bluuebunny/crossref_metadata_2025 huggingface dataset:
There Are Sex Differences in the Demographics and Risk Profiles of Emergency Department (ED) Patients With Atrial Fibrillation and Flutter, but no Apparent Differences in ED Management or Outcomes
Authors: Scheuermeyer Frank Xavier , Mackay Martha , Christenson Jim , Grafstein Eric , Pourvali Reza , Heslop Claire , MacPhee Jan , Ward John , Heilbron Brett , McGrath Lorraine , Humphries Karin
Published: August 2015

Objectives

In non–emergency department (ED) settings, women with atrial fibrillation and flutter (AFF) have different presentations, treatments, and outcomes than men: they are older, less likely to be treated with rhythm control strategies or appropriate anticoagulation, and more likely to have strokes. This has not been investigated in ED patients.

Methods

Records from consecutive ED patients from January 1 to December 31, 2009, with electrocardiogram‐proven AFF at two urban hospitals were collected. Review of administrative and clinical data identified patient demographics, clinical characteristics, comorbidities, and ED treatments. The regional ED database was queried to determine 30‐day and 1‐year follow‐up visits, and the provincial vital statistics database was referenced to obtain 30‐day and 1‐year mortality; all outcomes were stratified by sex. The primary outcome, which reflected overall appropriateness of ED care, was the proportion of patients who were discharged home at their index ED visits, who then had unscheduled 30‐day ED revisits. Secondary outcomes included the proportion of eligible patients who underwent acute rhythm control strategies and the proportion of high‐risk patients who had previously inadequately anticoagulation strategies corrected by the emergency physician. Additional outcomes included the ED length of stay (LOS) and 30‐day and 1‐year rates of stroke and death.

Results

A total of 1,112 records were reviewed: 470 women (42.3%) and 642 men. Women were a median 8 years (interquartile range = 3 to 13 years) older than men, had higher rates of cardiovascular comorbidities, and were more likely to present with atypical symptoms such as weakness or dyspnea. On their index ED visits, 50.2% of women and 41.3% of men were admitted. At 30 days, 39 of 234 (16.7%) women and 55 of 377 (14.6%) men who were discharged at their index ED visits had made revisits, for a risk difference of 2.1% (95% confidence interval = –3.9% to 8.5%). There were no apparent sex differences in the use of acute rhythm control or in the appropriateness of anticoagulation decisions. ED LOS was similar between women and men, as were 30‐day and 1‐year stroke or death rates.

Conclusions

Female ED AFF patients were older, had more comorbidities, and were more likely to be admitted. However, the overall management and outcomes, including 30‐day revisits, appeared to be similar to that of males, indicating that there appeared to be little sex‐based discrepancy in ED care and outcomes.
The new stimulant designer compound pentedrone exhibits rewarding properties and affects dopaminergic activity
Authors: Hwang Ji‐Young , Kim Jun‐Sub , Oh Ji‐Hwan , Hong Sa‐Ik , Ma Shi‐Xun , Jung Yang‐Hee , Ko Yong‐Hyun , Lee Seok‐Yong , Kim Hyoung‐Chun , Jang Choon‐Gon
Published: August 2015

Cathinone derivatives are new recreational drugs known to produce psychostimulant effects. However, unlike other psychostimulants, the addictive potential of cathinone derivatives has not been widely studied. Here, we investigated the effects of pentedrone, a type of cathinone derivative, on the dopaminergic system using reverse transcription polymerase chain reaction and Western blot. We also evaluated the addictive potential of pentedrone using conditioned place preference and self‐administration. We found that pentedrone increased the mRNA expression of dopamine 1 receptor, dopamine 2 receptor and dopamine transporter, as well as induced phosphorylation of cAMP response element‐binding protein in PC‐12 cells. Additionally, pentedrone at 3 and 10 mg/kg significantly increased conditioned place preference in mice, while pentedrone at 0.3 mg/kg/infusion significantly increased self‐administration in rats. Finally, we found that acute administration of pentedrone enhanced locomotor activity in a dose‐dependent manner. Collectively, these data suggest that the addictive properties of pentedrone may be due to its effects on the dopaminergic system.
How has microcredit supported agriculture? Evidence using panel data from Bangladesh
Authors: Khandker Shahidur R. , Koolwal Gayatri B.
Published: August 2015

Improving agricultural productivity has received a greater attention in recent years amid concerns about rising food insecurity, population pressures, and climate change. Many believe that better access to institutional credit, spanning microcredit as well as commercial and agricultural banks, can help rural households smooth risks, and access inputs and other technology to modernize agriculture and improve farm/nonfarm linkages. We use recently augmented household panel data spanning over 20 years in Bangladesh to examine the effects of rural credit expansion (both microcredit and formal bank channels) on outcomes for agricultural households. We find that microcredit has benefited households with lower landownings, raising agricultural income from activities such as livestock rearing that require less land, as well as nonfarm income diversification for all households, but with the strongest effect for landless or near‐landless households. We do not find effects of microcredit on crop income, but do, however, find that reported supply‐side credit constraints significantly lower crop income. Borrowing by both men and women has contributed to nonfarm income growth for marginal farmers, but only men's borrowing has contributed to nonfarm income growth among higher landowning groups.
Buffer stock savings by portfolio adjustment: evidence from rural India
Authors: Imai Katsushi S. , Malaeb Bilal
Published: August 2015

