-
Clinical Interventions in Aging 2022Malnutrition is very commonly encountered in palliative care centers (PCC), especially in geriatric patients. It is known that development of malnutrition increases...
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.
Topics: Humans; Aged; Nutrition Assessment; Prealbumin; Palliative Care; Malnutrition; Prognosis; C-Reactive Protein; Nutritional Status; Geriatric Assessment
PubMed: 36597427
DOI: 10.2147/CIA.S380536 -
PloS One 2019The unknown role of the carrier protein transthyretin (TTR) in mechanisms of functional recovery in the postischemic brain prompted us to study its expression following...
The unknown role of the carrier protein transthyretin (TTR) in mechanisms of functional recovery in the postischemic brain prompted us to study its expression following experimental stroke. Male C57/B6 mice (age 9 to 10 weeks) were subjected to permanent focal ischemia induced by photothrombosis (PT) and brain tissues were analyzed for ttr expression and TTR levels at 24 hours, 48 hours, 7 days and 14 days following the insult by RT-PCR, Western blot and immunohistochemistry. Fourteen days after PT, non-specific TTR-like immunoreactive globules were found in the ischemic core and surrounding peri-infarct region by immunohistochemistry that could not be allocated to DAPI positive cells. No TTR immunoreactivity was found when stainings were performed with markers for neurons (Neuronal Nuclei, NeuN), reactive astrocytes (glial fibrillary acidic protein, GFAP) or microglia (cluster of differentiation 68, CD68). In addition, we could not find TTR by immunoblotting in protein extracts obtained from the ischemic territory nor ttr expression by RT-PCR at all time points following PT. In all experiments, ttr expression in the choroid plexus and TTR in the mouse serum served as positive controls and recombinant legumain peptide as negative control. Together, our results indicate that TTR is not synthesized in brain resident cells in the ischemic infarct core and adjacent peri-infarct area. Thus, it seems unlikely that in situ synthesized TTR is involved in mechanisms of tissue reorganization during the first 14 days following PT.
Topics: Animals; Astrocytes; Brain; Brain Ischemia; Choroid Plexus; Disease Models, Animal; Gene Expression; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Microglia; Neurons; Prealbumin; RNA, Messenger
PubMed: 31479465
DOI: 10.1371/journal.pone.0221555 -
JCI Insight Apr 2022Amyloidosis involves stepwise growth of fibrils assembled from soluble precursors. Transthyretin (TTR) naturally folds into a stable tetramer, whereas conditions and...
Amyloidosis involves stepwise growth of fibrils assembled from soluble precursors. Transthyretin (TTR) naturally folds into a stable tetramer, whereas conditions and mutations that foster aberrant monomer formations facilitate TTR oligomeric aggregation and subsequent fibril extension. We investigated the early assembly of oligomers by WT TTR compared with its V30M and V122I variants. We monitored time-dependent redistribution among monomer, dimer, tetramer, and oligomer contents in the presence and absence of multimeric TTR seeds. The seeds were artificially constructed recombinant multimers that contained 20-40 TTR subunits via engineered biotin-streptavidin (SA) interactions. As expected, these multimer seeds rapidly nucleated TTR monomers into larger complexes, while having less effect on dimers and tetramers. In vivo, SA-induced multimers formed TTR-like deposits in the heart and the kidney following i.v. injection in mice. While all 3 variants prominently deposited glomerulus in the kidney, only V30M resulted in extensive deposition in the heart. The cardiac TTR deposits varied in size and shape and were localized in the intermyofibrillar space along the capillaries. These results are consistent with the notion of monomeric TTR engaging in high-avidity interactions with tissue amyloids. Our multimeric induction approach provides a model for studying the initiation of TTR deposition in the heart.
Topics: Amyloid; Animals; Mice; Prealbumin
PubMed: 35393947
DOI: 10.1172/jci.insight.150131 -
JACC. Heart Failure Feb 2021
Topics: Benzoxazoles; Cardiomyopathies; Heart Failure; Humans; Prealbumin
PubMed: 33422433
DOI: 10.1016/j.jchf.2020.12.001 -
BMC Pulmonary Medicine Jun 2024We aimed to determine whether systemic immune-inflammation index (SII) combined with prealbumin can provide better predictive power for postoperative pneumonia in...
