bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal Factors Associated With Infant Neurodevelopment in HIV-Exposed Uninfected Infants
Authors: Alcaide Maria L , Rodriguez Violeta J , Abbamonte John M , Ramlagan Shandir , Sifunda Sibusiso , Weiss Stephen M , Peltzer Karl , Jones Deborah L
Published: October 2019

Background

This study evaluated maternal factors associated with infant neurodevelopmental outcomes among HIV-exposed uninfected (HEU) infants in rural South Africa. This study followed pregnant women living with HIV pre- and postpartum and evaluated sociodemographic factors, use of antiretrovirals (ARVs), and mental health factors as predictors of HEU infant developmental outcomes (cognitive, receptive, and expressive communication, fine and gross motor skills).

Methods

Participants were 80 mother–infant dyads. Mothers were assessed during pregnancy, and HEU infant development was assessed at a mean (SD) of 13.36 (1.89) months of age.

Results

Women were an average (SD) of 28.9 (5.2) years of age, and infants were on average 13.4 (1.9) months old. An analysis of covariance indicated that infants whose mothers had ARV detected in dry blood spots at 32 weeks of pregnancy had lower functioning scores in the cognitive domain than those with undetected ARV (n = 14; M, 15.3 vs 17.2; P = .048). Antenatal physical intimate partner violence was also associated with delayed cognitive functioning (F (1, 74), 4.96; P = .029).

Conclusions

This study found risks for delayed infant cognitive development to be associated with the use of ARV during pregnancy and intimate partner violence, although findings merit replication due to the low sample size. Given the growing number of HEU infants, the necessity to better understand the potential toxicity of ARV exposure in utero is apparent. Similarly, the need for preventing intimate partner violence and screening for, and managing, developmental delays among these infants is increasing.
Implementation of amplitude-integrated electroencephalography in tertiary Canadian Neonatal Intensive Care Units—a longitudinal study
Authors: Grass Beate , Crosdale Blondel , Keyzers Matthew , Deshpande Poorva , Hahn Cecil , Ly Linh G , McNamara Patrick J
Published: October 2019

Aim

To investigate the implementation of amplitude-integrated electroencephalography (aEEG) as bedside monitoring tool of cerebral function in tertiary Canadian Neonatal Intensive Care Units (NICU) over the past decade.

Methods

Longitudinal study consisting of online surveys of neonatologists on the use of aEEG in 2009 and 2018.

Results

The response rate to the survey was 72 of 149 (49%) in 2009 and 18 of 30 (60%) in 2018, respectively. aEEG has been implemented in almost all (2009: 62.5%; 2018: 94%) tertiary Canadian NICUs. Two-thirds (2009: 67%; 2018: 71%) of the respondents considered information from aEEG tracing helpful in clinical practice. The main indications for aEEG were term neonates with hypoxic ischemic encephalopathy (2009 and 2018: 76%) and seizure detection/surveillance (2009: 88%; 2018: 94%). Teaching on aEEG has been implemented for neonatologists (2018: 100%) and health care providers (2018: 50%) in tertiary Canadian NICUs but there is a lack of standardization of training. Use of aEEG in preterm neonates (2009: 37%, 2018: 33%) and application of aEEG in research (18% reported occasional use) is less common.

Conclusion

aEEG is well established in tertiary Canadian NICUs to monitor cerebral function and detect seizure activity. There is a need to develop formalized aEEG training programs and methods to assess competence. Further implementation of aEEG in preterm neonates and research is desirable.
Why Do Firms Hold Cash? Evidence from Demographic Demand Shifts
Authors: Cunha Igor , Pollet Joshua
Published: October 2019

We exploit variation in demand induced by demographics to provide causal evidence of the precautionary motive of cash holdings. We show that firms significantly increase their cash levels in response to exogenous increases in investment opportunities. We also provide novel evidence of the dynamics of accumulation and use of cash. Financially constrained firms build their cash reserves using internal sources. Consequently, they start saving earlier and keep high cash levels longer. Unconstrained firms rely on external financing to both invest and build cash reserves, requiring them to save less and allowing them to incur lower costs of carry.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
CALIBRATION OF A TABLETOP CONFOCAL MICROBEAM X-RAY FLUORESCENCE SPECTROMETER FOR A QUANTITATIVE DEPTH PROFILES EVALUATION
Authors: Prokeš Radek , Trojek Tomáš
Published: October 2019

Confocal micro-beam X-ray fluorescence analysis (confocal micro-XRF) is a non-destructive analytical tool for investigation of sample composition that enables acquiring three-dimensionally resolved information. This work describes a calibration procedure of a laboratory confocal micro-XRF setup, which leads to determination of its characteristic parameters. The calibration is performed using a tabletop confocal micro-XRF spectrometer designed recently at the Czech Technical University in Prague. The calibration procedure performed within this work comprises the essential steps of the setup characterization: excitation spectrum calculation, experimental determination of energy-dependent confocal volume size and integral sensitivity and calculation of the spectrometer sensitivity function. The results of the setup calibration will be used for development of a procedure enabling quantitative evaluation of the measured depth profiles.
The Importance of Lobbying to Advance Health and Science Policy
Authors: Willson Peters D.
Published: October 2019

