bluuebunny/crossref_metadata_2025 huggingface dataset:
Pregnant Women's Attitudes and Knowledge in Relation to Access to Serum-Alpha-Fetoprotein Test
Authors: Sandén Marie-Louise , Bjurulf Per
Published: July 2017

Serum-Alpha-Fetoprotein (se-AFP) screening is a controversial issue in Sweden. In some areas the test has never been offered, in others it is routinely offered to all pregnant women and there are areas where the se-AFP test has been offered but is no longer available but for very special indications. This pseudoexperimental situations was used to analyze the effects of different information environments on attitudes to and knowledge of testing procedures at the antenatal clinics, especially the se-AFP test, and anxiety of malformations. Consecutive series of pregnant women in these three areas filled in questionnaires at their first visit, in the 22nd to 24th, and the 32nd to 35th weeks of pregnancy, and after delivery. The attitudes to prenatal screening were most positive in the routine screening area and most negative in the area which previously but no longer offers the test. The level of knowledge was somewhat higher in the routine screening area at the first visit to the clinic and increased substantially, especially in the routine screening area.
Health Care Utilization and Attitudes to Health Care Before and After Development Work in a Health Centre
Authors: Westman Güran , Eriksson Carl-Gunnar , von Post Hampus
Published: July 2017

In development work at the Vännäs Primary Health Care Centre (VPHCC) in northern Sweden, attitudes towards and the use of health care were studied from 1977 to 1979. Mail questionnaires were sent to random and independent samples of Vännäs inhabitants to collect data. A relative increase in the health centre physician consultancy rate was found when it was compared to other health care facilities. No change was seen in hospital utilization. Attitudes towards health information and health care accessibility were more positive after the development work. No change in attitudes to quality of health care as such was seen. The changes implemented at the VPHCC seemed to be a major cause for the results obtained as no such change was seen in the catchment area of the reference health centre.
Socioeconomic Differences in Smoking in an Urban Swedish Population
Authors: Boström Gunnel , Hallqvist Johan , Haglund Bo J.A. , Romelsjö Anders , Svanström Leif , Diderichsen Finn
Published: July 2017

Stockholm Health of the Population Study is a cross-sectional study carried out from 1984–85. Postal questionnaires, telephone interviews and health interviews were used to get information from a sample of 5,199 persons, 18–64 years of age, on health status, risk exposures, healthcare consumption and social factors. Non-participation with respect to the postal questionnaire was 36.8%. With subsequent telephone interviews and an invitation to a health interview, non-participation was reduced to 17.8%. The estimated prevalence of daily smoking increased from 36.1% to 38.7. The non-responders had a higher prevalence of daily smoking in all sub-groups. This effect of the efforts to reduce non-participation differed socially. The prevalence of smoking for men, 40–64 years of age, who were reached by telephone was 60.3%. Male professionals and intermediate non-manual workers, 40–64 years of age reached by telephone had a prevalence of smoking, which was twice as high as for the responders of the questionnaire (62.5 and 26.8%, respectively). In the younger age-group, non-responders had the same socioeconomic pattern in smoking as the responders. Independent of socioeconomic group, there was a tendency of ill or disabled smokers to respond more quickly than healthy smokers. Using a postal questionnaire with a high non-response rate might lead to an overestimation of socioeconomic differences and an underestimation of smoking prevalence.
‘I changed my life’s course’: The impact of the Helsingin Sanomat Foundation fellowship on the career path of a journalist
Authors: Lassila-Merisalo Maria
Published: July 2017

This study focuses on the fellowship program of Helsingin Sanomat Foundation, which has sent a hundred mid-career journalists from Finland to study abroad at prominent universities. Based on two surveys, one on the fellows (n = 45) and one on a control group (n = 52), the article discusses the impact the fellowship education has on the journalists and their careers. The surveys are complemented with in-depth interviews of 10 fellow journalists. The results are discussed in the context of protean career concept, and they indicate that the fellowship period has a notable positive impact on the career of an individual journalist, but a contradictory impact on the journalist’s home organization.
Suture-Button Device Stabilization Following Ring Finger Ray Amputation: A Comparative Cadaver Study
Authors: Morgan Emily N. , Means Kenneth R. , Paez Adrian G. , Parks Brent G. , Innis Peter C.
Published: July 2017

Background: The purpose of this study was to determine whether placing the suture-button device between the long and small finger metacarpals following ring finger ray amputation may better close the intermetacarpal gap and allow early range of motion without increasing the risk of malrotation than soft tissue repair alone. Methods: We performed ray amputation of the ring finger of 14 cadaver specimens by performing an osteotomy of the base of the ring finger metacarpal and then excising the remainder of the digit. We first performed a soft tissue repair of the transverse metacarpal ligaments and then cycled the fingers in simulated active flexion and extension on a custom computer-controlled device to re-create 6 weeks of range of motion. We then placed a suture-button device across the long and small finger metacarpals and tested the specimens again, thereby using each hand as an internal control. Results: The distance between the ring and small finger metacarpals was reduced following suture-button device placement compared with the initial control; this spacing was maintained following complete cycling of the fingers. The angle between the metacarpals was divergent following soft tissue repair, and then became slightly convergent after insertion of the suture-button device. None of the hands developed clinically relevant scissoring of the digits before or after application of the suture-button device. Conclusions: The suture-button device provides stable fixation to withstand early range of motion following ring finger ray amputation and significantly closes the gap and angle between the adjacent metacarpals without causing scissoring.
Looking forward to the past: An interdisciplinary discussion on the use of historical analogies and their effects
Authors: Ghilani Djouaria , Luminet Olivier , Erb Hans-Peter , Flassbeck Christine , Rosoux Valérie , Tames Ismee , Klein Olivier
Published: July 2017

