Amyloid Light-chain Amyloidosis Research Articles

Duodenal amyloidosis: a clinical case

BACKGROUND: Amyloidosis is a chronic systemic disease that, in some cases, affects the organs of the gastrointestinal tract.
 CLINICAL CASE DESCRIPTION: A 62-year-old patient complained of painless enlargement of the lymph nodes in the supraclavicular region on the left side according to the puncture biopsy of the lymph node — reactive lymphoid hyperplasia. During the examination, duodenal amyloidosis was accidentally detected. The results of additional studies to determine the type of amyloid were nonspecific. The patient refused to continue the examination.
 CONCLUSION: This clinical case of duodenal amyloidosis is unusual and clearly demonstrates the difficulties of diagnosis, including the absence of a clinic and the nonspecificity of the endoscopic and radiological picture during the examination. In addition, the absence of an established chronic disease characteristic of amyloid A amyloidosis and the results of laboratory and instrumental research methods, excluding amyloid light chain amyloidosis and transthyretin amyloidosis, emphasise the main role of clinicians in diagnosing the underlying disease.

Impact of Premedication De-Escalation on Incidence of Infusion-Related Reactions With Daratumumab.

Daratumumab is an anti-CD38 monoclonal antibody used to treat multiple myeloma and light chain amyloidosis. Because daratumumab may cause reactions after intravenous or subcutaneous (SC) administration, the manufacturer labeling recommends administration of premedications before every dose. Given incidence of infusion reactions appears to be rare after cycle 1, in April 2022, the Mayo Clinic implemented a practice change in which premedications were omitted from all daratumumab order sets after completion of cycle 1. This study investigated the safety of this practice. A retrospective chart review at the Mayo Clinic reviewed eligible patients with multiple myeloma or amyloid light-chain (AL) amyloidosis who received their first dose of daratumumab within the 4 months preceding the date of implementation (preimplementation group) or no more than 4 months after (postimplementation group) the date of implementation on April 13, 2022. Data were collected only from the first eight once per week doses of daratumumab. The primary outcome was the incidence of infusion-related reactions. Data analyzed used descriptive statistics. Nearly all patients (95.9%) received daratumumab by SC route of administration. Of the 97 patients in the preimplementation group, >90% received premedications throughout cycles 1 and 2, and five patients (5.2%) experienced infusion reactions. Of 72 patients in the postimplementation group, <20% received premedications during cycle 2 and three patients (4.2%) experienced infusion reactions. All infusion reactions occurred within the first daratumumab cycle, indicating elimination of cycle 2 premedications did not cause any infusion reactions. No patient experienced more than one infusion reaction. Omission of premedications after cycle 1 of daratumumab did not increase the incidence of infusion. Premedications may safely be omitted after cycle 1 of daratumumab when administered by the SC route.

Assessment of Tp-Te interval in patients with cardiac AL amyloidosis.

Prolonged Tp-Te interval is strongly associated with fatal ventricular arrhythmias and mortality. This association has been demonstrated in various diseases. However, the current literature does not give any information on Tp-Te interval in cardiac amyloid light-chain (AL) amyloidosis. We retrospectively screened 116 cardiac AL amyloidosis patients and 35 patients were included in the study. Demographic, laboratory, 12-lead electrocardiographic (QTc, Tp-Te V1-V6) and transthoracic echocardiographic data of the patients were analysed and compared with 35 healthy controls. QTc and Tp-Te V2-V5 were significantly prolonged in the cardiac AL amyloidosis group (p < 0.05). Also, there was a positive and statistically significant correlation between the parameters of QTc and Tp-Te V3-V6, and also between the parameters of interventricular septum thickness at enddiastole and Tp-Te V2-V5. We present the first strong evidence of prolonged Tp-Te intervals in patients with cardiac AL amyloidosis. There may also be a relationship between prolonged Tp-Te interval and the development of arrhythmia in this patient group, as in some other groups. There is a need for prospective studies examining the relationship of prolonged Tp-Te interval with arrhythmias and its prognostic significance in cardiac AL amyloidosis.

