bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Modeled Longitudinal CA-125 Kinetics and Survival of Ovarian Cancer Patients: A GINECO AGO MRC CTU Study
Authors: Colomban Olivier , Tod Michel , Leary Alexandra , Ray-Coquard Isabelle , Lortholary Alain , Hardy-Bessard Anne Claire , Pfisterer Jacobus , Du Bois Andreas , Kurzeder Christian , Burges Alexander , Péron Julien , Freyer Gilles , You Benoit 
Published: April 2019

Abstract

Purpose:
Regarding cancer antigen 125 (CA-125) longitudinal kinetics during chemotherapy, the actual predictive value of the Gynecologic Cancer Intergroup (GCIG) CA-125 response criterion is questioned. The modeled CA-125 elimination rate constant KELIM exhibited higher prognostic value in patients with recurrent ovarian cancer enrolled in the CALYPSO trial. The objective was to validate the higher predictive and prognostic values of KELIM during first-line treatments.

Experimental Design:
Data from three large phase III trials were analyzed: AGO OVAR 9 [learning set: carboplatin-paclitaxel (CP) ± gemcitabine; n = 1,288]; AGO OVAR 7 (validation set: CP ± topotecan; n = 192); and ICON7 (validation set: CP ± bevacizumab; n = 1,388). The CA-125 profiles were fit with a nonlinear mixed-effect model during the first 100 days, and the individual KELIM were calculated. KELIM prognostic and predictive values for survival were assessed against GCIG criterion and other prognostic factors in univariate/multivariate analyses.

Results:
The GCIG CA-125 endpoint provided no meaningful predictive/prognostic information. C-index analyses confirmed the higher predictive value of KELIM compared with GCIG criterion for progression-free survival and overall survival (OS). KELIM provided reproducible prognostic information. Patients with favorable KELIM ≥ upper tercile (0.0711 per days) consistently experienced better OS, with HRs between 0.44 and 0.58 (e.g., median OS &gt;65 months vs. &lt;35 months).

Conclusions:
Modeled KELIM provides higher predictive and prognostic information based on CA-125 longitudinal kinetics compared with GCIG response criteria during first-line chemotherapy. Integration of this endpoint in guidelines may be considered. Individual KELIM and survival simulations can be calculated at http://www.biomarker-kinetics.org/. Further assessment of the surrogate value of KELIM treatment–related variations in a GCIG meta-analysis is warranted.
See related commentary by Maitland et al., p. 5182
Combined MAPK Pathway and HDAC Inhibition Breaks Melanoma
Authors: Lombard David B. , Cierpicki Tomasz , Grembecka Jolanta 
Published: April 2019

Abstract

Summary:
In this issue, Maertens and colleagues demonstrate that HDAC3 inhibition potentiates the effects of MAPK pathway inhibitors in melanoma, including difficult-to-treat NRAS- and NF1-driven tumors, with MGMT expression serving as a biomarker for responsiveness to the BRAF/MEK/HDAC inhibitor combination. Mechanistically, this triple cocktail suppresses expression of genes involved in DNA repair, leading to enhanced killing of melanoma cells.
See related article by Maertens et al., p. 526.
Computed Tomography–Based Indexed Aortic Annulus Size to Predict Prosthesis-Patient Mismatch
Authors: Head Stuart J. , Reardon Michael J. , Deeb G. Michael , Van Mieghem Nicolas M. , Popma Jeffrey J. , Gleason Thomas G. , Williams Mathew R. , Radhakrishnan Sam , Fremes Stephen , Oh Jae K. , Chang Yanping , Boulware Michael J. , Kappetein Arie Pieter ,   for the SURTAVI Investigators
Published: April 2019

Background:
Hemodynamic performance of prostheses after transcatheter aortic valve replacement (TAVR) is generally better than after surgical aortic valve replacement (SAVR), especially in patients with a small native annulus size. However, it remains unclear whether differences are consistent for patients with a different propensity for developing prosthesis-patient mismatch (PPM), considering annulus size and body size of patients.