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.
Topics: Humans; Female; Male; Middle Aged; Pneumonia; Postoperative Complications; Aged; Prealbumin; Retrospective Studies; Pneumonectomy; Predictive Value of Tests; ROC Curve; Logistic Models; Inflammation
PubMed: 38862955
DOI: 10.1186/s12890-024-03086-7 -
JACC. Cardiovascular Imaging Jan 2022
Topics: Amyloidosis; Heart Atria; Humans; Muscular Diseases; Prealbumin; Predictive Value of Tests
PubMed: 34801458
DOI: 10.1016/j.jcmg.2021.08.005 -
General and Comparative Endocrinology Sep 2000Transthyretin (TTR) belongs to a group of proteins, which includes thyroxine-binding globulin and albumin, that bind to and transport thyroid hormones in the blood. TTR... (Review)
Review
Transthyretin (TTR) belongs to a group of proteins, which includes thyroxine-binding globulin and albumin, that bind to and transport thyroid hormones in the blood. TTR is also indirectly implicated in the carriage of vitamin A through the mediation of retinol-binding protein (RBP). It was first identified in 1942 in human serum and cerebrospinal fluid and was formerly called prealbumin for its ability to migrate faster than serum albumin on electrophoresis of whole plasma. It is a single polypeptide chain of 127 amino acids (14,000 Da) and is present in the plasma as a tetramer of noncovalently bound monomers. The major sites of synthesis of TTR in eutherian mammals, marsupials, and birds are the liver and choroid plexus but in reptiles it is synthesised only in the choroid plexus. The observation that TTR is strongly expressed in the choroid plexus but not in the liver of the stumpy-tailed lizard and the strong conservation of expression in the choroid plexus from reptiles to mammals have been taken as evidence to suggest that extrahepatic synthesis of TTR evolved first. The identification and cloning of TTR from the liver of an amphibian, Rana catesbeiana, and a teleost fish, Sparus aurata, and its absence from the choroid plexus of both species suggest an alternative model for its evolution. Protein modelling studies are presented that demonstrate differences in the electrostatic characteristics of the molecule in human, rat, chicken, and fish, which may explain why, in contrast to TTR from human and rat, TTR from fish and birds preferentially binds triiodo-l-thyronine.
Topics: Amino Acid Sequence; Animals; DNA, Complementary; Evolution, Molecular; Humans; Models, Molecular; Molecular Sequence Data; Molecular Structure; Phylogeny; Prealbumin; Sequence Homology
PubMed: 11017772
DOI: 10.1006/gcen.2000.7520 -
Aging Cell Dec 2017Deposition of amyloid is a common aging-associated phenomenon in several aging-related diseases. Osteoarthritis (OA) is the most prevalent joint disease, and aging is...
Deposition of amyloid is a common aging-associated phenomenon in several aging-related diseases. Osteoarthritis (OA) is the most prevalent joint disease, and aging is its major risk factor. Transthyretin (TTR) is an amyloidogenic protein that is deposited in aging and OA-affected human cartilage and promotes inflammatory and catabolic responses in cultured chondrocytes. Here, we investigated the role of TTR in vivo using transgenic mice overexpressing wild-type human TTR (hTTR-TG). Although TTR protein was detected in cartilage in hTTR-TG mice, the TTR transgene was highly overexpressed in liver, but not in chondrocytes. OA was surgically induced by destabilizing the medial meniscus (DMM) in hTTR-TG mice, wild-type mice of the same strain (WT), and mice lacking endogenous Ttr genes. In the DMM model, both cartilage and synovitis histological scores were significantly increased in hTTR-TG mice. Further, spontaneous degradation and OA-like changes in cartilage and synovium developed in 18-month-old hTTR mice. Expression of cartilage catabolic (Adamts4, Mmp13) and inflammatory genes (Nos2, Il6) was significantly elevated in cartilage from 6-month-old hTTR-TG mice compared with WT mice as was the level of phospho-NF-κB p65. Intra-articular injection of aggregated TTR in WT mice increased synovitis and significantly increased expression of inflammatory genes in synovium. These findings are the first to show that TTR deposition increases disease severity in the murine DMM and aging model of OA.