Immune checkpoint expression patterns on T cell subsets in light-chain amyloidosis: VISTA, PD-1, and TIGIT as potential therapeutic targets.

Amyloid light chain (AL) amyloidosis is a rare plasma cell dyscrasia with dismal prognosis. This study aims to investigate the T-cell immune checkpoint expression patterns in systemic AL amyloidosis and its relationship with clinicobiological traits. We examined the frequencies of V-domain immunoglobulin suppressor of T cell activation+ (VISTA+), programmed cell death 1+ (PD-1+), T cell immunoglobulin and mucin-domain-containing-3+ (Tim-3+), T cell immunoreceptor with Ig and ITIM domains+ (TIGIT+) T cells in peripheral blood (PB) and bone marrow (BM) from 19 patients with newly diagnosed AL amyloidosis. Patients with AL amyloidosis had significantly higher percentages of VISTA+ and PD-1+ T cells in PB than healthy individuals (HIs), with no statistical differences in BM. The percentages of some double-positive T cells in PB were also considerably higher in AL amyloidosis than those in HIs. Additionally, the patients with renal involvement had more PD-1+ and TIGIT+ T cells than the patients without, and PD-1+CD3+%, PD-1+CD4+%, PD-1+Treg% were positively correlated with 24-hour proteinuria levels. Furthermore, the AL amyloidosis patients had higher counts of PD-1+ Treg in PB than multiple myeloma (MM) patients, while the MM patients had higher counts of TIGIT+ T cells than AL amyloidosis patients. Collectively, this is the first report of elevated proportions of VISTA+ and PD-1+ T cells in PB of AL amyloidosis patients, indicating an immunosuppressive milieu, and the increased PD-1+ and TIGIT+ T cells were associated with renal damage. VISTA, PD-1, and TIGIT may be potential targets for reversing T-cell exhaustion in AL amyloidosis.

Amyloid Protein in AL-Amyloidosis. Natural History and Potential for Regression

Amyloid light chain amyloidosis is the most commonly seen form of systemic amyloidosis and is characterized by the accumulation of circulating monoclonal immunoglobulin light chain precursors arising from an abnormal clone of plasma cells. These light chain precursors demonstrate a propensity for misfolding, aggregation and deposition as highly stable fibrillar cross-linked beta sheets in various tissues and organs in a manner characteristic of other forms of systemic amyloidosis. There have been great advances in the treatment of the underlying plasma cell dyscrasia with improved long-term survival but the persistence of extracellular amyloid deposits in the tissues of vital organs, particularly the heart and kidney remains a significant cause of morbidity and mortality even in those patients in whom a hematological complete response has been achieved. This review focuses on the importance of early diagnosis and treatment on limiting the extent of amyloid protein accumulation and organ dysfunction and the current state of knowledge on the potential for resorption and clearance of these amyloid deposits in patients with amyloid light chain amyloidosis. The status of current novel anti-fibrillar agents is reviewed and future strategies for effectively intervening to improve organ function and survival these individuals is discussed.

Clinical characterization and outcomes of a cohort of colombian patients with AL Amyloidosis.