Methods and Results:

The SURTAVI trial (Surgical Replacement and Transcatheter Aortic Implantation) compared TAVR using a self-expandable valve with SAVR in intermediate-risk patients. Multidetector computed tomography–based aortic annulus size consisted of the perimeter-derived diameter, which was divided by body surface area to produce an indexed annulus size. Patients were categorized into a small (9–12 mm/m
2
), medium (>12–14 mm/m
2
), and large (>14–18 mm/m
2
) group according to indexed annulus size. We compared TAVR and SAVR for PPM, hemodynamics, and clinical, and functional outcomes through 1-year follow-up within the size groups. Patients who underwent TAVR received a larger prosthesis with increasing indexed annulus size (
P
<0.001), while there was no difference in prosthesis size in patients who underwent SAVR (
P
=0.74). Patients in all size groups had significantly larger indexed effective orifice area and lower mean gradients at discharge after TAVR versus SAVR. Rates of PPM were significantly lower with TAVR versus SAVR in all groups (
P
<0.001) and declined with larger indexed annulus sizes with both TAVR (
P
=0.04) and SAVR (
P
=0.03). Indexed annulus size was an independent predictor of PPM after TAVR and SAVR. Clinical outcomes were comparable between TAVR and SAVR across all groups, apart from a significantly higher rate of reintervention after TAVR versus SAVR in the large indexed annulus size group (2.5% versus 0%;
P
=0.01) but without significant interaction (
P
int
=0.81).

Conclusions:
Rates of PPM were significantly lower after TAVR than after SAVR across all groups of indexed annulus size, reflecting better hemodynamic performance of transcatheter versus surgical valves, irrespective of the propensity to develop PPM. More attention should be directed to prevention of PPM after SAVR. This information should be considered by the Heart Team to recommend a specific procedure or valve.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01586910.
Rapid Neurologic Improvement Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study
Authors: Heit Jeremy J. , Mlynash Michael , Kemp Stephanie M. , Lansberg Maarten G. , Christensen Soren , Marks Michael P. , Ortega-Gutierrez Santiago , Albers Gregory W. 
Published: April 2019

Background and Purpose—
Thrombectomy in late time windows leads to improved outcomes in patients with ischemic stroke due to large vessel occlusion. We determined whether patients with rapid neurological improvement (RNI) 24 hours after thrombectomy were more likely to have a favorable clinical outcome in the DEFUSE 3 study (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3).

Methods—
All patients who underwent thrombectomy in DEFUSE 3 were included. RNI was defined as a reduction of ≥8 on the National Institutes of Health Stroke Scale or National Institutes of Health Stroke Scale zero to one 24 hours after thrombectomy. Clinical outcomes were assessed by an ordinal analysis modified Rankin Scale score and a dichotomous analysis for 90-day independence (modified Rankin Scale score, 0–2).

Results—

Ninety-one patients in DEFUSE 3 underwent thrombectomy with follow-up data; 31 patients (34%) experienced RNI (RNI+) after thrombectomy and 60 patients (66%) did not (RNI−). Patient demographics and stroke presentation and imaging details were similar between RNI+ and RNI− patients. Reperfusion (Thrombolysis in Cerebral Infarction 2b-3) after thrombectomy was achieved in 26 (84%) RNI+ and 43 (72%) RNI− (
P
=0.2). Symptomatic intracranial hemorrhage occurred in no RNI+ and 8% of RNI− patients (
P
=0.2). RNI was associated with a favorable modified Rankin Scale shift at day 90 (odds ratio, 3.8; CI, 1.7–8.6;
P
=0.001) and higher rates of modified Rankin Scale zero to 2 (61% versus 37%; odds ratio, 2.7; CI, 1.1–6.7;
P
=0.03). Mortality was 3% in RNI+ versus 18% in RNI− (
P
=0.05). RNI+ patients had lower median 24-hour National Institutes of Health Stroke Scale (5 [interquartile range (IQR), 1–7] versus 13 [IQR, 7.5–21];
P
<0.001), smaller 24-hour infarction volume (21 [IQR, 5–32] versus 65 [IQR, 27–145] mL;
P
<0.001), and less 24-hour infarct growth (8 [IQR, 1–18] versus 37 [IQR, 16–105] mL;
P
<0.001) compared with RNI− patients. Hospital stay was shorter in RNI+ (3.7 [IQR, 2.9–7.1] versus 7.4 [IQR, 5.2–12.1] days in RNI−;
P
<0.001).

