Beaumont Health

About: Beaumont Health is a nonprofit organization based out in Royal Oak, Michigan, United States. It is known for research contribution in the topics: Medicine & Population. The organization has 1483 authors who have published 1448 publications receiving 15407 citations. The organization is also known as: William Beaumont Health System & Beaumont Hospitals.

Gene expression differences predict treatment outcome of merkel cell carcinoma patients.

Abstract: Due to the rarity of Merkel cell carcinoma (MCC), prospective clinical trials have not been practical. This study aimed to identify biomarkers with prognostic significance. While sixty-two patients were identified who were treated for MCC at our institution, only seventeen patients had adequate formalin-fixed paraffin-embedded archival tissue and followup to be included in the study. Patients were stratified into good, moderate, or poor prognosis. Laser capture microdissection was used to isolate tumor cells for subsequent RNA isolation and gene expression analysis with Affymetrix GeneChip Human Exon 1.0 ST arrays. Among the 191 genes demonstrating significant differential expression between prognostic groups, keratin 20 and neurofilament protein have previously been identified in studies of MCC and were significantly upregulated in tumors from patients with a poor prognosis. Immunohistochemistry further established that keratin 20 was overexpressed in the poor prognosis tumors. In addition, novel genes of interest such as phospholipase A2 group X, kinesin family member 3A, tumor protein D52, mucin 1, and KIT were upregulated in specimens from patients with poor prognosis. Our pilot study identified several gene expression differences which could be used in the future as prognostic biomarkers in MCC patients.

Functional regulation of an outer retina hyporeflective band on optical coherence tomography images.

Abstract: Human and animal retinal optical coherence tomography (OCT) images show a hyporeflective band (HB) between the photoreceptor tip and retinal pigment epithelium layers whose mechanisms are unclear. In mice, HB magnitude and the external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness appear to be dependent on light exposure, which is known to alter photoreceptor mitochondria respiration. Here, we test the hypothesis that these two OCT biomarkers are linked to metabolic activity of the retina. Acetazolamide, which acidifies the subretinal space, had no significant impact on HB magnitude but produced ELM-RPE thinning. Mitochondrial stimulation with 2,4-dinitrophenol reduced both HB magnitude and ELM-RPE thickness in parallel, and also reduced F-actin expression in the same retinal region, but without altering ERG responses. For mice strains with relatively lower (C57BL/6J) or higher (129S6/ev) rod mitochondrial efficacy, light-induced changes in HB magnitude and ELM-RPE thickness were correlated. Humans, analyzed from published data captured with a different protocol, showed a similar light-dark change pattern in HB magnitude as in the mice. Our results indicate that mitochondrial respiration underlies changes in HB magnitude upstream of the pH-sensitive ELM-RPE thickness response. These two distinct OCT biomarkers could be useful indices for non-invasively evaluating photoreceptor mitochondrial metabolic activity.

Can the Femoro-Epiphyseal Acetabular Roof (FEAR) Index Be Used to Distinguish Dysplasia from Impingement?

