bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteogenic actions of metoprolol in an ovariectomized rat model of menopause
Authors: Zang Yuan , Tan Quanchang , Ma Xiangyu , Zhao Xiong , Lei Wei
Published: June 2016

Objective:

Osteoporosis and hypertension are age-related chronic diseases with increased morbidity rates among postmenopausal women. Clinical epidemiological investigations have demonstrated that hypertensive patients treated with β1-selective β-blockers have a higher bone mineral density (BMD) and lower fracture risk. Nevertheless, no fundamental studies have examined the relationships between β1-selective β-blockers and these effects. The present study explored the effects and mechanisms of metoprolol in the in vitro treatment of osteoblasts and the in vivo treatment of ovariectomy-induced osteoporosis in rats.

Methods:

Primary osteoblasts were obtained by digestion of the cranial bones of 24-hour-old Sprague-Dawley rats. After metoprolol treatment, cell proliferation and differentiation capacities were assessed at the corresponding time points. In addition, 3-month-old female Sprague-Dawley rats (200-220 g) were divided into a sham-operated group (n = 8) and three ovariectomized (OVX) (bilateral removal of ovaries) groups as follows: vehicle (OVX; n = 8), low-dose metoprolol (L-M, oral, 120 mg/kg/d; n = 8), and high-dose metoprolol (H-M, oral, 240 mg/kg/d; n = 8). After 12 weeks of metoprolol treatment, BMD, microarchitecture, and biomechanical properties were evaluated.

Results:

The results indicated that the treatments with 0.01 to 0.1 μM metoprolol increased osteoblast proliferation, alkaline phosphatase activity, and calcium mineralization, and promoted the expression of osteogenic genes. The in vivo study indicated that administration of metoprolol to OVX rats resulted in maintenance of the BMDs of the L4 vertebrae. Moreover, amelioration of trabecular microarchitecture deterioration and preservation of bone biomechanical properties were detected in the trabecular bones of the OVX rats.

Conclusions:

Our findings indicate that metoprolol prevents estrogen deficiency-induced bone loss by increasing the number and enhancing the biological functions of osteoblasts, implying its potential use as an alternative treatment for postmenopausal osteoporosis in hypertensive patients.
Cognition and the menopause transition
Authors: Maki Pauline M. , Henderson Victor W.
Published: June 2016

Complaints about forgetfulness, “brain fog,” and difficulty concentrating are common in women transitioning through menopause. Women with these cognitive complaints often express concern about whether these problems are normal, related to menopause, or represent a symptom of Alzheimer disease or another serious cognitive disorder. In this Practice Pearl, we provide a brief summary of the scientific literature on the frequency of cognitive complaints in midlife women, the validity of complaints in relation to performance on standardized cognitive tests, and the influence of menopause on cognitive performance. We then offer recommendations for healthcare providers and women to address cognitive concerns.
Gynecomastia Management: An Evolution and Refinement in Technique at UT Southwestern Medical Center
Authors: Bailey Steven H. , Guenther Dax , Constantine Fadi , Rohrich Rod J.
Published: June 2016

Gynecomastia is a benign proliferation of male breast glandular tissue. Gynecomastia can affect men at any stage of life. Traditional treatment options involved excisional surgeries with periareolar or T-shaped scars, which can leave more visible scars on the chest. The technique presented represents a technique used by the senior author, which relies on ultrasonic liposuction and pull-through technique to remove breast tissue. A retrospective chart review was performed, including all patients who were treated, from 2000 to 2013 by the senior author, for gynecomastia. A deidentified database was created to record patient characteristics, including age, height, weight, ptosis, stage of gynecomastia, and gynecomastia classification. Surgical approaches, complications, and revisions were also recorded. Our experience includes 75 patients with all grades of gynecomastia from 2000 to 2013. These cases span the evolution of our technique to include direct pull-through excision with ultrasound-assisted liposuction. The distribution of the grades I, II, III, and IV ptosis was 30.6%, 36 %, 22.6%, and 10.6% respectively. There were no complications in this series. Only one patient with grade III ptosis required revision surgery. This technique provides a safe and aesthetically pleasing way to treat gynecomastia with a low need for revision.
Surgical Delay Facilitates Pedicled Nipple-sparing Mastectomy and Reconstruction in the Ptotic Patient
Authors: Schwartz Jean-Claude D. , Skowronksi Piotr P.
Published: June 2016

Significant ptosis is a relative contraindication for nipple-sparing mastectomy and reconstruction. Repositioning of the nipple on the reconstructed breast is best accomplished using a pedicled approach that is risky in the immediate setting. We utilized a surgical delay before reconstruction that allowed for repositioning of the nipple-areola complex on an inferior pedicle. This also allows for resizing of the nipple-areola complex, reliable complete coverage of the prosthesis with viable tissue, and creation of an ideal skin envelope in patients with skin excess. Here, we present the first description of a surgical delay to facilitate pedicled nipple-sparing mastectomy and reconstruction.
Disparate British Breast Reconstruction Utilization: Is Universal Coverage Sufficient to Ensure Expanded Care?
Authors: Offodile Anaeze C. , Guo Lifei
Published: June 2016

