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Amyloid Light Chain (AL) Amyloidosis is a rare disorder of protein misfolding and metabolism characterized by insoluble fibrils deposition in various tissues and organs, which could quickly progress and become fatal. The most frequently affected organ is heart being its involvement the most adverse prognostic feature. Kidney and liver could be other organ localizations, defining AL Amyloidosis as a multisystem disorder. Being Budd-Chiari syndrome (BCS) an uncommon congestive hepatopathy caused by blockage of hepatic veins in the absence of cardiac disorders, it could be rarely caused by a massive deposition of amyloid proteins into hepatic sinusoidal spaces, giving an uncommon clinical presentation of AL Amyloidosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Amyloidosis diagnosis relies on Congo red staining with immunohistochemistry and immunofluorescence for subtyping but lacks sensitivity and specificity. Laser-microdissection mass spectroscopy offers better accuracy but is complex and requires extensive sample preparation. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy offers a promising alternative for amyloidosis characterization. Cardiac tissue sections from nine patients with amyloidosis and 20 heart transplant recipients were analyzed using ATR-FTIR spectroscopy. Partial least squares discriminant analysis (PLS-DA), principal component analysis (PCA), and hierarchical cluster analysis (HCA) models were used to differentiate healthy post-transplant cardiac tissue from amyloidosis samples and identify amyloidosis subtypes [κ light chain ( n = 1), λ light chain ( n = 3), and transthyretin ( n = 5)]. Leave-one-out cross-validation (LOOCV) was employed to assess the performance of the PLS-DA model. Significant spectral differences were found in the 1700-1500 cm -1 and 1300-1200 cm -1 regions, primarily related to proteins. The PLS-DA model explained 85.8% of the variance, showing clear clustering between groups. PCA in the 1712-1711 cm -1 , 1666-1646 cm -1 , and 1385-1383 cm -1 regions also identified two clear clusters. The PCA and the HCA model in the 1646-1642 cm -1 region distinguished κ light chain, λ light chain, and transthyretin cases. This pilot study suggests ATR-FTIR spectroscopy as a novel, non-destructive, rapid, and inexpensive tool for diagnosing and subtyping amyloidosis. This study was limited by a small dataset and variability in measurements across different instruments and laboratories. The PLS-DA model's performance may suffer from overfitting and class imbalance. Larger, more diverse datasets are needed for validation.

Amyloid diseases including Alzheimer's, Parkinson's and over 30 others are incurable life-threatening disorders caused by abnormal protein deposition as fibrils in various organs. Cardiac amyloidosis is particularly challenging to diagnose and treat. Identification of the fibril-forming protein, which in the heart is usually amyloid transthyretin (ATTR) or amyloid immunoglobulin light chain (AL), is paramount to treatment. A transformative non-invasive diagnostic modality is imaging using technetium-labeled pyrophosphate or diphosphonate bone tracers, 99m Tc-PYP/DPD/HMDP. For unknown reasons, these tracers show preferential uptake by ATTR deposits. The tracer-binding moiety is unknown and potentially involves amyloid fibrils and/or amyloid-associated calcific deposits. We propose that, like in the bone, the tracers chelate to surface-bound Ca 2+ in amyloid. In high-affinity protein sites, Ca 2+ is coordinated by pairs of acidic residues. To identify such residues on amyloids, we harnessed atomic structures of patient-derived cardiac amyloids determined using cryogenic electron microscopy since 2019. These structures help explain why most but not all ATTR deposits uptake 99m Tc-PYP/DPD/HMDP radiotracers, while in AL the opposite is true. Moreover, fibril structures help explain greater microcalcification observed in ATTR vs. AL deposits. These findings may aid the diagnostics and therapeutic targeting of cardiac amyloidosis and are relevant to other amyloids.

Objective: To investigate the clinicopathological features of renal leukocyte chemokine type 2 amyloidosis (ALECT2). Methods: The prevalence, clinical characteristics, renal histopathological features, and renal outcome of 15 patients with ALECT2 by kidney biopsy were collected in the Department of Kidney Pathology, Shanxi Medical University Second Hospital, Taiyuan, China from January 1993 to December 2023. Immunohistochemistry and mass spectrometry for amyloid proteins were carried out. Results: Fifteen patients with ALECT2 were included in the study, representing 12.93% (15/116) of the renal biopsy-proven amyloidosis cases. There were 5 males and 10 females. The median age at diagnosis was 61 years. All patients had various degrees of proteinuria; 7 patients had nephrotic syndrome; 3 patients had renal insufficiency; 7 patients had microscopic hematuria. Renal biopsy showed that strongly orangophilic amyloid proteins distributed mainly in the renal cortical interstitium, vascular walls, the glomerular mesangium and/or glomerular basement membrane. Eight cases were diagnosed with ALECT2 alone and 7 cases combined with other renal diseases, including 4 cases with membranous nephropathy, 2 cases with IgA nephropathy, and 1 case with subacute tubular interstitial nephropathy. ALECT2 patients with concurrent renal disease showed a higher proteinuria level than those without (3.48 g/24 h versus 4.58 g/24 h). All patients were corroborated by immunohistochemistry to exhibit the specific location of LECT2 in the amyloid fibrils. Mass spectrometry analysis revealed LECT2 polypeptide in 9 patients. Except two patients with worsening renal function, the others showed stable renal function during the mean follow-up period of 12.5 months. Conclusions: ALECT2 is the second common type of renal amyloidosis in our center. The majority of ALECT2 patients show concurrent renal diseases, with a high rate of membranous nephropathy. Amyloid deposits distribute mainly in the cortical interstitium of the kidney, the glomerular mesangium and vascular walls. Mass spectrometry is the most sensitive and specific method for detecting LECT2 amyloidosis.

