The High Direct Medical Costs of Prader-Willi Syndrome.

OBJECTIVE: To assess medical resource utilization associated with Prader-Willi syndrome (PWS) in the US, hypothesized to be greater relative to a matched control group without PWS. STUDY DESIGN: We used a retrospective case-matched control design and longitudinal US administrative claims data (MarketScan) during a 5-year enrollment period (2009-2014). Patients with PWS were identified by Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 759.81. Controls were matched on age, sex, and payer type. Outcomes included total, outpatient, inpatient and prescription costs. RESULTS: After matching and application of inclusion/exclusion criteria, we identified 2030 patients with PWS (1161 commercial, 38 Medicare supplemental, and 831 Medicaid). Commercially insured patients with PWS (median age 10 years) had 8.8-times greater total annual direct medical costs than their counterparts without PWS (median age 10 years: median costs $14 907 vs $819; P < .0001; mean costs: $28 712 vs $3246). Outpatient care comprised the largest portion of medical resource utilization for enrollees with and without PWS (median $5605 vs $675; P < .0001; mean $11 032 vs $1804), followed by mean annual inpatient and medication costs, which were $10 879 vs $1015 (P < .001) and $6801 vs $428 (P < .001), respectively. Total annual direct medical costs were ∼42% greater for Medicaid-insured patients with PWS than their commercially insured counterparts, an increase partly explained by claims for Medicaid Waiver day and residential habilitation. CONCLUSION: Direct medical resource utilization was considerably greater among patients with PWS than members without the condition. This study provides a first step toward quantifying the financial burden of PWS posed to individuals, families, and society.

Novel blood biomarkers of human urinary bladder cancer.

PURPOSE: Recent data indicate that cDNA microarray gene expression profile of blood cells can reflect disease states and thus have diagnostic value. We tested the hypothesis that blood cell gene expression can differentiate between bladder cancer and other genitourinary cancers as well as between bladder cancer and healthy controls. EXPERIMENTAL DESIGN: We used Affymetrix U133 Plus 2.0 GeneChip (Affymetrix, Santa Clara, CA) to profile circulating blood total RNA from 35 patients diagnosed with one of three types of genitourinary cancer [bladder cancer (n = 16), testicular cancer (n = 10), and renal cell carcinoma (n = 9)] and compared their cDNA profiles with those of 10 healthy subjects. We then verified the expression levels of selected genes from the Affymetrix results in a larger number of bladder cancer patients (n = 40) and healthy controls (n = 27). RESULTS: Blood gene expression profiles distinguished bladder cancer patients from healthy controls and from testicular and renal cancer patients. Differential expression of a combined set of seven gene transcripts (insulin-like growth factor-binding protein 7, sorting nexin 16, chondroitin sulfate proteoglycan 6, and cathepsin D, chromodomain helicase DNA-binding protein 2, nell-like 2, and tumor necrosis factor receptor superfamily member 7) was able to discriminate bladder cancer from control samples with a sensitivity of 83% (95% confidence interval, 67-93%) and a specificity of 93% (95% confidence interval, 76-99%). CONCLUSION: We have shown that the gene expression profile of circulating blood cells can distinguish bladder cancer from other types of genitourinary cancer and healthy controls and can be used to identify novel blood markers for bladder cancer.

Novel mutations of epidermal growth factor receptor in localized prostate cancer.

We recently demonstrated that EGFR protein overexpression is more common in African American (AA) prostate cancer patients compared to Caucasian patients. We further examine EGFR dysregulation by determining EGFR mutation status in the tyrosine kinase (TK) domain in prostate cancer patients of different ethnicity. Normal and tumor DNA from 89 radical prostatectomy cases were studied for mutations in the EGFR TK domain using genomic DNA sequencing. We identified 4 novel missense mutations in exons 19, 20 and 21 of EGFR TK domain: 3 in Koreans and 1 in Caucasian but none in AA. We also identified 5 distinct synonymous DNA sequence changes, which did not alter the encoded amino acid, in exons 20 and 21 in 31/89 (35%) patients. Interestingly, these synonymous sequence changes were not observed in normal DNA in 7(23%) patients, indicating the presence of de novo somatic mutation to a new synonymous sequence. Our data reveal that EGFR missense mutation in the TK domain occurs in localized prostate cancer. Our data also demonstrate the presence of somatic mutation to a new synonymous sequence in a subset of patients. Larger population-based studies are required to define the association between EGFR mutations and the ethnic background of patients.

