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Background: This study aims to elucidate the significance of the preoperative fibrinogen to pre-albumin ratio (FPR) in predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC), a correlation not extensively explored previously., Methods: A cohort of 563 patients diagnosed with PDAC and subjected to radical surgical resection was examined. We meticulously documented a range of inflammatory markers, clinical-pathological features, and oncological outcomes. The prognostic value of preoperative FPR was assessed using Kaplan-Meier survival analysis and Cox proportional hazards regression modeling. Furthermore, the predictive accuracy of FPR was evaluated through time-dependent receiver operating characteristic (ROC) curves and decision curve analyses (DCA)., Results: The determined optimal threshold for FPR was 14.77, which facilitated the stratification of patients into groups with low and high FPR levels. Notably, patients in the high FPR cohort exhibited significantly reduced recurrence-free survival (RFS) and overall survival (OS) rates compared to their low FPR counterparts. Multivariate Cox regression analysis underscored FPR as an independent prognostic indicator for both RFS and OS. In comparison to the neutrophil-to-lymphocyte ratio (NLR), FPR demonstrated superior prognostic accuracy and clinical utility., Conclusion: The preoperative fibrinogen to pre-albumin ratio serves as an independent prognostic marker for RFS and OS among PDAC patients undergoing radical resection. Our findings suggest that FPR could be a valuable addition to the current prognostic models, potentially guiding therapeutic decision-making and patient management strategies in PDAC., (© 2024. The Author(s).)

Unhoused (UH) individuals experience burn injuries at a higher rate than domiciled individuals, and have poorer outcomes following injuries. One such mechanism proposed for worsened outcomes is secondary to poor nutrition. Access to proper nutrition and food insecurity are major barriers. Malnutrition has been shown to decrease wound tensile strength, increase infection rates, and prolong healing. The purpose of this study was to understand if albumin and prealbumin could help determine outcomes in UH patients and identify at-risk patients earlier in their hospital course. A retrospective chart review was conducted of UH patients from 2015 through 2023 at a large urban safety net hospital. Data collected included admission laboratory values including albumin and prealbumin. Outcomes studied included length of stay (LOS), Intensive Care Unit (ICU) days, ventilator days, and mortality. Data analysis for the effect of albumin and prealbumin included a zero-truncated negative binomial model for LOS, a negative binomial hurdle model for ICU LOS and ventilator days, and logistic regression for mortality. Three hundred and eighty-five patients met inclusion criteria and of these, 366 had albumin and 361 had prealbumin information. Adjusting for age, gender, and total body surface area, the fewest days in the hospital and lowest odds of admission to the ICU occurred for those with admission albumin values of approximately 3.4-3.5 g/dL. Each unit (g/dL) decrease in albumin was associated with 3.19 times the odds of death (95% CI: 1.42, 7.69). Each unit (mg/dL) decrease in prealbumin was associated with 1.19 times the odds of death (95% CI: 1.06, 1.35). Decreased admission albumin and prealbumin levels are associated with worse burn outcomes in UH patients. These nutritional biomarkers may aid in determining which UH patients are suffering from food insecurity at injury onset. Obtaining these values on admission may help burn providers target nutritional goals in their most vulnerable patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Previous studies have reported inconsistent results on the association between serum prealbumin level and survival outcomes in patients with gastric cancer. This meta-analysis aimed to determine the serum prealbumin level as a biomarker of survival outcomes in gastric cancer patients., Methods: Two independent reviewers conducted a thorough search of PubMed, Embase, and Web of Science databases until April 17, 2024. Studies reporting the association between serum prealbumin level and survival outcomes and presented the multivariable-adjusted relative risks for gastric cancer patients were included. The pooled HR and 95% CI were used to assess the strength of the association., Results: Twelve studies, with a total of 9,351 patients were included in the meta-analysis. The combined data showed that low serum prealbumin level was associated with shorter overall survival (HR 1.65; 95% CI 1.42-1.91) and disease-free survival (HR 1.39; 95% CI 1.14-1.70). Subgroup analysis showed that low serum prealbumin level significantly predicted poorer overall survival, regardless of patients' age, sample sizes, cutoff value for prealbumin level, and follow-up time., Conclusions: Low serum prealbumin level is an independent prognostic biomarker for shorter survival outcomes in patients with gastric cancer. Assessing serum prealbumin levels could potentially improve risk stratification for this disease.

Background: Systemic inflammation and altered metabolism are essential hallmarks of cancer. We hypothesized that the rapid turnover protein transthyretin (TTR) (half-life: 2-3 days), compared with the conventional marker albumin (21 days), better reflects the inflammatory/metabolic dynamics of pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and is a useful prognostic marker., Methods: Serum TTR and albumin levels were measured in 104 consecutive post-NAT PDAC patients before curative resection. The associations of preoperative TTR and albumin levels with overall survival (OS) after pancreatectomy were retrospectively analyzed., Results: The mean (SD) TTR and albumin levels were 21.6 (6.4) mg/dL (normal range: ≥22.0 mg/dL) and 3.9 (0.55) g/dL. A low (<22.0 mg/dL) post-NAT TTR level was associated with an advanced tumor stage and higher CEA and CRP levels. Patients with low TTR levels showed significantly worse OS compared with normal levels (3-year OS 39 % vs. 54 %, P = 0.037), although albumin levels did not. We modified prognostic biomarkers of systemic inflammation/metabolism, such as GPS, PNI, and CONUT scores, using the serum TTR instead of albumin level and successfully showed that modified scores were better associated with OS compared with original scores using serum albumin level., Conclusions: Our data suggest that the TTR level is a promising prognostic biomarker for PDAC patients after NAT., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background: Patients with idiopathic pulmonary fibrosis (IPF) often experience sarcopenia and malnutrition. However, this has not been fully examined through longitudinal surveys. This study investigated whether sarcopenia and malnutrition were associated with 1-year outcomes in IPF., Methods: We evaluated sarcopenia and nutritional status in 64 outpatients with IPF. We assessed the time-to-event for respiratory-related hospitalizations or deaths 12 months after enrollment. Sarcopenia was diagnosed by the criteria of the Asian Working Group for Sarcopenia, 2019. Nutritional status was assessed by serum transthyretin and the Geriatric Nutritional Risk Index (GNRI)., Results: The average age was 73.6 ± 7.9 years, and the percent predicted forced vital capacity (FVC) was 81.9 ± 15.7%. Of the 64 patients, 24 (37.5%) had sarcopenia. The median serum transthyretin level and mean GNRI were 23.8 mg/dL and 102, respectively. Eleven patients (17.2%) experienced respiratory-related hospitalization or death within the first year. Cox regression analysis showed that the % predicted diffusion capacity for carbon monoxide, lowest oxygen saturation in the 6-min walk test, serum transthyretin level, and GNRI were significant predictors of 1-year outcomes. The Kaplan-Meier method, which divided the patients into two groups based on a transthyretin level of 22.6 mg/dL, showed a significant difference (P < 0.001, log-rank test). Sarcopenia and the percent predicted FVC did not predict the 1-year outcomes., Conclusions: This pilot study represents the first longitudinal survey assessing patients with IPF for sarcopenia and malnutrition. Serum transthyretin levels may predict respiratory-related hospitalization or death within 1 year in patients with IPF., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: The objective of this study was to examine the effects of nutritional therapy in adult patients with severe burns., Methods and Study Design: Sixty adult patients with severe burns were enrolled. Data on nutritional intake through enteral nutrition (EN) or parenteral nutrition (PN) on days 7, 14, 21, and 28 post-injury were collected. Patients were divided into target and non-target groups according to whether their energy or protein intake reached the target. Age, length of ventilation, and total bilirubin (TBIL), albumin (ALB), prealbumin (pALB), and C-reactive protein (CRP) concentrations of patients were recorded., Results: The percentage of protein targets with protein delivery was lower than that of energy target with energy delivery. The ratio of PN protein to total protein was lower than that of PN energy to total energy on days 7, 14, 21, and 28 (p<0.001, p<0.001, p=0.001, and p=0.003, respectively). Compared to the non-target group on day 21, the target group was younger, had lower TBIL on day 7, higher ALB and pALB on day 21, and lower CRP on day 14 (p=0.025, p=0.021, p=0.028, p=0.029, and p=0.049, respectively). Multivariate logistic regression analysis showed that older age and longer ventilation were independent risk factors in patients who did not meet the nutritional target on day 21 (p=0.026 and p=0.043, respectively)., Conclusions: The protein intake of adult patients with severe burns was low. Compared to the non-target group, the target group had better laboratory test results. Older age and longer ventilation were independent risk factors for patients not meeting the nutritional target., Competing Interests: The authors declare no conflict of interest

This study aimed to evaluate the role of the C-reactive protein-to-prealbumin (CP) ratio and the C-reactive protein-to-albumin (CA) ratio as nutritional and prognostic markers. A retrospective study was conducted on hospitalized patients who underwent a nutritional assessment and the measurement of C-reactive protein, prealbumin, and albumin ( n = 274). Receiver operating characteristic (ROC) curve analysis was used. The area under the curve (AUC) of the CP ratio for predicting mortality was 0.644, 95%CI (0.571 to 0.717), and the CA ratio had an AUC of 0.593, 95%CI (0.518 to 0.669). The AUC of the CP ratio for the differential diagnosis between severe and moderate disease-related malnutrition (DRM) was 0.643, 95%CI (0.564 to 0.722), and the CA ratio had an AUC of 0.650, 95%CI (0.572 to 0.728). The CP and CA ratios showed greater accuracy in predicting mortality compared to C-reactive protein as an isolated marker ( p = 0.011 and p = 0.006, respectively). Both ratios also improved the ability of prealbumin and albumin to identify severe DRM ( p = 0.002 and p = 0.044, respectively). In conclusion, these results suggest that the CP and CA ratios may have a limited role in predicting mortality and identifying severe DRM by outperforming isolated protein markers.