Our intent is to improve the understanding of the ability of healthcare providers to deliver high-quality care as we approach an era of universal coverage. We adopted 2 unique vantage points in this article: (1) the mandated coverage for immediate breast reconstruction (IBR) surgery as a microcosmic surrogate for universal coverage overall and (2) we then scrutinized the respective IBR utilization rates in a contemporaneous system of 2 healthcare delivery models in the United Kingdom, that is, the public National Health Service trust versus private-sector hospitals. A literature review was performed for IBR rates across public trust and private-sector hospitals in the United Kingdom. The IBR rate among public trust hospitals was 17% compared with 43% in the private sector. In the trust hospital setting, the enactment of 2 government mandates, intended to increase the access to cancer care, seemed to fall short in maximizing the ability of surgical practitioners to deliver quality care to patients. Among women who did not receive IBR, 65% felt that they had received the sufficient amount of information to appropriately inform their decision. In addition, only 46% of this same cohort reported a consultation with a reconstructive surgeon preoperatively. Private-sector hospitals delivered better IBR care because of the likely presence of infrastructure and financial incentives for physicians. These results serve as a call for a better alignment between policy initiatives designed to expand care access and the perogatives of physicians to ensure an optimized delivery of the expanded care such policy mandates.
Assessing Physical Activity as a Core Component in Cardiac Rehabilitation
Authors: Kaminsky Leonard A. , Brubaker Peter H. , Guazzi Marco , Lavie Carl J. , Montoye Alexander H. K. , Sanderson Bonnie K. , Savage Patrick D.
Published: June 2016

Physical inactivity is a well-established major risk factor for cardiovascular disease. As such, physical activity counseling is 1 of the 10 core components of cardiac rehabilitation/secondary prevention programs recommended by the American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR). In addition, the ability to perform a physical activity assessment and report outcomes is 1 of the 10 core competencies of cardiac rehabilitation/secondary prevention professionals published by the AACVPR. Unfortunately, standardized procedures for physical activity assessment of cardiac rehabilitation patients have not been developed and published. Thus, the objective of this AACVPR statement is to provide an overview of physical activity assessment concepts and procedures and to provide a recommended approach for performing a standardized assessment of physical activity in all comprehensive cardiac rehabilitation programs following the core components recommendations.
Ocular Hypotensive Effect of ONO-9054, an EP3/FP Receptor Agonist: Results of a Randomized, Placebo-controlled, Dose Escalation Study
Authors: Harris Alon , Ward Caroline L. , Rowe-Rendleman Cheryl L. , Ouchi Takafumi , Wood Andrew , Fujii Akifumi , Serle Janet B.
Published: June 2016

Purpose:

To assess pharmacodynamic and safety profiles of ONO-9054 following single and multiple day dosing in subjects with ocular hypertension or open-angle glaucoma.

Materials and Methods:

This was a phase I, single-center, randomized, double-masked, placebo-controlled dose-escalation study. Nine subjects were randomized to each of ONO-9054 3, 10, 20, 30 μg/mL and 12 to placebo. Subjects received a single drop to each eye at 07:00±30 minutes (single dose). Following a 4-day no-treatment period, subjects were dosed once daily for 14 consecutive days (multiple day dosing). Intraocular pressure (IOP) was measured regularly and compared with baseline measurements. Ocular examinations assessed safety and tolerability.

Results:

Mean IOP decreased dose dependently. Following single dosing, IOP decreased from 22.9±4.0 to 15.9±2.3 mm Hg (ONO-9054, 30 μg/mL) at peak effect 9 hours postdose; the reduction in placebo-treated subjects was from 22.3±2.4 to 21.5±3.3 mm Hg. Following multiple day dosing, the greatest reduction in IOP occurred 1 hour postdose on day 18, from 23.3±0.6 to 15.1±2.4 mm Hg (ONO-9054, 10 μg/mL); the smallest reduction at this time was from 23.9±0.8 to 18.6±2.0 mm Hg (ONO-9054, 3 μg/mL). Pressures remained reduced on day 19, 25 hours after the last dose, when the lowest measurement was 15.8±2.1 mm Hg (ONO-9054, 10 μg/mL). Anterior uveitis and vitreous detachment were each reported in 2 subjects and considered moderate by the Investigator. Ocular hyperemia and tolerability symptoms were generally mild and transient.

Conclusions:

ONO-9054 was well-tolerated and elicited dose-dependent reductions in IOP, which were sustained for at least 24 hours following 2 weeks of consecutive daily dosing.
Influence of Test Strategy on Octopus Perimeter Cluster Mean Defect Values: Adaptive Bracketing Normal Strategy Versus Tendency-oriented Perimetry
Authors: Holló Gábor
Published: June 2016

Background/Purpose:

Using adaptive bracketing “normal” (N) strategy it has been shown that cluster trend analysis is useful for early detection of glaucomatous progression with Octopus perimetry. However, in clinical practice “tendency-oriented perimetry” (TOP) is mostly used. In TOP, responses given at neighboring points modify the threshold values, and this process does not respect cluster borders. In the current investigation, we evaluated the influence of test strategy on the cluster mean defect (cluster MD) values.

Materials and Methods:

Sixty-nine eyes with normal visual field and 63 glaucoma eyes with predominantly mild to moderate glaucomatous visual field defect underwent Octopus perimetry with N and TOP strategy on the same day. Cluster MD values and global parameters were compared between test strategies in each group.

Results:

In the normal group, all global parameters (P≤0.0003) and cluster MD for 6 uncorrected and 5 corrected clusters differed significantly between the strategies (P≤0.0052). In the glaucoma group, no significant difference was seen for global mean sensitivity and global MD, but square loss variance reflecting inhomogeneity was 1.0 dB lower with TOP (P<0.0001). Two uncorrected and 3 corrected clusters differed significantly (P≤0.0026) and several other clusters differed almost significantly between the strategies. The differences spread up to 1.9 dB without any systematic direction.

