bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Value Interviewing: A Call for Quality Improvement in the Match Process
Authors: Frush Benjamin W. , Byerley Julie
Published: December 2018

Within the Match process, current residency interview practices are inefficient for both applicants and programs. Problems include disorganized interview offers and scheduling, excessive numbers of applicant interviews, unclear postinterview communication policies, and the significant expenses entailed. To address these issues, the authors propose applying a quality improvement approach to create a high-value interview process that would decrease investments of time, money, and energy and improve the quality of the Match experience for both applicants and programs. They propose establishing an interview offer week to streamline and systematize the interview offer and scheduling process; placing an evidence-based cap on the number of interviews that applicants are allowed to schedule; and enforcing a moratorium on postinterview communication that would apply to both applicants and programs. Implementing these proposals would decrease expenses, improve the efficiency of this process for all involved, and demonstrate that quality improvement methods used to improve patient care can also be applied to improving medical student and physician experiences.
New Educator Roles for Health Systems Science: Implications of New Physician Competencies for U.S. Medical School Faculty
Authors: Gonzalo Jed D. , Chang Anna , Wolpaw Daniel R.
Published: December 2018

To address gaps in U.S. health care outcomes, medical education is evolving to incorporate new competencies, as well as to align with care delivery transformation and prepare systems-ready providers. These new health systems science (HSS) competencies—including value-based care, quality improvement, social determinants of health, population health, informatics, and systems thinking—require formal education and role modeling in both classroom and clinical settings. This is challenging because few faculty had formal training in how to practice or teach these concepts. Thus, these new competencies require both expanding current educators’ skills and a new cohort of educators, especially interprofessional clinicians. Additionally, because interprofessional teams are the foundation of many clinical learning environments, medical schools are developing innovative experiential activities that include interprofessional clinicians as teachers. This combination of a relative “expertise vacuum” within the current cohort of medical educators and expanding need for workplace learning opportunities requires a reimagining of medical school teachers. Based on experiences implementing HSS curricula at two U.S. medical schools (Penn State College of Medicine and University of California, San Francisco, School of Medicine, starting in 2013), this Perspective explores the need for new educator competencies and the implications for medical education, including the need to identify and integrate “new” educators into the education mission, develop faculty educators’ knowledge and skills in HSS, and acknowledge and reward new and emerging educators. These efforts have the potential to better align the clinical and education missions of academic health centers and cultivate the next generation of physician leaders.
S1 Pedicle Subtraction Osteotomy for Fixed Sagittal Imbalance and Lumbosacral Kyphosis
Authors: Bronson Wesley H. , Dai Amos , Protopsaltis Themistocles
Published: December 2018

S1 pedicle subtraction osteotomies (PSOs) are indicated in patients with fixed, high-grade L5–S1 spondylolisthesis or kyphosis secondary to a sacral fracture, who present with severe sagittal imbalance. Unlike lumbar PSOs, sacral osteotomies are rare, and there is a paucity of literature outlining techniques. Here, we present the indications, planning, technique, and outcomes for S1 PSOs.
Anatomic Considerations in the Lateral Transpsoas Interbody Fusion
Authors: Mai Harry T. , Schneider Andrew D. , Alvarez Andrew P. , Hashmi Sohaib Z. , Smith Justin T. , Freshman Ryan D. , Mitchell Sean M. , Qin Charles D. , Hsu Wellington K.
Published: December 2018

Study Design:

This is a retrospective case series.

Objective:

Define the anatomic variations and the risk factors for such within the operative corridor of the transpsoas lateral interbody fusion.

Summary of Background Data:

The lateral interbody fusion approach has recently been associated with devastating complications such as injury to the lumbosacral plexus, surrounding vasculature, and bowel. A more comprehensive understanding of anatomic structures in relation to this approach using preoperative imaging would help surgeons identify high-risk patients potentially minimizing these complications.

Materials and Methods:

Age-sex distributed, naive lumbar spine magnetic resonance imagings (n=180) were used to identify the corridor for the lateral lumbar interbody approach using axial images. Bilateral measurements were taken from L1–S1 to determine the locations of critical vascular, intraperitoneal, and muscular structures. In addition, a subcohort of scoliosis patients (n=39) with a Cobb angle >10 degrees were identified and compared.

Results:

Right-sided vascular anatomy was significantly more variant than left (9.9% vs. 5.7%; P=0.001). There were 9 instances of “at-risk” vasculature on the right side compared with 0 on the left (P=0.004). Age increased vascular anatomy variance bilaterally, particularly in the more caudal levels (P≤0.001). A “rising-psoas sign” was observed in 26.1% of patients. Bowel was identified within the corridor in 30.5% of patients and correlated positively with body mass index (P<0.001). Scoliosis increased variant anatomy of left-sided vasculature at L2–3/L3–4. Nearly all variant anatomy in this group was found on the convex side of the curvature (94.2%).

Conclusions:

Given the risks and complications associated with this approach, careful planning must be taken with an understanding of vulnerable anatomic structures. Our analysis suggests that approaching the intervertebral space from the patient’s left may reduce the risk of encountering critical vascular structures. Similarly, in the setting of scoliosis, an approach toward the concave side may have a more predictable course for surrounding anatomy.

Level of Evidence:

Level 3—study.
Impact of Altered Airway Pressure on Intracranial Pressure, Perfusion, and Oxygenation: A Narrative Review
Authors: Chen Han , Menon David K. , Kavanagh Brian P.
Published: December 2018

Objectives:

A narrative review of the pathophysiology linking altered airway pressure and intracranial pressure and cerebral oxygenation.

