bluuebunny/crossref_metadata_2025 huggingface dataset:
Shuffling through the Bargain Bin: Real-Estate Holdings of Public Firms*
Authors: Demirci Irem , Gurun Umit G , Yönder Erkan
Published: June 2019

Constructing a novel database on the real-estate holdings of public firms, we show that distressed firms sell their real-estate assets at a discount relative to healthy firms. We find that distress discount in real-estate assets is less pronounced for sellers with less liquidity-constrained industry peers and in machinery-heavy industries. We also document that asset redeployability and the availability of potential buyers are two important property-specific determinants of the distress discount. Additionally, firms’ property portfolios that are less redeployable with less potential buyers exacerbate the negative impact of financial distress on the cost of borrowing.
A robust implicit measure of facial attractiveness discrimination
Authors: Luo Qiuling , Rossion Bruno , Dzhelyova Milena
Published: June 2019

Decisions of attractiveness from the human face are made instantly and spontaneously, but robust implicit neural measures of facial attractiveness discrimination are currently lacking. Here we applied fast periodic visual stimulation coupled with electroencephalography (EEG) to objectively measure the neural coding of facial attractiveness. We presented different pictures of faces at 6 Hz, i.e. six faces/second, for a minute while participants attended to a central fixation cross and indicated whether the cross shortly changed color. Every other face in the stimulation was attractive and was replaced by a relatively less attractive face. This resulted in alternating more/less attractive faces at a 3 Hz rate, eliciting a significant increase in occipito-temporal EEG amplitude at 3 Hz both at the group and the individual participant level. This response was absent in two control conditions where either only attractive or only less attractive faces were presented. These observations support the view that face-sensitive visual areas discriminate attractiveness implicitly and rapidly from the human face.
An Assessment of Penetrance and Clinical Expression of Malignant Hyperthermia in Individuals Carrying Diagnostic Ryanodine Receptor 1 Gene Mutations
Authors: Ibarra Moreno Carlos A. , Hu Sally , Kraeva Natalia , Schuster Frank , Johannsen Stephan , Rueffert Henrik , Klingler Werner , Heytens Luc , Riazi Sheila
Published: June 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Malignant hyperthermia (MH) is a potentially lethal disorder triggered by certain anesthetics. Mutations in the ryanodine receptor 1 (RYR1) gene account for about half of MH cases. Discordance between the low incidence of MH and a high prevalence of mutations has been attributed to incomplete penetrance, which has not been quantified yet. The authors aimed to examine penetrance of MH-diagnostic RYR1 mutations and the likelihood of mutation carriers to develop MH, and to identify factors affecting severity of MH clinical expression.

Methods

In this multicenter case–control study, data from 125 MH pedigrees between 1994 and 2017 were collected from four European registries and one Canadian registry. Probands (survivors of MH reaction) and their relatives with at least one exposure to anesthetic triggers, carrying one diagnostic RYR1 mutation, were included. Penetrance (percentage of probands among all genotype-positive) and the probability of a mutation carrier to develop MH were obtained. MH onset time and Clinical Grading Scale score were used to assess MH reaction severity.

Results

The overall penetrance of nine RYR1 diagnostic mutations was 40.6% (93 of 229), without statistical differences among mutations. Likelihood to develop MH on exposure to triggers was 0.25 among all RYR1 mutation carriers, and 0.76 in probands (95% CI of the difference 0.41 to 0.59). Penetrance in males was significantly higher than in females (50% [62 of 124] vs. 29.7% [30 of 101]; P = 0.002). Males had increased odds of developing MH (odds ratio, 2.37; 95% CI, 1.36 to 4.12) despite similar levels of exposure to trigger anesthetics. Proband’s median age was 12 yr (interquartile range 6 to 32.5).

Conclusions

Nine MH-diagnostic RYR1 mutations have sex-dependent incomplete penetrance, whereas MH clinical expression is influenced by patient’s age and the type of anesthetic. Our quantitative evaluation of MH penetrance reinforces the notion that a previous uneventful anesthetic does not preclude the possibility of developing MH.
Positive Deviance to Address Health Equity in Quality and Safety in Obstetrics
Authors: HOWELL ELIZABETH A. , AHMED ZAINAB N. , SOFAER SHOSHANNA , ZEITLIN JENNIFER
Published: June 2019

Racial/ethnic disparities persist in obstetrical outcomes. In this paper, we ask how research in obstetrical quality can go beyond a purely quantitative approach to tackle the challenge of health inequity in quality and safety. This overview debriefs the use of positive deviance and mixed methods in others areas of medicine, describes the shortcomings of quantitative methods in obstetrics and presents qualitative studies carried out in obstetrics as well as the insights provided by this method. The article concludes by proposing positive deviance as a mixed methods approach to generate new knowledge for addressing racial and ethnic disparities in maternal outcomes.
Patent Blue V as an Alternative Stain for DMEK Grafts: Safety, Stain Retention, and Feasibility
Authors: Chen Shin-Yi , Tran Khoa D. , Wehrer Stephen , Potts Luke B. , Bauer Alex J. , Straiko Michael D. , Terry Mark A.
Published: June 2019

Purpose:

To determine whether Patent Blue V (PB) can be used as an alternative dye for staining Descemet membrane endothelial keratoplasty (DMEK) grafts.