Background: Total hip (THA) or knee (TKA) arthroplasty is still a traumatic and challenging operation that induces inflammation, with a particularly high risk of acute-phase reaction. The aim of this study was to predict the likelihood of implant-associated complications during the preoperative and postoperative course., Methods: The prospective observational, non-interventional study of patients diagnosed with primary knee or hip osteoarthrosis undergoing THA or TKA during the study period was conducted. The inflammatory and malnutrition parameters were collected for each patient one day before surgery, two days after surgery, and in outpatient follow-up., Results: Of 159 patients analysed, 12 developed implant-associated complications. The albumin, prealbumin, Intensive Care Infection Score (ICIS), Nutritional Risk Index, and white blood cell counts were found to be potential predictors. Notably, preoperative albumin levels significantly differed between groups with and without complications (P-value = 0.042)., Conclusion: Our study definitively shows that WBC, prealbumin, Nutritional Risk Index, ICIS as a novel marker, and significantly albumin, outperform C-reactive protein in predicting implant-associated complications in hip and knee arthroplasty., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Domecky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aims: Correctly characterizing malnutrition is a challenge. Transthyretin (TTR) rapidly responds to adequate protein intake/infusion, which could be used as a marker to identify malnutrition. Nutritional therapy is used to prevent malnutrition. Parenteral nutrition (PN) requires daily monitoring to determine whether what is being offered is adequate. This article aims to investigate whether the practice of measuring TTR is justified., Methods: Data from patients admitted to the ward or intensive care unit (ICU) were collected at three different times: within the first 72 h (T1) of PN use, on the 7th day (T2), and the 14th day (T3) after the initial assessment., Results: 302 patients were included; the average age was 48.3 years old; the prevalence of death was 22.2%, and 61.6% of the sample were male. TTR values and the effectiveness of nutritional support in these patients were not associated with the outcome; however, meeting caloric needs was related to the outcome ( p = 0.047). No association was found when TTR values were compared to the nutritional status. Thus, TTR was not a good indicator of nutritional risk or nutritional status in hospitalized patients., Conclusions: Undoubtedly, the TTR measurement was inversely proportional to CRP measurements. It was possible to conclude in this follow-up cohort of hospitalized patients that TTR values were not useful for determining whether the patient was malnourished, predicting death or effectiveness of nutritional support, yet based upon our analyses, a decrease in TTR greater than 0.024 units for every 1 unit increase in CRP might be due to ineffective nutritional supply.

Objective: To assess diet quality and its association with body and biochemical parameters in patients who underwent Roux-en-Y gastric bypass (RYGB)., Methods: Prospective observational study with individuals of both sexes subjected to RYGB. Body composition, biochemical parameters, and diet quality were assessed before and six months after RYGB. Diet quality was assessed by the Healthy Eating Index (HEI). Data were analyzed by the paired t-test or Wilcoxon signed-rank test, with a significance level of 5%. Spearman's correlation and simple linear regression were performed between variables., Results: The final sample included 34 patients. Their diet was classified as poor before and 6 mo after RYGB. BMI, fat mass, fat-free mass, waist perimeter, serum total protein, transthyretin, alpha-1-acid glycoprotein, and C-reactive protein decreased significantly (P < 0.05). Variations in the HEI score and caloric intake were associated with serum albumin and transthyretin (P < 0.05)., Conclusion: Poor diet quality was present before and six months after RYGB, and the study data suggest that poor diet quality is associated to a risk of loss of lean body mass and visceral protein six months after RYGB., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fabiano Kenji Haraguchi reports financial support was provided by Espírito Santo Research and Innovation Support Foundation (FAPES)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: We aimed to determine whether systemic immune-inflammation index (SII) combined with prealbumin can provide better predictive power for postoperative pneumonia in patients undergoing lung resection surgery., Methods: We identified eligible patients undergoing lung resection surgery at the Affiliated Hospital of Nantong University from March 2021 to March 2022. Demographic characteristics, clinical data, and laboratory information were collected and reviewed from the electronic medical records of the patients. To test the effect of the combined detection of SII and prealbumin, we made an equation using logistic regression analysis. The receiver operating characteristic curve (ROC) was plotted to evaluate the predictive powers, sensitivity, and specificity of prealbumin, SII, and SII combined with prealbumin. Decision curve analysis (DCA) was used to determine the clinical validity and net benefit of different methods of detection., Results: Totally 386 eligible patients were included with a median age of 62.0 years (IQR: 55.0, 68.0), and 57 (14.8%) patients presented with postoperative pneumonia within 7 days after surgery. The multivariate regression analysis showed that preoperative SII as continuous variable was associated with an increased risk of postoperative pneumonia (OR: 1.38, 95% CI: 1.19-2.83, P = 0.011), whereas the prealbumin as continuous variable remained as an independent protective predictor of postoperative pneumonia in the adjusted analysis (OR: 0.80, 95% CI: 0.37-0.89, P = 0.023). Compared to SII or prealbumin, the combined detection of preoperative SII and prealbumin showed a higher predictive power with area under curve of 0.79 (95% CI: 0.71-0.86, P < 0.05 for all). Additionally, DCA indicated that the combined detection was superior over preoperative SII or prealbumin alone in clinical validity and net benefit., Conclusion: Both preoperative SII and prealbumin are independent influencing factors for postoperative pneumonia after lung resection surgery. The combined detection of preoperative SII and prealbumin can significantly improve prediction capability to identify potential postoperative pneumonia-susceptible patients, facilitating early interventions to improve postoperative quality of life for surgical lung resection patients., (© 2024. The Author(s).)

Background: The primary aim of this study is to investigate the correlation between serum levels of fibrinogen-to-prealbumin ratio (FPR) and C-reactive protein-to-prealbumin ratio (CPR) and prognostic outcomes among patients with severe fever with thrombocytopenia syndrome (SFTS). SFTS, characterized by elevated mortality rates, represents a substantial public health challenge as an emerging infectious disease., Methods: The study included 159 patients with SFTS. Clinical and laboratory data were compared between the survival and death groups. Univariate and multivariate logistic regression analysis were utilized to identify independent risk factors for mortality. The predictive efficacy of FPR and CPR was evaluated using receiver operating characteristic (ROC) curve. Survival analysis was conducted using the Kaplan-Meier curve and the log-rank test was employed for comparison., Results: The death group exhibited significantly elevated levels of FPR and CPR compared to the survival group ( P < 0.05). Multivariate logistic regression analysis confirmed that both FPR and CPR independently correlated with a poorer prognosis among patients with SFTS. The ROC curve analysis indicated that FPR and CPR had superior predictive capabilities compared to C-reactive protein and fibrinogen. Kaplan-Meier survival analysis demonstrated that patients with SFTS who have FPR > 0.045 (log-rank test; χ2 = 17.370, P < 0.001) or CPR > 0.05 (log-rank test; χ2 = 19.442, P < 0.001) experienced significantly lower survival rates within a 30-day follow-up period., Conclusion: Elevated levels of FPR and CPR serve as distinct risk factors for mortality among patients with SFTS, indicating their potential to predict an unfavorable prognosis in these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Liu, Qiao and He.)

