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The Journal of Physical Chemistry... May 2024Heart tissue can experience a progressive accumulation of transthyretin (TTR), a small four subunit protein that transports holoretinol binding protein and thyroxine....
Heart tissue can experience a progressive accumulation of transthyretin (TTR), a small four subunit protein that transports holoretinol binding protein and thyroxine. This severe pathology is known as transthyretin amyloid cardiomyopathy. Numerous experimental studies indicated that the aggregation rate and toxicity of TTR fibrils could be altered by the presence of lipids; however, the role of plasmalogens in this process remains unknown. In this study, we investigate the effect of choline plasmalogens (CPs) with different lengths and saturations of fatty acids (FAs) on TTR aggregation. We found that CPs with saturated and unsaturated FAs strongly suppressed TTR aggregation. We also found that CPs with saturated FAs did not change the morphology of TTR fibrils; however, much thicker fibrillar species were formed in the presence of CPs with unsaturated FAs. Finally, we found that CPs with C16:0, C18:0, and C18:1 FAs substantially lowered the cytotoxicity of TTR fibrils that were formed in their presence.
Topics: Prealbumin; Plasmalogens; Humans; Amyloid; Protein Aggregates; Fatty Acids
PubMed: 38661515
DOI: 10.1021/acs.jpclett.4c00868 -
World Journal of Gastroenterology Apr 2024Portal hypertension (PHT), primarily induced by cirrhosis, manifests severe symptoms impacting patient survival. Although transjugular intrahepatic portosystemic shunt...
BACKGROUND
Portal hypertension (PHT), primarily induced by cirrhosis, manifests severe symptoms impacting patient survival. Although transjugular intrahepatic portosystemic shunt (TIPS) is a critical intervention for managing PHT, it carries risks like hepatic encephalopathy, thus affecting patient survival prognosis. To our knowledge, existing prognostic models for post-TIPS survival in patients with PHT fail to account for the interplay among and collective impact of various prognostic factors on outcomes. Consequently, the development of an innovative modeling approach is essential to address this limitation.
AIM
To develop and validate a Bayesian network (BN)-based survival prediction model for patients with cirrhosis-induced PHT having undergone TIPS.
METHODS
The clinical data of 393 patients with cirrhosis-induced PHT who underwent TIPS surgery at the Second Affiliated Hospital of Chongqing Medical University between January 2015 and May 2022 were retrospectively analyzed. Variables were selected using Cox and least absolute shrinkage and selection operator regression methods, and a BN-based model was established and evaluated to predict survival in patients having undergone TIPS surgery for PHT.
RESULTS
Variable selection revealed the following as key factors impacting survival: age, ascites, hypertension, indications for TIPS, postoperative portal vein pressure (post-PVP), aspartate aminotransferase, alkaline phosphatase, total bilirubin, prealbumin, the Child-Pugh grade, and the model for end-stage liver disease (MELD) score. Based on the above-mentioned variables, a BN-based 2-year survival prognostic prediction model was constructed, which identified the following factors to be directly linked to the survival time: age, ascites, indications for TIPS, concurrent hypertension, post-PVP, the Child-Pugh grade, and the MELD score. The Bayesian information criterion was 3589.04, and 10-fold cross-validation indicated an average log-likelihood loss of 5.55 with a standard deviation of 0.16. The model's accuracy, precision, recall, and F1 score were 0.90, 0.92, 0.97, and 0.95 respectively, with the area under the receiver operating characteristic curve being 0.72.
CONCLUSION
This study successfully developed a BN-based survival prediction model with good predictive capabilities. It offers valuable insights for treatment strategies and prognostic evaluations in patients having undergone TIPS surgery for PHT.
Topics: Humans; Hypertension, Portal; Bayes Theorem; Portasystemic Shunt, Transjugular Intrahepatic; Middle Aged; Female; Male; Retrospective Studies; Prognosis; Liver Cirrhosis; Treatment Outcome; Aged; Adult; Hepatic Encephalopathy; Risk Factors; Portal Pressure
PubMed: 38659484
DOI: 10.3748/wjg.v30.i13.1859 -
Medicine Apr 2024The 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...
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.
Topics: Humans; C-Reactive Protein; COVID-19; Inflammation; Lymphocytes; Neutrophils; Prealbumin; Prognosis; Retrospective Studies; ROC Curve; Aged; Middle Aged
PubMed: 38640293
DOI: 10.1097/MD.0000000000037809 -
International Journal of Molecular... Mar 2024Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is... (Review)
Review
Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (v) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 v carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis.
