Diffuse Deposits Research Articles

The role of in-channel vegetation in driving and controlling the geomorphic changes along a gravel-bed river

Gravel-bed rivers are fluvial systems featuring highly complex morphological and evolutionary patterns because of their configuration characterized by the contemporary presence of many distinct morphological units. Complexity can also be observed in the response of gravel-bed rivers to flow conditions, which can be highly varied. This work aims to analyze the evolution of gravel and vegetated areas in a gravel-bed river during a period of persistent low flow conditions, focusing also on the responses exhibited by the different types of riparian vegetation. To this end, a 2200 m-long segment of the Piave River (NE Italy) was considered. It was surveyed twice by LiDAR (August 2003 and August 2010), permitting the analysis of the spatial-temporal evolution of gravel and vegetated areas through both cover type analysis and the DoD technique. During the study period (August 2003 – August 2010), the flow conditions were constantly ordinary, i.e., under-bankfull. The cover type analysis stressed an increase of +115 % in vegetated areas, which have diffusely colonized the river corridor. However, the low flow conditions also induced geomorphic changes with 54 % of the study area affected by variations in surface elevation. The DoD computed a diffuse deposition over the main and secondary channels, while erosion was observed in specific areas of the main fluvial island and along the right floodplain. In terms of vegetation changes, five eroded patches were identified, which contributed to 60 % of the vegetated area entirely eroded in the study reach. These patches were mainly characterized by mature vegetation taller than the mean vegetation height observed over the study reach. Therefore, the analysis of the response of the Piave River to persistent under-bankfull flows stressed a complex evolution of the gravel and vegetated areas, which can be appreciated also because of low flow conditions, emphasizing the composite dynamics typical of a gravel-bed river. These results could improve riverine management considering vegetation structure and dimension, as well as the geomorphic settings of gravel-bed rivers in view of future low flow conditions.

#5132 POST-COVID-19 ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE: TWO CLINICAL CASES

Abstract Background and Aims Acute kidney injury is a common complication in patients hospitalized with COVID-19, has multiple aetiologies, and is usually multifactorial. We present two cases of anti-glomerular basement membrane (anti-GBM) disease diagnosed after SARS-CoV-2 infection, suggesting a causal correlation. Case Reports A 76-year-old female, with chronic kidney disease (serum creatinine 1.5mg/dL), hypertension, weight loss (16 Kg/6 months) and a pancreatic nodule under surveillance, presented to the emergency department with 1 week of nausea, vomits, diarrhoea and oliguria, as well as a history of mild SARS-CoV-2 infection 2 weeks before presentation. Lab work revealed severe anaemia (7.4 g/dL), inflammatory markers elevation, nephrotic proteinuria (proteinuria/creatininuria ratio 30 g/g), leucoerythrocyturia, serum creatinine of 19.3 mg/dL, hyperkalaemia and metabolic acidosis requiring dialysis induction. Renal ultrasound showed signs of chronicity and several cysts. Aetiological study disclosed positive anti-GBM antibody (1800 U/L) and negative ANCA. Complementary study failed to identify pulmonary involvement or neoplasms. Given the severity of the renal dysfunction along with the absence of alveolar haemorrhage, immunosuppression and plasmapheresis were not initiated. Patient was discharged and remains dialysis dependent. A 65-year-old male smoker with type 2 diabetes and combined pulmonary fibrosis and emphysema, presented in the emergency department with 2 months of asthenia, weight loss and anaemia, in addition to dyspnoea and haemoptysis in the past 3 days. Lab work exposed moderate anaemia (9.7 g/dL), elevated inflammatory markers, serum creatinine of 1.18 mg/dL (previously 0.8 mg/dL), leucoerythrocyturia and positive SARS-CoV-2 test. Angio-Computed Tomography exhibited known pulmonary fibrosis and possible bacterial superinfection. Despite antibiotic therapy (10 days of levofloxacin), haemoptysis remained and kidney function continuously worsened (serum creatinine 2.1 mg/dL). Complementary study showed positive ANCA-MPO (1125.4 U/L) and anti-GBM antibody (460.8U/L). Renal ultrasound was innocent. Kidney biopsy revealed: 6 glomeruli with cellular crescents with segmental necrosis, 3 with focal Bowman's capsule rupture; erythrocyte casts; intimal arterial fibrosis; moderate tubular atrophy; diffuse linear deposits of IgG. Immunosuppression was initiated with prednisolone (1 mg/Kg/day), cyclophosphamide (3x 12.5mg/Kg-750 mg, 2x 500 mg), rituximab (2x 1g), immunoglobulin (1x 2 g/Kg) and plasmapheresis (15 sessions). Kidney function continued to deteriorate (maximum serum urea 306 mg/dL, maximum serum creatinine 6.92 mg/dL) requiring dialysis induction 3 weeks after the beginning of immunosuppression. Even though haemoptysis ceased, the patient remains dialysis dependent 8 months after. Conclusion Literature reports an increase of Anti-GBM disease since the beginning of the pandemic. The presented cases support the apparent correlation, suggesting SARS-CoV-2 as a precipitant of this disease by endothelial injury with basal membrane exposure and autoantibody development. In the second case, the authors assume a subacute ANCA-MPO vasculitis with superimposed anti-GBM (eventually precipitated by COVID-19). Even though the causal association is not established, we highlight the importance of clinical suspicion of this rare aetiology in cases of acute kidney injury after SARS-CoV-2 infection.

