Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined ex...Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.展开更多
Cardiac amyloidosis(CA)is characterized by the deposition of the misfolded amyloid precursor proteins in the myocardium of the heart.The systemic form of CA is mainly caused by either the misfolded monoclonal immunogl...Cardiac amyloidosis(CA)is characterized by the deposition of the misfolded amyloid precursor proteins in the myocardium of the heart.The systemic form of CA is mainly caused by either the misfolded monoclonal immunoglobulin light chains(kappa and lambda)or transthyretin.[1]The clinical manifestations are mainly overlap with symptoms of other cardiovascular diseases mostly hypertrophic cardiomyopathy and heart failure.Some cases often overlooked and remains undiagnosed because of the atypical clinical manifestations,especially in the elderly.展开更多
Primary light chain amyloidosis is a rare hematologic disease with multi-organ involvement.Nearly one-third of patients with amyloidosis experience five or more consultations before diagnosis,which may lead to a poor ...Primary light chain amyloidosis is a rare hematologic disease with multi-organ involvement.Nearly one-third of patients with amyloidosis experience five or more consultations before diagnosis,which may lead to a poor prognosis due to delayed diagnosis.Early risk prediction based on artificial intelligence is valuable for clinical diagnosis and treatment of amyloidosis.For this disease,we propose an Evolutionary Neural Architecture Searching(ENAS)based risk prediction model,which achieves high-precision early risk prediction using physical examination data as a reference factor.To further enhance the value of clinic application,we designed a natural language-based interpretable system around the NAS-assisted risk prediction model for amyloidosis,which utilizes a large language model and Retrieval-Augmented Generation(RAG)to achieve further interpretation of the predicted conclusions.We also propose a document-based global semantic slicing approach in RAG to achievemore accurate slicing and improve the professionalism of the generated interpretations.Tests and implementation show that the proposed risk prediction model can be effectively used for early screening of amyloidosis and that the interpretation method based on the large language model and RAG can effectively provide professional interpretation of predicted results,which provides an effective method and means for the clinical applications of AI.展开更多
Amyloidosis is an infiltrative disease caused by extracellular protein deposition that has accumulated a lot of scientific production in recent years.Different types of amyloidosis can affect the heart.Transthyretin a...Amyloidosis is an infiltrative disease caused by extracellular protein deposition that has accumulated a lot of scientific production in recent years.Different types of amyloidosis can affect the heart.Transthyretin amyloidosis and light chain amyloidosis are the two most common types of cardiac amyloidosis.These entities have a poor prognosis,so accurate diagnostic techniques are imperative for determining an early therapeutic approach.Recent advances in cardiac imaging and diagnostic strategies show that these tools are safe and can avoid the use of invasive diagnostic techniques to histological confirmation,such as endomyocardial biopsy.We performed a review on the diagnostic and prognostic implications of different cardiac imaging techniques in cardiac amyloidosis.We mainly focus on reviewing echocardiography,cardiac magnetic resonance,computed tomography and nuclear imaging techniques and the different safety measurements that can be done with each of them.展开更多
Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis,except epidemic schistosomiasis.Among them,primary sclerosing cholangitis (PSC) might initiate...Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis,except epidemic schistosomiasis.Among them,primary sclerosing cholangitis (PSC) might initiate amyloid A protein deposition in diverse tissues,giving rise to systemic amyloidosis,due to a progressive and unresolved inflammatory process,and its possible association with inflammatory bowel diseases.Nevertheless,only one such case has been reported in the literature to date.We report a 69-year-old Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis,without any evidence of other inflammatory disorders.As a result of cholestasis in conjunction with biliary strictures and increased serum IgG4,the presence of IgG4 + plasma cells was examined systemically,resulting in unexpected documentation of Congo-red-positive amyloid deposits,but not IgG4 + plasma cells,in the liver,stomach and salivary glands.Elevated serum IgG4 is the hallmark of IgG4-related disease,including IgG4-associated cholangitis,but it has also been demonstrated in certain patients with PSC.Amyloid A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discriminating PSC from IgG4-associated cholangitis.展开更多
Amyloidosis is a rare disorder, characterized by the extracellular deposition of an abnormal fibrillar protein, which disrupts tissue structure and function. Amyloidosis can be acquired or hereditary, and systemic or ...Amyloidosis is a rare disorder, characterized by the extracellular deposition of an abnormal fibrillar protein, which disrupts tissue structure and function. Amyloidosis can be acquired or hereditary, and systemic or localized to a single organ, such as the gastrointestinal (GI) tract. Clinical manifestations may vary from asymptomatic to fatal forms. Primary amyloidosis (monoclonal immunoglobulin light chains, AL) is the most common form of amyloidosis. AL amyloidosis has been associated with plasma cell dyscrasias, such as, mul- tiple myeloma. Secondary amyloidosis is caused by the deposition of fragments of the circulating acute-phase reactant, serum amyloid A protein (SAA). Common causes of AA amyloidosis are chronic inflammatory dis-orders. Although GI symptoms are usually nonspecific, histopathological patterns of amyloid deposition are associated with clinical and endoscopic features. Amyloid deposition in the muscularis mucosae, submucosa, and muscularis propria has been dominant in AL amyloidosis, leading to polypoid protrusions and thickening of the valvulae conniventes, whereas granular amyloid deposition mainly in the propria mucosae has been related to AA amyloidosis, resulting in the fine granular appearance, mucosal friability, and erosions. As a result, AL amyloidosis usually presents with constipation, mechanical obstruction, or chronic intestinal pseudoobstruction while AA amyloidosis presents with diarrhea and malabsorption Amyloidotic GI symptoms are mostly refractory and have a negative impact on quality of life and survival. Diagnosing GI amyloidosis requires high suspicion of evaluating endoscopists. Because of the absence of specific treatments for reducing the abundance of the amyloidogenic precursor protein, we should be aware of certain associations between patterns of amyloid deposition and clinical and endoscopic features.展开更多