Amyloid light chain (AL) amyloidosis is characterized by amyloid fibril deposition derived from monoclonal immunoglobulin light chains, resulting in multiorgan dysfunction. Limited data exist on the clinical features of AL amyloidosis. This study aims to describe the clinical characteristics, treatments, and outcomes in Colombian patients with AL amyloidosis. A retrospective descriptive study was conducted at three high-complexity centers in Medellín, Colombia. Adults with AL amyloidosis diagnosed between 2012 and 2022 were included. Clinical, laboratory, histological, treatment, and survival data were analyzed. The study included 63 patients. Renal involvement was most prevalent (66%), followed by cardiac involvement (61%). Multiorgan involvement occurred in 61% of patients. Amyloid deposition was most commonly detected in renal biopsy (40%). Bortezomib-based therapy was used in 68%, and 23.8% received high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT-ASCT). Hematological response was observed in 95% of patients with available data. Cardiac and renal organ responses were 15% and 14%, respectively. Median overall survival was 45.1 months (95% CI: 22.2-63.8). In multivariate analysis, cardiac involvement was significantly associated with inferior overall survival (HR 3.27; 95% CI: 1.23-8.73; p=0.018), HDCT-ASCT had a non-significant trend towards improved overall survival (HR 0.25; 95% CI: 0.06-1.09; p=0.065). In this study of Colombian patients with AL amyloidosis, renal involvement was more frequent than cardiac involvement. Overall survival and multiorgan involvement were consistent with data from other regions of the world. Multivariate analysis identified cardiac involvement and HDCT-AHCT as possible prognostic factors.

Phase 2 Study of Daratumumab (DARA) Plus Bortezomib, Cyclophosphamide, and Dexamethasone (D-VCd) in a Diverse Patient Population with Newly Diagnosed Amyloid Light Chain (AL) Amyloidosis: Aquarius

Background: AL amyloidosis is a rare disorder in which deposition of insoluble amyloid fibrils composed of misfolded light chains in vital organs, such as the heart or kidney, leads to serious and life-threatening organ dysfunction. Cardiac involvement is the primary determinant of clinical outcomes for patients with AL amyloidosis, and survival expectations decrease with increasing cardiac stage. Subcutaneous DARA (DARA SC) in combination with VCd recently became the first and only approved treatment for newly diagnosed AL amyloidosis based on results of the phase 3 ANDROMEDA study. In the ANDROMEDA study, a higher hematologic complete response rate was consistently achieved with D-VCd versus VCd in patients with newly diagnosed AL amyloidosis, regardless of baseline cardiac stage (Kastritis E, et al. N Engl J Med. 2021;385[1]:46-58). However, cardiac involvement leads to challenges in the attribution of cardiac events to underlying disease and/or treatments. Additionally, among patients randomized to receive D-VCd in the ANDROMEDA study, 15.4% were Asian, 4.6% were Hispanic or Latino, and 3.1% were Black or African American, limiting the interpretation of safety, efficacy, and pharmacokinetic results among patients of different racial and ethnic backgrounds. Therefore, the ongoing phase 2 AQUARIUS (AMY2009) study will characterize the cardiac safety of different D-VCd treatment regimens in patients with newly diagnosed AL amyloidosis with cardiac involvement to identify potential mitigation strategies for cardiac toxicity, as well as better characterize the safety, efficacy, and pharmacokinetics of D-VCd among racial and ethnic minorities. Study Design and Methods: This ongoing multicenter, multicohort, open-label phase 2 study will enroll ~150 patients aged ≥18 years with newly diagnosed systemic AL amyloidosis and measurable disease from ~45 sites across 10 countries. Patients in Cohort 1 (n = ~120) will have cardiac involvement (AL amyloidosis Mayo Cardiac Stage II and Stage IIIa) with or without other organ involvement. Patients in Cohort 2 (n = ~30) will be of racial or ethnic minority (including ≥15 Black or African American patients) and have ≥1 organ affected by systemic AL amyloidosis. Patients in Cohort 1 will be stratified by baseline cardiac stage (Stages II and IIIa) and randomly assigned (2:1) to receive DARA SC plus immediate VCd (Arm A) or DARA SC plus deferred VCd (Arm B; Figure 1). In both arms, DARA SC (DARA 1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; 2,000 U/mL; ENHANZE ® drug delivery technology, Halozyme, Inc., San Diego, CA, USA]) will be administered QW during Cycles 1-2, Q2W during Cycles 3-6, and Q4W thereafter until a maximum of 24 cycles or the start of subsequent therapy. In Arm A, starting at Cycle 1 Day 1, VCd will be administered weekly in every 28-day cycle for a maximum of 6 cycles. In Arm B, starting at Cycle 4 Day 1, VCd will be administered weekly in every 28-day cycle for a maximum of 6 cycles. Patients in Cohort 2 will receive DARA SC plus immediate VCd. Several unique initiatives were incorporated into the study to enhance enrollment of patients of racial or ethnic minority in Cohort 2, including selecting sites from the ANDROMEDA study that enrolled racially/ethnically diverse patients, targeting new sites in diverse communities, raising awareness of AL amyloidosis and the AQUARIUS study among minority patients at the local and national levels, and educating sites on engagement of patients from diverse backgrounds. The first primary endpoint is incidence of any toxicity grade cardiac events for the different D-VCd treatment regimens (DARA SC + immediate VCd and DARA SC + deferred VCd). The second primary endpoint is trough serum concentration (C trough) of DARA at the end of QW dosing (Cycle 3 Day 1 predose). Efficacy evaluations include assessment of hematologic response and organ response. Data will be summarized using descriptive statistics. The first patient was enrolled on March 17, 2022. As of July 10, 2023, the study has enrolled 75 patients; 71 in Cohort 1 and 4 in Cohort 2. In the US, 2 of the 8 patients enrolled were of racial minority ( Figure 2). Efforts to increase enrollment of minorities continue to be optimized and new collaborative initiatives explored to ensure representative and diverse enrollment in clinical trials. The ClinicalTrials.gov Identifier is NCT05250973.