Government funding and policies are critical to academic medicine. Publicfunds sustain the education, research, and patient care missions of medical schools and teaching hospitals, and regulations govern the fulfillment of those missions. Consequently, both individuals and institutions often need to engage with those who develop these policies, including through lobbying. Lobbying fulfills a constitutionally protected right to petition the government for a redress of grievances, despite perceptions that it is instead only back-room dealing and insider influence. As an important part of the system of government in the United States, lobbying is subject to complex regulations, and failure to comply can result in substantial penalties, particularly for tax-exempt entities, of which almost all medical schools and the large majority of teaching hospitals are. In this Invited Commentary, the author briefly summarizes these regulations to complement the article in this issue by Lynch and colleagues. He then argues that while regulatory compliance is essential, it is not the same as lobbying effectively. For individual academic researchers to do that involves a number of considerations, including whether to coordinate their efforts with those of their institution to leverage the expertise and resources of the institution, to maximize their chances for success with policymakers.
Intraoperative Capsule Rupture, Postoperative Chemotherapy, and Survival of Women With Stage I Epithelial Ovarian Cancer
Authors: Matsuo Koji , Machida Hiroko , Yamagami Wataru , Ebina Yasuhiko , Kobayashi Yoichi , Tabata Tsutomu , Kaneuchi Masanori , Nagase Satoru , Enomoto Takayuki , Mikami Mikio
Published: October 2019

OBJECTIVE:

To examine the incidence and prognostic effects of intraoperative capsule rupture and to assess the effectiveness of postoperative chemotherapy for intraoperative tumor rupture in apparent stage I epithelial ovarian cancer.

METHODS:

This is a society-based retrospective observational study in Japan that examined 15,163 women with stage IA-IC1 epithelial ovarian cancer who underwent primary surgical treatment between 2002 and 2015. Associations between intraoperative capsule rupture and cause-specific survival, and between postoperative chemotherapy and cause-specific survival among intraoperatively ruptured cases were examined by histology type (clear cell n=6,107, endometrioid n=3,910, mucinous n=3,382, and serous n=1,764).

RESULTS:

Clear cell histology had the highest risk of intraoperative capsule rupture (57.3%), followed by endometrioid (48.8%), serous (41.8%), and mucinous (32.0%) histologies (P<.001). On multivariable analysis, clear cell type exhibited the largest effect of intraoperative capsule rupture on cause-specific survival (adjusted hazard ratio [HR] 1.99, 95% CI 1.45–2.75), followed by serous (adjusted HR, 1.61, 95% CI 0.84–3.11), mucinous (adjusted HR 1.28, 95% CI 0.79–2.09), and endometrioid (adjusted HR, 1.14, 95% CI 0.64–2.01) tumors. Postoperative chemotherapy for intraoperatively ruptured cases did not improve cause-specific survival in any histologic types in multivariable analysis: clear cell, adjusted HR 0.86, 95% CI 0.56–1.31; serous, adjusted HR 1.08, 95% CI 0.42–2.74; mucinous, adjusted HR 1.11, 95% CI 0.55–2.27; and endometrioid, adjusted HR 2.81, 95% CI 0.85–9.30 (all, P>.05). In the cohort-level analysis of ruptured cases (n=7,227), postoperative chemotherapy use has significantly decreased in mucinous (16.3% relative decrease), endometrioid (13.1% relative decrease), and clear cell (9.3% relative decrease) (all, P<.05); but, the cohort-level 5-year cause-specific survival rate did not change over time (all, P>.05).

CONCLUSION:

Among apparent stage I epithelial ovarian cancer, the clear cell type possesses a disproportionally high risk of capsule rupture during adnexectomy and is associated with the most adverse effect on survival. A decrease in the use of postoperative chemotherapy for intraoperatively ruptured cases in Japan is likely the result of increasing awareness of the absence of survival benefits.
Decreasing Opioid Use Postpartum
Authors: Rogers Rebecca G. , Nix Michael , Chipman Zachary , Breen Michael , Dieterichs Chad , Nutt Stephanie , Moxham Jamie , Chang Patrick , Rathouz Paul J. , Robertson Henry , Young Amy
Published: October 2019

OBJECTIVE:

To estimate the effects of an inpatient initiative to decrease opioid use among women admitted to labor and delivery.

METHODS:

We created a multimodal pain power plan with standard therapeutic postpartum activity goals rather than pain goals, tiered order sets with scheduled administration of nonsteroidal antiinflammatory drugs (NSAIDs), and embedded changes into the electronic health record. Before the multimodal pain power plan launch, pain was assessed on a 10-point scale; women received NSAIDs for pain levels of 3 or less and opioids for pain levels higher than 3. For this analysis, we included women who delivered at 5 hospitals in the 10 months before and 12 months after the multimodal pain power plan launch. Women with prior substance use disorder or complicated deliveries were excluded and we stratified analyses into women who delivered vaginally compared with by cesarean. Opioid use was converted to morphine milligram equivalent (MME). Women rated pain control in 24-hour blocks using individually ascertained cutoffs. A multivariable regression analysis was performed, and adjusted odds ratios are reported.