We present the case of a 66 year old male who presented with dyspnea and reduced exercise tolerance. Echocardiography demonstrated impaired left ventricular (LV) function and restrictive diastolic function with pronou...We present the case of a 66 year old male who presented with dyspnea and reduced exercise tolerance. Echocardiography demonstrated impaired left ventricular (LV) function and restrictive diastolic function with pronounced concentric left ventricular hypertrophy (LVH) without a history of hypertension and no aortic valve stenosis. Differential diagnostics of concentric LVH are discussed in detail. In the current case, cardiac amyloidosis (AL) amyloidosis was diagnosed and confirmed by serum amyloid P (SAP) scintigraphy and abdominal fat aspiration biopsy. This case shows the rapid decline in clinical condition with progression of cardiac involvement of AL. As discussed in detail, cardiac involvement in AL-amyloidosis generally denotes a poor prognosis, regardless of the method of treatment.展开更多
Primary tracheobronchial amyloidosis (TBA) is a rare pulmonary disease.A systematic review was performed on 64 cases of primary TBA in China and progress in the diagnosis and treatment of this disease is discussed.The...Primary tracheobronchial amyloidosis (TBA) is a rare pulmonary disease.A systematic review was performed on 64 cases of primary TBA in China and progress in the diagnosis and treatment of this disease is discussed.The Chinese biological and medical databases from 1970 to 2010 were searched and 75 cases of complete clinical and pathological data were identified.The clinical characteristics of the disease were summarized and longitudinal comparisons were made of diagnostic and treatment methods over time.The results showed that the morbidity associated with primary TBA has increased over recent years.The clinical manifestations were non-specific.Progressive dyspnea, cough and sputum were the most common symptoms.The percentage of patients undergoing computed tomography (CT) scan has increased over the years.The bronchoscopy and transbrochial lung biopsy (TBLB) were usually sufficient to establish the diagnosis.Treatment was reported for a total of 44 cases.Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration such as steroids and colchicines were reported to be effective in some patients.It is concluded that the demographic characteristics and clinical manifestations of primary TBA patients in China are largely consistent with findings reported in other countries.Dramatically more cases were reported in recent years, mainly due to the extensive application of bronchoscopy since 1990s.Chest CT scan provides important clues for the diagnosis of the disease.The definite diagnosis was confirmed by bronchoscopic findings and Congo red staining of biopsy specimen.Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration, such as steroids and colchicines were reported to be effective in some patients.展开更多
AMYLOIDOSIS is a benign process which can have systemic involvement. Though larynx is the common site of localized amyloidosis in the head and neck region,I it was seldom reported with heterochronous implication of bi...AMYLOIDOSIS is a benign process which can have systemic involvement. Though larynx is the common site of localized amyloidosis in the head and neck region,I it was seldom reported with heterochronous implication of bilateral ventricles. Here we report a case of laryngeal amyloidosis heterochronously localized at bilateral ventricles with tracheobronchial involvement. Combined with our experience we reviewed the literature, and discuss the pertinent managements of this condition.展开更多
We describe a case of 42-year-old female presenting with abdominal pain associated with loss of weight and fever for 8 mo. On evaluation she had gross hepatomegaly with raised alkaline phosphatase and raised GGT level...We describe a case of 42-year-old female presenting with abdominal pain associated with loss of weight and fever for 8 mo. On evaluation she had gross hepatomegaly with raised alkaline phosphatase and raised GGT levels with normal transaminases and bilirubin. On imaging she had diffuse enlargement of liver with heterogeneous contrast uptake in liver. Her viral marker and autoimmune markers were negative. Liver biopsy depicted massive deposition of amyloid in peri-sinusoidal spaces which revealed apple green birefringence on polarizing microscopy after Congo red staining. Cardiac and renal evaluation was unremarkable. Abdominal fat pad and rectum biopsy was negative for amyloid deposit. There was no evidence of primary amyloidosis as bone marrow examination was normal. Serum and urine immunofixation electrophoresis were normal. Immunoperoxidase staining for serum amyloid associated protein for secondary amyloidosis was negative from liver biopsy. We present this rare case of primary hepatic amyloidosis and review the literature regarding varied presentations of hepatic involvement in amyloidosis.展开更多
BACKGROUND Cardiac amyloidosis,a disease caused by the precipitation of amyloid proteins in the myocardial extracellular matrix has been historically difficult to diagnose due to lack of specific clinical manifestatio...BACKGROUND Cardiac amyloidosis,a disease caused by the precipitation of amyloid proteins in the myocardial extracellular matrix has been historically difficult to diagnose due to lack of specific clinical manifestations and necessity of biopsy to demonstrate amyloid deposition. However,advances in cardiovascular imaging techniques have facilitated earlier recognition of this disease. In addition,while once thought of as incurable,treatment strategies are emerging for cardiac amyloidosis,making early diagnosis essential.CASE SUMMARY We outline the case of a 73 years old African American female who was admitted with sudden onset shortness of breath and found to be in cardiogenic shock.Cardiac amyloidosis was suspected due to discordance between electrocardiogram and echocardiogram findings and this was subsequently confirmed with the aid of scintigraphy and an endomyocardial biopsy.CONCLUSION Our objective is to highlight the diagnostic evaluation and clinical implications of cardiac amyloidosis.展开更多