#5295 SECONDARY MEMBRANOUS NEPHROPATHY WITH IGA DEPOSITS IN A PATIENT WITH PRIMARY CILIARY DYSKINESIA

Abstract Background and Aims Membranous nephropathy and IgA nephropathy are two types of common glomerulonephritis worldwide. There are reports of the coexistence of these glomerulopathies, mostly with mesangial expansion and IgA deposits. Furthermore, primary ciliary dyskinesia is rarely associated to glomerulopathy. Thus, we report a case of a patient with primary ciliary dyskinesia with renal biopsy demonstrating membranous glomerulopathy associated with IgA and IgG deposits exclusively in glomerular basement membrane, without complement deposition. Method Case report. Results A 18 years-old man was referred from the nephropediatric outpatient clinic with subnephrotic hematuria and proteinuria. His medical history included a clinical diagnosis of primary ciliary dyskinesia due to a history of several respiratory infections since birth, asthma, rhinitis and bronchiectasis and a 15 years-old brother with a similar history. He was diagnosed with idiopathic thrombocytopenic purpura at age of one year-old and received prednisone. At 3 years-old he presented with nephrotic syndrome, hematuria and hypertension, and was treated with intravenous methylprednisolone and oral cyclophosphamide for three months. Renal biopsy demonstrated mesangial expansion and thickening of the glomerular basement membrane (GBM), without adequate material for immunofluorescence. Because proteinuria and hematuria persisted, the prednisone dose was increased to 2 mg/kg/day and cyclosporine was started. After 5 years on these medications, persisting with proteinuria, a second biopsy was performed and showed 16 glomeruli, three globally sclerosed and the others with diffuse thickening of the GBM, without other alterations, focal interstitial fibrosis and tubular atrophy and diffuse granular deposits of IgA 1+ and IgG 2+ along the GBM. Cyclosporine and prednisone were discontinued. At age of 18 years-old, he was admitted to adult glomerulonephritis clinic with significant developmental delay (weight 28.6kg and height 1.29m2), no edema and normal arterial blood pressure with RAAS inhibition. Laboratory tests: Hb 8.9 g/dL, serum iron 12 mcg/dL, Creatinine 0.7 mg/dL, albumine 2.3 g/dL. Serologies were negative for syphilis, hepatitis B and C, HIV, ANA and anti-DNA, with normal complement C3, C4 and C1q. Urinalysis revealed proteinuria 1+, hematuria 16.000/mL and proteinuria 1.400 mg/d. CT scan showed symmetrical bronchiectasis in both lungs, with mucoid endobronchial impingement and diffuse bronchial parietal thickening; and chronic post-thrombotic changes with calcified thrombi in the left renal vein, extending into the inferior vena cava. A third renal biopsy was performed showing 38 of 45 (84%) globally sclerosed glomeruli without mesangial matrix changes or capsular adhesions. GBM was thickened with spicules and holes and reactive podocytes. The tubulointerstitial compartment showed moderate atrophy and fibrosis (40-50%). Immunofluorescence microscopy evidenced strong immunoreactivity of IgG 3+/3+, IgA 3+/3+, Kappa 3+/3+ and Lambda 2+/3+, in granular pattern exclusively in GBM, without C3. Electron microscopy showed four sclerosed glomeruli, without deposits. Immunohistochemistry staining for IgG1 2+/3+, and it was negative for PLA2R, NELL-1, THSD7A, Exostosin-1 and 2, IgG 2, IgG3 and IgG4. The patient was maintained with supportive treatment, with RAAS inhibition and SGLT2 inhibitors, without immunosuppression. Conclusion This case highlights the codominance of IgG1 and IgA deposits along the MBG, without proliferation or mesangial deposition and without complement activation, in a patient with membranous nephropathy and primary ciliary dyskinesia, a condition rarely associated with glomerulopathies. Although rare, such renal biopsy findings reinforce the need for a better understanding of the different mechanisms of membranous nephritis, in addition to better understanding and management of treatment in this situation.

Amyloid goiter secondary to familial Mediterranean fever with E148Q mutation: A unique case.

Amyloid goiter secondary to familial Mediterranean fever with E148Q mutation: A unique case.

