bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological target-focused transcriptomic analysis of native vs cultured human and mouse dorsal root ganglia
Authors: Wangzhou Andi , McIlvried Lisa A. , Paige Candler , Barragan-Iglesias Paulino , Shiers Stephanie , Ahmad Ayesha , Guzman Carolyn A. , Dussor Gregory , Ray Pradipta R. , Gereau Robert W. , Price Theodore J.
Published: March 2020

Dorsal root ganglion (DRG) neurons detect sensory inputs and are crucial for pain processing. They are often studied in vitro as dissociated cell cultures with the assumption that this reasonably represents in vivo conditions. However, to the best of our knowledge, no study has directly compared genome-wide transcriptomes of DRG tissue in vivo versus in vitro or between laboratories and culturing protocols. Comparing RNA sequencing-based transcriptomes of native to cultured (4 days in vitro) human or mouse DRG, we found that the overall expression levels of many ion channels and G-protein–coupled receptors specifically expressed in neurons are markedly lower although still expressed in culture. This suggests that most pharmacological targets expressed in vivo are present under the condition of dissociated cell culture, but with changes in expression levels. The reduced relative expression for neuronal genes in human DRG cultures is likely accounted for by increased expression of genes in fibroblast-like and other proliferating cells, consistent with their mitotic status in these cultures. We found that the expression of a subset of genes typically expressed in neurons increased in human and mouse DRG cultures relative to the intact ganglion, including genes associated with nerve injury or inflammation in preclinical models such asBDNF,MMP9,GAL, andATF3. We also found a striking upregulation of a number of inflammation-associated genes in DRG cultures, although many were different between mouse and human. Our findings suggest an injury-like phenotype in DRG cultures that has important implications for the use of this model system for pain drug discovery.
Pattern of Smartphone Usage and Psychosocial Factors Affecting Smartphone Overdependence in Middle-Aged Women
Authors: Jeong Yeo Won , Oh Juyeon
Published: March 2020

Studies suggest that the prevalence of smartphone overdependence has increased in middle-aged individuals; however, little is known about factors that may influence smartphone overdependence among middle-aged women. This study assessed the patterns of smartphone usage and the psychosocial factors affecting smartphone overdependence in middle-aged women. Middle-aged women (n = 135) in South Korea completed the Smartphone Overdependence Scale, Ego Resiliency Scale, Profile of Mood States-Brief, Multidimensional Scale of Perceived Social Support, and Subjective Happiness Scale. The data were analyzed using univariate and multivariate logistic regression analyses. The mean smartphone duration per use was 13.41 ± 10.82 minutes, the mean frequency of smartphone usage per day was 23.06 ± 20.29, and the most used smartphone function was messaging. Smartphone overdependence occurred in 13 (9.63%) of the 135 middle-aged women, and higher tension (OR = 1.34, p = .011), less vigor (OR = 0.83, p = .040), and less social support from significant others (OR = 0.40, p = .010) were significantly associated with an increased likelihood of smartphone overdependence. This study has value as a first step in examining smartphone overdependence and its psychosocial predictive factors among middle-aged women. A smartphone overdependence intervention for middle-aged women could include activities that reduce tension, increase vigor, and enhance offline social support.
Telehealth monitoring of a hypertensive elderly patient with the new VITASENIOR-MT system: a case study
Authors: Pereira Telmo , Pires Gabriel , Jorge Dário , Santos Diogo
Published: March 2020

Telehealth technologies providing remote monitoring of health parameters are a promising approach for the management of arterial hypertension in the elderly. The VITASENIOR-MT platform was developed as a telehealth solution designed to contribute to improve the health condition and quality of life, promoting safe and independent living of the old adult. It is an ‘internet-of-things’-based solution relying on the interaction of the old adult with a TV-set to record biometric parameters and to receive warning and recommendations related to health and environmental sensor recordings. We present a pilot study with a male hypertensive patient, aged 81 years old, under anti-hypertensive treatment, with epilepsy, arthritis and paroxistic atrial fibrillation as major comorbidities. The VITASENIOR-MT was installed at the patient’s assisted-dwelling house and a remote follow-up was implemented for 2 months, monitoring daily blood pressure and heart rate, as well as weight and indoor environmental parameters.
Assessment of tumor response to definitive chemoradiotherapy and prognosis prediction in patients with esophageal cancer judged by PET response criteria in solid tumors: multicenter study in Japan
Authors: Kitajima Kazuhiro , Kaida Hayato , Nakatani Koya , Ishibashi Mana , Morita Takahiro , Nakajo Masatoyo , Tamaki Yukihisa , Minamimoto Ryogo
Published: March 2020

Objectives

The aim of the study was to evaluate PET response criteria in solid tumors (PERCIST) to indicate therapeutic response to definitive chemoradiotherapy, as well as prediction of recurrence and death in patients with esophageal cancer.

Methods

Before and after recieving definitive chemoradiotherapy, 181 patients with esophageal cancer underwent fluorodeoxyglucose-PET/computed tomography (FDG-PET/CT). PERCIST, reduction rates of tumor uptake and volume of whole lesions, tumor node metastasis (TNM) staging regarding progression-free survival (PFS), and overall survival (OS) were analyzed using log-rank and Cox methods.

