bluuebunny/crossref_metadata_2025 huggingface dataset:
Complications of Postoperative Epidural Analgesia For Oncologic Surgery
Authors: Su Jackson , Soliz Jose M. , Popat Keyuri U. , Gebhardt Rodolfo
Published: April 2019

Objective:

The risks of epidural analgesia (EA) differ depending on the population studied. We describe our experience with postoperative EA for oncologic surgery.

Materials and Methods:

We searched our Acute Pain Medicine database for cases in which postoperative EA was used between 2003 and 2012. We used word search to identify and catalog cases of neurological changes, magnetic resonance imaging or computed tomography of the spine, electromyography studies, and neurologist or neurosurgeon consultations. Medical records of patients with documented persistent neurological deficits and patients who had spine imaging or neurology consultations were reviewed further. In addition, we cross-checked medical records with billing diagnosis codes for spinal epidural abscess or hematoma.

Results:

We reviewed 18,895 cases in which postoperative EA was used. Complications included neurological symptoms in 2436 cases (12.9%), epidural insertion site abnormalities in 1062 cases (5.6%), complete epidural catheter migration in 829 cases (4.4%), epidural replacement in 619 cases (3.3%), and inadvertent dura puncture in 322 cases (1.7%). There were 6 cases of persistent deficits of uncertain etiology, 4 deep spinal infections (1:4724), and 2 cases of catheter tip shearing. No spinal epidural hematomas were identified (95% confidence interval, 0-0.0002).

Discussion:

Our findings provide a contemporary review of some risks associated with the use of postoperative EA for patients undergoing oncologic surgery. Despite a not-uncommon incidence of neurological changes, serious complications resulting in prolonged sequelae were rare.
Activating α4β2 Nicotinic Acetylcholine Receptors Alleviates Fentanyl-induced Respiratory Depression in Rats
Authors: Ren Jun , Ding Xiuqing , Greer John J.
Published: April 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Opioid analgesics are widely used for treatment of acute, postoperative, and chronic pain. However, activation of opioid receptors can result in severe respiratory depression. There is an unmet clinical need to develop a pharmacologic therapy to counter opioid-induced respiratory depression without interfering with analgesia. Further, additional advances to confront accidental lethal overdose with the use of fentanyl and other opioids are needed. Here, the authors test the hypothesis that activation of nicotinic receptors expressed within respiratory rhythm–generating networks would counter opioid-induced respiratory depression without compromising analgesia.

Methods

Respiratory neural discharge was measured using in vitro brainstem–spinal cord and medullary slice rat preparations. In vivo, plethysmographic recording, nociception testing, and righting reflexes were used to examine respiratory ventilation, analgesia, and sedation, respectively.

Results

The administration of nicotine, selective α4β2 nicotinic receptor agonist A85380, but not α7 nicotinic receptor agonist PNU282987, reversed opioid-induced respiratory depression in neonatal pups in vitro and in vivo. In adult rats in vivo, administration of A85380 (0.03 mg/kg), but not PNU282987, provides a rapid and robust reversal of fentanyl-induced decrease in respiratory rate (93.4 ± 33.7% of control 3 min after A85380 vs. 31 ± 20.5% of control after vehicle, n = 8 each, P < 0.001), without marked side effects. The coadministration of A85380 (0.06 mg/kg) with fentanyl or remifentanil markedly reduced respiratory depression and apneas, and enhanced the fentanyl-induced analgesia, as evidenced by increased paw withdrawal latency in Hargreaves plantar test (14.4 ± 2.8 s vs. vehicle: 11.3 ± 2.4 s, n = 8 each, P = 0.013) and decreased formalin-induced nocifensive duration (2.5 ± 2.4 min vs. vehicle: 5.4 ± 2.7 min, n = 8 each, P = 0.029).

Conclusions

The novel strategy of targeting α4β2 nicotinic acetylcholine receptors has the potential for advancing pain control and reducing opioid-induced respiratory depression and overdose.
Synchrotron Radiation-Based Reconstruction of the Human Spiral Ganglion: Implications for Cochlear Implantation
Authors: Li Hao , Schart-Morén Nadine , Rohani Seyed Alireza , Ladak Hanif M. , Rask-Andersen Helge , Agrawal Sumit
Published: April 2019

Objective:

To three-dimensionally reconstruct Rosenthal’s canal (RC) housing the human spiral ganglion (SG) using synchrotron radiation phase-contrast imaging (SR-PCI). Straight cochlear implant electrode arrays were inserted to better comprehend the electro-cochlear interface in cochlear implantation (CI).

Design:

SR-PCI was used to reconstruct the human cochlea with and without cadaveric CI. Twenty-eight cochleae were volume rendered, of which 12 underwent cadaveric CI with a straight electrode via the round window (RW). Data were input into the 3D Slicer software program and anatomical structures were modeled using a threshold paint tool.

Results:

The human RC and SG were reproduced three-dimensionally with artefact-free imaging of electrode arrays. The anatomy of the SG and its relationship to the sensory organ (Corti) and soft and bony structures were assessed.