Methods:

DMEK grafts from donor corneas were stained with 2.5% PB for 4 minutes (n = 2), 2.5% PB for 10 minutes (n = 2), or 0.06% trypan blue (TB) for 4 minutes (n = 1). The stain intensity of the grafts was compared initially and at different time points over a 15-minute period of balanced salt solution wash using a grading scale based on a serial dilution series of PB. Three additional grafts were stained with 2.5% PB for 10 minutes and used in mock surgeries to assess stain retention after injection and manipulation in a donor eye model for 25 minutes. To assess the safety of PB, DMEK grafts were prepared from 10 pairs of corneas where one cornea was stained with 0.06% TB for 4 minutes and the mate cornea was stained with 2.5% PB for 10 minutes. The grafts were preloaded and stored for 5 days in Optisol-GS at 2°C to 8°C, and endothelial cell loss was quantified using Calcein-AM staining and FIJI segmentation by 2 masked readers.

Results:

PB stain intensities were lighter than TB-stained grafts. Grafts stained with 2.5% PB for 10 minutes retained sufficient color for the 25-minute duration of mock surgery. The average endothelial cell loss for PB versus TB grafts was 21.6% ± 5.3% versus 20.2% ± 5.4% (P = 0.202) as determined by reader 1 and 23.6% ± 4.8% versus 21.2% ± 5.8% (P = 0.092) as determined by reader 2.

Conclusions:

PB is a viable alternative dye in DMEK grafts for applications where TB may not be available or approved for use.
Management of Invasive Fungal Disease in Neonates and Children
Authors: Ferreras-Antolín Laura , Sharland Mike , Warris Adilia
Published: June 2019

Invasive fungal diseases (IFD) are an important cause of morbidity and mortality in premature neonates and immunocompromised pediatric patients. Their diagnostic and therapeutic management remains a challenge. A nationwide survey was conducted among 13 of the largest pediatric units in the United Kingdom, to obtain insight in the current management of IFD in neonates and children. All responding centers were tertiary teaching centers. The use of fungal diagnostic tools and imaging modalities varied among centers. Antifungal prophylaxis was prescribed in most centers for extreme-low birth weight (LBW) infants and high-risk hemato-oncologic patients, but with a huge variety in antifungals given. An empirical treatment was favored by most centers in case of febrile neutropenia. First line therapy for candidemia consists of either fluconazole or liposomal amphotericin B, with voriconazole being first-line therapy for invasive aspergillosis. Disseminated invasive aspergillosis was most often mentioned as a reason to prescribe combination antifungal therapy. In conclusion, this survey reinforces the fact that there are still important aspects in the management of pediatric IFD which should ideally be addressed in pediatric clinical trials. Attention needs to be given the knowledge gaps as observed in the results of our survey to optimize the management of IFD in children and neonates.
Will Infant Hepatitis B Immunization Protect Adults?
Authors: Scheifele David W.
Published: June 2019

Globally, infant hepatitis B virus (HBV) immunization programs are markedly reducing the rate of chronic HBV infections among children <5 years of age. Desirable improvements include increased birth dose coverage and better prevention of perinatal HBV transmission. Follow-up studies show that by the teenage years most of those immunized as infants have lost circulating anti-HBs antibody and some fail to respond to challenge HBV vaccination, implying loss of protection from infection. With high exposure to HBV, such individuals can develop breakthrough HBV infection but this rarely leads to chronic infection, the main goal of prevention programs. While longer-term follow-up studies into adulthood are needed, current evidence does not support a need for booster immunization of otherwise healthy teens or young adults.
Nodding Syndrome: The Unresolved Mystery of a Pediatric Disease in Sub-Saharan Africa
Authors: Abd-Elfarag Gasim , van Hensbroek Michaël Boele
Published: June 2019

Nodding syndrome is a mysterious neurologic illness of unknown etiology, presenting with distinctive clinical features often at early age. Currently, it affects children in restricted geographical areas in South Sudan, Northern Uganda and Southern Tanzania and is associated with high mortality and morbidity, especially in the children with severe disease. In this paper, we will give an outline of what is known about nodding syndrome with respect to epidemiology, clinical presentation, etiology and treatment. In addition, a possible approach to resolving the mystery is presented.
Fluoxetine and Risk of Bleeding in Patients Aged 60 Years and Older Using the Korea Adverse Event Reporting System Database
Authors: Kim Seonji , Ko Young-Jin , Park Kyounghoon , Yang Bo Ram , Kim Mi-sook , Park Byung-Joo
Published: June 2019

Background

Depression, the leading cause of nonfatal disease burden, has a strong correlation with suicide and affects approximately 7% of the general elderly population. Adverse drug reactions in older patients are particularly important because of reduced drug metabolism, polypharmacy, drug-drug interactions, and drug-disease interactions. Fluoxetine is the first representative selective serotonin reuptake inhibitor but is associated with the possibility of hemorrhage based on its mechanism of action. Serious cases of gastrointestinal bleeding and cerebral hemorrhage have been reported, raising concerns about the safety of this drug.

Methods

We detected signals of bleeding risk associated with fluoxetine in an elderly population using the Korea Adverse Event Reporting System database. Reporting odds ratios and 95% confidence intervals (CIs) were calculated.