Understanding and Overcoming Biochemical Diversity in AL Amyloidosis

AbstractAmyloid fibril deposition causes progressive tissue damage and organ failure in the systemic amyloid diseases, and therapies that suppress aggregation lead to clinical benefit. Small molecules that prevent aggregation by binding to precursor proteins are effective for amyloid transthyretin (ATTR) amyloidosis. However, in amyloid light chain (AL) amyloidosis, fibrils are formed by antibody light chains and every patient has a unique protein sequence that aggregates. The highly diverse sequences of these light chains appear to determine whether an individual is at risk of amyloidosis, the distribution of amyloid deposits and the progression of disease. Light chains are therefore challenging drug targets. This review explores the parallels between AL amyloidosis and ATTR amyloidosis to describe the discovery of small molecules that can stabilize light chains. These molecules have potential as therapies for AL amyloidosis, highlighting potential opportunities for drug discovery in other diseases of protein misfolding.

Secondary Pure Red Cell Aplasia During Daratumumab/ Hyaluronidase Therapy for Multiple Myeloma

Predominantly autoimmune in origin, severe normochromic, normocytic anemia with reticulocytopenia in the setting of the normal production of leukocytes and megakaryocytic lineages is known as pure red cell aplasia (PRCA), which is unlike aplastic anemia in which all lineages are affected due to a stem cell defect. PRCA can be primary (such as autoimmune) or acquired, which can be an acute self-limited illness or a chronic disease that may be induced by medications, including immunotherapy such as monoclonal antibodies (mAbs). Daratumumab is a mAb directed against CD38 used for the treatment of multiple myeloma and systemic amyloid light-chain amyloidosis. The intravenous formulation of daratumumab received initial FDA approval, and later approval was received for the subcutaneous formulation daratumumab and hyaluronidase-fihj. The subcutaneous version increases patient convenience and has become the preferred route of administration since its approval. We herein present the case of a patient with multiple myeloma who developed acquired DNMT3A-positive PRCA while transitioning to daratumumab/hyaluronidase after initial treatment with daratumumab.

Endoscopic Manifestations and Clinical Characteristics of Localized Gastric Light-Chain Amyloidosis.

To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant.

