gastric cancer (GC). While its oncologic benefits are well established, its impact on surgical safety and long-term outcomes remain a matter of debate. This study evaluates the real-world effect of NACT on perioperative and oncologic outcomes in a high-volume Western center. Methods: Data from 254 patients who underwent gastrectomy with D2 lymphadenectomy for GC between March 2016 and January 2024 were prospectively collected and retrospectively analyzed. Patients were categorized into an upfront surgery group (n = 144, 56.7%) and a NACT group (n = 110, 43.3%). The primary outcome was to compare the two study groups in terms of perioperative outcomes, as well as overall (OS) and disease-free survival (DFS). Multivariate analyses were conducted to identify factors associated with perioperative complications and long-term survival. Results: Patients in the NACT group were younger (median age 65 vs. 72 years; p = 0.001) and had fewer comorbidities. NACT was associated with a higher incidence of proximal tumors (54–49.1% vs. 37–25.7%; p = 0.001), diffuse-type tumors (27–45.8% vs. 39–31.7%; p = 0.03), and lymph-node metastases (82–74.1% vs. 84–58%; p = 0.007). No significant differences were observed in median hospital stay (9 (7–16) and 10 (8–22) days for the upfront and NACT groups, respectively; p = 0.26), post-operative mortality (11–7.6% and 5–4.5% for the upfront and NACT groups, respectively; p = 0.32), and major complications (30–20.8% and 23–20.9% for the upfront and NACT groups, respectively; p = 0.99). Among patients receiving NACT, the FLOT regimen was associated with a lower rate of complications (12–16.2% vs. 11–30.5% in the non-FLOT cohort; p = 0.05) and reoperations (4–5.4% vs. 8–22.2% in the non-FLOT group; p = 0.008). Tumor location was identified as an independent predictor of perioperative complications (OR 4.7, 95% C.I.: 1.56–14.18; p = 0.006), while non-FLOT regimens were independently associated with higher reoperation rates (OR 0.22, 95% C.I.: 0.06–0.86; p = 0.003). Five-year OS was comparable between the two groups (44.6% in the NACT group vs. 47.7% in the upfront surgery group; p = 0.96). N+ status (OR 2.5, 95% C.I. 1.42–4.40; p = 0.001) and R+ margins (OR 1.89, 95% C.I. 0.98–3.65; p = 0.006) were negative independent prognostic factors for DFS. Conclusions: Although several selection biases limit the generalizability of our findings, our results suggest that NACT prior to gastrectomy for GC does not increase postoperative morbidity and mortality in appropriately selected patients. However, its use in elderly and polymorbid patients should be carefully considered to determine the safest and most effective therapeutic approach, particularly in selecting the appropriate chemotherapy regimen, to minimize the risk of postoperative complications requiring surgical reintervention. Full article
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15 pages, 1045 KiB  
Article
Physician Practice Affiliation Drives Site of Care Cost Differentials: An Opportunity to Reduce Healthcare Expenditures
by Deepak A. Kapoor, Mark Camel, David Eagle, Lauren C. Makhoul, Justin Maroney, Zhou Yang and Paul Berggreen
J. Mark. Access Health Policy 2025, 13(3), 36; https://doi.org/10.3390/jmahp13030036 - 24 Jul 2025
Viewed by 987
Abstract
The continued migration of physicians from independent practice to affiliation with larger entities has garnered significant scrutiny. These affiliation models include hospitals and health systems, payers and corporate entities, and management services organizations, which may or may not be private equity (PE)-backed. Data [...] Read more.