Conclusions:

Using TOP, cluster MD determined for one cluster is statistically and clinically significantly influenced by responses given at points outside the cluster. This may also influence cluster trend analysis for glaucomatous progression. Therefore, TOP, although fast and easily performed, is not the optimal procedure for cluster and corrected cluster analyses.
Combined Ahmed Glaucoma Valve Placement, Intravitreal Fluocinolone Acetonide Implantation and Cataract Extraction for Chronic Uveitis
Authors: Chang Ingrid T. , Gupta Divakar , Slabaugh Mark A. , Vemulakonda Gurunadh A. , Chen Philip P.
Published: June 2016

Purpose:

To report the outcomes of combined Ahmed glaucoma valve (AGV) placement, intravitreal fluocinolone acetonide implant, and cataract extraction procedure in the treatment of chronic noninfectious uveitis.

Patients and Methods:

Retrospective case series of patients with chronic noninfectious uveitis who underwent AGV placement, intravitreal fluocinolone acetonide implantation, and cataract extraction in a single surgical session performed at 1 institution from January 2009 to November 2014. Outcome measures included intraocular pressure (IOP) and glaucoma medication use. Secondary outcome measures included visual acuity, systemic anti-inflammatory medications, number of uveitis flares, and complications.

Results:

Fifteen eyes of 10 patients were studied, with a mean age of 40.3±15.7 and mean follow-up duration of 26 months (range, 13 to 39 mo). Before surgery, the IOP was 18.5±7.3 mm Hg and patients were using 1.5±1.5 topical glaucoma medications. At the 12-month follow-up, IOP was 12.8±3.2 mm Hg (P=0.01) and patients were using 0.5±0.8 (P=0.03) topical glaucoma medications. At 36 months of follow-up, late, nonsustained hypotony had occurred in 3 eyes (20%), and 1 eye (6%) had received a second AGV for IOP control. Before treatment, patients had 2.7±1.5 uveitis flares in the year before surgery while on an average of 2.1±0.6 systemic anti-inflammatory medications, which decreased to an average of 0.1±0.3 (P<0.01) flares the year after surgery while on an average of 0.4±1.1 (P<0.01) systemic medications.

Conclusion:

Combined AGV, intravitreal fluocinolone acetonide implant, and cataract extraction is effective in controlling IOP and reducing the number of glaucoma medications at 12 months after treatment in patients with chronic uveitis.
A Procedural and Educational Experience Following Creation of an Advanced Pediatric Endoscopy Service
Authors: Mezoff Ethan A. , Lin Tom K. , Kaul Ajay , Kocoshis Samuel , Putnam Phil , Pentiuk Scott
Published: June 2016

Advanced endoscopic procedures occur infrequently enough in pediatric patients to preclude effective maintenance of competence among all pediatric gastroenterologists. A recent study suggests that fellows are largely unable to achieve the prescribed case volume recommended to achieve competence. We sought to describe the procedural and educational experience following the creation of an advanced pediatric endoscopy service in response to declining confidence among practice members regarding advanced procedures. We found most advanced endoscopy cases (90%) were accomplished during routine business hours with little seasonal variation. Esophageal dilations occurred far more than all other procedures provided by this service. Control of nonvariceal bleeding, feeding tube placement, enteroscopy, and needle knife therapy, among others, were performed exclusively but relatively infrequently by members of this advanced endoscopy service. Fellows were present for many cases, although they participated in relatively few. We conclude that the creation of an advanced endoscopy service permits distillation of rare but technically demanding cases to few providers, ensuring maintenance of skills, although the role of fellows remains in question.
Impact of Environmental and Familial Factors in a Cohort of Pediatric Patients With Inflammatory Bowel Disease
Authors: Strisciuglio Caterina , Giugliano Francesca , Martinelli Massimo , Cenni Sabrina , Greco Luigi , Staiano Annamaria , Miele Erasmo
Published: June 2016

Objectives:

The primary role of environment on inflammatory bowel disease (IBD) onset has been recently stressed. We aimed to investigate the effect of environmental factors in an IBD pediatric cohort.

Methods:

A total of 467 subjects (264 IBD and 203 controls) were enrolled. All patients underwent a questionnaire including 5 different groups of environmental risk factors: family history of IBD and autoimmune diseases, perinatal period, home amenities and domestic hygiene, childhood diseases and vaccinations, and diet.

Results:

In a multivariate model, mother's degree (odds ratio [OR]: 5.5; 2.5–11.6), duration of breast feeding >3rd month (OR: 4.3; 1.6–10.5), father's employment (OR: 3.7; 1.2–8.7), gluten introduction <6th month (OR: 2.8; 1.5–5), number of siblings <2 (OR: 2.8; 1.5–5.3), and family history of autoimmune diseases (OR: 2.7; 1.4–5.3) were significant risk factors for Crohn disease. Low adherence to Mediterranean diet (OR: 2.3; 1.2–4.5), gluten introduction <6th month (OR: 2.8; 1.6–4.9), and number of siblings <2 (OR: 2; 1.1–3.6) were significant risk factors for ulcerative colitis. Owning pets (OR: 0.3; 0.1–0.7) and bed sharing (OR: 0.2; 0.1–0.6) were protective factors for Crohn disease, whereas owning pets (OR: 0.4; 0.2–0.8) and family parasitosis (OR: 0.07; 0.01–0.4) were protective factors for ulcerative colitis.

Conclusions:

Our study confirms that environmental factors are closely linked to IBD onset and may partly explain IBD rise in developed countries.
Remission in Pediatric Inflammatory Bowel Disease Correlates With Prescription Refill Adherence Rates
Authors: Samson Charles M. , Mager Douglas , Frazee Sharon , Yu Feliciano
Published: June 2016

Objectives:

The aim of the study was to use pharmacy benefit management (PBM) prescription claims data to assess refill adherence in pediatric inflammatory bowel disease (IBD) and correlate adherence with clinical outcomes in pediatric IBD.