Conclusions—
RNI following thrombectomy correlates with favorable clinical and radiographic outcomes and reduced hospital length of stay. RNI was a favorable prognostic sign following late-window thrombectomy in DEFUSE 3.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02586415.
Seasonal Changes in Water and Energy Balances over the Appalachian Region and Beyond throughout the Twenty-First Century
Authors: Fernandez Rodrigo , Zegre Nicolas 
Published: April 2019

AbstractThe Appalachian Mountains serve as a water source for important population centers in the eastern and midwestern United States. Despite this, the effects of climate change on the hydroclimatology of the region have not been thoroughly assessed, and its effects for water resources remain uncertain. In this study, we analyze the effects of climate change in a holistic approach to consider differential changes between atmospheric water supply (precipitation) and atmospheric water demand (potential evapotranspiration). We analyze the absolute and relative changes in both variables, as well as their relation (aridity index) and future projected shifts in their seasonality. Our findings show that precipitation is projected to increase in the northeastern part of the region and decrease in the southwest with a transition zone in the central Appalachians. Potential evapotranspiration increases consistently throughout the twenty-first century at a higher rate than precipitation, increasing the aridity of the region except for some small localized pockets at high elevations. The seasonality of precipitation indicates different shifts across the region related to changes in the dominant synoptic drivers of the region and changes in the seasonal characteristics of the land surface. All changes are exacerbated in the most extreme future climate scenario, highlighting the importance of local to global policies toward a more sustainable water resources development. In addition, we perform a basin-scale assessment on 20 major rivers with headwaters within the “Appalachian Region.” Our basin-scale results enforce the gridded regional results and indicate that, as temperatures continue to increase, lowland areas will rely more heavily on higher-elevation forested headwater catchments for water supply.
Relationships among Intermodel Spread and Biases in Tropical Atlantic Sea Surface Temperatures
Authors: Mohino Elsa , Rodríguez-Fonseca Belén , Mechoso C. Roberto , Losada Teresa , Polo Irene 
Published: April 2019

Abstract
State-of-the-art general circulation models show important systematic errors in their simulation of sea surface temperatures (SST), especially in the tropical Atlantic. In this work the spread in the simulation of climatological SST in the tropical Atlantic by 24 CMIP5 models is examined, and its relationship with the mean systematic biases in the region is explored. The modes of intermodel variability are estimated by applying principal component (PC) analysis to the SSTs in the region 70°W–20°E, 20°S–20°N. The intermodel variability is approximately explained by the first three modes. The first mode is related to warmer SSTs in the basin, shows worldwide connections with same-signed loads over most of the tropics, and is connected with lower low cloud cover over the eastern parts of the subtropical oceans. The second mode is restricted to the Atlantic, where it shows negative and positive loads to the north and south of the equator, respectively, and is connected to a too weak Atlantic meridional overturning circulation (AMOC). The third mode is related to the double intertropical convergence zone bias in the Pacific and to an interhemispheric asymmetry in the net radiation at the top of the atmosphere. The structure of the second mode is closer to the mean bias than that of the others in the tropical Atlantic, suggesting that model difficulties with the AMOC contribute to the regional biases.
Moral Hazard, Path Dependency and Failing Franchisors: Mitigating Franchisee Risk Through Participation
Authors: Gant Jennifer L L , Buchan Jenny 
Published: April 2019

AbstractEmployment relations are well understood. Business format franchising is a newer and rapidly evolving business expansion formula, also providing employment. This article compares the fates of employees and franchisees in their employer/franchisor insolvency. Whereas employees enjoy protection, franchisees continue to operate in conditions that have been described as Feudal. We identify the inherence of moral hazard, path dependency and optimism bias as reasons for the failure of policies and corporations laws, globally, to adapt to the franchise relationship. This failure comes into sharp focus during a franchisor’s insolvency. We demonstrate that the models of participation available to employees in the United States, Australia and the United Kingdom could be used to inform a re-balancing of the franchisees’ relationship with administrators and liquidators during the insolvency of their franchisor, providing franchisees with rights and restoring their dignity.
The importance of self-awareness: musings of a medical student
Authors: Ouliaris Calina 
Published: April 2019

Objective: Self-awareness is essential for combating burnout, promoting self-care, and wellbeing in health professionals. This article examines modern day roadblocks to developing this skill in medical practice and highlights some simple solutions for consideration. Conclusion: The capacity for self-awareness is essential to the modern-day physician seeking a long and fulfilling career. Mindfulness meditation and reflective writing are two simple, proven methods that can be easily implemented into medical training.
Drain or No Drain Following Pancreaticoduodenectomy: The Unsolved Dilemma
Authors: Zaghal A. , Tamim H. , Habib S. , Jaafar R. , Mukherji D. , Khalife M. , Mailhac A. , Faraj W. 
Published: April 2019