Abstract: BACKGROUND Classifying hips with structural deformity on the spectrum from impingement to dysplasia is often subjective and frequently inexact. Currently used radiographic measures may inaccurately predict a hip's morphological stability in borderline hips. A recently described radiographic measure, the Femoro-Epiphyseal Acetabular Roof (FEAR) index, has demonstrated an ability to predict stability in the borderline hip. This measure is attractive to clinicians because procedures can be used on the basis of a hip's pathomechanics. This study was designed to further validate and characterize the FEAR index in a skeletally immature population, in hips with dysplasia/femoroacetabular impingement (FAI), and in asymptomatic hips. QUESTIONS/PURPOSES (1) What are the characteristics of the FEAR index in children and how does the index change with skeletal maturation? (2) How does the FEAR index correlate with clinical diagnosis and surgical treatment in a large cohort of symptomatic hips and asymptomatic controls? (3) How does the FEAR index correlate with clinical diagnosis in the borderline hip (lateral center-edge angle [LCEA] 20°-25°) group? METHODS A total of 220 participants with symptomatic investigational hips with a clinical diagnosis of dysplasia or FAI between January 2008 and January 2018 were retrospectively collected from the senior author's practice. Investigational hips were excluded if they had any femoral head abnormalities preventing LCEA measurement (for example, Perthes disease), Tonnis osteoarthritis grade greater than 1, prior hip surgery, or prior femoral osteotomy. In the 220 participants, 395 hips met inclusion criteria. Once exclusion criteria were applied, 15 hips were excluded due to prior hip surgery or prior femoral osteotomy, and 12 hips were excluded due to femoral head deformity. A single hip was then randomly selected from each participant, resulting in 206 investigational hips with a mean age of 13 ± 3 years. Between January 2017 and December 2017, 70 asymptomatic control participants were retrospectively collected from the senior author's institutional trauma database. Control hips were included if the AP pelvis film had the coccyx centered over the pubic symphysis and within 1 to 3 cm of the superior aspect of the symphysis. Control hips were excluded if there was any fracture to the pelvis or ipsilateral femur or the participant had prior hip/pelvis surgery. After exclusion criteria were applied, 16 hips were excluded due to fracture. One hip was then randomly selected from each participant, resulting in 65 control hips with a mean age of 16 ± 8 years. Standardized standing AP pelvis radiographs were used to measure the FEAR index, LCEA, and Tonnis angle in the investigational cohort. Standardized false-profile radiographs were used to measure the anterior center-edge angle (ACEA) in the investigational cohort. Two blinded investigators measured the FEAR index with an intraclass correlation coefficient of 0.92 [95% CI 0.84 to 0.96]. Question 1 was answered by comparing the above radiographic measures in age subgroups (childhood: younger than 10 years; adolescence: 10 to 14 years old; maturity: older than 14 years) of dysplastic, FAI, and control hips. Question 2 was answered by comparing the radiographic measures in all dysplastic, FAI, control hips, and a subgroup of operatively or nonoperatively managed dysplasia and FAI hips. Question 3 was answered by comparing the radiographic measures in borderline (LCEA 20°-25°) dysplastic, FAI, and control hips. RESULTS The FEAR index was lower in older dysplastic of hips (younger than 10 years, 6° ± 9°; 10 to 14 years, 4° ± 10°; older than 14 years, 5° ± 9°; p < 0.001) and control hips (younger than 10 years, -6° ± 5°; 10 to 14 years, -15° ± 4°; older than 14 years, -16° ± 7°; p < 0.001). The diagnosis and age groups were independently correlated with the FEAR index (p < 0.001). The relationship between the FEAR index and diagnosis remained consistent in each age group (p = 0.11). The FEAR index was higher in all dysplastic hips (mean 5° ± 10°) than in asymptomatic controls (mean -13° ± 7°; p < 0.001) and FAI hips (mean -10° ± 11°; p < 0.001). Using -1.3° as a cutoff for FAI/control hips and dysplastic hips, 81% (112 of 139) of hips with values below this threshold were FAI/control, and 89% (117 of 132) of hips with values above -1.3° were dysplastic. The receiver operator characteristics area under the curve (ROC-AUC) was 0.91. Similarly, the FEAR index was higher in borderline dysplastic hips than in both asymptomatic borderline controls (p < 0.001) and borderline FAI hips (p < 0.001). Eighty-nine percent (33 of 37) of hips with values below this threshold were FAI/control, and 90% (37 of 41) of hips with values above -1.3° were dysplastic. The ROC-AUC for borderline hips was 0.86. CONCLUSION The FEAR index was associated with the diagnosis of hip dysplasia and FAI in a patient cohort with a wide age range and with varying degrees of acetabular deformity. Specifically, a FEAR index greater than -1.3° is associated with a dysplastic hip and a FEAR index less than -1.3° is associated with a hip displaying FAI. Using this reliable, developmentally based radiographic measure may help hip preservation surgeons establish a correct diagnosis and more appropriately guide treatment. LEVEL OF EVIDENCE LEVEL III, diagnostic study.

Calciphylaxis presenting as digital ischemia.