Data Sources:

Online search of PubMed and manual review of articles (laboratory and patient studies) of the altered airway pressure on intracranial pressure, cerebral perfusion, or cerebral oxygenation.

Study Selection:

Randomized trials, observational and physiologic studies.

Data Extraction:

Our group determined by consensus which resources would best inform this review.

Data Synthesis:

In the normal brain, positive-pressure ventilation does not significantly alter intracranial pressure, cerebral oxygenation, or perfusion. In injured brains, the impact of airway pressure on intracranial pressure is variable and determined by several factors; a cerebral venous Starling resistor explains much of the variability. Negative-pressure ventilation can improve cerebral perfusion and oxygenation and reduce intracranial pressure in experimental models, but data are limited, and mechanisms and clinical benefit remain uncertain.

Conclusions:

The effects of airway pressure and ventilation on cerebral perfusion and oxygenation are increasingly understood, especially in the setting of brain injury. In the face of competing mechanisms and priorities, multimodal monitoring and individualized titration will increasingly be required to optimize care.
Heterogeneity and Variability in Pressure Autoregulation of Organ Blood Flow: Lessons Learned Over 100+ Years
Authors: Meng Lingzhong , Wang Yingwei , Zhang Lina , McDonagh David L.
Published: December 2018

Objectives:

Pressure autoregulation is an organ’s intrinsic ability to maintain blood flow despite changes in perfusion pressure. The purpose of this review is to discuss autoregulation’s heterogeneity among different organs and variability under different conditions, a very clinically relevant topic.

Data Sources:

Systematic search of Ovid MEDLINE; nonsystematic search of PubMed, Google Scholar, and reference lists.

Study Selection:

Animal or human studies investigating the potency or variation of pressure autoregulation of any organs or the association between autoregulation and outcomes.

Data Extraction:

Two authors screened the identified studies independently then collectively agreed upon articles to be used as the basis for this review.

Data Synthesis:

Study details, including subjects, organ investigated, methods of blood pressure intervention and blood flow measurement, and values of the lower limit, upper limit, and plateau were examined. Comparative canine studies were used to demonstrate the heterogeneity of pressure autoregulation among different organs and validate the proposed scale for organ categorization by autoregulatory capacity. Autoregulatory variability is discussed per organ. The association between cerebral autoregulation and outcome is summarized.

Conclusions:

The organs with robust autoregulation are the brain, spinal cord, heart, and kidney. Skeletal muscle has moderate autoregulation. Nearly all splanchnic organs including the stomach, small intestine, colon, liver, and pancreas possess weak autoregulation. Autoregulation can be readily affected by a variety of clinically relevant factors. Organs with weak or weakened autoregulation are at a greater risk of suboptimal perfusion when blood pressure fluctuates. Cerebral autoregulation and outcomes are closely related. These lessons learned over 100+ years are instructive in clinical care.
Gastric cancer: epidemiology, biology, and prevention: a mini review
Authors: Lyons Kiara , Le Linh C. , Pham Yen T.-H. , Borron Claire , Park Jong Y. , Tran Chi T.D. , Tran Thuan V. , Tran Huong T.-T. , Vu Khanh T. , Do Cuong D. , Pelucchi Claudio , La Vecchia Carlo , Zgibor Janice , Boffetta Paolo , Luu Hung N.
Published: December 2018

Gastric cancer is one of the most common causes of cancer-related mortality worldwide. The objective of this article is to review the epidemiology and biology of gastric cancer risk. This literature review explores the biological, clinical, and environmental factors that influence the rates of this disease and discuss the different intervention methods that may not only increase the awareness of gastric cancer but also increase screening in efforts to reduce the risk of gastric cancer. Helicobacter pylori infection is the primary risk factor for gastric cancer. Additional risk factors include geographical location, age, sex, smoking, socioeconomic status, dietary intake, and genetics. Primary and secondary prevention strategies such as dietary modifications and screenings are important measures for reducing the risk of gastric cancer. Interventions, such as H. pylori eradication through chemoprevention trials, have shown some potential as a preventative strategy. Although knowledge about gastric cancer risk has greatly increased, future research is warranted on the differentiation of gastric cancer epidemiology by subsite and exploring the interactions between H. pylori infection, genetics, and environmental factors. Better understanding of these relationships can help researchers determine the most effective intervention strategies for reducing the risk of this disease.
A pilot clinical trial testing topical resiquimod and a xenopeptide as immune adjuvants for a melanoma vaccine targeting MART-1
Authors: Block Matthew S. , Nevala Wendy K. , Pang Yuan-Ping , Allred Jacob B. , Strand Carrie , Markovic Svetomir N.
Published: December 2018