Surface and treated wastewater are contaminated with highly complex mixtures of micropollutants, which may cause numerous adverse effects, often mediated by endocrine disruption. However, there is limited knowledge regarding some important modes of action, such as interference with thyroid hormone (TH) regulation, and the compounds driving these effects. This study describes an effective approach for the identification of compounds with the potential to bind to transthyretin (TTR; protein distributing TH to target tissues), based on their specific separation in a pull-down assay followed by non-target analysis (NTA). The method was optimized with known TTR ligands and applied to complex water samples. The specific separation of TTR ligands provided a substantial reduction of chromatographic features from the original samples. The applied NTA workflow resulted in the identification of 34 structures. Twelve compounds with available standards were quantified in the original extracts and their TH-displacement potency was confirmed. Eleven compounds were discovered as TTR binders for the first time and linear alkylbenzene sulfonates (LAS) were highlighted as contaminants of concern. Pull-down assay combined with NTA proved to be a well-functioning approach for the identification of unknown bioactive compounds in complex mixtures with great application potential across various biological targets and environmental compartments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background & Aims: Serum retinol (ROH) is commonly used for population level assessment of vitamin A status. High-performance liquid chromatography (HPLC) is considered most accurate method for measuring ROH. However, with the technical difficulty of using HPLC for routine assays, serum retinol-binding protein (RBP) measured by immunological assays is expected to be a surrogate marker for ROH, with reports of a close correlation between serum RBP and ROH. Nevertheless, RBP is not commonly tested to assess vitamin A status with concerns over RBP alterations under various physiopathological conditions. Thus, we reappraised the extent to which RBP could be used as a surrogate marker in representative disorders that alter serum RBP levels. As a related marker, diagnostic utility of transthyretin (TTR) was also evaluated., Methods: To evaluate the reliability of ROH and RBP assays, specimen stability was assessed in terms of (1) storage at 25, 4, -20, and -80 °C for 1-28 days, (2) five-cycle freeze-thawing, and (3) fluorescent light exposure for 1-14 days. Sources of variation (sex, age, body mass index [BMI], and drinking habits) and reference intervals for ROH, RBP, and TTR were determined in 617 well-defined healthy individuals. To investigate the influence of disorders that affect serum RBP, patients with five diagnostic groups were enrolled: 26 with chronic kidney disease (CKD); 13 with various malignancies in advanced stages (AdM), 12 with acute bacterial infections (ABI), 6 with liver cirrhosis (LC), and 26 with simple obesity (BMI ≥ 27 kg/m 2 )., Results: The stability of RBP and ROH in serum was confirmed under all conditions. In healthy individuals, serum ROH, RBP, and TTR were appreciably high in males with a slight increase in proportion to age and BMI. The major-axis regression line between RBP (x) and ROH (y) in healthy individuals was y = x, with a correlation coefficient of 0.986. In the LC, AdM, and ABI groups, similar strong correlations were observed; however, the regression lines were shifted slightly rightward from the healthy group line, indicating a positive bias in estimating ROH. Interestingly, the same analyses between TTR and ROH revealed similar strong linear relationships in all groups; however, the regression line of each group showed a leftward (opposite) shift from the healthy group line. Based on these observations, we developed a novel regression model composed of RBP and TTR, which gave much improved accuracy in estimating ROH, even under these pathological conditions., Conclusions: The perfect RBP-ROH correlation in healthy individuals indicates the utility of RPB as a surrogate marker for ROH. Nevertheless, under RBP-altered conditions, a slight overestimation of ROH is inevitable. However, when the TTR was tested together, the bias can be corrected almost perfectly using the novel ROH estimation formula comprising RBP and TTR., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Albumin-Bilirubin (ALBI) score, widely used in predicting long-term prognosis for patients with hepatocellular carcinoma (HCC), has limitations due to serum albumin variability. This study aimed to develop and validate the Prealbumin-Bilirubin (preALBI) score as a reliable alternative., Methods: A multicenter cohort of HCC patients who underwent hepatectomy was randomly divided into the training and validation cohorts. The preALBI score was developed using Cox regression models within the training cohort, incorporating serum prealbumin and bilirubin levels as crucial determinants. The survival predictive accuracy was evaluated and compared between the preALBI score with two other staging systems, including the ALBI score and the Child-Pugh grade., Results: A total of 2409 patients were enrolled. In the training cohort, the preALBI score demonstrated superior performance in predicting long-term survival after hepatectomy. The preALBI score was associated with the best monotonicity of gradients (linear trend χ 2 : 72.84) and homogeneity (likelihood ratio χ 2 : 74.69), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.663, 0.654, and 0.644, respectively). In addition, the preALBI was the most informative staging system in predicting survival (Akaike information criterion: 11325.65).The results remained consistent in both training and validation cohorts, indicating its reliable performance across different populations., Conclusion: The preALBI score, leveraging the stability of prealbumin, represents a promising tool for better patient stratification, providing more accurate prognostic predictions than the ALBI score and the Child-Pugh grade., Competing Interests: Declaration of competing interest We confirm that this work is original and has not previously been published. None of the authors have any financial disclosures or conflict of interest. Approval for this study was obtained from the Ethics Committee of the participating hospitals. All the authors have been involved in the design, performance, and interpretation of data of this study, and in drafting the article and its critical revision., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Aims: Serum prealbumin is considered to be a sensitive predictor of clinical outcomes and a quality marker for nutrition support. However, its susceptibility to inflammation restricts its usage in critically ill patients according to current guidelines. We assessed the performance of the initial value of prealbumin and dynamic changes for predicting the ICU mortality and the effectiveness of nutrition support in critically ill patients., Methods: This monocentric study included patients admitted to the ICU between 2009 and 2016, having at least one initial prealbumin value available. Prospectively recorded data were extracted from the electronic ICU charts. We used both univariable and multivariable logistic regressions to estimate the performance of prealbumin for the prediction of ICU mortality. Additionally, the association between prealbumin dynamic changes and nutrition support was assessed via a multivariable linear mixed-effects model and multivariable linear regression. Performing subgroup analysis assisted in identifying patients for whom prealbumin dynamic assessment holds specific relevance., Results: We included 3136 patients with a total of 4942 prealbumin levels available. Both prealbumin measured at ICU admission (adjusted odds-ratio (aOR) 0.04, confidence interval (CI) 95% 0.01-0.23) and its change over the first week (aOR 0.02, CI 95 0.00-0.19) were negatively associated with ICU mortality. Throughout the entire ICU stay, prealbumin dynamic changes were associated with both cumulative energy (estimate: 33.2, standard error (SE) 0.001, p < 0.01) and protein intakes (1.39, SE 0.001, p < 0.01). During the first week of stay, prealbumin change was independently associated with mean energy (6.03e-04, SE 2.32e-04, p < 0.01) and protein intakes (1.97e-02, SE 5.91e-03, p < 0.01). Notably, the association between prealbumin and energy intake was strongest among older or malnourished patients, those suffering from increased inflammation and those with high disease severity. Finally, prealbumin changes were associated with a positive mean nitrogen balance at day 7 only in patients with SOFA <4 (p = 0.047)., Conclusion: Prealbumin measured at ICU admission and its change during the first-week serve as an accurate predictor of ICU mortality. Prealbumin dynamic assessment may be a reliable tool to estimate the effectiveness of nutrition support in the ICU, especially among high-risk patients., Competing Interests: Conflict of interest E.P. received a research grant from Nestle Health Science, speaking honoraria from Fresenius Kabi & Baxter, and congressional reimbursement from Fresenius Kabi and Nutricia., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: Although numerous factors had been found to be associated with stroke-associated pneumonia (SAP), the underlying mechanisms of SAP remain unclear. Fibrinogen-prealbumin ratio (FPR) is a novel indicator that could balance the effects of inflammation and nutrition, which might reflect biological status of patients more comprehensively than other biomarkers. To date, FPR has not been explored in acute ischemic stroke patients. This study aims to explore the relationship between FPR and SAP., Materials and Methods: 900 stroke patients participated in this retrospective study and 146 healthy controls were recruited. Fibrinogen and prealbumin were measured within 24 hours on admission. FPR was calculated after dividing fibrinogen (g/L) by prealbumin (mg/L) × 1000. SAP was defined according to the modified Centers for Disease Control criteria., Results: 121 patients were diagnosed with SAP. Log 10 FPR was higher in stroke patients than healthy controls. In logistic regression analysis, log 10 FPR was independently associated with SAP (OR 15.568; 95% CI: 3.287-73.732; P=0.001). Moreover, after using ROC curve, the predictive power of "current standard"(defined as A2DS2 plus leukocyte count and log 10 hs-CRP) plus log 10 FPR (0.832[0.804-0.857]) was higher than "current standard" (0.811[0.782-0.837], P=0.0944) and A2DS2 plus log 10 FPR (0.801[0.772-0.828], P=0.0316). No significant difference was found between the predictive power of A2DS2 plus log 10 FPR and "current standard" (P =0.6342)., Conclusion: Higher FPR was observed in stroke patients compared with healthy controls and was significantly associated with SAP. FPR might provide useful clues for timely identification and treatment of SAP., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) presents a significant threat to individuals and healthcare systems due to its high recurrence rate. Accurate prognostic models are essential for improving patient outcomes. Gamma-glutamyl transpeptidase (GGT) and prealbumin (PA) are biomarkers closely related to HCC. This study aimed to investigate the predictive value of the GGT to PA ratio (GPR) and to construct prognostic nomograms for HCC patients without microvascular invasion., Methods: We retrospectively analyzed data from 355 HCC patients who underwent radical hepatectomy at Shengjing Hospital of China Medical University between December 2012 and January 2021. Patients were randomly assigned to a training cohort (n = 267) and a validation cohort (n = 88). The linearity of GPR was assessed using restricted cubic spline (RCS) analysis, and the optimal cut-off value was determined by X-tile. Kaplan-Meier survival curves and log-rank tests were used to investigate the associations between GPR and both progression-free survival (PFS) and overall survival (OS). Cox multivariate regression analysis identified independent risk factors, enabling the construction of nomograms. Time-dependent receiver operating characteristic (ROC) and calibration curves were used to evaluate the accuracy of the nomograms. Decision curve analysis (DCA) assessed the predictive value of the models., Results: Patients were categorized into GPR-low and GPR-high groups based on a GPR value of 333.33. Significant differences in PFS and OS were observed between the two groups (both P < 0.001). Cox multivariate analysis identified GPR as an independent risk factor for both PFS (OR = 1.80, 95% CI: 1.24-2.60, P = 0.002) and OS (OR = 1.87, 95% CI: 1.07-3.26, P = 0.029). The nomograms demonstrated good predictive performance, with C-index values of 0.69 for PFS and 0.76 for OS. Time-dependent ROC curves and calibration curves revealed the accuracy of the models in both the training and validation cohorts, with DCA results indicating notable clinical value., Conclusions: GPR emerged as an independent risk factor for both OS and PFS in HCC patients without microvascular invasion. The nomograms based on GPR demonstrated relatively robust predictive efficiency for prognosis., (© 2024. The Author(s).)