Objective: The objective of the study is to describe the characteristics of our first cohort of amyloidosis in a Latin America cardiovascular reference center in Colombia., Methods: This is a historic cohort study and data were taken from the electronic records of the Fundación Cardioinfantil-Instituto de cardiología; adult patients with a diagnosis of cardiac amyloidosis were included and a descriptive analysis was presented., Results: A total of 31 patients with amyloidosis were included. 17 were Transthyretin Amyloidosis (ATTR) subtype and 14 were AL subtype. An overall mortality of 25% was found. The mean age at diagnosis was 74 years, male sex predominant. More frequent comorbidities were hypertension and atrial fibrillation. The most frequent clinical presentation was congestive heart failure (75%), with mildly reduced ejection fraction (41.94%), followed by reduced ejection fraction (32.26%), and preserved ejection fraction (25.81%). In the ATTR subtype, a reduced ejection fraction was found at 41.18% and a mildly reduced ejection fraction at 35.29%., Conclusion: These results provide information on the most frequent type of amyloidosis and the late timing to diagnose in our historic cohort study, we present some of the baseline characteristics and most frequent approaches to diagnose Cardiac Amyloidosis that represents all challenges in clinical practice. Improvements are needed in the diagnosis and early treatment of these patients.

Systemic diseases can cause heart block owing to the involvement of the myocardium and thereby the conduction system. Younger patients (<60) with heart block should be evaluated for an underlying systemic disease. These disorders are classified into infiltrative, rheumatologic, endocrine, and hereditary neuromuscular degenerative diseases. Cardiac amyloidosis owing to amyloid fibrils and cardiac sarcoidosis owing to noncaseating granulomas can infiltrate the conduction system leading to heart block. Accelerated atherosclerosis, vasculitis, myocarditis, and interstitial inflammation contribute to heart block in rheumatologic disorders. Myotonic, Becker, and Duchenne muscular dystrophies are neuromuscular diseases involving the myocardium skeletal muscles and can cause heart block., Competing Interests: Disclosure Dr W.Z. Tzou is a consultant for or has received speaker honoraria, or research funding from Abbott, American Heart Association, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. Dr S.R.A. Sabzwari has no relevant disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Amyloidosis is characterized by extracellular amyloid protein deposition. When amyloidosis intersects with basal cell carcinoma (BCC), it introduces complex diagnostic challenges. This study explored the overlap between primary localized cutaneous amyloidosis (PLCA) and BCC, examining amyloid deposits in BCC, systemic amyloidosis risk in PLCA, and various treatment methods., Methods: Two case studies were discussed, followed by a literature review, in which PubMed, Web of Science, EMBASE, and the Cochrane Library databases were utilized. The search, covering studies from infinity up to January 2024, focused on "cutaneous amyloidosis," "basal cell carcinoma," and related terms. Articles in English detailing the clinical presentation, diagnostic methods, treatment, and outcomes of cutaneous amyloidosis mimicking BCC were included. Data extraction and synthesis were performed by two independent reviewers., Case Series: This study highlighted two cases exemplifying the complexity of diagnosing BCC and PLCA. The first case (a 64-year-old with a nodule on the cheek) and the second (a 67-year-old with a nodular lesion on the upper lip cheek) were initially suspected as BCC and were later identified as PLCA upon histopathological examination., Discussion: The diagnosis of amyloidosis within BCC nodules remains a diagnostic challenge. Although their coexistence is relatively prevalent, their local recurrence rates remain debatable. Various diagnostic and therapeutic approaches have been suggested, such as topical creams and phototherapy. However, none have garnered conclusive and consistent evidence to establish reliable clinical application., Conclusion: The findings emphasized the importance of considering alternative pathologies in differential diagnoses. Future research should focus on understanding systemic amyloidosis risks and optimizing care for both conditions., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction and Objectives: The tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/SPAP) ratio is a noninvasive surrogate of right ventricular to pulmonary circulation that has prognostic implications in patients with heart failure (HF) or pulmonary hypertension. Our purpose was to evaluate the prognostic value of the TAPSE/SPAP ratio in patients with cardiac amyloidosis., Methods: We used the database of the AMIGAL study, a prospective, observational registry of patients with cardiac amyloidosis recruited in 7 hospitals of the Autonomous Community of Galicia, Spain, from January 1, 2018 to October 31, 2022. We selected patients whose baseline TAPSE/SPAP ratio was calculated with transthoracic echocardiography. Long-term survival and survival free of HF hospitalization were assessed by means of 5 different multivariable Cox regression models. Median follow-up was 680 days., Results: We studied 233 patients with cardiac amyloidosis, among whom 209 (89.7%) had transthyretin type. The baseline TAPSE/SPAP ratio correlated significantly with clinical outcomes. Depending on the multivariable model considered, the adjusted hazard ratios estimated per 0.1mm/mmHg increase of baseline TAPSE/SPAP ratio ranged from 0.76 to 0.84 for all-cause mortality. Similarly, the ratios for all-cause mortality of HF hospitalization ranged from 0.79 to 0.84. The addition of the baseline TAPSE/SPAP ratio to the predictive model of the United Kingdom National Amyloidosis Centre resulted in an increase in Harrell's c-statistic from 0.662 to 0.705 for all-cause mortality and from 0.668 to 0.707 for all-cause mortality or HF hospitalization., Conclusions: Reduced TAPSE/SPAP ratio is an independent adverse prognostic marker in patients with cardiac amyloidosis., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Competing Interests: Conflict of interest None.