“ This is Munich all over again!”: Such comparisons between a present situation and a past one (i.e. a historical analogy) are common in public and political discourses. Historical analogies were used for centuries but have received increased interest in the last 50 years from scholars in political science, history, and psychology. Despite existing interdisciplinary exchanges, it remains difficult to identify the variables involved in the phenomenon as different methodologies and conceptualizations are used. Hence, we review part of this voluminous literature and suggest that the various effects related to the use of historical analogies can be grouped under four independent and non-mutually exclusive categories: representing a current situation, defining the roles of current actors, making decisions, and persuading others of a message. We conclude by acknowledging the limits of this current conceptualization and emphasizing its potential as a useful heuristic tool to organize findings in a way that makes them readable across various fields.
Breathing resistance in automated metabolic systems is high in comparison with the Douglas Bag method and previous recommendations
Authors: Ainegren Mats , Jensen Kurt , Rosdahl Hans
Published: July 2017

The purpose of this study was to investigate the resistance to breathing in metabolic systems used for the distribution and measurement of pulmonary gas exchange. A mechanical lung simulator was used to standardize selected air flow rates ([Formula: see text], L/s). The delta pressure (Δ p, Pa) between the ambient air and the air inside the equipment was measured in the breathing valve’s mouthpiece adapter for four metabolic systems and four types of breathing valves. Resistance for the inspiratory and expiratory sides was calculated as RES = (Δ p/[Formula: see text]) Pa/L/s. The results for resistance showed significant ( p < 0.05) between-group variance among the tested metabolic systems, breathing valves, and between most of the completed [Formula: see text]. The lowest resistance among the metabolic systems was found for a Douglas Bag system which had approximately half of the resistance compared to the automated metabolic systems. The automated systems were found to have higher resistance even at low [Formula: see text] in comparison with previous findings and recommendations. For the hardware components, the highest resistance was found for the breathing valves, while the lowest resistance was found for the hoses. The results showed that resistance in metabolic systems can be minimized through conscious choices of system design and hardware components.
Administrator Leadership Styles and Their Impact on School Nursing
Authors: Davis Charles R.
Published: July 2017

In comparison to other professional staff in an educational based setting, the registered professional school nurse has unique roles, responsibilities, education, training, and scope of practice. In carrying out this unique and specialized role, school nurses operate under a building administrator, the leader of the building and often the immediate supervisor of the school nurse. In addition, many school nurses in small districts are the only registered professional nurse employed by the school. The building administrator’s leadership style not only sets the tone for the day-to-day operations in the school but also impacts the school nurse functioning and program implementation. This article reviews the three most common types of leadership styles as defined by Kurt Lewin—laissez-faire, democratic, and coercive/authoritarian—and their potential impact on school nursing practice. In addition, the article provides recommendations for school nurses for successful practice with regard to supervisor leadership styles.
Ten thousand kilometre transfer of cardiogenic shock patients on venoarterial extracorporeal membrane oxygenation for emergency heart transplantation: Cooperation between Reunion Island and Metropolitan France
Authors: Charon Clément , Allyn Jérôme , Bouchet Bruno , Nativel Fréderic , Braunberger Eric , Brulliard Caroline , Martinet Olivier , Allou Nicolas
Published: July 2017

Background:

There is no heart transplantation centre on the French overseas territory of Reunion Island (distance of 10,000 km). The aim of this study was to describe the characteristics of cardiogenic shock adult patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) who were transferred from Reunion Island to mainland France for emergency heart transplantation.

Methods:

This retrospective observational study was conducted between 2005 and 2015. The characteristics and outcome of cardiogenic shock patients on VA-ECMO were compared with those of cardiogenic shock patients not on VA-ECMO.

Results:

Thirty-three cardiogenic shock adult patients were transferred from Reunion Island to Paris for emergency heart transplantation. Among them, 19 (57.6%) needed mechanical circulatory support in the form of VA-ECMO. Median age was 51 (33–57) years and 46% of the patients had ischaemic heart disease. Patients on VA-ECMO presented higher Sequential Organ Failure Assessment score ( p = 0.03). No death occurred during the medical transfer by long flight, while severe complications occurred in 10 patients (30.3%). Incidence of thromboembolic events, severe infectious complications and major haemorrhages was higher in the group of patients on VA-ECMO than in the group of patients not on VA-ECMO ( p <0.01). Seven patients from the VA-ECMO group (36.8%) and six patients from the non-VA-ECMO group (42.9%, p=0.7) underwent heart transplantation after a median delay of 10 (4–29) days on the emergency waiting list. After heart transplantation, one-year survival rates were 85.7% for patients on VA-ECMO and 83.3% for patients not on VA-ECMO ( p=0.91).