The empirical literature on household savings tends to treat savings simply as the residual of income minus consumption. This article takes a unique approach to reconstruct the cash and asset balances using detailed household transaction data on farm households in rural India and generates monthly and seasonal ICRISAT panel data for the period 1976–1983. We have found that households—irrespective of their landholding status—cope with temporary shocks quite well by using crop inventory, currency, and capital assets, rather than livestock, as buffer assets. The importance of portfolio adjustments in smoothing consumption is also confirmed by the use of a system of equations in which both portfolio and production decisions are made endogenous. It is concluded that not only the level but also the diversification of household assets are important for buffering consumption. As an extension, we have explored the monthly ICRISAT panel data for the period 2009–2012 in the same villages and have found a similar pattern in household portfolio responses to income shocks.
Distance‐ and near‐visual impairment in rural Chinese adults in Kailu, Inner Mongolia
Authors: Cheng Fang , Shan Li , Song Wulian , Fan Pan , Yuan Huiping
Published: August 2015

Purpose

To investigate the prevalence and causes of distance‐visual impairment and near‐vision impairment in a rural Chinese population in Inner Mongolia.

Methods

A population‐based, cross‐sectional study design was used to identify visual impairment in the Chinese aged 40 years and older living in Kailu County, Inner Mongolia. Low vision, blindness and near‐visual impairment (NVI) were defined according to World Health Organization (WHO) criteria.

Results

The overall prevalence of blindness and visual impairment based on the presenting visual acuity (VA) was 2.2% (95% CI: 1.8–2.6) and 9.8% (95% CI: 8.9–10.6), respectively, and was adjusted to 0.9% (95% CI: 0.6–1.2) and 4.7% (95% CI: 4.1–5.3) using best‐corrected visual acuity (BCVA), respectively. Taking the presenting VA into consideration, the leading cause of visual impairment and blindness was cataract (40.3%, 40.9%), followed by uncorrected refractive error (26.6%, 28.2%). According to the BCVA, the main cause of visual impairment and blindness was cataract (48.3%, 41.3%) followed by glaucoma (19.0%, 23.9%). Among the examined subjects, 80.3% had NVI, and 51.7% had presbyopia. Major barriers reported by NVI persons without near correction were lack of money to purchase prescription glasses and poor quality of the available ones (43.2%).

Conclusion

Visual impairment is a serious public health problem, and the main causes leading to visual impairment are treatable and preventable in the rural Chinese population in Inner Mongolia. Presbyopia, together with the low rate of spectacles and lack of appropriate refractive and presbyopia spectacles, is highly prevalent in rural China.
Systematic review: instruments to assess abdominal pain in irritable bowel syndrome
Authors: Mujagic Z. , Keszthelyi D. , Aziz Q. , Reinisch W. , Quetglas E. G. , De Leonardis F. , Segerdahl M. , Masclee A. A. M.
Published: August 2015

Background

Consensus on standard methods to assess chronic abdominal pain in patients with irritable bowel syndrome (IBS) is currently lacking.

Aim

To systematically review the literature with respect to instruments of measurement of chronic abdominal pain in IBS patients.

Methods

Systematic literature search was performed in PubMed/Medline databases for studies using pain measurement instruments in patients with IBS.

Results

One hundred and ten publications were reviewed. A multitude of different instruments is currently used to assess chronic abdominal pain in IBS patients. The single‐item methods, e.g. the validated 10‐point numeric rating scale (NRS), and questionnaires assessing gastrointestinal symptoms severity, focus mostly on the assessment of only the intensity of abdominal pain. Of these questionnaires, the validated IBS‐Symptom Severity Scale includes the broadest measurement of pain‐related aspects. General pain questionnaires and electronic momentary symptom assessment tools have been used to study abdominal pain in IBS patients, but have not yet been validated for this purpose. The evidence for the use of provocation tests, e.g. the rectal barostat with balloon distention, for measurement of abdominal pain in IBS is weak, due to the poor correlation between visceral pain thresholds assessed by provocation tests and abdominal pain as assessed by retrospective questionnaires.

Conclusions

The multitude of different instruments to measure chronic abdominal pain in IBS makes it difficult to compare endpoints of published studies. There is need for validated instruments to assess chronic abdominal pain in IBS patients, that overcome the limitations of the currently available methods.
Which non‐technical skills do junior doctors require to prescribe safely? A systematic review
Authors: Dearden Effie , Mellanby Edward , Cameron Helen , Harden Jeni
Published: August 2015

Aims

Prescribing errors are a major source of avoidable morbidity and mortality. Junior doctors write most in‐hospital prescriptions and are the least experienced members of the healthcare team. This puts them at high risk of error and makes them attractive targets for interventions to improve prescription safety. Error analysis has shown a background of complex environments with multiple contributory conditions. Similar conditions in other high risk industries, such as aviation, have led to an increased understanding of so‐called human factors and the use of non‐technical skills (NTS) training to try to reduce error. To date no research has examined the NTS required for safe prescribing.

The aim of this review was to develop a prototype NTS taxonomy for safe prescribing, by junior doctors, in hospital settings.

Methods

A systematic search identified 14 studies analyzing prescribing behaviours and errors by junior doctors. Framework analysis was used to extract data from the studies and identify behaviours related to categories of NTS that might be relevant to safe and effective prescribing performance by junior doctors. Categories were derived from existing literature and inductively from the data.