Topics: Humans; Prealbumin; Intermediate Filaments; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Polyneuropathies; Biomarkers
PubMed: 38612579
DOI: 10.3390/ijms25073770 -
Medicine Apr 2024To analyze the effect of an exercise-nutrition management model based on the Enhanced Recovery After Surgery (ERAS) concept on patients undergoing thoracoscopic radical... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of an ERAS-based exercise-nutrition management model in enhancing postoperative recovery for thoracoscopic radical resection of lung cancer: A randomized controlled trial.
BACKGROUND
To analyze the effect of an exercise-nutrition management model based on the Enhanced Recovery After Surgery (ERAS) concept on patients undergoing thoracoscopic radical surgery for lung cancer.
METHODS
From June 2019 to December 2022, 85 lung cancer patients who underwent thoracoscopic radical lung cancer surgery were randomly divided into 2 groups. The control group, consisting of 42 patients, received routine nursing care during the perioperative period. The study group, comprising 43 patients, implemented an exercise-nutrition management model based on the ERAS concept during the perioperative period. We compared general data, perioperative indicators, compliance, and complications between the 2 groups. Additionally, we assessed the nutritional status using the patient-generated subjective global assessment (PG-SGA), albumin (ALB), prealbumin (PA), and hemoglobin (Hb), as well as lung function, including forced expiratory volume in the first second (FEV1) and maximum voluntary ventilation (MVV), in the patient population following the Piper intervention.
RESULTS
In the study group, the times to first defecation and getting out of bed, the duration of thoracic drainage tube indwelling, and the length of hospital stay were shorter than those in the control group. The VAS scores on the 2nd and 3rd postoperative days were lower in the study group than in the control group (P < .05). Medication compliance was higher in the study group compared to the control group (P < .05). Post-intervention, the PG-SGA scores in the study group were lower, while PA, ALB, and Hb levels were higher than those in the control group (P < .05). The MVV, FEV1, and FVC values were higher in the study group than in the control group after the intervention (P < .05). The PFS and mMRC scores were lower in the study group compared to the control group after the intervention, and the QLQ-C30 scores were higher (P < .05). The incidence of complications was 6.98% in the study group, which was not significantly different from 11.90% in the control group (P > .05).
CONCLUSION
The exercise-nutrition management model, based on the ERAS concept, exhibits significant perioperative effects in patients undergoing thoracoscopic radical resection of lung cancer, improving their nutritional status and reducing complications.
Topics: Humans; Lung Neoplasms; Enhanced Recovery After Surgery; Nutrition Therapy; Postoperative Period; Perioperative Period; Albumins
PubMed: 38608111
DOI: 10.1097/MD.0000000000037667 -
Heliyon Apr 2024is a causative agent of bacterial meningitis in adults. However, there is little information regarding this infection. Therefore, this study comprehensively analyzed...
BACKGROUND
is a causative agent of bacterial meningitis in adults. However, there is little information regarding this infection. Therefore, this study comprehensively analyzed the clinical characteristics and prognosis of meningitis (KPM) patients.
METHODS
The clinical data of adult hospitalized patients with KPM were retrospectively collected from January 2015 to December 2022. The clinical characteristics and antibiotic resistance of KPM were evaluated. Meanwhile, a set of logistic regression models was constructed to identify prognostic factors for death. These prognostic factors were subsequently combined to develop a nomogram for predicting the risk of in-hospital mortality in individual patients. Finally, the receiver operating characteristic curve and calibrate plot were utilized to verify the performance of the nomogram.
RESULTS
This study included 80 adult patients with KPM, 58 (72.5%) of whom were males. The mortality rate was 45%. Among them, 74 (92.5%) were diagnosed with healthcare-associated meningitis. Thirty-seven carbapenem-resistant (CRKP) strains were susceptible to tigecycline, polymyxin, and ceftazidime/avibactam. CRKP (OR = 9.825, 95%CI = 2.757-35.011, P < 0.001), length of stay (OR = 0.953, 95%CI = 0.921-0.986, P = 0.005), and C-reactive protein-to-prealbumin ratio (CRP/PA, OR = 3.053, 95%CI = 1.329-7.016, P = 0.009) were identified as predictive factors for mortality using multivariate logistic regression. Finally, a nomogram for death prediction was established. The area under the curve of this nomogram was 0.900 (95% CI = 0.828-0.971).