We present the case of a 79-year-old man with rapidly progressive myopathy as the initial manifestation of light chain amyloidosis associated with multiple myeloma. The patient experienced progressive lower limb weakness resulting in difficulty climbing stairs. Ancillary tests revealed slightly elevated serum creatine kinase levels. The electromyogram revealed a diffuse myogenic pattern while muscle MRI indicated fatty replacement of the quadriceps muscles. Muscle biopsy revealed the presence of amyloid deposits in the vessel walls. An elevated level of lambda (246 mg/L) light chain was detected. The bone marrow aspiration results were consistent with the diagnosis of multiple myeloma. In conclusion, even if amyloid myopathy is a rare condition, routine screening for amyloid deposits in muscle biopsy is crucial and should be performed systematically. In the present case, it enabled a rapid diagnosis and the beginning of treatment., Competing Interests: Declaration of competing interest None of the authors reports a conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Modern medicine has increased the human lifespan. However, with an increase in average lifespan risk of amyloidosis increases. Amyloidosis is a condition characterized by protein misfolding and aggregation. Early detection of amyloidosis is crucial, yet conventional diagnostic methods are costly and lack precision, necessitating innovative tools. This review explores recent advancements in diverse amyloid detection methodologies, highlighting the need for interdisciplinary research to develop a miniaturized electrochemical biosensor leveraging nanotechnology. However, the diagnostics industry faces obstacles such as skilled labor shortages, standardized selection processes, and concurrent multi-analyte identification challenges. Research efforts are focused on integrating electrochemical techniques into clinical applications and diagnostics, with the successful transition of miniaturized technologies from development to testing posing a significant hurdle. Label-free transduction techniques like voltammetry and electrochemical impedance spectroscopy (EIS) have gained traction due to their rapid, cost-effective, and user-friendly nature., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To examine the clinical characteristics, diagnosis and treatment, and prognosis of ocular amyloidosis in a Chinese population., Methods: A retrospective case series study was conducted. The clinical data of 37 patients with ocular amyloidosis were collected and the clinical characteristics, diagnosis and treatment, and prognosis were summarized and analyzed., Results: The 37 patients included 12 males and 25 females ranging in age from 22 to 75 years, with median age of 49 years. The clinical signs and symptoms included a conjunctival mass in 37 patients (100%), periorbital discomfort or pain in 29 patients (61.9%), ptosis in 18 patients (23.8%), exophthalmos or eyeball displacement in 3 patients (14.3%), restricted eye movement in 2 patients (9.52%), vision loss in 1 patient (4.76%), and diplopia in 1 patient (4.76%). A total of 29 patients had only conjunctival involvement and 8 patients had concomitant orbital and conjunctival involvement. The main treatment for patients with conjunctival involvement was surgical resection. Thirty-one patients had stable disease, 4 patients progressed or relapsed, and 2 patients were lost to follow-up., Conclusion: Ocular amyloidosis most commonly presents as an eyelid or conjunctival mass or diffuse thickening and can also present as an orbital mass. Diagnosis is mainly dependent on histopathological examination. Surgery is the main treatment and is done to confirm the diagnosis to guide further treatment, preserve function, and prevent complications that threaten visual acuity. Close postoperative follow-up is necessary., (© 2024. The Author(s).)

In patients with cardiac amyloidosis, pericardial involvement is common, with up to half of patients presenting with pericardial effusions. The pathophysiological mechanisms of pericardial pathology in cardiac amyloidosis include chronic elevations in right-sided filling pressures, myocardial and pericardial inflammation due to cytotoxic effects of amyloid deposits, and renal involvement with subsequent uremia and hypoalbuminemia. The pericardial effusions are typically small; however, several cases of life-threatening cardiac tamponade with hemorrhagic effusions have been described as a presenting clinical scenario. Constrictive pericarditis can also occur due to amyloidosis and its identification presents a clinical challenge in patients with cardiac amyloidosis who concurrently manifest signs of restrictive cardiomyopathy. Multimodality imaging, including echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, is useful in the evaluation and management of this patient population. The recognition of pericardial effusion is important in the risk stratification of patients with cardiac amyloidosis as its presence confers a poor prognosis. However, specific treatment aimed at the effusions themselves is seldom indicated. Cardiac tamponade and constrictive pericarditis may necessitate pericardiocentesis and pericardiectomy, respectively., Competing Interests: Declaration of competing interest Dr. Klein reports serving on the advisory boards for Sobi and Pfizer. The other authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Amyloid deposition in tenosynovial structures precedes cardiac involvement up to 20 years. Therefore, a cardiological screening in patients with a history of tenosynovial manifestations of cardiac amyloidosis (CA) could lead to an increased number of early diagnoses., Methods: Patients with tenosynovial manifestations of CA (carpal tunnel syndrome, atraumatic biceps tendon rupture, lumbar spinal stenosis) have been identified by general practitioners and evaluated in a Referral Center for CA. Patients with a high suspicion of CA underwent the CA diagnostic pathway., Results: Among 50 General Practitioners (GP) contacted, 10 (20%) agreed to participate in the study for a total of 5615 patients ≥60 years. One hundred forty-five patients met the inclusion criteria, 2 of them already had a diagnosis of CA, and 57 agreed to undergo a cardiological evaluation (electrocardiography, echocardiography, NTproBNP assay). The median age was 73 [67-80] years and 31 (54%) were women. Eight patients were suggested to start the CA diagnostic pathway, five of them underwent a complete diagnostic evaluation for CA, three refused to complete the diagnostic exams and no new diagnoses were made., Conclusion: A screening program for CA in patients with tenosynovial manifestations identified by general practitioners is feasible, but may not yield a high rate of new diagnosis. In this study, we identified two patients who already had a diagnosis of CA, and among patients at high risk for CA, 37% refused to complete the diagnostic pathway. Increased awareness of CA among patients might increase participation and diagnostic yield in screening studies. Further validation of this protocol is needed to evaluate its diagnostic performance., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Rationale: Multiple myeloma (MM) with secondary amyloidosis (AL) is a rare clonal plasma cell proliferation disease, which causes dysfunction of multiple organs and tissues. We report a case of dysphagia as the first symptom in a patient with MM and secondary AL., Patient Concerns: The patient was a 73-year-old female, was admitted to our hospital, because of progressive dysphagia for 4 months and limb weakness for 1 month., Diagnoses: The bone marrow smear and pathology diagnosis revealed the presence of MM, while the biceps myopathy diagnosis indicated AL., Interventions: The VCD regimen consisted of bortezomib at a dosage of 1.9 mg on days 1, 8, 15, and 22, cyclophosphamide 0.4 g on days 1, 8, and 15, and dexamethasone at a dosage of 40 mg on days 1, 8, 15, and 22. The patient simultaneously received comprehensive treatment including anti-infective therapy, enhanced cardiac function, and nutritional support., Outcomes: The M protein in the blood and urine protein were negative, indicating a reduction in bone marrow plasma cells to 2%. Flow cytometric analysis revealed a minimal percentage 0.04%. As a result, complete remission was achieved., Lessons: The clinical manifestations of MM exhibit a wide range, with the symptoms of secondary injury causing significant disturbing, while the atypical symptoms of extramedullary manifestations pose challenges in diagnosing the disease., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