A vaccine that could expand melanoma-specific T cells might reduce the risk of recurrence of resected melanoma and could provide an alternative or adjunct to standard immunotherapy options. We tested the safety and immunogenicity of a vaccine coupling a melanoma-associated peptide with a xenogenic peptide (to promote epitope spreading) and/or resiquimod (to activate antigen-presenting cells). HLA-A2-positive patients with resected stage II, III, and IV melanoma were assigned to treatment on one of three schedules. All patients received three subcutaneous doses of the peptide MART-1a mixed with Montanide. In addition, patients on schedule 1 received the xenoantigen peptide Gag267–274, patients on schedule 2 received topical resiquimod, and patients on schedule 3 received both Gag267–274 and resiquimod. Blood samples were tested for the frequency of antigen-specific T cells by tetramer assay, as well as immune cell subtypes and plasma cytokine levels. Patients enrolled from October 2012 to December 2014, with 10 patients enrolling to each schedule. The most common adverse events were injection site reaction (26 patients) and fatigue (15 patients). Tetramer analysis revealed antigen-specific responses (defined as doubling of MART-1a-specific T cells from pretreatment to post-treatment) in 20, 60, and 40% of patients treated on schedules 1, 2, and 3, respectively. Vaccine treatment consisting of MART-1a peptide, Gag267–274, Montanide, and topical resiquimod was well-tolerated. The addition of the Gag267–274 xenoantigen was not associated with an increase in the response to MART-1a, whereas use of topical resiquimod was associated with a higher frequency of MART-1a-specific T-cell responses that did not meet statistical significance.
Racial Disparities in the Cardiac Computed Tomography Assessment of Coronary Artery Disease
Authors: El-Menyar Ayman , Abuzaid Ahmed , Elbadawi Ayman , McIntyre Matthew , Latifi Rifat
Published: December 2018

Coronary heart disease (CHD) represents a significant healthcare burden in terms of hospital resources, morbidity, and mortality. Primary prevention and early detection of risk factors for the development of CHD are pivotal to successful intervention programs and prognostication. Yet, there remains a paucity of evidence regarding differences in the assessment of these risk factors and the tools of assessment among different ethnicities. We conducted a narrative review to assess the utility of cardiac computed tomography, particularly coronary artery calcification (CAC), in different ethnicities. We also looked to see whether age, sex, comorbidities, and genetic background have peculiar influences on CAC. In this review, we highlight some of the pivotal studies regarding the question of CAC in relation to the development of CHD among different ethnicities. We identify several key trends in the literature showing that although African Americans have high rates of CHD, their risk of CAC may be relatively lower compared with other ethnicities. Similarly, South Asian patients may be at a high risk for adverse cardiac events due to elevated CAC. We also note that several studies are limited by small sample size and were based on 1 large cohort study. Future studies should include a large international prospective cohort to truly evaluate the effects of ethnicity on CAC and CHD risk. To appropriately apply CAC in the clinical practice, the variations in its scoring based on a subject’s age, sex, comorbidity, and ethnicity should be addressed and interpreted beforehand.
Low Serum Trough Concentrations and High Vancomycin Minimum Inhibitory Concentration in Methicillin-Sensitive Staphylococcus aureus From Hemodialysis Patients in Brazil
Authors: Vitória Michel Penedo da , Alvarenga Cristiane Gomes de Sousa , Vasconcellos Filho Lauro Monteiro , Birro Jéssica de Cássia Teixeira , Barbosa Maralisi Coutinho , Ferreira Mariana Abou Mourad , Schuenck Ricardo Pinto , Nunes Ana Paula Ferreira , Santos Kênia Valéria dos
Published: December 2018

Background:

The empiric antimicrobial therapy for bacteremia of long-term hemodialysis (HD) outpatients is currently based on the combination of vancomycin and gentamicin because of the high frequency of isolated Staphylococcus species. The vancomycin trough level range from 15 to 20 mcg/mL is expected for therapeutic success against methicillin-resistant Staphylococcus aureus with vancomycin minimum inhibitory concentration (MIC) ≥1.0 mcg/mL. Despite the availability of clinical practice guidelines for vancomycin therapeutic drug monitoring, these target serum concentrations are not reached in many patients.

Methods:

In this study, the authors investigated the vancomycin trough levels in 20 HD patients with S. aureus bacteremia and the antimicrobial susceptibility pattern of 45 S. aureus strains isolated from 45 HD patients. The vancomycin serum concentration was determined by chemiluminescent assay. The MIC was determined by broth microdilution method.

Results:

None of the HD patients included in this study had vancomycin trough concentrations within the therapeutic range. Also, the vancomycin MIC for most methicillin-sensitive S. aureus isolated from bacteremia was ≥1.0 mcg/mL.

Conclusions:

The therapeutic range of vancomycin was not achieved, and vancomycin MIC was surprisingly high in methicillin-sensitive S. aureus.
Evaluation of clinical meaningfulness of estrogen plus progesterone oral capsule (TX-001HR) on moderate to severe vasomotor symptoms
Authors: Constantine Ginger D. , Revicki Dennis A. , Kagan Risa , Simon James A. , Graham Shelli , Bernick Brian , Mirkin Sebastian
Published: December 2018

Objective:

The aim of this study was to determine the clinical meaningfulness of TX-001HR in reducing moderate to severe vasomotor symptoms (VMS) in menopausal women with a uterus.

Methods:

In the REPLENISH study (NCT01942668), women with moderate to severe hot flushes (≥7/d or ≥50/wk) were enrolled in a VMS substudy and randomized to four doses of daily TX-001HR (17β-estradiol/progesterone) or placebo. Participants assessed improvement of their VMS by the Clinical Global Impression and the Menopause-Specific Quality of Life (MENQOL) questionnaire, which were used to define clinical responders, clinically important differences (CIDs) or minimal CID (MCID) in VMS frequency. Response thresholds were determined by nonparametric discriminant analyses utilizing bootstrapping methods.

