bluuebunny/crossref_metadata_2025 huggingface dataset:
Periprocedural Management of Patients Undergoing Liver Resection or Embolotherapy for Neuroendocrine Tumor Metastases
Authors: Kwon Daniel H. , Paciorek Alan , Mulvey Claire K. , Chan Hilary , Fidelman Nicholas , Meng Lingzhong , Nakakura Eric K. , Zhang Li , Bergsland Emily K. , Van Loon Katherine
Published: April 2019

Objectives

The objective of this study was to describe the periprocedural management of patients with well-differentiated neuroendocrine tumors with hepatic metastases who underwent liver-directed procedures.

Methods

We performed a retrospective review of patients with metastatic neuroendocrine tumors who underwent liver resection, ablation, or embolotherapy at a single center from 2012 to 2016. The primary outcome was occurrence of documented carcinoid crisis (CC) or hemodynamic instability (HDI), defined as 10 minutes or more of systolic blood pressure less than 80 or greater than 180 mm Hg, or pulse greater than 120 beats per minute.

Results

We identified 75 patients who underwent liver resection/ablation (n = 38) or embolotherapy (n = 37). Twenty-four patients (32%) experienced CC or HDI (CC/HDI); CC occurred in 3 patients. No clinicopathologic or procedural factors, including procedure type, octreotide or long-acting somatostatin analog use, and history of carcinoid syndrome, were associated with CC/HDI. Grades 2 to 4 complications were reported in 42% of patients who experienced CC/HDI versus in 16% of patients who did not experience CC/HDI (P < 0.05).

Conclusions

A significant portion of patients developed CC/HDI, and these patients were more likely to develop severe postprocedural complications. Periprocedural octreotide use was not associated with lower CC/HDI occurrence, but continued use is advised given its safety profile until additional studies definitively demonstrate lack of benefit.
Risk and Predictors of Postoperative Morbidity and Mortality After Pancreaticoduodenectomy for Pancreatic Neuroendocrine Neoplasms
Authors: Partelli Stefano , Tamburrino Domenico , Cherif Rim , Muffatti Francesca , Moggia Elisabetta , Gaujoux Sébastien , Sauvanet Alain , Falconi Massimo , Fusai Giuseppe
Published: April 2019

Objectives

Pancreaticoduodenectomy (PD) is associated with a high risk of postoperative complications and mortality. The aim of this study was to compare postoperative morbidity after PD in patients undergoing resections for pancreatic neuroendocrine neoplasms (PanNENs) with patients undergoing the same resection for pancreatic ductal adenocarcinoma (PDAC).

Methods

Data of 566 patients from 3 European tertiary referral centers between 1998 and 2014 were considered.

Results

Overall, 566 patients (179 with PanNENs, 387 with PDAC) who underwent PD were analyzed. Patients with PanNENs were significantly younger (56 vs 64 years, P < 0.0001). The consistency of the pancreas was soft in 147 patients (82%) with PanNENs and in 162 patients (42%) with PDAC (P < 0.0001). Patients in the PanNENs group had a significantly higher rate of pancreatic fistula (P < 0.0001), bile leak (P = 0.004), abdominal collection (P = 0.017), and development of sepsis (P = 0.042). No differences in terms of overall postoperative complications, median length of stay, and in-hospital mortality were found. On multivariate analysis sex (male), PanNENs indication, blood transfusion, and a soft pancreatic texture were independent predictors of pancreatic fistula after PD.

Conclusions

Pancreaticoduodenectomy for PanNENs is associated with higher rate of surgical-specific postoperative complications than those for PDAC.
Long-Term Services and Supports
Authors: Treiger Teresa M.
Published: April 2019

Purpose/Objectives:

The Centers for Medicare & Medicaid Services (CMS) announced that beginning in 2019, Medicare Advantage (MA) health plans may begin offering additional benefits for nonmedical home services. In 2019, this change impacts the Long-Term Services and Supports (LTSS) landscape dramatically. This 2-part article describes LTSS, its traditional demographic and health care footprint, the regulatory and accreditation landscape, quality measurement and outcomes, and the critical importance of maintaining care continuity for individuals receiving LTSS. The objectives are to:

define LTSS,

identify client demographics,

identify delivery models,

discuss regulation and accreditation environments,

discuss quality improvement and outcomes initiatives,

identify promising practices and best practices, and

identify useful resources.

Primary Practice Setting(s):

Applicable to all health care sectors where case management is practiced.

Findings/Conclusions:

Historically, once Medicare recognizes a product or service, managed health plans and commercial insurance carriers follow suit. Professional case managers must become fluent in the language of LTSS, the implications of these CMS changes, and the impact on case management practice across the care continuum.

Implications for Professional Case Management Practice:

Professional case managers should understand LTSS, especially as it pertains to care transitions and continuity of health care services to our most vulnerable clients.
Integration of the National Comprehensive Cancer Network (NCCN) Distress Screening Tool as a Guidepost for Telephonic Oncology Case Management
Authors: Swanson Alysia Jean , Castel Liana DesHarnais , McKenna Patricia A. , Shen Yuming Albert , Sagar Bhuvana
Published: April 2019

Purpose of Study:

Cigna's oncology case management programs identified the opportunity for case managers to integrate distress screening as recommended by the National Comprehensive Cancer Network (NCCN) in oncology populations. Our purpose in conducting this study was to quantify oncology case management program improvements as a result of using the NCCN Distress Screening Tool to guide telephonic case management. The program improvements we measured comprised more efficient identification of biopsychosocial problems and appropriate resource referrals.