Cancer-associated Regional Ischemic Myopathy: A Rare Immune Myopathy (P9-8.008)

<h3>Objective:</h3> To describe clinical and pathological features of a rare immune myopathy featured by regional ischemia in the setting of cancer. <h3>Background:</h3> Regional ischemic immune myopathy (RIIM) is a rare disorder attributed to myovasculopathy and considered paraneoplastic. It has a high mortality rate. Contrary to dermatomyositis, where microvasculopathy leads to perifascicular pathology and sometimes muscle ischemia, RIIM is characterized by regional necrosis in border zones between perimysial vessels. <h3>Design/Methods:</h3> Review of patient’s clinical and laboratory findings. <h3>Results:</h3> An 81-year-old man manifested subacute proximal limb weakness, dysphagia, and 25-pound weight loss. He had stage IV prostate cancer, diagnosed 3 months prior to weakness-onset. Examination revealed mild facial weakness, flaccid dysarthria, moderate-to-severe neck and limb girdle weakness and atrophy. Videofluoroscopic swallow study showed severe oropharyngeal dysphagia with aspiration. CK was 689 U/L (normal 39–108 U/L) at presentation but 6,145 U/L six weeks earlier. Myositis-associated and HMGCR antibodies were negative. EMG showed proximal-predominant myopathic changes with fibrillation potentials. Muscle biopsy revealed several well-demarcated areas of ischemia involving adjacent fascicles. Necrotic fibers were in a similar early stage of necrosis with no macrophagic infiltration and diffuse sarcoplasmic C5b-9 deposition. A few small collections of perimysial perivascular inflammatory cells were present in the areas of the specimen not affected by ischemia. There was patchy capillary depletion and dilation; some capillaries in areas not affected by ischemia showed complement deposition. Myxovirus resistance protein A (MxA) expression occurred diffusely, especially in necrotic fibers, but without perifascicular predominance. Patient received IVIG 2g/Kg and prednisone 40 mg daily. The limb weakness stabilized while the dysphagia progressed. He expired 3 weeks later. <h3>Conclusions:</h3> RIIM is a rare myovasculopathy leading to muscle weakness in the setting of cancer. In keeping with published data, it has a poor prognosis. The identification of RIIM myopathological changes should trigger the search for underlying malignancy in patients without known cancer. <b>Disclosure:</b> Dr. Granger has nothing to disclose. Dr. Soontrapa has nothing to disclose. Dr. Klein has a non-compensated relationship as a Klein with Neurology Journal that is relevant to AAN interests or activities. Dr. Milone has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Milone has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Genetics, AAN. The institution of Dr. Milone has received research support from Mayo Clinic, CCaTS-CBD. The institution of Dr. Milone has received research support from Mayo Clinic, SGP Award. The institution of Dr. Milone has received research support from MDA for Care Center grant. The institution of Dr. Milone has received research support from Regenerative medicine Minnesota.

Clinical characterization of polycythemia vera associated with IgA nephropathy in a single Chinese center: A case series

Polycythemia vera (PV) is a myeloproliferative neoplasm which is characterized by excessive production of erythrocytes as well as myeloid and megakaryocytic proliferation. PV associated with IgA nephropathy (IgAN) has rarely been reported in the literature. The long-term renal prognosis of these patients is unknown. Clinical and pathological characteristics of 7 patients with renal biopsy-proven IgAN associated with PV were retrospectively analyzed. The 7 patients were all males, with a mean age of 49.1 ± 18.8 years when admitted to our hospital. Systemic symptoms include: hypertension in case 2, 3, 5, and 6, splenomegaly in case 2, 4, and 5, and multiple lacunar infarction in case 6. Bone marrow biopsy test revealed relative erythroid hyperplasia and atypical megakaryocyte proliferation which consistent with a chronic myeloproliferative neoplasm. All patients had JAK2V617F and BCR-ABL tested, and JAK2V617F positive in 2 patients. Mild mesangial proliferation was observed in 5 patients and moderate/severe mesangial proliferation in 2patients. Immunofluorescence mainly showed diffuse granular deposition of dominant IgA in mesangium. After follow-up of 56.7 ± 44.0 months, hemoglobin level was 144 ± 29 g/L and hematocrit lever was 0.470 ± 0.03, compared with 187 ± 29 g/L and 0.563 ± 0.087 respectively when admitted to our hospital. The urine protein was 0.85 ± 0.64 g/24 h compared with 3.97 ± 4.68 g/24 h. Case 3 progressed to end stage renal disease and had received hemodialysis for 5 years before renal transplantation. The results of this study showed that PV associated with IgAN mainly occurs in males and is often accompanied by hematuria and mild-to-moderate renal insufficiency. The long-term prognosis was good for most patients, and few progressed relatively quickly to end stage renal disease.

Anterior horn damage in brachial multisegmental amyotrophy with superficial siderosis and dural tear: an autopsy case report

BackgroundPatients with superficial siderosis (SS) rarely show brachial multisegmental amyotrophy with ventral intraspinal fluid collection accompanied with dural tear.Case presentationWe describe spinal cord pathology of a 58-year-old man who developed brachial multisegmental amyotrophy with ventral intraspinal fluid collection from the cervical to lumbar spinal levels accompanied with SS, dural tear, and snake-eyes appearance on magnetic resonance imaging (MRI). Radiological and pathological analyses detected diffuse and prominent superficial deposition of hemosiderin in the central nervous system. Snake-eyes appearance on MRI expanded from the C3 to C7 spinal levels without apparent cervical canal stenosis. Pathologically, severe neuronal loss at both anterior horns and intermediate zone was expanded from the upper cervical (C3) to middle thoracic (Th5) spinal gray matter, and these findings were similar to compressive myelopathy.ConclusionExtensive damage of the anterior horns in our patient may be due to dynamic compression induced by ventral intraspinal fluid collection.

