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Journal of Inflammation Research 2024The ratio of fibrinogen to prealbumin (FPR) is associated with the prognosis of many cancers. However, the prognostic significance of FPR in resectable gastric cancer...
BACKGROUND
The ratio of fibrinogen to prealbumin (FPR) is associated with the prognosis of many cancers. However, the prognostic significance of FPR in resectable gastric cancer has not been clarified.
METHODS
A total of 760 patients with resectable gastric cancer participated in this study. The receiver operating characteristic curve (ROC) was used to calculate the optimal cutoff value of each immunonutrition marker. Univariate and multivariate Cox regression analyses were used to confirm the prognostic value of FPR in patients with gastric cancer and to select appropriate variables for the construction of nomogram.
RESULTS
Utilizing ROC analysis, we calculated the optimal cutoff value for FPR and stratified 760 patients into high and low FPR groups. Subsequent examination revealed notable distinctions in baseline characteristics between these groups. For instance, Patients with higher FPR tend to be older and have more lymph node metastasis. Statistical analysis through the chi-square test confirmed the significance of these differences (P < 0.05). In addition, the results of the multivariate Cox proportional hazards regression analysis indicate that the factors related to OS were age (P = 0.001), T stage (P < 0.001), N stage (P < 0.001), radical resection (P < 0.001), and FPR (P < 0.024). The nomogram is composed of the above five variables. ROC analysis showed that the area under the curve (AUC) of the nomogram was 0.859 (95% CI: 0.831-0.887), and the sensitivity and specificity were 77.4% and 82.1%, respectively.
CONCLUSION
FPR is a potential marker in patients with resectable gastric cancer. The nomogram based on FPR shows good predictive ability, which is helpful for clinicians to judge the prognosis of patients and choose targeted treatment strategies.
PubMed: 38434582
DOI: 10.2147/JIR.S440832 -
Microbiology Spectrum Apr 2024This study is to explore the proportion of significant liver histopathology in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients...
UNLABELLED
This study is to explore the proportion of significant liver histopathology in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients with normal alanine aminotransferase (ALT) and investigate noninvasive indicators for predicting significant liver histopathology. A total of 201 HBeAg-negative chronic HBV-infected patients with normal ALT who underwent liver biopsy were involved in this study. Significant liver histological changes were defined as necroinflammation grade ≥2 (G ≥ 2) and/or fibrosis stage ≥2 (S ≥ 2). The results showed that 42.3% (85/201) and 45.8% (92/201) of the HBeAg-negative patients with normal ALT have significant liver necroinflammation (G ≥ 2) and fibrosis (S ≥ 2), respectively. High normal ALT (>22 U/L), high level of serum HBV DNA (>3.42 log IU/mL), and low level of prealbumin (PA) (<170 mg/L) were independent predictors for significant liver necroinflammation, and the predictive value of the combined indicators was 0.750 ( < 0.001), while high normal ALT (>24 U/L) and high level of FIB-4 (>1.53) were independent predictors for significant liver fibrosis, and the predictive value of the combined indicators was 0.740 ( < 0.001). In conclusion, more than 40% of HBeAg-negative patients with normal ALT have significant liver histopathology and require immediate antiviral treatment. ALT, PA, HBV DNA, and FIB-4 can independently predict significant liver inflammation and fibrosis for HBeAg-negative patients with normal ALT. Lowering the treatment threshold of ALT may benefit the HBeAg-negative chronic HBV-infected patients.
IMPORTANCE
Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients with normal alanine aminotransferase (ALT) were supposed to have a low risk of progression to cirrhosis or hepatocellular carcinoma, and it was recommended to regularly follow up or undergo liver biopsy to assess liver histopathology according to the major international guidelines. However, this study indicates that a considerable number of HBeAg-negative chronic HBV-infected patients with normal ALT have significant liver histopathology and require immediate antiviral treatment. Besides, several clinical commonly used noninvasive indicators were found that can be used to predict significant liver histopathology; thereby liver biopsy might be avoided for HBeAg-negative chronic HBV-infected patients with normal ALT.
