bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac effects of SGLT2 inhibitors: the sodium hypothesis
Authors: Bertero Edoardo , Prates Roma Leticia , Ameri Pietro , Maack Christoph 
Published: August 2017

Abstract
The effects of intense glycaemic control on macrovascular complications in patients with type 2 diabetes are incompletely resolved, and many glucose-lowering medications negatively affect cardiovascular outcomes. Recently, the EMPA-REG OUTCOME trial revealed that empagliflozin, an inhibitor of the sodium-glucose cotransporter 2 (SGLT2), substantially reduced the risk of hospitalization for heart failure, death from cardiovascular causes, and all-cause mortality in patients with type 2 diabetes mellitus at high cardiovascular risk. Although several mechanisms may explain this benefit, plasma volume contraction and a metabolic switch favouring cardiac ketone bodies oxidation have recently been proposed as the major drivers. Recent experimental work has prompted a novel and intriguing hypothesis, according to which empagliflozin may reduce intracellular sodium (Na+) load observed in failing cardiac myocytes by inhibiting the sarcolemmal Na+/H+ exchanger. Since elevated intracellular Na+ hampers mitochondrial Ca2+ handling and thereby, deteriorates energy supply and demand matching and the mitochondrial antioxidative defence systems, empagliflozin may positively affect cardiac function by restoring mitochondrial function, and redox state in the failing heart. Here, we review the current evidence for such a third mechanistic hypothesis, which may foster heart failure and diabetes research into a new direction which harbours several potential targets for therapeutic intervention.
Antibody therapy for the management of severe asthma with eosinophilic inflammation
Authors: Ohta Ken , Nagase Hiroyuki , Suzukawa Maho , Ohta Shin 
Published: August 2017

AbstractOne of the characteristic features of asthma is chronic airway inflammation typically with eosinophil infiltration. Most asthmatics can be treated successfully with conventional treatment appropriate for their severity, but in some severe cases, asthma cannot be well controlled even with thorough treatment and this condition is known as ‘refractory asthma’. To overcome severe refractory asthma, a new therapeutic strategy with biologics has been developed based on the knowledge of molecular mechanisms of airway inflammation in asthma, induced by the condition of high Th2-type responses and activation of eosinophils as well as allergic reactions. Humanized anti-human IgE antibody (anti-IgE; omalizumab) was the first biological preparation approved for treating asthma. Based on clinical evidence, treatment with anti-IgE (anti-IgE therapy) has been accepted as a new therapeutic approach for severe allergic asthma in adults since 2009 and in children since 2012 and has been shown to have ~60% efficacy. More recently, a humanized anti-IL-5 antibody (anti-IL-5; mepolizumab) was launched in June 2016 and has attracted great interest due to its potential effects. Several clinical studies are also ongoing to evaluate the biological preparations targeting IL-5 receptor α (IL-5Rα), IL-4 receptor α (IL-4Rα), which is shared by IL-4 and IL-13, thymic stromal lymphopoietin (TSLP) and IL-33. The new strategy with biologics targeting eosinophilic airway inflammation might open a new array for us to overcome severe refractory asthma in the future.
Impact of an emergency department electronic sepsis surveillance system on patient mortality and length of stay
Authors: Austrian Jonathan S , Jamin Catherine T , Doty Glenn R , Blecker Saul 
Published: August 2017

Abstract

Objective
The purpose of this study was to determine whether an electronic health record–based sepsis alert system could improve quality of care and clinical outcomes for patients with sepsis.

Materials and Methods
We performed a patient-level interrupted time series study of emergency department patients with severe sepsis or septic shock between January 2013 and April 2015. The intervention, introduced in February 2014, was a system of interruptive sepsis alerts triggered by abnormal vital signs or laboratory results. Primary outcomes were length of stay (LOS) and in-hospital mortality; other outcomes included time to first lactate and blood cultures prior to antibiotics. We also assessed sensitivity, positive predictive value (PPV), and clinician response to the alerts.