Results:

In the modified intent-to-treat VMS substudy population (n = 726), statistically significantly more Clinical Global Impression–based clinical responders were observed with TX-001HR than placebo for MCID (weekly reduction of ≥25 moderate to severe VMS: 82-88% vs 69%; all, P < 0.05) and CID (weekly reduction of ≥39 VMS: 68%-73% vs 52%; all, P < 0.05) at week 12. Week 4 results were similar. For Menopause Quality of Life–based analysis, significantly more clinical responders were observed with TX-001HR than placebo for MCID (weekly reduction of ≥34 VMS: 74%-81% vs 55%; all, P < 0.01) and CID (weekly reduction of ≥44 VMS: 61%-69% vs 42%; all, P < 0.01) at week 12.

Conclusions:

TX-001HR provided clinically meaningful improvements (as measured by 2 different methods), in addition to statistically significant reductions, in menopausal VMS frequency. TX-001HR may provide a new option, as a single oral capsule of estradiol and progesterone (identical to the hormones naturally occurring in women) for the treatment of moderate to severe VMS in menopausal women with a uterus.
The relationship between serum fibroblast growth factor 23, Klotho, and lumbar spine bone mineral density in northern Chinese postmenopausal women
Authors: Han Wen , Bai Xiao-juan , Han Lu-lu , Sun Xue-feng , Chen Xiang-mei
Published: December 2018

Objectives:

Changes in serum protein levels of fibroblast growth factor 23 (FGF23) and Klotho resulting from bone metabolism are still controversial. The purpose of this study was to observe the relationship between FGF23 and Klotho serum proteins and lumbar spine bone mineral density (LBMD) in northern Chinese postmenopausal women.

Methods:

This was a community-based cross-sectional study carried out in Shenyang, a northern Chinese city. The study included 355 postmenopausal women with an average age of 62.92 ± 8.78 years. FGF23 and Klotho serum proteins were measured using a sandwich enzyme immunoassay. LBMD was examined using dual-energy X-ray absorptiometry. Pearson's correlation and regression analyses were performed to investigate the associations among them.

Results:

The LgKlotho was positively correlated with LBMD (r = 0.105). There was a linear relationship between LgKlotho serum levels and LBMD (P = 0.007) after adjusting for BMI, and the relationship still existed after adjustments for many confounding variables (P = 0.045), including age, BMI, systolic blood pressure, diastolic blood pressure, total protein, total bilirubin, high-density lipoprotein cholesterol, fasting blood glucose, serum calcium, estimated glomerular filtration rate, serum uric acid, estradiol, cigarette smoking, alcohol consumption, milk intake, calcium and vitamin D supplements, physical exercise, and fracture history in postmenopausal women. FGF23 serum levels were, however, not significantly associated with LBMD.

Conclusions:

Klotho was positively correlated with LBMD, and there was a linear relationship between Klotho serum protein levels and LBMD; however, the levels of serum Klotho were not independently associated with reduced LBMD in northern Chinese postmenopausal women. Moreover, serum FGF23 levels were not significantly related to LBMD in this sample population.
Scleral Ischemia in Acute Ocular Chemical Injury: Long-Term Impact on Rehabilitation With Limbal Stem Cell Therapy
Authors: Gupta Nidhi , Singh Aastha , Mathur Umang
Published: December 2018

Purpose:

This study describes the impact of scleral ischemia on globe survival in cases of acute chemical injury and the outcome of limbal stem cell transplant in these eyes.

Methods:

This is a single-center, retrospective case study that reviews outcomes in all patients with acute chemical injury of grades IV and above who presented within 6 weeks from injury. The period of the study is between May 2012 and May 2017. Eyes presenting without scleral ischemia underwent amniotic membrane transplantation (group A), whereas eyes presenting with scleral ischemia underwent tenonplasty with amniotic membrane transplantation (group B). Simple limbal epithelial transplantation (SLET) was performed at 6 months in all consenting patients from both these groups. The primary outcome was defined as globe preservation at 3 months, whereas the secondary outcome was defined as SLET success at 1 year.

Results:

Twenty-three eyes of the 23 patients were included in our study. Of the 13 eyes in group B, 2 eyes developed phthisis and 2 eyes developed hypotony. None of the 10 eyes in group A developed hypotony or phthisis. The eyes that developed into hypotony and phthisis had presented with more extensive scleral ischemia (>180 degrees). In group B, 5 of 7 patients failed SLET. This was high compared with group A in which 2 of 8 patients failed SLET.

Conclusions:

The presence and extent of scleral ischemia are important prognostic factors when assessing recovery in eyes with acute chemical injury. The authors recommend that it be added as a poor prognostic indicator in the existing classifications of acute chemical injury.
Topical Rho-Associated Kinase Inhibitor, Y27632, Accelerates Corneal Endothelial Regeneration in a Canine Cryoinjury Model
Authors: Miyagi Hidetaka , Kim Soohyun , Li Jennifer , Murphy Christopher J. , Thomasy Sara M.
Published: December 2018

Purpose:

Corneal endothelial cell regeneration varies by species, with nonhuman primates (NHPs) and rabbits displaying low and high proliferative capacities, respectively. Recent studies report that topical application of rho-associated kinase (ROCK) inhibitors accelerates corneal endothelial wound healing in animal models and human patients with endothelial dysfunction. This study determines the regenerative capacity of canine corneal endothelial cells in vivo and their response to a topical ROCK inhibitor, Y27632, after transcorneal freezing.

Methods:

Right eyes of 6 beagles underwent transcorneal freezing; 10 mM ROCK inhibitor Y27632 or vehicle control was applied topically to both eyes at least 4 times daily for 56 days. Endothelial cell density was evaluated by in vivo confocal microscopy, and corneal thickness was measured by Fourier-domain optical coherence tomography (FD-OCT) and ultrasound pachymetry.

