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Open Heart Mar 2024Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative cardiac disorder caused by deposition of wild type or mutated transthyretin. As ATTR-CM is associated...
OBJECTIVE
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative cardiac disorder caused by deposition of wild type or mutated transthyretin. As ATTR-CM is associated with conduction disease, we sought to determine its prevalence in patients with idiopathic high-degree atrioventricular (AV) block requiring permanent pacemaker (PPM) implantation.
METHODS
Consecutive patients aged 70-85 years undergoing PPM implantation for idiopathic high-degree AV block between November 2019 and November 2021 were offered a 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scan. Demographics, comorbidities, electrocardiographic and imaging data from the time of device implantation were retrospectively collected.
RESULTS
39 patients (79.5% male, mean (SD) age at device implantation 76.2 (2.9) years) had a DPD scan. 3/39 (7.7%, all male) had a result consistent with ATTR-CM (Perugini grade 2 or 3). Mean (SD) maximum wall thickness of those with a positive DPD scan was 19.0 mm (3.6 mm) vs 11.4 mm (2.7 mm) in those with a negative scan (p=0.06). All patients diagnosed with ATTR-CM had spinal canal stenosis and two had carpal tunnel syndrome.
CONCLUSIONS
ATTR-CM should be considered in older patients requiring permanent pacing for high-degree AV block, particularly in the presence of left ventricular hypertrophy, carpal tunnel syndrome or spinal canal stenosis.
Topics: Humans; Male; Aged; Female; Atrioventricular Block; Retrospective Studies; Prevalence; Prealbumin; Carpal Tunnel Syndrome; Constriction, Pathologic; Amyloidosis
PubMed: 38538064
DOI: 10.1136/openhrt-2024-002606 -
Revista de La Facultad de Ciencias... Mar 2024The most common form of hereditary amyloidosis is associated with variants of transthyretin (TTR). Familial amyloidosis polyneuropathy associated with variants of TTR...
INTRODUCTION
The most common form of hereditary amyloidosis is associated with variants of transthyretin (TTR). Familial amyloidosis polyneuropathy associated with variants of TTR (FAP-TTR) is an infrequent, multisystemic disease, with predominant involvement of the peripheral nervous system. More than 130 pathogenic variants have been identified so far and most of them are amyloidogenic, being Val30Met the most frequently described.
CASE REPORT
A 74 year-old male was evaluated for progressive decreased sensitivity and associated loss of strength in four limbs in the previous two years, needing assistance for walking. Areflexia, bilateral tibialis anterior and gastrocnemius atrophy, bilateral anesthesia and apalesthesia were found in lower limbs. Bilateral hypoesthesia was reported in upper limbs. No painful dysesthesia, hyperalgesia or allodynia were found. DNA sequencing of the TTR gene led to the detection of the variant c.186G>C in heterozygous state. The resulting variant (Glu62Asp), located in the critical functional domain, has not been published before.
CONCLUSION
The importance of considering late onset, sporadic FAP-TTR as a differential diagnosis of cryptogenic polyneuropathy is highlighted.
Topics: Aged; Humans; Male; Amyloid Neuropathies, Familial; Prealbumin
PubMed: 38537102
DOI: 10.31053/1853.0605.v81.n1.40992 -
Human Genomics Mar 2024Coding mutations in the Transthyretin (TTR) gene cause a hereditary form of amyloidosis characterized by a complex genotype-phenotype correlation with limited... (Meta-Analysis)
Meta-Analysis
PURPOSE
Coding mutations in the Transthyretin (TTR) gene cause a hereditary form of amyloidosis characterized by a complex genotype-phenotype correlation with limited information regarding differences among worldwide populations.
METHODS
We compared 676 diverse individuals carrying TTR amyloidogenic mutations (rs138065384, Phe44Leu; rs730881165, Ala81Thr; rs121918074, His90Asn; rs76992529, Val122Ile) to 12,430 non-carriers matched by age, sex, and genetically-inferred ancestry to assess their clinical presentations across 1,693 outcomes derived from electronic health records in UK biobank.
RESULTS
In individuals of African descent (AFR), Val122Ile mutation was linked to multiple outcomes related to the circulatory system (fold-enrichment = 2.96, p = 0.002) with the strongest associations being cardiac congenital anomalies (phecode 747.1, p = 0.003), endocarditis (phecode 420.3, p = 0.006), and cardiomyopathy (phecode 425, p = 0.007). In individuals of Central-South Asian descent (CSA), His90Asn mutation was associated with dermatologic outcomes (fold-enrichment = 28, p = 0.001). The same TTR mutation was linked to neoplasms in European-descent individuals (EUR, fold-enrichment = 3.09, p = 0.003). In EUR, Ala81Thr showed multiple associations with respiratory outcomes related (fold-enrichment = 3.61, p = 0.002), but the strongest association was with atrioventricular block (phecode 426.2, p = 2.81 × 10). Additionally, the same mutation in East Asians (EAS) showed associations with endocrine-metabolic traits (fold-enrichment = 4.47, p = 0.003). In the cross-ancestry meta-analysis, Val122Ile mutation was associated with peripheral nerve disorders (phecode 351, p = 0.004) in addition to cardiac congenital anomalies (fold-enrichment = 6.94, p = 0.003).