Results
Mean LOS for patients with sepsis decreased from 10.1 to 8.6 days (P &lt; .001) following alert introduction. In adjusted time series analysis, the intervention was associated with a decreased LOS of 16% (95% CI, 5%-25%; P = .007, with significance of α = 0.006) and no change thereafter (0%; 95% CI, −2%, 2%). The sepsis alert system had no effect on mortality or other clinical or process measures. The intervention had a sensitivity of 80.4% and a PPV of 14.6%.

Discussion
Alerting based on simple laboratory and vital sign criteria was insufficient to improve sepsis outcomes. Alert fatigue due to the low PPV is likely the primary contributor to these results.

Conclusion
A more sophisticated algorithm for sepsis identification is needed to improve outcomes.
A Prospective Analysis of Neuromonitoring for Confirmation of Lead Placement in Dorsal Root Ganglion Stimulation
Authors: Falowski Steven M , Dianna Andreas 
Published: August 2017

Abstract

BACKGROUND
Dorsal root ganglion stimulation is a neuromodulation therapy used for chronic neuropathic pain. Typically, patients are awakened intraoperatively to confirm adequate placement.

OBJECTIVE
To determine whether neuromonitoring can confirm placement in an asleep patient.

METHODS
This is a prospective analysis of 12 leads placed in 6 patients. Lead confirmation was confirmed by awake intraoperative testing, as well as asleep testing utilizing neuromonitoring. Patients were used as their own control. Sensory and motor thresholds for each patient with awake and asleep neuromonitoring testing were recorded. Intraoperative impedance and postoperative programming were also recorded.

RESULTS
In each patient, paresthesias were generated prior to motor contractions in the awake patient. For each patient, somatosensory evoked potential responses were present after lowering below the dropout threshold of electromyogram responses with neuromonitoring. There were varying degrees of separation in the thresholds that did not appear to be consistent across level or diagnosis. Smaller degrees of separation between thresholds during awake testing also held true in the asleep patient. This was further confirmed with postoperative programming. Impedances did not alter the separation in thresholds or amount of stimulation required for responses. One patient was combative during awake testing, and therefore motor thresholds were not obtained. This same patient was determined to have a ventral placement, confirmed with awake and asleep neuromonitoring testing.

CONCLUSION
This series demonstrates that the proposed neuromonitoring protocol can be used in an asleep patient to assure proper positioning of the dorsal root ganglion electrode in the dorsal foramen by generating somatosensory evoked potential responses in the absence of electromyogram responses.
Medical Student Perceptions of Global Surgery at an Academic Institution: Identifying Gaps in Global Health Education
Authors: Mehta Ambar , Xu Tim , Murray Matthew , Casey Kathleen M. 
Published: August 2017

Purpose
Robust global health demands access to safe, affordable, timely surgical care for all. The long-term success of global surgery requires medical students to understand and engage with this emerging field. The authors characterized medical students’ perceptions of surgical care relative to other fields within global health.

Method
An optional, anonymous survey was given to all Johns Hopkins medical students from February to March 2016 to assess perceptions of surgical care and its role in global health.

Results
Of 480 students, 365 (76%) completed the survey, with 150 (41%) reporting global health interests. One-third (34%) of responding students felt that surgical care is one of two fields with the greatest potential global health impact in the future, second to infectious disease (49%). A minority (28%) correctly identified that trauma results in more deaths worldwide than obstetric complications or HIV/AIDS, tuberculosis, and malaria combined. Relative to other examined fields, students perceived surgical care as the least preventive and cost-effective, and few students (3%) considered adequate surgical care the best indicator of a robust health care system. Students believed that practicing in a surgical field was least amenable to pursuing a global health career, citing several barriers.