AIM: To study the clinical features of vitreous amyloidosis and the effect of vitrectomy for it. METHODS: We treated 6 eyes (4 Patients) with vitreous amyloidosis from 2008 to 2009, and followed up for 18-30 months af...AIM: To study the clinical features of vitreous amyloidosis and the effect of vitrectomy for it. METHODS: We treated 6 eyes (4 Patients) with vitreous amyloidosis from 2008 to 2009, and followed up for 18-30 months after vitrectomy. RESULTS: The visual acuity ranged from counting fingers to 3/50 before surgery and 15/50-40/50 after vitrectomy. No severe complication was observed. CONCLUSION: Vitrectomy is an effective and safe treatment for eyes with vitreous amyloidosis. A long period of follow-up after surgery should be performed.展开更多
BACKGROUND Primary cutaneous amyloidosis(PCA)is a chronic metabolic skin disease that has a detrimental impact on physical and mental health.It appears as mossy papules and severe itching,which is long-term and recurr...BACKGROUND Primary cutaneous amyloidosis(PCA)is a chronic metabolic skin disease that has a detrimental impact on physical and mental health.It appears as mossy papules and severe itching,which is long-term and recurrent.Traditional treatments are unsatisfactory,especially for refractory cases.Fire needle therapy,which is widely used in China,has shown good clinical efficacy,as well as advantages concerning safety and cost.Clinical reports about fire needle treatment of this disease are few at present.CASE SUMMARY We report two older men who had developed maculopapules with itchiness on the trunk and arms for more than 10-15 years.Due to the dermatopathological findings,PCA was our primary consideration.They received topical halometasone cream and pretreatment with fire needle for 8-16 wk.Both patients showed significant improvement of lesions.Neither patient had recurrence with a minimum of 2 years of follow-up.CONCLUSION Topical halometasone cream and pretreatment with fire needle could be a fast,safe,and economic treatment for PCA.展开更多
Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis （CA）, and to determine predictive value of high-sensitivity cardiac troponin T （hs-cTnT） in CA patients. Me...Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis （CA）, and to determine predictive value of high-sensitivity cardiac troponin T （hs-cTnT） in CA patients. Methods We recruited 102 consecutive CA cases and followed these patients for 5 years. We described their clinical characteristics at presentation and used a new, high-sensitivity assay to determine the concentration of cTnT in plasma samples from these patients. Results The patients with poor prognosis showed older age （56 ±12 years vs. 50 ±15 years, P=0.022）, higher incidences of heart failure （36.92%vs. 16.22%, P=0.041）, pericardial effusion （60.00%vs. 35.14%, P=0.023）, greater thickness of interventricular septum （IVS） （15 ±4 mm vs. 13 ±4 mm, P=0.034）, higher level of hs-cTnT （0.186 ±0.249 ng/mL vs. 0.044 ±0.055 ng/mL, P=0.001） and higher NT-proBNP （N-terminal pro-B-type natriuretic pep-tide） levels （11,742 ± 10,464 pg/mL vs. 6,031 ± 7,458 pg/mL, P=0.006）. At multivariate Cox regression analysis, heart failure （HR：1.78, 95%CI：1.09-2.92, P=0.021）, greater wall thickness of IVS （HR：1.44, 95%CI：1.04-3.01, P=0.0375） and higher hs-cTnT level （HR：6.16, 95%CI：2.20-17.24, P=0.001） at enrollment emerged as independent predictors of all-cause mortality. Conclusions We showed that hs-cTnT is associated with a very ominous prognosis, and it is also the strongest predictor of all-cause mortality in multivariate analysis. Examination of hs-cTnT concentrations provides valuable prognostic information concerning long-term outcomes.展开更多
BACKGROUND Lichen amyloidosis(LA)is a chronic,severely pruritic skin disease,which is the most common form of primary cutaneous amyloidosis.The treatment of LA has been considered to be difficult.LA may be associated ...BACKGROUND Lichen amyloidosis(LA)is a chronic,severely pruritic skin disease,which is the most common form of primary cutaneous amyloidosis.The treatment of LA has been considered to be difficult.LA may be associated with atopic dermatitis(AD),and in this setting,the treatment options may be more limited.Herein,we report four cases of LA associated with AD successfully treated by dupilumab.CASE SUMMARY In this article,we describe four cases of patients who presented with recurrent skin rash accompanied by severe generalized intractable pruritus,diagnosed with refractory LA coexisting with chronic AD.Previous treatments had not produced any apparent improvement.Thus,we administered dupilumab injection subcutaneously at a dose of 600 mg for the first time and 300 mg every 2 wk thereafter.Their lesions all markedly improved.CONCLUSION Dupilumab may be a new useful treatment for LA coexisting with AD.展开更多
INTRODUCTION Secondary amyloidosis is a rare but seriouscomplication of Crohn’s disease(CD).Theincidence of the association of secondaryamyloidosis in patients with CD has been reportedto be 0.5%-8% in Western countr...INTRODUCTION Secondary amyloidosis is a rare but seriouscomplication of Crohn’s disease(CD).Theincidence of the association of secondaryamyloidosis in patients with CD has been reportedto be 0.5%-8% in Western countries.However,in Japan,the number of patients with CDcomplicated by amyloidosis is limited.Thecharacteristics of their clinical manifestations andthe incidence of association are uncertain.Therefore,we report herein a patient with展开更多
BACKGROUND Lichenoid amyloidosis(LA)is a subtype of primary cutaneous amyloidosis characterized by persistent multiple groups of hyperkeratotic papules,usually on the lower leg,back,forearm,or thigh.LA may be associat...BACKGROUND Lichenoid amyloidosis(LA)is a subtype of primary cutaneous amyloidosis characterized by persistent multiple groups of hyperkeratotic papules,usually on the lower leg,back,forearm,or thigh.LA may be associated with several skin diseases,including atopic dermatitis(AD).The treatment of LA is considered to be difficult.However,as there is some overlap in the etiopathogenesis of LA and AD,AD treatment may also be effective for LA.CASE SUMMARY Case 1:A 70-year-old man was diagnosed with severe AD with LA based on large dark erythema and papules on the trunk and buttocks and dense hemispherical millet-shaped papules with pruritus on the extensor side of the lower limbs.He had a long history of the disease(8 years),with repeated and polymorphic skin lesions.Given the poor efficacy of traditional treatments,this patient was recommended to receive dupilumab treatment.At the initial stage,300 mg was injected subcutaneously every 2 wk.After 28 wk,the drug interval was extended to 1 mo due to the pandemic.Follow-up observations revealed that the patient reached an Eczema Area Severity Index of 90(skin lesions improved by 90%compared with the baseline)by the end of the study.Moreover,Investigator's Global Assessment score was 1,and scoring atopic dermatitis index and numeric rating scale improved by 97.7%and 87.5%compared with the baseline,respectively,with LA skin lesions having largely subsided.Case 2:A 30-year-old woman was diagnosed with severe AD with LA,due to dense and substantial papules on the dorsal hands similar to changes in cutaneous amyloidosis,and erythema and papules scattered on limbs and trunk with pruritus,present for 25 years.After 16 wk of dupilumab treatment,she stopped,and skin lesions completely subsided,without recurrence since the last follow-up.CONCLUSION Dupilumab shows rational efficacy and safety in the treatment of severe AD with LA,in addition to benefits in the quality of life of the patients.展开更多