CONCLUSIONS
KPM is a fatal disease associated with high incidence of healthcare-associated infections and carbapenem resistance. Moreover, CRKP, length of stay, and CRP/PA were found to be independent predictors of mortality.
PubMed: 38601552
DOI: 10.1016/j.heliyon.2024.e28010 -
Aging Clinical and Experimental Research Apr 2024Whether, and to what extent, frailty and other geriatric domains are linked to health status in patients with transthyretin cardiac amyloidosis (ATTR-CA) is unknown.
BACKGROUND
Whether, and to what extent, frailty and other geriatric domains are linked to health status in patients with transthyretin cardiac amyloidosis (ATTR-CA) is unknown.
AIMS
To determine the association of frailty with health status [defined by the Kansas City Cardiomyopathy Questionnaire (KCCQ)] in patients with ATTR-CA.
METHODS
Consecutive ATTR-CA patients undergoing cardiovascular assessment at a tertiary care clinic from September 2021 to September 2023 were invited to participate. KCCQ, frailty and social environment were recorded. Frailty was assessed using the modified Frailty Index (mFI), mapping 11 variables from the Canadian Study of Health and Aging (frailty ≥0.36).
RESULTS
Of 168 screened ATTR-CA patients, 138 [83% men, median age of 79 (75-84) years] were enrolled in the study. Median KCCQ was 66 (50-75). wtATTR-CA was the most prevalent form (N = 113, 81.9%). The most frequent cardiac variant was Ile68Leu (17/25 individuals with vATTR-CA). Twenty (14.5%) patients were considered frail, and prevalence of overt disability was 6.5%. At multivariable linear regression analysis, factors associated with worsening KCCQ were age at evaluation, the mFI, NYHA Class, and NAC Score. Gender, ATTR-CA type, phenotype, and LVEF were not associated with health status.
DISCUSSION
In older patients diagnosed with ATTR-CA, frailty, symptoms, and disease severity were associated with KCCQ.
CONCLUSIONS
Functional status is a determinant of quality of life and health status in older individuals with a main diagnosis of ATTR-CA. Future research may provide more in-depth knowledge on the association of frailty in patients with ATTR-CA with respect to quality of life and prognosis.
Topics: Male; Humans; Aged; Aged, 80 and over; Female; Quality of Life; Prealbumin; Frailty; Prospective Studies; Canada; Health Status; Amyloidosis
PubMed: 38598143
DOI: 10.1007/s40520-024-02750-6 -
PloS One 2024Amyloid deposition is a cause of restrictive cardiomyopathy. Patients who present with cardiac disease can be evaluated for transthyretin (TTR)-associated cardiac...
INTRODUCTION
Amyloid deposition is a cause of restrictive cardiomyopathy. Patients who present with cardiac disease can be evaluated for transthyretin (TTR)-associated cardiac amyloidosis using nuclear imaging with 99mTc-labeled pyrophosphate (PYP); however, light chain-associated (AL) cardiac amyloid is generally not detected using this tracer. As an alternative, the amyloid-binding peptide p5+14 radiolabeled with iodine-124 has been shown to be an effective pan-amyloid radiotracer for PET/CT imaging. Here, a 99mTc-labeled form of p5+14 peptide has been prepared to facilitate SPECT/CT imaging of cardiac amyloidosis.
METHOD
A synthesis method suitable for clinical applications has been used to prepare 99mTc-labeled p5+14 and tested for peptide purity, product bioactivity, radiochemical purity and stability. The product was compared with99mTc-PYP for cardiac SPECT/CT imaging in a mouse model of AA amyloidosis and for reactivity with human tissue sections from AL and TTR patients.
RESULTS
The 99mTc p5+14 tracer was produced with >95% yields in radiopurity and bioactivity with no purification steps required and retained over 95% peptide purity and >90% bioactivity for >3 h. In mice, the tracer detected hepatosplenic AA amyloid as well as heart deposits with uptake ~5 fold higher than 99mTc-PYP. 99mTc p5+14 effectively bound human amyloid deposits in the liver, kidney and both AL- and ATTR cardiac amyloid in tissue sections in which 99mTc-PYP binding was not detectable.
CONCLUSION
99mTc-p5+14 was prepared in minutes in >20 mCi doses with good performance in preclinical studies making it suitable for clinical SPECT/CT imaging of cardiac amyloidosis.