Conclusions
Medical students have several perceptions of global surgery that contradict current evidence and literature, which may have implications for their career choices. Opportunities to improve students’ global health knowledge and awareness of global surgery career paths include updating curricula, fostering meaningful international academic opportunities, and creating centers of global surgery and global health consortia.
Clinician–Investigator Training and the Need to Pilot New Approaches to Recruiting and Retaining This Workforce
Authors: Hall Alison K. , Mills Sherry L. , Lund P. Kay 
Published: August 2017

Clinician–investigators, also called physician–scientists, offer critical knowledge and perspectives that benefit research on basic science mechanisms, improved diagnostic and therapeutic approaches, population and outcomes medicine, health policy, and health services, yet few clinically trained health professionals pursue a research career. Sustaining this workforce requires attention to the unique challenges faced by investigators who must achieve clinical and research competence during training and their careers. These challenges include the duration of required clinical training, limited or discontinuous research opportunities, high levels of educational debt, balancing the dual obligations and rewards of clinical care and research, competition for research funding, and the need for leadership development after training. Women and individuals from underrepresented racial and ethnic groups comprise a small percentage of this workforce.
The authors summarize the recent literature on training for clinician–investigators, emphasizing approaches with encouraging outcomes that warrant broader implementation. Using this overview as background, they convened three workshops at the National Institutes of Health in 2016 to identify and refine key priorities for potential new pilot programs to recruit and retain the clinician–investigator workforce. From these workshops emerged three priorities for future pilot programs: (1) support for research in residency, (2) new research on-ramps for health professionals at multiple career stages, and (3) national networks to diversify and sustain clinician–investigator faculty. Implementation of any pilot program will require coordinated commitment from academic health centers, medical licensing/certification boards, professional societies, and clinician–investigators themselves, in addition to support from the National Institutes of Health.
Risk Factors Associated With Skin and Soft Tissue Infections Among Hospitalized People Who Inject Drugs
Authors: Phillips Kristina T. , Anderson Bradley J. , Herman Debra S. , Liebschutz Jane M. , Stein Michael D. 
Published: August 2017

Objectives:
Skin and soft tissue infections (SSTIs) are common among people who inject drugs (PWID), and can lead to serious morbidity and costly emergency room and hospital utilization. A range of high-risk injection practices may contribute to these infections. The goal of the current study was to examine risk practices that were associated with SSTIs in a sample of hospitalized PWID.

Methods:
PWID (N = 143; 40.6% female) were recruited from inpatient medical units at a large urban hospital and completed a baseline interview that focused on infection risk. Measures included demographics, substances used/injected, and self-report of SSTIs (ie, abscesses, ulcers, or cellulitis) within the past year. The Bacterial Infections Risk Scale for Injectors—a 7-item index—assessed specific behaviors expected to increase the risk of acquiring SSTIs (eg, injection without skin cleaning, intramuscular injection).

Results:
The sample was 58% Caucasian and averaged 38.7 (SD = 10.7) years of age. Ninety-three participants (65%) reported at least 1 SSTI within the past year. Using a logistic regression model, the Bacterial Infections Risk Scale for Injectors (odds ratio 1.87, P = 0.004) and total number of injections over the past 3 months (odds ratio 2.21, P = 0.002) were associated with past year SSTIs.

Conclusions:
In conclusion, rates of past-year SSTIs were high in this sample of hospitalized PWID. Results suggest that interventions should target specific injection practices to reduce infection risk.
Nitrite Inhalant Use and HIV Infection Among Chinese Men Who Have Sex With Men in 2 Large Cities in China
Authors: Wang Xiaofang , Li Yanqi , Wu Zunyou , Tang Zhenzhu , Reilly Kathleen H. , Nong Quanxing 
Published: August 2017

Objective:
This study aims to examine the role that nitrite inhalants play in HIV infection and risky sex behaviors among Chinese men who have sex with men (MSM).