Topics: Humans; Hepatitis B, Chronic; Hepatitis B e Antigens; Alanine Transaminase; DNA, Viral; Liver Cirrhosis; Fibrosis; Biomarkers; Antiviral Agents
PubMed: 38426768
DOI: 10.1128/spectrum.03941-23 -
The Journal of International Medical... Feb 2024In this study, we aimed to establish a new nomogram score to predict the occurrence of surgery-related pressure ulcers (SRPU) in patients undergoing cardiovascular...
OBJECTIVE
In this study, we aimed to establish a new nomogram score to predict the occurrence of surgery-related pressure ulcers (SRPU) in patients undergoing cardiovascular surgery.
METHODS
We conducted a retrospective study among patients who underwent cardiovascular surgery between February 2016 and November 2020.
RESULTS
We established a prediction model based on a logistic regression model and tested the calibration and discrimination. We included 1163 patients who had undergone cardiovascular surgery. We formulated the logistic regression model, with Logit(P) = -11.745 + 0.024 preoperative hemoglobin value + 0.118 serum sodium value - 0.014 prealbumin value - 0.213 intraoperative mean temperature - 0.058 minimum mean arterial pressure + 0.646 preoperative blood potassium value + 0.264 smoking frequency + 0.760 hypertension history + 0.536 age ≥70 years. In this model ,"+" indicates that the factor is positively related to the occurrence risk of SRPU and "-" indicates that the factor is negatively associated with SRPU risk. The predictive model and nomogram had good accuracy in estimating the risk of SRPU, with a C-index of 0.755 (95% confidence interval: 0.719-0.792).
CONCLUSIONS
The present model can be used to effectively screen patients with a high risk of SRPU to devise targeted nursing intervention strategies and ultimately reduce the incidence rate of SRPU.
Topics: Humans; Aged; Nomograms; Pressure Ulcer; Retrospective Studies; Calibration; Potassium; Organometallic Compounds
PubMed: 38422046
DOI: 10.1177/03000605241233149 -
Drugs Apr 2024Eplontersen (Wainua™) is a ligand-conjugated antisense oligonucleotide directed to TTR, which is being developed by Ionis Pharmaceuticals and AstraZeneca for the... (Review)
Review
Eplontersen (Wainua™) is a ligand-conjugated antisense oligonucleotide directed to TTR, which is being developed by Ionis Pharmaceuticals and AstraZeneca for the treatment of TTR-mediated amyloidosis (ATTR). Eplontersen, which is targeted to the liver by a ligand containing three N-acetyl galactosamine residues, binds to wild-type and variant TTR mRNA, thus reducing the levels of circulating TTR protein and amyloid deposition. Subcutaneous eplontersen reduced serum TTR levels, inhibited neuropathy progression and improved health-related quality of life in patients with polyneuropathy of hereditary ATTR (ATTRv-PN; v for variant) in a phase III trial. Based on these results, eplontersen was approved in the USA for the treatment of ATTRv-PN on 21 December 2023 and is currently undergoing regulatory review for a similar indication in the EU, the UK, Switzerland and Canada. Eplontersen is also undergoing phase III development for ATTR cardiomyopathy. This article summarizes the milestones in the development of eplontersen leading to this first approval for ATTRv-PN.
Topics: Humans; Amyloid Neuropathies, Familial; Prealbumin; Drug Approval; Oligonucleotides; Oligonucleotides, Antisense; Quality of Life; Clinical Trials, Phase III as Topic
PubMed: 38413492
DOI: 10.1007/s40265-024-02008-5 -
Tuberculosis (Edinburgh, Scotland) May 2024Tuberculosis (TB) is not only related to infection but also involves immune factors. This study explores the changes in T-lymphocyte subsets in children with TB who are...
BACKGROUND
Tuberculosis (TB) is not only related to infection but also involves immune factors. This study explores the changes in T-lymphocyte subsets in children with TB who are human immunodeficiency virus (HIV)-negative and examines their relationship using chest computed tomography (CT) scans. Additionally, the study identifies risk factors for severe TB (STB) in children and establishes relevant risk prediction models.