We are reporting a rare case of a patient with primary(AL) amyloidosis presenting with an acute non-varicealupper gastrointestinal hemorrhage in the absence ofother systemic involvement. The case report involves a58-y...We are reporting a rare case of a patient with primary(AL) amyloidosis presenting with an acute non-varicealupper gastrointestinal hemorrhage in the absence ofother systemic involvement. The case report involves a58-year-old woman with significant cardiac history andhereditary blood disorder who came in complaining ofabdominal pain and coffee-ground emesis for two days.Computed tomography(CT) scan of the abdomen andpelvis with contrast revealed segmental wall thickeningof the proximal jejunum with hyperdense, heterog-enous luminal content. Similar findings were evident inthe left lower small bowel region, suspicious for smallbowel hematoma and the possibility of intraluminalclots. Esophagogastroduodenoscopy performed postresuscitation showed punctate, erythematous lesionsthroughout the stomach as well as regions of smallbowel mucosa that appeared scalloped, ulcerated, andhemorrhaged on contact. Despite initial treatment for immunostain-positive focal cytomegalovirus gastritis, follow-up esophagogastroduodenoscopy after two months continued to demonstrate friable and irregular duodenal mucosa hinting at a different underlying etiol-ogy. Pathology reports from analyses of biopsy samples highlighted infiltration and expansion of the lamina pro-pria and submucosa. Subsequent staining with congo red/crystal violet and appropriate subtyping established the diagnosis of AL(kappa)-type amyloidosis. The sig-nificance of this case lies in the fact that our patient did not have the typically seen diagnostic systemic involvements-namely of heart and kidneys-usually seen in primary(AL) amyloidosis patients. It was the persis-tent endoscopic findings and biopsy results which gave clues to the physicians regarding the possibility of an abnormal protein-deposition entity.展开更多
AIM:To investigate the efficacy of the digitally reinforced hematoxylin-eosin polarization(DRHEP)technique for detection of amyloidosis in rectal biopsies.METHODS:One hundred hematoxylin-eosin(HE)stained rectal biopsi...AIM:To investigate the efficacy of the digitally reinforced hematoxylin-eosin polarization(DRHEP)technique for detection of amyloidosis in rectal biopsies.METHODS:One hundred hematoxylin-eosin(HE)stained rectal biopsies with Congo-red(CR)-positive amyloid depositions and 50 control cases with CRnegative amyloid-mimicking areas were scanned blinded to the CR results for amyloid depositions under both bright and polarized light,and digitally photographed using the DRHEP technique,to accentuate the faint birefringence observed in HE slides under polarization.The results of DRHEP and HE evaluation were statistically correlated with CR polarization results with respect to presence and localization of amyloid deposits as well as amyloid types.RESULTS:Amyloid deposits showed yellowish-green birefringence by DRHEP,which allowed identification of amyloidosis in 41 HE-unsuspected cases(P=0.016),31 of which only had vascular deposits.True positivity was higher,and false negativity and positivity were lower by DRHEP,compared to evaluation by HE(69%,31%,and 0.8%vs 33%,67%,and 33%,respectively;P<0.0001).The sensitivity,specificity,accuracy,and positive and negative predictive values for DRHEP were69%,98%,78.6%,98.5%,and 61.25%,respectively.Reasons for DRHEP false negativity were presence of extensive background birefringence in 12 cases,absence of CR birefringent vessel in 3 cases,and missing of the tiny deposits in 9 cases,which could be improved by experience,especially in the latter case.No correlation was found between age,gender,sites of deposits,or amyloid types.CONCLUSION:The DRHEP technique improves diagnostic accuracy when used as an adjunct or a prior step to CR staining,especially for cases with limited tissues for further analysis.展开更多
The release of proinfammatory cytokines during infam-mation represents an attempt to respond to injury, but it may produce detrimental effects. The infammasome is a large, multiprotein complex that drives proinfammato...The release of proinfammatory cytokines during infam-mation represents an attempt to respond to injury, but it may produce detrimental effects. The infammasome is a large, multiprotein complex that drives proinfammatory cytokine production in response to infection and tissue injury; the best-characterized inflammasome is the nod-like receptor protein-3 （NLRP3）. Once activated, infammasome leads to the active form of caspase-1, the enzyme required for the maturation of interleukin-1beta. Additional mechanisms bringing to renal inflammatory, systemic diseases and fibrotic processes were recently reported, via the activation of the inflammasome that consists of NLRP3, apoptosis associated speck-like protein and caspase-1. Several manuscripts seem to identify NLRP3 infammasome as a possible therapeutic target in the treatment of progressive chronic kidney disease. Serum amyloid A （SAA）, as acute-phase protein with also proinfammatory properties, has been shown to induce the secretion of cathepsin B and infammasome components from human macrophages. SAA is a well recognised potent activator of the NLRP3. Here we will address our description on the involvement of the kidney in autoinflammatory diseases driven mainly by secondary, or reactive, AA amyloidosis with a particular attention on novel therapeutic approach which has to be addressed in suppressing underlying inflammatory disease and reducing the SAA concentration.展开更多
基金supported by the National Natural Science Foundation of China,No.81472235(to HF)the Shanghai Jiao Tong University Medical and Engineering Project,Nos.YG2021QN53(to HF),YG2017MS71(to HF)+1 种基金the International Cooperation Project of the National Natural Science Foundation of China,No.82020108017(to DC)the Innovation Group Project of the National Natural Science Foundation of China,No.81921002(to DC).
