Search Results (53)

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

Background: Anastomotic leakage (AL) is a severe complication of colorectal surgery and is associated with high morbidity, mortality, and prolonged hospital stay. Current predictive models vary in complexity and utility, highlighting the need for clinically accessible and accurate tools. This study aimed to develop and validate the clinical framework–anastomotic leakage prediction score (CF–ALPS) score, a practical and accessible risk prediction model for AL that integrates patient-, tumor-, and surgery-related factors. Methods: A retrospective cohort of 294 patients who underwent colorectal surgery between 2019 and 2024 was analyzed. Patients were categorized into the AL (n = 84) and non-AL groups (n = 210). The factors included age, sex, hypoalbuminemia, and comorbidities. Tumor-related factors included lymph node stage and neoadjuvant therapy, while surgical variables included urgency, duration, and type of procedure. The outcomes evaluated were the incidence of AL, duration of hospital stay, and in-hospital mortality. Independent predictors were identified using multivariate logistic regression analysis. The CF–ALPS score, which was developed from significant predictors, was validated using ROC curve analysis and 10-fold cross-validation. Results: A total of 294 patients who underwent colorectal surgery were included, of whom 84 (28.57%) developed AL. A male predominance was observed in the AL group (73.81% vs. 36.19%; p = 0.001). Nutritional status played a critical role, with significantly lower albumin levels in AL patients (2.8 ± 0.5 g/dL vs. 3.5 ± 0.4 g/dL; p < 0.001). Independent predictors of AL included hypoalbuminemia (<3.0 g/dL, OR: 0.52, p < 0.001), ASA score (OR, 1.85; p = 0.004), advanced lymph node stage (N2/N3, OR: 1.94, p = 0.037), neoadjuvant therapy (OR, 2.89; p = 0.002), and emergent surgery (OR, 1.67; p = 0.042). These variables formed the basis of the CF–ALPS score, which assigns weighted points based on the magnitude of their ORs. The CF–ALPS model achieved a ROC AUC of 0.82 (95% CI: 0.75–0.89) with a sensitivity of 85.0% and specificity of 78.0%. A cutoff score ≥7 demonstrated optimal risk stratification, classifying patients into high- and low-risk groups with a positive predictive value (PPV) of 72.0% and a negative predictive value (NPV) of 88.0%. Cross-validation yielded a moderate AUC of 0.44 (SD = 0.062). Conclusions: The CF–ALPS score offers a simple and effective tool for AL risk prediction in colorectal surgery, emphasizing its practicality and clinical integration. Although its predictive accuracy was moderate, further prospective multicenter validation is warranted. Full article

Background/Objectives: The Sigma-1 receptor (Sigmar1), an intracellular chaperone protein, is ubiquitously expressed throughout the body, but its role in peripheral organs, such as the kidneys, remains unclear. Here, we investigated the protective effects and molecular mechanisms of SA4503, a selective Sigmar1 agonist, on Adriamycin (ADR)-induced renal glomerular injury. Methods: Using in vitro and in vivo models, we evaluated the effects of SA4503 on ADR-induced podocyte injury, including podocyte survival, albumin permeability, urinary albumin levels, and Sigmar1-nephrin interactions. NE-100, a Sigmar1 antagonist, was co-administered to validate the specificity of the effects of SA4503. Results: Sigmar1 was highly expressed in podocytes and mouse kidney tissues. SA4503 significantly reduced ADR-induced podocyte injury and urinary albumin leakage in mice. Mechanistically, SA4503 preserved Sigmar1-nephrin interactions, which were disrupted in ADR-treated kidneys. This protective effect was abolished by NE-100 co-treatment, confirming the Sigmar1-dependency of SA4503’s action. Conclusions: These findings demonstrate that the activation of Sigmar1 by SA4503 protects against ADR-induced podocyte injury and glomerular damage, likely by stabilizing Sigmar1-nephrin interactions. Therefore, Sigmar1 represents a promising therapeutic target for glomerular diseases such as nephrotic syndrome. Full article