Results

Complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD) shown by PERCIST were seen in 42 (23.2%), 113 (62.4%), 14 (7.7%), and 12 (6.6%) patients, respectively. Progression developed in 137 (75.7%) patients and 101 (56.1%) patients died (median follow-up 16.9, range 3.2–124.9 months). Those who achieved CMR showed significantly longer PFS and OS as compared with patients who did not (PMR, SMD, and PMD) (both P < 0.0001). In univariate analysis, initial clinical T status (P = 0.0048), N status (P = 0.011), and TNM stage (P = 0.0006), PERCIST (P < 0.0001), and reduction rate of peak lean body mass standardized uptake value (P < 0.0001), of metabolic tumor volume (P < 0.0001), and of total lesion glycolysis (TLG) (P < 0.0001) were associated with significantly increased OS. Multivariate analysis confirmed PERCIST [hazard ratio (HR): 13.15, 95% confidence interval (CI), 4.54–55.8; P < 0.0001], and TLG reduction rate (HR: 2.21, 95% CI, 1.04–4.68; P = 0.040) as independent OS predictors.

Conclusion

PERCIST is useful for evaluating therapeutic response to definitive chemoradiotherapy, and predicting progression and death in patients with esophageal cancer.
Restoration of I-131 whole body image using a Wiener filter
Authors: Pandey Anil Kumar , Santosh Yashwariya , Sharma Param D. , Yadav Divya , Bal Chandrashekhar , Kumar Rakesh
Published: March 2020

Introduction

The aim of the study was to restore I-131 whole body image using Wiener filter.

Material and methods

A set of 50 I-131 whole body images acquired using Symbia E dual head gamma camera with high energy general purpose collimator was used. The Gaussian point-spread function (PSF) characterised by the size (3, 5, 7, 9, 11, and 13 pixels) and corresponding standard deviation (0.5, 0.75, 1, 1.5, 1.75, and 2 pixels) and noise-to-signal power ratios (NSR: 0, 0.001, 0.01, 0.1, 0.2, 0.3, 0.4, and 0.5) were used as parameters for Wiener filter. Using the combinations of PSF and NSR, a total of 2450 images (50 × 49 = 2450 images, where 49 images include 1 input and 48 restored images for each input image) were generated and inspected by two nuclear medicine physicians. They selected one best image (the image which had less noise and better contrast between the lesion and background in comparison with the input image). Their results were analyzed.

Results

Compared to input image, the metastatic uptake in restored images was very easily perceived. The restored image obtained with PSF (size = 13, sigma = 2) and NSR = 0.3 had better signal-to-noise ratio in comparison to restored image obtained with PSF (size = 11, sigma = 1.75) and NSR = 0.2.

Conclusion

The restored images with PSF (size = 13, sigma = 2) and NSR = 0.3 were found to have superior image quality in comparison with its input image.
The Clinical Characteristics of Fractures in Pediatric Patients Exposed to Proton Pump Inhibitors
Authors: Fleishman Nathan , Richardson Troy , Attard Thomas
Published: March 2020

Objectives:

There are increasing concerns regarding proton pump inhibitor (PPI) use and the risk of fractures in adults. Few studies have evaluated this risk among pediatric patients. This study examined fractures and fracture location among pediatric patients exposed to PPI compared with those without documented exposure.

Study Design:

Encounters for patients 6 months to 15.5 years were identified between July 1, 2011 to December 31, 2015 in the Pediatric Hospital Information System database. Exclusion criteria was applied for chronic illnesses, conditions or medications predisposing to fracture. Encounters were classified as PPI encounters if a charge for PPI was documented. PPI encounters were propensity matched to non‐PPI encounters. Following initial encounter, patients were evaluated over a 2‐year period for hospitalizations resulting from fracture.

Results:

There was a statistically significant higher rate of fractures among the PPI‐exposed group (1.4% vs 1.2%, P = 0.019). Adjusting for remaining differences in sex, race, encounter type, payer, and resource intensity after matching, the difference remained statistically significant (P = 0.017) with an adjusted odds ratio (95% CI) of 1.2 (1.0‐‐1.4). Upper extremity was the most common location for fracture; however, the PPI cohort was more likely to suffer from lower extremity, rib, and spinal fractures (P = 0.01).

Conclusions:

This study suggests an increased risk of fracture among pediatric patients taking PPI. Among patients hospitalized with a fracture, those with PPI exposure had a higher rate of lower extremity, rib, and spine fractures compared with controls. This appeared to be a class effect not related to individual PPI agent.
Extraintestinal Manifestations Are Associated With Disease Severity in Pediatric Onset Inflammatory Bowel Disease
Authors: Jansson Sabine , Malham Mikkel , Paerregaard Anders , Jakobsen Christian , Wewer Vibeke
Published: March 2020

Objectives:

The aim of this study was to investigate a possible association between extraintestinal manifestations (EIM) and a more severe disease course in pediatric onset inflammatory bowel disease (pIBD).

Methods:

This study compares the disease course of pIBD patients (IBD diagnosis <15 years of age) with and without EIM in a population‐based cohort from Denmark. Patients diagnosed with pIBD between 1998 and 2008 were included in the study and followed until December 31, 2014. Data on phenotype, treatment, relapses, and the temporal relationship between IBD relapses and activity of EIM were collected at end of follow‐up by manual revision of patient charts.