Topics: Humans; Mice; Animals; Positron Emission Tomography Computed Tomography; Amyloidosis; Tomography, Emission-Computed, Single-Photon; Peptides; Amyloid; Cardiomyopathies; Prealbumin
PubMed: 38578730
DOI: 10.1371/journal.pone.0301756 -
Frontiers in Nutrition 2024Although stroke-related dysphagia has been shown to influence quality of life (QOL), the underlying mechanisms have yet to be uncovered.
How stroke-related dysphagia relates to quality of life: the mediating role of nutritional status and psychological disorders, and the moderating effect of enteral nutrition mode.
BACKGROUND
Although stroke-related dysphagia has been shown to influence quality of life (QOL), the underlying mechanisms have yet to be uncovered.
OBJECTIVE
This study aims to investigate the mediating role of nutritional status and psychological disorders in the relationship between stroke-related dysphagia and QOL in stroke patients and explore the moderating effect of enteral nutrition mode.
METHODS
In 2022, A questionnaire survey using stratified random sampling was conducted on 5,322 stroke patients with dysphagia, including Functional Oral Intake Scale (FOIS), Swallowing Quality of Life Questionnaire, Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) to assess dysphagia, QOL and psychological disorders, respectively, for each participant. Records of serum albumin, Hemoglobin, Total serum protein, serum prealbumin and Body mass index were enrolled to assess nutritional status.
RESULTS
FOIS demonstrated a significant positive predictive effect on QOL. Nutritional status and psychological disorders (PHQ-9 and GAD-7) mediated the relationship between FOIS and QOL. Nutritional status-psychological disorders showed a chain mediation effect in the relationship between FOIS and QOL. The moderating effect of enteral nutrition mode was observed.
CONCLUSION
The mediating role of nutritional status and psychological disorders with moderating effect of enteral nutrition mode in the relationship between dysphagia and QOL in stroke patients was found.
PubMed: 38549743
DOI: 10.3389/fnut.2024.1339694 -
Molecules (Basel, Switzerland) Mar 2024Design of amyloid β-protein (Aβ) inhibitors is considered an effective strategy for the prevention and treatment of Alzheimer's disease (AD). However, the limited...
Design of amyloid β-protein (Aβ) inhibitors is considered an effective strategy for the prevention and treatment of Alzheimer's disease (AD). However, the limited blood-brain barrier (BBB) penetration and poor Aβ-targeting capability restricts the therapeutic efficiency of candidate drugs. Herein, we have proposed to engineer transthyretin (TTR) by fusion of the Aβ-targeting peptide KLVFF and cell-penetrating peptide Penetratin to TTR, and derived a fusion protein, KLVFF-TTR-Penetratin (KTP). Moreover, to introduce the scavenging activity for reactive oxygen species (ROS), a nanocomposite of KTP and manganese dioxide nanoclusters (KTP@MnO) was fabricated by biomineralization. Results revealed that KTP@MnO demonstrated significantly enhanced inhibition on Aβ aggregation as compared to TTR. The inhibitory effect was increased from 18%, 33%, and 49% (10, 25, and 50 μg/mL TTR, respectively) to 52%, 81%, and 100% (10, 25, and 50 μg/mL KTP@MnO). In addition, KTP@MnO could penetrate the BBB and target amyloid plaques. Moreover, multiple ROS, including hydroxyl radicals, superoxide radicals, hydrogen peroxide, and Aβ-induced-ROS, which cannot be scavenged by TTR, were scavenged by KTP@MnO, thus resulting in the mitigation of cellular oxidative damages. More importantly, cell culture and in vivo experiments with AD nematodes indicated that KTP@MnO at 50 μg/mL increased the viability of Aβ-treated cells from 66% to more than 95%, and completely cleared amyloid plaques in AD nematodes and extended their lifespan by 7 d. Overall, despite critical aspects such as the stability, metabolic distribution, long-term biotoxicity, and immunogenicity of the nanocomposites in mammalian models remaining to be investigated, this work has demonstrated the multifunctionality of KTP@MnO for targeting Aβ in vivo, and provided new insights into the design of multifunctional nanocomposites of protein-metal clusters against AD.
Topics: Animals; Humans; Amyloid beta-Peptides; Alzheimer Disease; Cell-Penetrating Peptides; Manganese Compounds; Oxides; Prealbumin; Reactive Oxygen Species; Plaque, Amyloid; Mammals; Peptide Fragments
PubMed: 38543041
DOI: 10.3390/molecules29061405