Results

A total of 16,517 adverse events related to antidepressants were reported. The reporting odds ratios for fluoxetine were 2.34 (95% CI, 1.03–5.34) for total bleeding, 4.41 (95% CI, 1.60–12.15) for major bleeding, 2.06 (95% CI, 0.28–15.03) for gastrointestinal bleeding, and 6.12 (95% CI, 2.14–22.60) for brain hemorrhage compared with those of all other antidepressants.

Conclusions

We detected safety signals with total bleeding, major bleeding, and brain hemorrhage related to fluoxetine. For patients with a high risk of bleeding, such as the elderly population, prescribing antidepressants other than fluoxetine can be considered. The results of this study provide preliminary evidence of a relationship between fluoxetine and hemorrhage but have wide 95% CIs. Further pharmacoepidemiological studies will be needed to confirm the risk of bleeding associated with fluoxetine.
Practice Analysis Study: A Method for Residency Curriculum Development
Authors: Harro Cathy C. , Myers Robin O. , Perry Susan B. , Legters Kristine , Barry Joni , McCombe Waller Sandy
Published: June 2019

Background and Purpose.

Postprofessional residency education intended to advance specialty practice is common across health professions. Accrediting bodies use a variety of methods to define competencies and develop curricula. This paper describes the practice analysis survey used to determine advanced practice specialty competencies in physical therapy (PT), and the implications for the results of that process on residency curricula. The recently updated neurologic Description of Specialty Practice (DSP) is presented as an example.

Method/Model Description and Evaluation.

A nine-member Subject Matter Expert (SME) panel used a consensus process to develop knowledge and skill statements that represent contemporary neurologic specialty practice to construct a practice analysis survey. Survey respondents rated each statement along 3 dimensions: frequency and importance of the knowledge/skill, and the required level of judgment. The survey was sent to 995 neurologic certified specialists and an equal number of nonspecialists. Decision rules on data analysis DSP revision were determined by the SME panel a priori.

Outcomes.

One hundred thirty-one neurologic clinical specialists completed the survey (response rate = 13%). The revised DSP reflects new emphasis on: complex clinical decision making, judicious use of outcome measures, and prioritization of interventions; differential diagnosis and medical management; neuroplasticity and neural recovery; movement and task analysis; social responsibility and advocacy; and the role in health, wellness, and prevention. These changes represent the evolving knowledge, practice skills, and expanded role of the neurologic specialist, which must be incorporated into neurologic residency curricula.

Discussion and Conclusion.

This paper describes a method to guide curricula and learning outcomes for postprofessional residencies that is different from those used in entry-level PT programs. However, the practice analysis method is consistent with that used by other health professions. Systematic assessment of performance standards across the spectrum of PT education will continue to be important to distinguish specialists and support residency curricula.
Temporal trends in the practice of the transradial approach for percutaneous coronary intervention in a large tertiary center
Authors: Perl Leor , Bental Tamir , Assali Abid , Vaknin-Assa Hana , Greenberg Gabriel , Witberg Guy , Kornowski Ran
Published: June 2019

Objective

The transradial approach (TRA) has increasingly been adopted for the use of percutaneous coronary interventions (PCI), with reported clinical benefits. Little is known regarding the change in outcomes over time.

Patients and methods

From our large single-center PCI registry, we have analyzed 15 429 patients in two periods – 2008–2012 (period 1) and 2013–2017 (period 2). We examined the proportions of use of TRA, the influence on in-hospital outcomes, and adjusted long-term effects.

Results

The rate of TRA rose from 15.9% in period 1 to 69.1% in period 2, including in specific situations such as acute coronary syndrome, chronic total occlusion, bifurcation, calcified lesions, and unprotected left main PCI. In-hospital rates of bleeding were lower for TRA versus transfemoral artery (1.8 vs. 5.1%, overall, P < 0.001), as were rates of additional bleeding events in the following 12 months (1.3 vs. 2.4%, P < 0.001). Following multivariate analysis, use of TRA was associated with a lower 30-day and 4-year rate of the composite outcomes of death, myocardial infarction, target vessel revascularization, or coronary artery bypass surgery [at 4 years, hazard ratio (HR) = 0.86; 95% confidence interval (CI): 0.77–0.96; P = 0.007, during period 1 and HR = 0.62; 95% CI 0.55–0.7; P < 0.0001 during period 2]. Interaction analysis showed a stronger effect at the latter period (HR = 0.69, 95% CI: 0.59–0.81, P < 0.001).

Conclusion

Over a decade of follow-up, TRA has gained acceptance for different PCI scenarios, including complex patients – a course which is associated with consistent short and long-term clinical benefits.
Machine perfusion in kidney transplantation
Authors: Kataria Ashish , Magoon Sandeep , Makkar Binni , Gundroo Aijaz
Published: June 2019

Purpose of review

The shortage of kidneys for transplantation has led to an urgent need to efficiently utilize the available cadaveric kidneys. Efficient use of machine perfusion may potentially lead to increased use of marginal kidneys by lowering the incidence of delayed graft function (DGF) and improving graft outcomes.

Recent findings

Machine perfusion has had a resurgence in the last 10–15 years over static cold storage (SCS). Hypothermic machine perfusion (HMP), the most commonly utilized type of machine perfusion reduces the rates of DGF when compared with SCS with a trend towards improving the overall graft survival.