METHODS
We recruited 235 participants between 2018 and 2022, comprising 176 paediatric patients with TB who were HIV-negative and 59 age-matched children with bacterial community-acquired pneumonia (CAP). We quantitatively analysed and compared T-lymphocyte subsets between the two groups and among different types of TB infection. Both univariate and multivariate analyses of clinical and laboratory characteristics were conducted to identify independent risk factors for STB in children and to establish a risk prediction model.
RESULTS
The absolute counts of CD3, CD4 and CD8 T-cells in children with TB infection decreased significantly compared with bacterial CAP. The percentage of CD8 T-cells increased, whereas the percentage of CD4 T-cells did not change significantly. The absolute count of CD3, CD4 and CD8 T-cells in extrapulmonary TB (EPTB) was significantly higher than in extra-respiratory TB, with unchanged subset percentages. According to chest CT lesion classification, CD4 T-cell counts decreased significantly in S3 compared with S1 or S2, with no significant change in CD3 and CD8 T-cell counts and percentages. No significant differences were observed in lymphocyte subset counts and percentages between S1 and S2. Univariate analyses indicated that factors such as age, symptom duration, white blood cell count, platelet count, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate, prealbumin level, albumin level, globulin level, albumin/globulin (A/G) ratio, high-sensitivity C-reactive protein (Hs-CRP) level and CD4 and CD8 T-cell counts are associated with STB. Multivariate logistic regression analysis revealed that age, Hs-CRP level, NLR, symptom duration and A/G ratio are independent risk factors for STB in children. Increased age, Hs-CRP levels and NLR, along with decreased A/G, correlate with increased susceptibility to STB. A nomogram model, based on these independent risk factors, demonstrated an area under the receiver operating characteristics curve of 0.867 (95% CI: 0.813-0.921). Internal verification confirmed the model's accuracy, with the calibration curve approaching the ideal and the Hosmer-Lemeshow goodness-of-fit test showing consistent results (χ = 12.212, p = 0.142).
CONCLUSION
In paediatric patients with TB, the absolute counts of all lymphocyte subsets were considerably reduced compared with those in patients with bacterial CAP. Clinicians should consider the possibility of EPTB infection in addition to respiratory infections in children with TB who have higher CD3, CD4 and CD8 T-cell counts than the ERTB group. Furthermore, CD4 T-cell counts correlated closely with the severity of chest CT lesions. Age, symptom duration, A/G ratio, Hs-CRP level and NLR were established as independent risk factors for STB. The nomogram model, based on these factors, offers effective discrimination and calibration in predicting STB in children.
Topics: Humans; Child; C-Reactive Protein; Mycobacterium tuberculosis; T-Lymphocyte Subsets; Tuberculosis; Risk Factors; Lymphocyte Subsets; Lymphocyte Count; Latent Tuberculosis; HIV Infections; Globulins
PubMed: 38401266
DOI: 10.1016/j.tube.2024.102496 -
Supportive Care in Cancer : Official... Feb 2024Numerous studies have investigated the relationships between nutritional status and the prognosis of ovarian cancer (OC). However, the majority of these studies have...
Trends in nutritional status and factors affecting prognostic nutritional index in ovarian cancer patients during chemotherapy: a prospective longitudinal study based on generalized estimating equations.
PURPOSE
Numerous studies have investigated the relationships between nutritional status and the prognosis of ovarian cancer (OC). However, the majority of these studies have focused on pre-chemotherapy malnutrition, with limited attention given to dynamic changes in nutritional status during chemotherapy and the associated risk factors affecting the prognostic nutritional index (PNI) in OC women. This study aims to explore the variation trend in the nutritional status of OC women over time during chemotherapy and assess its predictive factors.
