U-shaped relationship between fasting blood glucose and urinary albumin-to-creatinine ratio in the general United States population.

Objective: The current controversy surrounding the association between fasting blood glucose (FBG) and albuminuria necessitates further investigation. Hence, the primary objective of this study was to examine the relationship between FBG and urinary albumin-to-creatinine ratio (UACR). Methods: A cohort of complete data from National Health and Nutrition Examination Survey (NHANES) participants (1999-2020) was analyzed. Linear regression analyses and a generalized additive model explored the association between FBG and UACR. Furthermore, the stability of this relationship across different populations was assessed. Results: The study involved a total of 20,264 participants who were identified as U.S. citizens. By employing linear regression analysis, a statistically significant relationship was observed between elevated FBG levels and an increase in UACR (P<0.0001). Additionally, using a generalized additive model analysis, a U-shaped correlation between FBG and UACR was identified. Further examination using threshold effect analysis indicated a turning point for FBG at 5.44 mmol/L. A noteworthy finding in multiple populations is the consistent U-shaped association between FBG and UACR, except for individuals with serum uric acid levels ≥420 µmol/L and those who refrain from alcohol consumption. Conclusion: The general U.S. population has a U-shaped nonlinear relationship between FBG and UACR.

Malnutrition in Head and Neck Free Flap Reconstruction as a Predictor of Adverse Outcomes.

INTRODUCTION: Malnutrition is associated with increased mortality in patients with head and neck (H&N) cancer. Because albumin levels are used as a surrogate for nutritional status, the purpose of this study is to assess whether malnutrition is associated with adverse postoperative outcomes in H&N free flap reconstruction. MATERIALS AND METHODS: The 2006-2018 National Surgical Quality Improvement Program Database was queried for patients undergoing flap procedures of the H&N based on Current Procedure Terminology codes. Patients were included if they were operated on by an otolaryngologist or when the primary surgical site was H&N. Nutritional status was categorized as malnourished (preoperative albumin level <3.5 g/dL) or normal (preoperative albumin level ≥3.5 g/dL). Major complications included pulmonary complications, cardiac complications, deep vein thrombosis/pulmonary embolism, and sepsis/septic shock. Minor complications included surgical infection, urinary tract infection, bleeding, and dehiscence. Data were analyzed via univariate chi-square and multivariate regression analyses. RESULTS: Of the patients, 2532 (83.3%) had normal albumin and 506 (16.7%) had hypoalbuminemia. Patients with hypoalbuminemia were more likely to have smoking history (P = 0.008), pulmonary comorbidity (P < 0.001), renal comorbidity (P = 0.018), disseminated cancer (P < 0.001), steroid use (P < 0.001), recent weight loss (P < 0.001), bleeding disorder (P = 0.023), and preoperative transfusion (P < 0.001). After adjustment for preoperative variance, malnourished patients were more likely to experience death (P < 0.001), return to operating room (P < 0.001), free flap failure (P = 0.008), pulmonary complication (P < 0.001), deep vein thrombosis/pulmonary embolism (P = 0.019), wound disruption (P = 0.042), intraoperative transfusion (P < 0.001), minor complication (P < 0.001), major complication (P < 0.001), and extended length of stay (P < 0.001). Of the patients with normal albumin, 2.1% experienced flap failure compared with 6.3% of patients with hypoalbuminemia. It should be noted that malnourished patients were 3.370 times more likely to experience flap failure (95% confidence interval, 1.383-8.212; P = 0.008) and 3.975 times more likely to experience death (95% confidence interval, 1.700-9.626; P = 0.001) than those with normal albumin. CONCLUSION: Malnutrition is associated with death, flap failure, minor complications, and other major complications following H&N free flap surgery, even after controlling for preoperative variance. Optimizing preoperative nutrition status before free flap procedures may ameliorate morbidity and mortality in H&N patients.

Trends of correlations between serum levels of growth hormone and insulin-like growth factor-I in general practice.