Impaired fibrinolysis and increased clot strength are potential risk factors for thrombosis in lymphoma

AbstractThrombosis and bleeding are significant contributors to morbidity and mortality in patients with hematological cancer, and the impact of altered fibrinolysis on bleeding and thrombosis risk is poorly understood. In this prospective cohort study, we investigated the dynamics of fibrinolysis in patients with hematological cancer. Fibrinolysis was investigated before treatment and 3 months after treatment initiation. A dynamic clot formation and lysis assay was performed beyond the measurement of plasminogen activator inhibitor 1, tissue- and urokinase-type plasminogen activators (tPA and uPA), plasmin-antiplasmin complexes (PAP), α-2-antiplasmin activity, and plasminogen activity. Clot initiation, clot propagation, and clot strength were assessed using rotational thromboelastometry. A total of 79 patients were enrolled. Patients with lymphoma displayed impaired fibrinolysis with prolonged 50% clot lysis time compared with healthy controls (P = .048). They also displayed decreased clot strength at follow-up compared with at diagnosis (P = .001). A patient with amyloid light-chain amyloidosis having overt bleeding at diagnosis displayed hyperfibrinolysis, indicated by a reduced 50% clot lysis time, α-2-antiplasmin activity, and plasminogen activity, and elevated tPA and uPA. A patient with acute promyelocytic leukemia also displayed marked hyperfibrinolysis with very high PAP, indicating extreme plasmin generation, and clot formation was not measurable, probably because of the extremely fast fibrinolysis. Fibrinolysis returned to normal after treatment in both patients. In conclusion, patients with lymphoma showed signs of impaired fibrinolysis and increased clot strength, whereas hyperfibrinolysis was seen in patients with acute promyelocytic leukemia and light-chain amyloidosis. Thus, investigating fibrinolysis in patients with hematological cancer could have diagnostic value.

Characterization of N-Terminal Asparagine Deamidation and Clipping of a Monoclonal Antibody.

This study presents a novel degradation pathway of a human immunoglobulin G (IgG) molecule featuring a light chain N-terminal asparagine. We thoroughly characterize this pathway and investigate its charge profiles using cation exchange chromatography (CEX) and capillary isoelectric focusing (cIEF). Beyond the well-documented asparagine deamidation into isoaspartic acid, aspartic acid, and succinimide intermediate, a previously unreported clipping degradation pathway is uncovered. This newly identified clipped N-terminal IgG variant exhibits a delayed elution in CEX, categorized as a "basic variant", while retaining the same main peak isoelectric point (pI) in cIEF. The influence of temperature and pH on N-terminal asparagine stability is assessed across various stressed conditions. A notable correlation between deamidation percentage and clipped products is established, suggesting a potential hydrolytic chemical reaction underlying the clipping process. Furthermore, the impact of N-terminal asparagine modifications on potency is evaluated through ELISA binding assays, revealing minimal effects on binding affinity. Sequence alignment reveals homology to a human IgG with the germline gene from Immunoglobulin Lambda Variable 6-57 (IGLV6-57), which has implications for amyloid light-chain (AL) amyloidosis. This discovery of the N-terminal clipping degradation pathway contributes to our understanding of immunoglobulin light chain misfolding and amyloid fibril deposition under physiological conditions.

P-436 Clonal hematopoiesis of indeterminate potential (CHIP) in patients with amyloid light chain (AL) amyloidosis

P-436 Clonal hematopoiesis of indeterminate potential (CHIP) in patients with amyloid light chain (AL) amyloidosis

Cardiovascular toxicity from therapies for light chain amyloidosis.

Amyloid light-chain (AL) amyloidosis is a hematological disorder characterized by abnormal proliferation of a plasma cell clone producing monoclonal free light chains that misfold and aggregate into insoluble fibrils in various tissues. Cardiac involvement is a common feature leading to restrictive cardiomyopathy and poor prognosis. Current first-line treatments aim at achieving hematological response by targeting the plasma cell clones, and these have been adapted from multiple myeloma therapy. Patients with AL amyloidosis often exhibit multiorgan involvement, making them susceptible to cancer therapy-related cardiovascular toxicity. Managing AL amyloidosis is a complex issue that requires enhanced knowledge of the cardio-oncological implications of hematological treatments. Future research should focus on implementing and validating primary and secondary prevention strategies and understanding the biochemical basis of oncological therapy-related damage to mitigate cardiovascular toxicity.