The continued migration of physicians from independent practice to affiliation with larger entities has garnered significant scrutiny. These affiliation models include hospitals and health systems, payers and corporate entities, and management services organizations, which may or may not be private equity (PE)-backed. Data on the impact of different physician affiliation models on cost of care is limited. We examined the relationship between provider affiliation model, site of care (SOC), and cost of care for certain high-volume procedures in procedure-intensive specialties for both Medicare and commercial insurance. We found that hospital-affiliated physicians are least likely—and PE-affiliated physicians are most likely—to provide care in lower-cost settings. For both Medicare and commercial insurance, SOC contributes meaningfully to procedure unit price, which is consistently greater in hospital-based settings. These findings suggest that the physician affiliation model and associated SOC cost differentials contribute materially to healthcare expenditures. As the Medicare cost differentials are set by statute and regulations, strategies such as site-neutral payments are needed to mitigate the monetary impact of historical and future physician practice migration. Full article
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7 pages, 184 KiB  
Article
Efficacy of Teduglutide in Pediatric Short Bowel Syndrome: Association with Citrulline Levels and Anatomical Location of Remnant Small Intestine
by Yudai Goto, Kouji Masumoto, Takato Sasaki, Kazuki Shirane, Tomohiro Aoyama, Naoya Sakamoto and Takahiro Jimbo
Children 2025, 12(8), 977; https://doi.org/10.3390/children12080977 - 24 Jul 2025
Viewed by 251
Abstract
Background/Objectives: Short bowel syndrome (SBS) is the leading cause of pediatric intestinal failure. Plasma citrulline is considered a marker indicating an enterocyte volume and may help evaluate the response to teduglutide; however, this interpretation may vary depending on the remnant bowel anatomy. Methods: [...] Read more.
Background/Objectives: Short bowel syndrome (SBS) is the leading cause of pediatric intestinal failure. Plasma citrulline is considered a marker indicating an enterocyte volume and may help evaluate the response to teduglutide; however, this interpretation may vary depending on the remnant bowel anatomy. Methods: We conducted a retrospective case series of four pediatric patients with SBS (aged < 15 years) who received teduglutide for 12 months at our hospital between 2018 and 2023. Changes in plasma citrulline levels and parenteral nutrition requirements were assessed in addition to bowel anatomy classification. Results: This study included two males and two females. All patients showed an increase in plasma citrulline levels and a reduction in the requirement for parenteral nutrition (PN) after 12 months of teduglutide treatment. In SBS type 2 (jejunocolic anastomosis), citrulline levels increased by 114% and 52%, with PN reduction rates of 100% and 30%, respectively. In SBS type 3 (jejunoileal anastomosis), citrulline levels increased by 13.6% and 34%, with PN reductions of 33% and 73%, respectively. Conclusions: Teduglutide treatment increased plasma citrulline levels and reduced PN levels in all cases. However, the magnitude of the citrulline change varied across bowel anatomy types, suggesting that the anatomical difference in the remnant bowel may influence the biomarker response. Further detailed pediatric cases are required to clarify the role of citrulline in evaluating GLP-2 analogue treatment outcomes. Full article
(This article belongs to the Section Pediatric Gastroenterology and Nutrition)
16 pages, 803 KiB  
Article
Temporal Decline in Intravascular Albumin Mass and Its Association with Fluid Balance and Mortality in Sepsis: A Prospective Observational Study
by Christian J. Wiedermann, Arian Zaboli, Fabrizio Lucente, Lucia Filippi, Michael Maggi, Paolo Ferretto, Alessandro Cipriano, Antonio Voza, Lorenzo Ghiadoni and Gianni Turcato
J. Clin. Med. 2025, 14(15), 5255; https://doi.org/10.3390/jcm14155255 - 24 Jul 2025
Viewed by 398
Abstract
Background: Intravascular albumin mass represents the total quantity of albumin circulating within the bloodstream and may serve as a physiologically relevant marker of vascular integrity and fluid distribution in sepsis. While low serum albumin levels are acknowledged as prognostic indicators, dynamic assessments [...] Read more.