Results:

Transcorneal freezing induced severe central corneal edema in dogs, with restoration of transparency occurring within 4 weeks. Y27632 significantly decreased corneal thickness by FD-OCT and ultrasound pachymetry in the acute phase and significantly increased endothelial cell density at days 28 and 42 post-cryoinjury, suggesting faster restoration of endothelial cell recovery.

Conclusions:

Canine corneal endothelial function recovers at a similar rate as NHPs but more slowly than rabbits after cryoinjury. Faster corneal endothelial wound healing was observed by in vivo confocal microscopy and FD-OCT in dogs treated with Y27632 versus vehicle controls. Thus, a canine cryoinjury model may be a useful alternative to NHPs in detecting a response to therapies directed at endothelial regeneration.
Comparison of the Intraocular Pressure Measured Using the New Rebound Tonometer Icare ic100 and Icare TA01i or Goldmann Applanation Tonometer
Authors: Nakakura Shunsuke , Mori Etsuko , Fujio Yuki , Fujisawa Yasuko , Matsuya Kanae , Kobayashi Yui , Tabuchi Hitoshi , Asaoka Ryo , Kiuchi Yoshiaki
Published: December 2018

Purpose:

We evaluated the agreement between the intraocular pressure (IOP) values of new rebound tonometer, Icare ic100, and Icare TA01i or Goldmann applanation tonometer (GAT).

Methods:

We studied one eye each of 106 subjects (57 with primary open-angle glaucoma, 49 healthy subjects). IOP was randomly measured twice with the patient in sitting position using the Icare ic100, Icare TA01i, and GAT. Tonometer measurements were evaluated using Bland-Altman analysis. The relationship between IOP difference (Icare ic100-GAT) and age, sex, disease, axial length, central corneal thickness (CCT), and corneal curvature was investigated using multivariate regression analysis.

Results:

IOPs measured using Icare ic100, Icare TA01i, and GAT were 11.7±3.0 (mean±standard deviation), 12.2±2.9, and 16.0±3.2 mm Hg, respectively (P<0.001, one-way analysis of variance). Icare ic100 showed significantly lower IOPs than GAT (P<0.05), but not than Icare TA01 (P>0.05; Tukey-Kramer test). Bland-Altman analysis revealed that the mean differences between Icare ic100 and Icare TA01i and those between Icare ic100 and GAT were −0.46 and −4.2 mm Hg, respectively (95% limits of agreement, −3.35 to 2.42 and −10.10 to 1.61 mm Hg, respectively). For IOP differences between Icare ic100 and GAT, parameters selected in the optimal model were CCT (coefficient, 20.3, P=0.029), corneal curvature (3.0, P=0.020), and glaucoma-normal (−1.0, P=0.004).

Conclusions:

The new rebound tonometer Icare ic100 almost constantly showed IOPs lower than GAT. The difference was affected by CCT, corneal curvature, and disease.
Minimally Invasive Periareolar Approach to Cor Triatriatum Repair
Authors: Gottschalk Byron H. , Fujii Satoru , Grant Aaron , Iglesias Ivan , Chu Michael W. A.
Published: December 2018

Cor triatriatum sinister is an uncommon cardiac abnormality characterized by a membrane that divides the left atrium into two chambers. Definitive management requires surgical resection, traditionally through sternotomy. Minimally invasive reparative techniques are associated with reduced blood loss, shorter hospitalization, faster recovery time, and improved cosmesis with excellent patient satisfaction. We present a 29-year-old woman with cor triatriatum sinister and associated atrial septal defect who underwent successful minimally invasive repair through a right periareolar approach.
Islet-cell autoantigen 69 mediates the antihyperalgesic effects of electroacupuncture on inflammatory pain by regulating spinal glutamate receptor subunit 2 phosphorylation through protein interacting with C-kinase 1 in mice
Authors: Han Kunyuan , Zhang Anqi , Mo Yunchang , Mao Tingting , Ji Binbin , Li Dan , Zhuang Xiuxiu , Qian Meizi , Chen Shuangdong , Wang Zhen , Wang Junlu
Published: December 2018

Electroacupuncture (EA) is widely used in clinical settings to reduce inflammatory pain. Islet-cell autoantigen 69 (ICA69) has been reported to regulate long-lasting hyperalgesia in mice. ICA69 knockout led to reduced protein interacting with C-kinase 1 (PICK1) expression and increased glutamate receptor subunit 2 (GluR2) phosphorylation at Ser880 in spinal dorsal horn. In this study, we evaluated the role of ICA69 in the antihyperalgesic effects of EA and the underlying mechanism through regulation of GluR2 and PICK1 in spinal dorsal horn. Hyperalgesia was induced in mice with subcutaneous plantar injection of complete Freund adjuvant (CFA) to cause inflammatory pain. Electroacupuncture was then applied for 30 minutes every other day after CFA injection. When compared with CFA group, paw withdrawal frequency of CFA+EA group was significantly decreased. Remarkable increases in Ica1 mRNA expression and ICA69 protein levels on the ipsilateral side were detected in the CFA+EA group. ICA69 expression reached the peak value around day 3. More importantly, ICA69 deletion impaired the antihyperalgesic effects of EA on GluR2-p, but PICK1 deletion could not. Injecting ICA69 peptide into the intrathecal space of ICA69-knockout mice mimicked the effects of EA analgesic and inhibited GluR2-p. Electroacupuncture had no effects on the total protein of PICK1 and GluR2. And, EA could increase the formation of ICA69-PICK1 complexes and decrease the amount of PICK1-GluR2 complexes. Our findings indicate that ICA69 mediates the antihyperalgesic effects of EA on CFA-induced inflammatory pain by regulating spinal GluR2 through PICK1 in mice.
Kappa opioid signaling in the central nucleus of the amygdala promotes disinhibition and aversiveness of chronic neuropathic pain
Authors: Navratilova Edita , Ji Guangchen , Phelps Caroline , Qu Chaoling , Hein Matthew , Yakhnitsa Vadim , Neugebauer Volker , Porreca Frank
Published: December 2018