文摘Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.
基金supported by the National Clinical Research Center for Geriatric Diseases Foundation of Chinese PLA General Hospital(NCRCG-PLAGH-2024007).
文摘Cardiac amyloidosis(CA)is characterized by the deposition of the misfolded amyloid precursor proteins in the myocardium of the heart.The systemic form of CA is mainly caused by either the misfolded monoclonal immunoglobulin light chains(kappa and lambda)or transthyretin.[1]The clinical manifestations are mainly overlap with symptoms of other cardiovascular diseases mostly hypertrophic cardiomyopathy and heart failure.Some cases often overlooked and remains undiagnosed because of the atypical clinical manifestations,especially in the elderly.
基金supported by Liaoning Province Key R&D Program Project(Grant Nos.2019JH2/10100027)in part by Grants from Shenyang Science and Technology Plan Project(Grant No.RC210469).
文摘Primary light chain amyloidosis is a rare hematologic disease with multi-organ involvement.Nearly one-third of patients with amyloidosis experience five or more consultations before diagnosis,which may lead to a poor prognosis due to delayed diagnosis.Early risk prediction based on artificial intelligence is valuable for clinical diagnosis and treatment of amyloidosis.For this disease,we propose an Evolutionary Neural Architecture Searching(ENAS)based risk prediction model,which achieves high-precision early risk prediction using physical examination data as a reference factor.To further enhance the value of clinic application,we designed a natural language-based interpretable system around the NAS-assisted risk prediction model for amyloidosis,which utilizes a large language model and Retrieval-Augmented Generation(RAG)to achieve further interpretation of the predicted conclusions.We also propose a document-based global semantic slicing approach in RAG to achievemore accurate slicing and improve the professionalism of the generated interpretations.Tests and implementation show that the proposed risk prediction model can be effectively used for early screening of amyloidosis and that the interpretation method based on the large language model and RAG can effectively provide professional interpretation of predicted results,which provides an effective method and means for the clinical applications of AI.
文摘Amyloidosis is an infiltrative disease caused by extracellular protein deposition that has accumulated a lot of scientific production in recent years.Different types of amyloidosis can affect the heart.Transthyretin amyloidosis and light chain amyloidosis are the two most common types of cardiac amyloidosis.These entities have a poor prognosis,so accurate diagnostic techniques are imperative for determining an early therapeutic approach.Recent advances in cardiac imaging and diagnostic strategies show that these tools are safe and can avoid the use of invasive diagnostic techniques to histological confirmation,such as endomyocardial biopsy.We performed a review on the diagnostic and prognostic implications of different cardiac imaging techniques in cardiac amyloidosis.We mainly focus on reviewing echocardiography,cardiac magnetic resonance,computed tomography and nuclear imaging techniques and the different safety measurements that can be done with each of them.
基金Supported by Grants-in-Aid for Clinical Research from National Hospital Organization,Grants-in-Aid for Scientific Research from the Ministry of Health,Labour and Welfare of Japan
文摘Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis,except epidemic schistosomiasis.Among them,primary sclerosing cholangitis (PSC) might initiate amyloid A protein deposition in diverse tissues,giving rise to systemic amyloidosis,due to a progressive and unresolved inflammatory process,and its possible association with inflammatory bowel diseases.Nevertheless,only one such case has been reported in the literature to date.We report a 69-year-old Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis,without any evidence of other inflammatory disorders.As a result of cholestasis in conjunction with biliary strictures and increased serum IgG4,the presence of IgG4 + plasma cells was examined systemically,resulting in unexpected documentation of Congo-red-positive amyloid deposits,but not IgG4 + plasma cells,in the liver,stomach and salivary glands.Elevated serum IgG4 is the hallmark of IgG4-related disease,including IgG4-associated cholangitis,but it has also been demonstrated in certain patients with PSC.Amyloid A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discriminating PSC from IgG4-associated cholangitis.