Primary Practice Setting:

Case managers in a large commercial health plan piloted integration of distress screening into telephonic case management among U.S. oncology customers experiencing a new diagnosis or care transition from September 2016 to April 2017.

Methodology and Sample:

A retrospective, matched case–control study was conducted among Cigna customers eligible for oncology case management. The pilot group of 317 received distress screening early in the oncology case management assessment. Outcomes included distress severity ranging from 0 to 10 (where 0 = no distress, 1–3 = mild, 4–7 = moderate, and 8–10 = severe), identification and number of biopsychosocial health problems, and percentage of direct resource referrals by case managers to supportive services.

Results:

More than half (54%) of the screened customers reported mild or greater distress, and there was a strong correlation between degree of distress and average numbers of biopsychosocial health problems or direct resource referrals. Screened customers were 16% more likely to be referred to internal and external resources than customers not screened with the tool (66% vs. 50%, χ2
p < .001).

Implications for Case Management Practice:

This study advances evidence-based oncology case management practice during care transitions by providing quantitative evidence for the utility of integrating the NCCN Distress Screening Tool into telephonic oncology case management. Using the tool (thermometer and problem list) to guide telephonic oncology case management and care coordination facilitated more tailored referrals to individuals with cancer enrolled in a large commercial health plan. On the basis of our findings, we integrated distress screening to address unmet biopsychosocial needs in patients with cancer.
Leveraging Interprofessional Team-Based Care Toward Case Management Excellence
Authors: Fink-Samnick Ellen
Published: April 2019

Health care teams continue to be a constructive way to approach, assess, coordinate, plan, and facilitate the care of clients and populations. Independent of practice setting, some type of team is in place, engaging different professionals and specialists. There has been considerable evolution of these teams over the years, with a heritage of terms to frame each one, including “multidisciplinary,” “interdisciplinary,” and “transdisciplinary.” However, these long-standing framings have been replaced by a timelier model that shifts both focus and aim of the team effort. Interprofessional team-based care (IPTBC) sets the tone for how students entering the industry are educated and empowers the workforce to a more intentional means to the care end. This is the first in a 2-part series focusing on the evolution and implementation of IPTBC across the industry. Part 1 focuses on the history and fundamental concepts of interprofessional models. Evidence and outcomes to promote the value proposition for IPTBC implementation are also provided.

Purpose/Objectives:

This article:

Reviews the evolution of health care teams;

Defines IPTBC;

Discusses the challenges to implementation of IPTBC; and

Identifies the implications for professional case management.

Primary Practice Setting(s):

Applicable to all health and behavioral health settings where case management is practiced.

Findings/Conclusions:

Interprofessional team-based care models demonstrate a successful means to achieve client-driven, quality, and cost-effective care across disease states and practice settings.

Implications for Case Management Practice:

With case management so closely linked to the fiscal imperatives of organizations, engagement in IPTBC is a necessity for every practice setting. Poor team collaboration contributes to unsuccessful outcomes for clients, increased costs, and concerning quality and risk management issues for the organization. The latest generation of value-based care initiatives and complex population health needs (e.g., social determinants of health, co-occurring physical and behavioral health) translates to greater pressures on case managers to maximize financial risk and attain their share of financial incentives (e.g., bonuses, shared savings) by avoiding readmissions, preventable complications, and duplicate services.
Making the Transition
Authors: Short Kathleen , Freedman Kara , Matays Jennie , Rosamilia Melody , Wade Kara
Published: April 2019

Purpose:

This article describes the impact of a hands-on critical care skills day led by clinical nurse specialist (CNS) to enhance junior nurses’ clinical skills. Program objectives included providing specialized skills training to meet the needs of high-acuity patient population and reviewing nurse-sensitive indicator–associated care bundles with the goal of increasing compliance.

Description of the Project:

An 8-hour program of lecture and hands-on skills was developed. Curriculum included nursing-sensitive indicators, sepsis management, complex tubes and drains, airway management, and emergency response. Clinical nurse specialists mentored senior nurses to colead program planning and execution. The program has been offered 9 times. Qualitative and quantitative data were collected on attendees.

Outcome:

Quantitative data analysis showed that 89% of the assessed components were affected by the program. Medium effect was noted in defibrillator skills, retrieving items from code care, care of suicidal patient, and sepsis screening. Qualitative data based on attendee survey are also presented and analyzed. Decreases in indwelling catheter utilization on select units are discussed.

Conclusion:

The CNS has the responsibility to ensure nursing practice is reflective of hospital policy and current evidence. This program demonstrates the impact of CNSs in staff education, mentorship, and competency assessment.
Pain Management Pillars for the Clinical Nurse Specialist
Authors: Klaess Cynthia C. , Urton Michael , Whitehead Phyllis , Rosier Patricia Kelly , Burnie Jeannie , Michel Marti
Published: April 2019

Purpose:

This article describes the work of the National Association of Clinical Nurse Specialists (NACNS) Opioid/Pain Management Task Force and provides guidance for the clinical nurse specialist (CNS) in evidence-based pain management interventions and organizational program development.