Background: Intravascular albumin mass represents the total quantity of albumin circulating within the bloodstream and may serve as a physiologically relevant marker of vascular integrity and fluid distribution in sepsis. While low serum albumin levels are acknowledged as prognostic indicators, dynamic assessments based on albumin mass remain insufficiently explored in patients outside the intensive care unit. Objectives: To describe the temporal changes in intravascular albumin mass in patients with community-acquired sepsis and to examine its relationship with fluid balance and thirty-day mortality. Methods: This prospective observational study encompassed 247 adults diagnosed with community-acquired sepsis who were admitted to a high-dependency hospital ward specializing in acute medical care. The intravascular albumin mass was calculated daily for a duration of up to five days, utilizing plasma albumin concentration and estimated plasma volume derived from anthropometric and hematologic data. Net albumin leakage was defined as the variation in intravascular albumin mass between consecutive days. Fluid administration and urine output were documented to ascertain cumulative fluid balance. Repeated-measures statistical models were employed to evaluate the associations between intravascular albumin mass, fluid balance, and mortality, with adjustments made for age, comorbidity, and clinical severity scores. Results: The intravascular albumin mass exhibited a significant decrease during the initial five days of hospitalization and demonstrated an inverse correlation with the cumulative fluid balance. A greater net leakage of albumin was associated with a positive fluid balance and elevated mortality rates. Furthermore, a reduced intravascular albumin mass independently predicted an increased risk of mortality at thirty days. Conclusions: A reduction in intravascular albumin mass may suggest ineffective fluid retention and the onset of capillary leak syndrome. This parameter holds promise as a clinically valuable, non-invasive indicator for guiding fluid resuscitation in cases of sepsis. Full article
(This article belongs to the Section Intensive Care)
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11 pages, 1677 KiB  
Article
Exposure to Treponema pallidum Alters Villous Histomorphology of Human Placentae
by Patience B. Tetteh-Quarcoo, Joana Twasam, John Ahenkorah, Bismarck Afedo Hottor, Nicholas T. K. D. Dayie, Stephen Opoku-Nyarko, Peter Ofori Appiah, Emmanuel Afutu, Fleischer C. N. Kotey, Eric S. Donkor, Emilia Asuquo Udofia, Nii Koney-Kwaku Koney, Benjamin Arko-Boham and Kevin Kofi Adutwum-Ofosu
Acta Microbiol. Hell. 2025, 70(3), 31; https://doi.org/10.3390/amh70030031 - 23 Jul 2025
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Abstract
Syphilis, which is caused by Treponema pallidum, remains one of the most common congenital infection worldwide and has tremendous consequences for the mother and her developing foetus if left untreated. The complexity of the exposure to this pathogen extends beyond the well-established [...] Read more.
Syphilis, which is caused by Treponema pallidum, remains one of the most common congenital infection worldwide and has tremendous consequences for the mother and her developing foetus if left untreated. The complexity of the exposure to this pathogen extends beyond the well-established clinical manifestations, as it can profoundly affect placental histomorphology. This study aimed to compare T. pallidum-exposed placental villi structures with healthy placentae at term to evaluate the histomorphological differences using stereology. In this case-control study conducted at term (38 weeks ± 2 weeks), 78 placentae were collected from the hospital delivery suites, comprising 39 cases (T. pallidum-exposed) and 39 controls (non-exposed), who were gestational age-matched with other potential confounders excluded. Blood samples from the umbilical vein and placental basal plate were tested for syphilis, using rapid diagnostic test (RDT) kits for T. pallidum (TP) antibodies (IgG and IgM) to classify placentae as exposed to T. pallidum (cases) and non-exposed (controls). Tissue sections were prepared and stained with haematoxylin and eosin, and the mean volume densities of syncytial knots, foetal capillaries, syncytial denuded areas, and intervillous spaces were estimated using stereological methods. Statistical analysis was performed to compare the mean values between the case and control groups. Stereological assessment revealed significant differences between the T. pallidum-exposed and non-exposed groups with regard to syncytial knots (p < 0.0001), syncytial denudation (p < 0.0001), and foetal capillaries (p < 0.0001), but no significant difference in the intervillous space was found (p = 0.1592). Therefore, our study shows, for the first time, that the histomorphology of human placental villi appears to be altered by exposure to T. pallidum. It will, therefore, be interesting to determine whether these changes in the placental villi translate into long-term effects on the baby. Full article
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13 pages, 2291 KiB  
Article
The Real-World Outcomes of a Population-Based Gastric Cancer Screening Program for 10 Years in an Urban City near Metropolitan Tokyo: The Usefulness of Early Detection of Gastric and Esophageal Cancer
by Hiroshi Yasuda, Tadateru Maehata, Yoshinori Sato, Hirofumi Kiyokawa, Masaki Kato, Yusuke Nakamoto, Takumi Komatsu and Keisuke Tateishi
Gastrointest. Disord. 2025, 7(3), 49; https://doi.org/10.3390/gidisord7030049 - 22 Jul 2025
Viewed by 235
Abstract
Objectives: To investigate the real-world outcomes of a population-based gastric cancer (GC) screening program in Kawasaki City, a major urban area with a growing aging population and relatively high screening participation rates. Methods: Between December 2012 and 2021, a total of 337,842 citizens [...] Read more.