METHODS
A prospective longitudinal study was conducted from January 2021 to August 2023. Body mass index (BMI), PNI, Nutritional Risk Screening (NRS) 2002, serum albumin, and prealbumin measurements were utilized to assess the nutritional status of OC women. Data were collected through face-to-face interviews before initial chemotherapy (T0) and during the first (T1), third (T2), and fifth (T3) cycles of chemotherapy. Generalized Estimating Equations (GEE) were employed for the analysis of potential predictive factors.
RESULTS
A total of 525 OC women undergoing chemotherapy completed the study. Significantly varied levels of BMI, PNI, and serum concentrations of hemoglobin, albumin, prealbumin, potassium, sodium, magnesium, and calcium were observed in these patients (p < 0.05). The prevalence of nutritional risk decreased over time during chemotherapy (p < 0.05). Nutritional parameters, including BMI, PNI, and the serum concentrations of albumin and prealbumin, exhibited an upward trend in nutritional status throughout the chemotherapy cycles (p < 0.05). Multivariate analysis indicated that higher levels of BMI, serum albumin, prealbumin, absolute lymphocyte count, and hemoglobin ≥ 110 g/L at admission were associated with elevated PNI after chemotherapy (β = 0.077, p = 0.028; β = 0.315, p < 0.001; β = 0.009, p < 0.001; β = 1.359, p < 0.001; β = - 0.637, p = 0.005).
CONCLUSION
Patients consistently demonstrated improvements in nutritional risk and status from the initiation to the completion of chemotherapy cycles. Nutritional monitoring of OC women, particularly those exhibiting abnormalities at the commencement of chemotherapy, is crucial. Targeted nutritional support programs should be developed to enhance the prognosis of OC women.
Topics: Humans; Female; Nutritional Status; Nutrition Assessment; Prealbumin; Prognosis; Prospective Studies; Longitudinal Studies; Serum Albumin; Hemoglobins; Ovarian Neoplasms; Retrospective Studies
PubMed: 38400912
DOI: 10.1007/s00520-024-08384-8 -
Medicina (Kaunas, Lithuania) Jan 2024Hereditary transthyretin amyloidosis (ATTRv) is a rare disease caused by pathogenic variants in the transthyretin () gene. More than 140 different disease-causing...
Hereditary transthyretin amyloidosis (ATTRv) is a rare disease caused by pathogenic variants in the transthyretin () gene. More than 140 different disease-causing variants in have been reported. Only a few individuals with a rare 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 variant at our center. 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 variant. During 2018-2021, the NM_000371.3:c.302C>T, NP_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 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 variant was identified in two phenotypically negative relatives at the ages of 33 and 47 years. c.302C>T is a rare 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.
Topics: Adult; Aged; Humans; Middle Aged; Amyloid Neuropathies, Familial; Cardiomyopathies; Electrocardiography; Prealbumin
PubMed: 38399526
DOI: 10.3390/medicina60020237 -
Molecules (Basel, Switzerland) Feb 2024Amyloidosis is a group of protein misfolding diseases, which include spongiform encephalopathies, Alzheimer's disease and transthyretin (TTR) amyloidosis; all of them...
Amyloidosis is a group of protein misfolding diseases, which include spongiform encephalopathies, Alzheimer's disease and transthyretin (TTR) amyloidosis; all of them are characterized by extracellular deposits of an insoluble fibrillar protein. TTR amyloidosis is a highly debilitating and life-threatening disease. Patients carry less stable TTR homotetramers that are prone to dissociation into non-native monomers, which in turn rapidly self-assemble into oligomers and, ultimately, amyloid fibrils. Liver transplantation to induce the production of wild-type TTR was the only therapeutic strategy until recently. A promising approach to ameliorate transthyretin (TTR) amyloidosis is based on the so-called TTR kinetic stabilizers. More than 1000 TTR stabilizers have already been tested by many research groups, but the diversity of experimental techniques and conditions used hampers an objective prioritization of the compounds. One of the most reliable and unambiguous techniques applied to determine the structures of the TTR/drug complexes is X-ray diffraction. Most of the potential inhibitors bind in the TTR channel and the crystal structures reveal the atomic details of the interaction between the protein and the compound. Here we suggest that the stabilization effect is associated with a compaction of the quaternary structure of the protein and propose a scoring function to rank drugs based on X-ray crystallography data.