Serum levels of growth hormone (GH) and insulin-like growth factor (IGF)-I are crucial in the diagnosis and management of GH-related diseases. However, these levels are affected by nutritional and metabolic status. To elucidate the correlations between GH and IGF-I in various conditions, a retrospective analysis was performed for adult patients in which GH levels were examined by general practitioners during the period from January 2019 to December 2021. Of 642 patients, 33 patients were diagnosed with acromegaly, 21 were diagnosed with GH deficiency (GHD), and 588 were diagnosed with non-GH-related diseases (NGRD). In contrast to the positive correlations found between the levels of GH and IGF-I in patients with acromegaly (R=0.50; P<0.001) and patients with GHD (R=0.39; P=0.08), a negative correlation was found in the NGRD group (R=-0.23; P<0.001). In that group, the results of multivariable analysis showed that GH levels were predominantly influenced by gender and body mass index (BMI), whereas IGF-I levels were modulated by albumin in addition to age and GH. Of note, in the NGRD group, there was an enhanced negative correlation between GH and IGF-I under conditions of BMI < 22 and albumin < 4.0 g/dL (R=-0.45; P<0.001), and the negative correlation between GH and IGF-I was reinforced by excluding patients with other pituitary diseases and patients taking oral steroids (R=-0.51; P<0.001 and R=-0.59; P<0.001, respectively). Collectively, the results indicate that attention should be given to the presence of a negative correlation between serum levels of GH and IGF-I, especially in lean and low-nutritious conditions.

Therapeutic drug monitoring in inflammatory bowel disease patients on vedolizumab.

OBJECTIVE: We aimed to investigate whether vedolizumab (VDZ) levels were associated with inflammatory markers or clinical or endoscopic scoring in inflammatory bowel disease (IBD). METHODS: Besides demographic data, clinical scoring, endoscopic data, and laboratory markers of IBD patients treated with VDZ from 2015 to 2020 who had trough levels drawn on maintenance therapy were collected at baseline and at follow-up (after at least 8 weeks on VDZ therapy or after change in dose frequency). Low drug levels were defined as VDZ trough <20 µg/mL. RESULTS: We identified 89 patients with a mean age of 42.9 years. Of the 90 total trough levels drawn, 61.1% were low. Among patients on every 8 week (Q8 week) VDZ dosing, 81.5% had low troughs. After increasing dosing frequency to Q4 weeks, all patients showed improvement in VDZ levels, but 30.6% remained <20 µg/mL. Higher VDZ levels on Q8 week dosing were associated with higher albumin levels (P = 0.01). While higher VDZ levels on Q4 week dosing were associated with higher albumin (P = 0.02), lower erythrocyte sedimentation rate (P = 0.04) and higher likelihood of having mild disease or endoscopic remission (P = 0.01). No significant association was found between VDZ levels and clinical scoring, body mass index, hemoglobin, vitamin D or platelet levels on either Q8 or Q4 week dosing. CONCLUSIONS: Higher VDZ troughs were associated with higher albumin, mild endoscopic disease or endoscopic remission. Patients who continue to have low VDZ troughs despite Q4 week dosing may require a change in therapy.

Poor Nutritional Status Is Associated with Death in a Population of Dialyzed Older Persons.

BACKGROUND: Older patients in hemodialysis have high prevalence of malnutrition that is often associated with rapid weight loss till cachexia. OBJECTIVES: We aimed to investigate whether in older patients undergoing hemodialysis the association between poor nutritional status and mortality may be independent of comorbidities and other risk factors. DESIGN: Retrospective longitudinal study. SETTING: Unit of Nephrology, Dialysis and Kidney Transplantation of the Policlinic Hospital of Milan, Milan, Italy. PARTICIPANTS: A total of 107 prevalent patients undergoing hemodialysis for at least three months. MEASUREMENTS: Sociodemographic, clinical, and biological data were recorded. Unintentional weight loss (UWL) was defined as loss of body weight > 5% in 3 months or > 10% in 6 months. We computed a 21-item Frailty Index that included clinical conditions associated with malnutrition and mortality in this population. Unadjusted and adjusted Cox proportional hazard models were performed to test the association of UWL, albumin and transferrin levels with death. Survival analyses based on Kaplan-Meier estimates were performed. RESULTS: Patients' age was 79 (±7.7) years; 38 (35%) were women. Thirty-one patients (29%) died during follow-up. Eighteen (16.8%) patients experienced UWL during the follow-up period. UWL was positively associated with death in the unadjusted model and even after the progressive inclusion of potential confounders. Low albumin levels were positively associated with death only in the unadjusted and partially adjusted models while low transferrin levels were not associated with death in none of the models. Mortality was significantly higher in those patients experiencing both UWL and albumin levels below 3.5 mg/dL. CONCLUSIONS: In older patients undergoing chronic hemodialysis UWL is associated with mortality independently of comorbidities and other risk factors. Patients presenting both UWL and low albumin levels were those experiencing the worst outcomes in terms of mortality.