Management of severe dengue remains a clinical challenge. This retrospective study evaluated clinical features and laboratory biomarkers associated with severe dengue at Hospital Sultanah Aminah Johor Bahru from 1 January 2022 to 31 March 2023. Records of 99 patients, categorized into ICU (51) and non-ICU (48) groups, were identified and analyzed using SPSS version 28.0. Sociodemographic details, clinical features and laboratory biomarkers were collected. Patients aged 50 and older, those with obesity, and those with pre-existing comorbidities were significantly more likely to be admitted to the ICU. The four most common warning signs in both cohorts were lethargy/restlessness/confusion, abdominal pain, persistent vomiting, and diarrhea. Fever, or history of fever, and thrombocytopenia were the two most common severe dengue criteria present in both cohorts. ICU patients exhibited more signs of plasma leakage and abnormal laboratory findings, including normal white cell count, hypoalbuminemia, hyperbilirubinemia, and elevated creatine kinase. In contrast, leukopenia and normal albumin, bilirubin, and creatine kinase levels were more common in non-ICU patients. Hyponatremia and raised lactate dehydrogenase were seen in both groups. This study highlighted key differences and similarities in clinical features and laboratory biomarkers between ICU and non-ICU patients, emphasizing the need for further research to develop a comprehensive risk assessment tool for predicting severe dengue that resulted in ICU admission. Full article

Hemodialysis (HD) is a critical treatment for patients with end-stage kidney disease (ESKD). The effectiveness of conventional dialyzers used there could be compromised during extended use due to limited blood compatibility of synthetic polymeric membranes and sub-optimal dialyzer design. In fact, blood flow in the hollow fiber (HF) membrane could trigger inflammatory responses and thrombus formation, leading to reduced filtration efficiency and limiting therapy duration, a consequence of flowing the patients’ blood through the lumen of each fiber while the dialysate passes along the inter-fiber space (IOF, inside-out filtration). This study investigates the development of HF membranes for “outside-in filtration” (OIF) in HD. In OIF, blood flows through the inter-fiber space while dialysate flows within the fiber lumens, reducing the risk of fiber clogging and potentially extending treatment duration. For the OIF mode, the membrane should have a blood-compatible outer selective layer in contact with the patient’s blood. We develop HFs for OIF via liquid-induced phase separation using PES/PVP (polyethersulphone/polyvinylpyrrolidone) blends. The fibers’ surface morphology (SEM, scanning electron microscopy), chemistry (ATR-FTIR—attenuated total reflection-Fourier transform infrared spectroscopy, XPS—X-ray photoelectron spectroscopy), transport properties, and uremic toxin removal from human plasma are evaluated and compared to commercial HFs. These membranes feature a smooth, hydrophilic outer layer, porous lumen, ultrafiltration coefficient of 13–34 mL m² h⁻¹ mmHg⁻¹, adequate mechanical properties, low albumin leakage, and toxin removal performance on par with commercial membranes in IOF and OIF. They offer potential for more efficient long-term HD by reducing clogging and systemic anticoagulation needs and enhancing treatment time and toxin clearance. Full article

Background: Accurate and rapid detection of COVID-19 remains critical for clinical management, especially in resource-limited settings. Current diagnostic methods face challenges in terms of speed and reliability, creating a need for complementary AI-based models that integrate diverse data sources. Objectives: This study aimed to develop and evaluate a multi-modal machine learning model that combines clinical biomarkers and chest X-ray images to enhance diagnostic accuracy and provide interpretable insights. Methods: We used a dataset of 250 patients (180 COVID-19 positive and 70 negative cases) collected from clinical settings. Biomarkers such as CRP, ferritin, NLR, and albumin were included alongside chest X-ray images. Random Forest and Gradient Boosting models were used for biomarkers, and ResNet and VGG CNN architectures were applied to imaging data. A late-fusion strategy integrated predictions from these modalities. Stratified k-fold cross-validation ensured robust evaluation while preventing data leakage. Model performance was assessed using AUC-ROC, F1-score, Specificity, Negative Predictive Value (NPV), and Matthews Correlation Coefficient (MCC), with confidence intervals calculated via bootstrap resampling. Results: The Gradient Boosting + VGG fusion model achieved the highest performance, with an AUC-ROC of 0.94, F1-score of 0.93, Specificity of 93%, NPV of 96%, and MCC of 0.91. SHAP and LIME interpretability analyses identified CRP, ferritin, and specific lung regions as key contributors to predictions. Discussion: The proposed multi-modal approach significantly enhances diagnostic accuracy compared to single-modality models. Its interpretability aligns with clinical understanding, supporting its potential for real-world application. Full article