Conclusions:

This study suggests the feasibility of very long-distance medical evacuation of cardiogenic shock patients on VA-ECMO for emergency heart transplantation, with acceptable long-term results.
A biomechanical comparison of the two- and four-hole side-plate dynamic hip screw in an osteoporotic composite femur model
Authors: Rog Dominik , Grigsby Phillip , Hill Zachary , Pinette William , Inceoglu Serkan , Zuckerman Lee
Published: July 2017

Objectives:

The objectives of this study were (1) to compare the axial and torsional stiffness of a dynamic hip screw with a two- and four-hole side-plate in a synthetic model of a healed and stable intertrochanteric femur fracture and (2) to evaluate the load to failure, as well as propensity to peri-implant fracture.

Methods:

Fourth-generation synthetic composite femur models, simulating osteoporotic bone, were implanted with 135° dynamic hip screws (DHS) with either a two- or four-hole side-plate with or without a stable intertrochanteric fracture. Specimens were cyclically loaded up to a nondestructive load to determine the axial and torsional stiffness. Constructs were then loaded to failure in axial compression emulating physiologic forces. Failure load and location of the peri-implant fractures were recorded.

Results:

Axial and torsional stiffness did not differ significantly between the two- and four-hole constructs in either model. Likewise, there was no significant difference in the load to failure. In the intact femurs, failure occurred either at the end of the plate at the distal screw or through the lag screw hole.

Conclusion:

The results of this study demonstrate that DHS constructs with a two- or four-hole side-plate are biomechanically comparable with regard to axial and torsional stiffness and load to failure in an osteoporotic composite femur model. In a healed intertrochanteric fracture model, a two-hole construct did not appear to be more prone to peri-implant fracture. To date, a biomechanical comparison of these two implants with regard to torsional forces has not been reported.
Raised compartment pressures are frequently observed with tibial shaft fractures despite the absence of compartment syndrome: A prospective cohort study
Authors: Ho Kelvin Lor Kah , Sing Nicholas Yeoh Ching , Wong Khai Phang , Huat Andy Wee Teck
Published: July 2017

Purpose:

To measure the intracompartmental pressures surrounding tibial fractures not exhibiting any clinical evidence of compartment syndrome. Our hypothesis was that pressures often exceed the recommended threshold of fasciotomy despite the absence of compartment syndrome, and hence diagnosis based on pressure measurements alone is unreliable.

Methods:

Thirteen consecutive patients with closed tibial shaft fractures without clinical suspicion of compartment syndrome, and who were planned for intramedullary nailing, were prospectively enrolled. Compartment pressures ( P) in all four compartments of the affected leg were measured at the start of surgery and immediately after tibial reaming, and differential pressures (delta P) were calculated based on the diastolic blood pressure prior to induction of anaesthesia.

Results:

No patients required reoperation in the post-operative period, as a result of an undiagnosed compartment syndrome. Using commonly quoted threshold pressure criteria, 62% (using P > 30 mmHg) and 23% of patients (using delta P < 30 mmHg) have been incorrectly diagnosed with compartment syndrome.

Conclusions:

We conclude that raised compartment pressures are frequently seen in patients with tibial shaft fractures; but in most cases, it does not equate to the presence of compartment syndrome. Diagnosis of compartment syndrome based on intracompartmental pressure measurements alone may result in unnecessary fasciotomies in a sizeable number of patients. Compartment syndrome remains a clinical diagnosis, and one which always needs to be considered when managing tibial fractures.
The Church in the Twenty-First-Century Diaspora: The Local Church on Mission
Authors: Nacpil Marian
Published: July 2017

What must the church be in an age of diaspora? This article gives a glimpse of the twenty-first-century global diaspora, which has radically changed the context for the church’s mission. Drawing examples from local churches in Toronto, it casts a spotlight on the fruitful witness of migrant Christians and argues that the opportunity for renewal is ripe in cities where many diaspora peoples live. For those pained by the loss of land and community, it encourages local churches to stand in solidarity with them, striving to see communities shaped by the love of Christ—loving God and neighbor and looking forward with hope to his glorious reign.
Case Report of Severe Weight Loss Possibly Associated with Methylphenidate
Authors: Chandramouli Jane B , Muller Barbara A
Published: July 2017

Objective:

To document a case of severe weight loss in an adult depressed patient being treated with methylphenidate, nefazodone, and electroconvulsive therapy (ECT).

Case Summary:

A 57-year-old white, postmenopausal, nonsmoking, retired nurse with major depressive disorder (status post-ECT) presented to her internist with an involuntary weight loss of >21 kg over six months. Medications included aspirin, hydrochlorothiazide, nefazodone, docusate sodium, methylphenidate, salsalate, and conjugated estrogen. An extensive workup included colonoscopy, abdominal computed tomography (CT) scan, head CT scan, chest X-ray, pelvic ultrasound, Pap smear, mammogram, thyroid function tests, liver function tests, serum electrophoresis, and serum chemistries. All test results were unremarkable.

