Systemic amyloidosis from A (AA) to T (ATTR): a review.

Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. There are over 15 types of systemic amyloidosis, each caused by a different precursor protein which promotes amyloid formation and tissue deposition. Amyloidosis can be acquired or hereditary and can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin and soft tissues. Symptoms are usually insidious and nonspecific resulting in diagnostic delay. The field of amyloidosis has seen significant improvements over the past decade in diagnostic accuracy, prognosis prediction and management. The advent of mass spectrometry-based shotgun proteomics has revolutionized amyloid typing and has led to the discovery of new amyloid types. Accurate typing of the precursor protein is of paramount importance as the type dictates a specific management approach. In this article, we review each type of systemic amyloidosis to provide the practitioner with practical tools to improve diagnosis and management of these rare disorders.

Whole-exome analysis reveals novel somatic genomic alterations associated with outcome in immunochemotherapy-treated diffuse large B-cell lymphoma.

Lack of remission or early relapse remains a major clinical issue in diffuse large B-cell lymphoma (DLBCL), with 30% of patients failing standard of care. Although clinical factors and molecular signatures can partially predict DLBCL outcome, additional information is needed to identify high-risk patients, particularly biologic factors that might ultimately be amenable to intervention. Using whole-exome sequencing data from 51 newly diagnosed and immunochemotherapy-treated DLBCL patients, we evaluated the association of somatic genomic alterations with patient outcome, defined as failure to achieve event-free survival at 24 months after diagnosis (EFS24). We identified 16 genes with mutations, 374 with copy number gains and 151 with copy number losses that were associated with failure to achieve EFS24 (P<0.05). Except for FOXO1 and CIITA, known driver mutations did not correlate with EFS24. Gene losses were localized to 6q21-6q24.2, and gains to 3q13.12-3q29, 11q23.1-11q23.3 and 19q13.12-19q13.43. Globally, the number of gains was highly associated with poor outcome (P=7.4 × 10(-12)) and when combined with FOXO1 mutations identified 77% of cases that failed to achieve EFS24. One gene (SLC22A16) at 6q21, a doxorubicin transporter, was lost in 54% of EFS24 failures and our findings suggest it functions as a doxorubicin transporter in DLBCL cells.

Nephrolithiasis in medullary sponge kidney: evaluation of clinical and metabolic features.

OBJECTIVE: Medullary sponge kidney (MSK) is a disorder characterized by tubular dilation of renal collecting ducts and cystic dilation of medullary pyramids that has been associated with stone disease. The significance of nephrolithiasis and the mechanisms by which it occurs are incompletely understood. We describe clinical and metabolic features of nephrolithiasis in a cohort of patients with MSK. METHODS: Records were reviewed of 56 patients, all with radiographic diagnosis of medullary sponge kidney and data collected pertaining to presentation, stone events and recurrences, stone composition, and metabolic profile to perform a descriptive study with median 3.7 years follow-up. RESULTS: Nephrolithiasis was confirmed radiographically in 39/56 patients (69.6%). No patient without evidence of nephrolithiasis developed a stone event, whereas 13/39 (33%) of those with nephrolithiasis developed a recurrent stone event. Stones were composed of calcium oxalate monohydrate, calcium oxalate dihydrate, calcium phosphate apatite, and uric acid. Metabolic profile was obtained for 26 of 39 (67%) stone-forming patients demonstrating abnormalities in 22/26 (84.6%). These included hypercalciuria, 58% (15/26); low urine volume, 35% (9/26); hyperuricosuria, 27% (7/26); hypocitraturia, 19% (5/26); elevated urine sodium, 15% (4/26); and hyperoxaluria, 12% (3/26). CONCLUSION: Many patients with MSK have no evidence of nephrolithiasis. Among those who do, recurrence is common, and metabolic profile and composition are varied as in the general stone-forming population.

Ureteroarterial fistula treatment with open surgery versus endovascular management: long-term outcomes.

PURPOSE: Ureteroarterial fistulas can be treated with open vascular or percutaneous arterial stent placement. We compared the long-term outcomes of each treatment. MATERIALS AND METHODS: A single center, retrospective review of ureteroarterial fistulas (1996 to 2008) was performed. RESULTS: We identified 20 ureteroarterial fistulas in 19 patients. All patients had undergone extirpative surgery with pelvic radiation in 74% and long-term ureteral stents in 84%. At a mean followup of 15.5 months (range 1 to 99) survival was 53%. Of the 70% (14 of 20) treated with percutaneous endovascular iliac artery stenting or embolization, 2 patients later required open vascular graft and 12 were treated with long-term ureteral stenting. Of the 30% (6 of 20) of patients treated with open surgical repair or bypass 2 required bypass revision and/or thrombectomy, and 4 had concomitant ureteral ligation or nephrectomy. Despite undergoing anticoagulation 10 patients (53%) experienced lower extremity morbidity including ulceration, ischemia and amputation. In each treatment group 2 patients had recurrent hemorrhage requiring a secondary procedure, leading to death in 2 for an overall 10% acute mortality rate. Overall noncause specific mortality of ureteroarterial fistulas was 47% and 10% to 20% was related to the fistula or treatment complications. CONCLUSIONS: Endovascular stenting is increasingly used in lieu of open techniques due to the high operative risk and comorbidities in patients with ureteroarterial fistulas. This retrospective review fails to identify a clear advantage for endovascular or open vascular surgical management. Thus, endovascular stenting is preferred in most cases. Regardless of therapy, patients are at risk for recurrent bleeding, lower extremity complications and stent/graft complications. The use of antibiotics and long-term anticoagulant therapy appear prudent but not proved.

Cyclin D1 positive follicular lymphoma.

This report describes an unusual case of cyclin D1 expression by an otherwise typical follicular lymphoma, of low histological grade. BCL2-IGH and CCND1-IGH fusions were identified by interphase fluorescence in situ hybridisation.

Psychomotor impairment and anticonvulsant therapy in adult epileptic patients.

Using a battery of simple tests, psychomotor performance was assessed in 11 healthy subjects, 14 untreated epileptic patients and 66 epileptics on chronic anticonvulsant medication. Significant differences were found between controls and untreated patients for choice reaction time, card sorting and Simple Simon memory game. Treated patients performed less well than both untreated epileptics and controls in choice reaction time (p less than 0.05; p less than 0.001), card sorting (p less than 0.01; p less than 0.001), Simple Simon (p less than 0.05; p less than 0.001) and finger tapping (p less than 0.05; p less than 0.001). Patients with centrencephalic epilepsy were slower than those with discrete focal EEG abnormalities in reaction time and card sorting. Patients receiving treatment with carbamazepine, phenytoin or sodium valproate alone all performed similarly to each other and to those patients taking anticonvulsant polypharmacy. Monotherapy patients with potentially "toxic" plasma anticonvulsant concentrations did no worse than those within or below the "therapeutic" range. Both the disease and its treatment reduce psychomotor performance. All major anticonvulsants appear to cause a similar degree of impairment across a wide range of concentrations. The effect of chronic anticonvulsant medication on "quality of life" should not be neglected in the pursuit of perfect seizure control.