Topics: Humans; Prealbumin; Crystallography, X-Ray; Amyloid Neuropathies, Familial; Amyloid
PubMed: 38398647
DOI: 10.3390/molecules29040895 -
Frontiers in Oncology 2024This study aimed to assess factors affecting the prognosis of early-stage hepatocellular carcinoma (HCC) patients undergoing ablation therapy and create a nomogram for...
INTRODUCTION
This study aimed to assess factors affecting the prognosis of early-stage hepatocellular carcinoma (HCC) patients undergoing ablation therapy and create a nomogram for predicting their 3-, 5-, and 8-year overall survival (OS).
METHODS
The research included 881 early-stage HCC patients treated at Beijing You'an Hospital, affiliated with Capital Medical University, from 2014 to 2022. A nomogram was developed using independent prognostic factors identified by Lasso and multivariate Cox regression analyses. Its predictive performance was evaluated with concordance index (C-index), receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).
RESULTS
The study identified age, tumor number, tumor size, gamma-glutamyl transpeptidase (GGT), international normalized ratio (INR), and prealbumin (Palb) as independent prognostic risk factors. The nomogram achieved C-indices of 0.683 (primary cohort) and 0.652 (validation cohort), with Area Under the Curve (AUC) values of 0.776, 0.779, and 0.822 (3-year, 5-year, and 8-year OS, primary cohort) and 0.658, 0.724, and 0.792 (validation cohort), indicating that the nomogram possessed strong discriminative ability. Calibration and DCA curves further confirmed the nomogram's predictive accuracy and clinical utility. The nomogram can effectively stratify patients into low-, intermediate-, and high-risk groups, particularly identifying high-risk patients.
CONCLUSIONS
The established nomogram in our study can provide precise prognostic information for HCC patients following ablation treatment and enable physicians to accurately identify high-risk individuals and facilitate timely intervention.
PubMed: 38384805
DOI: 10.3389/fonc.2024.1340286 -
Protein Science : a Publication of the... Mar 2024The mechanism that converts native human transthyretin into amyloid fibrils in vivo is still a debated and controversial issue. Commonly, non-physiological conditions of...
The mechanism that converts native human transthyretin into amyloid fibrils in vivo is still a debated and controversial issue. Commonly, non-physiological conditions of pH, temperature, or organic solvents are used in in vitro models of fibrillogenesis of globular proteins. Transthyretin amyloid formation can be achieved under physiological conditions through a mechano-enzymatic mechanism involving specific serine proteases such as trypsin or plasmin. Here, we investigate S52P and L111M transthyretin variants, both causing a severe form of systemic amyloidosis mostly targeting the heart at a relatively young age with heterogeneous phenotype among patients. Our studies on thermodynamics show that both proteins are significantly less stable than other amyloidogenic variants. However, despite a similar thermodynamic stability, L111M variant seems to have enhanced susceptibility to cleavage and a lower tendency to form fibrils than S52P in the presence of specific proteases and biomechanical forces. Heparin strongly enhances the fibrillogenic capacity of L111M transthyretin, but has no effect on the S52P variant. Fibrillar seeds similarly affect the fibrillogenesis of both proteins, with a stronger effect on the L111M variant. According to our model of mechano-enzymatic fibrillogenesis, both full-length and truncated monomers, released after the first cleavage, can enter into fibrillogenesis or degradation pathways. Our findings show that the kinetics of the two processes can be affected by several factors, such as intrinsic amyloidogenicity due to the specific mutations, environmental factors including heparin and fibrillar seeds that significantly accelerate the fibrillogenic pathway.
Topics: Humans; Glycosaminoglycans; Prealbumin; Amyloidosis; Amyloid; Heparin
PubMed: 38380705
DOI: 10.1002/pro.4931