In the history of amyloidosis studying the concept of liquids dyscrasia has been predominated and finally it is resulted in accepting a serum protein-precursor as a leading amyloidogenic factor in the disease pathogenesis. Consequently basic diagnostic and treatment strategy was aimed to find and eliminate this protein from the blood and this approach evidenced high effectiveness in most frequent AA and AL-amyloidosis characterized with anomaly high levels of precursors in the blood. At the same time there are less frequent and slower progressing inheritant forms of systemic amyloidosis including transthyretin induced, which are less depending on amyloidogenecity of amyloid precursor and because of that, in example, the effectiveness of transthyretin stabilizers or blockers of its synthesis is limited comparing with the precursor elimination in AA or AL. Developed in the middle of XX century a theory of local synthesis by macrophages is more preferable to describe the pathogenesis of these forms. And modern proteome analysis using give rise to confirm the key meaning of macrophage in the amyloidogenesis and proves necessity to know deeply mechanisms of macrophagial autophagia - basic tool of maintaining intracellular protein homeostasis. That is why it is difficult to hope on high effectiveness of chemical amyloid solvents in vivo, which being under macrophages regulation never could realize its chemical activities.

Background: Nasopharyngeal amyloidoma is a rare, locally aggressive tumor that has been reported in the English literature in only 38 cases to date, most of which were in the form of case reports. The present study was aimed to summarize the characteristics of this rare tumor, with the goal of providing new insights for diagnosis and treatment., Materials and Methods: We report three cases of nasopharyngeal amyloidoma diagnosed in our hospital following comprehensive medical examination and review the current literature on all cases of nasopharyngeal amyloidoma from PubMed. The journey of nasopharyngeal amyloidoma, including presentation, diagnostics, surgeries, and follow-up was outlined., Results: None of the three patients had systemic amyloidosis. CT and nasal endoscopy showed irregular masses obstructing the nasopharyngeal cavity. Congo red staining confirmed the deposition of amyloid, and immunohistochemical analysis showed that the amyloid deposition was the AL light chain type. Through literature review, we found that nasopharyngeal amyloidoma most commonly occurred in individuals over the age of 40, patients usually had a good prognosis after complete tumor resection; however, there were still cases of recurrence, and unresected patients were at risk of progression to systemic amyloidosis. The efficacy of radiotherapy and chemotherapy was currently uncertain., Conclusion: Early clinical and pathological diagnosis is crucial, and surgical intervention is the primary treatment option for this disease. Although patients usually have a favorable prognosis, long-term monitoring is necessary to detect potential relapses and initiate timely intervention., (© 2024. The Author(s).)

Background: Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the prevalence and prognostic impact of AS among patients with CA., Methods and Results: We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light-chain (AL) CA. CA patients' echocardiograms were re-analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population-based controls, all types of CA had higher age- and sex-standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) [1.09-3.64]; ATTRv: SRR, 3.41; 95%CI [1.64-4.60]; ATTRwt: SRR, 10.8; 95%CI [5.25-14.53]). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI [0.56-1.14]; ATTRv: SRR, 1.27; 95%CI [0.85-1.44]; ATTRwt: SRR, 4.01; 95%CI [2.71-4.54]). Among patients with ATTRwt, moderate or greater AS was not associated with increased all-cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI [0.42-1.19]; P =0.19)., Conclusions: Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.

Introduction: Primary (AL) systemic amyloidosis is an uncommon disorder in which immunoglobulin light chains are deposited in the tissues as amyloid, resulting in organ dysfunction. The initial symptoms are frequent fatigue and weight loss, and common manifestations include nephrotic syndrome, cardiomyopathy, peripheral neuropathy or hepatomegaly. Histological examination reveals some degree of amyloid deposition in virtually every organ system except the central nervous system (CNS). In contrast to the absence of CNS involvement, peripheral neuropathy is present in 17-36% of AL cases. The typical presentation of AL neuropathy is numbness in the feet, burning and aching pains with lancinating electrical sensations and loss of pain and thermal sensation in the distal limbs. Carpal tunnel syndrome may also co-exist in up to 21% of AL amyloidosis patients. A predominant effect of the disease on small-diameter sensory fibers is consistent with painful and autonomic symptoms. We present a unique case of clinical motor axonal neuropathy predating systemic amyloidosis. The patient provided his informed consent to the study.