Topics: Age Factors; Animals; Disease Models, Animal; Disease Progression; Humans; Immunohistochemistry; Male; Mice; Mice, Transgenic; Osteoarthritis; Prealbumin
PubMed: 28941045
DOI: 10.1111/acel.12665 -
Scientific Reports Sep 2018Transthyretin (TTR), a homotetrameric protein that transports thyroxine and retinol both in plasma and in cerebrospinal (CSF) fluid provides a natural protective...
Transthyretin (TTR), a homotetrameric protein that transports thyroxine and retinol both in plasma and in cerebrospinal (CSF) fluid provides a natural protective response against Alzheimer's disease (AD), modulates amyloid-β (Aβ) deposition by direct interaction and co-localizes with Aβ in plaques. TTR levels are lower in the CSF of AD patients. Zn, Mn and Fe transform TTR into a protease able to cleave Aβ. To explain these activities, monomer dissociation or conformational changes have been suggested. Here, we report that when TTR crystals are exposed to copper or iron salts, the tetramer undergoes a significant conformational change that alters the dimer-dimer interface and rearranges residues implicated in TTR's ability to neutralize Aβ. We also describe the conformational changes in TTR upon the binding of the various metal ions. Furthermore, using bio-layer interferometry (BLI) with immobilized Aβ(1-28), we observe the binding of TTR only in the presence of copper. Such Cu-dependent binding suggests a recognition mechanism whereby Cu modulates both the TTR conformation, induces a complementary Aβ structure and may participate in the interaction. Cu-soaked TTR crystals show a conformation different from that induced by Fe, and intriguingly, TTR crystals grown in presence of Aβ(1-28) show different positions for the copper sites from those grown its absence.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Copper; Humans; Iron; Manganese; Models, Molecular; Plaque, Amyloid; Prealbumin; Protein Binding; Protein Conformation; Protein Multimerization; Signal Transduction; Zinc
PubMed: 30213975
DOI: 10.1038/s41598-018-31808-5 -
International Journal of Molecular... Aug 2021Transthyretin (TTR) proteolysis has been recognized as a complementary mechanism contributing to transthyretin-related amyloidosis (ATTR amyloidosis). Accordingly,...
Transthyretin (TTR) proteolysis has been recognized as a complementary mechanism contributing to transthyretin-related amyloidosis (ATTR amyloidosis). Accordingly, amyloid deposits can be composed mainly of full-length TTR or contain a mixture of both cleaved and full-length TTR, particularly in the heart. The fragmentation pattern at Lys48 suggests the involvement of a serine protease, such as plasmin. The most common TTR variant, TTR V30M, is susceptible to plasmin-mediated proteolysis, and the presence of TTR fragments facilitates TTR amyloidogenesis. Recent studies revealed that the serine protease inhibitor, SerpinA1, was differentially expressed in hepatocyte-like cells (HLCs) from ATTR patients. In this work, we evaluated the effects of SerpinA1 on in vitro and in vivo modulation of TTR V30M proteolysis, aggregation, and deposition. We found that plasmin-mediated TTR proteolysis and aggregation are partially inhibited by SerpinA1. Furthermore, in vivo downregulation of SerpinA1 increased TTR levels in mice plasma and deposition in the cardiac tissue of older animals. The presence of TTR fragments was observed in the heart of young and old mice but not in other tissues following SerpinA1 knockdown. Increased proteolytic activity, particularly plasmin activity, was detected in mice plasmas. Overall, our results indicate that SerpinA1 modulates TTR proteolysis and aggregation in vitro and in vivo.
Topics: Age Factors; Amyloid; Amyloid Neuropathies, Familial; Amyloidosis; Animals; Disease Models, Animal; Female; Fibrinolysin; Hepatocytes; Humans; Male; Mice; Mice, Transgenic; Prealbumin; Proteolysis; alpha 1-Antitrypsin
PubMed: 34502397
DOI: 10.3390/ijms22179488