Metanephric adenoma in an 8-year-old child: case report and review of the literature.

Metanephric adenoma (MA) is a renal tumor that is rarely found in children. We present a case of MA that was incidentally discovered in an 8-year-old child on computed tomography. We also review the literature regarding this lesion in the pediatric population. There are certain imaging features of MA that may suggest the diagnosis preoperatively. Metanephric adenoma is often hyperechoic on sonography, hyperdense on noncontrast computed tomography scans, and of low signal intensity on T1- and T2-weighted magnetic resonance images. Nephron sparring surgery has been performed in several cases. However, the distinction of MA from other metanephric lesions as well as from Wilms' tumor and papillary renal cell carcinoma may not be readily apparent at the time of surgery.

Surgical repair of a left subclavian artery aneurysm causing stenosis of a left internal mammary graft-a case report.

Subclavian artery aneurysms are extremely rare, accounting for approximately 0.1% of peripheral artery aneurysms. We present a case of a proximal left subclavian arterial aneurysm in a patient status post previous coronary artery bypass grafting; the aneurysm was complicated by involvement of the left internal mammary artery that had been previously utilized to revascularize the left anterior descending artery. Ostial stenosis of the internal mammary artery secondary to the aneurysm was present. Simultaneous reoperative coronary bypass surgery and repair of the left subclavian aneurysm was performed, with a good result. This is the second case reported in the literature of concomitant subclavian artery aneurysm repair and coronary revascularization.

Ischemic complications after endovascular abdominal aortic aneurysm repair.

OBJECTIVES: Limb and pelvic ischemia are known complications after endovascular abdominal aortic aneurysm repair (EVAR). The objective of this paper is to present our experience with the incidence, presentation, and management of such complications. METHODS: Over 9 years 311 patients with aortic aneurysms underwent EVAR. A retrospective review identified 28 patients (9.0%) with ischemic complications. RESULTS: Among 28 patients with ischemic complications, 21 had lower extremity ischemia and 7 had pelvic ischemia: colon (n = 4), buttock (n = 2), and spinal cord (n = 2). Of the 21 patients with lower extremity ischemia, 15 had limb occlusions (71.4%), 3 due to embolization (14.7%) and 3 the result of common femoral artery thromboses (14.7%). Limb occlusions were manifested as severe acute arterial ischemia (n = 6), rest pain (n = 3), intermittent claudication (n = 5), and decreased femoral pulse (n = 1). Limb occlusions were managed with thrombectomy and stent placement (n = 4), femorofemoral bypass (n = 7), eventual explantation because of persistent endoleak (n = 1), and expectant management (n = 3). The 3 patients with occlusions managed expectantly all had intermittent claudication, which has subsequently improved. In the 6 patients with lower extremity ischemia due to embolization or common femoral artery injury presentation was acute, and embolectomy was performed, followed by femoral artery endarterectomy and patch angioplasty or placement of an interposition graft. One patient who had a prolonged postoperative course including cardiac arrest subsequently required distal bypass and ultimately above- knee amputation. Among the 7 patients with pelvic ischemia, 2 patients had unilateral hypogastric artery embolization before the original surgery. Among the patients with colonic ischemia, 3 were seen immediately postoperatively, and required colectomy and colostomy. Two patients who required urgent colectomy subsequently had multiple organ failure, and died in the perioperative period. One patient had abdominal pain 1 week after surgery, which was managed with bowel rest, with subsequent improvement. In 2 patients spinal cord ischemia developed immediately after surgery, which resulted in persistent paraplegia. Buttock ischemia developed in 2 patients, 1 of whom required fasciotomy because of gluteal compartment syndrome, and had transient renal failure. CONCLUSIONS: Ischemic complications are not uncommon after EVAR, and may exceed the incidence with open surgical repair. Limb ischemia is most often a result of limb occlusion, and can be successfully managed with standard interventions. Pelvic ischemia often results from atheroembolization despite preservation of hypogastric arterial circulation. Colonic and spinal ischemia are associated with the highest morbidity and mortality.