Chronic pain is associated with neuroplastic changes in the amygdala that may promote hyper-responsiveness to mechanical and thermal stimuli (allodynia and hyperalgesia) and/or enhance emotional and affective consequences of pain. Stress promotes dynorphin-mediated signaling at the kappa opioid receptor (KOR) in the amygdala and mechanical hypersensitivity in rodent models of functional pain. Here, we tested the hypothesis that KOR circuits in the central nucleus of the amygdala (CeA) undergo neuroplasticity in chronic neuropathic pain resulting in increased sensory and affective pain responses. After spinal nerve ligation (SNL) injury in rats, pretreatment with a long-acting KOR antagonist, nor-binaltorphimine (nor-BNI), subcutaneously or through microinjection into the right CeA, prevented conditioned place preference (CPP) to intravenous gabapentin, suggesting that nor-BNI eliminated the aversiveness of ongoing pain. By contrast, systemic or intra-CeA administration of nor-BNI had no effect on tactile allodynia in SNL animals. Using whole-cell patch-clamp electrophysiology, we found that nor-BNI decreased synaptically evoked spiking of CeA neurons in brain slices from SNL but not sham rats. This effect was mediated through increased inhibitory postsynaptic currents, suggesting tonic disinhibition of CeA output neurons due to increased KOR activity as a possible mechanism promoting ongoing aversive aspects of neuropathic pain. Interestingly, this mechanism is not involved in SNL-induced mechanical allodynia. Kappa opioid receptor antagonists may therefore represent novel therapies for neuropathic pain by targeting aversive aspects of ongoing pain while preserving protective functions of acute pain.
Effectiveness of Venlafaxine in Selective Serotonin Reuptake Inhibitor–Resistant Obsessive-Compulsive Disorder
Authors: Balachander Srinivas , Kodancha Prabhath Gujjadi , Arumugham Shyam Sundar , Sekharan Jaisoorya T. , Narayanaswamy Janardhanan C. , Reddy YC Janardhan
Published: December 2018

Background

Despite its favorable pharmacological profile and efficacy in major depression and anxiety disorders, evidence for the use of venlafaxine in obsessive-compulsive disorder (OCD) is limited. We sought to examine the real-world effectiveness of venlafaxine from a large database of an OCD clinic in India.

Methods

A total of 1704 consecutive patients who registered at the OCD clinic between June 2014 and December 2016 were evaluated with structured interviews and scales. Patients with symptomatic OCD (Yale-Brown Obsessive-Compulsive Severity ≥16) despite treatment with selective serotonin reuptake inhibitors and initiated on venlafaxine were included for analysis. The main outcome measures were response as defined by 35% or more reduction in the Yale-Brown Obsessive-Compulsive Severity total score and “all-cause discontinuation.”

Results

Of a total of 65 patients who were eligible for analysis, 29(45%) were responders at the end of 16 weeks and 27 (42%) continued to remain on venlafaxine. Repeated measures analysis of variance yielded significant reduction in the Yale-Brown Obsessive-Compulsive Severity total score (F(1.29, 82.4) = 56.54, P < 0.001, partial η2 = 0.469). On regression analysis, only lower insight (P = 0.048) predicted poor response.

Conclusions

The study suggests that venlafaxine may be useful in a proportion of patients with poor response to selective serotonin reuptake inhibitors and therefore requires to be studied in controlled trials.
Red, Dry, Itchy Plaques on Arms
Authors: Lee Kun W. , Jacob Sharon E.
Published: December 2018

Teledermatology describes dermatologic medical services provided through telecommunication technology. This case concerns a case of red, dry, itchy plaques on the arms.
Causes of acute respiratory failure in the immunocompromised host
Authors: Ferreyro Bruno L. , Munshi Laveena
Published: December 2018

Purpose of review

A wide spectrum of heterogeneous conditions can render a patient immunocompromised. Recent years have seen an increase in the number of immunocompromised patients given the earlier detection of conditions that require immunosuppressive therapies, changes in immunosuppressive regimens leading to increased survival or novel therapeutic advancements in oncologic care. Acute respiratory failure (ARF) is the leading cause of critical illness and mortality in this population. This review highlights the spectrum of causes of ARF in immunocompromised patients with a particular focus on acute toxicities of novel oncologic treatments.

Recent findings

Recent years have seen improved survival amongst critically ill immunocompromised patients with ARF. This is likely attributable to patient selection of immunosuppressive therapy, improved noninvasive microbiologic diagnostic techniques, improved antimicrobial prophylaxis, treatment, stewardship, and advancements in supportive care including intensive care. Infectious complications remain the leading cause of ARF in this population. However, one of the greatest challenges physicians continue to face is accurate identification of the cause of ARF, given the vast (and increasing) noninfectious causes of ARF across these patients. Emerging therapies, such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR T-cell) have contributed to this problem. Finally, undetermined ARF is reported in approximately 13% of immunocompromised and is associated with a worse prognosis.