Results:

Of 333 pIBD patients, 14 (4.2%) had EIM at time of diagnosis and 47 (14.1%) developed EIM during follow‐up. Median follow‐up time was 9.6 years for patients with EIM and 8.8 years for patients without. In ulcerative colitis, EIM were associated with an increased risk of biological treatment and surgery (hazard ratio: 2.6; 95% confidence interval [CI]: 1.3–5.5, P = 0.008 and 2.9 [95% CI: 1.1–7.7, P = 0.03], respectively). In Crohn disease, EIM were associated with an increased relapse rate (1.3 [95% CI: 1.1–1.5], P = 0.001). Lastly, we found a positive temporal relationship between relapse of IBD and EIM activity.

Conclusion:

The presence of EIM is associated with a more severe disease course in pIBD. This should be considered when deciding treatment options, as a more aggressive treatment approach could be warranted in patients with EIM. However, prospective studies are needed to fully evaluate this.
The Interaction Between Hematological Cancer Patients and Family Caregivers and Their Life Changes
Authors: Serçe Özgü , Günüşen Neslihan Partlak
Published: March 2020

Background

Diagnosis of hematological cancer affects patients and caregivers as a unit. Few studies have focused on the relationship between hematological cancer patients and their caregivers.

Objective

To explore (a) the interaction between patients receiving treatment for hematological cancer in a hematology-oncology clinic and their family caregivers and (b) perceived changes in lives of patients receiving treatment for hematological cancer in a hematology-oncology clinic and their family caregivers.

Methods

We used a qualitative descriptive design with a dyadic approach. The study sample included 11 patients with hematological cancer and 11 family caregivers selected through purposive sampling. In-depth interviews were conducted using a semistructured interview format.

Results

As a result of a content analysis, 3 themes emerged: hidden emotions, companionship, and life changes. Both the patients and the family caregivers described coping by hiding their feelings, thoughts, and needs and reducing communication with each other. Dyad members described commitment to each other and an increase in confidence. In addition, the patients and the family caregivers experienced changes in their roles and perspectives during the diagnosis and treatment process.

Conclusion

Patients with hematological cancer and family caregivers need nurses’ support. Nurses should be prepared to provide patient-caregiver–based interventions.

Implication for Practices

It is important that nurses take action to strengthen the relationship between patients and their caregivers, particularly with a focus on carrying out interventions to improve communication between them. Nurses can also strengthen dyads’ coping by drawing attention to positive developments in their perspectives and relationships.
Rural-Urban Differences in Neuroimmune Biomarkers and Health Status Among Women Living With Breast Cancer
Authors: Hulett Jennifer M. , Abshire Demetrius A. , Armer Jane M. , Millspaugh Rami , Millspaugh Joshua
Published: March 2020

Background

Because of chronic emotional and psychosocial stressors following breast cancer (BC) treatment, BC survivors are at risk of neuroimmune dysfunction in survivorship. Rural BC survivors experience more health disparities than urban BC survivors. Rural-urban residence as a variable on neuroimmune activity in extended BC survivorship continuum has not been explored.

Objective

To report the feasibility of studying relationships between neuroimmune activity and perceived health in rural and urban BC survivors.

Methods

Data from a pilot study of BC survivors (n = 41) were analyzed. Participants were rural (n = 16) and urban (n = 25). Participants completed Medical Outcomes Study Short-Form Version 2 Health Survey questionnaires and provided salivary specimens for analysis of salivary α-amylase (sAA), cortisol, and interleukin 6 (IL-6). Rural-Urban Commuting Area Codes were used to determine rural or urban residence.

Results

Differences in immune activity were observed between rural and urban BC survivors (U = 34, P < .05). No rural-urban group differences in neuroendocrine activity were observed. Relationships were observed between perceptions of mental health and sAA (P < .05) in rural BC survivors and between perceptions of mental health and IL-6 (P < .05) in urban BC survivors. Interleukin 6 was positively associated with perceptions of physical health (P < .05) in rural BC survivors.

Conclusion

Pilot data suggest rural-urban residence may be a factor in relationships between neuroimmune function (ie, sAA and IL-6) and perceived health status, particularly social functioning in women with BC. Additional studies with powered designs are indicated.

Implications for Practice

Although evidence is limited, data support the feasibility of studying relationships between sAA and IL-6 and perceptions of health in women with BC.
Oncology and Palliative Care Nurses’ Knowledge and Attitudes Toward Artificial Nutrition and Hydration for Patients at End of Life in Italy
Authors: Albanesi Beatrice , Piredda Michela , Marchetti Anna , Mastroianni Chiara , Magnani Caterina , Artico Marco , D’Angelo Daniela , Lusignani Maura , Ianni Andrea , De Marinis Maria Grazia
Published: March 2020

Background

Nutrition is a basic patients’ need and an important component of nursing. End-of-life cancer patients can experience difficulties in eating and drinking, sometimes requiring artificial nutrition and hydration (ANH). Nurses’ knowledge and attitudes greatly influence nursing care. Nurses may lack knowledge of ANH. To date, no study has explored the knowledge and attitudes of oncology and palliative care nurses toward end-of-life ANH.

Objective

To describe oncology and palliative care nurses’ knowledge of and attitudes toward ANH.

Methods

A multicenter cross-sectional study was conducted in 7 regions of Italy using the Italian version of the Questionnaire on Knowledge and Attitudes in Providing ANH for Terminal Cancer Patients. Attitudes were divided into benefits and burdens of providing ANH. Data were analyzed by descriptive statistics.

Results

High percentages of oncology and palliative care nurses showed reasonable knowledge about ANH. More disagreement was evidenced about benefits and burdens of ANH, and lower importance was given to them.