Rapid Eye Movement Sleep, Neurodegeneration, and Amyloid Deposition in Aging.

Rapid eye movement (REM) sleep is markedly altered in Alzheimer's disease (AD), and its reduction in older populations is associated with AD risk. However, little is known about the underlying brain mechanisms. Our objective was to investigate the relationships between REM sleep integrity and amyloid deposition, gray matter volume, and perfusion in aging. We included 121 cognitively unimpaired older adults (76 women, mean age 68.96 ± 3.82 years), who underwent a polysomnography, T1-weighted magnetic resonance imaging, early and late Florbetapir positron emission tomography scans to evaluate gray matter volume, perfusion, and amyloid deposition. We computed indices reflecting REM sleep macro- and microstructural integrity (ie, normalized electroencephalographic spectral power values). Voxel-wise multiple regression analyses were conducted between REM sleep indices and neuroimaging data, controlling for age, sex, education, the apnea-hypopnea index, and the apolipoprotein E ε4 status. Lower perfusion in frontal, anterior and posterior cingulate, and precuneus areas was associated with decreased delta power and electroencephalographic slowing (slow/fast frequencies ratio), and increased alpha and beta power. To a lower extent, similar results were obtained between gray matter volume and delta, alpha, and beta power. In addition, lower REM sleep theta power was more marginally associated with greater diffuse amyloid deposition and lower gray matter volume in fronto-temporal and parieto-occipital areas. These results suggest that alterations of REM sleep microstructure are associated with greater neurodegeneration and neocortical amyloid deposition in older adults. Further studies are warranted to replicate these findings, and determine whether older adults exhibiting REM sleep alterations are more at risk of cognitive decline and belonging to the Alzheimer's continuum. ANN NEUROL 2023;93:979-990.

Serum amyloidosis: a cardiac amyloidosis.

A 75-year old male with a history of membranoproliferative glomerulonephritis requiring kidney transplant, carpal tunnel, and peripheral neuropathy presented with new heart failure. An echocardiogram revealed moderate, concentric left ventricular hypertrophy (LVH) despite normal electrocardiographic voltage. To evaluate for the aetiology of unexplained LVH, a cardiac magnetic resonance (CMR) was performed which showed increased wall thickness with markedly increased T1 relaxation time and extensive, near-transmural late gadolinium enhancement throughout the myocardium (Panels A–C, green arrows), findings highly concerning for cardiac amyloidosis (CA). Despite this, a 21.5 mCi Tc-99 m pyrophosphate (Tc-PyP) scan and comprehensive serum (Panels D and E) and urine light chain analysis showed no evidence of transthyretin or immunoglobulin light chain CA, respectively. Despite these negative findings, the patient was referred for endomyocardial biopsy due to high clinical concern for CA. His biopsy revealed diffuse myocardial amyloid deposition (Panels E and F) which was ultimately identified as serum amyloid A (AA) protein on mass spectrometry. AA-CA is a rare form of cardiac amyloidosis caused by deposition of SAA protein—an acute phase reactant—in the myocardium. This disorder is most commonly observed in patients with longstanding chronic inflammatory conditions and is frequently missed by conventional light chain and Tc-PyP analysis. Renal dysfunction is a key feature of AA-CA and is present in a most cases. This case highlights the importance of having a low threshold to pursue further testing including invasive tissue biopsy when typical CA CMR features are present even in the absence of confirmatory non-invasive testing.

A CASE OF ORPHAN HYALINE FIBROMATOSIS SYNDROME IN UKRAINE

Background. Hyaline fibromatosis syndrome is a rare, highly dramatic, autosomal recessive multisystem disorder. The basis of the disease is the abnormal diffuse deposition of hyaline material in the connective tissue and internal organs. Mutations in the CMG2 gene (also known as the ANTXR2 gene) cause the disease. CMG2 encodes a transmembrane protein involved in endothelial development. Hyaline fibromatosis syndrome involves two allelic diseases that have the same phenotype. These are infantile systemic hyalinosis and juvenile hyaline fibromatosis. Common signs of these diseases are pain, joint contractures, skin lesions (thickening of the skin with areas of hyperpigmentation, pearl-sized nodules or papules), subcutaneous nodules on the head, neck, and extremities, gingival hypertrophy, osteopenia, protein-losing enteropathy, increased susceptibility to infectious diseases. Diseases differ in the time of the first clinical signs onset, the severity of the course, and the life expectancy of patients. In the case of infantile systemic hyalinosis, the prognosis is fatal. Hyaline fibromatosis syndrome is an orphan disease that is very difficult to diagnose. There is no pathogenetic treatment for the disease today. Clinical case. We described a case of hyaline fibromatosis syndrome in a boy who was observed and treated at the Municipal Non-Profit Enterprise of Sumy Regional Council "Regional Children's Clinical Hospital" (Ukraine). The diagnosis was made based on medical and genetic analysis. The early manifestation of symptoms and the severe course of the disease forced us to think about infantile systemic hyalinosis in the child. Along with characteristic external phenotypic signs, severe enteropathy with protein loss and persistent infections were observed in the child. As far as we know, this is the first case of the disease diagnosed in Ukraine. This publication aims to draw medical professionals' attention to the diversity of the course of genetic diseases in children. Comprehensive care, timely and symptomatic treatment make it possible to prolong the life of patients.