Discussion:

Methylphenidate was eventually suspected to be contributing to the sudden weight loss in our patient, due to its anorexic effects and a temporal association between the initiation of this drug and the weight loss. However, a MEDLINE search of adverse effects associated with methylphenidate did not identify reports of weight loss of this magnitude. Moreover, published reviews of psychostimulant treatment in adult patients with depressive disorders indicate that anorexia and weight loss are usually not observed.

Conclusions:

This case associates the use of methylphenidate, nefazodone, and ECT for the treatment of depression with significant weight loss in an adult. As the differential diagnosis for involuntary weight loss is expansive, secondary causes such as medications should be considered as possible cofactors precipitating weight loss.
Analytic and Informational Requirements in Disease Management Proposals: A Managed Care Perspective
Authors: Langley Paul C , Martin Robert E
Published: July 2017

Objective:

To outline informational and analytic requirements that one healthcare management system has implemented to ensure that disease management submissions meet common standards for evaluation and review.

Context:

The need for guidelines to support the scope and quality of submissions for disease management negotiation and contracting.

Design:

A series of task definitions are proposed to support three stages in the submission, negotiation, and implementation process: A preliminary submission, establishment of a disease state management agreement, and implementation of the disease state management agreement.

Discussion:

These guidelines are designed to assist companies in meeting minimum standards in their disease state management submissions. The minimum standards relate to their appreciation of the analytic complexities involved, the need to access the appropriate data sources, and the need to meet minimum contracting requirements for program delivery. Not only does application of these guidelines place all potential partners on an equal basis and allow a systematic assessment of competing proposals, but also the degree of uncertainty associated with such agreements, notably in the process of negotiation, is reduced substantially.

Conclusions:

Unless guidelines are implemented by managed care organizations, the prospects for entering into successful disease state management agreements may be uncertain.
Suspected Ofloxacin-Induced Seizures in an Elderly Patient
Authors: Aruna Augustine S , Tam Carlos W , Anderson Deborah S
Published: July 2017

Objective:

To report a case of probable ofloxacin-induced seizures.

Case Summary:

A 74-year-old white man received a single intravenous dose of ofloxacin administered over a 60-minute period. Approximately 4 hours later, he developed seizure-like tremors in all extremities, fecal incontinence, and shortness of breath with harsh, labored breathing. Ofloxacin was discontinued, and the seizure-like tremors subsided within 4 hours of onset.

Discussion:

The time course of events suggested that ofloxacin was the cause of a suspected seizure in this patient. Other causes of seizure were ruled out. Seizures have been reported in less than 1% of patients receiving ofloxacin.

Conclusions:

Ofloxacin can cause seizures, and healthcare providers should be aware of the potential for this adverse effect.
Effects of Continuous and Cyclic Hormone Replacement Therapy on the Lipoprotein Profile in Postmenopausal Women
Authors: Wilken Lori A , Casper Kristin B , Hagmeyer Kathleen O
Published: July 2017

Objective:

To provide an overview of the information concerning cyclic and continuous hormone replacement therapy (HRT) and the effects of the various regimens on the lipid profile.

Data Sources:

MEDLINE (January 1966–December 1996) and Index Medicus (January 1995-December 1996) searches were conducted to identify relevant studies and review articles. Bibliographies of selected articles also were reviewed.

Study Selection:

Studies addressing continuous and cyclic use of a progesterone formulation along with daily conjugated equine estrogen (CEE) and their effects on the lipid profiles of postmenopausal women were selected for review.

Data Extraction:

Applicable data were selected and used in a review format.

Data Synthesis:

CEE has been shown to increase high-density-lipoprotein cholesterol, which may decrease the risk of cardiovascular heart disease. Medroxyprogesterone acetate (MPA) has been added to CEE for postmenopausal HRT to prevent endometrial hyperplasia and cancer. However, MPA negates the beneficial effects of CEE on the lipid profile. Many different HRT regimens, both continuous and cyclic, are being used to increase compliance and to decrease adverse effects. Which regimen offers the best lipid profile results is evaluated in this article.

Conclusions:

The lipid profile effects of HRT using continuous MPA are not significantly different from those obtained with cyclic MPA. Use of a continuous MPA regimen may also offer the long-term advantages of less vaginal bleeding and increased compliance.
Correlation of the Medication Management Evaluation Instrument with Compliance in Geriatric Patients
Authors: Fritsch Michelle A , Gray Cristina D
Published: July 2017

Objective:

To assess the Medication Management Evaluation Instrument (MMEI), which has been shown to detect patient difficulties in compliance but has never been correlated with actual compliance. The goal was to determine the value of this instrument as a predictor of compliance difficulties.

Methods:

Volunteer patients in the Kansas City Veterans Affairs Medical Center currently enrolled in the Geriatric Evaluation and Management Clinic participated in this study. The MMEI, the Jacob's Cognitive Capacity Screening Examination (CCSE), and a pill count (at enrollment and at 6 wk) were conducted on all patients with medications meeting the inclusion criteria.

Results:

Twenty-two patients participated in the study, with eight compliance data dropouts. Follow-up averaged 44.7 days (range 32–62). The mean age was 71.3 years (range 66–81). The CCSE score was significantly lower in those who had problems defining how to take a medication four times daily than in those who did not (p = 0.002). Compliance ranged from 27.1% to 189% (>100% indicates overcompliance). The CCSE average score was 25.1/30 (range 17–30). Other measures in the MMEI were not statistically significant.