Introduction: Amyloid light chain (AL) amyloidosis is a multisystem disease with significant variability in patient presentation. This case describes the presentation and workup of a patient with unique multiorgan involvement on initial presentation., Case Presentation: A 69-year-old African American male presented with weakness, leg swelling, and shortness of breath. Initial workup demonstrated acute heart failure and acute-on-chronic renal failure with nephrotic range proteinuria (5.78 protein to creatinine ratio). Further workup showed elevated serum protein electrophoresis, urine protein electrophoresis, and light chains. Subsequent renal biopsy showed lambda-restricted AL-type renal amyloidosis., Discussion: A variety of systemic presentations have been described in the literature; however, concurrent heart and renal failure as primary presentation is uncommon., Conclusions: This case emphasizes the importance of considering systemic inflammatory diseases, such as amyloidosis, in the differential diagnoses of patients with unexplained multiorgan disease. Early diagnosis and treatment initiation are essential for improving patient outcomes. Improved recognition of common clinical manifestations and laboratory abnormalities will likely improve outcomes through earlier diagnosis., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)

Objective: We aimed to review the literature on the clinical presentation, renal pathology, treatment, and outcome of renal manifestations in adult-onset Still's disease (AOSD)., Methods: We used PRISMA guidelines for our systematic review and included all English-language original articles from inception till September 15, 2023, on AOSD and kidney involvement in any form. Data on patient demographics, diagnostic criteria, clinical presentation, renal pathology, treatment employed including dialysis, outcome, cause of death were collected and analyzed., Results: The median age at the diagnosis of renal issues was 37, with a higher prevalence among females (58.1%). Among the cases, 28 experienced renal problems after being diagnosed with AOSD, 12 had simultaneous diagnoses of renal issues and AOSD, and in 4 cases, renal problems appeared before AOSD diagnosis. Out of the 44 cases, 36 underwent renal biopsy, revealing various pathology findings including AA amyloidosis (25%), collapsing glomerulopathy (11.4%), thrombotic microangiopathy (TMA) (11.4%), IgA nephropathy (9.1%), minimal change disease (6.8%), and others. Some cases were clinically diagnosed with TMA, proximal tubular dysfunction, or macrophage activation syndrome-related acute kidney injury. Treatment approaches varied, but glucocorticoids were commonly used. Renal involvement was associated with increased mortality and morbidity, with 6 out of 44 patients passing away, 4 progressing to end-stage renal disease (ESRD), and data on 2 cases' outcomes not available., Conclusion: Renal manifestations in AOSD are diverse but rarely studied owing to the rarity of the disease. Studies with larger data would be essential to study further on the pathogenesis and implications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Amyloidosis is a complex group of rare disorders characterized by the deposition of misfolded proteins in the extracellular space of various tissues and organs, leading to progressive organ dysfunction. The kidneys constitute a very common site affected, most notably by immunoglobulin-mediated (light chain, heavy chain, and light and heavy chain amyloidosis), but other types that include serum amyloid A (AA) amyloidosis and leukocyte chemotactic factor 2 amyloidosis, along with mutant proteins in several hereditary forms of amyloidosis such as transthyretin, fibrinogen α-chain, gelsolin, lysozyme, and apolipoproteins AI/AII/AIV/CII/CIII amyloidosis have been incriminated as well. The clinical presentation is variable and can range from minimal proteinuria for leukocyte chemotactic factor 2 amyloidosis to a full-blown nephrotic syndrome for AA amyloidosis. Clinical correlation, genetic analysis, and adequate tissue typing through a kidney biopsy are essential to make the correct diagnosis, especially when a family history of amyloidosis is absent. Except for AA and transthyretin amyloidosis, the treatment is usually purely supportive. Kidney transplantation is an acceptable form of treatment for end-stage kidney disease in all types of non-Ig-mediated renal amyloidosis., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Amyloidosis is a rare, heterogeneous group of diseases characterized by extracellular infiltration and deposition of misfolded fibrils in different organs and tissues. A timely diagnosis is important as it can improve outcome. Echocardiography has emerged as a powerful tool to prompt suspicion and refer patients to second-level evaluation to reach a definitive diagnosis. In this scenario, new echo techniques offer new insight into the cardiac amyloidosis (CA) pathophysiology and clinical course. The present review aims to describe the developments in echocardiographic assessment of patients with suspected CA and it summarizes new available echocardiographic scores able to guide a definite diagnosis., Competing Interests: Disclosure G. Limongelli received unrestricted research grant from Pfitzer. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Many patients with amyloidosis undergo carpal tunnel release (CTR) before amyloidosis diagnosis and before developing cardiac or other serious disease manifestations. The purposes of this study were to examine if our patient population had a similar prevalence of positive amyloidosis diagnoses to that in prior studies and to describe the results of implementing a screening program for amyloidosis., Methods: We retrospectively reviewed the biopsy results and subsequent interventions for all patients who underwent screening tenosynovial biopsy during CTR from March 2020 through December 2021. Amyloid screening was offered to patients who met the criteria for increased risk of disease using an appropriateness screening algorithm., Results: Seventy-five (48%) of 156 patients who underwent CTR met the eligibility criteria for amyloidosis testing. Of the 62 patients who agreed to undergo tenosynovial biopsy, 14 had amyloid-positive biopsy specimens (10 men and 4 women). All patients with positive tenosynovial biopsies had bilateral carpal tunnel syndrome and wild-type transthyretin amyloid subtype. One patient was diagnosed and started treatment for otherwise asymptomatic cardiac amyloidosis., Conclusions: The incidence of amyloid-positive tenosynovial biopsy results from CTR was 22.5% in patients using the criteria from an appropriateness screening algorithm, which was higher than previously reported. Implementation of a screening program for patients undergoing CTR requires a multidisciplinary approach and may result in early diagnosis and lifesaving interventions for patients with amyloidosis., Type of Study/level of Evidence: Differential diagnosis/symptom prevalence study, II., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Amyloidosis is a systemic condition characterized by multiple organs involvement. A multidisciplinary and multimodal approach in assessing patients is pivotal and recommended by the international scientific societies. Biomarkers represent an essential noninvasive tool to increase the suspicion of disease and orient further workup and clinical management of patients. This review provides an updated contemporary focus on the clinical use of biomarkers in cardiac amyloidosis, emphasizing their role in both the diagnostic and prognostic setting and discussing future perspective of emerging biomarkers., Competing Interests: Disclosure The authors have nothing to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aortic valve stenosis and cardiac amyloidosis, particularly transthyretin-related, often coexist and share a common clinical and demographic profile. Several pathophysiological hypotheses have been proposed regarding the causes of this association, neither of which fully substantiated in practice. The key to detect the coexistence of cardiac amyloidosis and aortic valve stenosis lies in clinical suspicion. It is possible to hypothesize concurrent cardiac amyloidosis in patients with aortic valve stenosis with the aid of clinical, electrocardiographic, echocardiographic, and extracardiac "red flags". Subsequent non-invasive diagnostic steps are often sufficient to establish a definitive diagnosis. The early diagnosis of this condition is pivotal since the presence of dual pathology worsens patient's prognosis, especially without intervention. Available data on treatment show a better outcome in terms of survival and cardiovascular events in patients undergoing percutaneous correction of valvular heart disease rather than medical therapy alone, regardless of the presence of cardiac amyloidosis. Furthermore, it seems that cardiac amyloidosis does not impact survival after transcatheter aortic valve replacement, even if higher rates of rehospitalizations have been described. Indeed, percutaneous treatment of valvular heart disease is currently considered the primary therapeutic option. Subsequently a disease-modifying treatment for transthyretin amyloidosis may be considered in order to delay disease progression and improve outcomes, even if specific data are still lacking.