Results

A prototype taxonomy of relevant categories (situational awareness, decision making, communication and team working, and task management) and elements was constructed.

Conclusions

This prototype will form the basis of future work to create a tool that can be used for training and assessment of medical students and junior doctors to reduce prescribing error in the future.
Diabetic Ketoacidosis in a Patient with Type 2 Diabetes After Initiation of Sodium–Glucose Cotransporter 2 Inhibitor Treatment
Authors: Storgaard Heidi , Bagger Jonatan I. , Knop Filip K. , Vilsbøll Tina , Rungby Jørgen
Published: August 2015

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) were recently introduced for the treatment of type 2 diabetes (T2D). SGLT2i lower plasma glucose by inhibiting the renal reuptake of glucose leading to glucosuria. Generally, these drugs are considered safe to use. However, recently, SGLT2i have been suggested to predispose to ketoacidosis. Here, we present a case of diabetic ketoacidosis (DKA) developed in an obese, poorly controlled male patient with T2D treated with the SGLT2i dapagliflozin. He was admitted with DKA 5 days after the initiation of treatment with the SGLT2i dapagliflozin. On admission, the primary symptoms were nausea and dizziness, and he was hypertensive (170/103) and tachycardic (119 bpm) and had mild hyperglycaemia (15.3 mmol/l), severe ketonuria and severe metabolic acidosis (pH 7.08). He responded well to infusions of insulin, glucose and saline and was discharged after 72 hr with insulin as the only glucose‐lowering therapy. After 1 month, dapagliflozin was reintroduced as add‐on to insulin with no recurrent signs of ketoacidosis. During acute illness or other conditions with increased insulin demands in diabetes, SGLT2i may predispose to the formation of ketone bodies and ensuing acidosis.
National Survey and Community Advisory Board Development for a Bipolar Disorder Biobank
Authors: Frye Mark A , Doederlein Allen , Koenig Barbara , McElroy Susan L , Nassan Malik , Seymour Lisa R , Biernacka Joanna M , Daniels Allen S
Published: August 2015

Objectives

The aim of the present study was to engage a national advocacy group and local stakeholders for guidance in developing a bipolar disorder biobank through a web‐based survey and a community advisory board.

Methods

The Depression and Bipolar Support Alliance and the Mayo Clinic Bipolar Biobank conducted a national web‐based survey inquiring about interest in participating in a biobank (i.e., giving DNA and clinical information). A community advisory board was convened to guide establishment of the biobank and identify key deliverables from the research project and for the community.

Results

Among 385 survey respondents, funding source (87%), professional opinion (76%), mental health consumer opinion (79%), and return of research results (91%) were believed to be important for considering study participation. Significantly more patients were willing to participate in a biobank managed by a university or clinic (78.2%) than one managed by government (63.4%) or industry (58.2%; both p < 0.001). The nine‐member community advisory board expressed interest in research to help predict the likelihood of bipolar disorder developing in a child of an affected parent and which medications to avoid. The advisory board endorsed the use of a comprehension questionnaire to evaluate participants' understanding of the study (e.g., longevity of DNA specimens, right to remove samples, accessing medical records) as a means to strengthen the informed consent process.

Conclusions

These national survey and community advisory data support the merit of establishing a biobank to enable studies of disease risk, provided that health records and research results are adequately protected. The goals of earlier diagnosis and individualized treatment of bipolar disorder were endorsed.
Celecoxib adjunctive therapy for acute bipolar mania: a randomized, double‐blind, placebo‐controlled trial
Authors: Arabzadeh Somayeh , Ameli Niusha , Zeinoddini Atefeh , Rezaei Farzin , Farokhnia Mehdi , Mohammadinejad Payam , Ghaleiha Ali , Akhondzadeh Shahin
Published: August 2015

Objectives

Recent research has focused on the inflammatory cascade as a key culprit in the etiology of bipolar disorder. We hypothesized that celecoxib, via its anti‐inflammatory properties, may have a therapeutic role in mood disorder.

Methods

Forty‐six inpatients with the diagnosis of acute bipolar mania without psychotic features participated in a parallel, randomized, double‐blind, placebo‐controlled trial, and underwent six weeks of treatment with either celecoxib (400 mg daily) or placebo as an adjunctive treatment to sodium valproate. Patients were evaluated using the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS). The primary outcome measure with respect to efficacy was the mean decrease in YMRS score from baseline to the study endpoint, which was compared between the two groups.

Results

A significant difference was observed in the change in YMRS scores on Day 42 compared to baseline in the two groups (p < 0.001). The changes at the endpoint compared to baseline were −29.78 ± 21.78 (mean ± standard deviation) and −21.78 ± 7.16 for the celecoxib and placebo groups, respectively. A significantly higher remission rate was observed in the celecoxib group (87.0%) than the placebo group (43.5%) at Week 6 (p = 0.005). General linear model repeated measures demonstrated a significant effect for the time × treatment interaction on the YMRS scores [F(2.27,99.98) = 6.67, p = 0.001].

Conclusions

Celecoxib is an effective adjuvant therapy in the treatment of manic episodes (without psychotic features) of bipolar mood disorder. The mood‐stabilizing role of the drug might be mediated via its action on the inflammatory cascade.
Early treatment with atorvastatin exerts parenchymal and vascular protective effects in experimental cerebral ischaemia
Authors: Potey C , Ouk T , Petrault O , Petrault M , Berezowski V , Salleron J , Bordet R , Gautier S
Published: August 2015

Background and Purpose

From the clinical and experimental data available, statins appear to be interesting drug candidates for preventive neuroprotection in ischaemic stroke. However, their acute protective effect is, as yet, unconfirmed.