Conclusions:

Higher cognitive function was found to correlate with better management of complex regimens. On the basis of these data, the MMEI score does not appear to correlate with compliance. Changes in study design and increased power may provide better assessment of correlation.
State Prescription Label Requirements in the United States
Authors: Rappaport Harvey M
Published: July 2017

Objective:

To determine the current legal requirements for prescription labels and to explore the usefulness of this information in determining the utility of a standardized prescription label.

Data Sources:

State prescription label regulations were requested from Board of Pharmacy executives.

Study Selection:

Label requirements for prescriptions dispensed in community, noninstitutional pharmacies were selected for review.

Data Extraction:

Data were compiled, sorted by state, and analyzed as either federally mandated or additional state requirements. Additional state requirements were divided into 16 categories and analyzed by category.

Data Synthesis:

Responses were received from all 50 states. Five states did not list all federal label requirements. Medication name was the most frequently added requirement, followed by medication strength and name of manufacturer if the medication was generic. Only in New Jersey are pharmacists allowed to add directions not included in the prescription.

Conclusions:

States were consistent in the proper use of federal prescription label requirements. However, there was little agreement on what additional information should appear on the label. Nevertheless, there appears to be consensus for the name of the medication to be on the label. There also appears to be fairly strong consensus that medication strength and quantity should appear on the label. There is little interest in expanding the current directions-for-use requirement. Finally, the results support the utility of a standardized prescription label format.
Technical Challenges in the Clinical Application of Radiomics
Authors: Shaikh Faiq A. , Kolowitz Brian J. , Awan Omer , Aerts Hugo J. , von Reden Anna , Halabi Safwan , Mohiuddin Sohaib A. , Malik Sana , Shrestha Rasu B. , Deible Christopher
Published: July 2017

Radiomics is a quantitative approach to medical image analysis targeted at deciphering the morphologic and functional features of a lesion. Radiomic methods can be applied across various malignant conditions to identify tumor phenotype characteristics in the images that correlate with their likelihood of survival, as well as their association with the underlying biology. Identifying this set of characteristic features, called tumor signature, holds tremendous value in predicting the behavior and progression of cancer, which in turn has the potential to predict its response to various therapeutic options. We discuss the technical challenges encountered in the application of radiomics, in terms of methodology, workflow integration, and user experience, that need to be addressed to harness its true potential.
Bidirectional Text Messaging to Monitor Endocrine Therapy Adherence and Patient-Reported Outcomes in Breast Cancer
Authors: Mougalian Sarah S. , Epstein Lianne N. , Jhaveri Ami P. , Han Gang , Abu-Khalaf Maysa , Hofstatter Erin W. , DiGiovanna Michael P. , Silber Andrea L.M. , Adelson Kerin , Pusztai Lajos , Gross Cary P.
Published: July 2017

Introduction

Up to 40% of patients with breast cancer may not adhere to adjuvant endocrine therapy. Therapy-related adverse effects (AEs) are important contributors to nonadherence. We developed a bidirectional text-message application, BETA-Text, that simultaneously tracks adherence, records symptoms, and alerts the clinical team.

Patients and Methods

We piloted our intervention in 100 patients. The intervention consisted of text messages to which patients responded for 3 months: daily, evaluating adherence; weekly, evaluating medication-related AEs; and monthly, regarding barriers to adherence. Concerning responses prompted a telephone call from a clinic nurse. The primary objective was to assess patient acceptance of this intervention using self-reported surveys. To compare participants with the general population at our institution, we assessed 100 consecutively treated patients as historical controls using medical record review.

Results

We approached 141 consecutive patients, 100 (71%) of whom agreed to participate and 89 of whom completed the intervention. A majority of patients reported that the intervention was easy to use (98%) and helpful in taking their medication (96%). Four patients discontinued therapy before 3 months, and 93% of patients who continued therapy took ≥ 80% of their medication. The frequency of AEs reported by participants via text was higher than that reported in clinical trials: hot flashes (72%), arthralgias (53%), and vaginal symptoms (35%). Approximately 39% of patients reported one or more severe AE that prompted an alert to the provider team to call the patient.

Conclusion

A daily bidirectional text-messaging system can monitor adherence and identify AEs and other barriers to adherence in real time without inconveniencing patients. AEs of endocrine therapy, as detected using this texting approach, are more prevalent than reported in clinical trials.
Prospective Evaluation of Magnetic Resonance Imaging and [18F]Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography at Diagnosis and Before Maintenance Therapy in Symptomatic Patients With Multiple Myeloma Included in the IFM/DFCI 2009 Trial: Results of the IMAJEM Study
Authors: Moreau Philippe , Attal Michel , Caillot Denis , Macro Margaret , Karlin Lionel , Garderet Laurent , Facon Thierry , Benboubker Lotfi , Escoffre-Barbe Martine , Stoppa Anne-Marie , Laribi Kamel , Hulin Cyrille , Perrot Aurore , Marit Gerald , Eveillard Jean-Richard , Caillon Florence , Bodet-Milin Caroline , Pegourie Brigitte , Dorvaux Veronique , Chaleteix Carine , Anderson Kenneth , Richardson Paul , Munshi Nikhil C. , Avet-Loiseau Herve , Gaultier Aurelie , Nguyen Jean-Michel , Dupas Benoit , Frampas Eric , Kraeber-Bodere Françoise
Published: July 2017

Purpose

Magnetic resonance imaging (MRI) and positron emission tomography–computed tomography (PET-CT) are important imaging techniques in multiple myeloma (MM). We conducted a prospective trial in patients with MM aimed at comparing MRI and PET-CT with respect to the detection of bone lesions at diagnosis and the prognostic value of the techniques.

