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.

MRI and its role in the evaluation and surgical decision making in patients with challenging IPP presentations: descriptions of MRI findings and algorithm for patient management.

UNLABELLED: Study Type - Diagnostic (case series) Level of Evidence 4 What's known on the subject? and What does the study add? It is known that magnetic resonance imaging (MRI) is safe and effective for imaging patients with inflatable penile prostheses (IPPs). Previous series have reported results of MRI for imaging series of patients with IPPs. The impact on management in particular with regard to salvage procedures is not well defined. This study represents the largest known experience with MRI evaluation of IPPs. This also provides an algorithm that assists with decisions regarding utilization of MRI and treatment planning based on results. OBJECTIVE: • In some patients who undergo placement of an inflatable penile prosthesis (IPP) the device may function inadequately. We describe the use of magnetic resonance imaging (MRI) for anatomical localization and detection of prosthesis malrotation, angulation, displacement and erosion in IPPs with equivocal clinical examination. PATIENTS AND METHODS: • We prospectively performed MRI by a defined protocol including T1-weighted imaging, and transaxial, sagittal and coronal fat-saturated fast spin-echo T2-weighted imaging in both deflated and inflated states to evaluate patients seen at our referral centre for IPP-related complaints. • We retrospectively reviewed 32 such MRI studies performed as a supplement to clinical examination between 2000 and 2008. RESULTS: • Of 32 cases, 75% (24/32) underwent surgical intervention. Of these, 45% (11/24) underwent device salvage procedures including cylinder revision in 33% (8/24), cylinder replacement in 8% (2/24) and pump replacement in 4% (1/24). • MRI was most useful for determination of surgical approach in those with abnormal physical examination, and for justification of either surgical or expectant management in those with indeterminate physical examination. CONCLUSIONS: • MRI is safe and effective for imaging genitourinary prostheses. • We found MRI to be a valuable adjunct for evaluation of IPP-related complaints when clinical examination is equivocal as it detected a variety of prosthetic and corporal abnormalities and impacted management decisions regarding observation, replacement or device salvage procedures. • We provide technique, results and an algorithm that can be beneficial in this complex subset of patients.

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.

Readmission Rates Associated with Pharmacist Involvement in a Geriatric Transitional Care Management Clinic.

OBJECTIVE: To evaluate the impact of a post-discharge pharmacist telephone call on 30- and 90- day readmission rates as part of a transitional care management (TCM) service in a geriatric patient-centered medical home (PCMH). METHODS: Adults 60 years of age and older who had established primary care at the PCMH for at least one year and were discharged from the hospital between 7/1/2013 and 2/21/2016 were included. Readmission rates for patients who received and did not receive a pharmacist TCM phone call were compared. Secondary data analysis was conducted between individuals who received all three components of the service compared with those who received on a nurse navigator plus primary care provider (PCP) visit. RESULTS: Among 513 discharges of unique patients (mean age, 80.4 years; women 63%), 269 (52.4%) received a pharmacist phone call. Readmission rates at 30 days were 8.9% for patients who received a pharmacist TCM phone call compared to 12.7% for those who did not receive this service (OR 0.67 [95% CI, 0.38-1.18; P=0.17]). When comparing only those individuals who received all three components of the service (pharmacist, nurse navigator, and PCP) (n=215) compared to those who received only a nurse navigator plus PCP visit (n=66), there was no difference in 30-day readmission rates (7.9% vs. 10.6%, p=0.49). However, there were significantly fewer readmissions within 90-days (16.3% vs. 31.8%, p=0.01). CONCLUSION: Pharmacist phone calls as part of an interdisciplinary TCM service did not result in a statistically significant difference regarding readmission rates at 30 days; however, patients who received all three components of the service had significantly fewer readmissions at 90 days, compared to patients who did not speak with a pharmacist but did complete a visit with a nurse navigator and physician. Future research is needed to determine which patients may benefit the most from this service and to identify strategies to increase patient participation.

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.

Ontogenic development of brown adipose tissue in Angus and Brahman fetal calves.

Brahman calves experience greater neonatal mortality than Angus calves if cold-stressed. To establish a developmental basis for this, three fetuses of each breed type were taken at 96, 48, 24, 14, and 6 d before expected parturition, and at parturition. Overall fetal BW tended (P = 0.08) to be greater for Angus than for Brahman fetuses. There was no difference between breed types in total brown adipose tissue (BAT) mass or grams of BAT/kg BW. Brown adipocyte density decreased 56%, whereas lipogenesis from acetate and glucose in vitro decreased 97% during the last 96 d of gestation in both breed types. Glycerolipid synthesis from palmitate declined by 85% during the last trimester but still contributed 98% to total lipid synthesis at birth. The fetal age x breed interaction was significant for lipogenesis from glucose (P = 0.05) and palmitate (P = 0.005); rates were higher at 96 d before birth in Brahman BAT but declined to similar rates by birth. Uncoupling protein-1 (UCP1) mRNA tripled during gestation in both breed types (P = 0.002), whereas mitochondrial cross-sectional area did not change (P = 0.14) during gestation. Neither the breed nor the age x breed effect was significant (P > or = 0.24) for UCP1 mRNA concentration or mitochondrial cross-sectional area. In both breed types, a marked decrease in BAT UCP1 mRNA between 24 and 14 d prepartum was associated with a similar reduction in lipogenesis from palmitate and a noticeable change in BAT mitochondrial morphology, as the mitochondria became more elongated and the cristae became more elaborate. Uncoupling protein-1 mRNA initially was elevated in Angus tailhead s.c. adipose tissue, but was barely detectable by birth, and tended to be greater overall (P = 0.09) in Angus than in Brahman BAT. If uncoupling protein activity in s.c. adipose tissue persists after birth, then s.c. adipose tissue may contribute more to thermogenesis in Angus newborn calves than in Brahman calves. In contrast, we did not observe differences in ontogenic development of perirenal BAT that could explain the documented differences in thermogenic capacity between Angus and Brahman newborn calves.

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.

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.

Controlled evaluation of a supplementary dose of carbamazepine on psychomotor function in epileptic patients.

The effect of an additional dose of 400 mg carbamazepine (CBZ) on a series of simple psychomotor tests was investigated in 8 patients with epilepsy receiving chronic CBZ monotherapy in a balanced randomised double-blind placebo controlled cross-over study. Psychomotor testing and blood sampling for total and free CBZ and CBZ 10,11 epoxide (CBZ-E) concentrations were performed at 10, 12, 14, 16 and 18 h after the extra dose which was administered at 23.00 h on the previous evening. The CBZ increment produced significant impairment of choice reaction recognition time from 10-16 h after the dose total choice reaction time at 12 h card sorting at 12 h sedation scoring at 12 h. No significant effect on critical flicker fusion threshold, finger tapping or simple memory testing was noted. No patient reported increased side-effects in the placebo phase while 5 noted new symptoms likely to be attributable to the additional CBZ. Areas under the concentration-time curves from 10-18 h were higher following CBZ than placebo for total and free CBZ and CBZ-E concentrations. This study has demonstrated decrements in performance of a series of simple psychomotor tests in epileptic patients receiving a supplemental CBZ dose. Patients with epilepsy who require high CBZ concentrations for optimal control of seizures may be at risk of concurrent impairment of psychomotor function. Simple objective measures of performance may help in assessing the benefit-risk ratio.