Methods:

We identified 362 pediatric patients with IBD seen at Washington University from 9/1/2012 to 8/31/2013 and matched them within Express Scripts’ member eligibility files for clients allowing use of prescription drug data for research purposes. Maintenance IBD medication possession ratios (MPR) were determined through PBM prescription claims data and chart review. Demographic and prospectively captured physician global assessments (PGA) were retrospectively extracted from the medical record. MPR was analyzed as continuous data and also dichotomized as greater or less than 80%.

Results:

Among our 362 patients, we matched 228 (63%) within Express Scripts’ eligibility data files. Of those, 78 patients were continuously eligible for benefits and had at least one outpatient prescription IBD medication prescribed. Their mean MPR was 0.63 ± 0.31 (standard deviation) and 40% had an MPR ≥80%. Patients in clinical remission had a higher mean MPR than those with an active PGA (0.72 ± 0.28 vs 0.51 ± 0.32, P = 0.002) and patients whose MPR were ≥80% were more likely to have a PGA of remission than those with whose MPR were <80% (84% vs 43%, P = <0.001).

Conclusions:

We found a significant association between refill adherence and clinical remission. Nonadherence was common and was more common in adolescents. Use of PBM databases to identify and intervene on patients with poor adherence may improve outcomes in pediatric IBD.
Predominant Neurologic Manifestations Seen in a Patient With a Biallelic Perforin1 Mutation (PRF1; p.R225W)
Authors: Madkaikar Manisha , Gupta Maya , Dixit Ashish , Patil Veerendra
Published: June 2016

Neurological manifestations in familial hemophagocytic lymphohistiocytosis (FHL) are common, seen in up to 73% of patients in their course of disease. However, in majority of the cases central nervous system manifestations are associated with other clinical and laboratory parameters of hemophagocytic lymphohistiocytosis. We report here a case with FHL2 in whom hemophagocytic lymphohistiocytosis was a presenting manifestation which responded to specific therapy, however, there was isolated central nervous system relapse while patient was in remission and off therapy. FHL2 was confirmed on the basis of reduced perforin expression and homozygous mutation in PRF1at codon 637 in exon 3 (c.673C>T p.Arg225Trp).
The Expression Pattern of p120-Catenin is Associated With Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer
Authors: Liu Yang , Wang Si , Dong Qian-Ze , Liu Nan , Han Yong , Zhang Xiu-Peng , Fan Chui-Feng , Wang En-Hua
Published: June 2016

Background:

Previous research connects p120-catenin (p120ctn) with epidermal growth factor receptor (EGFR) signaling pathways, which presents a potential role for p120ctn in EGFR tyrosine kinase inhibitor (EGFR-TKIs) resistance. However, a direct correlation between the expression pattern of p120ctn in solid tumors and the therapeutic effect of EGFR-TKIs has not yet been demonstrated.

Methods and Results:

In this study, the expression pattern of p120ctn was examined in patients with the EGFR gene mutation in lung adenocarcinoma, and p120ctn was found to have different patterns of expression even in the same mutation type. The therapeutic effect of EGFR-TKIs was investigated in these patients, and patients with an abnormal expression of p120ctn were found to be more likely to have drug resistance. A gefitinib-resistant lung cancer cell line was established and alterations in the p120ctn expression pattern were also observed in vitro.

Conclusions:

Therefore, this study demonstrates that the expression pattern of p120ctn is associated with acquired resistance to EGFR-TKIs in lung cancer, providing information toward addressing the problem of drug resistance in patients with non–small cell lung cancer.
Expression of Minichromosome Maintenance Proteins in Actinic Keratosis and Squamous Cell Carcinoma
Authors: Stojkovic-Filipovic Jelena , Brasanac Dimitrije , Bosic Martina , Boricic Novica , Lekic Branislav
Published: June 2016

Minichromosome maintenance (MCM) proteins are a group of proteins involved in DNA replication and cell-cycle regulation. Because they are associated with DNA through G1 into S phase, MCM proteins are potentially specific indicators of cell proliferation that could be valuable markers of dysplasia, and preinvasive and invasive malignant tumors. To analyze MCM protein expression patterns in actinic keratosis (AK), Bowen disease (BD), and cutaneous squamous cell carcinoma (SCC), we performed immunohistochemical staining of MCM2, -5, and -7 on tissue microarray blocks from 91 AK, 50 BD, and 174 SCC samples. The distribution and semiquantitatively assessed number of positive cells were analyzed in relation to the type of the lesion and the SCC prognostic parameters (grade, diameter, and thickness). Basal expression of all 3 proteins was observed more frequently in AK, whereas the distribution in BD was predominantly diffuse (P<0.001). All 3 proteins showed peripheral distribution in most well-differentiated SCC and diffuse distribution in poorly differentiated tumors (P<0.001). Using the 50% cut-off value, there was a statistically significant difference among AK, BD, and SCC (P<0.001). In addition, all MCM proteins showed highly significant differences (P<0.001) between well-differentiated SCC and both moderately and poorly differentiated SCC. The diffuse distribution and 50% cut-off value of positive cells revealed statistically significant associations of all MCM proteins with SCC thicker than 6 mm. Our results suggest a role for MCM proteins in the progression of in situ keratinocytic lesions and their association with high-risk features in SCC.
Immunohistochemical Profiles of Endometrioid Endometrial Carcinomas With and Without Metastatic Disease
Authors: Geels Yvette P. , van der Putten Louis J.M. , van Tilborg Angela A.G. , Nienhaus Birgit E.C. , van den Berg-van Erp Saskia H. , Snijders Marc P.L.M. , van der Wurff Anneke , Massuger Leon F.A.G. , Bulten Johan , Pijnenborg Johanna M.A.
Published: June 2016