Patients and Methods

One hundred thirty-four patients received a combination of lenalidomide, bortezomib, and dexamethasone (RVD) with or without autologous stem-cell transplantation, followed by lenalidomide maintenance. PET-CT and MRI were performed at diagnosis, after three cycles of RVD, and before maintenance therapy. The primary end point was the detection of bone lesions at diagnosis by MRI versus PET-CT. Secondary end points included the prognostic impact of MRI and PET-CT regarding progression-free (PFS) and overall survival (OS).

Results

At diagnosis, MRI results were positive in 127 of 134 patients (95%), and PET-CT results were positive in 122 of 134 patients (91%; P = .33). Normalization of MRI after three cycles of RVD and before maintenance was not predictive of PFS or OS. PET-CT became normal after three cycles of RVD in 32% of the patients with a positive evaluation at baseline, and PFS was improved in this group (30-month PFS, 78.7% v 56.8%, respectively). PET-CT normalization before maintenance was described in 62% of the patients who were positive at baseline. This was associated with better PFS and OS. Extramedullary disease at diagnosis was an independent prognostic factor for PFS and OS, whereas PET-CT normalization before maintenance was an independent prognostic factor for PFS.

Conclusion

There is no difference in the detection of bone lesions at diagnosis when comparing PET-CT and MRI. PET-CT is a powerful tool to evaluate the prognosis of de novo myeloma.
New Model for Estimating Glomerular Filtration Rate in Patients With Cancer
Authors: Janowitz Tobias , Williams Edward H. , Marshall Andrea , Ainsworth Nicola , Thomas Peter B. , Sammut Stephen J. , Shepherd Scott , White Jeff , Mark Patrick B. , Lynch Andy G. , Jodrell Duncan I. , Tavaré Simon , Earl Helena
Published: July 2017

Purpose

The glomerular filtration rate (GFR) is essential for carboplatin chemotherapy dosing; however, the best method to estimate GFR in patients with cancer is unknown. We identify the most accurate and least biased method.

Methods

We obtained data on age, sex, height, weight, serum creatinine concentrations, and results for GFR from chromium-51 (51Cr) EDTA excretion measurements (51Cr-EDTA GFR) from white patients ≥ 18 years of age with histologically confirmed cancer diagnoses at the Cambridge University Hospital NHS Trust, United Kingdom. We developed a new multivariable linear model for GFR using statistical regression analysis.51Cr-EDTA GFR was compared with the estimated GFR (eGFR) from seven published models and our new model, using the statistics root-mean-squared-error (RMSE) and median residual and on an internal and external validation data set. We performed a comparison of carboplatin dosing accuracy on the basis of an absolute percentage error > 20%.

Results

Between August 2006 and January 2013, data from 2,471 patients were obtained. The new model improved the eGFR accuracy (RMSE, 15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with all published models. Body surface area (BSA)–adjusted chronic kidney disease epidemiology (CKD-EPI) was the most accurate published model for eGFR (RMSE, 16.30 mL/min; 95% CI, 15.34 to 17.38 mL/min) for the internal validation set. Importantly, the new model reduced the fraction of patients with a carboplatin dose absolute percentage error > 20% to 14.17% in contrast to 18.62% for the BSA-adjusted CKD-EPI and 25.51% for the Cockcroft-Gault formula. The results were externally validated.

Conclusion

In a large data set from patients with cancer, BSA-adjusted CKD-EPI is the most accurate published model to predict GFR. The new model improves this estimation and may present a new standard of care.
Exceptional Chemotherapy Response in Metastatic Colorectal Cancer Associated With Hyper-Indel–Hypermutated Cancer Genome and Comutation of POLD1 and MLH1
Authors: Sharma Manish R. , Auman James T. , Patel Nirali M. , Grilley-Olson Juneko E. , Zhao Xiaobei , Moschos Stergios J. , Parker Joel S. , Yin Xiaoying , Hayward Michele C. , Polite Blase N. , Marangon Elena , Posocco Bianca , Toffoli Giuseppe , Hayes D. Neil , Innocenti Federico
Published: July 2017

Purpose

A 73-year-old woman with metastatic colon cancer experienced a complete response to chemotherapy with dose-intensified irinotecan that has been durable for 5 years. We sequenced her tumor and germ line DNA and looked for similar patterns in publicly available genomic data from patients with colorectal cancer.