This study aimed to assess the frequency and association between transthyretin-derived (ATTR) amyloidosis and sarcoidosis in a large autopsy cohort including many cases of sudden cardiac death (SCD). We identified 73 sporadic ATTR amyloidosis cases and 11 sarcoidosis cases, among which we found two cases with concomitant ATTR amyloidosis and sarcoidosis (2.4% of all cases; 2.7% within the sporadic ATTR group). The first case involved a 92-year-old man who experienced SCD. In this patient's heart, we observed ATTR deposition and noncaseating epithelioid granulomas consistent with sarcoidosis. Focally, ATTR deposits and granulomas co-localized, with histiocyte phagocytosis of transthyretin-immunoreactive fragments. However, in most lesions, they were distributed independently. The second case was that of an 86-year-old woman who also experienced SCD. In this patient, we detected ATTR deposition in the heart and lung, while noncaseating epithelioid granulomas were only observed in the lung, liver, kidney, and thyroid. Furthermore, no co-localization of the two lesions was observed. Based on these findings, we concluded that the coexistence of ATTR amyloidosis and sarcoidosis was likely coincidental. Nevertheless, despite the rarity of the combination of these two diseases, it should be recognized as a potential cause of SCD, especially among elderly people., Competing Interests: Declaration of competing interest Non declared, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Nutritional support is essential in burn care. There are few studies investigating the effect of nutrition on burn healing. The purpose of this study was to determine the relationship between perioperative serum prealbumin levels and the probability of autologous skin graft take in burned patients., Materials and Methods: A prospective observational study was carried out with burned adults recruited consecutively from April 2019 until September 2021. Serum prealbumin was determined perioperatively. The percentage of graft take was evaluated over the first 5 postoperative dressing changes. Time until full epithelialization (absence of wounds) was also registered., Results: A total of 60 patients were recruited, mostly middle-aged people with moderate flame burns. Serum prealbumin levels and graft take had a weak-moderate, nonlinear, statistically significant correlation. They were also an independent predictor of full epithelialization on the fifth dressing change, together with burn depth. Higher perioperative serum prealbumin levels were significantly associated with a reduction in time until full epithelialization., Conclusions: Perioperative serum prealbumin levels are significantly correlated with the probability of split-thickness skin autograft take in burned patients and with a reduced time to achieve complete epithelialization. They were an independent predictor of full graft take., Competing Interests: Declaration of Competing Interest None of the authors has any financial interest in any of the products, devices, or drugs mentioned in this manuscript., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-prealbumin ratio (CPAR) are novel markers of inflammation. The CPAR is an indicator of inflammation and malnutrition. We evaluated NLR and CPAR in combination as indicators of disease severity and prognosis in hospitalized older patients with coronavirus disease 2019 (COVID-19). A total of 222 hospitalized patients with COVID-19 (aged > 60 years) were divided into non-severe and severe groups. The severe group was subdivided into the surviving and deceased subgroups. We retrospectively assessed the predictive power of NLR and CPAR in combination (NLR + CPAR) to determine the prognosis of hospitalized older patients with COVID-19. The NLR and CPAR were significantly higher in the severe group than in the non-severe group (P < .001). Furthermore, the NLR and CPAR were higher in the deceased subgroup than in the surviving subgroup (P < .001). Pearson correlation analysis showed a highly significant positive correlation between NLR and CPAR (P < .001, r = 0.530). NLR + CPAR showed an area under the curve of 0.827 and sensitivity of 83.9% in the severe group; the area under the curve was larger (0.925) and sensitivity was higher (87.1%) in the deceased subgroup. The receiver operating characteristic curve of NLR + CPAR was significantly different from the receiver operating characteristic curves of either biomarker alone (P < .001). Kaplan-Meier analysis showed that patients in the severe group with elevated NLR + CPAR had a significantly lower 90-day survival rate than patients who lacked this finding (odds ratio 7.87, P < .001). NLR + CPAR may enable early diagnosis and assessment of disease severity in hospitalized older patients with COVID-19. This may also enable the identification of high-risk older patients with COVID-19 at the time of admission., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Malnutrition is associated with complications and mortality in patients of hip fracture. Prealbumin may be more suitable than albumin to accurately predict the prognosis of hip fracture in elderly patients. We found that prealbumin concentration was nonlinearly associated with mortality in elderly patients with hip fracture, and an inflection point effect was observed., Objective: To evaluate the association between prealbumin concentration at admission and mortality in elderly patients with hip fractures., Methods: Elderly patients with hip fractures were screened between Jan 2015 and Sep 2019. Demographic and clinical characteristics of the patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between prealbumin concentration at admission and mortality. All analyses were performed using EmpowerStats and the R software., Results: This cohort study included 2387 patients who met the study criteria. The mean follow-up was 37.64 months. The prealbumin concentration was 162.67 ± 43.2 mg/L. Multivariate Cox regression showed that prealbumin concentration was associated with mortality in geriatric patients with hip fracture (hazard ratio [HR] = 0.95, 95% confidence intervals [CI]: 0.93-0.97, P < 0.0001). In addition, an inflection point effect was observed in the nonlinear association. The inflection point was 162.2 mg/L. If it is less than this inflection point, then every 10 mg/L increase in prealbumin was associated with a 7% reduction in the risk of death (HR = 0.93, 95%CI: 0.90-0.96, P < 0.0001). When greater than the inflection point, there was no difference in the risk of death (HR = 0.99, 95%CI: 0.95-1.03, P = 0.5127)., Conclusion: The prealbumin concentrations at admission were nonlinearly associated with long-term mortality in geriatric hip fractures, and 162.2 mg/L could be considered a prognostic factor of mortality risk., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

The classic findings have been well described for light-chain amyloid involving the liver. In addition to light chain, however, many additional proteins are now known to be amyloidogenic and can involve the liver. A total of 58 surgical pathology specimens with amyloid deposits were analyzed for patterns of amyloid deposition, including amyloid from light chain lambda (N = 17), light chain kappa (N = 15), transthyretin (N = 15), serum amyloid A (N = 4), apolipoprotein A1 (N = 4), fibrinogen alpha (N = 2), LECT2 (N = 1). Amyloid deposits predominately targeted the liver vasculature, including the walls of the hepatic arteries, portal veins, and sinusoids. While there was overlap, light chain amyloid predominately involved the sinusoids, while transthyretin amyloid predominately targeted the hepatic arteries, especially the larger ones in the hilum and larger portal tracts. Serum amyloid A formed nodular deposits that started in the portal vasculature but then extended into the portal tract stroma, leading to large, bulbous, portal-based amyloid deposits. Apolipoprotein A amyloid also formed large portal-based nodules. Fibrinogen was mild and subtle on H&E and predominately affected portal veins. Amyloid deposits in hilar nerves were prominent with amyloid light chain, transthyretin, and apolipoprotein A1. In conclusion, the histology of hepatic amyloid is diverse and shows several distinct clusters of findings that can aide in recognition in surgical pathology specimens., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