Despite reduction in the rates of DGF by HMP, its effect on long-term renal and patient outcomes is not clearly known. There is limited clinical literature in the use of normothermic machine perfusion (NMP) but a few pilot studies have shown its potential to resuscitate commonly discarded kidneys. In addition to preservation, machine perfusion also allows for various diagnostic and therapeutic interventions during the preservation period to assess and optimize the viability of the procured kidney.
Growing Teratoma Syndrome After Chemotherapy For Ovarian Immature Teratoma
Authors: Imran Hamayun , Siddiqui Abdul H. , Wilson Felicia , Pashankar Farzana
Published: June 2019

The management of ovarian immature teratoma (IT) presents several challenges. It occurs both in children and adults and therefore is managed by pediatric oncologists as well as adult and gynecologic oncologists. Treatment approach; however, varies significantly. Unlike pediatric patients in whom surgery is considered the mainstay of treatment, adult providers routinely prescribe postoperative chemotherapy. Management of recurrent IT can be challenging. Growing teratoma syndrome may occur after treatment of recurrent IT. We report the development and management of this phenomenon in a pediatric patient who had several recurrences of her IT.
Pediatric Colorectal Cancer: A Heterogenous Entity
Authors: Cortez-Pinto João , Claro Isabel , Francisco Inês , Lage Pedro , Filipe Bruno , Rodrigues Paula , Chaves Paula , Albuquerque Cristina , Dias Pereira António
Published: June 2019

Introduction:

Colorectal cancer (CRC) is extremely rare in pediatric age. A poor outcome has been reported.

Aims:

We aimed to characterize a group of pediatric CRC patients.

Materials and Methods:

All patients with CRC below 18 years old registered in our Familial Cancer Risk Clinic (2002-2016) were included. Clinical and histologic features were evaluated. Germline mutations, microsatellite instability, and DNA mismatch repair proteins expression were analyzed.

Results:

Five patients were included (3 males; mean age at diagnosis: 14.2 years (range, 9 to 17 y) and 4/5 had family history of cancer in second-degree relatives. With a maximum follow-up of 5.6 years, 2/5 patients died after 10 and 24 months, and 1 recurred after 15 months. All tumors were ≥pT3N2 and 3/5 presented signet ring cells/mucinous histology, corresponding to cases with stronger family history of cancer. Nevertheless, all CRCs analyzed (n=4) were microsatellite stable and/or expressed all mismatch repair proteins. Loss of heterozygosity for the 3 Bethesda dinucleotide markers was detected in 1/3 informative CRCs. A likely pathogenic germline MSH2 mutation was identified in only 1 patient.

Conclusions:

Pediatric CRC presented advanced disease and poor prognosis. These tumors had distinct histologic and molecular presentations, resembling features from different carcinogenic pathways, thus suggesting a heterogenous nature.
Measuring Community Mobility in Survivors of Stroke Using Global Positioning System Technology: A Prospective Observational Study
Authors: Hanke Timothy A. , Hwang Sungsoon , Keller Sarah , Zielke Donna , Hailey Tisha , Nathaniel Krumdick , Evans Christian C.
Published: June 2019

Background and Purpose:

Returning to community mobility is important for people recovering from a stroke, yet few studies have directly measured this construct following inpatient rehabilitation. Using global positioning system (GPS) technology, we examined community mobility of survivors of stroke (SS) over the first year after discharge and compared them to an age-matched comparison group without neurological impairment.

Methods:

We conducted a prospective observational study that included SS (n = 14) and age- and location-matched comparison subjects (CS; n = 6). All participants identified target locations important to their community mobility goals and wore a GPS unit during the first, fifth and ninth weeks after discharge, or from baseline for CS, and at 26 and 52 weeks' follow up. The 6-minute walk test (SMWT), Berg balance test (BBT), Reintegration to Normal Living (RNLI), and Short Form-36 Quality of Life Survey Physical Functioning domain (SF-36-PF) were collected. Number of trips and percentage of targets visited were extracted from GPS data.

Results:

Twelve of 14 SS completed 9 weeks, 7 completed the full year, and no CS withdrew. The SS took fewer trips and attained fewer targets compared with CS at weeks 1 and 9, but not at weeks 5, 26, and 52. All 4 clinical outcome measures were significantly correlated to trips (Spearman r for SMWT = 0.5067, BBT = 0.3841, RNLI = 0.4119, and SF-36-PF = 0.4192).

Discussion and Conclusions:

Directly measured community mobility in SS was decreased through 9 weeks following discharge from inpatient rehabilitation. The limited strength of bivariate correlations between clinical measures and number of trips supported the uniqueness of the community mobility construct.

Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A277).
Sudden Infant Death After Vaccination
Authors: Osawa Motoki , Nagao Ryoko , Kakimoto Yu , Kakiuchi Yasuhiro , Satoh Fumiko
Published: June 2019