Conclusions:

SR-PCI and computer-based three-dimensional reconstructions demonstrated the relationships among implanted electrodes, angular insertion depths, and the SG for the first time in intact, unstained, and nondecalcified specimens. This information can be used to assess stimulation strategies and future electrode designs, as well as create place-frequency maps of the SG for optimal stimulation strategies of the human auditory nerve in CI.
Left Ventricular Noncompaction: Diagnostic Approach, Prognostic Evaluation, and Management Strategies
Authors: Di Fusco Stefania Angela , Lucà Fabiana , Madeo Andrea , Massimiliano Rao Carmelo , Iorio Annamaria , Rizzo Massimiliano , Dalila Luisella Delcre Sara , Colivicchi Furio , Gabrielli Domenico , Paolo Pino Giuseppe , Massimo Gulizia Michele
Published: April 2019

Left ventricular noncompaction cardiomyopathy is a heart disease with relevant potential complications including heart failure, life-threatening arrhythmias, and embolic events. In order to prevent adverse outcomes, it is crucial to appropriately recognize and manage this cardiomyopathy. In this paper, we report the main clinical presentations and imaging modalities used for diagnosis, including echocardiography and magnetic resonance imaging. We highlight the role of a comprehensive functional cardiac evaluation and the possible prognostic implications of both systolic and diastolic dysfunction. Furthermore, we summarize clinical factors and imaging findings which have prognostic significance. Finally, we discuss the main management strategies based on phenotypic expressions which are aimed at treating symptoms and preventing complications.
The Preventive Role of Angiotensin Converting Enzyme Inhibitors/Angiotensin-II Receptor Blockers and β-Adrenergic Blockers in Anthracycline- and Trastuzumab-Induced Cardiotoxicity
Authors: Blanter Julia B. , Frishman William H.
Published: April 2019

Anthracycline (doxorubicin) and trastuzumab treatments for cancer patients have been known to cause cardiotoxicity. The current recommendations for prevention of cardiac events from cancer chemotherapies are largely based on opinion. The American Society of Clinical Oncology recommends active screening and prevention of modifiable cardiovascular risk factors. The risk factors are defined as tobacco use, high blood pressure, high cholesterol, alcohol use, obesity, and physical inactivity. Beta-adrenergic blockers and angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) have been the mainstay of treatment for heart failure patients with reduced left ventricular ejection fraction for many years. This review analyzed the use of beta-adrenergic blockers and ACE inhibitors/ARBs as protection against cardiomyopathy caused by anthracyclines and trastuzumab. Although many more studies are warranted, it was concluded that the addition of a beta-blocker early in the treatment of cancer patients who are undergoing anthracycline or trastuzumab treatment can have beneficial effects in preserving left ventricular ejection fraction and preventing chemotherapy-induced cardiotoxicity. The effects are more apparent in the short term. More studies of the long-term effects are warranted, as are the additive effects of using a beta-blocker and ACE inhibitor/ARB together to prevent chemotherapy-induced cardiotoxicity.
Pregnancy Complications as a Window to Future Cardiovascular Disease
Authors: Dassanayake Maya , Langen Elizabeth , Davis Melinda B.
Published: April 2019

Pregnancy is a time of significant hemodynamic, metabolic, and hormonal stress that can unmask underlying subclinical cardiovascular abnormalities, and pregnancy-related complications may serve as early warning signs for future risk of cardiovascular disease. The increased recognition of these sex-specific risk factors could identify women who may benefit from more intensive risk factor modification to reduce morbidity and mortality later in life. In this review, we describe several pregnancy-related complications that have been associated with the risk of cardiovascular disease, including hypertensive disorders of pregnancy, gestational diabetes mellitus, preterm delivery, and pregnancy loss. Pregnancy-associated risk factors must be identified to fully assess a woman’s future cardiovascular risk and may influence strategies for risk reduction.
Myocardial Injury After Noncardiac Surgery: A Systematic Review and Meta-Analysis
Authors: Smilowitz Nathaniel R. , Redel-Traub Gabriel , Hausvater Anais , Armanious Andrew , Nicholson Joseph , Puelacher Christian , Berger Jeffrey S.
Published: April 2019

Myocardial injury after noncardiac surgery (MINS) is a common postoperative complication associated with adverse cardiovascular outcomes. The purpose of this systematic review was to determine the incidence, clinical features, pathogenesis, management, and outcomes of MINS. We searched PubMed, Embase, Central and Web of Science databases for studies reporting the incidence, clinical features, and prognosis of MINS. Data analysis was performed with a mixed-methods approach, with quantitative analysis of meta-analytic methods for incidence, management, and outcomes, and a qualitative synthesis of the literature to determine associated preoperative factors and MINS pathogenesis. A total of 195 studies met study inclusion criteria. Among 169 studies reporting outcomes of 530,867 surgeries, the pooled incidence of MINS was 17.9% [95% confidence interval (CI), 16.2–19.6%]. Patients with MINS were older, more frequently men, and more likely to have cardiovascular risk factors and known coronary artery disease. Postoperative mortality was higher among patients with MINS than those without MINS, both in-hospital (8.1%, 95% CI, 4.4–12.7% vs 0.4%, 95% CI, 0.2–0.7%; relative risk 8.3, 95% CI, 4.2–16.6, P < 0.001) and at 1-year after surgery (20.6%, 95% CI, 15.9–25.7% vs 5.1%, 95% CI, 3.2–7.4%; relative risk 4.1, 95% CI, 3.0–5.6, P < 0.001). Few studies reported mechanisms of MINS or the medical treatment provided. In conclusion, MINS occurs frequently in clinical practice, is most common in patients with cardiovascular disease and its risk factors, and is associated with increased short- and long-term mortality. Additional investigation is needed to define strategies to prevent MINS and treat patients with this diagnosis.
Angiopoietin-Like 3 Protein Inhibition: A New Frontier in Lipid-Lowering Treatment
Authors: Lang William , Frishman William H.
Published: April 2019