Patients and Methods

Tumor DNA was obtained from a biopsy before therapy, and germ line DNA was obtained from blood. Tumor and germline DNA were sequenced using a commercial panel with approximately 250 genes. Whole-genome amplification and exome sequencing were performed for POLE and POLD1. A POLD1 mutation was confirmed by Sanger sequencing. The somatic mutation and clinical annotation data files from the colon (n = 461) and rectal (n = 171) adenocarcinoma data sets were downloaded from The Cancer Genome Atlas data portal and analyzed for patterns of mutations and clinical outcomes in patients with POLE- and/or POLD1-mutated tumors.

Results

The pattern of alterations included APC biallelic inactivation and microsatellite instability high (MSI-H) phenotype, with somatic inactivation of MLH1 and hypermutation (estimated mutation rate > 200 per megabase). The extremely high mutation rate led us to investigate additional mechanisms for hypermutation, including loss of function of POLE. POLE was unaltered, but a related gene not typically associated with somatic mutation in colon cancer, POLD1, had a somatic mutation c.2171G>A [p.Gly724Glu]. Additionally, we noted that the high mutation rate was largely composed of dinucleotide deletions. A similar pattern of hypermutation (dinucleotide deletions, POLD1 mutations, MSI-H) was found in tumors from The Cancer Genome Atlas.

Conclusion

POLD1 mutation with associated MSI-H and hyper-indel–hypermutated cancer genome characterizes a previously unrecognized variant of colon cancer that was found in this patient with an exceptional response to chemotherapy.
Inherited Mutations in Men Undergoing Multigene Panel Testing for Prostate Cancer: Emerging Implications for Personalized Prostate Cancer Genetic Evaluation
Authors: Giri Veda N. , Obeid Elias , Gross Laura , Bealin Lisa , Hyatt Colette , Hegarty Sarah E. , Montgomery Susan , Forman Andrea , Bingler Ruth , Kelly William K. , Dicker Adam P. , Winheld Stephanie , Trabulsi Edouard J. , Chen David Y.T. , Lallas Costas D. , Allen Brian A. , Daly Mary B. , Gomella Leonard G.
Published: July 2017

Purpose

Multigene panels are commercially available for the evaluation of prostate cancer (PCA) predisposition, which necessitates tailored genetic counseling (GC) for men. Here we describe emerging results of Genetic Evaluation of Men, prospective multigene testing study in PCA to inform personalized genetic counseling, with emerging implications for referrals, cancer screening, and precision therapy.

Patients and Methods

Eligibility criteria for men affected by or at high risk for PCA encompass age, race, family history (FH), and PCA stage/grade. Detailed demographic, clinical, and FH data were obtained from participants and medical records. Multigene testing was conducted after GC. Mutation rates were summarized by eligibility criteria and compared across FH data. The 95% CI of mutation prevalence was constructed by using Poisson distribution.

Results

Of 200 men enrolled, 62.5% had PCA. Eleven (5.5%; 95% CI, 3.0% to 9.9%) had mutations; 63.6% of mutations were in DNA repair genes. FH of breast cancer was significantly associated with mutation status ( P = .004), and FH that met criteria for hereditary breast and ovarian cancer syndrome was significantly associated with PCA (odds ratio, 2.33; 95% CI, 1.05 to 5.18). Variants of uncertain significance were reported in 70 men (35.0%). Among mutation carriers, 45.5% had personal/FH concordant with the gene. A tailored GC model was developed based on emerging findings.

Conclusion

Multigene testing for PCA identifies mutations mostly in DNA repair genes, with implications for precision therapy. The study highlights the importance of comprehensive genetic evaluation for PCA beyond metastatic disease, including early-stage disease with strong FH. Detailed FH is important for referrals of men for genetic evaluation. The results inform precision GC and cancer screening for men and their male and female blood relatives.
Comprehensive Molecular Characterization of Urachal Adenocarcinoma Reveals Commonalities With Colorectal Cancer, Including a Hypermutable Phenotype
Authors: Kardos Jordan , Wobker Sara E. , Woods Michael E. , Nielsen Matthew E. , Smith Angela B. , Wallen Eric M. , Pruthi Raj S. , Hayward Michele C. , McGinty Katrina A. , Grilley-Olson Juneko E. , Patel Nirali M. , Weck Karen E. , Black Peter , Parker Joel S. , Milowsky Matthew I. , Hayes D. Neil , Kim William Y.
Published: July 2017

Purpose

Urachal adenocarcinoma is a rare type of primary bladder adenocarcinoma that comprises less than 1% of all bladder cancers. The low incidence of urachal adenocarcinomas does not allow for an evidence-based approach to therapy. Transcriptome profiling of urachal adenocarcinomas has not been previously reported. We hypothesized that an in-depth molecular understanding of urachal adenocarcinoma would uncover rational therapeutic strategies.

Patients and Methods

We performed targeted exon sequencing and global transcriptome profiling of 12 urachal tumors to generate a comprehensive molecular portrait of urachal adenocarcinoma. A single patient with an MSH6 mutation was treated with the anti–programmed death-ligand 1 antibody, atezolizumab.