Sudden infant deaths might be attributable to adverse reaction to vaccination, but separating them from coincidental occurrences is difficult. This study retrospectively investigated vaccination-related details and postmortem findings for 57 cases of sudden death in children 2 years or younger. Data were extracted from autopsy files at the Department of Forensic Medicine, Tokai University School of Medicine. Vaccination histories were available in 50 cases based on the maternity passbook. Of the 32 cases in which any vaccines were administered, 7 infants (21.9%) had received immunization within 7 days of death. The most frequent vaccine cited as the last immunization before death was Haemophilus influenzae B. Although a temporal association of vaccines with sudden death was present for two 3-month-old and one 14-month-old infants in whom death occurred within 3 days of receiving the H. influenzae type b and other vaccinations, a definitive relationship between the vaccine and death could not be identified. Histopathological examinations revealed pneumonia and upper respiratory infection as contributing to death in their cases. Moreover, all 3 cases showed hemophagocytosis in the spleen and lymph nodes, which are similar features to hemophagocytic lymphohistiocytosis. Judgment of the disorders as truly related to vaccination is difficult, but suspicious cases do exist. Forensic pathologists must devote more attention to vaccination in sudden infant death cases.
Does Simian Virus 40 (SV40) Have a Role in UK Malignant Pleural Mesothelioma? No Role is Identified in a Sensitive RNA In Situ Hybridization Study on Potentially Affected Birth Cohorts
Authors: Alchami Fouad S. , Attanoos Richard L. , Gibbs Allen , Morgan Fiona , Jasani Bharat
Published: June 2019

Background:

Simian virus 40 (SV40)-contaminated polio vaccine was accidentally administered to about one-third of the UK population receiving polio vaccines between 1956 and 1962. SV40 was subsequently demonstrated to be a carcinogenic virus in experimental and animal models. Since then, the SV40 oncogenic protein large T antigen (SV40 Tag) has been shown to cause malignant transformation of asbestos-treated human pleural mesothelial cells and malignant pleural mesotheliomas in asbestos-exposed SV40 Tag transgenic mice. The present study was designed to investigate the possible association of SV40 Tag with human malignant pleural mesothelioma samples from birth cohorts of the UK population exposed to combined peak levels of asbestos and SV40-contaminated polio vaccines.

Materials and Methods:

Tumor and background lung tissue microarrays prepared from archival surgical specimens of 139 pleural mesothelioma cases, collected over a period of 8 years (1998 to 2005), were analyzed. These represented birth cohorts overlapping with the period 1950 to 1960, exposed to a high level of both asbestos and SV40-contaminated live polio vaccines. SV40 Tag mRNA expression was investigated using a highly sensitive and specific SV40 Tag RNA in situ hybridization detection method on the basis of the novel RNAscope technology.

Results:

SV40 Tag RNA was not detected in any of the 127 evaluable tumor cases, despite appropriate results obtained for the external positive and negative controls included.

Conclusion:

The complete absence of SV40 Tag mRNA in this large series of cases contradicts experimental evidence suggestive of SV40 link with asbestos-exposed malignant pleural mesotheliomas in the UK population. Alternative explanations of the negative findings are discussed to exclude possible confounding factors.
Comparison of 11C-Choline and 11C-Methionine PET/CT in Multiple Myeloma
Authors: Lapa Constantin , Kircher Malte , Da Via Matteo , Schreder Martin , Rasche Leo , Kortüm K. Martin , Einsele Hermann , Buck Andreas K. , Hänscheid Heribert , Samnick Samuel
Published: June 2019

Purpose

PET/CT with both 11C-choline and 11C-methionine has recently been reported to offer advantages over 18F-FDG for imaging in multiple myeloma (MM). The aim of this study was to directly compare the diagnostic performance of both non-FDG radiotracers in MM patients.

Methods

Nineteen patients with a history of MM (n = 18) or solitary bone plasmacytoma (n = 1) underwent both 11C-choline and 11C-methionine PET/CT for diagnostic imaging. In this retrospective analysis, scans were compared on a patient and on a lesion basis. In 12 patients, respective tracer uptake in the iliac crest was correlated with the extent of malignant bone marrow plasma cell infiltration.

Results

11C-methionine detected more intramedullary MM lesions in 8 (42.1%) of 19 patients. In the remainder (11/19 [57.9%]), both 11C-choline and 11C-methionine provided equal results. 11C-methionine demonstrated higher lesion-to-muscle ratios (P = 0.0001). In the 12 patients in whom a recent bone marrow biopsy was available, SUVmean as well as SUVmax correlated significantly with the degree of malignant plasma cell infiltration for both 11C-methionine (SUVmean: r = 0.85, P < 0.001; SUVmax: r = 0.82, P = 0.001) and 11C-choline (SUVmean: r = 0.72, P < 0.008; SUVmax: r = 0.73; P = 0.006).

Conclusions

Our data suggest that 11C-methionine PET/CT might be more sensitive than 11C-choline PET/CT for the detection of active MM lesions.
Favorable Response After Only One Cycle of Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE in a Patient With Metastatic Merkel Cell Carcinoma
Authors: Moghadam Soroush Zarehparvar , Divband Ghasemali , Shakeri Sara , Aryana Kamran
Published: June 2019

A 77-year-old man with a history of metastatic Merkel cell carcinoma and debilitating painful cutaneous lesions was referred to our nuclear medicine department for peptide receptor radionuclide therapy with 177Lu-DOTATATE as ultimate therapeutic option. Post-treatment whole body scan showed multiple zones of 177Lu-DOTATATE uptake in the metastatic regions, which revealed significant improvement within the next 10 days of therapy. Peptide receptor radionuclide therapy in metastatic Merkel cell carcinoma is an effective therapeutic option that should be considered in earlier stages of the disease.
Readmission rates and associated factors following rib cage injury
Authors: Baker Jennifer E. , Skinner Mitchell , Heh Victor , Pritts Timothy A. , Goodman Michael D. , Millar D. Anderson , Janowak Christopher F.
Published: June 2019

BACKGROUND

There remains a lack of knowledge about readmission characteristics after sustaining rib fractures. We aimed to determine rates, characteristics, and predictive/protective factors associated with unexpected reevaluation and readmission after rib cage injury.