文摘Amyloidosis is a rare disorder, characterized by the extracellular deposition of an abnormal fibrillar protein, which disrupts tissue structure and function. Amyloidosis can be acquired or hereditary, and systemic or localized to a single organ, such as the gastrointestinal (GI) tract. Clinical manifestations may vary from asymptomatic to fatal forms. Primary amyloidosis (monoclonal immunoglobulin light chains, AL) is the most common form of amyloidosis. AL amyloidosis has been associated with plasma cell dyscrasias, such as, mul- tiple myeloma. Secondary amyloidosis is caused by the deposition of fragments of the circulating acute-phase reactant, serum amyloid A protein (SAA). Common causes of AA amyloidosis are chronic inflammatory dis-orders. Although GI symptoms are usually nonspecific, histopathological patterns of amyloid deposition are associated with clinical and endoscopic features. Amyloid deposition in the muscularis mucosae, submucosa, and muscularis propria has been dominant in AL amyloidosis, leading to polypoid protrusions and thickening of the valvulae conniventes, whereas granular amyloid deposition mainly in the propria mucosae has been related to AA amyloidosis, resulting in the fine granular appearance, mucosal friability, and erosions. As a result, AL amyloidosis usually presents with constipation, mechanical obstruction, or chronic intestinal pseudoobstruction while AA amyloidosis presents with diarrhea and malabsorption Amyloidotic GI symptoms are mostly refractory and have a negative impact on quality of life and survival. Diagnosing GI amyloidosis requires high suspicion of evaluating endoscopists. Because of the absence of specific treatments for reducing the abundance of the amyloidogenic precursor protein, we should be aware of certain associations between patterns of amyloid deposition and clinical and endoscopic features.
文摘We present the case of a 66 year old male who presented with dyspnea and reduced exercise tolerance. Echocardiography demonstrated impaired left ventricular (LV) function and restrictive diastolic function with pronounced concentric left ventricular hypertrophy (LVH) without a history of hypertension and no aortic valve stenosis. Differential diagnostics of concentric LVH are discussed in detail. In the current case, cardiac amyloidosis (AL) amyloidosis was diagnosed and confirmed by serum amyloid P (SAP) scintigraphy and abdominal fat aspiration biopsy. This case shows the rapid decline in clinical condition with progression of cardiac involvement of AL. As discussed in detail, cardiac involvement in AL-amyloidosis generally denotes a poor prognosis, regardless of the method of treatment.
基金supported by the grants from Natural Science Foundation of Zhejiang Province (No.Y2080323)Zhejiang Provincial Science and Technology Administration (No.2009R100310 and No.2008C03002-2)Health Department of Zhejiang Province (No.2009QN010)
文摘Primary tracheobronchial amyloidosis (TBA) is a rare pulmonary disease.A systematic review was performed on 64 cases of primary TBA in China and progress in the diagnosis and treatment of this disease is discussed.The Chinese biological and medical databases from 1970 to 2010 were searched and 75 cases of complete clinical and pathological data were identified.The clinical characteristics of the disease were summarized and longitudinal comparisons were made of diagnostic and treatment methods over time.The results showed that the morbidity associated with primary TBA has increased over recent years.The clinical manifestations were non-specific.Progressive dyspnea, cough and sputum were the most common symptoms.The percentage of patients undergoing computed tomography (CT) scan has increased over the years.The bronchoscopy and transbrochial lung biopsy (TBLB) were usually sufficient to establish the diagnosis.Treatment was reported for a total of 44 cases.Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration such as steroids and colchicines were reported to be effective in some patients.It is concluded that the demographic characteristics and clinical manifestations of primary TBA patients in China are largely consistent with findings reported in other countries.Dramatically more cases were reported in recent years, mainly due to the extensive application of bronchoscopy since 1990s.Chest CT scan provides important clues for the diagnosis of the disease.The definite diagnosis was confirmed by bronchoscopic findings and Congo red staining of biopsy specimen.Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration, such as steroids and colchicines were reported to be effective in some patients.
基金Supported by Zhejiang Province Welfare Technology Applied ResearchProgram(2012C33096)
文摘AMYLOIDOSIS is a benign process which can have systemic involvement. Though larynx is the common site of localized amyloidosis in the head and neck region,I it was seldom reported with heterochronous implication of bilateral ventricles. Here we report a case of laryngeal amyloidosis heterochronously localized at bilateral ventricles with tracheobronchial involvement. Combined with our experience we reviewed the literature, and discuss the pertinent managements of this condition.
文摘We describe a case of 42-year-old female presenting with abdominal pain associated with loss of weight and fever for 8 mo. On evaluation she had gross hepatomegaly with raised alkaline phosphatase and raised GGT levels with normal transaminases and bilirubin. On imaging she had diffuse enlargement of liver with heterogeneous contrast uptake in liver. Her viral marker and autoimmune markers were negative. Liver biopsy depicted massive deposition of amyloid in peri-sinusoidal spaces which revealed apple green birefringence on polarizing microscopy after Congo red staining. Cardiac and renal evaluation was unremarkable. Abdominal fat pad and rectum biopsy was negative for amyloid deposit. There was no evidence of primary amyloidosis as bone marrow examination was normal. Serum and urine immunofixation electrophoresis were normal. Immunoperoxidase staining for serum amyloid associated protein for secondary amyloidosis was negative from liver biopsy. We present this rare case of primary hepatic amyloidosis and review the literature regarding varied presentations of hepatic involvement in amyloidosis.
文摘BACKGROUND Cardiac amyloidosis,a disease caused by the precipitation of amyloid proteins in the myocardial extracellular matrix has been historically difficult to diagnose due to lack of specific clinical manifestations and necessity of biopsy to demonstrate amyloid deposition. However,advances in cardiovascular imaging techniques have facilitated earlier recognition of this disease. In addition,while once thought of as incurable,treatment strategies are emerging for cardiac amyloidosis,making early diagnosis essential.CASE SUMMARY We outline the case of a 73 years old African American female who was admitted with sudden onset shortness of breath and found to be in cardiogenic shock.Cardiac amyloidosis was suspected due to discordance between electrocardiogram and echocardiogram findings and this was subsequently confirmed with the aid of scintigraphy and an endomyocardial biopsy.CONCLUSION Our objective is to highlight the diagnostic evaluation and clinical implications of cardiac amyloidosis.
