Objective-ElevatedIn vitro, SAA enrichment increased high-density lipoprotein (HDL) binding to heparan sulfate proteoglycans, and immunoprecipitation experiments using plasma from apoE Ϫ/Ϫ and LDLR Ϫ/Ϫ mice demonstrated that SAA was present on both apoA-I-containing and apoB-containing lipoproteins. Conclusions-In chow-fed apoEϪ/Ϫ and LDLR Ϫ/Ϫ mice, SAA is deposited in murine atherosclerosis at all stages of lesion development, and SAA immunoreactive area correlates highly with lesion area, apoA-I area, apoB area, and perlecan area. These findings are consistent with a possible role for SAA-mediated lipoprotein retention in atherosclerosis.

IMPORTANCE Population-based information on the distribution of histologic diagnoses associated with skin biopsies is unknown. Electronic medical records (EMRs) enable automated extraction of pathology report data to improve our epidemiologic understanding of skin biopsy outcomes, specifically those of melanocytic origin.OBJECTIVE To determine population-based frequencies and distribution of histologically confirmed melanocytic lesions. DESIGN, SETTING, AND PARTICIPANTSA natural language processing (NLP)-based analysis of EMR pathology reports of adult patients who underwent skin biopsies at a large integrated health care delivery system in the US Pacific Northwest from January 1, 2007, through December 31, 2012.EXPOSURES Skin biopsy procedure. MAIN OUTCOMES AND MEASURESThe primary outcome was histopathologic diagnosis, obtained using an NLP-based system to process EMR pathology reports. We determined the percentage of diagnoses classified as melanocytic vs nonmelanocytic lesions. Diagnoses classified as melanocytic were further subclassified using the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) reporting schema into the following categories: class I (nevi and other benign proliferations such as mildly dysplastic lesions typically requiring no further treatment), class II (moderately dysplastic and other low-risk lesions that may merit narrow reexcision with <5-mm margins), class III (eg, melanoma in situ and other higher-risk lesions warranting reexcision with 5-mm to 1-cm margins), and class IV/V (invasive melanoma requiring wide reexcision with Ն1-cm margins and potential adjunctive therapy). Health system cancer registry data were used to define the percentage of invasive melanoma cases within MPATH-Dx class IV (stage T1a) vs V (Նstage T1b).RESULTS A total of 80 368 skin biopsies, performed on 47 529 patients, were examined. Nearly 1 in 4 skin biopsies were of melanocytic lesions (23%; n = 18 715), which were distributed according to MPATH-Dx categories as follows: class I, 83.1% (n = 15 558); class II, 8.3% (n = 1548); class III, 4.5% (n = 842); class IV, 2.2% (n = 405); and class V, 1.9% (n = 362). CONCLUSIONS AND RELEVANCEApproximately one-quarter of skin biopsies resulted in diagnoses of melanocytic proliferations. These data provide the first population-based estimates across the spectrum of melanocytic lesions ranging from benign through dysplastic to malignant. These results may serve as a foundation for future research seeking to understand the epidemiology of melanocytic proliferations and optimization of skin biopsy utilization.

Nephrogenic systemic fibrosis (NSF) is a progressive, debilitating, and emotionally distressing disease that can affect patients with renal dysfunction. Prevention, early recognition and early treatment are essential to limiting its impact. The most significant risk factors for developing NSF are chronic or significant acute kidney disease (usually necessitating dialysis) and the administration of gadolinium-containing contrast agents (GCCA). Early symptoms include swelling, redness, pruritus, and pain in the limbs, sometimes with muscle weakness. Early signs are edema, erythema, and occasionally palpable warmth of the involved extremities; there may be florid scleral telangiectasia resembling conjunctivitis. We must redouble our efforts to avoid the administration of GCCA to patients with renal insufficiency. The most effective treatment for NSF to date is maximization of renal function via medical therapy or transplantation. There are data to support a beneficial effect from extracorporeal photopheresis, and all patients can gain from physical therapy.

Little is known about the modifying effects of age on the skeletal response to intermittent treatment with PTH. We therefore compared the response of 63 aged (18 month old) and 61 young-adult (3 month old) C57BL/6 mice to 4 wk of daily sc injections of either vehicle or h(1-34)PTH at a dose of 95 ng/g body weight. The increase in total body bone mineral density (BMD), compared with vehicle-treated animals, was similar in aged and young-adult mice (+5.6 vs. +6.3%). Aged animals demonstrated a greater increase in spinal BMD than their younger counterparts (+12.0 vs. +5.1%, P = 0.01; absolute increment: 57 x 10(-4) vs. 28 x 10(-4) g/cm(2)). Microcomputed tomography analyses in a subset of the vertebrae showed a trend toward higher L5 trabecular bone volume fraction in the PTH-treated aged animals (+40.2 vs. +19.6%). Vertebral histomorphometry demonstrated a greater PTH-induced increase in osteoblast number in aged vs. young-adult animals (694 vs. 396 cells/mm(2)). In contrast, in the femur the PTH-induced increase in BMD tended to be greater in the young-adult than the aged animals, although this did not reach statistical significance (8.1 vs. 4.2%). The numbers of osteoblast progenitors and mineralizing colonies in cultured marrow were unaffected by PTH treatment in either group. We conclude that aging differentially impacts the regional skeletal response to PTH such that the increase in BMD in the spine is augmented, whereas that in the femur is unaffected. Effects on osteoblast progenitor recruitment do not seem to be the basis for these changes.