Diagnosis for Chinese patients with light chain amyloidosis: a scoping review

Background Amyloid light chain (AL) amyloidosis is the most common systemic amyloidosis. The objective of this scoping review was to map the available literature on the diagnosis of AL amyloidosis in China. Materials and Methods The published academic papers related to the diagnosis of AL amyloidosis were screened from 1 January 2000 to 15 September 2021. Chinese patients who have suspected AL amyloidosis were included. The included studies were categorized into accuracy studies and descriptive studies based on if the studies supplied the diagnostic accuracy data or not. The information on the diagnostic methods reported by included studies was synthesized. Results Forty-three articles were included for the final scoping review, with 31 belonging to descriptive studies and 12 having information on diagnostic accuracy. Although cardiac involvement was second top in Chinese patients with AL amyloidosis, a cardiac biopsy was rare. Next, we found light chain classification and monoclonal (M-) protein identification were essential methods for the diagnosis of AL amyloidosis in China. In addition, some combined tests (e.g. immunohistochemistry and serum free light chain, immunohistochemistry and immunofixation electrophoresis, and serum free light chain and immunofixation electrophoresis) can increase the sensitivity of the diagnosis. Finally, several adjuvant methods (e.g. Imaging, N-terminal-pro hormone BNP, and brain natriuretic peptide test) were important for AL amyloidosis diagnosis. Conclusion This scoping review details the characteristics and results of the recently published studies on diagnosing AL Amyloidosis in China. Biopsy is the most important method for AL Amyloidosis diagnosis in China. In addition, combined tests and some adjuvant methods played essential roles in the diagnosis. Further research is required to determine an acceptable and feasible diagnostic algorithm after symptom onset. REGISTRATION: INPLASY2022100096 KEY MESSAGES This scoping review details the characteristics and results of the recently published studies on diagnosing Amyloid light chain (AL) Amyloidosis in China. Biopsy is the most important method for AL Amyloidosis diagnosis in China. Combined tests and some adjuvant methods played essential roles in the diagnosis.

Linear discriminant analysis on electrocardiogram achieved classification of cardiac involvement status in amyloid light-chain amyloidosis

ObjectivesCardiac amyloidosis (CA) is the most crucial determinant of amyloid light-chain (AL) amyloidosis patients' prognosis. We attempted cardiac involvement prediction by 12‑lead electrocardiograph (ECG) and echocardiography (UCG) in AL amyloidosis patients. Materials and methodsFifty patients with histologically confirmed AL amyloidosis underwent gadolinium-enhanced magnetic resonance imaging (Gd-MRI), and CA was assessed using late gadolinium enhancement. ECG and UCG parameters were measured on admission. Fisher's linear discriminant analysis was used to create a model for predicting CA using the ECG and UCG parameters. ResultsPrediction by five ECG parameters [QTc(B), QRS-T-angle, III-QRS, aVF-QRS, and V3-R] showed the best performance. Average sensitivity and specificity in the modeling sets, utilizing a linear discriminator based on these five variables, were 99.2 % and 96.8 % and in validation sets, 94.2 % and 90.3 %, respectively. In addition, we tested this model on an additional 26-patient cohort and survival analysis using the Kaplan-Meier method, and significant differences between CA positively predicted and negatively predicted patients were observed. ConclusionHere, we suggest the application of a condensed classical multivariate statistical technique for the diagnosis of CA. It can be used as a guide to invasive endomyocardial biopsy for those in whom Gd-MRI is contraindicated and as a guide for repeat Gd-MRI in follow-up of AL amyloidosis.