Experimental Approach

Male C57Bl6/JRj mice were subjected to middle cerebral artery occlusion and treated acutely with atorvastatin (10–20 mg·kg−1 day−1; 24 or 72 h). Functional recovery (neuroscore, forelimb gripping strength and adhesive removal test) was assessed during follow‐up and lesion volume measured at the end. Vasoreactivity of the middle cerebral artery (MCA), type IV collagen and FITC‐dextran distribution were evaluated to assess macrovascular and microvascular protection. Activated microglia, leucocyte adhesion and infiltration were chosen as markers of inflammation.

Key Results

Acute treatment with atorvastatin provided parenchymal and cerebral protection only at the higher dose of 20 mg·kg−1·day−1. In this treatment group, functional recovery was ameliorated, and lesion volumes were reduced as early as 24 h after experimental stroke. This was associated with vascular protection as endothelial function of the MCA and the density and patency of the microvascular network were preserved. Acute atorvastatin administration also induced an anti‐inflammatory effect in association with parenchymal and vascular mechanisms; it reduced microglial activation, and decreased leucocyte adhesion and infiltration.

Conclusions and Implications

Acute atorvastatin provides global cerebral protection, but only at the higher dose of 20 mg·kg−1·day−1; this was associated with a reduction in inflammation in both vascular and parenchymal compartments. Our results suggest that atorvastatin could also be beneficial when administered early after stroke.
The positive correlation between maternal size and offspring size: fitting pieces of a life‐history puzzle
Authors: Rollinson Njal , Rowe Locke
Published: August 2015

The evolution of investment per offspring (I) is often viewed through the lens of the classic theory, in which variation among individuals in a population is not expected. A substantial departure from this prediction arises in the form of correlations between maternal body size andI, which are observed within populations in virtually all taxonomic groups. Based on the generality of this observation, we suggest it is caused by a common underlying mechanism. We pursue a unifying explanation for this pattern by reviewing all theoretical models that attempt to explain it. We assess the generality of the mechanism upon which each model is based, and the extent to which data support its predictions. Two classes of adaptive models are identified: models that assume that the correlation arises from maternal influences on the relationship betweenIand offspring fitness [w(I)], and those that assume that maternal size influences the relationship betweenIand maternal fitness [W(I)]. The weight of evidence suggests that maternal influences onw(I) are probably not very general, and even for taxa where maternal influences onw(I) are likely, experiments fail to support model predictions. Models that assume thatW(I) varies with maternal size appear to offer more generality, but the current challenge is to identify a specific and general mechanism upon whichW(I) varies predictably with maternal size. Recent theory suggests the exciting possibility that a yet unknown mechanism modifies the offspring size–number trade‐off function in a manner that is predictable with respect to maternal size, such thatW(I) varies with size. We identify two promising avenues of inquiry. First, the trade‐off might be modified by energetic costs that are associated with the initiation of reproduction (‘overhead costs’) and that scale withI, and future work could investigate what specific overhead costs are generally associated with reproduction and whether these costs scale withI. Second, the trade‐off might be modified by virtue of condition‐dependent offspring provisioning coupled with metabolic factors, and future work could investigate the proximate cause of, and generality of, condition‐dependent offspring provisioning. Finally, drawing on the existing literature, we suggest that maternal sizeper seis not causatively related to variation inI, and the mechanism involved in the correlation is instead linked to maternal nutritional status or maternal condition, which is usually correlated with maternal size. Using manipulative experiments to elucidate why females with high nutritional status typically produce large offspring might help explain what specific mechanism underlies the maternal‐size correlation.
Deletion status of p16 in effusion smear preparation correlates with that of underlying malignant pleural mesothelioma tissue
Authors: Hida Tomoyuki , Matsumoto Shinji , Hamasaki Makoto , Kawahara Kunimitsu , Tsujimura Tohru , Hiroshima Kenzo , Kamei Toshiaki , Taguchi Kenichi , Iwasaki Akinori , Oda Yoshinao , Honda Hiroshi , Nabeshima Kazuki
Published: August 2015

Differentiating malignant pleural mesothelioma (MPM) cells morphologically from reactive mesothelial hyperplasia cells is problematic. Homozygous deletion (HD) of p16 (CDKN2A), detected by FISH, is a good marker of malignancy and is useful to differentiate between these cells. However, the correlation between the p16 status of effusion smears and that of the underlying MPM tissues has not been investigated. We used p16‐specific FISH to investigate 20 cases of MPM from which both effusion cytologic smears and histologic specimens were available. In five cases, histologic specimens included both an invasive component and surface mesothelial proliferation. In 14 cases (70%), MPM cells in both tissue sections and effusion smears were p16 HD‐positive. Conversely, MPM cells in the remaining six tumors (30%) were p16 HD‐negative in both tissue sections and effusion smears. For all five MPM cases with surface mesothelial proliferations and invasive components, the effusion smears, surface mesothelial proliferations, and invasive MPM components all displayed p16 deletion. Moreover, the extent to which p16 was deleted in smears highly correlated with the extent of p16 deletion in tissues. The p16 deletion percentages were also similar among smears, tissue surface proliferations, and invasive components. In cases with clinical and radiologic evidence of a diffuse pleural tumor, detection of p16 deletion in cytologic smear samples may permit MPM diagnosis without additional tissue examination. However, the absence of p16 deletion in cytologic smear samples does not preclude MPM.
Prognostic value of 18F‐fluoroazomycin arabinoside PET/CT in patients with advanced non‐small‐cell lung cancer
Authors: Saga Tsuneo , Inubushi Masayuki , Koizumi Mitsuru , Yoshikawa Kyosan , Zhang Ming‐Rong , Tanimoto Katsuyuki , Horiike Atsushi , Yanagitani Noriko , Ohyanagi Fumiyoshi , Nishio Makoto
Published: August 2015

