A Pilot Comparative Study of Quantitative Ultrasound, Conventional Ultrasound, and MRI for Predicting Histology-Determined Steatosis Grade in Adult Nonalcoholic Fatty Liver Disease.

OBJECTIVE: The purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound (QUS) parameters, attenuation coefficient and backscatter coefficient, in comparison with conventional ultrasound (CUS) and MRI-estimated proton density fat fraction (PDFF) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS: In this prospectively designed pilot study, 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014. Subjects underwent QUS, CUS, and MRI examinations within 100 days of clinical-care liver biopsy. QUS parameters (attenuation coefficient and backscatter coefficient) were estimated using a reference phantom technique by two analysts independently. Three-point ordinal CUS scores intended to predict steatosis grade (1, 2, or 3) were generated independently by two radiologists on the basis of QUS features. PDFF was estimated using an advanced chemical shift-based MRI technique. Using histologic examination as the reference standard, ROC analysis was performed. Optimal attenuation coefficient, backscatter coefficient, and PDFF cutoff thresholds were identified, and the accuracy of attenuation coefficient, backscatter coefficient, PDFF, and CUS to predict steatosis grade was determined. Interobserver agreement for attenuation coefficient, backscatter coefficient, and CUS was analyzed. RESULTS: CUS had 51.7% grading accuracy. The raw and cross-validated steatosis grading accuracies were 61.7% and 55.0%, respectively, for attenuation coefficient, 68.3% and 68.3% for backscatter coefficient, and 76.7% and 71.3% for MRI-estimated PDFF. Interobserver agreements were 53.3% for CUS (κ = 0.61), 90.0% for attenuation coefficient (κ = 0.87), and 71.7% for backscatter coefficient (κ = 0.82) (p < 0.0001 for all). CONCLUSION: Preliminary observations suggest that QUS parameters may be more accurate and provide higher interobserver agreement than CUS for predicting hepatic steatosis grade in patients with NAFLD.

Chronic Abdominal Wall Pain: An Under-Recognized Diagnosis Leading to Unnecessary Testing.

Chronic abdominal wall pain (CAWP) refers to a condition wherein pain originates from the abdominal wall itself rather than the underlying viscera. According to various estimates, 10% to 30% of patients with chronic abdominal pain are eventually diagnosed with CAWP, usually after expensive testing has failed to uncover another etiology. The most common cause of CAWP is anterior cutaneous nerve entrapment syndrome. The diagnosis of CAWP is made using an oft-forgotten physical examination finding known as Carnett's sign, where focal abdominal tenderness is either the same or worsened during contraction of the abdominal musculature. CAWP can be confirmed by response to trigger point injection of local anesthetic. Once diagnosis is made, treatment ranges from conservative management to trigger point injection and in refractory cases, even surgery. This review provides an overview of CAWP, discusses the cost and implications of a missed diagnosis, compares somatic versus visceral innervation, describes the pathophysiology of nerve entrapment, and reviews the evidence behind available treatment modalities.

Massive Esophageal Variceal Bleeding as a Rare Complication of Sickle Cell Anemia.

A 24-year-old man with sickle cell anemia presented with fatigue, dark stool, and coffee ground emesis. He was found to have large esophageal varices and experienced massive variceal hemorrhage in the hospital. The varices were caused by diffuse splanchnic venous thrombosis, and his only risk factor for hypercoagulability was sickle cell anemia. Splanchnic venous thrombosis due to sickle cell anemia is exceedingly rare.

Acute Esophageal Necrosis Presenting With Henoch-Schönlein Purpura.

A 63-year-old woman with abdominal pain and melena developed a palpable, purpuric rash and acute kidney injury. Skin and kidney biopsy confirmed Henoch-Schönlein purpura. Upper endoscopy revealed diffuse, circumferential, black-appearing mucosa of the esophagus consistent with acute esophageal necrosis (AEN), also known as black esophagus. AEN is a very rare cause of gastrointestinal hemorrhage with a high mortality risk. To our knowledge, there have been no prior reports of AEN associated with Henoch-Schonlein purpura or other vasculitis.