Description:

In September 2016, the NACNS commissioned a group of pain management experts to identify the resources that CNSs need to address appropriate opioid use and pain management in various practice settings. Challenges faced by CNSs related to opioids and pain management were identified through NACNS Conference forums and a pain management survey of NACNS members.

Outcome:

On the basis of member input, the task force highlighted key components, or pain pillars, necessary for optimal pain management. Use of these pillars can guide the CNS and healthcare organizations to develop comprehensive pain management practices that provide the foundation for safe, effective, and individualized patient care.

Conclusions:

As an expert in clinical, professional, and systems leadership, the CNS is ideally suited to convene interprofessional groups focused on pain management including development of organizational philosophies, policies, and evidence-based care.
Risk of Severe Intraventricular Hemorrhage in the First Week of Life in Preterm Infants Transported Before 72 Hours of Age*
Authors: Shipley Lara , Gyorkos Timea , Dorling Jon , Tata Laila J. , Szatkowski Lisa , Sharkey Don
Published: April 2019

Objectives:

Evaluate the risk of severe intraventricular hemorrhage, in the first week of life, in preterm infants undergoing early interhospital transport.

Design:

Retrospective cohort study.

Setting:

Tertiary neonatal centers of the Trent Perinatal Network in the United Kingdom.

Patients:

Preterm infants less than 32 weeks gestation, who were either born within and remained at the tertiary neonatal center (inborn), or were transferred (transported) between centers in the first 72 hours of life.

Interventions:

None.

Measurements and Main Results:

Multivariable logistic regression models adjusting for key confounders were used to calculate odds ratios for intraventricular hemorrhage with 95% CIs for comparison of inborn and transported infants. Cranial ultrasound findings on day 7 of life. Secondary analyses were performed for antenatal steroid course and gestational age subgroups. A total of 1,047 preterm infants were included in the main analysis. Transported infants (n = 391) had a significantly higher risk of severe (grade III/IV) intraventricular hemorrhage compared with inborns (n = 656) (9.7% vs 5.8%; adjusted odds ratio, 1.69; 95% CI, 1.04–2.76), especially for infants born at less than 28 weeks gestation (adjusted odds ratio, 1.83; 95% CI, 1.03–3.21). Transported infants were less likely to receive a full antenatal steroid course (47.8% vs 64.3%; p < 0.001). A full antenatal steroid course significantly decreased the risk of severe intraventricular hemorrhage irrespective of transport status (odds ratio, 0.33; 95% CI, 0.2–0.55). However, transported infants less than 28 weeks gestation remained significantly more likely to develop a severe intraventricular hemorrhage despite a full antenatal steroid course (adjusted odds ratio, 2.84; 95% CI, 1.08–7.47).

Conclusions:

Preterm infants transported in the first 72 hours of life have an increased risk of early-life severe intraventricular hemorrhage even when maternal antenatal steroids are given. The additional burden of postnatal transport could be an important component in the pathway to severe intraventricular hemorrhage. As timely in-utero transfer is not always possible, we need to focus research on improving the transport pathway to reduce this additional risk.
Effect of sustained experimental muscle pain on joint position sense
Authors: Summers Simon J. , Schabrun Siobhan M. , Hirata Rogerio P. , Graven-Nielsen Thomas , Cavaleri Rocco , Chipchase Lucy S.
Published: April 2019

Introduction:

Joint position sense (JPS) is impaired in clinical musculoskeletal pain conditions, but when this impairment develops in the transition from initial to prolonged pain is not known.

Objectives:

This study assessed whether progressively developing sustained experimentally induced muscle pain impacts JPS in healthy individuals.

Methods:

Twenty-eight healthy individuals received injection of nerve growth factor (NGF) into the right extensor carpi radialis brevis muscle on days 0 and 2 to induce sustained pain and hyperalgesia. Wrist JPS was assessed 2 days before day 0 (day −2), before the injection on days 0 and 2, and on days 4 and 14. Joint position sense was quantified as the ability to return the wrist to a neutral position following movements in the direction of radial and ulnar deviation. A 3-dimensional motion analysis system was used to calculate absolute, relative, and joint-angle repositioning errors. Numerical rating scale scores of pain intensity, body chart pain drawings, and pressure pain thresholds (PPTs) were recorded on each day.

Results:

Compared with baseline, pressure pain thresholds decreased while pain intensity and area increased at day 2 (P < 0.001) and day 4 (P < 0.001) before returning to baseline on day 14 (P > 0.13). Relative to day 0, there was no change in wrist JPS at day 2, 4, and 14 following movements in either target direction (P > 0.05).

Conclusion:

Despite the presence of sustained muscle pain and hyperalgesia for 4 days at the elbow, no statistical change in wrist joint position error was observed. These findings suggest that pain and hyperalgesia lasting as long as 4 days does not impair JPS.
Ultrasound as a Useful Tool in the Diagnosis of Rheumatoid Arthritis in Patients With Undifferentiated Arthritis
Authors: Gutierrez Marwin , Bertolazzi Chiara , Castillo Edwin , Reyes-Long Samuel , Clavijo-Cornejo Denise , Santos-Moreno Pedro
Published: April 2019

Background

Nowadays, rheumatologists face challenges in finding an effective method to classify and treat patients with undifferentiated arthritis (UA). There is a need for new tools that could ensure accurate characterization of inflammatory processes in these patients.