CONCLUSIONS
Overall, these findings highlight that TTR amyloidogenic mutations present ancestry-specific and ancestry-convergent associations related to a range of health domains. This supports the need to increase awareness regarding the range of outcomes associated with TTR mutations across worldwide populations to reduce misdiagnosis and delayed diagnosis of TTR-related amyloidosis.
Topics: Humans; Prealbumin; Mutation; Amyloidosis; Phenotype; Genetics, Population
PubMed: 38523305
DOI: 10.1186/s40246-024-00596-7 -
Translational Vision Science &... Mar 2024To investigate the choroidal vascularity index (CVI) and choroidal structural changes in children with nephrotic syndrome.
PURPOSE
To investigate the choroidal vascularity index (CVI) and choroidal structural changes in children with nephrotic syndrome.
METHODS
This was a cross-sectional study involving 45 children with primary nephrotic syndrome and 40 normal controls. All participants underwent enhanced depth imaging-optical coherence tomography examinations. An automatic segmentation method based on deep learning was used to segment the choroidal vessels and stroma, and the choroidal volume (CV), vascular volume (VV), and CVI within a 4.5 mm diameter circular area centered around the macular fovea were obtained. Clinical data, including blood lipids, serum proteins, renal function, and renal injury indicators, were collected from the patients.
RESULTS
Compared with normal controls, children with nephrotic syndrome had a significant increase in CV (nephrotic syndrome: 4.132 ± 0.464 vs. normal controls: 3.873 ± 0.574; P = 0.024); no significant change in VV (nephrotic syndrome: 1.276 ± 0.173 vs. normal controls: 1.277 ± 0.165; P = 0.971); and a significant decrease in the CVI (nephrotic syndrome: 0.308 [range, 0.270-0.386] vs. normal controls: 0.330 [range, 0.288-0.387]; P < 0.001). In the correlation analysis, the CVI was positively correlated with serum total protein, serum albumin, serum prealbumin, ratio of serum albumin to globulin, and 24-hour urine volume and was negatively correlated with total cholesterol, low-density lipoprotein cholesterol, urinary protein concentration, and ratio of urinary transferrin to creatinine (all P < 0.05).
CONCLUSIONS
The CVI is significantly reduced in children with nephrotic syndrome, and the decrease in the CVI parallels the severity of kidney disease, indicating choroidal involvement in the process of nephrotic syndrome.
TRANSLATIONAL RELEVANCE
Our findings contribute to a deeper understanding of how nephrotic syndrome affects the choroid.
Topics: Child; Humans; Nephrotic Syndrome; Cross-Sectional Studies; Choroid; Fovea Centralis; Cholesterol
PubMed: 38512284
DOI: 10.1167/tvst.13.3.18 -
Scientific Reports Mar 2024Pediatric perforated appendicitis, prone to multiple complications, necessitates identifying potential serum biomarkers for early diagnosis and intervention. A...
Pediatric perforated appendicitis, prone to multiple complications, necessitates identifying potential serum biomarkers for early diagnosis and intervention. A cross-sectional study was conducted on patients under 16 with acute appendicitis, admitted to Hainan Women and Children's Medical Center from January 2019 to July 2023. The patients were categorized into perforated and non-perforated groups. Among the 313 included patients, 106 (33.87%, 95% CI 28.59-39.14%) developed perforation. The C-reactive protein to prealbumin ratio (CPA) showed a significant difference between the perforated and non-perforated groups [6.63 (2.9-13.02) vs. 0.7 (0.11-2.18), p < 0.001]. The AUC of CPA on the ROC curve was 0.691 (95% CI 0.513-0.869, p = 0.084) in patients under 4. In patients aged 4-9, the sensitivity of CPA > 3 predicting perforation was 76.2%, with a specificity of 81.6%, and an AUC of 0.816 (95% CI 0.747-0.886, p < 0.001). For patients aged 9-16, the sensitivity of CPA > 2.2 predicting perforation was 85%, with a specificity of 85.7%, and an AUC of 0.919 (95% CI 0.859-0.979, p < 0.001). CPA > 3 and CPA > 2.2 can predict perforated appendicitis in patients aged 4-9 and 9-16, respectively.