This study evaluated the prognostic value of positron emission tomography/computed tomography (PET/CT) using 18F‐fluoroazomycin arabinoside (FAZA) in patients with advanced non‐small‐cell lung cancer (NSCLC) compared with 18F‐fluorodeoxyglucose (FDG). Thirty‐eight patients with advanced NSCLC (stage III, 23 patients; stage IV, 15 patients) underwent FAZA and FDG PET/CT before treatment. The PET parameters (tumor‐to‐muscle ratio [T/M] at 1 and 2 h for FAZA, maximum standardized uptake value for FDG) in the primary lesion and lymph node (LN) metastasis and clinical parameters were compared concerning their effects on progression‐free survival (PFS) and overall survival (OS). In our univariate analysis of all patients, clinical stage and FAZA T/M in LNs at 1 and 2 h were predictive of PFS (P = 0.021, 0.028, and 0.002, respectively). Multivariate analysis also indicated that clinical stage and FAZA T/M in LNs at 1 and 2 h were independent predictors of PFS. Subgroup analysis of chemoradiotherapy‐treated stage III patients revealed that only FAZA T/M in LNs at 2 h was predictive of PFS (P = 0.025). The FDG PET/CT parameters were not predictive of PFS. No parameter was a significant predictor of OS. In patients with advanced NSCLC, FAZA uptake in LNs, but not in primary lesions, was predictive of treatment outcome. These results suggest the importance of characterization of LN metastases in advanced NSCLC patients.
Pomalidomide alone or in combination with dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma
Authors: Matsue Kosei , Iwasaki Hiromi , Chou Takaaki , Tobinai Kensei , Sunami Kazutaka , Ogawa Yoshiaki , Kurihara Mari , Midorikawa Shuichi , Zaki Mohamed , Doerr Thomas , Iida Shinsuke
Published: August 2015

This phase 1, open‐label, dose‐escalation study investigated the tolerated dose (recommended dose), safety, efficacy, and pharmacokinetics of pomalidomide alone or pomalidomide plus low‐dose dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma. Twelve patients were enrolled. Patients received pomalidomide 2 mg (Cohort 1) or 4 mg (Cohort 2) orally on day 1 and days 3–21 of a 28‐day cycle. The tolerated dose of pomalidomide was determined to be 4 mg given on days 1–21 of a 28‐day cycle. Efficacy outcomes with pomalidomide plus low‐dose dexamethasone were consistent with those of previous studies. Responses (partial response or better) were achieved by three patients (25%; 1 [17%] in Cohort 1 and 2 [33%] in Cohort 2), and the median time to response was 6.4 months overall (9.0 months for Cohort 1 and 4.2 months for Cohort 2). The median progression‐free survival was 5.5 months overall (5.1 months for Cohort 1 and not reached for Cohort 2). The most frequently occurring grade ≥3 adverse events were neutropenia (67%), anemia (25%), lymphopenia (25%), and pneumonia (25%), consistent with previous studies of pomalidomide plus low‐dose dexamethasone in refractory or relapsed and refractory multiple myeloma. Further investigation of pomalidomide is recommended for Japanese patients with refractory or relapsed and refractory multiple myeloma. This study was registered with ClinicalTrials.gov (NCT01568294).
Longitudinal evaluation of the natural history of conservatively managed nonfunctioning pituitary adenomas
Authors: Lenders Nèle , Ikeuchi Seira , Russell Anthony W , Ho Ken KY , Prins Johannes B , Inder Warrick J
Published: August 2015

Context

The optimal management of nonfunctioning pituitary adenomas presenting without symptomatic mass effect remains uncertain. The objective of this study was to elucidate the natural history of nonfunctioning pituitary adenomas managed conservatively.

Design

Volumetric evaluation of tumour growth in serial pituitary MRI scans by a single observer and retrospective review of changes in pituitary function.

Patients

Patients with nonfunctioning pituitary adenomas who underwent at least 2 serial pituitary MRI scans over ≥6 months between 2003 and 2013 prior to any intervention.

Measurements

Primary end‐point was a ≥20% increase in volume or surgery. Secondary end‐points were rate of pituitary dysfunction and pituitary apoplexy.

Results

Fifty nonfunctioning pituitary adenomas (23 macroadenomas and 27 microadenomas, mean age 49, range 17–85 years) were identified. Mean follow‐up was 36 months (range 6–79). An increase in volume occurred in macroadenomas (P < 0·01) but not in microadenomas (P = 0·44). A ≥20% increase in volume occurred in nine of 23 macroadenomas compared with two of 27 microadenomas (P < 0·05). Five macroadenomas (one with new visual field defect) and one microadenoma proceeded to surgery (P = 0·08). Hormone deficiency was present in four of 24 macroadenomas vs 0 of 27 microadenomas (P < 0·05) at baseline, while new hormone deficiency developed in only two macroadenomas during follow‐up. Pituitary apoplexy occurred in one microadenoma. A growth rate of >10 mm3/month assessed at approximately 2 years of follow‐up among the macroadenoma group was highly predictive (sensitivity and specificity of 90%) of a ≥20% increase in volume or surgery.