Conclusions

Some misconceptions and a low level of awareness exist among some nurses about ANH. More nursing studies should be conducted and extended to different care settings. Moreover, guidelines should be reinforced with a nursing perspective to better define nurses’ role in the decision-making process on ANH.

Implications for Practice

This exploration of nurses’ knowledge of and attitudes toward ANH in end-of-life cancer patients can contribute to an understanding of how nurses can be involved in better meeting cancer patients’ nutritional needs at the end of life.
Irritability Disorders in Adults
Authors: Yager Joel
Published: March 2020

Research into irritability has focused largely on its developmental and child-adolescent manifestations. Although irritability appears to be as elemental an experience as anxiety or depression, diagnoses highlighting irritability as the focal ingredient have yet to be delineated for adults. Instead, irritability-related diagnoses in adults have largely emphasized externalizing behaviors, depressed mood, and personality. Consequently, patients complaining of irritability are sometimes shoehorned into diagnostic categories that they do not experience as authentic representations of their lived experiences. This article proposes that the symptom of irritability might be productively reenvisioned as a focal point, analogous to anxiety and depression, around which irritability-related syndromes and disorders in adults might coalesce. If anxiety, depressive, insomnia, and pain disorders, why not irritability disorders? Both state and trait characteristics of irritability can lend themselves to DSM diagnostic frames. Based on clinical observations, specific irritability disorders in adults can be envisioned, modeled as Irritability Disorder of Adulthood, Irritability Disorder Secondary to Another Medical Condition, Substance-Induced Irritability Disorder, Adjustment Disorder With Irritable Mood, and the like. Further delineation of irritability phenomena, syndromes, and possible disorders in adults is warranted to advance investigation, guide assessment, and improve treatment.
Sleep Duration Change and Cognitive Function
Authors: Lian Ying , Zhang Jie , Jia Cun-Xian
Published: March 2020

This study aimed to investigate the relationship between sleep duration and cognitive function in Chinese people older than 45 years, using data from the China Health and Retirement Longitudinal Study. The baseline survey was conducted in 2011 and the second and third wave surveys were conducted in 2013 and 2015, respectively. Multiple linear regression models were used to evaluate all associations. A total of 5811 individuals were included. No significant associations were found between short or long sleep duration at baseline and cognitive function. Compared with no change in sleep duration, a decrease in sleep duration by 2 hours or more and an increase in sleep duration by 2 hours or more were associated with worse global cognitive function, withβ(95% confidence intervals [CIs]) of −0.42 (−0.70 to −0.14) and −0.34 (−0.67 to −0.01), respectively. In men, an increase of 2 hours or more in sleep duration was associated with lower global cognitive score (β= −0.64; 95% CI, −1.19 to −0.08), whereas in women, a decrease of 2 hours or more in sleep duration was associated with lower global cognitive score (β= −0.42; 95% CI, −0.78 to −0.06). Our study demonstrated that longitudinal sleep duration change was associated with cognitive function. Our findings indicate the need to consider changes in sleep duration when estimating risk and suggest that targeted strategies should be put forward for routine sleep screening and to maintain regular sleep patterns.
Autistic Traits in Men With Substance Use Disorder
Authors: Işık Ümit , Çokünlü Yusuf , Şimşek Fulya , Demirel Başak , Kılıç Faruk , Demirdaş Arif , Eren İbrahim
Published: March 2020

There has been no study in the literature evaluating autistic traits (ATs) in men with substance use disorders (SUDs). Therefore, we performed the current study to evaluate whether there is a relation between the ATs among men with SUDs and normal controls. A total of 142 men with SUDs and 109 age and sex-matched healthy controls were included in the current study. Present attention deficit hyperactivity disorder (ADHD) symptoms of the participants were evaluated using the Adult ADHD Self-Report Scale. The autism spectrum quotient (AQ) was used to evaluate ATs. The current study found that higher AQ imagination and lower AQ attention to detail scores predicted SUDs after controlling for AQ subscales and present ADHD symptoms. This study shows that ATs may be engaged in the development of SUDs. To explore the connection between ATs and SUDs, more research is needed.
Transactional Sex and Incident Chlamydia and Gonorrhea Among Black Men Who Have Sex With Men in Atlanta, Georgia
Authors: Rucinski Katherine B. , Eaton Lisa A. , Learner Emily R. , Watson Ryan J. , Maksut Jessica L. , Earnshaw Valerie A.
Published: March 2020

Background

Black men who have sex with men (BMSM) are disproportionately affected by sexually transmitted infections (STI), including chlamydia and gonorrhea. Transactional sex is an hypothesized risk factor for STI acquisition in BMSM.

Methods

We estimated the association of transactional sex with incident chlamydia/gonococcal infection among BMSM using longitudinal data from a randomized trial in Atlanta (2012–2015). BMSM were eligible for inclusion if they tested human immunodeficiency virus (HIV)-antibody-negative and reported both ≥2 male sex partners and any condomless anal sex in the last year. We defined chlamydia/gonorrhea incidence as the first occurrence of either rectal or urogenital chlamydia or gonococcal infections after a negative result at enrollment. We used Poisson regression to estimate the incidence rate (IR) for chlamydia/gonorrhea over 12 months. Incidence rate ratios (IRR) compared estimates by reported experience of transactional sex. Subgroup analyses assessed potential heterogeneity by age and sexual identity.