Association of Albuminuria With Chronic Kidney Disease Progression in Persons With Chronic Kidney Disease and Normoalbuminuria : A Cohort Study.

BACKGROUND: Albuminuria is a major risk factor for chronic kidney disease (CKD) progression, especially when categorized as moderate (30 to 300 mg/g) or severe (>300 mg/g). However, there are limited data on the prognostic value of albuminuria within the normoalbuminuric range (<30 mg/g) in persons with CKD. OBJECTIVE: To estimate the increase in the cumulative incidence of CKD progression with greater baseline levels of albuminuria among persons with CKD who had normoalbuminuria (<30 mg/g). DESIGN: Multicenter prospective cohort study. SETTING: 7 U.S. clinical centers. PARTICIPANTS: 1629 participants meeting criteria from the CRIC (Chronic Renal Insufficiency Cohort) study with CKD (estimated glomerular filtration rate [eGFR], 20 to 70 mL/min/1.73 m2) and urine albumin-creatinine ratio (UACR) less than 30 mg/g. MEASUREMENTS: Baseline spot urine albumin divided by spot urine creatinine to calculate UACR as the exposure variable. The 10-year adjusted cumulative incidences of CKD progression (composite of 50% eGFR decline or kidney failure [dialysis or kidney transplantation]) from confounder adjusted survival curves using the G-formula. RESULTS: Over a median follow-up of 9.8 years, 182 of 1629 participants experienced CKD progression. The 10-year adjusted cumulative incidences of CKD progression were 8.7% (95% CI, 5.9% to 11.6%), 11.5% (CI, 8.8% to 14.3%), and 19.5% (CI, 15.4% to 23.5%) for UACR levels of 0 to less than 5 mg/g, 5 to less than 15 mg/g, and 15 mg/g or more, respectively. Comparing persons with UACR 15 mg/g or more to those with UACR 5 to less than 15 mg/g and 0 to less than 5 mg/g, the absolute risk differences were 7.9% (CI, 3.0% to 12.7%) and 10.7% (CI, 5.8% to 15.6%), respectively. The 10-year adjusted cumulative incidence increased linearly based on baseline UACR levels. LIMITATION: UACR was measured once. CONCLUSION: Persons with CKD and normoalbuminuria (<30 mg/g) had excess risk for CKD progression, which increased in a linear fashion with higher levels of albuminuria. PRIMARY FUNDING SOURCE: None.

Particulate polycyclic aromatic hydrocarbons and metals, DNA methylation and DNA methyltransferase among middle-school students in China.

The main components of particulate matter (PM) had been reported to change DNA methylation levels. However, the mixed effect of PM and its constituents on DNA methylation and the underlying mechanism in children has not been well characterized. To investigate the association between single or mixture exposures and global DNA methylation or DNA methyltransferases (DNMTs), 273 children were recruited (110 in low-exposed area and 163 in high-exposed area) in China. Serum benzo[a]pyridin-7,8-dihydroglycol-9, 10-epoxide (BPDE)-albumin adduct and urinary metals were determined as exposure markers. The global DNA methylation (% 5mC) and the mRNA expression of DNMT1, and DNMT3A were measured. The linear regression, quantile-based g-computation (QGC), and mediation analyses were performed to investigate the effects of individual and mixture exposure. We found that significantly lower levels of % 5mC (P < 0.001) and the mRNA expression of DNMT3A in high-PM exposed group (P = 0.031). After adjustment for age, gender, BMI z-score, detecting status of urinary cotinine, serum folate, and white blood cells, urinary arsenic (As) was negatively correlated with the % 5mC. One IQR increase in urinary As (19.97 µmol/mol creatinine) was associated with a 11.06 % decrease in % 5mC (P = 0.026). Serum BPDE-albumin adduct and urinary cadmium (Cd) were negatively correlated with the levels of DNMT1 and DNMT3A (P < 0.05). Mixture exposure was negatively associated with expression of DNMT3A in QGC analysis (ß: -0.19, P < 0.001). Mixture exposure was significantly associated with decreased % 5mC in the children with non-detected cotinine or normal serum folate (P < 0.05), which the most contributors were PAHs and As. The mediated effect of hypomethylation through DNMT1 or DNMT3A pathway was not observed. Our findings indicated that individual and mixture exposure PAHs and metal components had negative associations with global DNA methylation and decreased DNMT3A expression significantly in school-age individuals.

[Pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma: a prospective phaseâ ¡study].

Objective: To evaluate the efficacy and safety of pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC). Methods: This was a prospective, single-arm, open label, phase 2 clinical study enrolling patients at the Cancer Hospital of the Chinese Academy of Medical Sciences with R/M HNSCC treated with pembrolizumab plus nab-paclitaxel and cisplatin or carboplatin. After six cycles of treatment, patients received pembrolizumab as maintenance therapy until disease progression or intolerable toxicity or completion of 35 cycles of treatment. The primary endpoint was objective response rate, and secondary endpoints included overall survival, progression-free survival, and safety profile. Efficacy was evaluated according to the response evaluation criteria in solid tumors 1.1, survival analysis was performed using the Kaplan-Meier method, and adverse events were assessed using the America National Cancer Institute Common Terminology Criteria for Adverse Events 5.0. Results: A total of 30 patients with R/M HNSCC were enrolled from 23 April 2021 to 22 March 2023, including 28 males and 2 females, with a median age of 67 years. The median follow-up time was 14.5 months, the objective response rate was 70.0%, the disease control rate was 96.7%, and the median progression-free survival and overall survival of all patients were 11.6 months and 18.8 months, respectively. Median duration of response was up to 17.3 months. Grade≥3 treatment-related adverse events were leukopenia (26.7%), neutropenia (26.7%), peripheral neurotoxicity (3.3%), rash (3.3%), hyperalgesia (3.3%), and immune-related pneumonitis (3.3%). The most common immune-related adverse event was hypothyroidism (40.0%). Conclusion: Pembrolizumab combined with nab-paclitaxel and platinum shows encouraging antitumor activity accompanied with a manageable safety profile in untreated R/M HNSCC patients in China.

[Phase â ¡ clinical trial of PD-1 inhibitor combined with chemotherapy for locally advanced resectable oral squamous cell carcinoma].

Objective: To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma. Methods: This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis. Results: A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups (P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group (P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death (P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion: The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

[Prediction of pathological remission of head and neck squamous cell carcinoma patients after neoadjuvant immunochemotherapy and construction of clinical model based on clinical features and inflammatory markers].

Objective: To analyze the potential clinical biological factors influencing the major pathological response (MPR) to neoadjuvant immunochemotherapy in patients with resectable head and neck squamous cell carcinoma (HNSCC). Methods: This retrospective study enrolled patients with resectable HNSCC who underwent neoadjuvant immunochemotherapy at Sun Yat-sen University Cancer Center from June 1, 2019 to December 31, 2021. Binary logistic regression was used to analyze the correlation between clinical characteristics, inflammatory markers and MPR, and a nomogram model was constructed. The calibration curve and decision curve analysis were used to verify the predictive ability and accuracy of the nomogram model. Results: A total of 173 patients were included in the study, with 141 males and 32 females, aged from 22 to 83 years. After pathological assessment, the patients were divided into two groups: MPR group (108 cases) and non MPR group (65 cases). Logistics regression analysis indicated that the patients with HPV+oropharyngeal cancer, partial response or complete response by imaging assessment, low pre-treatment platelet/lymphocyte ratio, low pre-treatment C reactive protein/albumin ratio and lower pre-and post-treatment C reactive protein/albumin ratio difference were more likely to have MPR (all P<0.05). Nomogram model was constructed based on the above factors, with a C-index of 0.826 (95%CI: 0.760-0.892), and the calibration curve and decision curve analysis confirmed the prediction accuracy of the model. Conclusion: This study shows that many factors are related to MPR of patients with resectable HNSCC receiving neoadjuvant immunochemotherapy and the constructed nomogram model helps to develop personalized treatment strategies for the patients.

Ustekinumab effectiveness in Crohn's disease with lesions in the intestines.