Competing Interests: Disclosures None.

Purpose of Review: Amyloid A (AA) amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders. Here, we review the epidemiology, causes, pathogenesis, clinical features, and diagnostic and therapeutic strategies of AA amyloidosis., Recent Findings: The incidence of AA amyloidosis has declined due to better treatment of the underlying diseases. Histopathological examination is the gold standard of diagnosis, but magnetic resonance imaging can be used to detect cardiac involvement. There is yet no treatment option for the clearance of amyloid fibril deposits; therefore, the management strategy primarily aims to reduce serum amyloid A protein. Anti-inflammatory biologic agents have drastically expanded our therapeutic armamentarium. Kidney transplantation is preferred in patients with kidney failure, and the recurrence of amyloidosis in the allograft has become rare as transplant recipients have started to benefit from the new agents. The management of AA amyloidosis has been considerably changed over the recent years due to the novel therapeutic options aiming to control inflammatory activity. New agents capable of clearing amyloid deposits from the tissues are still needed., (© 2024. The Author(s).)

Paraproteinemias are a group of complex diseases associated with an overproduction of a monoclonal immunoglobulin that can cause a diversity of kidney disorders and end-organ damage. In this review, we focus on paraprotein-mediated glomerular diseases. Kidney biopsy plays a crucial role in diagnosing these disorders, enabling the identification of specific histological patterns. These lesions are categorized into organized (such as amyloidosis, immunotactoid glomerulopathy, fibrillary glomerulonephritis, cryoglobulinemic glomerulonephritis, and monoclonal crystalline glomerulopathies) and nonorganized deposits (such as monoclonal Ig deposition disease and proliferative glomerulonephritis with monoclonal Ig deposits) based on the characteristics of immunofluorescence findings and the ultrastructural appearance of deposits on electron microscopy. This review aims to provide an update, highlight, and discuss clinicopathological aspects such as definition, epidemiology, clinical manifestations, mechanisms of kidney injury, histological features, and diagnostic procedures., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Amyloid-related diseases, such as Alzheimer's and Parkinson's disease, are devastating conditions caused by the accumulation of abnormal protein aggregates known as amyloid fibrils. While assays involving animal models are essential for understanding the pathogenesis and developing therapies, a wide array of standard analytical techniques exists to enhance our understanding of these disorders. These techniques provide valuable information on the formation and propagation of amyloid fibrils, as well as the pharmacokinetics and pharmacodynamics of candidate drugs. Despite ethical concerns surrounding animal use, animal models remain vital tools in the search for treatments. Regardless of the specific animal model chosen, the analytical methods used are usually standardized. Therefore, the main objective of this review is to categorize and outline the primary analytical methods used in in vivo assays for amyloid-related diseases, highlighting their critical role in furthering our understanding of these disorders and developing effective therapies.