RESULTS:

We compared the 6,892 women who delivered 10 months before the pain power plan launch to the 7,527 who delivered in the 12 months after the launch. The mean cohort age was 29.6±6.0 years; the majority (75%) were white. Risk of opioid use decreased by 26% among women who delivered vaginally (risk ratio [RR] 0.74; 95% CI [0.68, 0.81]) and 18% among women who delivered by cesarean (RR 0.82; 95% CI [0.72, 0.92]). Among women who received opioids, mean MME use decreased 21% (RR 0.79; 95% CI [0.70, 0.88]) and 54% (RR 0.46; 95% CI [0.35, 0.61]) in the vaginal and cesarean delivery groups, respectively. Fewer women reported acceptable pain levels, with decreases of 82–69% (P<.01) and 82–74% (P<.01) in the vaginal and cesarean delivery groups, respectively. Within the postlaunch cesarean delivery group, women also reported that they were less likely to have their pain well controlled on the Hospital Consumer Assessment of Healthcare Providers and Systems questionnaires (82% vs 62%,P<.01).

CONCLUSION:

A standardized multimodal pain power plan reduced opioid use among a large cohort of women admitted to labor and delivery in Central Texas. Despite meeting functional goals, some women reported increased pain during their hospital stay.
Venous involvement in inflammatory disorders
Authors: Seyahi Emire
Published: October 2019

Purpose of review

To review the association of venous thrombosis and inflammatory disorders.

Recent findings

Various systemic inflammatory diseases of which Behçet's syndrome is the prototype are associated with an increased risk of venous thrombosis. Recent data indicate that venous wall thickness is increased among Behçet's syndrome patients with no history of venous thrombosis and thrombosis in Behçet's syndrome could be a unique model of inflammation-induced thrombosis. Patients with inflammatory bowel disease (IBD) have a two to three time-fold increased risk of developing thromboembolic complications compared with general population. The risk of venous thrombosis is increased after surgical interventions and is higher in ulcerative colitis compared with Crohn's disease. Despite similarities with Behçet's syndrome, anticoagulation is advised as the main treatment in IBD, while there is uncertainty about the duration of antithrombotic prophylaxis. Antineutrophil cytoplasmic antibody-associated vasculitides and ankylosing spondylitis are also other inflammatory disorders associated with a thrombotic risk.

Underlying mechanisms of venous thrombosis in inflammatory disorders are not clearly understood. How we might prevent thrombosis, should we screen asymptomatic patients, what should we use for the treatment (immunosuppression or anticoagulation or both) and what should be the duration of this treatment also need to be addressed. Finally, the link between inflammation and thrombosis should be more intensively studied.
Impact of Increased Intracranial Pressure on Pupillometry: A Replication Study
Authors: Al-Obaidi Sameer Z. , Atem Folefac D. , Stutzman Sonja E. , Olson DaiWai M.
Published: October 2019

Objectives:

In a diverse, multicenter population, to confirm or refute the conclusions that pupillary light reflex changes are associated with increased intracranial pressure.

Design:

Replication study.

Patients:

Within the Establishing Normative Data for Pupillometer Assessments in Neuroscience Intensive Care registry there were 273 patients (16,221 pupillary observations) that included both intracranial pressure and pupillometry values.

Measurements and Main Results:

To evaluate findings by the previous author, we explored for differences among measures of the pulmonary light reflex obtained from automated pupillometry with ICP values dichotomized as < 15 mm Hg (normal) versus ≥ 15 mm Hg (elevated). Analysis of t-test indicates statistically significant differences for all right and left mean pupilometer values, except right latency (p = 0.3000) and repeated measure mixed model (p = 0.0001). In the setting of increased intracranial pressure, mean pupilometer values were lower for both left and right eyes comparing to normal intracranial pressure, except right neurologic pupil index (3.98, 3.92;p = 0.0300) and left latency (0.27, 0.25; p < 0.0001).

Conclusions:

Our findings confirm and extend those of McNett et al Worsening measures of the pupillary light reflex using automated pupillometry are associated with elevated intracranial pressure.
Neurocritical Care for Extracorporeal Membrane Oxygenation Patients
Authors: Cho Sung-Min , Farrokh Salia , Whitman Glenn , Bleck Thomas P. , Geocadin Romergryko G.
Published: October 2019

Objectives:

To review the neurocritical care aspects of patients supported by extracorporeal membrane oxygenation, including cerebral physiology, neurologic monitoring, use of sedatives and anti-seizure medications, and prevalence and management of extracorporeal membrane oxygenation associated brain injury.

Data Sources:

PubMed database search using relevant search terms related to neurologic complications, neurocritical care management, and brain injury management in patients with extracorporeal membrane oxygenation.

Study Selection:

Articles included original investigations, review articles, consensus statements and guidelines.

Data Extraction:

A detailed review of publications performed and relevant publications were summarized.

Data Synthesis:

We found no practice guidelines or management strategies for the neurocritical care of extracorporeal membrane oxygenation patients. Such patients are at high risk for hypoxic-ischemic brain injury, intracranial hemorrhage, cerebral edema, and brain death. Improving clinical outcomes will depend on better defining the neurologic complications and underlying pathophysiology that are specific to extracorporeal membrane oxygenation. Currently, insufficient understanding of the pathophysiology of neurologic complications prevents us from addressing their etiologies with specific, targeted monitoring techniques and interventions.