An 85-year-old woman visited our hospital with a complaint of asymptomatic gross hematuria. Cystoscopy showed a non-papillary sessile tumor about 3 cm in size. Magnetic resonance imaging (MRI) suggested invasion of surrounding fat tissue. Thoracoabdominal contrast-enhanced computed tomography (CT) showed no tumor of the upper urinary tract or metastasis. We diagnosed the tumor as bladder cancer cT3N0M0 and performed transurethral bladder tumor resection 22 days after her first visit. No tumor was found at the time of surgery. We resected a reddened area to include a muscle layer and performed random biopsy. Hematoxylin and eosin stain showed eosinophilic tuberous tissue that stained with Congo red around blood vessels in the subepithelial stroma and the muscle layer. There was no dysplasia in the bladder epithelium. Therefore, we diagnosed the case as bladder amyloidosis. Immunostaining of the amyloid subtype revealed transthyretin amyloid (ATTR) amyloidosis. Bence-Jones protein in urine was negative, M protein was not detected in serum protein electrophoresis, and serum amyloid A was at the threshold. Scintigraphy for 99m Tc pyrophosphoric acid was positive in the myocardium. No genetic disorder was detected. We concluded that it was systemic ATTRwt amyloidosis as above. The patient did not wish to be treated for the systemic amyloidosis. Thirteen months after surgery, the patient showed no signs of recurrence in the bladder. As cardiac function is a prognostic factor in systemic amyloidosis, we need to consider the possibility of systemic amyloidosis when diagnosing bladder amyloidosis.

Background and Objectives: Hereditary transthyretin amyloidosis (ATTRv) is a rare disease caused by pathogenic variants in the transthyretin ( TTR ) gene. More than 140 different disease-causing variants in TTR have been reported. Only a few individuals with a rare TTR variant, c.302C>T, p.(Ala101Val) (historically known as p.(Ala81Val)), primarily associated with cardiac ATTRv, have been described. Therefore, our aim was to analyze the clinical characteristics of individuals with the identified c.302C>T TTR variant at our center. Materials and Methods: We analyzed data from individuals with ATTRv who were diagnosed and treated at Vilnius University Hospital Santaros Klinikos. ATTRv was confirmed by negative hematological analysis for monoclonal protein, positive tissue biopsy or bone scintigraphy and a pathogenic TTR variant. Results: During 2018-2021, the TTR NM&#95;000371.3:c.302C>T, NP&#95;000362.1:p.(Ala101Val) variant was found in one individual in a homozygous state and in three individuals in a heterozygous state. The age of onset of symptoms ranged from 44 to 74 years. The earliest onset of symptoms was in the individual with the homozygous variant. A history of carpal tunnel syndrome was identified in two individuals. On ECG, three individuals had low QRS voltage in limb leads. All individuals had elevated NT-proBNP and hsTroponine I levels on baseline laboratory tests and concentric left ventricular hypertrophy on transthoracic echocardiography. The individual with the homozygous c.302C>T TTR variant had the most pronounced polyneuropathy with tetraparesis. Other patients with the heterozygous variant had more significant amyloid cardiomyopathy. When screening family members, the c.302C>T TTR variant was identified in two phenotypically negative relatives at the ages of 33 and 47 years. Conclusions: c.302C>T is a rare TTR variant associated with ATTRv cardiomyopathy. The homozygous state of this variant was not reported before, and is associated with earlier disease onset and neurological involvement compared to the heterozygote state.

Purpose: Nutritional biomarkers like serum prealbumin, transferrin, retinol-binding protein (RBP), C-reactive protein (CRP), leptin, and insulin-like growth factor 1 (IGF1) have the inherent ability to diagnose undernutrition objectively before it is clinically manifested. The primary objective of the study was to evaluate the diagnostic efficacy of the specific nutritional biomarkers in predicting post-operative complications., Methods: A prospective cohort study was conducted in the department of surgery and included all patients aged 18 years and above who underwent elective abdominal surgery. Demographic details and clinical and surgical details were documented from the case records. Nutritional biomarker assay was done at admission. The post-operative complications occurring until discharge were graded using the Clavien-Dindo classification. The diagnostic accuracy of the specific nutritional biomarkers in predicting post-operative complications was assessed., Results: A total of 320 patients were included in the study. Of these, 126 (39.38%) developed post-operative complications. Major complications accounted for 19.05% of the complications, while 80.95% were minor complications. Patients with blood prealbumin level less than 17.287 mg/dL had a higher incidence of complications (p < 0.001). Serum transferrin levels less than 168.04 mg/dL and IGF1 levels less than < 44.51 ng/ml showed increased incidence of complications (p < 0.001). The AUC was found to be the highest for serum IGF1 with 0.7782. Sensitivity was equally high for IGF1 and serum transferrin, with 76.98% for the former and 76.19% for the latter., Conclusion: Specific nutritional biomarkers, like serum prealbumin and transferrin, were efficient in predicting postoperative complications of patients before undergoing elective abdominal surgeries even after adjusting for confounders. This can facilitate preoperative corrective measures to lower the overall postoperative complications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To investigate the changes of serum prealbumin (PA) expression level in patients with oral and maxillofacial space infections and its significance., Methods: Patients hospitalized at the Affiliated Hospital of Xuzhou Medical University from January 2020 to September 2021 were selected and divided into infected and non-infected group. One hundred and twenty-one patients with moderate to severe oral and maxillofacial gap infections were in the infected group, and 128 patients without infection were in the non-infected group. In the infected group, PA, high-sensitivity C-reactive protein (hs-CRP) and white blood cell count (WBC) levels and related clinical parameters were measured at 1, 3 and 7 d of admission. In the non-infected group, PA, hs-CRP and WBC levels were measured at 1 d of admission. SPSS 23.0 software package was used to statistically analyze the relationship between PA levels and various laboratory and clinical parameters., Results: PA levels in the infected group were significantly lower than those in the non-infected group at 1 d of admission. PA levels in the infected group showed an overall increasing trend at different time points, and PA was negatively correlated with pain intensity and positively correlated with mouth opening(P＜0.05). The diagnostic sensitivity was 90.91% and the specificity was 92.97% for PA≤19.85 mg/dL, which can be used as the best diagnostic threshold. The diagnostic efficacy can be improved when combined with hs-CRP and WBC. Logistic regression analysis showed that low PA level was an independent risk factor for patients requiring intensive care after surgery (P＜0.05)., Conclusions: PA is an effective tool for the early diagnosis and evaluation of the efficacy of oral and maxillofacial interstitial infections, and can be used as a reference indicator to assess prognosis.

Background: Because of the shorter half-life as compared with albumin, serum prealbumin concentrations have been proposed to be useful nutrition biomarkers for the assessment of patients at nutrition risk. In a post hoc analysis of patients at nutrition risk from a randomized controlled nutrition trial, we tested the hypothesis that (1) prealbumin is associated with higher all-cause 180-day mortality rates and that (2) individualized nutrition support compared with usual-care nutrition more effectively improves survival at 30 days in patients with low prealbumin levels compared with patients with normal prealbumin levels., Methods: We performed a prespecified cohort study in patients included in the pragmatic, Swiss, multicenter randomized controlled EFFORT trial comparing the effects of individualized nutrition support with usual care. We studied low prealbumin concentrations (<0.17 g/L) in a subgroup of 517 patients from one participating center., Results: A total of 306 (59.2%) patients (mean age 71.9 years, 53.6% men) had low admission prealbumin levels (<0.17 g/L). There was a significant association between low prealbumin levels and mortality at 180 days (115/306 [37.6%] vs 47/211 [22.3%], fully adjusted hazard ratio [HR]=1.59, 95% CI 1.11-2.28; P = 0.011). Prealbumin levels significantly improved the prognostic value of the Nutritional Risk Screening total score regarding mortality prediction at short- and long-term. The difference in mortality between patients receiving individualized nutrition support and usual-care nutrition was similar for patients with low prealbumin levels compared with patients with normal prealbumin levels (HR=0.90 [95% CI=0.51-1.59] vs HR=0.88 [95% CI=0.35-2.23]) with no evidence for interaction (P = 0.823)., Conclusion: Among medical inpatients at nutrition risk, low admission prealbumin levels correlated with different nutrition markers and higher mortality risk, but patients with low or high prealbumin levels had a similar benefit from nutrition support. Further studies should identify nutrition markers that help further personalize nutrition interventions., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Background: Dialysis is the most commonly used renal replacement therapy in patients with end-stage renal disease. The mortality rate of hemodialysis patients is 15-20%, with cardiovascular complications being the most common. There is an association between the severity of atherosclerosis and both the development of protein-calorie malnutrition and inflammatory mediators. The aim of this study was to assess the relationship between biochemical markers of nutritional status, body composition and survival in hemodialysis patients., Methods: Fifty-three hemodialysis patients were included in the study. Serum albumin, prealbumin, and IL-6 levels were measured, as well as body weight, body mass index, fat content and muscle mass. The five-year survival of patients was calculated using Kaplan-Meier estimators. The long-rank test was used for univariate comparison of survival curves, and the Cox proportional hazards model was used for multivariate analysis of survival predictors., Results: There were 47 deaths, 34 of which were due to cardiovascular disease. The hazard ratio (HR) for age in the middle-aged group (55-65 years) was 1.28 (confidence interval [CI] 0.58, 2.79) and 5.43 (CI 2.1, 14.07; statistically significant) for the oldest age group (over 65 years). A prealbumin level above 30 mg/dl was associated with an HR of 0.45 (CI 0.24, 0.84). Serum prealbumin (odds ratio [OR] = 5.23; CI 1.41, 19.43; p = 0.013) and muscle mass (OR = 7.5; CI 1.31, 43.03; p = 0.024) were significant predictors of all-cause mortality., Conclusions: Prealbumin level and muscle mass were associated with increased mortality risk. Identification of these factors may improve the survival of hemodialysis patients.