Sexual, irritative, and voiding outcomes, following stereotactic body radiation therapy for prostate cancer.

BACKGROUND: Urinary symptoms and sexual dysfunction are the two most common complaints following prostate radiotherapy. The impact of hypofractionated treatment on sexual function, irritative symptoms, and voiding symptoms has not been determined within the same patient population. Here we present our institutional data on sexual function, voiding function, irritative symptoms, and treatment response following SBRT. METHODS: This retrospective analysis includes 102 non-metastatic patients treated with SBRT at a single institution between May 2008 and September 2014. The course of radiotherapy consisted of 36.25 Gy (range 35-40) over five daily fractions. International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM), and PSA were recorded at baseline, 1, 3, 6, 9, 12, 18, 24, and 36 months after treatment. RESULTS: Median patient age was 72 years old with a median follow-up of 4.3 years. Pretreatment IPSS-I score was 5.21, increasing to 6.97 (p < .001) after 1 month. The mean IPSS-I score returned close to baseline after 3 months to 5.86 and decreased to below baseline after 2 years to 5.09. At 3 months, 9 months, and 2 years, 47.5, 76.2, and 91.1% of patients had reached IPSS-I resolution. The mean IPSS-O score prior to treatment was 5.31 and there was an increase in the score to 6.45 (p = 0.344) at 1 month. The score remained close to baseline and decreased to 4.00 at 2 years and significantly decreased to 3.74 (p = 0.035) at 3 years. 64.4, 82.1, and 96.0% of patients had IPSS-O resolution by 3 months, 9 months, and 2 years. The mean SHIM score prior to treatment was 13.52 and continually decreased to below baseline a year after treatment to 10.56 (p < .001). SHIM score began to improve at 18 months, but was still significantly less than baseline at 12.12 (p = .01). CONCLUSIONS: While an increase in AUA/IPSS score initially occurred, all patients resume normal activities immediately following treatment and the AUA/IPSS symptoms improved from baseline. Irittative symptoms take longer to resolve when compared to obstructive voiding symptoms in patients treated with SBRT. Three year PSA response, reported toxicity, erectile function preservation, and urinary function improvement, shows favorable results.

Age- and gender-related differences in cortical geometry and microstructure: Improved sensitivity by regional analysis.

OBJECTIVE: While the importance of cortical structure quantification is increasingly underscored by recent literature, conventional analysis techniques obscure potentially important regional variations in cortical structure. The objective of this study was to characterize the spatial variability in cortical geometry and microstructure at the distal radius and tibia using high resolution peripheral quantitative computed tomography (HR-pQCT). We show that spatially-resolved analysis is able to identify cortical sub-regions with increased sensitivity to the effects of gender and aging. METHODS: HR-pQCT scans of 146 volunteers (92 female/54 male) spanning a wide range of ages (20-78years) were analyzed. For each subject, radius and tibia scans were obtained using a clinical HR-pQCT system. Measures describing geometry (cortical bone thickness (Ct.Th)), microstructure (porosity (Ct.Po), pore diameter (Ct.Po.Dm), and pore size heterogeneity (Ct.Po.Dm SD)), and cortical bone density were calculated from the image data. Biomechanical parameters describing load and stress distribution were calculated using linear finite element analysis. Cortical quadrants were defined based on anatomic axes to quantify regional parameter variation. Subjects were categorized by gender, and age, and menopausal status for analysis. RESULTS: Significant regional variation was found in all geometric and microstructural parameters in both the radius and tibia. In general, the radius showed more pronounced and significant variations in all parameters as compared with the tibia. At both sites, Ct.Po displayed the greatest regional variations. Correlation coefficients for Ct.Po and Ct.Th with respect to load and stress distribution provided evidence of an association between regional cortical structure and biomechanics in the tibia. Comparing women to men, differences in Ct.Po were most pronounced in the anterior quadrant of the radius (36% lower in women (p<0.01)) and the posterior quadrant of the tibia (27% lower in women (p<0.01)). Comparing elderly to young women, differences in Ct.Po were most pronounced in the lateral quadrant of the radius (328% higher in elderly women (p<0.001)) and the anterior quadrant of the tibia (433% higher in elderly women (p<0.001)). Comparing elderly to young men, the most pronounced age differences were found in the anterior radius (205% higher in elderly men, (p<0.001)) and the anterior tibia (190% higher in elderly men (p<0.01)). All subregional Ct.Po differences provided greater sensitivity to gender and age effects than those based on the global means. CONCLUSION: These results show significant regional variation in all geometric and microarchitectural parameters studied in both the radius and tibia. Quantification of region-specific parameters provided increased sensitivity in the analysis of age- and gender-related differences, in many cases providing statistically significant differentiation of groups where conventional global analysis failed to detect differences. These results suggest that regional analysis may be important in studies of disease and therapeutic effects, particularly where microstructural parameters based on global analyses have thus far failed to identify a response in bone quality.