Conclusions

Nonfunctioning pituitary macroadenomas have a greater tendency to grow and require surgical intervention while microadenomas rarely progress.
Lettuce contact allergy
Authors: Paulsen Evy , Andersen Klaus E.
Published: August 2015

Lettuce (Lactuca sativa L.) and its varieties are important vegetable crops worldwide. They are also well‐known, rarely reported, causes of contact allergy. As lettuce allergens and extracts are not commercially available, the allergy may be underdiagnosed. The aims of this article are to present new data on lettuce contact allergy and review the literature. Lettuce is weakly allergenic, and occupational cases are mainly reported. Using aimed patch testing in Compositae‐allergic patients, two recent Danish studies showed prevalence rates of positive lettuce reactions of 11% and 22%. The majority of cases are non‐occupational, and may partly be caused by cross‐reactivity. The sesquiterpene lactone mix seems to be a poor screening agent for lettuce contact allergy, as the prevalence of positive reactions is significantly higher in non‐occupationally sensitized patients. Because of the easy degradability of lettuce allergens, it is recommended to patch test with freshly cut lettuce stem and supplement this with Compositae mix. As contact urticaria and protein contact dermatitis may present as dermatitis, it is important to perform prick–to–prick tests, and possibly scratch patch tests as well. Any person who is occupationally exposed to lettuce for longer periods, especially atopics, amateur gardeners, and persons keeping lettuce‐eating pets, is potentially at risk of developing lettuce contact allergy.
Concomitant colonic disease (Montreal L3) and re‐resectional surgery are predictors of clinical recurrence following ileocolonic resection for Crohn's disease
Authors: Morar P. S. , Faiz O. , Hodgkinson J. D. , Zafar N. , Koysombat K. , Purcell M. , Hart A. , Warusavitarne J.
Published: August 2015

Aim

Ileocolonic resection is reserved for patients with moderate to severe Crohn's disease. Postoperative clinical recurrence can occur in up to 55% of patients within 5 years. Predicting the risk of recurrence is key in deciding upon appropriate treatment strategies. This study aims to determine the incidence of postoperative clinical recurrence and predictors of recurrence in a specialist institution.

Method

The clinical case records of 142 patients who underwent either a one‐stage or two‐stage procedure for ileocolonic Crohn's disease from 1 January 2005 to 31 December 2010 were reviewed. Preoperative, perioperative and postoperative variables were extracted. Postoperative clinical recurrence was defined as an initiation or change in medical treatment for recurrent symptoms with endoscopic or radiological evidence of active disease. Time to clinical recurrence was measured in months after surgery. Univariate and multivariate analyses were performed.

Results

Over the 6‐year period, follow‐up data were obtained on 142 patients over a median of 28.5 months. Clinical recurrence was demonstrated in 59 (41.5%) patients. The proportion of patients with clinical recurrence at 5 years was 48.2%. Predictors of recurrence included a re‐resection for recurrent disease [hazard ratio (HR) 1.9; 95% CI 1.1–3.3; P = 0.02] and ileocolonic disease (HR 1.7; 95% CI 1.0–2.9; P = 0.05).

Conclusion

Identifying the predictors for postoperative clinical recurrence is important for determining the postoperative strategy. This study provides a unique perspective on the incidence of recurrence and associated predictors from the perspective of a specialist unit.
Role of icodextrin in the prevention of small bowel obstruction. Safety randomized patients control of the first 300 in the ADEPT trial
Authors: Sakari T. , Sjödahl R. , Påhlman L. , Karlbom U.
Published: August 2015

Aim

Adhesions are the most common cause of small bowel obstruction (SBO). The costs of hospitalization and surgery for SBO are substantial for the health‐care system. The adhesion‐limiting potential of icodextrin has been shown in patients undergoing surgery for gynaecological diseases. A randomized, multicentre trial in colorectal cancer surgery started in 2009 with the aim of evaluating whether icodextrin could reduce the long‐term risk of surgery for SBO. Because of some concerns about complications (especially anastomotic leakage) after icodextrin use, a preplanned interim analysis of morbidity and mortality was conducted.

Method

Patients with colorectal cancer without metastasis were randomized 1:1 to receive standard surgery, with or without instillation of icodextrin in the abdominal cavity. For the first 300 patients, the 30‐day follow‐up data were collected from the Swedish ColoRectal Cancer Registry (SCRCR). Pre‐, per‐ and postoperative data, morbidity and mortality were analysed.

Results

Of the 300 randomized patients, 288 had a data file in the SCRCR. Twelve patients did not have cancer and another five did not have a resection, leaving 283 for analysis. The authors were blinded to the randomization groups. Demographic data were similar in both groups. The overall complication rate was 24% in Group 1 and 23% in Group 2 (P = 0.89). Four cases of anastomotic leakage were reported in Group 1 and five were reported in Group 2 (P = 1.0). Mortality, intensive care unit (ICU) stay and re‐operations did not differ between the groups.