Angiopoietin-like 3 protein (ANGPTL3) is an inhibitor of both lipoprotein lipase and endothelial lipase in humans. Population studies indicate a relationship between loss of function mutations in ANGPTL3 and favorable reductions in triglycerides and non- high-density lipoprotein cholesterol. In addition, loss of function mutations is associated with a reduced risk of coronary artery disease. Whereas ANGPTL3’s role in human lipid metabolism has yet to be fully clarified, it is unlikely that ANGPTL3 impacts cholesterol uptake via the low-density lipoprotein-receptor, unlike the proprotein convertase subtilisin/kexin9 inhibitors. In contrast to other forms of lipid-lowering therapy, ANGPTL3 inhibition may improve insulin sensitivity. The promise of this new therapy, particularly its independence from the low-density lipoprotein-receptor, has prompted the creation of a monoclonal antibody inhibitor; evinacumab. Evinacumab has shown favorable lipid-lowering action in both human and mouse models. Efficacy trials are currently ongoing and will be completed in the near future. In addition, ANGPTL3 inhibition via an antisense oligonucleotide was performed in healthy human subjects, which resulted in a dose-dependent reduction in circulating ANGPTL3 levels and an antiatherogenic lipid profile. When tested in mouse models, administration of the antisense oligonucleotide caused a reduction in progression of atherosclerosis. Further investigation is required to evaluate the efficacy, safety and net benefit of clinical ANGPTL3 inhibition before it can be accepted into clinical practice.
Optimizing Pediatric Dosing Recommendations and Treatment Management of Antiretroviral Drugs Using Therapeutic Drug Monitoring Data in Children Living With HIV
Authors: Waalewijn Hylke , Turkova Anna , Rakhmanina Natella , Cressey Tim R. , Penazzato Martina , Colbers Angela , Burger David M. ,   on behalf of the Pediatric Antiretroviral Working Group (PAWG)
Published: April 2019

Introduction:

This review summarizes the current dosing recommendations for antiretroviral (ARV) drugs in the international pediatric guidelines of the World Health Organization (WHO), US Department of Health and Human Services (DHHS), and Pediatric European Network for Treatment of AIDS (PENTA), and evaluates the research that informed these approaches. We further explore the role of data generated through therapeutic drug monitoring in optimizing the dosing of ARVs in children.

Methods:

A PubMed search was conducted for the literature on ARV dosing published in English. In addition, the registration documentation of European Medicines Agency and the US Food and Drug Administration for currently used ARVs and studies referenced by the WHO, DHHS, and EMA guidelines were screened. Resulting publications were screened for papers containing data on the area under the concentration–time curve, trough concentration, and peak concentration. Studies with enrolled participants with a median or mean age of ≥18 years were excluded. No restriction on publishing date was applied.

Discussion and conclusion:

Pediatric ARV dosing is frequently based on data obtained from small studies and is often simplified to facilitate dosing in the context of a public health approach. Pharmacokinetic parameters of pediatric ARVs are subject to high interpatient variation and this leads to a potential risk of underdosing or overdosing when drugs are used in real life. To ensure optimal use of ARVs and validate dosing recommendations for children, it is essential to monitor ARV dosing more thoroughly with larger sample sizes and to include diverse subpopulations. Therapeutic drug monitoring data generated in children, where available and affordable, have the potential to enhance our understanding of the appropriateness of simplified pediatric dosing strategies recommended using a public health approach and to uncover suboptimal dosing or other unanticipated issues postmarketing, further facilitating the ultimate goal of optimizing pediatric ARV treatment.
Hospital risk-based payments and physician employment: Impact on financial performance
Authors: Bazzoli Gloria J.
Published: April 2019

Background

Hospital involvement in risk-based payment and employment of physicians can have a large impact on their profitability. Risk-based reimbursement approaches with third-party payers and provider-sponsored insurance products hold hospital organizations financially accountable for a range of patient services. Direct employment of physicians can add new revenue sources for the hospital but comes at the high cost of physician compensation packages.

Purpose

Risk bearing and physician employment have multifaceted effects on hospital profitability. The objective of this study is to assess overall financial implications of these arrangements.

Methodology

Fixed-effects estimation with American Hospital Association, Centers for Medicare & Medicaid Services, and Area Health Resource File data are used for the period 2012–2015. Key measures include indicators of hospital involvement in risk-based payments and the number of employed physicians by specialty. Hospital and market factors that could affect profitability are controlled in the analysis.

Results

Increases in employed hospitalists for hospitals with risk-based payment arrangements had a beneficial effect on their profitability. No significant association existed between profits and increased physician employment for hospitals lacking such payment arrangements and for increased nonhospitalist physician employment in hospitals with these arrangements.

Conclusions

Hospitals that hold some degree of financial responsibility for patient care have learned how to deploy employed hospitalists to their financial advantage. The unique role of hospitalists in expediting and coordinating patient care may yield the cost control that hospitals need to succeed under risk-based payment arrangements.