Objective

The aim of this study was to investigate if a characterization of UA patients using ultrasound (US) may help to fulfill the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) classification criteria in a real-life cohort.

Methods

We conducted a cross-sectional study in 2 rheumatology care clinics. Patients not fulfilling the 2010 ACR/EULAR RA criteria were included. On the examination day, all patients underwent a physical examination, radiography, and US. The 7-joint US score was adopted to scan all patients. The US was performed according to EULAR criteria and interpreted by Outcome Measures in Rheumatology definitions. Gray-scale and power Doppler synovitis and tenosynovitis were scored. Bone erosions were also evaluated during the US examination.

Results

A total of 204 patients were included. The diagnosis was modified from UA to RA in 86 patients (42.1%). Also, the final score of the 2010 ACR/EULAR RA classification criteria changed from a mean of 4.6 to 6.5 after the US examination. In addition to synovitis, a wide range of tenosynovitis and bone erosions were detected by US. Synovitis was more frequently detected in second metacarpophalangeal joint followed by second metatarsophalangeal joint (MTPj) and fifth MTPj. The tendons of the wrist and second and third fingers were the most affected. In relation to bone erosions, second metacarpophalangeal joint and fifth MTPj were the joints with more proportion of anatomical damage.

Conclusions

The US demonstrated to be useful to help accurately classify as RA patients previously diagnosed with UA.
Application of Dextroscope in a Rare Type of Angiomatous Meningioma Characterized With Coral-Like Vessels
Authors: Ma Shun-Chang , Yang Jun , Jia Wang
Published: April 2019

A 43-year-old female diagnosed with meningioma was admitted to our department. Preoperative imaging revealed a spherical lesion located in the sphenoid ridge with obvious enhancement and inhomogeneous density into 3 layers on magnetic resonance (MR) images, coral-like vessel images inside the tumor was obtained after the raw computed tomography angiography data were imported into the Dextroscope virtual-reality system. Due to her progressive headache and visual deterioration, surgery was performed after comprehensive study in the Dextroscope system, details about the correlation among skull base, lesion, branches of internal carotid artery, and vessels inside the tumor were well demonstrated in this system. It is diagnosed as a rare type of angiomatous meningioma, based on the abnormal manifestation on images, which even make it important to make further evaluation before making any surgical plan. Surgical resection has been the optimal treatment for most meningiomas and is meticulously performed accordingly. The patient is doing fine with no evidence of tumor recurrence on recent MR scans.
Treatment of Panfacial Fractures and Three-Dimensional Outcome Analysis: The Occlusion First Approach
Authors: Choi Jong Woo , Kim Min Ji
Published: April 2019

Successful management of panfacial fractures requires an understanding of the component fracture patterns and the ability to relate them anatomically to the stable elements of the skull. However, there is no widespread agreement on the ideal approach to treatment of panfacial fractures and several techniques have been proposed. Here, the authors suggest the “occlusion first” approach, a technique that involves larger segment reduction as the initial step to provide an appropriate occlusal plane.

This retrospective study included data from patients undergoing open reduction and internal fixation of panfacial fractures between March 2005 and November 2017 by the occlusion first technique. The degree of reduction in the mid and lower face was evaluated using 3D CT. The causes of injury, combined fracture, and multidisciplinary consultation during postoperative management were reviewed.

The study population comprised 61 patients (47 male, 14 female) with a mean age of 47.6 years (range, 9–76 years). Analysis of 3D CT scans obtained from 42 patients showed no significant difference in hemifacial volume in the postoperative period (left hemifacial volume: 206.48 ± 68.35 cm3, right: 205.17 ± 66.27 cm3, P = 0.436).

The occlusion first approach, with initial reduction of larger segments, enables effective reconstruction of the multiple segments involved in panfacial fractures. The authors have demonstrated that this technique successfully restores the entire face, improves surgical reduction, acts as an orientation aid during surgery, and provides a template for the smaller segments. Therefore, this approach can facilitate the accurate and efficient reduction and fixation of panfacial fractures.
Tumor Long-interspersed Nucleotide Element-1 Methylation Level and Immune Response to Esophageal Cancer
Authors: Kosumi Keisuke , Baba Yoshifumi , Okadome Kazuo , Yagi Taisuke , Kiyozumi Yuki , Yoshida Naoya , Watanabe Masayuki , Baba Hideo
Published: April 2019

Objective:

To examine the relationship between tumor long-interspersed nucleotide element-1 (LINE-1) methylation level and immune response to esophageal cancer.

Background:

Evidence points to a correlation between the abundance of immune cells and a favorable prognosis in esophageal cancer patients. Accumulating evidence indicates a critical role of tumor LINE-1 hypomethylation in the aggressive behavior of esophageal cancer, which in turn leads to an unfavorable prognosis.

Methods:

Utilizing a nonbiased database of 292 resected esophageal cancers, we measured tumor LINE-1 methylation level by pyrosequencing assay, and examined the relationship between LINE-1 methylation and the density of T cells (CD8 and FOXP3) and the lymphocytic reaction patterns (follicle lymphocytic reaction, peritumoral lymphocytic reaction, stromal lymphocytic reaction, and tumor-infiltrating lymphocytes) in esophageal carcinoma tissue.