Topics: Humans; Child; Female; Appendicitis; C-Reactive Protein; Prealbumin; Cross-Sectional Studies; Retrospective Studies
PubMed: 38509094
DOI: 10.1038/s41598-024-55108-3 -
Nutricion Hospitalaria Mar 2024symptom clusters (SCs) are highly prevalent among patients diagnosed with primary liver cancer. Malnutrition poses a heightened risk for a more pronounced total symptom...
INTRODUCTION
symptom clusters (SCs) are highly prevalent among patients diagnosed with primary liver cancer. Malnutrition poses a heightened risk for a more pronounced total symptom cluster score.
OBJECTIVE
this study aimed to identify SCs and assess the nutritional status of patients undergoing transcatheter arterial chemoembolization (TACE). Furthermore, it aimed to investigate the association between nutritional status and symptom clusters.
METHODS
primary liver cancer patients who were scheduled to receive TACE were recruited. Symptoms data were collected using the MD Anderson Symptom Inventory (MDASI-C) and the Symptom Module specific to Primary Cancer (TSM-PLC). Nutritional assessment relied on the Nutritional Risk Screening-2002 (NRS-2002) and blood biochemistry. The SCs were extracted using exploratory factor analysis, while the relationship between SCs and nutritional status was evaluated using Spearman correlation analysis.
RESULTS
the study included 226 patients, four distinct symptom clusters emerged: emotional-psychological symptom cluster, upper gastrointestinal symptom cluster, post-embolization-related symptom cluster, and liver function impairment symptom cluster. 68.14 % of patients were found to be at high risk of malnutrition. Our study revealed significant differences in Scs scores between patients at risk of malnutrition and those without such risk (p < 0.050). Notably, we observed a positive correlation between NRS-2002 scores and the scores of all symptom clusters (r = 0.205 to 0.419, p < 0.001), while a negative correlation was observed between prealbumin levels and the scores of all symptom clusters (r = -0.183 to -0.454, p < 0.001).
CONCLUSION
the study highlights the high risk of malnutrition among liver cancer patients receiving TACE and the positive correlation between high malnutrition risk and Scs scores.
PubMed: 38501819
DOI: 10.20960/nh.04936 -
The Israel Medical Association Journal... Mar 2024Cardiac amyloidosis (CA) is characterized by the extracellular deposition of misfolded protein in the heart. Precise identification of the amyloid type is often...
BACKGROUND
Cardiac amyloidosis (CA) is characterized by the extracellular deposition of misfolded protein in the heart. Precise identification of the amyloid type is often challenging, but critical, since the treatment and prognosis depend on the disease form and the type of deposited amyloid. Coexistence of clinical conditions such as old age, monoclonal gammopathy, chronic inflammation, or peripheral neuropathy in a patient with cardiomyopathy creates a differential diagnosis between the major types of CA: amyloidosis light chains (AL), amyloidosis transthyretin (ATTR) and amyloidosis A (AA).
OBJECTIVES
To demonstrate the utility of the Western blotting (WB)-based amyloid typing method in patients diagnosed with cardiac amyloidosis where the type of amyloid was not obvious based on the clinical context.
METHODS
Congo red positive endomyocardial biopsy specimens were studied in patients where the type of amyloid was uncertain. Amyloid proteins were extracted and identified by WB. Mass spectrometry (MS) of the electrophoretically resolved protein-in-gel bands was used for confirmation of WB data.
RESULTS
WB analysis allowed differentiation between AL, AA, and ATTR in cardiac biopsies based on specific immunoreactivity of the electrophoretically separated proteins and their characteristic molecular weight. The obtained results were confirmed by MS.
CONCLUSIONS
WB-based amyloid typing method is cheaper and more readily available than the complex and expensive gold standard techniques such as MS analysis or immunoelectron microscopy. Notably, it is more sensitive and specific than the commonly used immunohistochemical techniques and may provide an accessible diagnostic service to patients with amyloidosis in Israel.
Topics: Humans; Amyloidosis; Amyloid; Amyloidogenic Proteins; Cardiomyopathies; Blotting, Western; Amyloid Neuropathies, Familial; Prealbumin
PubMed: 38493325
DOI: No ID Found -
Frontiers in Surgery 2024To explore the effectiveness of a multidisciplinary treatment (MDT) integrated intervention model in the perioperative management of patients with infectious nonunion.
OBJECTIVE
To explore the effectiveness of a multidisciplinary treatment (MDT) integrated intervention model in the perioperative management of patients with infectious nonunion.
METHODS
80 patients with infectious bone defects treated in our hospital from January 2020 to January 2023 were selected. They were classified into MDT-integrated perioperative group (study group) and conventional control group according to the different management patterns, with 40 cases each. The incidence of wound infection, pin tract infection, delayed bone healing, deep vein thrombosis (DVT), joint stiffness, and nutritional indicators were compared between the two groups.