Pyrrolidine bis-cyclic guanidines with antimicrobial activity against drug-resistant Gram-positive pathogens identified from a mixture-based combinatorial library.

The rapid rise in antibiotic-resistant Gram-positive bacterial infections prompted us to explore the development of novel strategies for synthesis of large chemical libraries amenable to high-throughput screening for antimicrobial activities. Here we report the solid-phase synthesis of a 738,192 member pyrrolidine bis-cyclic guanidine chemical library with 26 different amino acids at three positions of diversity and 42 carboxylic acids at the fourth position. This synthetic combinatorial library was developed for positional scanning and screened for bacteriostatic and bactericidal activities against the important human pathogen methicillin-resistant Staphylococcus aureus (MRSA). The eight compound mixtures exhibiting bactericidal activity (10 microg/mL) against MRSA were used to direct the synthesis of 36 individual compounds that were then screened for activity against MRSA, vancomycin-resistant Enterococcus faecalis (VRE), and two Gram-negative bacterial species. At least 20 individual compounds were bactericidal for MRSA at 2.5 microg/mL, with a subset of these compounds showing bactericidal activities (10 microg/mL) against the other species tested. This approach demonstrates the capability to synthesize and screen a complex library to yield promising antimicrobials that address a critical need for novel infectious disease therapeutics.

The bicalutamide 150 mg early prostate cancer program: findings of the North American trial at 7.7-year median followup.

PURPOSE: We describe the results of North American Trial 23 of the bicalutamide (Casodex) early prostate cancer program in the context of the overall early prostate cancer program findings. MATERIALS AND METHODS: In Trial 23, 3,292 men with T1b-4, N0-Nx (N+ not allowed) M0 prostate cancer who had undergone radical prostatectomy or radiotherapy at 96 specialist referral centers in the United States (2,974) and Canada (318) were randomized 1:1 to 150 mg bicalutamide daily or placebo in addition to standard care for 2 years. RESULTS: In Trial 23 at a 7.7-year median followup there were few clinical events in the bicalutamide or standard care groups and the rates of objective progression were 15.4% and 15.3%, respectively. Mortality rates were 12.9% in the treatment group and 12.3% in the standard care group, including 11.2% and 11.0% for nonprostate cancer deaths in the absence of objective progression and 1.6% and 0.9%, respectively, for mortality due to prostate cancer. No differences in the primary end points (objective progression-free and overall survival) were seen between patients treated with bicalutamide and those treated with standard care alone. Bicalutamide (150 mg) significantly improved time to PSA progression (HR 0.80, 95% CI 0.72 to 0.90, p <0.001). The tolerability profile of bicalutamide was similar to that previously described. CONCLUSIONS: In Trial 23 the current data suggest that early or adjuvant therapy may not benefit patients at low risk for recurrence, such as those with localized disease. The findings of Trial 23 contrast with the results in the overall early prostate cancer program and in other published literature, in which bicalutamide has been shown to provide significant clinical benefit for locally advanced disease.