Results:

LINE-1 hypomethylation was associated with male gender and advanced stage cancer (P = 0.03 and P = 0.048, respectively). Tumor LINE-1 methylation level was significantly positively associated with peritumoral lymphocytic reaction (P = 0.004), but not with others. Compared with LINE-1 hypermethylation group, LINE-1 hypomethylation group showed much lower level of peritumoral lymphocytic reaction (univariable odds ratio 0.32, 95% confidence interval 0.16–0.64, P = 0.002). In multivariable model to control for potential confounders including disease stage, the similar finding was observed (multivariable odds ratio 0.31, 95% confidence interval 0.14–0.66, P = 0.004).

Conclusions:

Tumor LINE-1 hypomethylation level is associated with a diminished peritumoral lymphocytic reaction, providing impetus for further investigations on potential interactive roles of tumor LINE-1 hypomethylation and host immunity in esophageal cancer development.
Procedure-specific Training for Robot-assisted Distal Pancreatectomy
Authors: Klompmaker Sjors , van der Vliet Walderik J. , Thoolen Stijn J. , Ore Ana Sofia , Verkoulen Koen , Solis-Velasco Monica , Canacari Elena G. , Kruskal Jonathan B. , Khwaja Khalid O. , Tseng Jennifer F. , Callery Mark P. , Kent Tara S. , Moser A. James
Published: April 2019

Objective:

To train practicing surgeons in robot-assisted distal pancreatectomy (RADP) and assess the impact on 5 domains of healthcare quality.

Background:

RADP may reduce the treatment burden compared with open distal pancreatectomy (ODP), but studies on institutional training and implementation programs are scarce.

Methods:

A retrospective, single-center, cohort study evaluating surgical performance during a procedure-specific training program for RADP (January 2006 to September 2017). Baseline and unadjusted outcomes were compared “before training” (ODP only; June 2012). Exclusion criteria were neoadjuvant therapy, vascular- and unrelated organ resection. Run charts evaluated index length of stay (LOS) and 90-day comprehensive complication index. Cumulative sum charts of operating time (OT) assessed institutional learning. Adjusted outcomes after RADP versus ODP were compared using a secondary propensity-score-matched (1:1) analysis to determine clinical efficacy.

Results:

After screening, 237 patients were included in the before-training (133 ODP) and after-training (24 ODP, 80 RADP) groups. After initiation of training, mean perioperative blood loss decreased (−255 mL, P<0.001), OT increased (+65 min, P < 0.001), and median LOS decreased (−1 day, P < 0.001). All other outcomes remained similar (P>0.05). Over time, there were nonrandom (P < 0.05) downward shifts in LOS, while comprehensive complication index was unaffected. We observed 3 learning curve phases in OT: accumulation (<31 cases), optimization (case 31–65), and a steady-state (>65 cases). Propensity-score-matching confirmed reductions in index and 90-day LOS and blood loss with similar morbidity between RADP and ODP.

Conclusion:

Supervised procedure-specific training enabled successful implementation of RADP by practicing surgeons with immediate improvements in length of stay, without adverse effects on safety.
Surgery Improves Survival After Neoadjuvant Therapy for Borderline and Locally Advanced Pancreatic Cancer
Authors: Rangelova Elena , Wefer Agnes , Persson Saga , Valente Roberto , Tanaka Kimitaka , Orsini Nicola , Segersvärd Ralf , Arnelo Urban , Del Chiaro Marco
Published: April 2019

Objective:

Neoadjuvant therapy (NAT) has become part of the multimodality treatment for borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC).

Summary Background Data:

It is currently uncertain which are the preferable NAT regimens, who benefits from surgery, and whether more aggressive surgical strategy is motivated.

Methods:

A retrospective cohort analysis was performed for all patients with BRPC/LAPC discussed and planned for NAT at multidisciplinary conference at Karolinska University Hospital from 2010 to 2017.

Results:

Of 233 patients eligible, 168 (72%) received NAT and were reevaluated for possibility of resection. A total of 156 (67%) patients (mean 64 yrs, 53% male) had pancreatic adenocarcinoma, comprising the study group for survival analysis. LAPC was diagnosed in 132 patients (85%), BRPC in 22 (14%), and resectable tumor in 2 (1.3%). Fifty patients (40.3%) received full-dose NAT. Only 54 (34.6%) had FOLFIRINOX. The overall survival among resected patients was similar for BRPC and LAPC (median survival 15.0 vs 14.5 mo, P = 0.4; and 31.9 vs 21.8 mo, P = 0.7, respectively). Resected patients had better survival than nonresected, irrespective of the type or whether full-dose NAT was given (median survival 22.4 vs 12.7 mo; 1-, 3-, and 5-yr survival: 86.4%, 38.9%, 26.9% vs 52.2%, 1.5%, 0%, respectively (P < 0001). For all preoperative values of Ca 19-9, surgical resection had positive impact on survival.