Objective: Malnutrition is very commonly encountered in palliative care centers (PCC), especially in geriatric patients. It is known that development of malnutrition increases morbidity and mortality. In this study, we aimed to investigate the effectiveness of commonly used nutritional assessment parameters in predicting prognosis in geriatric patients diagnosed in PCC with malnutrition., Methods: Our study included 1451 patients aged ≥65 years, who were diagnosed with malnutrition in PCC between 2016-2020 and did not yet start receiving nutritional support. Demographic data, comorbidities, The Nutritional Risk Screening 2002 (NRS-2002), body mass index (BMI), albumin, prealbumin and C-reactive protein (CRP) values of the patients were recorded. Prognostic course was evaluated by dividing the patients into 3 groups, namely mortal patients during PCC follow-up, patients transferred from PCC to Intensive Care (ICU) and patients discharged to home from PCC., Results: Logistic Regression analysis showed that low albumin levels affected transfer to ICU (P<0.05). Elevated NRS-2002 and low albumin and prealbumin levels were found to be factors affecting mortality (P<0.05). Areas under the ROC Curve were calculated to attain patients' differential diagnosis. The area under the ROC Curve of low albumin in patients transferred to ICU was found to be significant (P<0.05). In the differential diagnosis of patients with mortal course, the area under the ROC Curve of low albumin and prealbumin and high CRP was found to be significant (P<0.05)., Conclusion: We found that BMI had no prognostic predictive effects in geriatric PCC patients with malnutrition. We concluded that NRS-2002 and high CRP and low albumin and prealbumin can be used to predict mortality. In addition, we found that low albumin indicates a poor prognosis and predicts patients to be transferred to ICU., Competing Interests: The authors declare no conflicts of interest in this work., (© 2022 Deligöz and Ekinci.)

Malnutrition and autonomic dysfunction are associated with poor outcomes, mortality, and psychological problems after stroke. Relevant laboratory biomarkers include serum albumin, prealbumin, and transferrin. Heart rate variability (HRV), a noninvasive measurement, can objectively measure autonomic nervous system (ANS) function. The relationship between HRV and nutritional biomarkers in stroke patients has not been studied. This study aimed to examine the relationship between nutritional biomarkers and HRV parameters in stroke patients. We retrospectively recruited 426 patients with subacute stroke who were examined for nutritional biomarkers, such as serum albumin, prealbumin, and transferrin, and underwent 24 h ambulatory Holter electrocardiography. Patients were divided into groups according to their nutritional biomarker status. Differences in HRV parameters between nutritional biomarker-deficient and normal groups were assessed. Pearson's correlation and multiple regression analyses were used to verify the relationship between HRV parameters and nutritional biomarkers. HRV parameters were significantly lower in the nutritional biomarker-deficient groups. In addition, there was a significant association between HRV parameters and nutritional biomarkers. Serum albumin, prealbumin, and transferrin levels were associated with ANS function, as measured by HRV, and their deficiency may be a predictive factor for the severity of ANS dysfunction in stroke patients.

Background: Lumbar spinal stenosis (LSS) is a common reason for spine surgery in which ligamentum flavum is resected. Transthyretin (TTR) amyloid is an often unrecognized and potentially modifiable mechanism for LSS that can also cause TTR cardiac amyloidosis. Accordingly, older adult patients undergoing lumbar spine (LS) surgery were evaluated for amyloid and if present, the precursor protein, as well as comprehensive characterization of the clinical phenotype., Methods: A prospective, cohort study in 2 academic medical centers enrolled 47 subjects (age 69 ± 7 years, 53% male) undergoing clinically indicated LS decompression. The presence of amyloid was evaluated by Congo Red staining and in those with amyloid, precursor protein was determined by laser capture microdissection coupled to mass spectrometry (LCM-MS). The phenotype was assessed by disease-specific questionnaires (Swiss Spinal Stenosis Questionnaire and Kansas City Cardiomyopathy Questionnaire) and the 36-question short-form health survey, as well as biochemical measures (TTR, retinol-binding protein, and TTR stability). Cardiac testing included technetium-99m-pyrophosphate scintigraphy, electrocardiograms, echocardiograms, and cardiac biomarkers as well as measures of functional capacity., Results: Amyloid was detected in 16 samples (34% of participants) and was more common in those aged ≥ 75 years of age (66.7%) compared with those <75 years (22.3%, p < 0.05). LCM-MS demonstrated TTR as the precursor protein in 62.5% of participants with amyloid while 37.5% had an indeterminant type of amyloid. Demographic, clinical, quality-of-life measures, electrocardiographic, echocardiographic, and biochemical measures did not differ between those with and without amyloid. Among those with TTR amyloid (n = 10), one subject had cardiac involvement by scintigraphy., Conclusions: Amyloid is detected in more than a third of older adults undergoing LSS. Amyloid is more common with advancing age and is particularly common in those >75 years old. No demographic, clinical, biochemical, or cardiac parameter distinguished those with and without amyloid. In more than half of subjects with LS amyloid, the precursor protein was TTR indicating the importance of pathological assessment., (© 2022 The American Geriatrics Society.)

Background: Serum prealbumin level is slightly higher, whereas albumin is lower in peritoneal dialysis (PD) than hemodialysis (HD) patients. It is unknown whether albumin to prealbumin ratio (APR) is associated with mortality risk among PD patients. This study aimed to evaluate the clinical implications of APR and its prediction value on long-term outcomes of PD patients., Methods: The study population were prevalent PD patients at a tertiary hospital. Based on APR, a total of 220 PD patients were divided into 3 groups: group 1: top tertile, median APR: 121.1; IQR:109.5-131.9 (n = 73, male: 37%; age: 59±13); group 2: middle tertile, median APR: 97.1; IQR 93.5-100.0 (n = 73, male:37%; age: 54±14), and group3: bottom tertile, median APR: 81.3; IQR:76.8-85.0 (n = 74, male:38%; 54±11). Patients were followed up for a maximum of 5 years. Outcome of interest was all-cause mortality., Results: Group 1 was characterized by older age, higher prevalence of diabetes, lower nPCR, higher Davies score and hs-CRP level. APR positively correlated to hs-CRP (β = 0.149, p = 0.045), but negatively correlated to nPCR (β = -0.161, p = 0.034). Hyperprealbuminemia, accounting for 0%, 23.3%, and 82.4% in groups 1,2, and 3, was associated with a lower risk for mortality (HR:0.41, 95%CI = 0.23-0.73). The cumulative survival is significantly lower in group 1 than the other two groups. By multivariable Cox regression, APR (HR:1.02; 95%CI:1.01-1.03) was found to be an independent predictor of long-term mortality., Conclusion: PD patients with high APR are characterized by having more comorbidities and marked malnutrition-inflammation status, and are associated with long-term mortality, whereas hyperprealbuminemia and lower APR are favorable prognostic factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Severe acute pancreatitis (SAP) is a common abdominal disorder contributing to high mortality and open laparotomy rates. The role of exogenous infused albumin in fluid resuscitation or continuous therapy has always been an unanswered question. In early stage after onset, SAP patients with higher serum albumin or prealbumin show a better prognosis. In this study, we tried to disclose the linkage between albumin/prealbumin and SAP prognosis and establish a new goal-directed therapy involving albumin and prealbumin. Pearson's chi-squared test and the Mann-Whitney U test were used to compare the descriptive data between surviving and non-surviving patients. Three days, 4-7 days, 8-14 days and 15-28 days after SAP onset were defined as stages 1-4. The average concentrations of albumin and prealbumin were calculated, and receiver operating characteristic (ROC) curves were drawn to screen out the best cutoff values associated with poor prognostic outcomes, including laparotomy and failure to survive. Kaplan-Meier survival curves and log-rank tests were used to validate the effect of the cut-off values. A total of 199 admitted patients were enrolled in this study. According to the analysis of the ROC curve, the serum albumin value should be raised to 35, 37, 40 and 42 g/L in the 1-4 stage after onset. Serum prealbumin values should be raised to 108, 180, and 181 g/L in stages 2-4 after onset. The validity of the above data was confirmed by Kaplan-Meier survival curves. Serum albumin and prealbumin levels in the early stage of SAP are significantly relevant to prognosis. Albumin should be infused from the fluid resuscitation stage to continuous therapy in order to reach the targets mentioned above. The increase in prealbumin depends on the early initiation of enteral nutrition and this also helps to ameliorate the prognosis., (© 2022. The Author(s).)