Results

This analysis included 416 BMSM, of whom 191 (46%) were gay-identified, 146 (42%) reported a history of transactional sex, and 57 (14%) had prevalent chlamydia/gonococcal infection at baseline. Over a median of 1 year of follow-up, an additional 55 men tested laboratory-positive for chlamydia/gonorrhea (IR, 17.3 per 100 person-years). Transactional sex was not associated with chlamydia/gonorrhea incidence overall. However, among gay-identified BMSM, transactional sex was associated with incident chlamydia/gonorrhea (IRR, 2.9; 95% confidence interval, 1.2–6.8).

Conclusions

Economic and social vulnerabilities may motivate engagement in high-risk sexual behaviors through commodified sex, potentially increasing the burden of STIs among BMSM. In this investigation, the relationship between transactional sex and chlamydia/gonorrhea was not homogenous across BMSM with diverse sexual identities in Atlanta, suggesting that within select sexual networks, transactional sex may drive STI risks. Delivering accessible and targeted STI screening for marginalized BMSM should be prioritized for STI and HIV prevention.
Cost-effectiveness of a Dual (Immunohistochemistry and Fluorescence In Situ Hybridization) HER2/neu Testing Strategy on Invasive Breast Cancers
Authors: Hariri Nosaibah , Zare Somaye , Murphy James , Fadare Oluwole
Published: March 2020

The American Society of Clinical Oncology and the College of American Pathologists recommend that human epidermal growth factor receptor 2 (HER2)/neu status be determined for all invasive breast cancers. Although the most commonly used modalities to determine HER2/neu status, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), generally give concordant results, a small but consistent discordance rate between them has been demonstrated in prior studies. Most institutions in the United States use a “reflex testing strategy” for determining HER2/neu status. In a reflex testing strategy, cancers are screened with IHC, and FISH is reflexively performed only if the IHC results are classified as equivocal. Other institutions perform both tests on all cancers to maximize diagnostic accuracy (dual testing strategy). The cost-effectiveness of dual testing and reflex testing strategies are comparatively assessed herein. A decision analysis model was established comparing these 2 testing strategies. Model probabilities were obtained from an institutional invasive breast cancer cohort. Quality-adjusted life-years (QALYs) and cost estimates were extracted from published literature. All costs were converted to 2018 US$ values using the consumer price index. One-way sensitivity analysis was performed, as well as probabilistic sensitivity analyses with acceptability curves. A total of 1247 consecutive invasive breast cancer specimens were tested with a dual strategy. By IHC, 65%, 28%, and 10% were negative, equivocal, and positive, respectively. By FISH, 87% and 13% were HER2/neu-negative and HER2/neu-positive, respectively. Six patients whose cancers were IHC-positive (3+) were found to be FISH-negative. These 6 represented 5% of the 119 cases with HER2/neu 3+ scores and 0.55% of the 1082 cases with HER2/neu-negative results by FISH. Sixteen (2%) of 809 cases with a negative IHC result were ultimately classified as HER2/neu-amplified by FISH. These 16 cases constituted 10% of all cases that were ultimately classified as HER2/neu-amplified by FISH. Overall, a reflex testing strategy was found to be less costly than a dual testing strategy ($44,470.99 vs. $45,908.86, respectively), but was also less effective (10.28 vs. 10.30 QALYs). The incremental cost-effectiveness ratio was $70,051.55/QALY. In conclusion, in this single institutional cohort of breast cancers, a dual testing strategy to determine HER2/neu status was found to be more cost-effective than a reflex testing strategy.
Endometrial Carcinomas with a “Serous” Component in Young Women Are Enriched for DNA Mismatch Repair Deficiency, Lynch Syndrome, and POLE Exonuclease Domain Mutations
Authors: Conlon Niamh , Da Cruz Paula Arnaud , Ashley Charles W. , Segura Sheila , De Brot Louise , da Silva Edaise M. , Soslow Robert A. , Weigelt Britta , DeLair Deborah F.
Published: March 2020

Endometrial carcinoma (EC), as described by Bokhman, has historically been classified as Type I (low-grade, hormone-dependant, young patients, good prognosis) or Type II (high-grade, hormone-independent, older patients, poor prognosis). This classification is no longer pragmatic, however, as EC is a much more heterogeneous disease. Four molecular subtypes of EC were identified by The Cancer Genome Atlas (TCGA), and subsequent studies have demonstrated its utility in predicting prognosis. While endometrial serous carcinoma (ESC), the prototypical Type II EC, largely occurs in older women, younger women with ESC were not accounted for in the Bokhman model and were underrepresented in the TCGA study. We hypothesized that a subset of ESCs in young patients do not represent bona fide serous carcinomas but rather high-grade endometrioid carcinomas mimicking a serous phenotype. We identified ESCs and mixed endometrioid/serous carcinomas in women <60 years (n=37), and analyzed their clinical, morphologic, immunohistochemical, and molecular characteristics. Sixteen percent showed mismatch repair deficiency (MMR-D) and 11% were diagnosed with Lynch syndrome. Additionally, 16% of cases tested harbored a hotspot POLE exonuclease domain mutation (POLE-EDM). Morphologically, 47% of tumors showed confirmatory endometrioid features, including atypical hyperplasia, a low-grade endometrioid carcinoma component, or squamous differentiation. Clinically, the overall survival in patients with MMR-D and POLE-EDM was significantly better than that of patients without these features (P=0.0329). In conclusion, ESCs in young patients comprise a heterogeneous group of tumors, demonstrating diverse clinical, immunohistochemical, morphologic, and molecular features which have implications for prognosis and adjuvant therapy.
Schedule-based Family-centered Rounds: A Novel Approach to Achieve High Nursing Attendance and Participation
Authors: Kipps Alaina K. , Albert Marisa S. , Bomher Sean , Cheung Shirley , Feehan Shannon , Kim Joseph
Published: March 2020

Introduction:

Bedside nurse (RN) presence during family-centered rounds (FCR) enhances communication and collaboration for safer, higher-quality care.1–3 At our institution, RN participation in FCR was variable and lower than desired. The content discussed at each bedside during rounds was inconsistent, contributing to the irregular achievement of established FCR checklist items.