Practice Implications

Hospitals are still on a learning curve in determining how to structure incentives for their nonhospitalist employed physicians. To the extent that employment of these nonhospitalist physicians has not yet had a detrimental effect on hospital profits, a window of opportunity exists for hospitals to develop enhanced approaches to align primary care and specialist physicians to achieve financial aims.
It’s how we communicate! Exploring face-to-face versus electronic communication networks in multidisciplinary teams
Authors: Mascia Daniele , Rinninella Emanuele , Pennacchio Nicola Walter , Cerrito Lucia , Gasbarrini Antonio
Published: April 2019

Background

Previous research suggests that multidisciplinary team communication networks enhance knowledge exchange, learning, and quality of care in health organizations. However, little is known about team members’ reliance on face-to-face versus electronic-based communication networks for information and knowledge exchange.

Purpose

The aim of the study was to describe patterns of face-to-face versus electronic-based communication networks in a multidisciplinary team and to explore the relationships between team communication networks and performance, measured as promptness of treatment implementation.

Methodology

We collected data on work-based communication among members of a multidisciplinary tumor board (MDT) in a large Italian research hospital. A social network survey was administered in 2016 to all board members to gather network data on face-to-face interaction and the use of electronically based communication channels (e-mail, text messages, and WhatsApp) for sharing clinical knowledge. Twenty physicians (71%) completed the survey. Archival data were accessed to obtain detailed information about 222 clinical cases discussed over a 1-year period during weekly MDT meetings. Minutes of board meetings were used to link all discussed cases to team members. We used the multiple regression quadratic assignment procedure (MR-QAP) to study associations between team member characteristics and communication networks. Negative binomial regression was employed to test relationships between team communication networks and performance.

Results

MDT members relied on different communication channels for knowledge sharing. The geographical proximity of team members positively predicted the frequency of face-to-face interaction. Physicians’ seniority was related to the use of WhatsApp as a communication channel; greater interaction of this type was observed between team members of different seniority. Performance was related positively to face-to-face communication networks but negatively to communication via WhatsApp.

Practice Implications

Although team communication networks are important for knowledge exchange, health administrators must pay attention to the increasing propensity of team members to rely on electronic-based communication. The use of these easy-to-use tools can hinder the quality of group discussion and debate.
The Impact of PI3‐kinase/RAS Pathway Cooperating Mutations in the Evolution of KMT2A‐rearranged Leukemia
Authors: Esposito Maria Teresa
Published: April 2019

Supplemental Digital Content is available in the text
EHA Research Roadmap on Hemoglobinopathies and Thalassemia: An Update
Authors: Iolascon Achille , De Franceschi Lucia , Muckenthaler Martina , Taher Ali , Rees David , de Montalembert Mariane , Rivella Stefano , Eleftheriou Androulla , Cappellini Maria Domenica
Published: April 2019

The inherited disorders of hemoglobin, which include sickle cell disease and thalassemias, are the most common and widespread distributed monogenic disorders. Due to a selective advantage in malaria regions, these hemoglobin defects are particularly frequent in Africa, Asia, or in the Mediterranean areas, where malaria was endemic until the last century. In recent decades, the globalization of migration has contributed to generate multiethnic European societies. Due to migration from countries or regions with high hemoglobinopathy frequencies such as Africa, Middle East, or Asia, large numbers of patients with these disorders are living in almost every European country today. Furthermore, the numbers are increasing because of increasing refugee flows toward Europe. Additional requirements are the development of European recommendations and guidelines for diagnosis and effective therapeutic approaches. These, together with the advancement of clinical trials using new drugs and therapeutic procedures could ameliorate the quality of life of patients affected with these diseases and increase their life expectancy. Lastly, coordinated efforts should be made to develop diagnostic pathways for thalassemias and hemoglobinopathies, in order to plan interventions, including prenatal diagnosis and cure. For these reasons, the development of new tools to reliably diagnose anemias is urgently needed and fits well with the needs of personalized medicine. In the last 15 years, hematology research has made many big leaps forward. Our general aim will be to solve several hematologic problems using these new approaches. We expect that the development of such a diagnostic tool will improve timely diagnosis throughout Europe, especially in those countries where it is difficult to gain access to “classical” diagnostic tests.
Factors That Influence the Success of Contact Lens Fitting in Presbyopes: A Multicentric Survey
Authors: Zeri Fabrizio , Di Censi Manuele , Livi Stefano , Ercoli Antonio , Naroo Shehzad A.
Published: April 2019

Objectives:

To evaluate the key factors behind successful and unsuccessful wear of contact lenses (CLs) for patients with presbyopia.

Method:

A multicenter survey was conducted using a questionnaire, in eight CL centers, among two groups of presbyopes: successful wearers (SWs), who were presbyopic and wearing CLs successfully, and unsuccessful wearers (UWs), who tried unsuccessfully to wear CLs to manage their presbyopia and had stopped wearing CLs.