Conclusions:

A large knowledge gap exists in our understanding and treatment of extracorporeal membrane oxygenation-related neurologic complications. A systematic and multidisciplinary approach is needed to reduce the prevalence of these complications and to better manage the neurologic sequelae of extracorporeal membrane oxygenation in a way that will improve patient outcomes.
Parents' Consumer Preferences for Early Childhood Behavioral Intervention in Primary Care
Authors: Riley Andrew R. , Walker Bethany L. , Wilson Anna C. , Hall Trevor A. , Stormshak Elizabeth A. , Cohen Deborah J.
Published: October 2019

Objective:

Early childhood parenting interventions are increasingly delivered in primary care, but parental engagement with those interventions is often suboptimal. We sought to better understand parents' preferences for the content and delivery method of behavioral health guidance in pediatric primary care and to determine the relationship of those preferences with demographic characteristics, child behavior problems, and parenting style.

Methods:

Participants were 396 parents of young children recruited from primary care offices. We collected measures of parental preferences (including behavioral topics, intervention strategies, and methods of delivery) for behavioral intervention in primary care, child behavior symptoms, parenting style, and demographic characteristics. Descriptive statistics were used to identify parents' most preferred behavioral topics and intervention delivery methods. We used a hierarchical regression approach to determine whether parenting style predicted parents' preferences beyond demographic and child-level factors.

Results:

Nearly all parents (96%) endorsed a behavioral topic (e.g., aggression) as important. Most preferred to receive intervention during routine medical appointments. Child behavior problems correlated with parents' overall interest in behavioral guidance, but clinically significant symptoms did not differentiate interest in any single topic. Socioeconomic factors and negative parenting practices predicted some parental preferences. Notably, lax parenting generally predicted higher interest in behavioral intervention, whereas hostile and physically controlling parenting predicted lower interest.

Conclusion:

Most parents are interested in behavioral guidance as part of primary care, but their preferences for the content and delivery of that guidance vary by known socioeconomic, child, and parenting risk factors. Tailoring intervention to parents' preferences may increase engagement with available interventions.
Should We Judge Stroke Risk by Static or Dynamic Risk Scores? A Focus on the Dynamic Nature of Stroke and Bleeding Risks in Patients With Atrial Fibrillation
Authors: Domek Magdalena , Gumprecht Jakub , Mazurek Michał , Chao Tze-Fan , Lip Gregory Y. H.
Published: October 2019

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and a major risk factor for stroke. The number of patients with AF is predicted to increase in the next few decades. AF has also negative impact on quality of life as well as it significantly increases the risk of cardiovascular disease and overall mortality. Because the stroke is a pivotal outcome of AF, its prevention with the use of anticoagulation therapy constitutes an important component of AF management. The decision on oral anticoagulants' prescription should be based on appropriate risk stratification to allow for comprehensive assessment of benefit/hazard ratio of stroke and bleeding along with patients' preference. Several risk scores for stroke and bleeding as well as for stroke and systemic embolism have been developed, mainly in patients on vitamin K antagonists. AF guidelines stress the need for repetitive evaluation of thromboembolic and bleeding risks to tailor optimal AF management. Indeed, risk is not a static “one off” process and it should be adjusted for dynamic nature of risk factors. However, most risk scores are calculated according to baseline characteristics of patients, but the older the patients get, the more comorbidities they acquire, which influences stroke risk significantly. Hence, the default management of every patient with AF should include a regular reassessment of stroke and bleeding risk factors.
Ginsenoside Re Preserves Cardiac Function and Ameliorates Left Ventricular Remodeling in a Rat Model of Myocardial Infarction
Authors: Yu Yonghui , Sun Jinghui , Liu Jiangang , Wang Peili , Wang Chenglong
Published: October 2019

Ginsenoside Re, an herbal ingredient from ginseng, has been demonstrated to protect the heart from various cardiovascular diseases. In this study, we investigated the protective effects and mechanisms of ginsenoside Re (Gin-Re) on cardiac function and left ventricular remodeling in a rat model of myocardial infarction (MI). After ligating the left anterior descending coronary artery, Wistar rats were treated with Gin-Re (135 mg/kg) by gavage everyday for 4 weeks. Serological detection showed that Gin-Re significantly inhibited myocardial injury and attenuated oxidative stress in MI rats. Echocardiographic observation showed that Gin-Re significantly improved cardiac function and prevented left ventricular dilatation induced by MI. Pathological observation found that Gin-Re significantly decreased interstitial fibrosis in the left ventricle of MI rats. Compared with the MI group, Gin-Re treatment promoted AMPKα phosphorylation, decreased TGF-β1 expression, and attenuated Smad2/3 activation. After Gin-Re treatment, the phosphorylation of FAK, PI3K p110α, and Akt was enhanced in MI rats, while PI3K p110β showed no difference compared with the MI group. These results indicate that Gin-Re may improve MI-induced cardiac dysfunction and mitigate ventricular remodeling through regulation of the AMPK/TGF-β1/Smad2/3 and FAK/PI3K p110α/Akt signaling pathways.
Hospitalized patients quantify verbal pain intensity descriptors: methodological issues and values for 26 descriptors
Authors: Schlaeger Judith M. , Cain Kevin C. , Myklebust Erin K. , Powell-Roach Keesha L. , Dyal Brenda W. , Wilkie Diana J.
Published: October 2019