RESULTS
The rates of wound infection ( = 0.042), pin tract infection of Grade II or above ( = 0.006), delayed bone healing ( = 0.006), DVT ( = 0.033), and joint stiffness ( = 0.023) in the MDT integrated perioperative (study) group were significantly lower than those in the conventional care group ( < 0.05). With the extension of intervention time, the changes in body weight, levels of serum albumin (ALB), pre-albumin (PA), hemoglobin (Hb), and serum sodium (Na) in the study group were higher than those in the conventional care group ( < 0.05).
CONCLUSION
The application of the MDT integrated intervention model in the perioperative period of patients with infectious nonunion is beneficial in reducing the risks of wound infection and pin tract infection of Grade II or above, lowering the incidence rates of lower limb DVT and joint stiffness, and reducing the risk of malnutrition, demonstrating high clinical application value.
PubMed: 38481610
DOI: 10.3389/fsurg.2024.1335157 -
Journal of the American College of... Mar 2024Cardiac amyloidosis is increasingly recognized as a treatable form of heart failure. Highly effective specific therapies have recently become available for the 2 most... (Review)
Review
Cardiac amyloidosis is increasingly recognized as a treatable form of heart failure. Highly effective specific therapies have recently become available for the 2 most frequent forms of cardiac amyloidosis: immunoglobulin light chain amyloidosis and transthyretin (ATTR) amyloidosis. Nevertheless, initiation of specific therapies requires recognition of cardiac amyloidosis and appropriate characterization of the amyloid type. Although noninvasive diagnosis is possible for ATTR cardiac amyloidosis, histological demonstration and typing of amyloid deposits is still required for a substantial number of patients with ATTR and in all patients with light chain amyloidosis and other rarer forms of cardiac amyloidosis. Amyloid histological typing can be performed using different techniques: mass spectrometry, immunohistochemistry, and immunoelectron microscopy. This review describes which patients require histological confirmation of cardiac amyloidosis along with when and how to type amyloid deposits in histologic specimens. Furthermore, it covers the characteristics and limitations of the different typing methods that are available in clinical practice.
Topics: Humans; Plaque, Amyloid; Amyloidosis; Amyloid; Heart Failure; Immunohistochemistry; Amyloidogenic Proteins; Prealbumin; Amyloid Neuropathies, Familial; Cardiomyopathies
PubMed: 38479957
DOI: 10.1016/j.jacc.2024.01.010 -
Journal of Hepatocellular Carcinoma 2024The aim of the study is to identify and evaluate multifaceted factors impacting the survival of elderly cirrhotic HCC patients following ablation therapy, with the goal...
PURPOSE
The aim of the study is to identify and evaluate multifaceted factors impacting the survival of elderly cirrhotic HCC patients following ablation therapy, with the goal of constructing a nomogram to predict their 3-, 5-, and 8-year overall survival (OS).
PATIENTS AND METHODS
A retrospective analysis was conducted on 736 elderly cirrhotic HCC patients who underwent ablation therapy between 2014 and 2022. LASSO regression, random survival forest (RSF), and multivariate Cox analyses were employed to identify independent prognostic factors for OS, followed by the development and validation of a predictive nomogram. Harrell's concordance index (C-index), calibration plot and decision curve analysis (DCA) were used to assess the performance of the nomogram. The nomogram was finally utilized to stratify patients into low-, intermediate-, and high-risk groups, aiming to assess its efficacy in precisely discerning individuals with diverse overall survival outcomes.
RESULTS
Alcohol drinking, tumor number, globulin (Glob) and prealbumin (Palb) were identified and integrated to establish a novel prognostic nomogram. The nomogram exhibited strong discriminative ability with C-indices of 0.723 (training cohort) and 0.693 (validation cohort), along with significant Area Under the Curve (AUC) values for 3-year, 5-year, and 8-year OS in both cohorts (0.758, 0.770, and 0.811 for training cohort; 0.744, 0.699 and 0.737 for validation cohort). Calibration plots substantiated its consistency, while DCA curves corroborated its clinical utility. The nomogram further demonstrated exceptional effectiveness in discerning distinct risk populations, highlighting its robust applicability for prognostic stratification.
CONCLUSION
Our study successfully developed and validated a robust nomogram model based on four key clinical parameters for predicting 3-, 5- and 8-year OS among elderly cirrhotic HCC patients following ablation therapy. The nomogram exhibited a remarkable capability in identifying high-risk patients, furnishing clinicians with invaluable insights for postoperative surveillance and tailored therapeutic interventions.
PubMed: 38468611
DOI: 10.2147/JHC.S450825