Introduction: Both atrial fibrillation (AF) and amyloidosis increase stroke risk. We evaluated the best anticoagulation strategy in AF patients with coexistent amyloidosis., Methods: Consecutive AF patients with concomitant amyloidosis were divided into two groups based on the postablation stroke-prophylaxis approach; group 1: left atrial appendage occlusion (LAAO) in eligible patients and group 2: oral anticoagulation (OAC). Group 1 patients were further divided into Gr. 1A: LAAO + half-does NOAC (HD-NOAC) for 6 months followed by aspirin 81 mg/day and Gr. 1B: LAAO + HD-NOAC. In group 1 patients, with complete occlusion at the 45-day transesophageal echocardiogram, patients were switched to aspirin, 81 mg/day at 6 months. In case of leak, or dense "smoke" in the left atrium (LA) or enlarged LA, they were placed on long-term half-dose (HD) NOAC. Group 2 patients remained on full-dose NOAC during the whole study period., Results: A total of 92 patients were included in the analysis; group 1: 56 and group 2: 36. After the 45-day TEE, 31 patients from group 1 remained on baby-aspirin and 25 on HD NOAC. At 1-year follow-up, four stroke, one TIA and six device-thrombus were reported in group 1A, compared to none in patients in group 1B (5/31 vs. 0/25, p = .03). No bleeding events were reported in group 1, whereas group 2 had five bleeding events (one subdural hematoma, one retinal hemorrhage, and four GI bleedings). Additionally, one stroke was reported in group 2 that happened during brief discontinuation of OAC., Conclusion: In patients with coexistent AF and amyloidosis, half-dose NOAC following LAAO was observed to be the safest stroke-prophylaxis strategy., (© 2024 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Introduction: Insulin-derived amyloidosis (AIns), a skin complication in patients with diabetes, causes impaired insulin absorption. This systematic review aims to get a better understanding of this overlooked condition., Methods: Comprehensive literature searches were performed in Scopus, PubMed, EMBASE, and Web of Science databases until June 17, 2023. From 19,343 publications, duplicate and irrelevant records were eliminated by title, and the full texts of the remaining studies were examined for validity. Clinical, pathological, and therapeutic findings were extracted from 44 papers., Results: Forty-four articles were studied that covered 127 insulin-treated patients with diabetes. From the 62 patients with reported age and sex, males had a mean age of 58 years, and females 68.5 years. While AIns were twice as likely to develop in men (66.13 %) as in women (33.87 %), the administered insulin dose was significantly higher in males (p = 0.017). The most common insulin injection site was the abdominal wall (77.63 %). Histological findings showed the presence of amorphous material with the occasional presence of lymphocytes, plasma cells, macrophages, adipocytes, histocytes, and giant cells. The mean HbA1c level was 8.8 % and the need for receiving insulin was increased in AIns. Changing the site of insulin injections and/or surgically removing the nodules were the most common treatments to obtain better insulin uptake and controlled serum glucose levels., Conclusion: This study highlights the importance of AIns, proper rotation of insulin injection site, and post-treatment patient follow-up to recognize and prevent the development of amyloid nodules., 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 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Keywords: amyloidosis; atrial fibrillation; atrial flutter; hypertrophy, left ventricular EN amyloidosis atrial fibrillation atrial flutter hypertrophy, left ventricular 1730 1732 3 11/29/22 20221129 NES 221129 Atrial fibrillation (AF) and atrial flutter (AFL) are common in patients with transthyretin cardiac amyloidosis (ATTR-CM) and can present years before diagnosis of ATTR-CM.[1] Prior data from our amyloidosis center, which serves both urban and rural parts of the Pacific Northwest, demonstrated an AF/AFL prevalence of 73% among patients with wild type or hereditary ATTR-CM2 - a treatable cause of heart failure if recognized in a timely fashion.[3] Technetium-99m pyrophosphate scintigraphy (Tc-99m PYP) is a simple, noninvasive diagnostic option[3] that allows for screening of ATTR-CM in broader populations, however, there is paucity of data regarding screening for ATTR-CM in patients with AF/AFL. Footnotes 1 Nonstandard Abbreviations and Acronyms AF atrial fibrillation AFL atrial flutter ATTR-CM transthyretin cardiac amyloidosis LV left ventricular LVH left ventricular hypertrophy Tc-99m PYP technetium-99m pyrophosphate scintigraphy 2 For Sources of Funding and Disclosures, see page 1732. Graph In the present study, where systematic screening for ATTR-CM in patients with LVH and AF/AFL was instituted, routine screening of more than 1600 AF/AFL patients resulted in 65 patients undergoing Tc-99m PYP - of which only 1 patient was diagnosed with ATTR-CM. [Extracted from the article]

Introduction: An amyloidosis is a group of diseases associated with the deposition of abnormal protein fibrils in the tissues. Primary amyloidosis (AL) type is the most common form of systemic amyloidosis encountered in clinical settings resulting from the deposition of abnormal light chains associated with underlying plasma cell dyscrasia. Amyloid deposits are rarely seen in bone marrow aspirate smears. Methods: Amyloidosis occurs as a result of the deposition of autologous proteins, which, when viewed under a light microscope, appear as eosinophilic, acellular, amorphous deposits. Results: We presented a case of AL amyloidosis presenting with cardiac manifestations and detected to have amyloid deposits in bone marrow aspirates. Conclusion: To the best of our knowledge, reporting amyloid deposition in bone marrow aspirate smears is very rare and unusual, with sparse mention of its occurrence in literature. Careful examination of bone marrow aspirate for this striking finding leads us to a quicker diagnosis of amyloidosis for a prompt determination of therapeutic protocol, improving the outcomes for the patients. [ABSTRACT FROM AUTHOR]

Background: Cardiac amyloidosis (CA) is a set of amyloid diseases with usually predominant cardiac symptoms, including light-chain amyloidosis (AL), hereditary variant transthyretin amyloidosis (ATTRv), and wild-type transthyretin amyloidosis (ATTRwt). CA are characterized by high heterogeneity in phenotypes leading to diagnosis delay and worsened outcomes.Objectives: The authors used clustering analysis to identify typical clinical profiles in a large population of patients with suspected CA.Methods: Data were collected from the French Referral Center for Cardiac Amyloidosis database (Hôpital Henri Mondor, Créteil), including 1,394 patients with suspected CA between 2010 and 2018: 345 (25%) had a diagnosis of AL, 263 (19%) ATTRv, 402 (29%) ATTRwt, and 384 (28%) no amyloidosis. Based on comprehensive clinicobiological phenotyping, unsupervised clustering analyses were performed by artificial neural network-based self-organizing maps to identify patient profiles (clusters) with similar characteristics, independent of the final diagnosis and prognosis.Results: Mean age and left ventricular ejection fraction were 72 ± 13 years and 52% ± 13%, respectively. The authors identified 7 clusters of patients with contrasting profiles and prognosis. AL patients were distinctively located within a typical cluster; ATTRv patients were distributed across 4 clusters with varying clinical presentations, 1 of which overlapped with patients without amyloidosis; interestingly, ATTRwt patients spread across 3 distinct clusters with contrasting risk factors, biological profiles, and prognosis.Conclusions: Clustering analysis identified 7 clinical profiles with varying characteristics, prognosis, and associations with diagnosis. Especially in patients with ATTRwt, these results suggest key areas to improve amyloidosis diagnosis and stratify prognosis depending on associated risk factors. [ABSTRACT FROM AUTHOR]