Conclusions:

All patients with BRPC/LAPC who do not progress during NAT should be considered for surgical resection, irrespective of the type or dose of NAT given. Higher levels of Ca 19-9 should not be considered an absolute contraindication for resection.
Does Rectocele on Defecography Equate to Rectocele on Physical Examination in Patients With Defecatory Symptoms?
Authors: Wallace Shannon L. , Torosis Michele , Rogo-Gupta Lisa
Published: April 2019

Objectives

Our primary objective was to determine the association between rectocele size on defecography and physical examination in symptomatic patients. Our secondary objective was to describe the associations between both defecography and physical examination findings with defecatory symptoms and progression to surgical repair of rectocele.

Methods

We performed a retrospective review of all patients referred to a female pelvic medicine and reconstructive surgery clinic with a diagnosis of rectocele based on defecography and/or physical examination at a single institution from 2003 to 2017. Patients who did not have defecatory symptoms, did not undergo defecography imaging, or did not have a physical examination in a female pelvic medicine and reconstructive surgery clinic within 12 months of defecography imaging were excluded.

Results

Of 200 patients, 181 (90.5%) had a rectocele diagnosed on defecography and 170 (85%) had a rectocele diagnosed on physical examination. Pearson and Spearman tests of correlation both showed a positive relationship between the rectocele size on defecography and rectocele stage on physical examination; however, one was not reliable to predict the results of the other (Pearson correlation = 0.25; Spearman ρ = 0.29). The strongest predictor of surgery was rectocele stage on physical examination (P < 0.001). Size of rectocele on defecography was not a strong independent predictor for surgery (P = 0.01), although its significance improved with the addition of splinting (P = 0.004).

Conclusions

Our results suggest that rectocele on defecography does not necessarily equate to rectocele on physical examination in patients with defecatory symptoms. Rectocele on physical examination was more predictive for surgery than rectocele on defecography.
The Utility of ECMO After Liver Transplantation: Experience at a High-volume Transplant Center and Review of the Literature
Authors: Braun Hillary J. , Pulcrano Marisa E. , Weber Daniel J. , Padilla Benjamin E. , Ascher Nancy L.
Published: April 2019

Background.

Extracorporeal membrane oxygenation (ECMO) artificially supports respiratory and cardiac function when conventional techniques fail. ECMO has been described as a treatment modality for acute pulmonary and cardiac failure following orthotopic liver transplantation (OLT). Here, we present a series of adult OLT recipients placed on ECMO after transplantation for both respiratory and cardiac indications and review the literature on the role of ECMO in the setting of OLT.

Methods.

For the patient series, we cross-referenced all patients who underwent OLT at our institution between 2007 and 2018 with the ECMO database of our institution and described these cases. For the literature review, we identified cases and series that described the use of ECMO after liver transplantation in adult recipients.

Results.

A total of 1792 patients underwent OLT. Eight patients were placed on ECMO (0.4%), 5 men and 3 women aged 28 to 68 years (4 venovenous and 4 venoarterial). Three of (38%) 8 patients survived to discharge and are alive today. In the literature, we identified 3 series and 12 case reports of ECMO following OLT, with the majority of the literature derived from the Asian OLT experience.

Conclusions.

ECMO following liver transplantation should be considered as a viable rescue strategy in patients with severe cardiopulmonary failure. ECMO is particularly effective if the cause of cardiopulmonary failure is recognized promptly and is thought to be transient. This is the largest series in the United States and demonstrates a 38% survival rate, which is comparable to other reports in the literature from Asia.
Update on C1 Esterase Inhibitor in Human Solid Organ Transplantation
Authors: Berger Mel , Lefaucheur Carmen , Jordan Stanley C.
Published: April 2019

Complement plays important roles in both ischemia-reperfusion injury (IRI) and antibody-mediated rejection (AMR) of solid organ allografts. One approach to possibly improve outcomes after transplantation is the use of C1 inhibitor (C1-INH), which blocks the first step in both the classical and lectin pathways of complement activation and also inhibits the contact, coagulation, and kinin systems. C1-INH can also directly block leukocyte-endothelial cell adhesion. C1-INH contrasts with eculizumab and other distal inhibitors, which do not affect C4b or C3b deposition or noncomplement pathways. Authors of reports on trials in kidney transplant recipients have suggested that C1-INH treatment may reduce IRI and delayed graft function, based on decreased requirements for dialysis in the first month after transplantation. This effect was particularly marked with grafts with Kidney Disease Profile Index ≥ 85. Other clinical studies and models suggest that C1-INH may decrease sensitization and donor-specific antibody production and might improve outcomes in AMR, including in patients who are refractory to other modalities. However, the studies have been small and often only single-center. This article reviews clinical data and ongoing trials with C1-INH in transplant recipients, compares the results with those of other complement inhibitors, and summarizes potentially productive directions for future research.
Report of a Leprosy case in Singapore: an age-old disease not to be forgotten in developed countries with low-prevalence settings
Authors: Tan Yen Ee , Yeo Yi Wei , Ang David Jia Qiang , Chan Michelle Mei Fung , Pang Shiu Ming , Sng Li-Hwei
Published: April 2019

Introduction. Leprosy is rarely reported in developed countries with low-prevalence settings. Its diagnosis may be missed due to its low frequency in non-endemic regions, as well as its long incubation period. The report describes an imported leprosy case of a healthcare worker in Singapore.