Conclusion

The pre‐planned safety analysis of the first 300 patients enrolled in this randomized trial did not show any differences in adverse effects related to the use of icodextrin. All data were gathered from the SCRCR, giving us a strong message that we can continue to include patients in the trial.
Re‐exposure to beta cell autoantigens in pancreatic allograft recipients with preexisting beta cell autoantibodies
Authors: Mujtaba Muhammad Ahmad , Fridell Jonathan , Book Benita , Faiz Sara , Sharfuddin Asif , Wiebke Eric , Rigby Mark , Taber Tim
Published: August 2015

Re‐exposure to beta cell autoantigens and its relevance in the presence of donor‐specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty‐three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma‐associated antigen 2 (IA‐2), insulin (micro‐IAA [mIAA]), and islet‐specific zinc transporter isoform‐8 (ZnT8). Twenty‐five (75.7%) had pre‐transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA‐2 n = 2, GA65 + mIAA+IA‐2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA‐2 (>0.16), and ZnT8 (p > 0.07) were observed between pre‐transplant and post‐transplant at 6 or 12 months. A decrease in mIAA from pre‐ to post‐6 months (p < 0.0001), 12 months (p < 0.0001), and from post‐6 to post‐12 months (p = 0.0002) was seen. No new BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow‐up (three yr). Re‐exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction.
Ultrasound as a diagnostic tool in the investigation of a pony with intestinal lymphoma
Authors: Sherlock C. , Dawson L. , Mair T.
Published: August 2015

A 21‐year‐old New Forest pony presented for evaluation of lethargy and colic. Transcutaneous abdominal ultrasonography revealed a cavitary, thick walled, mass‐like lesion that appeared continuous with the small intestine. The thick walls of the mass‐like lesion were of heterogeneous echogenicity with hyperechoic foci extending from the hyperechoic luminal surface to within the wall and there was loss of normal wall layering. These findings were confirmed grossly at exploratory celiotomy and histopathological examination of affected tissues confirmed lymphoma. The ultrasound findings facilitated a preoperative presumptive diagnosis that allowed informed decision‐making and aided case management.
An unusual cyst‐like lesion in the metaphysis of the tibia in a horse
Authors: Stöcker D. S. , Ohlerth S. , Grest P. , Mackenthun E. , Bettschart‐Wolfensberger R. , Kümmerle J. M.
Published: August 2015

A 6‐year‐old Haflinger gelding was presented with a chronic right hindlimb lameness. Scintigraphy, radiography and computed tomography confirmed an active large cyst‐like lesion in the distal metaphysis of the right tibia. A transcortical surgical approach was used to curette the lesion and fill it with an autologous bone graft and a calcium phosphate bone substitute material. Histopathology revealed mild histiocytic inflammatory changes, mild fibrosis and bone necrosis. This case report describes an unusual cyst‐like lesion in the tibial metaphysis of a horse.
Pathological fracture through a subchondral bone cyst in the proximal phalanx of a horse
Authors: Williams J. M. , Santschi E. M.
Published: August 2015

A 12‐year‐old Morgan broodmare presented for a nonweightbearing right forelimb lameness. Radiography and computed tomography confirmed the presence of a pathological fracture of the proximal first phalanx through a large subchondral bone cyst (SBC) in the right forelimb and a large SBC in the proximal first phalanx of the left forelimb. Surgical repair of the large palmar medial eminence fracture of the proximal first phalanx fracture was performed using bone screws placed in lag fashion placed through stab incisions after debridement and bone grafting of the SBCs. Approximately 6 months after surgery the mare was ambulating comfortably at pasture. This case report describes a fracture through a large subchondral bone cyst in a horse despite chronicity and ongoing bone remodelling. Careful consideration regarding exercise or use should be considered in horses with large SBCs.
Retrospective analysis of factors associated with outcome of proximal interphalangeal joint arthrodesis in 82 horses including Warmblood and Thoroughbred sport horses and Quarter Horses (1992–2014)
Authors: Herthel T. D. , Rick M. C. , Judy C. E. , Cohen N. D. , Herthel D. J.
Published: August 2015

Reasons for performing study

Outcomes associated with arthrodesis of the proximal interphalangeal (PIP) joint in Quarter Horses used for Western performance activities are well documented but little is known regarding outcomes for other types of horses.

Objectives

To identify factors associated with outcomes, including breed and activity, after arthrodesis of the PIP joint in Warmbloods, Thoroughbreds and Quarter Horses.

Study design

Retrospective case series.

Methods

Surgical case records of 82 Quarter Horses principally engaged in Western performance and Thoroughbred or Warmblood breeds principally engaged in showing, showjumping and dressage, with arthrodesis of the PIP joint were reviewed. Arthrodesis was performed with either 3 transarticular cortex bone screws placed in lag fashion, a dynamic compression plate (DCP) with 2 transarticular cortex bone screws placed in lag fashion, or a locking compression plate (LCP) with 2 transarticular cortex bone screws placed in lag fashion. Demographic data, clinical presentation, radiographic findings, surgical technique, post operative treatment and complications were recorded. Long‐term follow‐up was obtained for all 82 horses.