Results:

A total of 237 completed questionnaires were returned; 178 from SWs and 59 from UWs. Successful wearers used CLs 5.8±1.5 days a week and additional reading spectacles were never used by half of the SWs. Among SWs, the most important reason to continue wearing CLs was convenience (61%), whereas among UWs, the most important reason to discontinue wearing CLs was poor vision (80%). A logistic regression analysis showed that the absence of astigmatism (P<0.05), a higher subjective satisfaction (P<0.05), a better subjective perceived vision at distance (P<0.01), and a lower subjective loss of visual contrast (P<0.05) were able to predict the success of CL use for presbyopia.

Conclusions:

This study explores the predictors for determining successful or unsuccessful CL wear in presbyopes. Among ophthalmic, demographic, lifestyle, and subjective variables, the latter seems to be of greater importance in determining the success of CL wear. Therefore, it is necessary that subjective variables are taken into account by the CL practitioner when approaching presbyopic CL fitting in practice.
Correlation Between Anterior Corneal Elevation Differences in Main Meridians and Corneal Astigmatism
Authors: Batres Laura , Piñero David , Carracedo Gonzalo
Published: April 2019

Purpose:

To assess the correlation between anterior corneal elevation (ACE) and anterior corneal astigmatism (ACA) obtained with two different topographers in healthy subjects at different corneal diameters.

Methods:

A retrospective, comparative, and observational study was conducted. Topography data from 305 patients obtained with the Oculus Pentacam (Oculus, Wetzlar, Germany) and Sirius (CSO, Florence, Italy) systems were collected. Subjects were divided into four groups depending on the magnitude of ACA. The ACE was evaluated in the principal meridians at 2, 3, and 4 mm from the corneal apex. The difference in ACE between meridians (ACE-M) and in superior–inferior and nasal–temporal semimeridians (ACE-SM) was calculated.

Results:

A strong positive correlation between ACE-M and ACA with both topographers was found for all corneal diameters (P<0.001). A linear equation to calculate the ACE-M differences as a function of the astigmatism at 8 mm of diameter was obtained: y=23.417x+1.40, where y is ACE-M in microns and x is ACA in diopters. Significant differences in ACE along SM were found for all groups studied according to the magnitude of ACA for the horizontal SM (P>0.001). The temporal meridian was more elevated at 4- and 6-mm diameters, and the nasal semimeridian was the most elevated for 8 mm.

Conclusion:

Anterior corneal astigmatism and elevation differences are strongly correlated, providing more corneal topography knowledge that could be applied in the contact lens fitting. A toric orthokeratology lens may be indicated in ACA greater than 0.75 D.
Zone of Clear Single Binocular Vision in Myopic Orthokeratology
Authors: Gifford Kate L. , Gifford Paul , Hendicott Peter L. , Schmid Katrina L.
Published: April 2019

Purpose:

To examine the zone of clear single binocular vision (ZCSBV) in myopic children and young adults after 12 months of orthokeratology (OK) wear, in comparison with single-vision soft contact lens (SCL) wear.

Methods:

Twelve children (8–16 years) and 8 adults (18–29 years) were assessed with a series of near-point binocular vision tests when myopia was corrected using single-vision SCLs and again after 1 and 12 months of OK wear, and axial length was measured. The ZCSBV was constructed for baseline SCL wear and after 12 months of OK wear.

Results:

After 1 month of OK wear, increased accommodative responses were noted in children (C) and adults (A) as increased binocular amplitude (C:P=0.03, A:P=0.04) and reduced accommodative lag (C:P=0.01, A:P=0.01). Divergence reserves improved after 1 month in both groups (P<0.04), and a near exophoric shift was evident at 12 months (C:P=0.01, A:P=0.04). All changes at 1 month maintained stability at 12 months. An increase in accommodation and vergence responses without reduction in range resulted in an expansion of the ZCSBV in both age groups. Axial length did not significantly change in either children (P=0.25) or adults (P=0.72).

Conclusion:

In both pediatric and young adult myopes, the ZCSBV expands toward a more divergent, increased accommodation response in OK compared with SCL wear. This occurs without a corresponding loss of convergence or accommodation deactivation, indicating improved depth of focus. These findings are relevant to visual acceptance and possible mechanisms of OK's efficacy for myopia control.
Imaging vs quantitative sensory testing to predict chronic pain treatment outcomes
Authors: Davis Karen D.
Published: April 2019

In this article, I review the concept of personalized pain management and consider how brain imaging and quantitative sensory testing can be used to derive biomarkers of chronic pain treatment outcome. I review how different modalities of brain imaging can be used to acquire information about brain structure and function and how this information can be linked to individual measures of pain.
Pointer-kindreds and pain: big lessons from small families
Authors: Waxman Stephen G.
Published: April 2019

Small families carrying rare mutations, which I call “pointer-kindreds,” can teach us important lessons. Here, I provide some examples from the field of pain.
New approach for investigating neuropathic allodynia by optogenetics
Authors: Tsuda Makoto
Published: April 2019