METHODS

A retrospective review was performed based on trauma patients evaluated at an urban Level I trauma center from January 2014 to December 2016. Adult patients sustaining blunt trauma with more than one rib fracture or a sternomanubrial fracture were defined as having moderate to severe rib cage injury. Exclusion criteria included penetrating injury, death during initial hospitalization, and only one rib fracture. Reevaluation was defined as presenting at a hospital within 90 days of discharge urgently or emergently. Demographics, injury characteristics, comorbidities, complications, imaging, and readmission data were collected. Univariate and multivariate analysis was performed with a significance of p less than 0.05.

RESULTS

During the study period, 11,667 patients underwent trauma evaluation, of which 1,717 patients were found to have a moderate to severe rib cage injury. Within 90 days, 397 (23.1%) of patients underwent reevaluation, while 177 (10.3%) required readmission. One hundred forty-two (8.3%) patients were reevaluated specifically for chest-related complaints, and 55 (3.2%) required readmission. On univariate analysis, Injury Severity Score greater than 15, hospital length of stay longer than 7 days, intensive care unit (ICU) length of stay longer than 3 days, a worsened chest x-ray at discharge, a psychiatric comorbidity, a smoking comorbidity, deep vein thrombosis, unplanned readmission to the ICU, and unplanned intubation were higher in the overall reevaluation cohort. On multivariate analysis, age of 15 years to 35 years, Risk Assessment Profile score greater than 8, hypertension, psychiatric comorbidity, current smoker, and unplanned return to the ICU on index admission were predictive of reevaluation of overall reevaluation.

CONCLUSION

Moderate to severe rib cage injury is associated with high rates of reevaluation and readmission. Younger patients who smoke and required a return to the ICU are at greater risk for readmission.

LEVEL OF EVIDENCE

Level IV, Prognostic and Epidemiologic.
Long-term Outcomes Following Kidney Transplantation From Donors With Acute Kidney Injury
Authors: Heilman Raymond L. , Smith Maxwell L. , Smith Byron H. , Kumar Anjushree , Srinivasan Ananth , Huskey Janna L. , Khamash Hasan A. , Jadlowiec Caroline C. , Mathur Amit K. , Moss Adyr A. , Reddy Kunam S.
Published: June 2019

Background.

Kidneys from deceased donors with acute kidney injury (AKI) are more likely to be discarded because of concerns for poor outcomes after transplantation. The aim of this study was to determine the long-term outcomes of a large cohort of patients transplanted utilizing kidneys from deceased donors with AKI.

Methods.

All patients receiving a deceased donor kidney transplant during a recent 10-year period were included. Acute Kidney Injury Network (AKIN) criteria were used to classify the donors. Donor kidneys with >10% cortical necrosis or more than mild chronic changes were discarded. The primary outcome is the combined endpoint of death or graft loss.

Results.

The cohort included 1313 kidneys from 974 donors, AKIN stage 0 (no AKI) in 319 (24.3%), stage 1 in 370 (28.2%), stage 2 in 177 (13.5), and stage 3 in 447 (34.0%). Estimated 5-year graft survival (95% confidence interval) was 78.5% (72.5-84.5), 77.8% (72.8-82.1), 83.8% (76.8-88.9), and 84.6% (79.5-88.7) for AKIN donor stage 0 to 3, respectively (log-rank P = 0.10). After adjusting for baseline differences, the hazard ratio (95% confidence interval) for the combined endpoint for the AKIN stage 3 group (relative to AKIN 0 group) was 0.70 (0.45-1.10). Delayed graft function occurred in 44.6% and 75.4% of AKIN 2 and 3 groups, as compared to 33.9% and 33.5% in AKIN 0 and 1 (P < 0.001).

Conclusion.

We conclude that transplanting selected kidneys from deceased donors with AKI with preimplantation biopsy showing <10% cortical necrosis and no more than mild chronic changes have excellent long-term graft survival.
A Nationwide Survey of Hepatitis E Virus Infection and Chronic Hepatitis in Heart and Kidney Transplant Recipients in Japan
Authors: Owada Yohei , Oshiro Yukio , Inagaki Yuki , Harada Hiroshi , Fujiyama Nobuhiro , Kawagishi Naoki , Yagisawa Takashi , Usui Joichi , Akutsu Naotake , Itabashi Yoshihiro , Saito Kazuhide , Watarai Yoshihiko , Ichimaru Naotsugu , Imamura Ryoichi , Kyakuno Miyaji , Ide Kentaro , Shibuya Yuichi , Okabe Yasuhiro , Ono Minoru , Sasaki Konosuke , Shiose Akira , Yamagishi Kazumasa , Ohnishi Hiroshi , Nagashima Shigeo , Takahashi Masaharu , Yuzawa Kenji , Okamoto Hiroaki , Ohkohchi Nobuhiro
Published: June 2019

Background.

Recently, chronic hepatitis E has been reported in solid organ transplant (SOT) recipients in European countries. Previously, we clarified the prevalence of hepatitis E virus (HEV) infection in Japanese liver transplant recipients and identified 2 chronic hepatitis E patients infected by blood transfusion. However, the rate of HEV infection in recipients of SOTs other than liver in Japan remains unclear, so we conducted a nationwide survey to clarify the prevalence of chronic HEV infection in Japanese heart and kidney transplant recipients.