Ustekinumab is prescribed for the treatment of patients with steroid-resistant moderate to severe Crohn's disease. We investigated its clinical outcome in patients with small and large intestinal lesions. Patients who were newly administered ustekinumab between March 2014 and December 2020 at Hamamatsu University Hospital were included in the study. The primary endpoint was Crohn's disease activity index score at baseline and weeks 8, 24, and 48 after the initiation of treatment, and secondary endpoints were albumin, hemoglobin, and C-reactive protein at these time points. Ustekinumab treatment retention was examined in both groups; the 2 groups were compared using the Friedman test, Mann-Whitney U test, or Fisher exact test. Overall, Crohn's disease activity index scores improved between baseline and 48 weeks, but the difference was not significant. However, there was a significant improvement between baseline and 48 weeks in patients with lesions in the small intestine only. Overall, patients showed significant improvement in albumin levels between baseline and 48 weeks but not in C-reactive protein or hemoglobin levels. When limited to patients with lesions in the small intestine, albumin and hemoglobin levels showed significant improvement. Both types showed high rates of treatment retention, although there was no significant difference. Ustekinumab appears to be a safe and effective treatment option that may be particularly effective in patients with lesions in the small intestine only.

Analysis of related factors of CRA in lung cancer patients with different serum iron levels: A retrospective cohort study.

BACKGROUND: Serum iron, an essential component of hemoglobin (Hb) synthesis in vivo, is a crucial parameter for evaluating the body's iron storage and metabolism capacity. Iron deficiency leads to reduced Hb synthesis in red blood cells and smaller red blood cell volume, ultimately resulting in iron-deficiency anemia. Although serum iron cannot independently evaluate iron storage or metabolism ability, it can reflect iron concentration in vivo and serve as a good predictor of iron-deficiency anemia. Therefore, exploring the influence of different serum iron levels on anemia and diagnosing and treating iron deficiency in the early stages is of great significance for patients with lung cancer. AIM: This study aims to explore the related factors of cancer-related anemia (CRA) in lung cancer and construct a nomogram prediction model to evaluate the risk of CRA in patients with different serum iron levels. METHODS: A single-center retrospective cohort study was conducted, including 1610 patients with lung cancer, of whom 1040 had CRA. The relationship between CRA and its influencing factors was analyzed using multiple linear regression models. Lung cancer patients were divided into two groups according to their serum iron levels: decreased serum iron and normal serum iron. Each group was randomly divided into a training cohort and a validation cohort at a ratio of 7:3. The influencing factors were screened by univariate and multivariate logistic regression analyses, and nomogram models were constructed. The area under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the models. RESULTS: CRA in lung cancer is mainly related to surgery, chemotherapy, Karnofsky Performance Status (KPS) score, serum iron, C-reactive protein (CRP), albumin, and total cholesterol (p < 0.05). CRA in lung cancer patients with decreased serum iron is primarily associated with albumin, age, and cancer staging, while CRA in lung cancer patients with normal serum iron is mainly related to CRP, albumin, total cholesterol, and cancer staging. The area under the ROC curve of the training cohort and validation cohort for the prediction model of lung cancer patients with decreased serum iron was 0.758 and 0.760, respectively. Similarly, the area under the ROC curve of the training cohort and validation cohort for the prediction model of lung cancer patients with normal serum iron was 0.715 and 0.730, respectively. The calibration curves of both prediction models were around the ideal 45° line, suggesting good discrimination and calibration. DCA showed that the nomograms had good clinical utility. CONCLUSION: Both models have good reliability and validity and have significant clinical value. They can help doctors better assess the risk of developing CRA in lung cancer patients. CRP is a risk factor for CRA in lung cancer patients with normal serum iron but not in patients with decreased serum iron. Therefore, whether CRP and the inflammatory state represented by CRP will further aggravate the decrease in serum iron levels, thus contributing to anemia, warrants further study.

Prognostic significance of inflammation scores in malignant mesothelioma.