Background and aims: There is no consensus regarding the routine placement of intra-abdominal drains after pancreaticoduodenectomy. We aim to determine the effects of intraperitoneal drain placement during pancreaticoduodenectomy on 30-day postoperative morbidity and mortality. Methods: Patients who underwent pancreaticoduodenectomy for pancreatic tumors were identified from the 2014–2015 American College of Surgeons—National Surgical Quality Improvement Program Database. Univariate and multivariate analyses adjusting for known prognostic variables were performed. A subgroup analysis was performed based on the risk for development of postoperative pancreatic leak determined by the pancreatic duct caliber, parenchymal texture, and body mass index. Results: A total of 6858 patients with pancreatic tumors who underwent pancreaticoduodenectomy were identified in the 2014–2015 American College of Surgeons—National Surgical Quality Improvement Program Database dataset. In all, 87.4% of patients had intraperitoneal drains placed. A 30-day mortality rate was higher in the no-drain group (2.9% vs. 1.7%, P = 0.003). Patients in the drain group had a higher incidence of overall morbidity (49.5% vs. 41.2%, P = 0.0008), delayed gastric emptying (18.1% vs. 13.7%, P = 0.004), pancreatic fistulae (19.4% vs. 9.9%, P ⩽ 0.0001), and prolonged length of hospital stay over 10 days (43.7% vs. 34.9%, P < 0.0001). Subgroup analysis based on risk categories revealed a higher 30-day mortality rate in the no-drain group among patients with high-risk features (3.1% vs. 1.6%, P = 0.02). Delayed gastric emptying and pancreatic fistula development remained significantly higher in the drain group only in the high-risk category. Prolonged length of hospital stay and composite morbidity remained higher in the drain group regardless of the risk category. Conclusion: To our knowledge, this is the largest study to date that aims at clarifying the pros and cons of the intraperitoneal drain placement during pancreaticoduodenectomy for pancreatic tumors. We showed a higher 30-day mortality rate if drain insertion was omitted during pancreaticoduodenectomy in patients with softer pancreatic textures, smaller pancreatic duct caliber, and body mass index over 25. Postoperative 30-day morbidity rate was higher if a drain was inserted regardless of the risk category. Further randomized controlled trials with prospective evaluation of stratification factors for fistula risk are needed to establish a clear recommendation.
Impact of Medicare Continuous Subcutaneous Insulin Infusion Policies in Patients With Type 1 Diabetes
Authors: Argento Nicholas B. , Liu Jingwen , Hughes Allyson S. , McAuliffe-Fogarty Alicia H. 
Published: April 2019

Background: The Centers for Medicare and Medicaid Services (CMS) has numerous requirements for coverage of continuous subcutaneous insulin infusion (CSII; insulin pump). Due to recent improvements in diabetes treatment, people with type 1 diabetes are living longer, resulting in an increase in the number of individuals who are eligible for Medicare and are impacted by CMS policies regarding CSII. Methods: Two hundred forty-one adults with type 1 diabetes who had been on CSII with CMS coverage for at least 6 months were surveyed. Median age was 67 years, mean A1c was 7.0%, 64% were women, 93% were white, and the median type 1 diabetes duration was 42 years. Participants reported median CSII use of 15 years and 82% were on CSII before starting CMS. Results: Of those starting CSII while on CMS, challenges included cost of supplies (29%) or the insulin pump (24%). The majority (57.5%) reported issues with obtaining supplies, the most common problems being delays in release of supplies (29%), difficulty getting paperwork completed (23.5%), and seeing a health care provider every 90 days (18%). Participants reported changing their CSII behaviors because of supply delays (39%) including leaving site in place >3 days (64%), and reusing pump supplies (34%). Consequently, participants reported adverse outcomes including more erratic (48%) or higher (42%) blood glucose and pain or irritation at sites (34%). Conclusion: This study concluded that current CMS CSII policies promote adverse CSII behaviors and outcomes in type 1 diabetes and thus call for changes in the CMS CSII policies.
Quality of Life and Impact of Endoscopic Sinus Surgery in Adult Patients With Cystic Fibrosis
Authors: Lazio Maria S. , Luparello Paolo , Mannelli Giuditta , Santoro Giovanni P. , Bresci Silvia , Braggion Cesare , Gallo Oreste , Maggiore Giandomenico 
Published: April 2019