Methods.

A total of 99 heart and 2526 kidney transplant recipients in 17 hospitals in Japan were examined for the presence of the IgG class of anti-HEV antibodies as well as for serum HEV RNA.

Results.

The prevalence of anti-HEV IgG among heart and kidney transplant recipients was 7.07% (7/99) and 4.08% (103/2526), respectively. One heart transplant patient (1.01%) and 11 kidney transplant patients (0.44%) were found to be positive for HEV RNA. The HEV isolates from all viremic patients were typed as genotype 3. Four patients developed chronic hepatitis E after transplantation. Three patients were treated with ribavirin; their liver enzymes normalized, and HEV RNA became negative immediately. Sustained virologic response was achieved in all cases.

Conclusions.

This is the first nationwide survey of HEV infection in Japanese heart and kidney transplant recipients. The prevalence of anti-HEV IgG and HEV RNA in heart and kidney transplant recipients in Japan was lower than that in European countries. Of note, 42% of viremic transplant patients developed chronic hepatitis.
Induction of Accommodation by Anti–complement Component 5 Antibody-based Immunosuppression in ABO-incompatible Heart Transplantation
Authors: Park Sunjoo , Lee Jae-Ghi , Jang Joon Young , Ryu Jung-Hwa , Kim Dong jo , Chang Shin Jae , Kim Hyori , Chung Junho , West Lori , Yang Jaeseok
Published: June 2019

Background.

Plasmapheresis in combination with immunoglobulin and rituximab is often used to induce accommodation in ABO-incompatible (ABOi) living-donor transplantation; however, this regimen cannot be applied to cases of ABOi deceased-donor transplantation. Here, we investigated whether an anti–complement component 5 (C5) antibody-based regimen can induce accommodation in ABOi heart transplantation.

Methods.

Both IgM and IgG anti-blood type A antibodies were induced in wild-type mice by sensitization using human blood type A antigen. Heterotopic ABOi heart transplantation was performed from human blood type A-transgenic C57BL/6J mice to sensitized wild-type DBA/2 mice.

Results.

Either anti-C5 antibody or conventional triple immunosuppressants (corticosteroid, tacrolimus, mycophenolate mofetil) alone did not induce accommodation in majority of ABOi heart allografts, whereas their combination induced accommodation in more than 70% of cases despite the presence of anti-A antibodies. The combination therapy markedly suppressed the infiltration of T cells and macrophages into ABOi allografts, despite mild deposition of IgG and C4d. T-cell activation and differentiation into Th1, Th2, and Th17 cells were suppressed along with CD49dhighCD4+ T and follicular helper T cells in the combination treatment group. CD24+ B cells, including both CD24+CD23+ marginal zone B cells and CD24+CD23− T2-marginal zone B cells, were increased in the accommodation group.

Conclusions.

C5 inhibitor-based immunosuppression induced accommodation in murine ABOi heart transplantation, presenting a promising strategy for ABOi deceased-donor transplantation.
Sex and Gender Considerations in Transplant Research: A Scoping Review
Authors: Laprise Claudie , Cole Katherine , Sridhar Vikas Srinivasan , Marenah Tida , Crimi Cassandra , West Lori , Foster Bethany J. , Pilote Louise , Sapir-Pichhadze Ruth
Published: June 2019

Background.

In response to the promotion of sex and gender integration in health-related research, we conducted a scoping review evaluating to what extent sex and gender were considered in the transplantation literature.

Methods.

We searched Medline and Embase for manuscripts published between January 1946 and October 2016. Two reviewers independently selected manuscripts describing clinical research on stem cells, tissues, or solid organ transplantation with ≥20 participants, which mentioned “sex” and/or “gender” in the title or abstract. For each eligible manuscript, 2 of 5 reviewers extracted data on study design, population (transplant candidates, recipients, donors), transplant type, and study outcomes. We evaluated whether the terms “sex” and “gender” were applied according to their correct definitions and how these variables were handled at the level of study design and analysis.

Results.

Of 7565 search results, 2107 manuscripts met the inclusion criteria. Sex and gender were applied interchangeably in more than half of the studies (57.5%). Rarely were sex or gender, when applied correctly, considered in the primary study question (13.3% and 25.0%, respectively). The majority of the studies considered these variables as confounders (74.6% for sex and 68.2% for gender), and a minority considered them as effect measure modifiers (2.8% for sex and 5.0% for gender).

Conclusions.

Despite a growing awareness of the need to integrate sex and gender in health research, education is required to ensure accurate and meaningful consideration of these concepts. We outline strategies for integrating sex and gender in allotransplantation and donation research during study design and analysis.
Modelling the impact of tuberculosis preventive therapy: the importance of disease progression assumptions
Authors: Sumner Tom , White Richard G.
Published: June 2019

Background

Following infection with Mycobacterium tuberculosis (M.tb) individuals may rapidly develop tuberculosis (TB) disease or enter “latent” infection state with a low risk of progression to disease. The mechanisms underlying this process are incompletely known. Mathematical models use a variety of structures and parameterisations to represent this progression from infection with M.tb to disease. This structural and parametric uncertainty may affect the predicted impact of interventions leading to incorrect conclusions and decision making.