Mechanical allodynia is pain caused by normally innocuous mechanical stimuli and is a cardinal and intractable symptom of neuropathic pain. Roles of low-threshold mechanoreceptors (LTMRs), including Aβ fibers, in mechanical allodynia have previously been proposed, but the necessity and sufficiency of LTMRs in allodynia have not been fully determined. Recent technological advances have made it possible to achieve subpopulation-specific ablation, silencing or stimulation, and to dissect and elucidate complex neuronal circuitry. Recent studies using an optogenetic approach have shown that activation of LTMRs, including Aβ fibers that genetically express channelrhodopsin-2, by illuminating blue light to the skin elicit morphine-resistant withdrawal behaviors after nerve damage. Whole-cell recording has revealed that optical Aβ stimulation after nerve injury causes excitation of lamina I dorsal horn neurons, which are normally silent by this stimulation. Moreover, Aβ stimulation after nerve injury results in activation of central amygdaloid neurons and produces aversive behaviors. In summary, these findings indicate that optogenetics is a powerful approach for investigating LTMR-derived pain (resembling mechanical allodynia) with sensory and emotional features after nerve injury and for discovering novel and effective drugs to treat neuropathic pain.
Translational neuropathic pain research
Authors: Attal Nadine , Bouhassira Didier
Published: April 2019

The traditional translational approach in neuropathic pain research has mainly consisted to date in translating basic findings from animal models of nerve injury to the clinic. Because of the difficulty to extrapolate mechanisms from animals to humans, an inverse translational approach (“top–down”) has been advocated and contributed to the development of therapy. In particular, a number of treatments such as neurostimulation techniques have been initially assessed in patients and then translated to animal models for further investigation of their mechanisms. Therapeutic approaches based on an in-depth assessment of sensory phenotypes, suggestive of mechanisms, have also been implemented. The biggest trend in recent translational research is to investigate mechanisms or predict therapeutic response in patients by integrating multimodal approaches. The present narrative review emphasizes these various aspects of translational research in neuropathic pain.
Deconstructing biomarkers for chronic pain: context- and hypothesis-dependent biomarker types in relation to chronic pain
Authors: Reckziegel Diane , Vachon-Presseau Etienne , Petre Bogdan , Schnitzer Thomas J. , Baliki Marwan N. , Apkarian A. Vania
Published: April 2019

This review expounds on types and properties of biomarkers for chronic pain, given a mechanistic model of processes underlying development of chronic pain. It covers advances in the field of developing biomarkers for chronic pain, while outlining the general principles of categorizing types of biomarkers driven by specific hypotheses regarding underlying mechanisms. Within this theoretical construct, example biomarkers are described and their properties expounded. We conclude that the field is advancing in important directions and the developed biomarkers have the potential of impacting both the science and the clinical practice regarding chronic pain.
Structure–function relationships in peripheral nerve contributions to diabetic peripheral neuropathy
Authors: Frank Tessa , Nawroth Peter , Kuner Rohini
Published: April 2019

Diabetes mellitus (DM) is a major global health concern, affecting more than 9% of the world population. The most common complication of DM is diabetic peripheral neuropathy (DPN), which leads to neuropathic pain in as many as 50% of patients. Despite its prevalence, there is neither good prevention of nor treatments for DPN, representing a major gap in care for the many who are afflicted. It has long been known from patient studies that both small and large primary afferent fibers undergo structural changes in DPN; however, the exact functional contributions of these changes to DPN symptomology are unknown, necessitating animal studies. This review first presents the commonly used mouse models of DPN resulting from both type 1 and type 2 DM. It then discusses structural changes in Aβ, Aδ, and C fibers throughout the progression of DPN and their respective contributions to painful DPN in both human patients and DM mouse models. Finally, it highlights remaining questions on sensory neuron structure–function relationships in painful DPN and how we may address these in mouse models by using technological advances in cell-specific modulation. Only when these structure–function relationships are understood, can novel targeted therapeutics be developed for DPN.
The role of quantitative sensory testing in the prediction of chronic pain
Authors: Treede Rolf-Detlef
Published: April 2019

Quantitative sensory testing (QST) is a formal variant of a time-honoured clinical examination technique in neurology, the sensory examination. Prototypical QST profiles have been found in human surrogate models of peripheral sensitization, central sensitization, and deafferentation. Probabilistic sorting of individual patients to any combination of these profiles has been developed, and there is emerging evidence for the predictive value of such sensory profiles for treatment efficacy. This way, QST aids in diagnostics of individual patients and may help guide their care in the future. Deficits in “dynamic” QST have been proposed as predictors of chronic pain (impaired descending inhibition and delayed recovery from central sensitization). Several psychological factors had previously been found to be predictors of pain chronicity (catastrophizing, self-efficacy, and neuroticism). The relative importance of psychological vs sensory testing predictors has not been evaluated. It is likely that both will have differential roles in clinical practice.
The ED-PACT Tool Initiative: Communicating Veterans' Care Needs After Emergency Department Visits
Authors: Cordasco Kristina M. , Saifu Hemen N. , Song Hyun-Sung , Hsiao Jonie J. , Khafaf Mana , Doyle Brian , Rubenstein Lisa V. , Chrystal Joya G. , Bharath Purnima , Ganz David A.
Published: April 2019

Background:

Communication failures between providers threaten patient safety.

Purpose:

We developed, implemented, and formatively evaluated the ED-PACT Tool, which uses the Veterans Health Administration's (VA) electronic health record to send messages from emergency department (ED) providers to primary care patient-aligned care team (PACT) registered nurses (RNs) for Veterans discharged home from the ED with urgent or specific follow-up needs.

Methods:

We used Plan-Do-Study-Act quality improvement methodology.