#3597 MONOCLONAL GAMMOPATHY AS A RISK FACTOR FOR ARTERIOVENOUS FISTULA PRIMARY FAILURE

Abstract Background and Aims Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis (HD) in most patients. However, postoperative complications such as primary failure (PF) with a reported incidence between 20-60% remain a major problem. Patients diagnosed with monoclonal gammopathy (MG) are at increased risk of thrombotic events, either due to the disease itself or the chemotherapy used for its treatment. The aim of this study was to evaluate whether the presence of MG was associated with primary AVF failure. Method We performed a retrospective single-center case-control study including 103 patients observed in our vascular access consultation for planning their first HD access. Demographic and clinical data were collected, such as the presence of diabetes, hypertension, cardiovascular disease and MG. Distal AVF was the access of choice when possible. Primary failure was defined as incapacity to use AVF for HD because of failure to mature or thrombosis. Univariate analysis was performed, and a logistic regression was applied to access predictors of PF. A p-value inferior to 0,05 indicated statistical significance. Results In total 14 (13.6%) patients had MG (11 multiple myeloma, 1 light-chain deposition disease, 1 proliferative glomerulonephritis with monoclonal immunoglobulin deposits and 1 amyloid light-chain amyloidosis). Regarding the AVF location, 13 patients constructed a constructed a distal AVF and 1 patient a proximal AVF. When compared to the group of 89 patients who did not have MG, there were no significance differences in sex, age, prevalence of diabetes and cardiovascular disease neither in AVF construction site. Arterial hypertension was more frequent in the group of patients without MG (93.2% versus 64.3%, p = 0.007). PF occurred in 57.1% (8/14) of patients with MG and in 27% (24/89) of those without MG (p = 0.032). In logistic regression, the presence of MG was the only predictor of primary AVF failure (OR 4.39 95% CI: 1.23-15.75). Conclusion In our study, we found that a patient with monoclonal gammopathy has a 4-fold increased risk for primary AVF failure comparing to the general chronic kidney disease patients. Therefore, a careful evaluation must be made when planning for AVF placement in these patients, balancing individual life's expectancies and monoclonal gammopathy prognosis.

Cardiac Amyloidosis Imaging.

Differentiation between amyloid light-chain (AL) and amyloid transthyretin (ATTR) cardiac amyloidosis is critical because of the differences in treatment. AL cardiac amyloidosis is treated with chemotherapy or stem-cell transplantation. ATTR cardiac amyloidosis is treated with disease-modifying

Colonic amyloidosis: Rare endoscopic findings mimicking a depressed neoplastic lesion.

A colonic depressed lesion was found in a 77-year-old man and suspected as a neoplastic lesion using conventional endoscopy. Magnifying endoscopy, however, did not support it and biopsy revealed the lesion to be AL amyloidosis.

Droxidopa for refractory neurogenic orthostatic hypotension in amyloid light chain amyloidosis

Neurogenic orthostatic hypotension (nOH) secondary to amyloidosis is a rare condition associated with significant blood pressure (BP) drops and problematic symptoms for patients. There is limited literature on the management of nOH secondary to amyloidosis. In this report, we describe a case on a 60-year-old female with an extensive past medical history, including amyloidosis, pulmonary hypertension, heart failure with preserved ejection fraction, and episodic hypotension, who presents to the hospital with dizziness and home systolic BP readings in the 80s. Due to hypoperfusion, she eventually developed acute kidney failure and was transferred to the intensive care unit (ICU) for intermittent continuous renal replacement therapy with pressor support using norepinephrine. She had difficulty maintaining adequate BPs while on midodrine, so fludrocortisone, followed by pseudoephedrine, were added to improve her pressures. She was subsequently transferred out of the ICU, but her BPs still remained low, and she was not able to sit up without getting dizzy. Droxidopa was eventually added on to help treat her refractory nOH. After droxidopa initiation, her BPs improved and she was able to sit up without dizziness and was finally discharged home. This case report demonstrates the therapeutic usefulness of droxidopa in improving both BPs and symptoms in refractory nOH secondary to amyloidosis.