A minority of endometrial carcinomas present at an advanced stage with a poor prognosis, and should be identified to individualize treatment. Immunohistochemical markers have been studied, but most have not been directly linked to metastasis. This study analyzes the immunohistochemical profile of endometrioid endometrial carcinomas (EECs) with and without metastases, and corresponding metastases. Tissue microarray slides from stage I EECs, stage III-IV EECs, and corresponding metastases were stained and scored for expression of β-catenin, E-cadherin, ER, PR, PTEN, p16, MLH1, PMS2, L1CAM, p53, p21, and MIB1. Scores were compared between primary stage I and III-IV EECs, stage III-IV EECs, and the corresponding metastases, and between intra-abdominal and distant metastases. Primary tumors with distant metastases had a significantly lower ER expression than those without metastases or with intra-abdominal metastases. Distant metastases had a significantly lower PR expression than the corresponding primary tumor and intra-abdominal metastases. In contrast, p16 and PTEN expression was significantly higher in intra-abdominal metastases compared with corresponding primary tumors. Immunohistochemistry predicts both presence and location of EEC metastases. Loss of ER and PR was related to distant spread, and increased expression of PTEN and p16 was related to intra-abdominal spread. Additional research should assess the use of these markers in the diagnostic workup as well as the possibility to target metastases through these markers.
Factor XIII Subunit A Immunohistochemical Expression is Associated With Inferior Outcomes in Acute Promyelocytic Leukemia
Authors: Raval Jay S. , Berg Aaron N. , Djokic Miroslav , Roth Christine G. , Rollins-Raval Marian A.
Published: June 2016

Coagulation factor XIII subunit A (FXIIIa) intracellular expression has been described in platelets, megakaryocytes, monocytic cells, and leukemic blasts. Flow cytometric-based studies have suggested prognostic implications of FXIIIa expression, especially within the acute promyelocytic leukemia (APL) subgroup of acute myeloid leukemia (AML); however, its prognostic correlate by immunohistochemistry (IHC) is unknown. The aims of this study were to (1) define the clinicopathologic features of FXIIIa IHC-positive AML and (2) compare APL with other AML subtypes. Eighty-seven bone marrow biopsies or clot/particle preparations from our institution were evaluated with FXIIIa IHC. The study cohort consisted of bone marrow evaluations of 36 consecutive pretherapy APL, 42 selected pretherapy non-APL AML, and 9 negative staging cases. FXIIIa IHC expression was correlated with clinical and pathologic features and overall survival (OS). Leukemic blast FXIIIa cytoplasmic positivity was noted in 56% (20/36) APL and 74% (31/42) non-APL AML (P=0.10). FXIIIa IHC expression was associated with inferior OS within the APL cohort (P=0.04). No OS differences were noted in comparing FXIIIa IHC expression in all AML (P=0.17), or FXIIIa IHC expression within favorable, intermediate or adverse cytogenetic groups (P=0.14, 0.22 and 0.87, respectively). FXIIIa IHC expression is observed among a broad spectrum of AML subtypes and is not characterized by specific pathologic features. However, within the APL subgroup, FXIIIa IHC expression is associated with an inferior outcome and may be useful for additional prognostic risk stratification.
Retrospective Analysis of Atypical Glands Suspicious for Carcinoma in Transurethral Resection of Prostate
Authors: Chen Sonja , Patil Pallavi A. , Lepe Marcos , Lombardo Kara A. , Amin Ali , Matoso Andres
Published: June 2016

Prostate biopsies with foci of atypical glands suspicious, but not diagnostic of carcinoma (ATYP) are associated with an increased risk of cancer diagnosis in subsequent biopsies. The significance of similar findings in transurethral resections of the prostate (TURP) is unknown. A total of 1338 specimens without a diagnosis of cancer were retrieved from our surgical pathology files from 1994 through 2014. Of these, 18 cases (1.3%) were identified with the diagnosis of ATYP. Immunohistochemistry (IHC) for p63, high molecular weight cytokeratin, and racemase (PIN4) was performed in all cases. The cases were grouped based on the main benign mimicker of cancer that could not be excluded from the differential diagnosis and prevented a definitive diagnosis. Adenosis accounted for 50% of the cases (9/18), 33.3% of the cases (6/18) were cautery artifact, 11% of the cases (2/18) were basal-cell hyperplasia with nucleoli and 5.6%, a single case, cribriform clear cell hyperplasia could not be excluded. Eight patients had follow-up biopsies and 2 were diagnosed with prostatic adenocarcinoma Gleason grade 3+3=6; both were alive 3 years after initial diagnosis. Although the most frequent benign mimickers that prevent a definitive diagnosis of cancer in needle biopsies are the small size of the atypical foci, PIN and partial atrophy, in TURPs, they are adenosis and cautery artifact. The rate of cancer diagnosed in follow-up is similar or lower than in patients with prior benign prostate needle biopsies and significantly lower than in patients with a prior diagnosis of ATYP in biopsies of the peripheral zone.
Reflex Estrogen Receptor (ER) and Progesterone Receptor (PR) Analysis of Ductal Carcinoma In Situ (DCIS) in Breast Needle Core Biopsy Specimens
Authors: VandenBussche Christopher J. , Cimino-Mathews Ashley , Park Ben Ho , Emens Leisha A. , Tsangaris Theodore N. , Argani Pedram
Published: June 2016