Methods:

Using a scheduling tool with a prioritization algorithm and set time allotment/patient, we implemented schedule-based family-centered rounds (SBFCR) on a pediatric acute care unit. Primary outcome metrics included RN attendance and participation. We tracked rounding checklist compliance, parent presence on rounds, and adherence to the schedule. Surveys provided information on provider and family satisfaction. Perceived impact on teaching was the balancing measure because the structure discouraged spending extra time at the cost of team tardiness for the next patient.

Results:

We created a schedule for 95% workweek days, with the rounding order kept for 93%. Mean RN attendance increased from 69% to 87% and participation increased from 48% to 80% with SBFCR (P < 0.001 for each). FCR checklist compliance increased from 60% to 94% (P < 0.001). Families felt more informed and able to attend; their presence at rounds rose from 66% to 85% (P < 0.001). Most faculty and trainees felt SBFCR was efficient and observed increased teaching with SBFCR.

Conclusions:

SBFCR provides an organizational framework for increased RN attendance and participation as well as greater family presence during rounds. The system elevated provider satisfaction with rounding without degrading the perceived educational experience.
Therapeutic Interventions to Reduce Radiation Induced Dermal Injury in a Murine Model of Tissue Expander Based Breast Reconstruction
Authors: Luby Alexandra O. , Snider Alicia E. , Mandair Gurjit S. , Urlaub Kevin M. , Lynn Jeremy V. , Nelson Noah S. , Donneys Alexis , Ettinger Russell E. , Gurtner Geoffrey C. , Kohn David , Buchman Steven R.
Published: March 2020

Background

Radiation therapy (XRT) induced dermal injury disrupts type I collagen architecture. This impairs cutaneous viscoelasticity, which may contribute to the high rate of complications in expander-based breast reconstruction with adjuvant XRT. The objective of this study was to further elucidate the mechanism of radiation-induced dermal injury and to determine if amifostine (AMF) or deferoxamine (DFO) mitigates type I collagen injury in an irradiated murine model of expander-based breast reconstruction.

Methods

Female Lewis rats (n = 20) were grouped: expander (control), expander-XRT (XRT), expander-XRT-AMF (AMF), and expander-XRT-DFO (DFO). Expanders were surgically placed. All XRT groups received 28 Gy of XRT. The AMF group received AMF 30 minutes before XRT, and the DFO group used a patch for delivery 5 days post-XRT. After a 20-day recovery period, skin was harvested. Atomic force microscopy and Raman spectroscopy were performed to evaluate type I collagen sheet organization and tissue compositional properties, respectively.

Results

Type I collagen fibril disorganization was significantly increased in the XRT group compared with the control (83.8% vs 22.4%; P = 0.001). Collagen/matrix ratios were greatly reduced in the XRT group compared with the control group (0.49 ± 0.09 vs 0.66 ± 0.09; P = 0.017). Prophylactic AMF demonstrated a marked reduction in type I collagen fibril disorganization on atomic force microscopy (15.9% vs 83.8%; P = 0.001). In fact, AMF normalized type I collagen organization in irradiated tissues to the level of the nonirradiated control (P = 0.122). Based on Raman spectroscopy, both AMF and DFO demonstrated significant differential protective effects on expanded-irradiated tissues. Collagen/matrix ratios were significantly preserved in the AMF group compared with the XRT group (0.49 ± 0.09 vs 0.69 ± 0.10; P = 0.010). β-Sheet/α-helix ratios were significantly increased in the DFO group compared with the XRT group (1.76 ± 0.03 vs 1.86 ± 0.06; P = 0.038).

Conclusions

Amifostine resulted in a significant improvement in type I collagen fibril organization and collagen synthesis, whereas DFO mitigated abnormal changes in collagen secondary structure in an irradiated murine model of expander-based breast reconstruction. These therapeutics offer the ability to retain the native microarchitecture of type I collagen after radiation. Amifostine and DFO may offer clinical utility to reduce radiation induced dermal injury, potentially decreasing the high complication rate of expander-based breast reconstruction with adjuvant XRT and improving surgical outcomes.
Myofascial Flap Closure in Treatment for Patients With Craniocervical Instability and Ehlers-Danlos Syndrome
Authors: Lu Connie , Wald Gal , Marano Andrew A. , Greenfield Jeffrey P. , Baaj Ali A. , Otterburn David M.
Published: March 2020

Introduction

The benefits of decompression and fusion for patients with craniocervical instability are well described. However, complications such as wound breakdown and need for unplanned reoperation frequently occur. Recent studies have shown advantages of myofascial flap closure for various spinal procedures. This study investigated whether closure with myofascial flaps after surgery for craniocervical instability decreases complications with further subgroup analysis of patients with Ehlers-Danlos syndrome (EDS).