Bilateral ocular deposit of chlorpromazine

Chlorpromazine is a medication widely used in psychiatry for the treatment of psychoses, especially schizophrenia. Since 1964, published articles have been correlating this medication with the appearance of ocular alterations. In this paper, we report the case of a 65-year-old patient with ocular effects due to long-term therapy with chlorpromazine. Biomicroscopy of both eyes presented diffuse granular brown deposits, most prominent at the deep stroma and corneal endothelium level. Also showed anterior subcapsular brown deposits with a stellate pattern [...]

Neuropathological autopsy findings in an individual with Alzheimer’s disease who received long‐term treatment with lecanemab (BAN2401)

AbstractBackgroundAnti‐amyloid antibodies administered to patients with Alzheimer’s disease can result in marked reduction of brain amyloid as measured by neuroimaging with amyloid PET ligands. However, there is a lack of pathological data. Here we present neuropathological findings in a patient who received ∼173 weeks of (interrupted) treatment with lecanemab (BAN2401), a humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated β‐amyloid species (protofibrils) and insoluble fibrils, in a Phase 2 study (NCT01767311, Alz Res Therapy 2021;13:80).MethodBrain autopsy was performed on an ∼85 year old whose lecanemab treatment history over 6 years was: 79 weeks 10mg/kg monthly in the double‐blind (DB) phase, then 98 weeks without treatment, then 94 weeks at 10mg/kg biweekly in the open‐label extension (OLE) phase, followed by ∼12 weeks of treatment discontinuation prior to death.ResultClinically, memory symptoms started age ∼77. Study entry was at age ∼80, with mild dementia, CDR 0.5, CDR‐SB 3, and MMSE 24. Florbetapir PET scan was positive at baseline, and negative after 53 weeks DB treatment and at start of OLE. These findings and clinical measures are shown in Table 1. ARIA was not observed during the study. Autopsy showed low brain weight (1052g) with diffuse atrophy, including hippocampi, consistent with atrophy seen on clinical MRI scans. Microscopic findings showed tau pathology including tangles and threads (by AT8 antibody and Bielschowsky staining) throughout neocortex (Braak NF stage VI; B3). Beta‐amyloid immunohistochemical stain (6E10) showed only modest amyloid load (Thal phase 2; A1), with near‐absence of diffuse amyloid deposits and only scattered clusters of neuritic plaques (CERAD stage B; C2).ConclusionIn this autopsy of an individual with Alzheimer’s disease treated with lecanemab, neuropathological changes showed tau and β‐amyloid deposits. However, the pattern of significant tau pathology, accompanied by only a mild degree of β‐amyloid deposits, (A1B3C2), is uncommon in typical (untreated) Alzheimer’s disease. For example, in the NACC neuropathology dataset, only 2% of brains with Braak B2 or B3 show Thal stage A0 or A1. This pattern suggests that lecanemab treatment resulted in a reduction in brain amyloid, consistent with the amyloid PET scanning results in this patient.

Closure of a dural defect as a cause of superficial siderosis: does early dural repair lead to a better outcome? Illustrative case.

Superficial hemosiderosis (SS) of the central nervous system is a rare condition that is caused by chronic, repeated hemorrhage into the subarachnoid space. The subsequent deposition of hemosiderin in the brain and spinal cord causes neurological deterioration. In this report, the authors describe a repair procedure for SS associated with a dural defect in the thoracic spine. A 75-year-old man presented with tinnitus symptoms that began about 1 year prior. Subsequently, his hearing loss progressed, and he gradually became unsteady on walking. Magnetic resonance imaging (MRI) of the head showed diffuse hemosiderin deposition on the surface of the cerebellum. Thoracic MRI showed ventral cerebrospinal fluid leakage of T2-7, and computed tomography myelography showed leakage of contrast medium that appeared to be a dural defect. Dural closure was successful, and MRI showed decreased fluid collection ventral to the dura. The patient's symptoms of wobbliness on walking and tinnitus improved dramatically from the postoperative period. Dural abnormalities of the spine must always be considered as one of the causes of SS. Early dural closure is an effective means of preventing the progression of symptoms.