Patients often tell others about their pain using their own verbal descriptors of pain intensity, but the meaning of this pain language is not universally evident, which could contribute to misinterpretation about pain severity. The study purpose was to discover the intensity values of verbal pain intensity descriptors. The 248 randomly selected inpatients used a visual analogue scale to assign a value to each of 26 pain intensity descriptors. Each participant completed 36 randomly ordered visual analogue scales, 10 of which were replications. Except for descriptors with medians close to 0 or 100 mm, there was large, across-person variability for the descriptors. For example, medians ± SD for some exemplar descriptors were no pain 0.7 ± 2.4; mild 16.2 ± 12.2; discomforting 31.3 ± 22.2; distressing 55.3 ± 24; horrible 87.8 ± 13.6; and excruciating 94.6 ± 9.3. Test–retest reliability indicated small within-person variability on scores assigned to each descriptor. Thirteen descriptors showed some statistically significant but rather small effects of presentation order. Findings contribute estimates for the magnitude of pain represented by each of the 26 descriptors. Clinicians, text data miners, and researchers should consider these values as they interpret the meaning of the descriptors that they hear in daily practice or research settings or that they find in electronic health records, email messages, or social media posts. Despite the wide variability in the magnitude of each descriptor, findings provide insights about the intensity of pain when individuals use verbal pain intensity descriptors in conversations, social media, or clinical encounters.
Genetics of syndromic and nonsyndromic aortopathies
Authors: Rigelsky Christina M. , Moran Rocio T.
Published: October 2019

Purpose of review

To review the literature and provide a summary of management of syndromic and nonsyndromic aortopathies.

Recent findings

The number of newly identified genetic causes for aortopathies have continued to increase over the past 10 years. The number of reported individuals with most hereditary aneurysm genes is small but increasing with more publications focusing describing the natural history caused by each gene.

Aortopathy can present as an isolated finding or present as part of a larger genetic syndrome. Advances in genetic testing technology has shed light on the increasing importance of molecular diagnostics in the evaluation and management of patients with hereditary aortic disease. Molecular diagnostics and family phenotyping can aide in the diagnosis and management of pediatric patients with aortic disease.
Linking innate immunity and chronic antibody-mediated allograft rejection
Authors: Gill Ronald G. , Lin Christine M.
Published: October 2019

Purpose of review

To summarize recent findings linking donor-specific antibodies with innate immunity resulting in chronic allograft rejection.

Recent findings

Studies in recent years highlight the significance of donor-specific antibodies (DSA) in both acute and chronic allograft rejection. Since chronic rejection is the leading cause of graft failure, this review centers on the contribution of three areas of innate immunity of particular recent focus: complement, NK cells, and macrophages. Recent advances indicate the diverse roles that complement components play both in directly initiating allograft injury and indirectly by contributing to enhanced alloreactivity. NK cells also have emerged as an additional innate response that directly links DSA with chronic graft injury. Finally, recent studies identify alternatively activated macrophages as an additional arm of innate immunity contributing to chronic allograft rejection.

Chronic allograft rejection involves a significant contribution of DSA and differing pathways of the innate immune system. However, key issues remain unresolved. First, it is not always clear which of these varied sources of innate immunity contributing to chronic rejection may be antibody dependent. Moreover, it is not yet clear if these innate pathways represent independent routes that contribute to chronic rejection or rather act in concert to mediate allograft injury.
The Role of Surgery in High-risk Neuroblastoma
Authors: Ryan Anne L. , Akinkuotu Adesola , Pierro Agostino , Morgenstern Daniel A. , Irwin Meredith S.
Published: October 2019

Although intensive multimodal treatment has improved outcomes for patients with high-risk neuroblastoma, the specific role of primary tumor resection remains controversial. Many studies have been designed to determine whether the extent of surgical resection impacts survival; however, these reports have demonstrated conflicting results. There is also ongoing debate regarding the timing of primary tumor resection, with subtle differences in the approach between the large pediatric oncology cooperative consortia. Most of the published literature to date has been approached from a surgical viewpoint. Although most evidence supports surgery as part of the local control approach for high-risk neuroblastoma, recommendations for timing and extent of surgical resection are not consistent. This review summarizes our current understanding from the perspectives of both the pediatric oncologist and pediatric surgeons and discusses how the objectives of neuroblastoma primary surgical resection are different from that of other malignancies. Furthermore, this commentary will address how retrospective surgical outcome data may be interpreted in the setting of modern era high-risk neuroblastoma treatment.
Prognostic Factors of ICU Mortality in Pediatric Oncology Patients With Pulmonary Complications
Authors: Kim Kyunghoon , Kim Seongkoo , Lee Jae Wook , Yoon Jong-Seo , Chung Nack Gyun , Cho Bin
Published: October 2019

Objective:

This study aimed to determine prognostic factors associated with mortality in pediatric oncology patients admitted to the intensive care unit (ICU) with pulmonary complications.

Materials and Methods:

This retrospective cohort study included patients 21 years of age with underlying oncologic diseases admitted to the ICU of a Korean Tertiary Referral Hospital with pulmonary complications from April 2009 to March 2017. Patients admitted for perioperative management or nonpulmonary complications were excluded. Demographic, laboratory, and clinical parameters (eg, Glasgow Coma Scale [GCS], pediatric Sequential Organ Failure Assessment [pSOFA], and Pediatric Logistic Organ Dysfunction [PELOD] scores) were reviewed.

Results:

Overall, 110 patients (62 male, 56.3%) with a median age of 13 years (interquartile range: 8 to 16 y) were studied. The median ICU stay was 8 days (interquartile range: 4.25 to 16 d). Forty-five (40.9%) patients required mechanical ventilation. The overall mortality rate was 59.1% (65/110 patients). A multivariate logistic regression identified a low GCS score, peripheral oxygen saturation/fraction of inspired oxygen ratio, and hematocrit and increased total bilirubin as significantly associated with increased mortality. The pSOFA and PELOD scores on days 1 and 3 postadmission predicted in-ICU mortality, with corresponding areas under the curve of 0.80/0.76 and 0.87/0.83, respectively.