Results:

Between November 1, 2015, and November 30, 2017, the tool was used to send 4,899 messages in one local VA healthcare system (ED and associated primary care clinics). Formative evaluation revealed that providers and RNs perceive the tool as providing substantial benefit for coordinating post-ED care. Patient-aligned care team leaders reported that RN training and “buy-in” facilitated tool implementation, while insufficient staffing posed a barrier. Emergency department providers noted the advantage of having a standardized and reliable system for communicating with PACTs.

Conclusions/Implications:

The ED-PACT Tool encapsulates several best practices (standardized processes, “closed-loop” communication, embedding into workflow) to facilitate communication between VA ED and follow-up care providers. Our development process illustrates key lessons in quality improvement and innovation implementation including the value of using rapid-cycle improvement methodology, with interprofessional collaboration and representatives from intended spread sites.
Circulating tumor cells in pancreatic cancer: a review
Authors: Habib Joseph R. , Yu Jun
Published: April 2019

Pancreatic cancer remains one of the deadliest types of cancer with little or no recent evidence of significant improvement in survival. This is, in large part, due to the current unavailability of effective screening or even early detection methods. Circulating tumor cells (CTCs), particularly with the rapidly improving methods for isolation, enrichment, and characterization methods, have emerged as the next best hope to overcome these challenges. This paper reviews the current state-of-the-art of CTC technologies with particular focus on the various isolation and enrichment methods based on liquid biopsy, the current limitations of these technologies and, consequently, the areas of further research and improvements in CTC methods that are needed to translate it to the clinical setting of routine diagnosis, treatment, and management of pancreatic cancer.
Incidence and Risk Factors Associated With 30-Day Readmission for Alcoholic Hepatitis
Authors: Garg Sushil K. , Sarvepalli Shashank , Singh Dupinder , Obaitan Itegbemie , Peeraphatdit Thoetchai , Jophlin Loretta , Asrani Sumeet K. , Shah Vijay H. , Leise Michael D.
Published: April 2019

Background:

Alcohol abuse and liver disease are associated with high rates of 30-day hospital readmission, but factors linking alcoholic hepatitis (AH) to readmission are not well understood. We aimed to determine the incidence rate of 30-day readmission for patients with AH and to evaluate potential predictors of readmission.

Methods:

We used the Nationwide Readmissions Database to determine the 30-day readmission rate for recurrent AH between 2010 and 2014 and examined trends in readmissions during the study period. We also identified the 20 most frequent reasons for readmission. Multivariate survey logistic regression analysis was used to identify factors associated with 30-day readmission.

Results:

Of the 61,750 index admissions for AH, 23.9% were readmitted within 30-days. The rate of readmission did not change significantly during the study period. AH, alcoholic cirrhosis, and hepatic encephalopathy were the most frequent reasons for readmission. In multivariate analysis female sex, leaving against medical advice, higher Charlson comorbidity index, ascites, and history of bariatric surgery were associated with earlier readmissions, whereas older age, payer type (private or self-pay/other), and discharge to skilled nursing-facility reduced this risk.

Conclusions:

The 30-day readmission rate in patients with AH was high and stable during the study period. Factors associated with readmission may be helpful for development of consensus-based expert guidelines, treatment algorithms, and policy changes to help decrease readmission in AH.
Older Adult Perspectives Toward Surveillance Colonoscopy
Authors: Calderwood Audrey H. , Cazares Kathy , O’Connor Sharon
Published: April 2019

Goals and Background:

Surveillance colonoscopy is the most common indication for colonoscopy in older adults, yet factors involved in patient decision-making are poorly defined. We sought to understand general perspectives of older adults toward surveillance colonoscopy.

Study:

We conducted 2 in-person, 90-minute semistructured focus groups at a rural, tertiary care, academic facility with a total of 20 English-speaking participants with a history of colon polyps. We also obtained baseline characteristics including information to calculate life expectancy using the Schonberg Index, a validated measure of 5-year and 9-year mortality.

Results:

Participant ages ranged from 75 to 89, 67% were female, and 61% had a life expectancy of ≤9 years. Major common themes included reasons for and against getting a surveillance colonoscopy, and preferences and opinions surrounding discontinuing surveillance. Fear of cancer, trust in the colonoscopy procedure, and provider advice played prominent roles in patient decisions to return for surveillance. Most felt they should make screening decisions with input from providers, and that providers should engage them in these decisions and base recommendations on their patients’ personal history and health, not on how old they are or on actuarial data.

Conclusions:

This small, qualitative study suggests that older adults familiar with surveillance colonoscopy prefer patient-centered decision-making on when to discontinue testing and want support and information from providers when making choices. The evidence also suggests that participants value provider communication and trust their advice. Future work will use this information to create a larger patient survey on attitudes and beliefs toward surveillance colonoscopy.
Impact of Automated Time-released Reminders on Patient Preparedness for Colonoscopy
Authors: Nayor Jennifer , Feng Aiden , Qazi Taha , Hurwitz Shelley , Saltzman John R.
Published: April 2019

Goals:

To evaluate the effect of an automated time-released colonoscopy reminder program on preparation quality and the rates of canceled procedures.

Background:

Patients missing colonoscopy appointments or arriving with inadequate bowel preparations result in delays in care and increase in health care costs.