OBJECTIVE: The relationship between inflammatory markers and survival in many cancers has been investigated previously. Inflammatory markers may also offer the possibility of predicting surveillance in patients with malignant mesothelioma. Our study seeks to enhance comprehension of how variables such as the nutritional status and inflammation indices of malignant mesothelioma patients impact the disease's progression and prognosis. PATIENTS AND METHODS: This study included patients who were treated at the Erciyes University Medical Oncology Clinic between 2010 and 2022 and diagnosed with malignant mesothelioma. This is a retrospective single-center cohort study. Receiver Operating Characteristic (ROC) analysis was applied to determine the inflammation markers' optimal cut-off values with high sensitivity and specificity. Patients were categorized based on these values. The differences in overall survival (OS) and progression-free survival (PFS) between categorized groups were assessed using Log-rank curves and Kaplan-Meier tests. Multivariate analysis was performed using Cox regression analysis on statistically significant data. The relationship between inflammation markers and malignant mesothelioma survival was evaluated. RESULTS: There are 115 patients in this study. Pre-treatment high neutrophil to lymphocyte ratio (NLR) (HR: 1.34, 95% CI: 1.12-2.83, p=0.04), high pan-immune inflammation value (PIIV) (HR: 2.01, 95% CI: 1.32-4.79, p=0.03), and high systemic inflammation response index (SIRI) (HR: 1.34, 95% CI: 1.2-2.78, p=0.04) were associated with poor OS. Conversely, high advanced lung cancer inflammation index (ALI) (HR: 0.73, 95% CI: 0.53-0.84, p=0.03) and high hemoglobin-albumin-lymphocyte and platelet (HALP) (HR: 0.67, 95% CI: 0.23-0.78, p=0.02) were associated with favorable survival. CONCLUSIONS: Our study investigated the prognostic value of various inflammation markers in malignant mesothelioma patients and suggests that composite formulas like NLR, PIIV, SIRI, ALI, and HALP that incorporate CBC cells and nutritional parameters like albumin, height, and weight could more consistently and accurately predict malignant mesothelioma prognosis.

Biodegradable suture development-based albumin composites for tissue engineering applications.

Recent advancements in the field of biomedical engineering have underscored the pivotal role of biodegradable materials in addressing the challenges associated with tissue regeneration therapies. The spectrum of biodegradable materials presently encompasses ceramics, polymers, metals, and composites, each offering distinct advantages for the replacement or repair of compromised human tissues. Despite their utility, these biomaterials are not devoid of limitations, with issues such as suboptimal tissue integration, potential cytotoxicity, and mechanical mismatch (stress shielding) emerging as significant concerns. To mitigate these drawbacks, our research collective has embarked on the development of protein-based composite materials, showcasing enhanced biodegradability and biocompatibility. This study is dedicated to the elaboration and characterization of an innovative suture fabricated from human serum albumin through an extrusion methodology. Employing a suite of analytical techniques-namely tensile testing, scanning electron microscopy (SEM), and thermal gravimetric analysis (TGA)-we endeavored to elucidate the physicochemical attributes of the engineered suture. Additionally, the investigation extends to assessing the influence of integrating biodegradable organic modifiers on the suture's mechanical performance. Preliminary tensile testing has delineated the mechanical profile of the Filament Suture (FS), delineating tensile strengths spanning 1.3 to 9.616 MPa and elongation at break percentages ranging from 11.5 to 146.64%. These findings illuminate the mechanical versatility of the suture, hinting at its applicability across a broad spectrum of medical interventions. Subsequent analyses via SEM and TGA are anticipated to further delineate the suture's morphological features and thermal resilience, thereby enriching our comprehension of its overall performance characteristics. Moreover, the investigation delves into the ramifications of incorporating biodegradable organic constituents on the suture's mechanical integrity. Collectively, the study not only sheds light on the mechanical and thermal dynamics of a novel suture material derived from human serum albumin but also explores the prospective enhancements afforded by the amalgamation of biodegradable organic compounds, thereby broadening the horizon for future biomedical applications.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma: A case report.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited effective treatment especially after first-line chemotherapy. The human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC) positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC. CASE SUMMARY: We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn't have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy. CONCLUSION: PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

C-reactive protein to albumin ratio as a prognostic tool for predicting intravenous immunoglobulin resistance in children with kawasaki disease: a systematic review of cohort studies.