Background Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasian population. Due to its pathological mechanism, chronic rhino sinusitis (CRS) associated or not with nasal polyposis usually occurs in adults and affects close to one-half of all CF patients. The goal of our work was to evaluate the impact of endoscopic sinus surgery (ESS) in the quality of life (QoL) of the CF patients and demonstrate an improvement of the functional outcomes in the patients undergoing the surgical procedure rather than in the not treated ones. Methodology: We studied 54 adult patients affected by CF. Lund–Kennedy, Lund–Mackay scores, and Sino-Nasal Outcome Test-22 (SNOT-22) were analyzed. Results Twenty-two (40.7%) of the 54 CF patients underwent ESS. This group presented more likely complaints consistent with CRS. Lund–Kennedy and Lund–Mackay scores appeared higher in the ESS group: 10 (range of 6–12) and 16 (range of 12–20), respectively. SNOT-22 showed median values for non-ESS and ESS group of 17.5 (range of 3–68) and 44 (range of 10–73), respectively. Conclusions ESS represents the best option to improve clinical QoL of CF patients who do not response to conventional medical therapy.
Incidental findings in pancreas screening programs for high‐risk individuals: Results from three European expert centers
Authors: Ibrahim Isaura S , Brückner Catharina , Carrato Alfredo , Earl Julie , Inderson Akin , de Vos tot Nederveen Cappel Wouter H , Mintziras Ioannis , Matthäi Elvira , Figiel Jens , Wasser Martin , Moreau Hans , Bonsing Bert , Slater Emily P , Bartsch Detlef K , Vasen Hans FA 
Published: April 2019

BackgroundWidespread abdominal imaging has led to a substantial increase in the detection of incidentalomas. Currently, an increasing number of centers offer surveillance of the pancreas to individuals at high risk (IARs) of pancreatic ductal adenocarcinoma (PDAC).ObjectiveThe aims of this study were to evaluate the frequency and type of incidental findings in a magnetic resonance imaging (MRI)‐based surveillance program for IARs for PDAC, and to discuss the benefit of detecting these lesions.MethodsThe outcome of MRI screening was reviewed in 568 individuals from three long‐term pancreas surveillance programs conducted at three large European expert centers. All MRIs were studied in detail for the presence of incidental lesions.ResultsThe most common lesions were liver cysts, renal cysts and liver hemangioma, which together comprised 75% of all lesions. Only five (0.9%) patients underwent surgery for a benign lesion. Cancer was detected in 11 patients (1.9%); early detection of tumors was beneficial in at least five cases.ConclusionThe present study demonstrates that extrapancreatic incidentaloma is a common finding in IARs for PDAC, but rarely requires additional treatment. CDKN2A‐p16‐Leiden mutation carriers were the only patient group found to harbor a substantial number of cancers, and detection resulted in benefit in several cases.
Healthcare staff perceptions of integrated care in a programme for complex chronic patients admitted to hospital because of heart failure (ProMIC)
Authors: Domingo Cristina , Regidor Iratxe , Alonso Edurne , Besga Ariadna , Orozco Domingo , Nuño Roberto 
Published: April 2019

Introduction Patients with heart failure are usually a frail population characterised by complex care needs. To ensure an integrated care approach, it is necessary to work collaboratively across organisational boundaries. The purpose of this study is to measure and understand the perception of collaboration between clinicians participating in a comprehensive care programme for patients with heart failure, known as PROMIC. Methods A sequential mixed-method study design was used. A sample of PROMIC clinicians completed a survey in which they evaluated 10 dimensions of collaboration in 2010 and in 2014. The perspectives of clinicians were studied more in depth in a focus group in 2012, which was analysed using content analysis. Outcomes: Professionals’ perception of collaboration showed an improvement by 1.18 points (53%) over the period 2010–14. The comprehensive programme proved to be of major support to the professionals. Sometimes, the study participants did not feel prepared to manage cases due to the complexity of the situations with regard to patients’ care. Both, the quantitative and the qualitative methods, showed up a congruent information about the positive perception of participants of the programme itself and the collaboration. Discussion The complexity of care processes and the need for continuity of care mean that large-scale collaboration is necessary between care levels as well as major interdisciplinary teamwork, to achieve the best possible outcomes in terms of health. ProMIC intervention has helped to improve professionals’ perception in terms of collaboration between levels.