Most institutions reflexively test all breast core needle biopsy specimens showing ductal carcinoma in situ (DCIS) for estrogen receptor (ER) and progesterone receptor (PR). However, 5 factors suggest that this reflex testing unnecessarily increases costs. First, ER/PR results do not currently impact the next step in standard therapy; namely, surgical excision. Second, a subset of surgical excisions performed for DCIS diagnosed on core needle biopsy will harbor infiltrating mammary carcinoma, which will then need to be retested for ER/PR. Third, because ER and PR labeling is often heterogeneous in DCIS, negative results for ER/PR on small core needle biopsy specimens should logically be repeated on surgical excision specimens with larger amounts of DCIS to be sure that the result is truly negative. Fourth, many patients with pure ER/PR-positive DCIS after surgical excision will decline hormone therapy, so any ER/PR testing of their DCIS is unnecessary. Fifth, PR status in DCIS has no proven independent value. We now examine the unnecessary added costs associated with reflex ER/PR testing of DCIS on core needle biopsy specimens due to these factors. We reviewed 58 core needle biopsies showing pure DCIS that also had a resulting surgical excision specimen at our institution over a period of 2 years. No patient received neoadjuvant hormone therapy. On surgical excision, 5 (8.6%) had only benign findings, 44 (75.9%) had pure DCIS, and 9 (15.5%) had DCIS with invasive mammary carcinoma. The 9 cases with invasive mammary carcinoma in the surgical excision specimen (16%) and the 4 pure DCIS in surgical excision specimens that were ER/PR negative on core needle biopsy would need repeat ER/PR testing. The total unnecessary increased cost of core needle biopsy specimen testing of these 13 cases was $8148.92 ($140/patient for the 58 patients in the study). We found that ER/PR testing results impacted patient management in only 16/49 pure DCIS cases after surgical excision (33%), indicating that ER/PR testing costing $20,685.72 ($357/patient in the study) had been performed unnecessarily. PR testing could have been omitted in the 16 cases in which ER/PR results were used, which would have saved $5014.72, or $86.46 per patient. Extrapolating the increased cost of $583 per DCIS diagnosis on core needle biopsy to 60,000 new cases of DCIS in the United States each year, reflex core needle biopsy ER/PR testing unnecessarily increases costs by approximately $35 million. We recommend that ER/PR not be reflexively ordered on core needle biopsy specimens or surgical excision specimens containing DCIS, but instead that ER alone be performed on surgical excision specimens only when hormone therapy is a serious consideration after medical oncology consultation.
Point-of-Care Ultrasound Integrated Into a Staged Diagnostic Algorithm for Pediatric Appendicitis
Authors: Doniger Stephanie J. , Kornblith Aaron
Published: June 2016

Objectives

We hypothesized that point-of-care ultrasound (POCUS) is as accurate as radiology-performed ultrasound in evaluating children with clinical concern for appendicitis. As part of a staged approach, we further hypothesized that POCUS could ultimately decrease computed tomography (CT) utilization.

Methods

This was a prospective, convenience sampling of patients aged 2 to 18 years presenting with abdominal pain to a pediatric emergency department. Those patients with prior abdominal imaging, pregnant, or unable to tolerate the examination were excluded. An algorithm was followed: POCUS was first performed, followed by a radiology-performed ultrasound, and then a CT as necessary. The main outcome measure was the accuracy of the POCUS in diagnosing of appendicitis. This was compared with radiology-performed ultrasound. We also examined whether certain patient or clinical characteristics influenced the performance of POCUS. Lastly, we determined the amount by which CT scans were decreased through this staged algorithm.

Results

Forty patients were enrolled and underwent a POCUS examination. A total of 16 (40%) had pathology-confirmed appendicitis. Point-of-care ultrasound had a sensitivity of 93.8% (95% confidence interval [CI], 69.7%–98.9%) and specificity of 87.5% (95% CI, 67.6%–97.2%). Radiology-performed ultrasound had a sensitivity of 81.25% (95% CI, 54.3%–95.7%) and specificity of 100% (95% CI, 85.6%–100%). The radiology-performed and POCUS examinations had very good agreement (κ = 0.83, P < 0.0005). Patient characteristics including body mass index did not have an affect on the POCUS. However, POCUS identified all patients with an Alvarado score higher than 6. Overall, the reduction in CT examinations was 55%.

Conclusions

In pediatric patients presenting with clinical concern for acute appendicitis, a staged algorithm that incorporates POCUS is accurate and has the potential to decrease CT scan utilization.
Measuring the Transrectal Diameter on Point-of-Care Ultrasound to Diagnose Constipation in Children
Authors: Doniger Stephanie J. , Dessie Almaz , Latronica Cornelia
Published: June 2016

Objectives

The aim of the study was to determine the test performance characteristics for point-of-care ultrasound in diagnosing constipation, through measuring the transrectal diameter (TRD). We sought to develop a sonographic numeric cutoff value for diagnosing constipation. Secondary objectives included whether certain patient characteristics would affect the TRD measurement and the accuracy of the TRD in comparison with abdominal radiographs.

Methods

We conducted a prospective, cohort study of pediatric patients between the age of 4 and 17 years, presenting with abdominal pain to a pediatric emergency department. A point-of-care ultrasound was performed with a phased array transducer (5-1 MHz). In addition to a thorough history and physical examination, each patient was administered with the Rome III questionnaire, which served as the criterion standard for the diagnosis of constipation. Radiographs and enema treatments were performed at the discretion of the treating attending physician. When enemas were administered, a postenema TRD measurement was obtained.