Results

Urachal adenocarcinoma closely resembles colorectal cancer at the level of RNA expression, which extends previous observations that urachal tumors harbor genomic alterations that are found in colorectal adenocarcinoma. A subset of tumors was found to have alterations in genes that are associated with microsatellite instability ( MSH2 and MSH6) and hypermutation ( POLE). A patient with an MSH6 mutation was treated with immune checkpoint blockade, which resulted in stable disease.

Conclusion

Because clinical trials are next to impossible for patients with rare tumors, precision oncology may be an important adjunct for treatment decisions. Our findings demonstrate that urachal adenocarcinomas molecularly resemble colorectal adenocarcinomas at the level of RNA expression, are the first report, to our knowledge, of MSH2 and MSH6 mutations in this disease, and support the consideration of immune checkpoint blockade as a rational therapeutic treatment of this exceedingly rare tumor.
All My Relatives: Exploring Nineteenth-Century Lakota Ontology and Belief
Authors: Posthumus David C.
Published: July 2017

This article is a reinterpretation of the ethnohistorical literature on the Lakota or Western (Teton) Sioux from a Descolian animist perspective. Applying key insights from what has been called the “ontological turn,” in particular, the dual notions of interiority and physicality and an extended notion of personhood that includes nonhumans as well as humans, this article demonstrates how a new animist framework can connect and articulate otherwise disparate and obscure elements of Lakota ethnography, offering new and exciting insights, along with the potential for a deeper understanding of traditional Lakota culture.
Tg(Th-Cre)FI172Gsat (Th-Cre)defines neurons that are required for full hypercapnic and hypoxic reflexes
Authors: Sun Jenny J. , Ray Russell S.
Published: July 2017

The catecholaminergic system has been implicated in many facets of breathing control and offers an important target to better comprehend the underlying etiologies of both developmental and adult respiratory pathophysiologies. Here we used a noninvasive DREADD based pharmaco-genetic approach to acutely perturb Tg(Th-Cre)FI172Gsat (Th-Cre) defined neurons in awake and unrestrained mice in an attempt to characterize catecholaminergic function in breathing. We report that clozapine-N-oxide (CNO)-DREADD mediated inhibition of Th-Cre defined neurons results in blunted ventilatory responses under respiratory challenge. Under a hypercapnic challenge (5%CO2/21%O2/74%N2), perturbation of Th-Cre neurons results in reduced fR, V̇e, and V̇e/V̇o2. Under a hypoxic challenge (10%O2/90%N2), we saw reduced fR,V̇e, and V̇o2 in addition to instability in both interbreath interval and tidal volume resulting in a Cheyne-Stokes like respiratory pattern. These findings demonstrate the necessity of Th-Cre defined neurons for the hypercapnic and hypoxic ventilatory responses and breathing stability during hypoxia. However, given the expanded non-catecholaminergic expression domains of the Tg(Th-Cre)FI172Gsat mouse line found in the brainstem, full phenotypic effect cannot be assigned solely to catecholaminergic neurons. Nonetheless, this work identifies a key respiratory population that may lead to further insights into the circuitry that maintains respiratory stability in the face of homeostatic challenges.
Inwardly rectifying potassium channels influence Drosophila wing morphogenesis by regulating Dpp release
Authors: Dahal Giri Raj , Pradhan Sarala Joshi , Bates Emily Anne
Published: July 2017

Loss of embryonic ion channel function leads to morphological defects, but the underlying reason for these defects remains elusive. Here, we show that inwardly rectifying potassium (Irk) channels regulate release of the Drosophila bone morphogenetic protein Dpp in the developing fly wing and that this is necessary for developmental signaling. Inhibition of Irk channels decreases the incidence of distinct Dpp-GFP release events above baseline fluorescence while leading to a broader distribution of Dpp-GFP. Work by others in different cell types has shown that Irk channels regulate peptide release by modulating membrane potential and calcium levels. We found calcium transients in the developing wing, and inhibition of Irk channels reduces the duration and amplitude of calcium transients. Depolarization with high extracellular potassium evokes Dpp release. Taken together, our data implicate Irk channels as a requirement for regulated release of Dpp, highlighting the importance of the temporal pattern of Dpp presentation for morphogenesis of the wing.
Cell interactions, signals and transcriptional hierarchy governing placode progenitor induction
Authors: Hintze Mark , Prajapati Ravindra Singh , Tambalo Monica , Christophorou Nicolas A. D. , Anwar Maryam , Grocott Timothy , Streit Andrea
Published: July 2017

In vertebrates, cranial placodes contribute to all sense organs and sensory ganglia and arise from a common pool of Six1/Eya2+ progenitors. Here we dissect the events that specify ectodermal cells as placode progenitors using newly identified genes upstream of the Six/Eya complex. We show in chick that two different tissues, namely the lateral head mesoderm and the prechordal mesendoderm, gradually induce placode progenitors: cells pass through successive transcriptional states, each identified by distinct factors and controlled by different signals. Both tissues initiate a common transcriptional state but over time impart regional character, with the acquisition of anterior identity dependent on Shh signalling. Using a network inference approach we predict the regulatory relationships among newly identified transcription factors and verify predicted links in knockdown experiments. Based on this analysis we propose a new model for placode progenitor induction, in which the initial induction of a generic transcriptional state precedes regional divergence.