Study:

We initiated a quality improvement program which included switching to a split-dose preparation and delivering preparation instructions and appointment reminders via text messages and emails sent with an automated time-released HIPAA-compliant software platform. All patients scheduled for a colonoscopy from March through June 2017 were enrolled unless mobile phone, email, or preparation type data was missing (nonintervention cohort). Primary outcome metrics were the rate of adequate bowel preparation and the rate of canceled procedures. Outcomes of the intervention group were compared with outcomes from colonoscopies performed from March through June 2016 (baseline cohort).

Results:

There were 1497 patients (40.7% male, mean age 56.4 y) enrolled in the automated reminder program. Compared with the baseline cohort, the rate of adequate bowel preparation increased from 88.5% to 96.2% (P<0.0001). The rate of canceled procedures decreased from 6.1% to 4.3% (P=0.02). On multivariable analysis, the automated reminder program improved adequate preparation quality 2.85-fold (95% confidence interval, 2.03-3.99; P<0.0001). Sensitivity analysis comparing the intervention to nonintervention cohorts showed that improvement in preparation quality was attributable to the automated reminder program.

Conclusions:

Implementation of automated time-released colonoscopy preparation reminders via text messages and emails improved patient preparedness for colonoscopy, with significantly improved bowel preparation quality and fewer canceled procedures.
Thromboelastography-guided Blood Product Transfusion in Cirrhosis Patients With Variceal Bleeding
Authors: Rout Gyanranjan , Shalimar  , Gunjan Deepak , Mahapatra Soumya J. , Kedia Saurabh , Garg Pramod K. , Nayak Baibaswata
Published: April 2019

Goals:

The aim of this study was to assess the use of thromboelastography (TEG)-directed blood product transfusion in cirrhotic patients with acute variceal bleeding compared with conventional transfusion for correction of coagulopathy.

Background:

Coagulopathy is common in patients with cirrhosis. Recommendations for correction of conventional parameters of coagulation—platelets and the international normalized ratio before endoscopy in patients with acute variceal bleeding—need more validation.

Study:

In this randomized controlled trial, cirrhotic patients with severe coagulopathy and acute variceal bleeding were randomized to either TEG-guided blood product transfusion or conventional transfusion from March 2017 to December 2017. The primary outcome was the difference in the amount of fresh frozen plasma and platelet units transfused between the groups. Secondary outcomes were rebleeding at 5 days and 42 days, and 6-week mortality.

Results:

Of the 60 recruited patients, 30 each were randomized to the TEG and conventional transfusion groups. There were no differences in baseline characteristic and endoscopic findings between the 2 groups. Four subjects in the TEG group received blood product transfusions versus all in the conventional transfusion group (13.3% vs. 100%; P<0.001). The control of bleeding on initial endoscopy was similar in the 2 groups. Rebleeding in the TEG and conventional transfusion groups at 5 days was similar [1 (3.3%) vs. 4 (13.3%), P=0.167], whereas it was significantly less in the TEG group at 42 days [3 (10%) vs. 11 (36.7%), P=0.012]. Mortality at 6 weeks was seen in 4 (13.3%) in the TEG group and in 8 (26.7%) patients in the conventional transfusion group (P=0.176).

Conclusions:

TEG-guided strategy was associated with reduced blood product transfusion to correct coagulopathy without compromising hemostasis in cirrhotic patients (Clinical trial ID: CTRI/2017/02/007864).
Risk factors of malignant fluorodeoxyglucose-avid lymph node on preablation positron emission tomography in patients with papillary thyroid cancer undergoing radioiodine ablation therapy
Authors: Cho Sang-Geon , Kwon Seong Young , Kim Jahae , Cho Dong-Hyeok , Na Myung Hwan , Kang Sae-Ryung , Yoo Su Woong , Song Ho-Chun
Published: April 2019

F-18 fluorodeoxyglucose (FDG)-avid metastatic lesions are associated with a poor response to radioiodine ablation therapy (RIT) in papillary thyroid cancer (PTC). This study evaluated the significance of preablative FDG positron emission tomography (PET) for the assessment of risk factors and frequency of malignant FDG-avid lymph nodes in patients with PTC undergoing RIT.

The study included 339 consecutive patients (mean age 46.3 ± 12.5 y; 260 females) with PTC referred for the first RIT and who underwent routine preablative FDG PET between April 2011 and February 2013. FDG-avid lymph nodes (FALNs) were identified using retrospective image reviews. The frequency of malignant FALN (mFALN), its contribution to persistent or recurrent PTC, and its risk factors were analyzed.

Among the patients, 112 had FALNs (33.0%): 11 mFALNs (3.2%) and 101 benign FALNs (bFALNs, 29.8%). mFALN contributed to 55% of persistent or recurrent PTC after RIT, which was observed in 20 of 339 patients (5.9%) during the post-RIT follow-up. Among preoperative risk factors, suspicious extrathyroidal extension and lateral neck lymph node metastasis on imaging studies were associated with mFALN. Among postoperative risk factors, T3/T4 and N1b stages, higher stimulated thyroglobulin, and higher numbers of metastatic lymph nodes and dissected lymph nodes, were associated with mFALN.

mFALNs were observed in a small number of patients with PTC undergoing RIT, but it contributed 55% of total recurrent or persistent disease. Increased frequency of mFALNs is associated with more advanced PTC. Preablative FDG PET has value in evaluation of patients with RIT-resistant lesions and may help determine further treatment strategies.