We present a case of primary systemic amyloidosis diagnosed by endoscopic sinus surgery. A 75-year-old woman had blurred vision in her left eye; computed tomography and magnetic resonance imaging showed shadows of the bilateral paranasal sinuses. Endoscopic sinus surgery was performed, and amyloidosis was diagnosed by histopathology. She had previously been diagnosed with amyloidosis of the stomach, and therefore, she was diagnosed with primary systemic amyloidosis. A systemic workup for additional amyloid deposits revealed no evidence of other diseases. The patient remained under follow-up without further treatment, as no further amyloid deposition or progression of the lesions was seen. Amyloidosis is a rare condition characterized by the deposition of abnormal protein filaments in the extracellular tissue. Generally, systemic amyloidosis does not involve the head and neck region, and the presence of amyloid in the nasal and paranasal sinus mucosa is more likely to be indicative of a localized process. However, in our patient, the lesions were located in both the sinonasal tract and the stomach, indicating systemic amyloidosis. To our knowledge, there have been no previous reports of systemic amyloidosis involving the sinonasal tract, and therefore, we consider this case to be extremely rare. [ABSTRACT FROM AUTHOR]

Background Amyloidosis is a devastating multisystemic disease resulting from organ deposition of misfolded proteins and subsequent organ dysfunction. An accurate diagnosis relies frequently on biopsies and microscopy techniques to detect amyloid deposition. We evaluated the diagnostic performance of Congo red staining using polarized light (PM) and fluorescence microscopy (FM) techniques in renal amyloidosis. Methods We performed a retrospective and prospective analysis of all renal biopsies submitted at a large quarternary hospital in Sydney, Australia, that had undergone PM and FM evaluation using Congo red staining. Identification of amyloid fibrils on electron microscopy was considered the reference method. Results PM and FM displayed very high sensitivity and specificity in correctly identifying amyloid deposits in renal biopsies that tested positive via Congo red staining. Comparison of the diagnostic statistics revealed that they are diagnostically equivalent. Conclusion In the diagnosis of renal amyloidosis on biopsy, evaluation of Congo red staining may be reliably performed via PM or FM. [ABSTRACT FROM AUTHOR]

Introduction: Hyperechoic renal cortex in a normal-sized kidney has a range of causes, some of which irreparably damage the kidney and should initiate further investigations. Case Report: We present a 72-year-old woman with longstanding bronchiectasis, noticed to have worsening renal function. Renal tract ultrasonography showed hyperechoic normal-sized kidneys. Renal biopsy confirmed amyloidosis. Discussion: Imaging findings in renal amyloidosis tend to be non-specific and are not always present. However, ultrasonography findings of hyperechoic cortex in normal-sized kidneys should not be ignored. Conclusion: Renal impairment from blood chemistry in addition to hyperechoic kidneys may be the key to diagnosing secondary amyloidosis in a patient with bronchiectasis, a rare association but important to recognise. [ABSTRACT FROM AUTHOR]

Objective: To propose an algorithm for the management of bladder amyloidosis based on a systematic review of the literature, given that the bladder is the second most commonly affected organ of the urinary tract in the course of systemic or localized amyloidosis.Methods: We searched PubMed, Cochrane Library and Scopus databases utilizing PRISMA methodology from inception to November 30, 2020 (PROSPERO: CRD42020207855).Results: We included 76 studies with 184 patients (9 case series and 67 case reports). Presenting symptoms of bladder amyloidosis comprised of hematuria, irritative or obstructive urinary symptoms, and cystitis-like symptoms. The diagnosis of amyloidosis was established by histologic examination of specimens retrieved during transurethral resection of bladder lesions. Complete endoscopic resection, the cornerstone of management of localized disease, was feasible in 89.1% cases. The included patients were followed up for a mean of 54 months, within which 65 patients (35.3%) recurred. The time to first amyloidosis recurrence was 20 months (range: 1-168). Additionally, 16 individuals presented with concomitant bladder amyloidosis and bladder cancer, while 4 developed bladder malignancy during follow-up. Due to the frequent and early recurrences of patients with bladder amyloidosis, a check-up cystoscopy at 3, 12, and 24 months' after initial resection is recommended. Recurrences should be managed with transurethral resection, while intravesical instillations of dimethyl sulfoxide (DMSO) and cystectomy should be reserved for refractory cases.Conclusion: We propose a management algorithm for bladder amyloidosis based on the available evidence for this rare benign entity that mimics bladder cancer. [ABSTRACT FROM AUTHOR]

Primary cutaneous amyloidosis is a rare disease, characterized by the deposition of amyloid in the dermis, in the absence of systemic involvement. It has been linked especially to autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, primitive biliary cholangitis. We present a case of a patient with primitive biliary cholangitis who developed lichen amyloidosis. This association has been rarely reported in the literature. [ABSTRACT FROM AUTHOR]