Case presentation. A Filipino nursing personnel presented with a persistent non-tender erythematous plaque over his right upper back for many years despite topical treatment. He had the lesion before coming to Singapore but decided to seek medical consultation only after the lesion progressed with new erythematous papules developing over his face, trunk and upper limbs. Punch biopsies of skin lesions revealed fite-positive bacilli, which were identified to be

Mycobacterium leprae

by GenoType LepraeDR v1 assay (Hain LifeScience, Germany). No mutation was detected at rpoB (rifampicin), gyrA (ofloxacin) and folP1 (dapsone) gene targets. He was started on multi-drug therapy and responded to the treatment. The only prolonged close contact he had was his housemate who was screened and given a single dose of rifampicin as chemoprophylaxis.

Conclusion. In non-endemic settings, awareness is crucial in diagnosing leprosy. The availability of molecular testing and multi-disciplinary management are essential in the confirmation and control of this disease of public health importance.
Phylogenomics reveal that Mycobacterium kansasii subtypes are species-level lineages. Description of Mycobacterium pseudokansasii sp. nov., Mycobacterium innocens sp. nov. and Mycobacterium attenuatum sp. nov.
Authors: Tagini Florian , Aeby Sébastien , Bertelli Claire , Droz Sara , Casanova Carlo , Prod’hom Guy , Jaton Katia , Greub Gilbert
Published: April 2019

Among the species

Mycobacterium kansasii

, seven subtypes have been previously reported based on the PCR and the restriction fragment length polymorphism of the gene hsp65. Here, we used whole-genome sequencing to refine

M. kansasii

taxonomy and correct multiple inconsistencies. Average nucleotide identity (ANI) values between

M. kansasii

subtypes ranged from 88.4 to 94.2 %, lower than the accepted 95–96 % cut-off for species delineation. In addition,

Mycobacterium gastri

was closer to the

M. kansasii

subtypes 1, 2, 3, 4 and 5 than

M. kansasii

subtype 6. The recently described species

Mycobacterium persicum

shared 99.77 % ANI with

M. kansasii

subtype 2. Consistent with the ANI results, the digital DNA–DNA hybridization value was below the 70 % threshold for species delineation between subtypes and above it within subtypes as well as between subtype 2 and

M. persicum

. Furthermore, core-genome phylogeny confirmed the current

M. kansasii

species to be polyphyletic. Hence, we propose (i)

Mycobacterium
pseudokansasii sp. nov., replacing subtype 3, with the type strain MK142T(=CCUG 72128T=DSM 107152T), (ii)

Mycobacterium
innocens sp. nov., replacing subtype 5, with the type strain MK13T (=CCUG 72126T=DSM 107161T), and (iii)

Mycobacterium
attenuatum sp. nov., replacing subtype 6, with the type strain MK41T(=CCUG 72127T=DSM 107153T). Subtype 4 represents a new species-level lineage based on the genomic data but no strain was available. No genome sequence or strain was available for subtype 7. The proposed nomenclature will facilitate the identification of the most pathogenic subtype 1 as

M. kansasii

by clinicians while the new species names suggest the attenuated pathogenicity of the other subtypes.
Modeling Bottom-Up and Top-Down Attention with a Neurodynamic Model of V1
Authors: Berga David , Otazu Xavier
Published: April 2019

Previous studies suggested that lateral interactions of V1 cells are responsible, among other visual effects, of bottom-up visual attention (alternatively named visual salience or saliency). Our objective is to mimic these connections with a neurodynamic network of firing-rate neurons in order to predict visual attention. Early visual subcortical processes (i.e. retinal and thalamic) are functionally simulated. An implementation of the cortical magnification function is included to define the retinotopical projections towards V1, processing neuronal activity for each distinct view during scene observation. Novel computational definitions of top-down inhibition (in terms of inhibition of return and selection mechanisms), are also proposed to predict attention in Free-Viewing and Visual Search tasks. Results show that our model outpeforms other biologically-inpired models of saliency prediction while predicting visual saccade sequences with the same model. We also show how temporal and spatial characteristics of inhibition of return can improve prediction of saccades, as well as how distinct search strategies (in terms of feature-selective or category-specific inhibition) can predict attention at distinct image contexts.
Bayesian variable selection with a pleiotropic loss function in Mendelian randomization
Authors: Gkatzionis Apostolos , Burgess Stephen , Conti David V , Newcombe Paul J
Published: April 2019

Mendelian randomization is the use of genetic variants as instruments to assess the existence of a causal relationship between a risk factor and an outcome. A Mendelian randomization analysis requires a set of genetic variants that are strongly associated with the risk factor and only associated with the outcome through their effect on the risk factor. We describe a novel variable selection algorithm for Mendelian randomization that can identify sets of genetic variants which are suitable in both these respects. Our algorithm is applicable in the context of two-sample summary-data Mendelian randomization and employs a recently proposed theoretical extension of the traditional Bayesian statistics framework, including a loss function to penalize genetic variants that exhibit pleiotropic effects. The algorithm offers robust inference through the use of model averaging, as we illustrate by running it on a range of simulation scenarios and comparing it against established pleiotropy-robust Mendelian randomization methods. In a real data application, we study the effect of systolic and diastolic blood pressure on the risk of suffering from coronary heart disease. Based on a recent large-scale GWAS for blood pressure, we use 395 genetic variants for systolic and 391 variants for diastolic blood pressure. Both traits are shown to have significant risk-increasing effects on coronary heart disease risk.
Ancestry-specific polygenic scores and SNP heritability of 25(OH)D in African- and European-ancestry populations
Authors: Hatchell Kathryn E. , Lu Qionshi , Hebbring Scott J. , Michos Erin D. , Wood Alexis C. , Engelman Corinne D.
Published: April 2019