Methods

A retrospective review of patients presenting to Weill Cornell Medical Center from 2010 to 2017 for craniocervical surgery was performed. All patients who underwent craniocervical surgery, regardless of plastic surgical involvement, were included in the study. Data including patient demographics, comorbidities, EDS diagnosis, surgical history, complications, and follow-up information were collected and analyzed.

Results

Data from 57 patients were analyzed. Eighteen patients (31.6%) had craniocervical surgery without myofascial flap closure, whereas 39 (68.4%) had surgery with flap closure. In the nonflap group, 9 patients required unplanned reoperation (50%). In the flap group, there were 5 patients requiring unplanned reoperation (15%). For reoperation, the Fisher exact test 2-tailed P value is 0.0096. Of those 57 patients, 24 had EDS: 5 (20.8%) had no flap closure, whereas 19 (79.2%) had flap closure. In the no-flap group, 3 patients required unplanned reoperation (60%). In the flap group, 5 patients required unplanned reoperation (21%). For reoperation, the Fisher exact test 2-tailed P value is 0.1265.

Conclusions

Patients undergoing surgery for craniocervical instability may benefit from myofascial flap closure even if they have EDS. Mobilizing well-vascularized tissue can decrease rates of reoperation.
An Important Gallbladder Pathology Mimicking Gallbladder Carcinoma: Xanthogranulomatous Cholecystitis: A Single Tertiary Center Experience
Authors: Bolukbasi Hakan , Kara Yasin
Published: March 2020

Background:

Xanthogranulomatous cholecystitis (XGC) is an uncommon, focal, or diffuse destructive inflammatory disease of the gallbladder mimicking or being together with the gallbladder carcinoma. This study aimed to evaluate the diagnosis, treatment, and outcomes of patients with XGC as a single tertiary center experience in the light of literature.

Materials and Methods:

Data about 34 patients with XGC identified after evaluating 2212 cholecystectomy specimens between January 2013 and December 2018 in a single tertiary center were documented to determine demographics (sex, age), clinical symptoms and findings, biochemical and imaging clues and operative findings, duration of hospitalization, postoperative complications, and histopathologic results.

Results:

Thirty-four patients with XGC were evaluated (17 male and 17 female patients with a mean age of 53; range, 25 to 78). Preoperative diagnosis was chronic calculous cholecystitis in 5 patients, cholelithiasis in 12 cases, acute calculous cholecystitis in 16 and emphysematous cholecystitis in 1 patient. Ultrasound was performed in all patients, computerized tomography in 11, contrast-enhanced magnetic resonance imaging in 9, and magnetic resonance cholangiopancreatography in 7 patients. None of the patients were diagnosed preoperatively. All patients received laparoscopic cholecystectomy, among whom 9 were converted to open. Partial cholecystectomy was performed in 1 patient. One patient with gallbladder adenocarcinoma was treated with radical cholecystectomy. XGC has nonspecific clinical and radiologic findings; thus, preoperative diagnosis is generally absent. Open cholecystectomy is the recommended treatment modality. Conversion to open is frequently necessary after laparoscopy. Complete cholecystectomy is the ultimate goal; however, partial cholecystectomy may be preferred to protect the structures of the hepatic hilum. Preoperative imaging studies (ultrasound or computerized tomography) of 34 patients showed a gallbladder stone in 18 patients, microlithiazis in 12 patients, sludge in 10 patients, and gallbladder sclerosis in 5 patients.

Conclusions:

Diagnosis of XGC and differentiation from gallbladder carcinoma may be difficult through preoperative or peroperative studies, even imaging is useful; the definitive diagnosis depends exclusively on pathologic examination. The surgeon should be prepared for every possibility.
Outcomes of Liver Transplant Recipients With Acute-on-Chronic Liver Failure Based on EASL-CLIF Consortium Definition: A Single-center Study
Authors: Agbim Uchenna , Sharma Anuj , Maliakkal Benedict , Karri Saradasri , Yazawa Masahiko , Goldkamp William , Podila Pradeep S.B. , Vanatta Jason M. , Gonzalez Humberto , Molnar Miklos Z. , Nair Satheesh P. , Eason James D. , Satapathy Sanjaya K.
Published: March 2020

Background.

The impact of acute-on-chronic liver failure (ACLF) defined by European Association for the Study of the Liver-Chronic Liver Failure in liver transplant (LT) recipients has not been well characterized. The aim of the study was to assess early posttransplant morbidity and survival of ACLF patients.

Methods.

Eight hundred twenty-five consecutive LT patients (04/2006–03/2013) were included in a retrospective analysis. Of the 690 evaluable patients, 589 had no ACLF, and the remaining 101 were grouped into ACLF Grades 1–3 (ACLF Grade 1: 50 [49.5%], ACLF Grade 2: 32 [31.7%], and ACLF Grade 3: 19 [18.8%]).

Results.

LT recipients transplanted in the context of ACLF had significantly increased serum creatinine (2.27 ± 1.16 versus 0.98 ± 0.32; P < 0.0001), and inferior 1-year graft (90% versus 78%; P < 0.0001) and patient survival (92% versus 82%; P = 0.0004) by Kaplan-Meier survival analysis; graft and patient survival correlated negatively with increasing severity of ACLF. One-year graft and patient survival were lower in those with high ACLF (Grade 2 and 3) irrespective of Model for End-Stage Liver Disease compared with other groups. The ACLF group had longer intensive care unit stays (10.6 ± 19.5 versus 4.2 ± 9; P < 0.0001), hospital stays (20.9 ± 25.9 versus 11.7 ± 11.4; P < 0.0001), and increased surgical re-exploration (26.7 % versus 14.6%, P = 0.002).