Purpose: To investigate the effect of tolcapone on cerebrospinal fluid (CSF) transthyretin (TTR) tetramer stability in patients with hereditary transthyretin (ATTRv) amyloidosis., Methods: A total of 9 patients were enrolled in the study (3 men, 50.3 ± 14.4 years old). Three patients had central nervous system (CNS) involvement. Patients were assigned to receive tolcapone 300 mg/day or 600 mg/day for 7 days. Plasma and CSF were collected at baseline and 2 h after the final tolcapone dose., Results: The mean CSF tolcapone and 3-O-Methyltolcapone (3-OMT) concentration were 39.4 ± 36.3 ng/mL and 26.0 ± 4.9 ng/mL, respectively, after 7 days of tolcapone dosing. Tolcapone and 3-OMT were detected in the CSF of patients with or without CNS symptoms. The mean total study drug (tolcapone + 3-OMT) to TTR molar ratio in CSF was 1.15 ± 0.59. Orally administered tolcapone significantly increased CSF TTR concentration and decreased monomer content under semi-denaturing conditions. Eight adverse events (AEs) were reported in 6 patients. All AEs were mild in severity and resolved., Conclusions: Tolcapone was able to cross the blood brain-barrier, highlighting its potential to decrease CNS manifestations of ATTRv amyloidosis. Tolcapone was well tolerated by patients with ATTRv amyloidosis.

Background: We have demonstrated that protein aggregation plays a pivotal role in the pathophysiology of preeclampsia and identified several aggregated proteins in the circulation of preeclampsia patients, the most prominent of which is the serum protein TTR (transthyretin). However, the mechanisms that underlie protein aggregation remain poorly addressed., Methods: We examined TTR aggregates in hypoxia/reoxygenation-exposed primary human trophoblasts (PHTs) and the preeclampsia placenta using complementary approaches, including a novel protein aggregate detection assay. Mechanistic analysis was performed in hypoxia/reoxygenation-exposed PHTs and Ttr transgenic mice overexpressing transgene-encoded wild-type human TTR or Ttr -/- mice. High-resolution ultrasound analysis was used to measure placental blood flow in pregnant mice., Results: TTR aggregation was inducible in PHTs and the TCL-1 trophoblast cell line by endoplasmic reticulum stress inducers or autophagy-lysosomal disruptors. PHTs exposed to hypoxia/reoxygenation showed increased intracellular BiP (binding immunoglobulin protein), phosphorylated IRE1α (inositol-requiring enzyme-1α), PDI (protein disulfide isomerase), and Ero-1, all markers of the unfolded protein response, and the apoptosis mediator caspase-3. Blockade of IRE1α inhibited hypoxia/reoxygenation-induced upregulation of Ero-1 in PHTs. Excessive unfolded protein response activation was observed in the early-onset preeclampsia placenta. Importantly, pregnant human TTR mice displayed aggregated TTR in the junctional zone of the placenta and severe preeclampsia-like features. High-resolution ultrasound analysis revealed low blood flow in uterine and umbilical arteries in human TTR mice compared with control mice. However, Ttr -/- mice did not show any pregnancy-associated abnormalities., Conclusions: These observations in the preeclampsia placenta, cultured trophoblasts, and Ttr transgenic mice indicate that TTR aggregation is an important causal contributor to preeclampsia pathophysiology.

Purpose: Although C-reactive protein to prealbumin ratio (CPR) can predict the outcomes of several types of cancer surgeries, little is known about the implication of CPR in patients undergoing esophagectomy for esophageal squamous cell carcinoma (ESCC)., Methods: Between 2009 and 2018, 682 consecutive ESCC patients who underwent curative esophagectomy were enrolled. The clinicopathological factors and prognoses were compared between the groups stratified by preoperative CPR levels. A logistic regression model was used to determine the risk factors of postoperative pneumonia. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used to elucidate prognostic factors., Results: There were more elderly patients, more males, and more advanced clinical T and N categories in the high CPR group than in the low CPR group. Also, the incidence of postoperative pneumonia was significantly higher in the high CPR group than in the low CPR group (32.4% vs. 20.3%, p < 0.01). In multivariate analyses, high CPR was one of the independent predictive factors for postoperative pneumonia (OR, 1.71; 95% CI, 1.15-2.54; p < 0.03). Moreover, high CPR was an independent prognostic factor for overall, cancer-specific, and recurrence-free survivals (HR 1.62; 95% CI 1.18-2.23; p < 0.01, HR 1.57; 95% CI 1.08-2.32; p = 0.02, HR 1.42; 95% CI 1.06-1.90; p = 0.02)., Conclusion: Preoperative CPR was found to be a useful inflammatory and nutritional indicator for predicting the occurrence of pneumonia and prognosis in patients with ESCC undergoing esophagectomy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Plasma transthyretin may be engaged in glucose regulation. We aimed to investigate the association between plasma transthyretin levels and the risk of newly diagnosed T2DM and impaired glucose regulation (IGR) in a Chinese population. We conducted a case-control study including 1244 newly diagnosed T2DM patients, 837 newly diagnosed IGR patients, and 1244 individuals with normal glucose tolerance (NGT) matched by sex and age. Multivariate logistic regression analysis was utilized to estimate the independent association of plasma transthyretin concentrations with the risk of T2DM and IGR. Plasma transthyretin concentrations were significantly higher in T2DM and IGR patients compared with control subjects (p < 0.005). After multiple adjustment and comparison with the lowest quartile of plasma transthyretin concentrations, the odds ratios (95% confidence intervals) of T2DM and IGR in the highest quartile were 2.22 (1.66, 2.98) and 2.29 (1.72, 3.05), respectively. Plasma transthyretin concentrations also showed a great performance in predicting the risk of T2DM (AUC: 0.76). Moreover, a potential nonlinear trend was observed. Our results demonstrated that higher plasma transthyretin concentrations, especially more than 290 mg/L, were associated with an increased risk of T2DM and IGR. Further studies are warranted to confirm our findings and elucidate the potential mechanisms.

Aim: To evaluate the association of serum prealbumin level with adverse outcomes in heart failure (HF) patients by conducting a meta-analysis. Methods: A comprehensive literature search was conducted in both international and Chinese databases to identify the cohort studies that reported the association of serum prealbumin level with all-cause mortality and composite endpoints of death/heart failure readmission in HF patients. Results: Eight studies involving 2439 patients were eligible. Low prealbumin level was associated with higher risk of all-cause mortality (adjusted risk ratio [RR] 1.89; 95% CI: 1.35-2.65) and composite endpoints (adjusted RR 3.08; 95% CI: 1.43-6.64). Conclusions: Low serum prealbumin level may be an independent predictor of all-cause mortality/heart failure readmission in HF patients.