Results

Fifty subjects were “constipated” or “nonconstipated,” as determined by the Rome III questionnaire. A TRD cutoff of 3.8 cm or greater correlated with the diagnoses of constipation (P < 0.001). Ultrasound-diagnosed constipation had a sensitivity of 86% (95% confidence interval, 69%–96%), specificity of 71% (95% CI, 53%–85%), negative predictive value of 0.87 (95% CI, 0.68–0.95), and positive predictive value of 0.70 (95% CI, 0.52–0.84). The TRD measurement was not affected by patient physical characteristics or bladder fullness. In 7 patients, an enema was administered. There was an overall mean (SD) decrease of 1.22 (1.62) cm; this difference was not statistically significant (P = 0.093). Abdominal radiographs were performed in 25 patients. When compared with abdominal radiographs, ultrasound had a higher specificity of 71% (95% CI, 53%–85%), but this difference was not statistically significant. Ultrasound performed similarly to abdominal radiographs with regard to sensitivity 86% (95% CI, 67%–95%), positive predictive value of 0.70 (95% CI, 0.52–0.84), and negative predictive value of 0.87 (0.68–0.95). In 22 of 25 patients who received radiographs, the ultrasound diagnosis was the same as the radiologist read of the radiographs. Potentially, 88% of radiographs could have been avoided in these patients.

Conclusions

In pediatric patients with abdominal pain, there is a strong correlation of an enlarged TRD with constipation. Our results suggest that point-of-care ultrasound is a useful adjunct for diagnosing constipation and has the potential to replace the use of abdominal radiographs.
Cannabinoid Poisoning by Hemp Seed Oil in a Child
Authors: Chinello Matteo , Scommegna Salvatore , Shardlow Alison , Mazzoli Francesca , De Giovanni Nadia , Fucci Nadia , Borgiani Paola , Ciccacci Cinzia , Locasciulli Anna , Calvani Mauro
Published: June 2016

We report a case of mild cannabinoid poisoning in a preschool child, after 3-week ingestion of hemp seed oil prescribed by his pediatrician to strengthen his immune system. The patient presented neurological symptoms that disappeared after intravenous hydration. A possible mild withdrawal syndrome was reported after discharge. The main metabolite of Δ9-tetrahydrocannabinol was detected in urine, and very low concentration of Δ9-tetrahydrocannabinol was detected in the ingested product. This is, as far as we know, the first report of cannabinoid poisoning after medical prescription of hemp seed oil in a preschool child.
Postexposure prophylaxis after hepatitis C occupational exposure in the interferon-free era
Authors: Hughes Heather Y. , Henderson David K.
Published: June 2016

Purpose of review

Healthcare personnel are at risk for occupational exposures to bloodborne pathogens. Primary prevention remains the first line of defense, but secondary prevention measures known to be effective should be implemented when percutaneous exposures occur. Hepatitis C virus (HCV) is a major infectious cause of liver-related morbidity and mortality. Chronic HCV treatment has changed dramatically, with many all-oral directly acting anti-HCV antiviral (DAA) regimens now available. Evidence for the use of DAAs as postexposure prophylaxis (PEP) after occupational exposures to HCV is summarized here.

Recent findings

Little new evidence supports the use of antivirals in acute HCV infection. Several preliminary studies have examined the use of DAAs or host target agents in chronic HCV treatment. Effective HCV PEP requirements likely include pan-genotypic activity and a high barrier to resistance. One investigational DAA has shown promising results as an efficacious option for all genotypes in chronic HCV treatment and may ultimately represent a potential HCV PEP agent.

Insufficient supporting data exist to endorse the use of DAAs for PEP after HCV occupational exposures; additional studies examining efficacy, duration, and cost-effectiveness are needed. Development of more oral drugs possessing a high barrier of resistance and equal activity against all HCV genotypes is anticipated.
Healthcare-associated infections in the elderly: what's new
Authors: Katz Morgan J. , Roghmann Mary-Claire
Published: June 2016

Purpose of review

The high-risk population and current lack of knowledge regarding appropriate infection prevention in the long-term care (LTC) setting has contributed to substantial rates of resistance and healthcare-associated infections in this arena. More evidence-based research on LTC is necessary, particularly now that the elderly population is increasing.

Recent findings

Proposed government mandates highlight the urgent need to combat antimicrobial resistance in the LTC setting. Recent studies focusing on unique strategies for the prevention of transmission and infection with multidrug-resistant organisms in nursing homes are discussed, as well as attempts to formulate clear antimicrobial stewardship programs.

The long-term setting has unique challenges to instituting effective infection control precautions, therefore current accepted methods used in acute-care facilities need to be modified. Recent data suggest that prevention of transmission in LTC may be achieved with focus on high-risk patients or specific care-based activities rather than colonization status. Antimicrobial stewardship and consultation with specialized physicians may be important measures to combat resistance and adverse events in LTC. The prevention of unnecessary antibiotic use in palliative care may reduce rates of resistance as well as discomfort for terminal patients.
Characterization of a Novel Hafnium-Based X-ray Contrast Agent
Authors: Frenzel Thomas , Bauser Marcus , Berger Markus , Hilger Christoph Stephan , Hegele-Hartung Christa , Jost Gregor , Neis Christian , Hegetschweiler Kaspar , Riefke Björn , Suelzle Detlev , Pietsch Hubertus
Published: June 2016

Objective

Characterization of BAY-576, a new x-ray contrast agent which is not based on iodine, but rather on the heavy metal hafnium. Compared with iodine, hafnium provides better x-ray absorption in the energy range of computed tomography (CT) and allows images of comparable quality to be acquired at a significantly reduced radiation dose.