Objectives: To investigate the real-world outcomes of a population-based gastric cancer (GC) screening program in Kawasaki City, a major urban area with a growing aging population and relatively high screening participation rates. Methods: Between December 2012 and 2021, a total of 337,842 citizens in Kawasaki City underwent population-based GC screening, leading to the detection of 1087 GC cases. Esophageal cancer (EC) has been recorded since 2016, with 236 cases detected. To evaluate the short- and long-term clinical outcomes of screening-detected GC and EC, we conducted a retrospective study using the electronic medical records of patients treated at our hospital, a high-volume institution for GC and EC treatment in the city. As a control group, we included 34 GC and EC cases diagnosed based on symptoms at our hospital in 2018. Results: Among the 1087 GC cases detected through population-based screening, 102 cases treated at our hospital were included in the analysis. Of them, 91 patients (89%) were diagnosed with early-stage GC. All screening-detected GC cases underwent either surgery (27 cases) or endoscopic submucosal dissection (75 cases). The five-year survival rates for GC were 90% in males and 86% in females. Eighteen EC cases were also included in the study. The five-year survival rate for screening-detected advanced GC was 70.0%, while for screening-detected EC, it was 100%. Both survival rates were significantly higher than those for symptom-diagnosed GC (30.0%) and EC (40.8%). Conclusions: The prognosis of GC and EC detected through population-based endoscopic screening is significantly better than that of cancers diagnosed based on symptoms. This underscores the effectiveness of endoscopic screening as a valuable tool for the early detection of upper gastrointestinal tract cancers. Full article
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12 pages, 845 KiB  
Article
Preoperative Outcome Predictors in Aortic Valve Replacement: A Single-Center Retrospective Study
by Ilenia Foffa, Augusto Esposito, Ludovica Simonini, Roberta Lombardi, Maria Serena Parri, Angelo Monteleone, Pier Andrea Farneti and Cecilia Vecoli
J. Clin. Med. 2025, 14(15), 5196; https://doi.org/10.3390/jcm14155196 - 22 Jul 2025
Viewed by 267
Abstract
Background: Several blood biomarkers have shown a major role in predicting major adverse complications (MACs) in patients who have undergone cardiac surgery. Here, we aimed to investigate the possible role of the blood urea nitrogen (BUN) to serum albumin ratio (BAR) and [...] Read more.
Background: Several blood biomarkers have shown a major role in predicting major adverse complications (MACs) in patients who have undergone cardiac surgery. Here, we aimed to investigate the possible role of the blood urea nitrogen (BUN) to serum albumin ratio (BAR) and the inflammatory prognostic index (IPI) in predicting major adverse complication after surgical aorta valve replacement (SAVR). Methods: The clinical, echocardiographic, and clinical-chemistry laboratory data of 195 patients who underwent SAVR were evaluated. The post-surgical MACs (death, surgical re-exploration, myocardial infarction and cerebral ischemia) during the hospitalization were recorded. Univariate and multivariate logistic regression analyses were studied by comparing the basic clinical features, echocardiographic parameters, and patients’ hematological indices between patients with or without MACs. Results: The mean age was 66.1 years, and 62.5% were males. Logistic regression analysis showed that the left atrium volume (LAV), BAR, and IPI as either continuous or categorical variables were independently associated with MACs. Moreover, we found a combined effect of higher LAV with a higher value of BAR or IPI. Combined higher levels of LAV and BAR increased the risk of developing MACs by 9.8 (CI 95% = 2.8–34.3, p = 0.0003), while higher values of LAV and IPI increased the risk of developing MACs by 4.5. Conclusions: Higher levels of BAR and IPI, alone or in combination with higher LAVs, showed an independent predictive value of MACs after SAVR. These findings strongly support the importance of evaluating easily available biomarkers of the pre-operative status of patients in order to predict adverse outcomes. Full article
(This article belongs to the Section Cardiovascular Medicine)
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