Conclusion:

Several clinical scores and factors may predict mortality in pediatric oncology patients with pulmonary complications.
Promoting Community Awareness of Lung Cancer Screening Among Disparate Populations
Authors: Williams Lovoria B. , Looney Stephen W. , Joshua Thomas , McCall Amber , Tingen Martha S.
Published: October 2019

Background

Lung cancer is the no. 1 cause of cancer death in the United States. Racial/ethnic minority and medically underserved populations suffer higher mortality than whites. Early detection through uptake of low-dose computed tomography (LDCT) among screening-eligible adults may mitigate high mortality. However, nearly 5 years since the publication of the US Preventive Services Task Force lung cancer screening guideline, population awareness of LDCT is low, and only 4% of screening-eligible adults have undergone screening.

Objective

This project used an education intervention to change participants’ knowledge, attitudes, and beliefs about cancer risk factors and lung cancer and to connect eligible individuals to LDCT screening and tobacco cessation services.

Interventions/Methods

Community-engaged strategies were used to deliver a 4-week educational program in 13 community sites. Trained community health workers delivered the intervention. The intervention was guided by the Health Belief Model. Data were collected by survey to 481 participants; 93% were African American, the majority was female (73.1%), mean age was 58.3 (SD, 10.9) years.

Results

There were knowledge increase regarding lung cancer screening (P = .001), a significant decrease in Perceived Severity and Perceived Barriers subscales (P = .001), and an overall increase in response to Perceived Benefits of lung cancer screening and Self-efficacy (P = .001). Fifty-four percent of tobacco users engaged in cessation; 38% of screening-eligible participants underwent LDCT screening.

Conclusions

Community health workers are effective in increasing awareness of lung cancer screening and affecting behavior change among disparate populations.

Implications for Practice

Community health workers may have a clinical role in LDCT shared decision making.
Potent nonopioid antinociceptive activity of telocinobufagin in models of acute pain in mice
Authors: Feitosa Geissy I.M.C. , Carvalho Isabella F. , Coelho Edivaldo B.S. , Monteiro Marla R.B. , Medeiros Rafael L. , Carvalho Ellaine D.F. , A. Silva Paulo T. , Carvalho Dóris M.F. , Uchoa Daniel E.A. , Silveira Edilberto R. , Santos Cláudia F. , Nascimento Nilberto R. , Carvalho Maria-Denise F. , Cardi Bruno A. , Carvalho Krishnamurti M.
Published: October 2019

Introduction:

In recent decades, several researches have been conducted in search of new analgesics that do not present the side effects of opioids. In this context, animal venoms contain natural painkillers that have been used for the development of new analgesics.

Objective:

The aims of this study were to evaluate the antinociceptive effects of telocinobufagin (TCB), a bufadienolide isolated from Rhinella jimi venom, in murine acute pain models, and to verify the participation of the opioid system in these effects.

Methods:

TCB was purified from R. jimi venom by high-performance liquid chromatography, and its structure was confirmed by spectrometric techniques. TCB was administered intraperitoneally (i.p.) (0.062, 0.125, 0.25, 0.5, and 1 mg·kg−1) and orally (p.o.) (0.625, 1.125, 2.5, 5, and 10 mg·kg−1) in mice, which were then subjected to pain tests: acetic acid–induced writhing, formalin, tail-flick, and hot-plate. Involvement of the opioid system in TCB action was evaluated by naloxone i.p. injected (2.5 mg·kg−1) 20 minutes before TCB administration. In addition, the TCB action on the μ, δ, and κ opioid receptors was performed by radioligand binding assays.

Results:

In all the tests used, TCB showed dose-dependent antinociceptive activity with more than 90% inhibition of the nociceptive responses at the doses of 1 mg·kg−1 (i.p.) and 10 mg·kg−1 (p.o.). Naloxone did not alter the effect of TCB. In addition, TCB did not act on the μ, δ, and κ opioid receptors.

Conclusion:

The results suggest that TCB may represent a novel potential nonopioid therapeutic analgesic for treatment of acute pains.
Emotions in Social Relationships and Their Implications for Health and Disease: Introduction to the Special Issue of Psychosomatic Medicine
Authors: Uchino Bert N. , Eisenberger Naomi I.
Published: October 2019

Social relationships and emotions are important to health and disease, but research in this area has largely progressed along parallel and distinct historical paths. These areas are critically linked because relationships are among the most powerful elicitors of health-relevant emotions and emotions can in turn influence relationships for better or worse. Conceptually, relationships and emotions can have mediational, reciprocal, and interactive influences on health outcomes, associations that seem dependent on the broader sociocultural context. The articles in this issue of Psychosomatic Medicine are based on a joint meeting of the American Psychosomatic Society and the Society for Affective Science titled “Emotions in social relationships: implications for health and disease.” Recent research and conceptual models that fall at the interface of relationships, emotions, and health are highlighted in this special issue. Future work that capitalizes on these links will be critical if this area is to fulfill its potential in terms of new scientific insights and intervention opportunities.
Dabigatran Reversal With Idarucizumab in Patients Requiring Urgent Surgery
Authors: Levy Jerrold H. , van Ryn Joanne , Sellke Frank W. , Reilly Paul A. , Elsaesser Amelie , Glund Stephan , Kreuzer Jörg , Weitz Jeffrey I. , Pollack Charles V.
Published: October 2019

Objective:

To further examine anticoagulation reversal and clinical outcomes in dabigatran treated patients requiring urgent surgery or procedural interventions.