Abstract 12887: Lightning Strikes Twice - A Case of Light Chain and Attr Amyloidosis

The most common subsets of amyloidosis that affect the heart include light chain (AL) and transthyretin (ATTR). While both types cause diffuse amyloid fibril deposition within the interstitial space of the myocardium, they arise from two different precursors. AL amyloidosis results from misfolded monoclonal light chains, whereas ATTR amyloidosis results from misfolded transthyretin monomers. This distinction is essential as it suggests that a diagnosis of one disease does not exclude the existence of the other. We present a unique case of a patient with evidence of both systemic ATTR and AL amyloidosis occurring concurrently. An 80-year-old male with a past medical history of severe mitral regurgitation S/p mechanical mitral valve replacement, rotator cuff tear, bilateral carpal tunnel syndrome, and multiple hospitalizations for decompensated systolic heart failure was referred to cardiomyopathy clinic. He presented with class III New York Heart Association (NYHA) symptoms, including significant limitations in activity due to dyspnea. An echocardiogram demonstrated severe left ventricular hypertrophy with a low global longitudinal strain, an apical sparing pattern suspicious of amyloidosis. Monoclonal gammopathy workup showed an elevated lambda free light chain. Subsequent bone marrow biopsy demonstrated plasma cell dyscrasia and amyloid deposition in hypocellular bone marrow. Mass spectrometry showed both lambda light chain and transthyretin amyloid protein. He had elevated cardiac biomarkers, speaking for advanced cardiac involvement, together with nephrotic range proteinuria. He was started on chemotherapy/immunotherapy, with daratumumab, bortezomib and dexamethasone. He was in end stage heart failure requiring inotropic support. Few weeks after chemotherapy, he transitioned toward hospice care. In conclusion, we present a rare case of ATTR and AL amyloidosis coinciding simultaneously that demonstrates the importance of having high index of suspicion for this disease, a stepwise and thorough diagnostic approach highlighting the importance of mass spectroscopy after amyloid protein detection.

Topographic Distribution Pattern in Hepatic Amyloidosis Presenting with Portal Hypertension

The liver is often involved in both primary and secondary forms of amyloidosis. Significant clinical evidence of portal hypertension is relatively uncommon and seems to be related to the reduced sinusoidal lumen and increased resistance to blood flow due to massive perisinusoidal amyloid deposits. The relationships between the pattern and extent of amyloid deposition in patients presenting with portal hypertension have not yet been clearly demonstrated. This study is focusing on the topographic distribution of amyloidosis in patients presenting with portal hypertension. The study included biopsy-proven cases of hepatic amyloidosis. The clinical, biochemical, and serological data, involvement of the extrahepatic organs, and HVPG values were recorded. Tissue sections were re-evaluated for the distribution patterns of amyloid deposits. We had 41 patients with hepatic amyloidosis, of which, 32 were male. A mixed pattern (sinusoidal and vascular) was the most common (32/41; 78%). Hepatic venous pressure gradient was available in 21 cases. Portal hypertension was found in 14 patients (14/21; 67%). Cases of portal hypertension were found to have a sinusoidal pattern (3/14; 21.4%), vascular pattern (1/14; 7.1%), or a mixed sinusoidal and vascular pattern (10/14; 71.4%). Those not having portal hypertension showed hepatic artery (HA) involvement in 6/7 (85.7%) cases. A comparative analysis between portal hypertension (PTH) and non-PTH groups showed that HA amyloid deposition was dominant in the non-PTH group (6/7; 85.7%) and sinusoidal deposition in the PTH group (13/14; 92.8%). The difference was found to be significant (P<0.05). We found that portal hypertension was noted in cases with diffuse sinusoidal deposition or mixed sinusoidal with portal vein deposition. In the non-PHT group, the deposition was mainly in HA alone.

Modeled dispersal patterns for wood and grass charcoal are different: Implications for paleofire reconstruction

Sedimentary charcoal records provide useful perspectives on the long-term controls and behavior of fire in the Earth System. However, a comprehensive understanding of the nuances, biases, and limitations of charcoal as a fire proxy is necessary for reliable paleofire interpretations. Here, we use a charcoal dispersal model to answer the following questions: (1) How does the dispersal of wood and grass charcoal particles differ? (2) Do traditional conceptual models of charcoal dispersal reliably characterize grass charcoal dispersal? We find that small differences in shape (length:width (L:W)) and density of grass and wood charcoal can cause substantial differences in particle dispersal and source area. Whereas the modeled dispersal of wood charcoal shows a localized deposition signal which decays with distance, grass charcoal shows more diffuse deposition lacking a localized center (for both &gt;125 µm and &gt;60 µm). Although paleofire research has typically not distinguished between fuel types when interpreting source area, we show that the dispersal of charcoal derived from different fuels is unlikely to be uniform. Because differences in localization, production, and preservation could bias aggregate charcoal accumulation, caution should be taken when interpreting wood and grass-derived charcoal particles preserved in the same record. Additionally, we propose an alternative, dual background conceptual model of grass charcoal dispersal, as the traditional, two-component (peak and background) conceptual model does not accurately characterize the modeled dispersal of grass charcoal. Lastly, this mismatch of conceptualizations of dispersal mechanics implies that grass charcoal may not fit the criteria necessary for peak analysis techniques.