Abstract: A 31-year-old woman with end-stage renal disease (ESRD) secondary to membranoproliferative glomerulonephritis presented with gradually worsening severe right hand pain that started during hemodialysis. Physical examination revealed livedo reticularis present on the right hand along with cyanotic digits, and a peri-ungal eschar on the third digit (Fig. 1a). Decreased right radial and ulnar pulses were present. The initial phosphorous level was 8.5 mg/dL. The patient had been hyperphosphatemic for several years prior to presentation. An arterial doppler study with duplex of the right hand was negative for a thrombus but revealed diminished waveforms in the digits. A right hand X-ray study showed vascular calcifications of both the radial and ulnar arteries and soft tissue calcifications along the digits (Fig. 1b). A skeletal survey revealed extensive soft tissue, and vascular calcifications of the bilateral calves and distal common carotid arteries (Fig. 1c). She was diagnosed with calcific uremic arteriolopathy (CUA), and started on sodium thiosulfate during dialysis. CUA is a rare condition of extensive microvascular calcifications that progress to livedo reticularis and nonhealing ulcers. It should be a diagnostic consideration in patients with painful, subcutaneous nodules, plaques, or necrosis. The most significant risk factor for the development of CUA is persistently raised plasma phosphate levels, as was seen in our patient. This is thought to induce the disease due to the precipitation of calcium phosphate crystals into smalland medium-sized vessels. Frequently, patients will have non-compliance with medications, a lowphosphate diet, and dialysis treatment prior to the onset of calciphylaxis. Other risk factors that follow include: increasing age, increasing length of time on dialysis therapy, dyslipidemia, presence of diabetes, corticosteroids and immunosuppression [1]. Skin biopsy is infrequently performed for diagnosis because of poor healing and risk for secondary infections [2]. X-ray studies can emphasize and suggest the correct diagnosis in the setting of chronic dialysis. Treatment is aimed at controlling underlying hyperparathyroidism with bisphosphonates, parathyroidectomy, or cinacalcet in addition to dialysis in ESRD. Sodium thiosulfate is another treatment option; it displaces calcium ions from calcium deposits to form calcium thiosulfate, which is then dialyzed or excreted by functioning kidneys [3]. N. Kazanji (&) J. Falatko S. Neupane Department of Internal Medicine, Beaumont Health System, 3601 W 13 Mile Rd, Royal Oak, MI 48073, USA e-mail: noora.kazanji@beaumont.edu

National Cancer Database Comparison of Radical Cystectomy vs Chemoradiotherapy for Muscle‐Invasive Bladder Cancer: Implications of Using Clinical vs Pathologic Staging

Abstract: PURPOSE To test the hypothesis that bladder preservation therapy consisting of definitive chemoradiotherapy (chemoRT) results in similar overall survival rates to radical cystectomy/chemotherapy when balancing baseline patient characteristics and initial (preoperative) clinical stage. MATERIALS/METHODS A total of 7,322 patients with stage II-IV, M0 bladder cancer who were treated with cystectomy/chemo (N = 5,664) or definitive chemoRT (N = 1,658) were identified from the National Cancer Database. Baseline patient characteristics were compared using Pearson's chi-square, Fisher's exact test, and Wilcoxon's rank sum tests. Cox regressions were used to investigate for variables significantly correlated with overall survival (OS). OS was compared between cystectomy/chemo vs chemoRT before and after propensity score matched pair analyses using Kaplan-Meier curves and log-rank tests. RESULTS Patients who underwent cystectomy/chemo were significantly younger than ones treated with definitive chemoRT (mean age 63.7 vs 75.2; P < 0.001). Age, race, Charlson/Deyo Comorbidity Score (CDCS), clinical stage, insurance status, and type of facility significantly correlated with OS (P < 0.05 for all covariates). Patients treated with cystectomy/chemo were younger, healthier with better CDCS, and more likely treated at academic facilities. Before matched pair analyses, OS was significantly better when treated with cystectomy/chemo (3 year 56.4%; 5 year 45.9%) compared to chemoRT (3 year 47.3%; 5 year 33.2%) (P < 0.001); 28.6% of patients undergoing cystectomy were upstaged at the time of surgery. After matched pair analyses matching age, race, sex, CDCS, clinical (presurgical) stage, insurance, and facility type (N = 1,750), OS was no longer significantly different between cystectomy/chemo (3 year 52.1% and 5 year 41.0%) vs chemoRT (3 year 53.3% and 5 year 40.1%) (P = 0.5). CONCLUSIONS Patients treated with cystectomy/chemo were significantly younger and healthier compared to those treated with chemoRT. Once these factors were accounted for in propensity score matched pair analyses using clinical stage, overall survival was not significantly different between cystectomy/chemo and an organ-sparing approach with definitive chemoRT.