Background:

Idarucizumab, a humanized monoclonal antibody fragment, reverses dabigatran anticoagulation.

Methods:

Data from surgical and procedural patients in RE-VERSE AD, a multicenter, open-label, single-arm, prospective cohort of dabigatran reversal were evaluated. A total of 202 patients in this group received 5 g of idarucizumab before surgery or procedures.

Results:

The interventions included 49 abdominal, 45 orthopedic, 34 vascular, 8 neurologic, and 4 genitourinary surgical procedures, or 29 catheter-based cases, 20 cases for drainage, and 8 diagnostic procedures. Five patients did not undergo their intended intervention after receiving idarucizumab. Complete reversal of the dabigatran anticoagulant effect occurred within minutes in almost all patients, with normal hemostasis in more than 91% of patients. The median time from the first vial of idarucizumab to surgery or procedures was less than 2 hours in all groups except neurosurgery, where it was 3.3 hours. Fresh frozen plasma and packed red cells were the most frequently transfused blood products. Postreversal thromboembolic events occurred in 10 (5%) patients at 30 days, 5 of whom had restarted anticoagulation before the event. Overall 30-day mortality was 12.6%. There were no serious adverse safety signals due to idarucizumab dosing.

Conclusions:

Idarucizumab facilitates management of patients requiring urgent procedures by providing rapid dabigatran reversal, and is the only agent of its class studied in surgical patients.
Autologous haematopoietic stem cell therapy for multiple sclerosis: a review for supportive care clinicians on behalf of the Autoimmune Diseases Working Party of the European Society for Blood and Marrow Transplantation
Authors: Ismail Azza , Sharrack Basil , Saccardi Riccardo , Moore John J. , Snowden John A.
Published: October 2019

Purpose of review

In this review, we summarize the recently published literature that demonstrates the efficacy and safety of autologous haematopoietic stem cell therapy (AHSCT) in multiple sclerosis (MS) and highlight the importance of supportive care required for the safe and well-tolerated delivery of AHSCT.

Recent findings

MS is an autoimmune inflammatory and degenerative disorder of the central nervous system (CNS). In the majority of patients, the illness runs a relapsing remitting course (RRMS), culminating in a secondary progressive phase with gradual accumulation of fixed disabilities. Currently available disease-modifying therapies suppress CNS inflammation but have a limited effect on preventing disease progression for which there remains no effective therapy. Over the last two decades, there has been increasing evidence that AHSCT is a highly effective therapeutic strategy for treatment-resistant inflammatory types of MS, especially RRMS. Concerns about the safety of AHSCT in MS, usually a nonlife-threatening disease, have previously limited its use. However, AHSCT can now be delivered safely with major long-term benefits because of increasing transplant centre experience, judicious patient selection and good supportive care.

MS is currently the fastest growing indication for AHSCT in Europe. Supportive care before, during and after the transplant period is key to the successful delivery of AHSCT.
A Pilot Study of Postoperative Animal Welfare as a Guidance Tool in the Development of a Kidney Autotransplantation Model With Extended Warm Ischemia
Authors: Lohmann Stine , Eijken Marco , Møldrup Ulla , Møller Bjarne K. , Hunter James , Moers Cyril , Ploeg Rutger J. , Baan Carla C. , Jespersen Bente , Keller Anna Krarup
Published: October 2019

Background.

This pilot study aimed to maintain acceptable animal welfare in the development of a porcine autotransplantation model with severe and incremental renal ischemic injury, a model for usage in future intervention studies. Secondary aims were to develop and test methods to collect blood and urine without the need to restrain or use sedative and avoid transportation to optimize welfare of the pig.

Methods.

Kidneys from 7 female pigs were subjected to incremental durations of warm ischemia (WI) 30, 45, or 75 minutes by left renal artery and vein clamping. After static cold storage, contralateral nephrectomy was performed, and the injured graft was autotransplanted and animals observed for 14 days. Animal welfare was assessed and recorded using a structured scoring sheet before and 4 days after the kidney autotransplantation. Furthermore, blood samples were drawn daily the first week and every second day the following week using a semi-central venous catheter. An ostomy bag around the genitals was tested for urine collection. Measured glomerular filtration rate was calculated using renal clearance of chromium-51-labeled ethylenediamine tetraacetic acid on day 14.

Results.

None of the 7 animals died during the follow-up. The animal welfare was moderately affected when applying 75 minutes of WI (n = 2), and for that reason WI was not further increased. Pigs with lower WI had no observed welfare issues. With 75 minutes of WI peak, plasma creatinine was 1486 and 1317 µmol/L, reached on day 4. Lowest glomerular filtration rate levels were observed in the pigs with 75 minutes of WI.

Conclusions.

WI up to 75 minutes caused the intended severely impaired renal function without significantly compromising animal welfare. Blood and urine was collected postoperatively without sedation of the pigs or use of a metabolic cage.
Cytokine Profiles in Children After Pediatric Kidney Transplantation With Acute Cellular Compared to Chronic Antibody-mediated Rejection and Stable Patients: A Pilot Study
Authors: Borsum Nadja , Verboom Murielle , Ahlenstiel-Grunow Thurid , Pape Lars
Published: October 2019

Background.