Infectious complications are still the leading cause of ARF in immunocompromised patients. However, noninfectious complications, derived from the underlying disease or treatment, should be always considered, including novel therapies, such as ICIs and CAR T cells. Further research should focus in improving the diagnostic rate in this subgroup.
Rare respiratory diseases in the ICU: when to suspect them and specific approaches
Authors: Gibelin Aude , Parrot Antoine , Fartoukh Muriel , de Prost Nicolas
Published: December 2018

Purpose of review

A prompt identification of the cause of acute respiratory failure (ARF)/acute respiratory distress syndrome (ARDS) is required in order to initiate a targeted treatment. Yet, almost 10% of ARDS patients have no identified ARDS risk factor at ARDS diagnosis. Numerous rare causes of ARF have been reported in this setting. The purpose of this review is to delineate the main rare causes of ARF/ARDS and to provide clinicians with a pragmatic diagnostic work-up.

Recent findings

Recent epidemiological data have proposed the identification of a subgroup of ARDS patients lacking exposure to common risk factors. These can be categorized as having immune, drug-induced, malignant and idiopathic diseases. A standardized diagnostic work-up including chest imaging, the objective assessment of left heart filling pressures, bronchoalveolar lavage fluid microbiological investigations and cytological analysis, immunological tests and search for pneumotoxic drugs may allow for identifying the cause of ARF in most cases. Open lung biopsy should be considered in other cases.

A prompt identification of the cause of ARF is required to initiate a targeted treatment. Patients with no identified ARDS risk factor should undergo a comprehensive and hierarchized diagnostic work-up.
New physiological insights in ventilation during cardiopulmonary resuscitation
Authors: Cordioli Ricardo L. , Grieco Domenico L. , Charbonney Emmanuel , Richard Jean-Christophe , Savary Dominique
Published: December 2018

Purpose of review

In the setting of cardiopulmonary resuscitation (CPR), classical physiological concept about ventilation become challenging. Ventilation may exert detrimental hemodynamic effects that must be balanced with its expected benefits. The risks of hyperventilation have been thoroughly addressed, even questioning the need for ventilation, emphasizing the need to prioritize chest compression quality. However, ventilation is mandatory for adequate gas exchange as soon as CPR is prolonged. Factors affecting the capability of chest compressions to produce alveolar ventilation are poorly understood. In this review, we discuss the conventional interpretation of interactions between ventilation and circulation, from the perspective of novel physiological observations.

Recent findings

Many patients with cardiac arrest exhibit ‘intrathoracic airway closure.’ This phenomenon is associated with lung volume reduction, impedes chest compressions to generate ventilation and overall limits the delivered ventilation. This phenomenon can be reversed by the application of small levels of positive end-expiratory pressure. Also, a novel interpretation of the capnogram can rate the magnitude of this phenomenon, contributing to clarify the physiological meaning of exhaled CO2 and may help assess the real amount of delivered ventilation.

Recent advances in the understanding of ventilatory physiology during CPR shows that capnogram analysis not only provides information on the quality of resuscitation but also on the amount of ventilation produced by chest compressions and on the total amount of ventilation.
Weight stigma and its impact on paediatric care
Authors: Palad Carl J. , Yarlagadda Siddharth , Stanford Fatima Cody
Published: December 2018

Purpose of review

This review aims to evaluate current research findings relevant to weight stigmatization, to acknowledge the deleterious impact it has on the health of the paediatric population and to provide insight to optimize future guidelines for the treatment of individuals with overweight and obesity.

Recent findings

Obesity prevalence continues to rise in the USA with estimates in children from ages 2–19 years of 18.5%, an all-time high. With the increase in obesity, there has been a concomitant increase in weight stigma, which affects both youth and general population across varied levels of socioeconomic status and body sizes.

Weight stigma is a contributing phenomenon to the current obesity epidemic, as individuals with stigmatized experiences (weight-based teasing, bullying, victimization) have increased risks for acquiring adverse health outcomes that encompass the physical, behavioural and psychological. Weight stigma can also lead affected individuals to internalize such experiences which decrease their overall quality of life. Sources of stigma may come from peers, family, educators, media, as well as healthcare professionals, as highlighted in this review. Efforts to establish prevention and treatment strategies for weight stigma may generate further traction to help improve global obesity rates.

Video abstract

http://links.lww.com/COE/A15
The diagnostic performance of a simplified blood test (SteatoTest-2) for the prediction of liver steatosis
Authors: Poynard Thierry , Peta Valentina , Munteanu Mona , Charlotte Frederic , Ngo Yen , Ngo An , Perazzo Hugo , Deckmyn Olivier , Pais Raluca , Mathurin Philippe , Myers Rob , Loomba Rohit , Ratziu Vlad
Published: December 2018

Background

Serum biomarkers of steatosis such as the SteatoTest are recommended for large-scale screening studies, because imaging is less accessible and more expensive.

Aims

The primary aim of this retrospective analysis of prospective studies was to construct a new SteatoTest-2 that was not inferior to the reference first-generation SteatoTest, but that did not include BMI or bilirubin, as these two components can increase test variability because of the assessment of weight and height and in case of Gilbert syndrome or hemolysis, respectively.

Patients and methods

Five different subsets of 2997 patients with biopsies were evaluated for test construction and validation, and four to assess the prevalence of steatosis in target populations with increasing risks of steatosis. The performance of the SteatoTest-2 was compared with the reference test, using the noninferiority test (0.10 margin) and the Lin concordance coefficient.