BACKGROUND: Intravenous immunoglobulin (IVIG) is the primary treatment for Kawasaki disease (KD). However, 10-20% of KD patients show no response to IVIG treatment, making the early prediction of IVIG resistance a key focus of KD research. Our aim is to explore the application of the C-reactive protein to albumin ratio (CAR) for predicting IVIG resistance in children with KD through meta-analysis. METHODS: Cochrane Library, PubMed, MEDLINE, EMbase, CNKI, WanFang, the Chinese Biomedical Database, and CQVIP were searched up to November 2023 for cohort studies on predicting IVIG-resistant KD using the CAR. Articles were selected based on pre-established inclusion and exclusion criteria after extracting literature data and assessing them using the QUADAS-2.0 tool for evaluating the accuracy of diagnostic tests. Stata 15.0 software was used for meta-analysis. RESULTS: Four Chinese and English literature reports were included in this meta-analysis. The results revealed the presence of a threshold effect and high heterogeneity among the included studies. The combined sensitivity for CAR predicting IVIG-resistant KD was calculated as 0.65 (95% CI 0.58-0.72), specificity as 0.71 (95% CI 0.57-0.81), and the area under the curve (AUC) as 0.70 (95% CI 0.66-0.74) using the random-effects model. The combined positive likelihood ratio was 2.22 (95% CI 1.35-3.65), the combined negative likelihood ratio was 0.49 (95% CI 0.35-0.69), and the diagnostic odds ratio was 5 (95% CI 2-10). CONCLUSION: CAR is an auxiliary predictive indicator with moderate diagnostic value that provides guidance in the early treatment of the disease, demonstrating a certain predictive value that warrants further investigation. However, CAR cannot yet be considered as a definitive diagnostic or exclusionary marker for IVIG-resistant KD. Therefore, multi-center, large sample, and high-quality long-term follow-up trials are warranted to confirm the current findings.

Serum PM20D1 levels in patients with idiopathic pulmonary arterial hypertension and its clinical significance.

OBJECTIVE: This study aimed to investigate the serum levels of Peptidase M20 domain containing 1 (PM20D1) in idiopathic pulmonary arterial hypertension (IPAH) patients and examine its association with lipid metabolism, echocardiography, and hemodynamic parameters. METHODS: This prospective observational research enrolled 103 IPAH patients from January 2018 to January 2022. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum PM20D1 levels in all patients before treatment within 24 h of admission. Demographic data, echocardiography, hemodynamic parameters and serum biomarkers were also collected. RESULTS: The IPAH patients in the deceased group had significantly elevated age, right atrial (RA), mean pulmonary arterial pressure (mPAP), mean right atrial pressure (mRAP), pulmonary capillary wedge pressure (PCWP), pulmonary vascular resistance (PVR) and significantly decreased 6 min walking distance (6MWD) and tricuspid annulus peak systolic velocity (TASPV). IPAH patients showed significant decreases in serum PM20D1, low-density lipoprotein cholesterol (LDL-C), and albumin (ALB). Additionally, PM20D1 was negatively correlated with RA, NT-proBNP and positively correlated with PVR, ALB, 6MWD, and TAPSV. Moreover, PM20D1 has the potential as a biomarker for predicting IPAH patients' prognosis. Finally, logistic regression analysis indicated that PM20D1, ALB, NT-proBNP, PVR, TASPV, RA and 6MWD were identified as risk factors for mortality in IPAH patients. CONCLUSION: Our findings indicated that the serum levels of PM20D1 were significantly decreased in IPAH patients with poor prognosis. Moreover, PM20D1 was identified as a risk factor associated with mortality in IPAH patients.

Navigating the future of diabetes: innovative nomogram models for predicting all-cause mortality risk in diabetic nephropathy.

OBJECTIVE: This study aims to establish and validate a nomogram model for the all-cause mortality rate in patients with diabetic nephropathy (DN). METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016. A random split of 7:3 was performed between the training and validation sets. Utilizing follow-up data until December 31, 2019, we examined the all-cause mortality rate. Cox regression models and Least Absolute Shrinkage and Selection Operator (LASSO) regression models were employed in the training cohort to develop a nomogram for predicting all-cause mortality in the studied population. Finally, various validation methods were employed to assess the predictive performance of the nomogram, and Decision Curve Analysis (DCA) was conducted to evaluate the clinical utility of the nomogram. RESULTS: After the results of LASSO regression models and Cox multivariate analyses, a total of 8 variables were selected, gender, age, poverty income ratio, heart failure, body mass index, albumin, blood urea nitrogen and serum uric acid. A nomogram model was built based on these predictors. The C-index values in training cohort of 3-year, 5-year, 10-year mortality rates were 0.820, 0.807, and 0.798. In the validation cohort, the C-index values of 3-year, 5-year, 10-year mortality rates were 0.773, 0.788, and 0.817, respectively. The calibration curve demonstrates satisfactory consistency between the two cohorts. CONCLUSION: The newly developed nomogram proves to be effective in predicting the all-cause mortality risk in patients with diabetic nephropathy, and it has undergone robust internal validation.