Different patterns of plasma cytokines can be expected in the case of chronic active-antibody-mediated (cAMR) and acute cellular rejection (AR) after kidney transplantation (KTx).

Methods.

IL-2, 4, 6, 10, 17A, tumor necrosis factor alpha, and interferon gamma were measured in 51 pediatric KTx recipients at time of renal biopsy (17 AR, 14 cAMR, 20 normal). Patients were divided into a training (n = 30) and a validation (n = 21) set.

Results.

IL-6 was significantly higher in AR patients and significantly lower in the case of cAMR. In children with s-creatinine increase, IL-6 values were significantly different between AR and cAMR. IL-10 levels showed similar tendencies. For IL-2, 4, 17A, tumor necrosis factor alpha, and interferon gamma, no differences were found. In the independent validation cohort, the receiver operating characteristic area under the curve for IL-6 was 0.79 and 0.70 for AR and cAMR. In children with AR, an IL-6 <1141 fg/ml, and in those with cAMR, an IL-6 >721 fg/ml was associated with a specificity of 86%/76%, a sensitivity of 71%/80%, a positive predictive value of 56%/45%, and a negative predictive value of 92%/94%.

Conclusions.

In this pilot study, the plasma IL-6 level is a promising biomarker to identify pediatric kidney transplant recipients free from AR and cAMR and might help to distinguish between both entities, whereas there is only a nonsignificant trend toward the usability of IL-10. Validation in larger cohorts in combination with other biomarkers are warranted.
Insulin-Independent Reversal of Type-1 Diabetes Following Transplantation of Adult Brown Adipose Tissue Supplemented With IGF-1
Authors: Gunawardana Subhadra C. , Piston David W.
Published: October 2019

Background.

As our previous publications show, it is feasible to reverse type 1 diabetes (T1D) without insulin in multiple mouse models, through transplantation of embryonic brown adipose tissue (BAT) in the subcutaneous space. Embryonic BAT transplants result in rapid and long-lasting euglycemia accompanied by decreased inflammation and regenerated healthy white adipose tissue, with no detectable increase in insulin. To translate this approach to human patients, it is necessary to establish practical alternatives for embryonic tissue. Adult adipose tissue transplants or BAT-derived stem cell lines alone fail to reverse T1D. A likely reason is transplant failure resulting from lack of growth factors abundant in embryonic tissue. Adding growth factors may enable transplants to survive and vascularize as well as stimulate adipogenesis and decrease inflammation in the surrounding host tissue. Previous data points to insulin like growth factor 1 (IGF-1) as the most likely candidate. Embryonic BAT abundantly expresses IGF-1, and embryonic BAT transplant recipients exhibit increased plasma levels of IGF-1. Therefore, we tested the ability of temporary administration of exogenous IGF-1 to enable adult BAT transplants to correct T1D.

Methods.

Fresh BAT from healthy adult CB7BL/6 donors were transplanted in the subcutaneous space of hyperglycemic nonobese diabetic recipients. Exogenous IGF-1 was administered daily for a week following transplant, at 100 µg/kg SC.

Results.

Adult BAT transplants with IGF-1 supplementation produced rapid long-lasting euglycemia at a 57% success rate, in contrast with no recovery in the control groups who received adult BAT alone, IGF-1 alone, or no treatment.

Conclusions.

Temporary supplementation with IGF-1 enables adult BAT transplants to correct T1D phenotypes independent of insulin, providing a possible route to translate this treatment to human patients.
Incidentally Detected Malignancies in Lung Transplant Explants
Authors: Amratia Dhruv A. , Hunt William R. , Neujahr David , Veeraraghavan Srihari
Published: October 2019

Background.

Active malignancy diagnosed within 5 years is an absolute contraindication for lung transplantation. In this study, we evaluated the rate of incidental malignancies detected in explanted lungs at our institution and assessed the posttransplant survival in patients with nonsmall cell lung cancer (NSCLC).

Methods.

A retrospective chart review of lung transplant recipients at our institution from February 1999 to June 2017 was conducted. A literature review was performed to evaluate the prevalence and survival outcomes in patients with unexpected malignancies.

Results.

From 407 patients who underwent lung transplantation, 9 (2.2%) were discovered to have malignant neoplasms. There were 3 cases of adenocarcinoma, 3 cases of adenocarcinoma in situ, 2 cases of squamous cell carcinoma, and 1 case of metastatic renal cell carcinoma. An extensive literature review found 12 case reports or case series reporting malignancy discovered at the time of lung transplantation. The overall prevalence of incidental neoplasms among 6746 recipients is around 1.5% (n = 103). The most common neoplasms discovered included adenocarcinoma (n = 56, 54%) and squamous cell carcinoma (n = 29, 28%). The overall 3-year survival was 54.4% for patients with localized NSCLC compared to 5.7% for those with nonlocalized disease.

Conclusions.

Unidentified malignancies occur despite aggressive radiographic surveillance with poor posttransplant outcomes in patients with advanced malignancy. Malignancy-related radiographic findings may be missed pretransplant secondary to architectural distortion of lung parenchyma related to end-stage lung disease or because of the critical timing of surgery when donor lungs are available.