文摘AIM: To study the clinical features of vitreous amyloidosis and the effect of vitrectomy for it. METHODS: We treated 6 eyes (4 Patients) with vitreous amyloidosis from 2008 to 2009, and followed up for 18-30 months after vitrectomy. RESULTS: The visual acuity ranged from counting fingers to 3/50 before surgery and 15/50-40/50 after vitrectomy. No severe complication was observed. CONCLUSION: Vitrectomy is an effective and safe treatment for eyes with vitreous amyloidosis. A long period of follow-up after surgery should be performed.
基金Supported by the Shandong Scientific Technology Program,No.2015GSF118003the Jinan Science and Technology Plan Projects,No.201503019.
文摘BACKGROUND Primary cutaneous amyloidosis(PCA)is a chronic metabolic skin disease that has a detrimental impact on physical and mental health.It appears as mossy papules and severe itching,which is long-term and recurrent.Traditional treatments are unsatisfactory,especially for refractory cases.Fire needle therapy,which is widely used in China,has shown good clinical efficacy,as well as advantages concerning safety and cost.Clinical reports about fire needle treatment of this disease are few at present.CASE SUMMARY We report two older men who had developed maculopapules with itchiness on the trunk and arms for more than 10-15 years.Due to the dermatopathological findings,PCA was our primary consideration.They received topical halometasone cream and pretreatment with fire needle for 8-16 wk.Both patients showed significant improvement of lesions.Neither patient had recurrence with a minimum of 2 years of follow-up.CONCLUSION Topical halometasone cream and pretreatment with fire needle could be a fast,safe,and economic treatment for PCA.
文摘Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis （CA）, and to determine predictive value of high-sensitivity cardiac troponin T （hs-cTnT） in CA patients. Methods We recruited 102 consecutive CA cases and followed these patients for 5 years. We described their clinical characteristics at presentation and used a new, high-sensitivity assay to determine the concentration of cTnT in plasma samples from these patients. Results The patients with poor prognosis showed older age （56 ±12 years vs. 50 ±15 years, P=0.022）, higher incidences of heart failure （36.92%vs. 16.22%, P=0.041）, pericardial effusion （60.00%vs. 35.14%, P=0.023）, greater thickness of interventricular septum （IVS） （15 ±4 mm vs. 13 ±4 mm, P=0.034）, higher level of hs-cTnT （0.186 ±0.249 ng/mL vs. 0.044 ±0.055 ng/mL, P=0.001） and higher NT-proBNP （N-terminal pro-B-type natriuretic pep-tide） levels （11,742 ± 10,464 pg/mL vs. 6,031 ± 7,458 pg/mL, P=0.006）. At multivariate Cox regression analysis, heart failure （HR：1.78, 95%CI：1.09-2.92, P=0.021）, greater wall thickness of IVS （HR：1.44, 95%CI：1.04-3.01, P=0.0375） and higher hs-cTnT level （HR：6.16, 95%CI：2.20-17.24, P=0.001） at enrollment emerged as independent predictors of all-cause mortality. Conclusions We showed that hs-cTnT is associated with a very ominous prognosis, and it is also the strongest predictor of all-cause mortality in multivariate analysis. Examination of hs-cTnT concentrations provides valuable prognostic information concerning long-term outcomes.
文摘BACKGROUND Lichen amyloidosis(LA)is a chronic,severely pruritic skin disease,which is the most common form of primary cutaneous amyloidosis.The treatment of LA has been considered to be difficult.LA may be associated with atopic dermatitis(AD),and in this setting,the treatment options may be more limited.Herein,we report four cases of LA associated with AD successfully treated by dupilumab.CASE SUMMARY In this article,we describe four cases of patients who presented with recurrent skin rash accompanied by severe generalized intractable pruritus,diagnosed with refractory LA coexisting with chronic AD.Previous treatments had not produced any apparent improvement.Thus,we administered dupilumab injection subcutaneously at a dose of 600 mg for the first time and 300 mg every 2 wk thereafter.Their lesions all markedly improved.CONCLUSION Dupilumab may be a new useful treatment for LA coexisting with AD.
基金Grant-in-Aid 10670518(to Osamu Saitoh)for Scientific Research from the Ministry of Education,Science,Sports,and Culture,Japan
文摘INTRODUCTION Secondary amyloidosis is a rare but seriouscomplication of Crohn’s disease(CD).Theincidence of the association of secondaryamyloidosis in patients with CD has been reportedto be 0.5%-8% in Western countries.However,in Japan,the number of patients with CDcomplicated by amyloidosis is limited.Thecharacteristics of their clinical manifestations andthe incidence of association are uncertain.Therefore,we report herein a patient with
基金Supported by National Natural Science Foundation of China,No.81803160Scientific Development Program of Jilin Province,No.20200801078GH.