Objective: To determine whether the urinary excretion of podocyte degradation products varies according to PCOS phenotype and metabolic syndrome (MetS). Methods: The concentrations of podocalyxin (PDX) and nephrin, chronic markers of podocyte damage, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute glomerular damage, were analyzed in the morning urine samples of 50 PCOS patients and 50 healthy controls matched by age and BMI. Albuminuria was assessed by calculating the urine albumin–creatinine ratio (uACR). Results: The PDX, nephrin and NGAL concentrations of PCOS participants were significantly higher than those of the control group. While PDX, nephrin and NGAL levels of classic phenotypes were similar, they were higher than ovulatory and non-hyperandrogenic phenotypes. Significant increases in urinary levels of each podocyte protein were detected in PCOS patients with MetS compared to patients without MetS. A positive significant correlation between podocyte proteins and BMI, systolic blood pressure, testosterone, glucose, HOMA-IR and uACR. After adjusting for age and BMI, podocyte proteins were an independent risk factor for microalbuminuria. The incidence of microalbuminuria in PCOS increased 6-fold compared to controls. The frequency of microalbuminuria was higher in classical phenotypes than in ovulatory phenotype. The frequency of microalbuminuria in PCOS patients with MetS was 6.5 times higher than in PCOS patients without MetS. Conclusions: In PCOS accompanied by hyperandrogenemia or metabolic syndrome, leakage of acute and chronic podocyte breakdown products into the urine becomes more pronounced. Full article

The clinical consequences of perioperative albumin extravasation accompanying major abdominal surgery remain underexplored. We retrospectively reviewed the data of patients who underwent cytoreductive surgery (CRS) and hyperthermic intraoperative peritoneal chemotherapy (HIPEC). Parameters of albumin kinetics, including serum albumin concentration decrease (∆Alb) and extravasated albumin level (Alb_shift), were assessed from surgery until postoperative day (POD) 3. Logistic regression analysis identified factors associated with major complications. The association of albumin kinetics with major complications was evaluated using receiver operating characteristic (ROC) curve analysis. Serum albumin levels decreased during surgery and subsequently increased. Of the 121 analyzed patients, 25 (21%) developed major complications. The ∆Alb and Alb_shift during surgery and on POD 3 were greater in patients who developed major complications than in those who did not (12 ± 12 vs. 6 ± 14, p = 0.032, and 127.5 (71.9) vs. 48.5 (44.9), p < 0.001, respectively). Perioperative ∆Alb and Alb_shift were associated with major complications. The areas under the ROC curve of Alb_shift during the 3 days post-surgery and Alb_shift on POD 3 were 0.843 and 0.910, respectively. Alb_shift during the 3 days post-surgery and Alb_shift on POD 3 were correlated with complications (p < 0.05). In conclusion, perioperative albumin loss was associated with major complications in patients undergoing CRS and HIPEC. Alb_shift was associated with serious complications. Full article

Background: Online hemodiafiltration (OHDF) has a lower mortality rate than hemodialysis (HD). We aimed to investigate the impact of the albumin leakage on the mortality of patients receiving HD or OHDF. Methods: In this single-center study, consecutive patients receiving renal replacement therapy between January and April 2018 were retrospectively registered. Using (1:1) propensity score matching, 3-year all-cause mortality was compared between patients receiving HD and OHDF, and the impact of albumin leakage on the mortality rate in both groups was investigated. Results: Of the 460 patients, 137 patients receiving HD were matched with an equal number of patients receiving OHDF. OHDF was associated with higher albumin leakage (p < 0.001) and a lower mortality than HD (log-rank test, p < 0.001). Albumin leakage was associated with mortality in patients receiving HD (per 1 g increase, hazard ratio (HR): 0.495, 95% confidence interval (CI): 0.275–0.888) and patients receiving OHDF (per 1 g increase, HR: 0.734, 95% CI: 0.588–0.915). Patients receiving HD, with the highest albumin leakage tertile (>3 g), had a similar mortality rate to patients receiving OHDF, with similar albumin leakage. Conclusions: The negative relationship between albumin leakage and mortality suggests the benefit of removing middle- to -large-molecular-weight substances to improve survival. Full article