Presumed Bietti crystalline dystrophy with optic nerve head drusen: a case report

BackgroundBietti crystalline dystrophy is primarily a retinal dystrophy caused by a CYP4V2 mutation and typically presents with crystalline retinal deposits in the posterior fundus.Case presentationWe present the case of an otherwise healthy 39-year-old Iranian woman with no family history of ocular disease who suffered with progressive vision loss that had started 2 years prior to presentation. Ocular examination revealed blurry optic nerve head margin and diffuse retinal crystalline deposit in both eyes. Spectral domain optical coherence tomography images showed retinal crystals, located mostly in outer retinal layers, with some areas of outer retinal tubulation and attenuation of outer retinal layers. Crystalline deposits were better visualized on near-infrared images as hyperreflective spots. Fundus autofluorescence images showed hyperautofluorescence areas on optic nerve head consistent with optic nerve head drusen and large hypoautofluorescence areas in posterior retina consistent with retinal pigment epithelium atrophy. Cystinosis was ruled out by blood testing.ConclusionBietti crystalline dystrophy may be associated with optic nerve head drusen.

ODP502 Nodular Pretibial Myxedema without Graves’ Orbitopathy: A Case Report

Abstract Background Nodular myxedema is an uncommon skin manifestation of autoimmune thyroid disease. Almost always associated with significant orbitopathy from the deposition of glycosaminoglycans by stimulated fibroblasts. Clinical Case A 57-year-old male presented to dermatology clinic with multiple, non-tender, non-erythematous, nodular lesions of the distal left leg, which had been increasing in size and number over the past one year. The initial clinical impression was lipoma, versus leiomyoma, versus pilomatricoma. The pathology report from punch biopsy of one of the lesions revealed diffuse dermal mucin deposition, consistent with pretibial myxedema. The patient was then referred to endocrinology. His symptoms included increasing fatigue and weight gain of 20.4 kilograms over the last 7 years. He had long-standing history of untreated hypothyroidism and tobacco use disorder. There was no known history of hyperthyroidism, neither thyromegaly, acropachy, nor any signs of orbitopathy were found on examination. Laboratory tests revealed a mildly elevated TSH (5.491 uIU/ml, reference 0.450-5.491 uIU/ml), normal free thyroxine (0.98 ng/dl, reference 0.45-1.80 ng/dl) and elevated anti-microsomal antibody (66. 0 IU/mL, reference &amp;lt;9. 00 IU/ml). Following the pathology report, thyroid stimulating immunoglobulin was requested and found to be elevated (322%, reference &amp;lt;140%). Thyroid ultrasound showed estimated volume of 5. 04 and 2.96 ml for the right and left thyroid lobes, respectively, and only one sub-centimeter nodule. Treatment with levothyroxine was started. Conclusion Thyroid dermopathy, including pretibial myxedema, is attributed to high serum concentrations of thyroid stimulating immunoglobulin leading fibroblasts to deposit mucopolysaccharides in the papillary and reticular dermis. The resulting nonpitting edema can occur anywhere in the skin, despite its notorious penchant for the anterior tibial region. Thyroid dermopathy is seen in 4.3% of patients with Graves’ disease in general, and 15% of patients with Graves’ orbitopathy 1 . Thyroid dermopathy is very rare in the absence of concurrent orbitopathy. Here we present a very unusual case of biopsy-confirmed nodular pretibial myxedema in the absence of current or remote history of known hyperthyroidism, and without any apparent orbitopathy. Presentation: No date and time listed

PSAT010 Severe Cholestatic Jaundice (Stauffer Syndrome) as a Rare Paraneoplastic Manifestation in Adrenocortical Carcinoma