Abstract: The impact of serum prealbumin in patients with esophageal carcinoma after undergoing esophagectomy remains unclear, we speculated that serum prealbumin is associated with anastomotic leak (AL) after surgery, low serum prealbumin level may lead to AL. The aim of the study was to evaluate the relationship between serum prealbumin levels and AL after esophagectomy, to explore the value of serum prealbumin as an early predictor of AL after esophagectomy.Between January 2014 and December 2018, 255 patients were enrolled in this study, their basic characteristics and perioperative serum prealbumin levels were retrospectively analyzed. Statistical analysis by t test, nonparametric test and logistic regression were used to analyze data for patients with and without AL. Based on a receiver operator characteristic curve, a cut-off value for serum prealbumin levels as a predictor of AL was determined.Among the 255 patients, 18 patients were diagnosed with AL. The overall AL rate was 7.0% (18/255) including 12 cases of intrathoracic AL and 6 cases of cervical AL. By univariate analysis, we identified postoperative serum prealbumin level as a risk factor for AL (P < .001). Multivariate analysis also demonstrated postoperative serum prealbumin level (P = .028) to be an independent risk factor for AL. The best cut-off value of postoperative serum prealbumin level was 131 mg/L for predicting AL, with 83.3% sensitivity and 72.2% specificity.Postoperative serum prealbumin level was significantly associated with AL. it may help the early prediction of postoperative AL., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Familial amyloidotic polyneuropathy (FAP) is caused by a mutation in the transthyretin (TTR) gene. In addition, deposition of wild-type TTR can cause senile systemic amyloidosis (SSA). To date, we have produced several transgenic mouse models for FAP and SSA by introducing TTR genes with different promoters or mutations. However, mouse TTR can associate with human TTR to produce hybrid tetramers in transgenic mice. Thus, these transgenic mice cannot be used to test the efficacy of a new therapy. In this study, we attempted to construct an optimized mouse model to verify a new therapy. The TTR gene consists of 4 exons and 3 introns. We prepared two gRNAs, one for the exon 1 and the other for exon 4, and a single donor vector carrying the whole TTR gene in which mouse exons were replaced with human exons. Using these vectors, we produced a TTR exon-humanized mouse with human exons and mouse introns using genome editing technology. These TTR exon-humanized mice showed normal TTR expression patterns in terms of serum TTR level and spatial specificity. These TTR exon-humanized mice will be useful for devising new treatment methods for FAP, including gene therapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM), which is still a major reason for blindness. Transthyretin (TTR) and retinol-binding protein (RBP) are thought to be related to the pathogenesis both in T2DM and T1DM. We aimed to investigate the association between serum levels of TTR, RBP, RBP/TTR ratio, and DR., Methods: This retrospective study involved 188 T1DM inpatients divided into two groups: patients with DR (n = 95) and patients without DR (n = 93). Data of serum levels on lipids and inflammation were collected. Multiple logistic regression analysis was performed to research the association between TTR, RBP, RBP/TTR, and diabetic retinopathy in T1DM., Results: Compared with patients without DR, those with DR have a higher level of TTR (207 versus 195 mg/L, p = 0.034) and RBP4 (36.85 versus 25.68 mg/L, p < 0.001). Significant differences were also observed between two groups with respect to body mass index (BMI), blood pressure (BP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), homocysteine, apolipoprotein B (APOB), leucocyte, monocyte, neutrophil, and uric acid (p < 0.05 for all). TTR, RBP, and RBP/TTR were positively correlated with BP, BMI, TG, LDL, homocysteine, APOB, and uric acid. A multivariate logistic regression model revealed individuals with RBP4 level in the highest quartile had 58.95 times higher risk of developing diabetic retinopathy than those in the lowest quartile., Conclusions: In conclusion, TTR, RBP, and RBP/TTR ratio are risk factors of DR in T1DM. They are potential markers and targets for diagnosis and treatment of DR., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

In this study, we aimed to analyze whether serum prealbumin and transferrin have a higher sensitivity than albumin for detecting malnutrition and predicting survival in esophageal cancer patients. A total of 212 patients were prospectively enrolled. Serum albumin, prealbumin, and transferrin were analyzed by enzyme-linked immunosorbent assays. The association of nutritional markers with survival was analyzed. We found that malnutrition was presented in 44.5% of the patients, while 56.6% were unaware of their body weight change. The area under the curve for diagnosing malnutrition was largest for prealbumin, followed by transferrin and albumin, with optimal breakpoints of 21 mg/dL, 206 mg/dL, and 4.3 g/dL, respectively, for diagnosing malnutrition. The diagnostic sensitivity for malnutrition was 34.1-63.4% with a single marker and this increased to 80.5% with all 3 markers. In patients with normal albuminemia (≥ 4.3 g/dL), a low level of prealbumin and/or transferrin predicted malnutrition and poor prognosis. Multivariate Cox regression analysis confirmed that a low level of the nutritional marker was an independent poor prognostic factor. In conclusion, serum prealbumin and transferrin outperformed albumin in identifying esophageal cancer patients with malnutrition and poor prognosis. Checking all three markers will help with the early diagnosis of malnutrition and enable timely intervention.

Introduction: Prealbumin is a marker of malnutrition and inflammation. It has been associated with poor prognosis in cardiovascular disease, but less is known in stroke patients. Our objective was to evaluate the association of prealbumin levels at admission with prognosis in patients with stroke treated with mechanical thrombectomy., Methods: Retrospective study of a prospective database of consecutive patients treated with mechanical thrombectomy. Clinical, radiological, and blood parameters including serum prealbumin, and prognostic variables such as respiratory infection, in-hospital mortality, and the modified Rankin scale at 3 months were collected., Results: We included 319 patients between 2018 and 2019. Prealbumin levels were significantly lower in patients older than 80 years, women, patients with a prestroke Rankin score >2, a glomerular filtrate rate <60 mL/min, and in those with atrial fibrillation. Regarding prognostic variables, prealbumin levels were not associated with respiratory infection. Low prealbumin levels were associated with poor functional prognosis (Rankin score >2), in-hospital mortality, and 3-month mortality. In multivariate analysis, prealbumin was an independent risk factor associated with mortality at 3 months, OR 0.92 [0.86-0.98], p = 0.019., Conclusion: Lower prealbumin levels at admission behaved as an independent predictor of long-term mortality in patients treated with mechanical thrombectomy. These results should be replicated in other cohorts., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Nowadays, with an upward trend in the prevalence of intracerebral amyloidosis, it is of great significance to use fluorescent probes for early diagnosis in vitro. In this study, a quinoline-derived D-A-D type chemosensor was rationally designed and synthesized as a probe for the sensitive detection of tetrameric transthyretin (WT-TTR)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aim: Amyloidosis is a systemic or localized disease of protein deposition characterized by amorphous eosinophilic morphology and positivity of Congo Red staining. The typing of amyloidosis is becoming increasingly important because therapeutic agents for each amyloidosis type have been developed. Herein, the authors review the autopsy cases at an institution to reveal the putative Japanese characteristics of each amyloidosis type and evaluate the clinicopathological significance of each type., Materials and Methods: A total of 131 autopsy cases of systemic and localized amyloidosis were retrieved for classification by immunohistochemistry. Immunohistochemistry for transthyretin, amyloid A (AA), immunoglobulin light-chain kappa and lambda, and β2-microglobulin was performed for all cases., Results: The 131 amyloidosis cases were classified as follows: 71 cases (54.2%) of transthyretin amyloidosis, 32 cases (24.4%) of AA amyloidosis, 8 cases (6.1%) of light-chain amyloidosis, and 5 cases (3.8%) of β2-microglobulin amyloidosis, along with 15 equivocal cases (11.5%). All cases showed myocardial involvement of amyloidosis. Histopathologically, the transthyretin type was significantly associated with the interstitial and nodular patterns, and with the absence of the perivascular and endocardial patterns. The AA type was significantly associated with the perivascular and endocardial patterns, and with the absence of the nodular pattern., Conclusion: The authors revealed the putative characteristics of cardiac amyloidosis in Japan by using autopsy cases. About 90% of amyloidosis cases were successfully classified using only commercially available antibodies., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Abstract: We designed this study to assess the effectiveness of prealbumin as an indicator of growth as well as a nutritional marker in neonates.Between March 2017 and June 2019, we measured serum prealbumin concentrations of 80 neonates in neonatal intensive care unit at birth, postnatal day 14 and 28, and classified them into 3 groups (early preterm, late preterm, and term infants). And we examined correlation among prealbumin levels, nutritional intake, and anthropometric measurements (weight, length, and head circumference) in neonates.Prealbumin measured on the 14th postnatal day in early preterm infants showed significant correlations with the length, weight, and head circumference z-scores. Prealbumin levels increased with time in the late preterm and term groups. At birth, prealbumin levels were the lowest in late preterm babies, implying that they are nutritionally deficient and need nutritional support. At postnatal day 28, the prealbumin levels of many preterm infants did not reach those seen in term babies at birth, suggesting the presence of extrauterine growth restriction.Prealbumin can be considered as an indicator of sufficient growth in early preterm infants., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The aim of this study was to investigate the nutritional status, determinants of nutritional status, and adequacy of energy and nutrient intake of older family caregivers (FC). Nutritional status was measured using the Mini Nutritional Assessment (MNA), plasma albumin, plasma pre-albumin, and blood hemoglobin concentrations. Dietary intake was assessed with a three-day food record. Comorbidity (B -0.283, 95% CI: -0.492, -0.073), quality of life (B 0.045, 95% CI: 0.018, 0.072) and energy intake (B 0.001, 95% CI: 0.000, 0.002) were significantly associated with the MNA scores of the older FCs ( n = 125). It was common for FCs to have lower than recommended intakes of energy and several nutrients, independent of the risk of malnutrition assessed by the MNA. Over half of the FCs had inadequate intake of protein, vitamin A, folate, and fiber, and 25-40% of the FCs had a low intake of vitamin D, vitamin E, thiamine, magnesium, iron, and selenium. It is important to follow both the nutritional status and dietary intake of older FCs regularly to find those with lower than recommended nutrient intake and to avoid poor nutritional status and its adverse effects hampering their ability to serve as FCs.