Anastomotic leakage (AL) remains the main cause of post-esophagectomy morbidity and mortality. Early detection can avoid sepsis and reduce morbidity and mortality. This study evaluates the diagnostic accuracy of the Nun score and its components as early detectors of AL. This single-center observational cohort study included all esophagectomies from 2010 to 2020. C-reactive protein (CRP), albumin (Alb), and white cell count (WCC) were analyzed and NUn scores were calculated. The area under the curve statistic (AUC) was used to assess their predictive accuracy. A total of 74 of the 668 patients (11%) developed an AL. CRP and the NUn-score proved to be good diagnostic accuracy tests on postoperative day (POD) 2 (CRP AUC: 0.859; NUn score AUC: 0.869) and POD 4 (CRP AUC: 0.924; NUn score AUC: 0.948). A 182 mg/L CRP cut-off on POD 4 yielded a 87% sensitivity, 88% specificity, a negative predictive value (NPV) of 98%, and a positive predictive value (PPV) of 47.7%. A NUn score cut-off > 10 resulted in 92% sensitivity, 95% specificity, 99% NPV, and 68% PPV. Albumin and WCC have limited value in the detection of post-esophagectomy AL. Elevated CRP and a high NUn score on POD 4 provide high accuracy in predicting AL after esophageal cancer surgery. Their high negative predictive value allows to select patients who can safely proceed with enhanced recovery protocols. Full article

Compromised blood-retinal barrier (BRB) integrity is a significant factor in ocular diseases like uveitis and retinopathies, leading to pathological vascular permeability and retinal edema. Adherens and tight junction (AJ and TJ) dysregulation due to retinal inflammation plays a pivotal role in BRB disruption. We investigated the potential of ICG001, which inhibits β-catenin-mediated transcription, in stabilizing cell junctions and preventing BRB leakage. In vitro studies using human retinal endothelial cells (HRECs) showed that ICG001 treatment improved β-Catenin distribution within AJs post lipopolysaccharide (LPS) treatment and enhanced monolayer barrier resistance. The in vivo experiments involved a mouse model of LPS-induced ocular inflammation. LPS treatment resulted in increased albumin leakage from retinal vessels, elevated vascular endothelial growth factor (VEGF) and Plasmalemmal Vesicle-Associated Protein (PLVAP) expression, as well as microglia and macroglia activation. ICG001 treatment (i.p.) effectively mitigated albumin leakage, reduced VEGF and PLVAP expression, and reduced the number of activated microglia/macrophages. Furthermore, ICG001 treatment suppressed the surge in inflammatory cytokine synthesis induced by LPS. These findings highlight the potential of interventions targeting β-Catenin to enhance cell junction stability and improve compromised barrier integrity in various ocular inflammatory diseases, offering hope for better management and treatment options. Full article

Septic shock is characterized by endothelial dysfunction, leading to tissue edema and organ failure. Heparan sulfate (HS) is essential for vascular barrier integrity, possibly via albumin as a carrier. We hypothesized that supplementing fluid resuscitation with HS would improve endothelial barrier function, thereby reducing organ edema and injury in a rat pneumosepsis model. Following intratracheal inoculation with Streptococcus pneumoniae, Sprague Dawley rats were randomized to resuscitation with a fixed volume of either Ringer’s Lactate (RL, standard of care), RL supplemented with 7 mg/kg HS, 5% human albumin, or 5% human albumin supplemented with 7 mg/kg HS (n = 11 per group). Controls were sham inoculated animals. Five hours after the start of resuscitation, animals were sacrificed. To assess endothelial permeability, 70 kD FITC-labelled dextran was administered before sacrifice. Blood samples were taken to assess markers of endothelial and organ injury. Organs were harvested to quantify pulmonary FITC-dextran leakage, organ edema, and for histology. Inoculation resulted in sepsis, with increased lactate levels, pulmonary FITC-dextran leakage, pulmonary edema, and pulmonary histologic injury scores compared to healthy controls. RL supplemented with HS did not reduce median pulmonary FITC-dextran leakage compared to RL alone (95.1 CI [62.0–105.3] vs. 87.1 CI [68.9–139.3] µg/mL, p = 0.76). Similarly, albumin supplemented with HS did not reduce pulmonary FITC-dextran leakage compared to albumin (120.0 [93.8–141.2] vs. 116.2 [61.7 vs. 160.8] µg/mL, p = 0.86). No differences were found in organ injury between groups. Heparan sulfate, as an add-on therapy to RL or albumin resuscitation, did not reduce organ or endothelial injury in a rat pneumosepsis model. Higher doses of heparan sulfate may decrease organ and endothelial injury induced by shock. Full article

Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans. While models exist for the induction of renal failure, none are optimized for the implantation of devices to the retroperitoneal vasculature. We successfully piloted an embolization-to-implantation protocol enabling the first implant of a silicon nanopore membrane hemodialyzer (SNMHD) in a swine renal failure model. Renal arterial embolization is a non-invasive approach to near-total nephrectomy that preserves retroperitoneal anatomy for device implants. Silicon nanopore membranes (SNM) are efficient blood-compatible membranes that enable novel approaches to RRT. Yucatan minipigs underwent staged bilateral renal arterial embolization to induce renal failure, managed by intermittent hemodialysis. A small-scale arteriovenous SNMHD prototype was implanted into the retroperitoneum. Dialysate catheters were tunneled externally for connection to a dialysate recirculation pump. SNMHD clearance was determined by intermittent sampling of recirculating dialysate. Creatinine and urea clearance through the SNMHD were 76–105 mL/min/m² and 140–165 mL/min/m², respectively, without albumin leakage. Normalized creatinine and urea clearance measured in the SNMHD may translate to a fully implantable clinical-scale device. This pilot study establishes a path toward therapeutic testing of the clinical-scale SNMHD and other implantable RRT devices. Full article

Background: This study aims to clarify the perioperative risk factors and short-term prognosis of central bisectionectomy (CB) for hepatocellular carcinoma (HCC). Methods: Surgical data from 142 selected patients out of 171 HCC patients who underwent anatomical CB (H458) between 2005 and 2020 were collected from 17 expert institutions in a single-arm retrospective study. Results: Morbidities recorded by the International Study Group of Liver Surgery (ISGLS) from grade BC post-hepatectomy liver failure (PHLF) and bile leakage (PHBL), or complications requiring intervention were observed in 37% of patients. A multivariate analysis showed that increased blood loss (iBL) > 1500 mL from PHLF (risk ratio [RR]: 2.79), albumin level < 4 g/dL for PHBL (RR, 2.99), involvement of segment 1, a large size > 6 cm, or compression of the hepatic venous confluence or cava by HCC for all severe complications (RR: 5.67, 3.75, 6.51, and 8.95, respectively) (p < 0.05) were significant parameters. Four patients (3%) died from PHLF. HCC recurred in 50% of 138 surviving patients. The three-year recurrence-free and overall survival rates were 48% and 81%, respectively. Conclusions: Large tumor size and surrounding tumor involvement, or compression of major vasculatures and the related iBL > 1500 mL were independent risk factors for severe morbidities in patients with HCC undergoing CB. Full article

Early detection of pharyngocutaneous fistula (PCF) after total laryngectomy (TL) could prevent severe complications such as major vessel rupture. We aimed to develop prediction models for detecting PCF in the early postoperative period. We retrospectively analyzed patients (N = 263) who received TL between 2004 and 2021. We collected clinical data for fever (>38.0 °C) and blood tests (WBC, CRP, albumin, Hb, neutrophils, lymphocytes) on postoperative days (POD) 3 and 7, and fistulography on POD 7. Clinical data were compared between fistula and no fistula groups, and significant factors were selected using machine learning. Using these clinical factors, we developed improved prediction models for PCF detection. Fistula occurred in 86 (32.7%) patients. Fever was significantly (p < 0.001) more common in the fistula group, and ratios (POD 7 to 3) of WBC, CRP, neutrophils, and neutrophils-to-lymphocytes (NLR) were significantly higher (all p ≤ 0.001) in the fistula group than in the no fistula group. Leakage on fistulography was more common in the fistula group (38.2%) than in the no fistula group (3.0%). The area under curve (AUC) of fistulography alone was 0.68, but predictive models using a combination of fistulography, WBC at POD 7, and neutrophil ratio (POD 7/POD 3) showed better diagnostic performance (AUC of 0.83). Our predictive models may detect PCF early and accurately, which could reduce fatal complications following PCF. Full article