Materials and Methods

A range of standard methods were used to explore the physicochemistry of BAY-576 as well as its tolerability in in vitro assays, its pharmacokinetics and toxicology in rats, and its performance in CT imaging in rabbits.

Results

BAY-576 is an extraordinarily stable chelate with a metal content of 42% (wt/wt) and with excellent water solubility. Formulations of 300 mg Hf/mL exhibited viscosity (3.3–3.6 mPa) and osmolality (860–985 mOsm/kg) in the range of nonionic x-ray agents. No relevant effects on erythrocytes, the coagulation, or complement system or on a panel of 87 potential biological targets were observed. The compound did not bind to plasma proteins of a number of species investigated. After intravenous injection in rats, it was excreted fast and mainly via the kidneys. Its pharmacokinetics was comparable to known extracellular contrast agents. A dose of 6000 mg Hf/kg, approximately 10 to 20 times the expected diagnostic dose, was well tolerated by rats with only moderate adverse effects. Computed tomography imaging in rabbits bearing a tumor in the liver demonstrated excellent image quality when compared with iopromide at the same contrast agent dose in angiography during the arterial phase. At 70% of the radiation dose, BAY-576 provided a contrast-to-noise ratio of the tumor, which was equivalent to iopromide at 100% radiation dose.

Conclusions

The profile of BAY-576 indicates its potential as the first compound in a new class of noniodine x-ray contrast agents, which can contribute to the reduction of the radiation burden in contrast-enhanced CT imaging.
“One-Stop Shop”
Authors: Riffel Philipp , Zoellner Frank G. , Budjan Johannes , Grimm Robert , Block Tobias K. , Schoenberg Stefan O. , Hausmann Daniel
Published: June 2016

Aims and Objectives

The purpose of the present study was to evaluate a recently introduced technique for free-breathing dynamic contrast-enhanced renal magnetic resonance imaging (MRI) applying a combination of radial k-space sampling, parallel imaging, and compressed sensing. The technique allows retrospective reconstruction of 2 motion-suppressed sets of images from the same acquisition: one with lower temporal resolution but improved image quality for subjective image analysis, and one with high temporal resolution for quantitative perfusion analysis.

Materials and Methods

In this study, 25 patients underwent a kidney examination, including a prototypical fat-suppressed, golden-angle radial stack-of-stars T1-weighted 3-dimensional spoiled gradient-echo examination (GRASP) performed after contrast agent administration during free breathing. Images were reconstructed at temporal resolutions of 55 spokes per frame (6.2 seconds) and 13 spokes per frame (1.5 seconds). The GRASP images were evaluated by 2 blinded radiologists. First, the reconstructions with low temporal resolution underwent subjective image analysis: the radiologists assessed the best arterial phase and the best renal phase and rated image quality score for each patient on a 5-point Likert-type scale.

In addition, the diagnostic confidence was rated according to a 3-point Likert-type scale. Similarly, respiratory motion artifacts and streak artifacts were rated according to a 3-point Likert-type scale.

Then, the reconstructions with high temporal resolution were analyzed with a voxel-by-voxel deconvolution approach to determine the renal plasma flow, and the results were compared with values reported in previous literature.

Results

Reader 1 and reader 2 rated the overall image quality score for the best arterial phase and the best renal phase with a median image quality score of 4 (good image quality) for both phases, respectively. A high diagnostic confidence (median score of 3) was observed. There were no respiratory motion artifacts in any of the patients. Streak artifacts were present in all of the patients, but did not compromise diagnostic image quality.

The estimated renal plasma flow was slightly higher (295 ± 78 mL/100 mL per minute) than reported in previous MRI-based studies, but also closer to the physiologically expected value.

Conclusions

Dynamic, motion-suppressed contrast-enhanced renal MRI can be performed in high diagnostic quality during free breathing using a combination of golden-angle radial sampling, parallel imaging, and compressed sensing. Both morphologic and quantitative functional information can be acquired within a single acquisition.
Current Controversies in Lung Cancer Staging
Authors: Carter Brett W. , Godoy Myrna C.B. , Wu Carol C. , Erasmus Jeremy J. , Truong Mylene T.
Published: June 2016

Lung cancer remains the leading cause of cancer-related mortality in the United States, and accurate staging of disease plays an important role in the formulation of treatment strategies and optimization of patient outcomes. The International Association for the Study of Lung Cancer has recently proposed changes to the upcoming eighth edition of the tumor, node, and metastasis (TNM-8) staging system used for lung cancer. This revised classification is based on significant differences in patient survival identified on analysis of a new large international database of lung cancer cases. Key changes include: further modifications to the T descriptors based on 1 cm increments in tumor size; grouping of tumors resulting in partial or complete lung atelectasis/pneumonitis; grouping of tumors involving a main bronchus with respect to distance from the carina; reassignment of diaphragmatic invasion; elimination of mediastinal pleural invasion as a descriptor; and further subdivision of metastatic disease into distinct descriptors based on the number of extrathoracic metastases and involved organs. Because of these changes, several new stage groups have been developed, and others have shifted. Although TNM-8 represents continued improvement upon modifications previously made to the staging system, reflecting an evolving understanding of tumor behavior and patient management, several limitations and unaddressed issues persist. Understanding the proposed revisions to TNM-8 and awareness of key limitations and potential controversial issues still unaddressed will allow radiologists to accurately stage patients with lung cancer and optimize treatment decisions.