Methods

We used a simple dynamic transmission model to explore the effect of uncertainty in model structure and parameterisation on the predicted impact of scaling up preventive therapy. We compared three commonly used model structures and used parameter values from two different data sources. Models 1 and 2 are equally consistent with observations of the time from infection to disease. Model 3, produces a worse fit to the data, but is widely used in published modelling studies. We simulated treatment of 5% of all M.tb infected individuals per year in a population of 10,000 and calculated the reduction in TB incidence and number needed to treat to avert one TB case over 10 years.

Results

The predicted impact of the preventive therapy intervention depended on both the model structure and the parameterisation of that structure. For example, at a baseline annual TB incidence of 500/100,000, the impact ranged from 11% to 27% and the number needed to treat to avert one TB case varied between 38 and 124. The relative importance of structure and parameters varied depending on the baseline incidence of TB.

Discussion

Our analysis shows that the choice of model structure and the parameterisation can influence the predicted impact of interventions. Modelling studies should consider incorporating structural uncertainty in their analysis. Not doing so may lead to incorrect conclusions on the impact of interventions.
Robin Hood: non-fitting, non-smoothing image detrending for bleaching correction
Authors: Nolan Rory , Iliopoulou Maro , Siebold Christian , Jones E. Yvonne , Padilla-Parra Sergi
Published: June 2019

Recent advances in protein labelling—gene tagging with CRIPSR-Cas9—have made it possible to label proteins of interest endogenously. This represents a major breakthrough in the field of quantitative microscopy, especially when quantifying protein-protein interactions. This is because over-expression of labelled proteins may cause a distortion in localization, function and perhaps artificially force protein-protein interactions due to crowding effects. A microscopy technique that is particularly well suited to detect protein interactions with low photon budgets is number and brightness (N&B). Detrending (removal of global trends in data) is a necessary pre-processing step to N&B calculations, but all current detrending methods perform poorly at low intensities. Here, we present the Robin Hood automatic detrending algorithm which performs well at low intensities, evaluating it with simulated and low photon budget live cell images. RH is available as an ImageJ plugin and as an R package.

STATEMENT OF SIGNIFICANCE

Fluorescence microscopy in general and Fluorescence fluctuation methods in particular are very much dependent on detrend algorithms and so far, the user needs to decide an arbitrary number to correct for bleaching when using the box plot or the running average approach. Here, we have developed a tool available to everybody as an ImageJ plugin that is automatic, user-free and able to correct bleached images with very low photon counts.
Myo1e modulates the recruitment of B cells to inguinal lymph nodes
Authors: Girón-Pérez Daniel Alberto , Vadillo Eduardo , Schnoor Michael , Santos-Argumedo Leopoldo
Published: June 2019

The recruitment of leukocyte to high endothelium venules and their migration to the lymph nodes are critical steps to initiate an immune response. Cell migration is regulated by the actin cytoskeleton where myosins have a very import role. Myo1e is a long tail class I myosin highly expressed in B cells that not have been studied in the context of cell migration. By using anin vivomodel, through the use of intravital microscopy, we demonstrated the relevance of Myo1e in the adhesion and the migration of B cells in high endothelial venules. These observations were confirmed byin vitroexperiments. We also registered a reduction in the expression of integrins and F-actin in the protrusion of B lymphocytes membrane. Deficiencies in vesicular trafficking can explain the decrease of integrins on the surface. Interestingly, Myo1e is associated with focal adhesion kinase (FAK). The lack of Myo1e affected the phosphorylation of FAK and AKT, and the activity of RAC-1, disturbing the FAK/PI3K/RAC-1 signaling pathway. Together, our results indicate critical participation of Myo1e in the mechanism of B cell migration.

Summary statement

Myo1e participate in the adhesion and migration in the high endothelial venules by regulation of integrins and the PI3K/FAK/RAC-1 signaling pathway.
Optogenetic stimulation of the VTA modulates a frequency-specific gain of thalamocortical inputs in infragranular layers of the auditory cortex
Authors: Brunk Michael G. K. , Deane Katrina E. , Kisse Martin , Deliano Matthias , Vieweg Silvia , Ohl Frank W. , Lippert Michael T. , Happel Max F. K.
Published: June 2019

Background

Reward associations during auditory learning induce cortical plasticity in the primary auditory cortex. A prominent source of such influence is the ventral tegmental area (VTA), which conveys a dopaminergic teaching signal to the primary auditory cortex. It is currently unknown, however, how the VTA circuitry thereby influences cortical frequency information processing and spectral integration. In this study, we therefore investigated the temporal effects of direct optogenetic stimulation of the VTA onto spectral integration in the auditory cortex on a synaptic circuit level by current-source-density analysis in anesthetized Mongolian gerbils.

Results

While auditory lemniscal input predominantly terminates in the granular input layers III/IV, we found that VTA-mediated modulation of spectral processing is relayed by a different circuit, namely enhanced thalamic inputs to the infragranular layers Vb/VIa. Activation of this circuit yields a frequency-specific gain amplification of local sensory input and enhances corticocortical information transfer, especially in supragranular layers I/II. This effects further persisted over more than 30 minutes after VTA stimulation.

Conclusions

Altogether, we demonstrate that the VTA exhibits a long-lasting influence on sensory cortical processing via infragranular layers transcending the signaling of a mere reward-prediction error. Our findings thereby demonstrate a cellular and circuit substrate for the influence of reinforcement-evaluating brain systems on sensory processing in the auditory cortex.