[Clinical characteristics of COVID-19 infection in patients undergoing hemodialysis].

OBJECTIVE: To analyze the clinical characteristics of hemodialysis patients with corona virus disease 2019 (COVID-19) in a single-center from Beijing. METHODS: Patients with COVID-19 who received regular hemodialysis at Peking University Third Hospital from November 30, 2022 to January 4, 2023 were selected as the study objects. Clinical symptoms, severity and duration of symptoms during the period of virus positive were investigated in the form of questionnaires, and the basic information of the patients, as well as the results of blood tests (routine blood and blood biochemistry, etc.) before and after infection, dialysis treatment and the outcome of the disease were collected by consulting medical records. RESULTS: A total of 203 subjects were included in this study, including 148 mild cases (72.91%), 23 medium cases (11.33%), 32 severe and critical cases (15.76%), and 16 (7.88%) deaths occured during the follow-up. Clinical symptoms mainly included respiratory symptoms (among which 81.77% had cough, 68.97% had expectoration), fever (81.28%) and fatigue (65.52%), and fatigue and weakness had the longest duration [9 (5, 15) days] among all symptoms. Twenty-six patients (12.8%) reduced the dialysis sessions [1 (1, 2) times], 25 patients (12.32%) had the behavior of early finishing dialysis (27 times), reducing the dialysis time by 30.0 (20.0, 30.5) minutes. Univa-riate analysis showed that the hemoglobin, creatinine, urea nitrogen and ultrafiltration decreased signi-ficantly after infection (P < 0.05). There were significant differences in age, albumin, hemoglobin, creatinine levels and vascular access types among the patients with different clinical subtypes, and the changes of dialysis sessions, fever, expectoration and fatigue degree were also different among the patients with different clinical subtypes (P < 0.05). Multivariate Logistic regression analysis showed that age (OR=1.051, 95%CI: 1.017-1.086, P=0.003) and albumin levels (OR=0.905, 95%CI: 0.803-1.019, P=0.098) corrected by fever, expectoration and fatigue levels were still associated with the occurrence of pneumonia. CONCLUSION: The morbidity of pneumonia and the proportion of deaths in hemodialysis patients with COVID-19 were higher, and some clinical symptoms lasted for a longer time than the general population. During the infection period, the incidence of dialysis-related complications increased, hemoglobin and nutritional status decreased. Elderly patients and patients with low albumin level had a higher risk of developing pneumonia after infection.

Improving appropriate use of intravenous albumin: results of a single-centre audit and multifaceted intervention.

BACKGROUND: Intravenous albumin has limited indications supported by randomised controlled trials, yet it is often prescribed for indications not supported by evidence. AIM: To reduce unnecessary transfusion of albumin. INTERVENTIONS: Under the leadership of a multidisciplinary quality improvement team, evidence-based recommendations were disseminated in tandem with a new electronic order set, an educational strategy, qualitative interviews with prescribers and a return policy change to reduce wastage. IMPLEMENTATION AND EVALUATION: Interventions were introduced in a staggered fashion. The primary outcome, appropriate use of albumin, was monitored and quantified using pre-intervention and post-intervention audits. Process measures included statistical process run charts of monthly usage of 5% and 25% albumin and wastage. Data on length of stay (hospital and intensive care), new inpatient starts on kidney replacement and mortality were collected as balancing measures. RESULTS: Appropriate albumin usage based on indication increased from 30% to 50% (p<0.0001). There was significantly less overall albumin usage in the post-intervention period compared with the pre-intervention period (negative coefficient, p<0.0001), driven by a major reduction in the utilisation of the 5% formulation (p<0.0001). Overall albumin usage was significantly lower in the post-intervention period, decreasing from 800 to 450 vials per month. The intervention resulted in significantly less wastage (negative coefficient, p=0.017). Mortality, length of stay and new starts on kidney replacement therapy remained constant throughout the study period. CONCLUSION: Improved prescribing of albumin was achieved with a multifaceted approach. Substantial and sustained reductions in usage were achieved without negatively impacting patient-important outcomes. The estimated annual savings for the purchase cost of albumin was CAN $300 000. We provide a structured process for other organisations to optimise their use of albumin.