Context

Vitamin D inadequacy, assessed by 25-hydroxyvitamin D [25(OH)D], affects around 50% of adults in the United States and is associated with numerous adverse health outcomes. Blood 25(OH)D concentrations are influenced by genetic factors that may determine how much vitamin D intake is required to reach optimal 25(OH)D. Despite large genome-wide association studies (GWASs), only a small portion of the genetic factors contributing to differences in 25(OH)D levels has been discovered.

Objective

Therefore, knowledge of a fuller set of genetic factors could be useful for risk prediction of 25(OH)D inadequacy, personalized vitamin D supplementation, and prevention of morbidity and mortality from deficient 25(OH)D.

Design

Using PRSice and weights from published African- and European-ancestry GWAS summary statistics, ancestry-specific polygenic scores (PGSs) were created to capture a more complete set of genetic factors.

Patients or Other Participants

Participants (European ancestry n=9,569, African ancestry n=2,761) came from three cohort studies.

Main Outcome Measure(s)

Blood concentrations of 25(OH)D.

Results

The PGS for African ancestry was derived using all input SNPs (a p-value cut-off of 1.0) and had an R2of 0.3%; for European ancestry, the optimal PGS used a p-value cut-off of 3.5×10−4in the target/tuning dataset and had an R2of 1.0% in the validation cohort. Those with highest genetic risk had 25(OH)D that was 2.8-3.0 ng/ml lower than those with lowest genetic risk (p=0.0463 to 3.2×10−13), requiring an additional 467 to 500 IU of vitamin D intake to maintain equivalent 25(OH)D.

Conclusions

PGSs are a powerful predictive tool that could be leveraged for personalized vitamin D supplementation to prevent the negative downstream effects of 25(OH)D inadequacy.
In silico evidence of unique behaviors of methionine in an in-register parallel beta-sheet amyloid, suggestive of its possible contribution to strain diversity of amyloids
Authors: Otaki Hiroki , Taguchi Yuzuru , Nishida Noriyuki
Published: April 2019

Mechanism of strain diversity of prions is a long-standing conundrum, because prions consist solely of abnormal isoform of prion protein (PrPSc) devoid of genetic material. Pathogenic properties of prions are determined by conformations of the constituent PrPScaccording to the protein-only hypothesis, and alterations to even a single residue can drastically change the properties when the residue is located at a critical position for the structure of PrPSc. Interestingly, methionine (Met) is often recognized as the polymorphic or species-specific residues responsible for species/strain barriers of prions, implying its unique influences on the structures of PrPSc. However, how it is unique is difficult to demonstrate due to lack of the detailed structures of PrPSc. Here we analyzed influences of Met substitutions on structures of an in-register parallel β-sheet amyloid of α-synuclein (αSyn) by molecular dynamics (MD) simulation, to extrapolate the results to PrPSc. The MD simulation revealed that Met uniquely stabilized a U-shaped β-arch of the Greek-key αSyn amyloid, whereas other hydrophobic amino acids tended to destabilize it. The stabilizing effect of Met was attributable to the long side chain without Cβ branching. Our findings exemplify specifically how and in what structure of an in-register parallel β-sheet amyloid Met can uniquely behave, and are suggestive of its influences on structures of PrPScand strain diversity of prions. We also discuss about relations between α-helix propensity and local structures of in-register parallel amyloids.
Peax Interactive Visual Pattern Search in Sequential Data Using Unsupervised Deep Representation Learning
Authors: Lekschas Fritz , Peterson Brant , Haehn Daniel , Ma Eric , Gehlenborg Nils , Pfister Hanspeter
Published: April 2019

We present Peax, a novel feature-based technique for interactive visual pattern search in sequential data, like time series or data mapped to a genome sequence. Visually searching for patterns by similarity is often challenging because of the large search space, the visual complexity of patterns, and the user’s perception of similarity. For example, in genomics, researchers try to link patterns in multivariate sequential data to cellular or pathogenic processes, but a lack of ground truth and high variance makes automatic pattern detection unreliable. We have developed a convolutional autoencoder for unsupervised representation learning of regions in sequential data that can capture more visual details of complex patterns compared to existing similarity measures. Using this learned representation as features of the sequential data, our accompanying visual query system enables interactive feedback-driven adjustments of the pattern search to adapt to the users’ perceived similarity. Using an active learning sampling strategy, Peax collects user-generated binary relevance feedback. This feedback is used to train a model for binary classification, to ultimately find other regions that exhibit patterns similar to the search target. We demonstrate Peax’s features through a case study in genomics and report on a user study with eight domain experts to assess the usability and usefulness of Peax. Moreover, we evaluate the effectiveness of the learned feature representation for visual similarity search in two additional user studies. We find that our models retrieve significantly more similar patterns than other commonly used techniques.