Results

Osteoarthritis of the PIP joint was the most common presenting condition requiring arthrodesis, which was performed with either the 3 screw technique (n = 41), DCP fixation (n = 22), or LCP fixation (n = 19). Post operatively, 23/31 (74%) Warmbloods/Thoroughbreds and 44/51 (87%) Quarter Horses achieved successful outcomes. Thirteen of 23 (57%) Warmbloods/Thoroughbreds and 24 of 38 (63%) Quarter Horses, used for athletic performance, returned to successful competition. Within this subgroup of horses engaged in high‐level activity, regardless of breed type, horses undergoing hindlimb arthrodesis were significantly more likely to return to successful competition (73%; 33/45) than those with forelimb arthrodesis (25%; 4/16, P = 0.002).

Conclusions

Arthrodesis of the PIP joint in Warmbloods/Thoroughbreds and Quarter Horses results in a favourable outcome for return to their intended use and athletic competition.
MT1‐MMP recognition by ERM proteins and its implication in CD44 shedding
Authors: Terawaki Shin‐ichi , Kitano Ken , Aoyama Miki , Mori Tomoyuki , Hakoshima Toshio
Published: August 2015

Membrane type 1‐matrix metalloproteinase (MT1‐MMP) is a key enzyme involved in tumor cell invasion by shedding their cell‐surface receptor CD44 anchored with F‐actin through ezrin/radixin/moesin (ERM) proteins. We found the cytoplasmic tail of MT1‐MMP directly binds the FERM domain of radixin, suggesting F‐actin‐based recruitment of MT1‐MMP to CD44 for invasion. Our crystal structure shows that the central region of the MT1‐MMP cytoplasmic tail binds subdomain A of the FERM domain, and makes an antiparallel β‐β interaction with β2A‐strand. This binding mode is distinct from the previously determined binding mode of CD44 to subdomain C. We showed that radixin simultaneously binds both MT1‐MMP and CD44, indicating ERM protein‐mediated colocalization of MT1‐MMP and its substrate CD44 and anchoring to F‐actin. Our study implies that ERM proteins contribute toward accelerated CD44 shedding by MT1‐MMP through ERM protein‐mediated interactions between their cytoplasmic tails.
The risk of upgrade for atypical ductal hyperplasia detected on magnetic resonance imaging‐guided biopsy: a study of 100 cases from four academic institutions
Authors: Khoury Thaer , Li Zaibo , Sanati Souzan , Desouki Mohamed M , Chen Xiwei , Wang Dan , Liu Song , Karabakhtsian Rouzan , Kumar Prasanna , Reig Beatriu
Published: August 2015

Aims

To identify variables that can predict upgrade for magnetic resonance imaging (MRI)‐detected atypical ductal hyperplasia (ADH).

Methods and results

We reviewed 1655 MRI‐guided core biopsies between 2005 and 2013, yielding 100 (6%) cases with ADH. The pathological features of ADH and MRI findings were recorded. An upgrade was considered when the subsequent surgical excision yielded invasive carcinoma (IC) or ductal carcinoma in situ (DCIS). The rate of ADH between institutions was 3.3–7.1%, with an average of 6%. A total of 15 (15%) cases had upgrade, 12 DCIS and three IC. When all cases were included, only increased number of involved cores was statistically significant (P = 0.02). When cases with concurrent lobular neoplasia (LN) were excluded (n = 14), increased number of ADH foci and increased number of involved cores were statistically significant (P = 0.002, P = 0.009). We analysed the data separately from a single institution (n = 61). Increased number of foci, increased number of total cores and involved cores and larger ADH size predicted upgrade with statistical significance.

Conclusions

The incidence of ADH in MRI‐guided core biopsy is rare. The rate of upgrade is comparable to mammographically detected ADH, warranting surgical excision. Similar to mammographically detected lesions, the volume of the ADH predicts the upgrade.
Differential nuclear ATRX expression in sarcomas
Authors: Koelsche Christian , Renner Marcus , Johann Pascal , Leiss Irina , Sahm Felix , Schimmack Simon , Wardelmann Eva , Renker Eva‐Kristin , Schirmacher Peter , Korshunov Andrey , von Deimling Andreas , Mechtersheimer Gunhild
Published: August 2015

Aim

Nuclear α‐thalassemia/mental retardation X‐linked (ATRX) loss and alternative lengthening of telomeres (ALT) are linked in distinct malignancies. We therefore aimed to determine the nuclear ATRX expression correlated with ALT in a comprehensive series of sarcomas.

Methods and results

A total of 573 formalin‐fixed paraffin‐embedded sarcomas comprising 28 entities were investigated for nuclear ATRX expression by immunohistochemistry. Telomere‐specific fluorescence in‐situ hybridization (FISH) was used to determine the ALT phenotype in 50 sarcomas with complete or heterogeneous ATRX loss. Complete nuclear ATRX loss was detected in 58 of 573 sarcomas, all high‐grade, with the highest prevalence in undifferentiated pleomorphic sarcomas (38%) and pleomorphic liposarcomas (38%), followed by dedifferentiated liposarcomas (24%), osteosarcomas (21%), leiomyosarcomas (17%), myxofibrosarcomas (11%) and malignant peripheral nerve sheath tumours (4%). Interestingly, a further 20 sarcomas, all belonging to the aforementioned entities with complete ATRX loss, presented with a heterogeneous ATRX expression pattern. ALT was observed in 41 of 42 sarcomas with complete ATRX loss, but only in two of eight sarcomas with heterogeneous expression.

Conclusion

Nuclear ATRX loss, either complete or heterogeneous, is encountered in a considerable number of high‐grade sarcomas with non‐specific genetic alterations. A causal relationship with ALT might be indicated at least in cases with a complete nuclear ATRX loss.