Abstract Introduction Adrenocortical Carcinoma (ACC) is a rare and often aggressive malignancy arising from the adrenal cortex. Rarely, ACC can be associated with a paraneoplastic syndrome, such as tumor-associated hypoglycemia due to insulin-like growth factor-2 secretion, hyperreninemic hyperaldosteronism, erythropoietin-associated polycythemia, and leukocytosis due to chemokine release from the tumor. Stauffer syndrome is a paraneoplastic syndrome characterized by reversible cholestasis in the absence of liver metastases, most frequently described in the context of renal cell carcinoma. Our case is the first reported association between Stauffer syndrome and ACC. Clinical Case A 38-year-old man presented with nausea, vomiting, painless jaundice, pruritus, and weight loss. Laboratory evaluation revealed an elevated total bilirubin of 8.7 mg/dL (N&amp;lt;1.3), the INR was elevated secondary to the cholestasis from vitamin K insufficiency. Computed tomography (CT) scan revealed a 20.4 cm, heterogeneous left adrenal mass with central necrosis concerning for ACC. There was no evidence of liver metastases. Additional laboratory workup showed elevated DHEA-sulfate of 1764.2 ug/dL (N&amp;lt;568.9), ACTH of 18 pg/mL (N&amp;lt;7-63), cortisol of 18.30 mcg/dL (N&amp;lt;19.50), androstenedione of 247 ng/dL (N&amp;lt;150), estradiol of 123 pg/mL (N&amp;lt;41), testosterone of 237 ng/dL (N&amp;lt;871), aldosterone of 11 ng/dL (N&amp;lt;=21), and plasma renin activity of 14 ng/mL/hr (N&amp;lt;4.3). Plasma metanephrines and catecholamines were normal. The patient's condition deteriorated rapidly with progressive renal failure and uremia requiring intensive care unit admission for continuous renal replacement therapy and critical care optimization preoperatively. The patient's total bilirubin increased to 34.5 mg/dL, which prompted liver biopsy. This revealed no evidence of cirrhosis or hepatic metastasis. Therefore, severe cholestasis was attributed to Stauffer syndrome, a paraneoplastic cholestatic jaundice from the underlying adrenal mass. The patient underwent exploratory laparotomy with left adrenalectomy, left nephrectomy, left ureterolysis, and wedge liver biopsy. Histopathology showed a necrotic ACC with tumor invasion into the adrenal capsule, no lymphovascular invasion, margins uninvolved, and Ki-67 index of 40%. Kidney parenchyma exhibited diffuse pigment casts. The liver specimen contained diffuse bile deposits and minimal chronic inflammation in the portal tracts, consistent with Stauffer syndrome. Postoperatively, the patient had rapid improvement in his renal function, and bilirubin level normalized after several weeks. Mitotane therapy was deferred until the complete recovery of the liver function. Conclusion Our case highlights a unique presentation of paraneoplastic hepatic dysfunction with jaundice associated with newly diagnosed ACC. Although Stauffer syndrome is one of the most characteristic paraneoplastic syndromes associated with renal cell carcinoma and other malignancies, paraneoplastic hepatic dysfunction associated with ACC has not been previously reported. The patient had rapid improvement of hyperbilirubinemia after surgical resection of the tumor. Stauffer syndrome should be considered in patients with ACC with liver dysfunction and jaundice without evidence of liver metastases. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Coronary flow reserve by PET 13N-ammonia in patients with hereditary transthyretin amyloidosis with and without cardiac involvement

Abstract Background Transthyretin Cardiac amyloidosis (ATTR) presents with diffuse deposition of amyloid fibrils in the heart. Biomarkers of cardiac involvement such as troponins are often elevated even in early disease stages, reflecting direct cardiomyocyte damage and coronary microvascular dysfunction by amyloid deposits. Objectives Evaluate global and segmental coronary flow reserve (CFR) by PET 13N-ammonia in patients with hereditary Transtirretina Amyloidosis with and without cardiac involvement. Methodology Thirty-eight ATTR mutation carrier patients (18 with cardiac amyloidosis and 20 without cardiac amyloidosis underwent CFR study by PET 13N-ammonia. Cardiac involvement was defined by means of echocardiography, with an end-diastolic interventricular septal wall thickness ≥12 mm or positive endomyocardial biopsy or grade II or III nuclear scintigraphy using bone avid radiotracers. The Mann-Whitney test was used to compare the values of coronary flow reserve between the groups. The effect size was calculated using the Wilcox method and 95% confidence intervals, obtained by bootstrapping. A multivariate linear regression model was applied to identify the main determinants of global coronary flow reserve. Results Compared with patients without cardiac involvement, patients with cardiac involvement were older (69±8 vs. 41±11 years old; p&amp;lt;0,001), had worse NYHA functional classification, higher left ventricular mass index (198±51 g/m2 x 75±19 g/m2; p&amp;lt;0,001), thicker interventricular septum (17,9±3,4 mm vs. 8,7 ± mm; p&amp;lt;0,001]. Coronary flow reserve values were significantly lower in the cardiac amyloidosis group globally (1,8±0,4 vs. 2,9±0,7; p&amp;lt;0,001) and in all analyzed segments (p&amp;lt;0.01). The apical segments were also affected when comparing group with and without cardiac involvement (2,0±1 vs. 3,0±0,7; P=0,002), suggesting absence of microvascular apical preservation. In multivariable linear regression analyses, age and BNP were the main factors associated to coronary reserve flow. The reduction in global CRF was 0,25, 0,08 and 0,17 points, on average, for each decade of life, for each 100 mg/dl of serum BNP and for each 0,1 heart to contralateral lung ratio uptake in 3-hour caption on TcPYP scintigraphy respectively. Conclusion Patients with cardiac amyloidosis present lower coronary flow reserve both globally and segmental compared to mutation carrier without cardiac amyloidosis. The evaluation of Coronary flow reserve by PET 13N-ammonia may be a worthwhile tool in cardiac involvement in TTR patients. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Pfizer