Conclusions.

Patients with ACLF undergoing LT have significantly higher resource utilization, inferior graft survival and patient survival, and renal dysfunction at 1 year. The combination of ACLF and Model for End-Stage Liver Disease can be considered when determining the suitability for potential transplantation.
Urine Recirculation Improves Hemodynamics and Enhances Function in Normothermic Kidney Perfusion
Authors: Weissenbacher Annemarie , Voyce Daniel , Ceresa Carlo D.L. , Soares Maria F. , Roberts Ian S. , Hunter James P. , Cook Andrew , Ploeg Rutger J. , Coussios Constantin C. , Friend Peter J.
Published: March 2020

Background.

The study compares urine recirculation (URC) to urine replacement (UR) with Ringer’s lactate in a porcine normothermic kidney machine perfusion (NMP) model using a preclinical prototype device.

Methods.

Kidney pairs were recovered uninjured (as live-donor nephrectomy) and perfused consecutively. Pig kidneys (n = 10) were allocated to either NMP with URC (n = 5) or NMP with volume replacement (n = 5). Cold ischemia time was either 2 or 27 hours for the first or second perfusion (URC or UR) of a kidney pair. An autologous blood-based perfusate, leukocyte-filtered, was used and NMP performed up to 24 hours. Perfusion parameters, biochemistry/metabolic parameters were monitored and samples collected.

Results.

Physiological mean arterial pressures and flows were achieved in both groups but were sustainable only with URC. Significantly higher arterial flow was observed with URC (326.7 ± 1.8 versus 242.5 ± 14.3 mL/min, P = 0.001). Perfusate sodium levels were lower with URC, 129.6 ± 0.7 versus 170.3±2.7 mmol/L, P < 0.001). Stable physiological pH levels were only observed with URC. Perfusate lactate levels were lower with URC (2.2 ± 0.1 versus 7.2 ± 0.5 mmol/L, P < 0.001). Furthermore, the hourly rate of urine output was lower with URC and closer to physiological levels (150 versus 548 mL/h, P = 0.008). Normothermic kidney perfusion with URC was associated with longer achievable durations of perfusion: the objective in all experiments was a 24-hour perfusion, but this was not achieved in every case. The mean perfusions were 17.3 ± 9.2 hours with URC versus 5.3 ± 1.3 hours NMP with UR; P = 0.02. There appeared to be no differences in baseline tubular condition with and without URC.

Conclusions.

URC facilitates long-term kidney NMP in a porcine model. Perfusate homeostasis and stability of renal arterial flow throughout the perfusion period was only achievable with URC, independent of cold ischemia time duration.
Upper Vertical Spatial Neglect With A Right Temporal Lobe Stroke
Authors: Morris Michael , Mańkowska Aleksandra , Heilman Kenneth M.
Published: March 2020

Individuals with a hemispheric infarction often reveal inattention to, or neglect of, contralesional lateral space (ie, hemispatial neglect). Individuals with a bilateral ventral temporal-occipital lesion have been shown to demonstrate upper vertical neglect, and those with a bilateral parietal-occipital lesion have been shown to demonstrate lower vertical neglect. However, to our knowledge, there have been no reports of individuals with vertical neglect from a unilateral hemispheric lesion. We report on a 72-year-old, right-handed male who developed transient left hemiparesis. On examination, he had left facial weakness and he bisected horizontal lines to the left of the midline (ie, ipsilesional neglect). In addition, on a line bisection test involving nine vertical line bisections, he demonstrated downward deviation in the majority of the trials; healthy individuals deviate upward. On brain imaging, our patient revealed a cerebral infarction, primarily affecting the right temporal lobe; the temporal lobes contain the ventral attentional network that allocates attention upward. There is also some evidence that, whereas the right hemisphere mediates attention upward, the left mediates attention downward. Therefore, injury to the right temporal lobe may account for our patient’s upward neglect with downward deviation. However, further studies are needed to better understand the pathophysiology of vertical neglect.
Uncovering complex central autonomic networks at rest: a functional magnetic resonance imaging study on complex cardiovascular oscillations
Authors: Valenza Gaetano , Passamonti Luca , Duggento Andrea , Toschi Nicola , Barbieri Riccardo
Published: March 2020

This study aims to uncover brain areas that are functionally linked to complex cardiovascular oscillations in resting-state conditions. Multi-session functional magnetic resonance imaging (fMRI) and cardiovascular data were gathered from 34 healthy volunteers recruited within the human connectome project (the ‘100-unrelated subjects' release). Group-wise multi-level fMRI analyses in conjunction with complex instantaneous heartbeat correlates (entropy and Lyapunov exponent) revealed the existence of a specialized brain network, i.e. a complex central autonomic network (CCAN), reflecting what we refer to as complex autonomic control of the heart. Our results reveal CCAN areas comprised the paracingulate and cingulate gyri, temporal gyrus, frontal orbital cortex, planum temporale, temporal fusiform, superior and middle frontal gyri, lateral occipital cortex, angular gyrus, precuneous cortex, frontal pole, intracalcarine and supracalcarine cortices, parahippocampal gyrus and left hippocampus. The CCAN visible at rest does not include the insular cortex, thalamus, putamen, amygdala and right caudate, which are classical CAN regions peculiar to sympatho-vagal control. Our results also suggest that the CCAN is mainly involved in complex vagal control mechanisms, with possible links with emotional processing networks.