文摘BACKGROUND Lichenoid amyloidosis(LA)is a subtype of primary cutaneous amyloidosis characterized by persistent multiple groups of hyperkeratotic papules,usually on the lower leg,back,forearm,or thigh.LA may be associated with several skin diseases,including atopic dermatitis(AD).The treatment of LA is considered to be difficult.However,as there is some overlap in the etiopathogenesis of LA and AD,AD treatment may also be effective for LA.CASE SUMMARY Case 1:A 70-year-old man was diagnosed with severe AD with LA based on large dark erythema and papules on the trunk and buttocks and dense hemispherical millet-shaped papules with pruritus on the extensor side of the lower limbs.He had a long history of the disease(8 years),with repeated and polymorphic skin lesions.Given the poor efficacy of traditional treatments,this patient was recommended to receive dupilumab treatment.At the initial stage,300 mg was injected subcutaneously every 2 wk.After 28 wk,the drug interval was extended to 1 mo due to the pandemic.Follow-up observations revealed that the patient reached an Eczema Area Severity Index of 90(skin lesions improved by 90%compared with the baseline)by the end of the study.Moreover,Investigator's Global Assessment score was 1,and scoring atopic dermatitis index and numeric rating scale improved by 97.7%and 87.5%compared with the baseline,respectively,with LA skin lesions having largely subsided.Case 2:A 30-year-old woman was diagnosed with severe AD with LA,due to dense and substantial papules on the dorsal hands similar to changes in cutaneous amyloidosis,and erythema and papules scattered on limbs and trunk with pruritus,present for 25 years.After 16 wk of dupilumab treatment,she stopped,and skin lesions completely subsided,without recurrence since the last follow-up.CONCLUSION Dupilumab shows rational efficacy and safety in the treatment of severe AD with LA,in addition to benefits in the quality of life of the patients.
文摘We are reporting a rare case of a patient with primary(AL) amyloidosis presenting with an acute non-varicealupper gastrointestinal hemorrhage in the absence ofother systemic involvement. The case report involves a58-year-old woman with significant cardiac history andhereditary blood disorder who came in complaining ofabdominal pain and coffee-ground emesis for two days.Computed tomography(CT) scan of the abdomen andpelvis with contrast revealed segmental wall thickeningof the proximal jejunum with hyperdense, heterog-enous luminal content. Similar findings were evident inthe left lower small bowel region, suspicious for smallbowel hematoma and the possibility of intraluminalclots. Esophagogastroduodenoscopy performed postresuscitation showed punctate, erythematous lesionsthroughout the stomach as well as regions of smallbowel mucosa that appeared scalloped, ulcerated, andhemorrhaged on contact. Despite initial treatment for immunostain-positive focal cytomegalovirus gastritis, follow-up esophagogastroduodenoscopy after two months continued to demonstrate friable and irregular duodenal mucosa hinting at a different underlying etiol-ogy. Pathology reports from analyses of biopsy samples highlighted infiltration and expansion of the lamina pro-pria and submucosa. Subsequent staining with congo red/crystal violet and appropriate subtyping established the diagnosis of AL(kappa)-type amyloidosis. The sig-nificance of this case lies in the fact that our patient did not have the typically seen diagnostic systemic involvements-namely of heart and kidneys-usually seen in primary(AL) amyloidosis patients. It was the persis-tent endoscopic findings and biopsy results which gave clues to the physicians regarding the possibility of an abnormal protein-deposition entity.
文摘AIM:To investigate the efficacy of the digitally reinforced hematoxylin-eosin polarization(DRHEP)technique for detection of amyloidosis in rectal biopsies.METHODS:One hundred hematoxylin-eosin(HE)stained rectal biopsies with Congo-red(CR)-positive amyloid depositions and 50 control cases with CRnegative amyloid-mimicking areas were scanned blinded to the CR results for amyloid depositions under both bright and polarized light,and digitally photographed using the DRHEP technique,to accentuate the faint birefringence observed in HE slides under polarization.The results of DRHEP and HE evaluation were statistically correlated with CR polarization results with respect to presence and localization of amyloid deposits as well as amyloid types.RESULTS:Amyloid deposits showed yellowish-green birefringence by DRHEP,which allowed identification of amyloidosis in 41 HE-unsuspected cases(P=0.016),31 of which only had vascular deposits.True positivity was higher,and false negativity and positivity were lower by DRHEP,compared to evaluation by HE(69%,31%,and 0.8%vs 33%,67%,and 33%,respectively;P<0.0001).The sensitivity,specificity,accuracy,and positive and negative predictive values for DRHEP were69%,98%,78.6%,98.5%,and 61.25%,respectively.Reasons for DRHEP false negativity were presence of extensive background birefringence in 12 cases,absence of CR birefringent vessel in 3 cases,and missing of the tiny deposits in 9 cases,which could be improved by experience,especially in the latter case.No correlation was found between age,gender,sites of deposits,or amyloid types.CONCLUSION:The DRHEP technique improves diagnostic accuracy when used as an adjunct or a prior step to CR staining,especially for cases with limited tissues for further analysis.
文摘The release of proinfammatory cytokines during infam-mation represents an attempt to respond to injury, but it may produce detrimental effects. The infammasome is a large, multiprotein complex that drives proinfammatory cytokine production in response to infection and tissue injury; the best-characterized inflammasome is the nod-like receptor protein-3 （NLRP3）. Once activated, infammasome leads to the active form of caspase-1, the enzyme required for the maturation of interleukin-1beta. Additional mechanisms bringing to renal inflammatory, systemic diseases and fibrotic processes were recently reported, via the activation of the inflammasome that consists of NLRP3, apoptosis associated speck-like protein and caspase-1. Several manuscripts seem to identify NLRP3 infammasome as a possible therapeutic target in the treatment of progressive chronic kidney disease. Serum amyloid A （SAA）, as acute-phase protein with also proinfammatory properties, has been shown to induce the secretion of cathepsin B and infammasome components from human macrophages. SAA is a well recognised potent activator of the NLRP3. Here we will address our description on the involvement of the kidney in autoinflammatory diseases driven mainly by secondary, or reactive, AA amyloidosis with a particular attention on novel therapeutic approach which has to be addressed in suppressing underlying inflammatory disease and reducing the SAA concentration.