Results

Areas under the receiver operating characteristic curve of the SteatoTest-2 were noninferior to the reference test (P<0.001). Areas under the receiver operating characteristic curve varied in the SteatoTest-2 and the reference test according to subsets and the prevalence of steatosis, with 0.772 [95% confidence interval (CI): 0.713–0.820] versus 0.786 (95% CI: 0.729–0.832) in the 2997 cases with biopsy and 0.822 (95% CI: 0.810–0.834) versus 0.868 (95% CI: 0.858–0.878) in the 5776 cases including healthy individuals without risk factors of steatosis as controls, respectively. The Lin coefficient was highly concordant (P<0.001), from 0.74 (95% CI: 0.74–0.74) in presumed NAFLD to 0.91 (95% CI: 0.89–0.93) in the construction subset.

Conclusion

The SteatoTest-2 is simpler and noninferior to the first-generation SteatoTest for the diagnosis of steatosis, without the limitations of BMI and bilirubin.
Indirect Estimation of Race/Ethnicity for Survey Respondents Who Do Not Report Race/Ethnicity
Authors: Dembosky Jacob W. , Haviland Amelia M. , Haas Ann , Hambarsoomian Katrin , Weech-Maldonado Robert , Wilson-Frederick Shondelle M. , Gaillot Sarah , Elliott Marc N.
Published: December 2018

Background:

Researchers are increasingly interested in measuring race/ethnicity, but some survey respondents skip race/ethnicity items.

Objectives:

The main objectives of this study were to investigate the extent to which racial/ethnic groups differ in skipping race/ethnicity survey items, the degree to which this reflects reluctance to disclose race/ethnicity, and the utility of imputing missing race/ethnicity.

Research Design:

We applied a previously developed method for imputing race/ethnicity from administrative data (Medicare Bayesian Improved Surname and Geocoding 2.0) to data from a national survey where race/ethnicity was usually self-reported, but was sometimes missing. A linear mixed-effects regression model predicted the probability of self-reporting race/ethnicity from imputed racial/ethnic probabilities.

Subjects:

In total, 508,497 Medicare beneficiaries responding to the 2013–2014 Medicare Consumer Assessment of Healthcare Providers and Systems surveys were included in this study.

Measures:

Self-reported race/ethnicity and estimated racial/ethnic probabilities.

Results:

Black beneficiaries were most likely to not self-report their race/ethnicity (6.6%), followed by Hispanic (4.7%) and Asian/Pacific Islander (4.7%) beneficiaries. Non-Hispanic whites were the least likely to skip these items (3.2%). The 3.7% overall rate of missingness is similar to adjacent demographic items. General patterns of item missingness rather than a specific reluctance to disclose race/ethnicity appears to explain the elevated rate of missing race/ethnicity among Asian/Pacific Islander and Hispanic beneficiaries and most but not all among Black beneficiaries. Adding imputed cases to the data set did not substantially alter the estimated overall racial/ethnic distribution, but it did modestly increase sample size and statistical power.

Conclusions:

It may be worthwhile to impute race/ethnicity when this information is unavailable in survey data sets due to item nonresponse, especially when missingness is high.
Direct detection, capsular typing and β-lactamase resistance genes in Haemophilus influenzae isolated from sinusitis samples
Authors: Eshaghi Hamid , Abdolsalehi Mohammad R. , Mohammadi Mohsen , Khodabandeh Mahmoud , Kafshgari Ramin , Pournajaf Abazar , Hasannejad-Bibalan Meysam , Yaghoubi Sajad , Torki Alireza , Gholami Mehrdad
Published: December 2018

Objective:

Haemophilus influenzae is the causative agent of invasive and noninvasive infections such as chronic obstructive lung disease exacerbation, sinusitis, otitis media, and conjunctivitis. The study was undertaken to direct detection, capsular typing, and investigate the occurrence of β-lactamase resistance genes in H. influenzae strains isolated from sinusitis samples.

Materials and methods:

We investigated the presence of H influenzae in 137 sinusitis samples obtained from the patients had referred to Rasoole-Akram Hospital in Tehran in 2017. DNA extraction was performed according to the QIAamp kit. polymerase chain reaction (PCR) amplification was performed with specific primers to determine H. influenzae and capsular-typing and to detect resistance genes.

Results:

Eleven samples were positive for the presence of H. influenzae. Overall, 5, 2, and 4 isolates were H. influenzae type b, type A, and nontypeable H. influenzae, respectively. Of 11 isolates of H. influenzae, only two isolates (18%) were β-lactamase positive and carried the TEM-1 gene, but others were negative for the ROB-1 gene. As well, the current study showed that 45.5% (n; five of 11 encapsulated H. influenzae) of isolates were type b, which were the predominant types.

Conclusion:

Our data suggest that the conventional PCR can help increase detection rates of bacterial cause of sinusitis and resistance genes in clinical samples for effective treatment in individual sensitive to invasive infection.
Treponema pallidum subsp. pallidum DNA and RNA in Semen of a Syphilis Patient Without Genital or Anal Lesions
Authors: Godornes Charmie , Ciccarese Giulia , Drago Francesco , Giacani Lorenzo
Published: December 2018

Treponema pallidum subsp. pallidum DNA and RNA were detected in a semen specimen of a syphilis patient with no genital or anal sores and no clinically evident orchitis. No nucleic acids were found in a urine sample of the same patient collected immediately before the semen sample. Exposure to the syphilis agent through semen could account for transmission episodes in the absence of direct contact with a syphilitic sore.