Methods:
The study consisted of a baseline and a follow-up survey conducted in Beijing and Nanning, China. The baseline study recruited participants through online advertisements and peer referral to complete a questionnaire interview, oral rapid HIV test, and blood HIV and syphilis tests. The follow-up included a questionnaire interview, and optional oral and/or blood HIV testing. Questionnaires collected information about sociodemographic and behavioral characteristics. Univariable and multivariable logistic regression analyses were performed to evaluate associations between characteristics and nitrite inhalant use.

Results:
One-third (29.8%) of 510 participants at baseline reported nitrite inhalant use during male-male sex in the past 6 months. Nitrite inhalant use was associated with higher odds of HIV infection (odds ratio 2.0, 95% confidence interval 1.1–3.7). Factors associated with nitrite inhalant use were as follows: never married, currently living in Beijing, not willing to test for HIV with oral self-test kit, and seeking male sex partners via the internet. In follow-up, 270 of 317 responded MSM reported having male-male sex after baseline and 17% of them used nitrite inhalants during sex.

Conclusions:
MSM who use nitrite inhalants are more likely to engage in risky HIV behaviors and have higher HIV infection risk than those who do not. Identifying MSM who use nitrite inhalants for targeted HIV interventions, such as HIV testing, might make HIV-prevention efforts more efficient among this population.
Genetics in inclusion body myositis
Authors: Rothwell Simon , Lilleker James B. , Lamb Janine A. 
Published: August 2017

Purpose of review
To review the advances in our understanding of the genetics of inclusion body myositis (IBM) in the past year.

Recent findings
One large genetic association study focusing on immune-related genes in IBM has refined the association within the human leukocyte antigen (HLA) region to HLA-DRB1 alleles, and identified certain amino acid positions in HLA-DRB1 that may explain this risk. A suggestive association with CCR5 may indicate genetic overlap with other autoimmune diseases. Sequencing studies of candidate genes involved in related neuromuscular or neurodegenerative diseases have identified rare variants in VCP and SQSTM1. Proteomic studies of rimmed vacuoles in IBM and subsequent genetic analyses of candidate genes identified rare missense variants in FYCO1. Complex, large-scale mitochondrial deletions in cytochrome c oxidase-deficient muscle fibres expand our understanding of mitochondrial abnormalities in IBM.

Summary
The pathogenesis of IBM is likely multifactorial, including inflammatory and degenerative changes, and mitochondrial abnormalities. There has been considerable progress in our understanding of the genetic architecture of IBM, using complementary genetic approaches to investigate these different pathways.
Comparison of Clinical Findings of Congenital Muscular Torticollis Between Patients With and Without Sternocleidomastoid Lesions as Determined by Ultrasonography
Authors: Han Mi-Hyang , Kang Jin Young , Do Hyun Jung , Park Hyun Suk , Noh Hyun Jin , Cho Yun-Hwa , Jang Dae-Hyun 
Published: August 2017

Aim:
To compare clinical findings for patients with congenital muscular torticollis (CMT) between those with and without a sternocleidomastoid (SCM) lesion.

Methods:
Medical records of 182 patients with CMT were retrospectively reviewed and the patients were divided into SCM lesion and nonlesion groups by ultrasonographic results. Intrauterine position, age, duration of therapy, rotation/tilting side, and the passive range of motion and angle of the neck were compared.

Results:
There were 74 SCM lesion and 108 nonlesion cases. The mean age at the first visit was 55.3 days in the SCM lesion group and 146.6 days in the nonlesion group. The mean therapy time in the nonlesion group was 66.5 days, significantly shorter than for the SCM lesion group (117.5 d). Tilting and rotation of the head in the same direction was observed only in the nonlesion group (n=9, 8.3%). Rotational limitation of the affected muscle side was 22.6 degree in the SCM lesion and 3.6 degree in the nonlesion group, and the tilting limitation was 19.2 degree in the SCM lesion and 10.4 degree in the nonlesion group.

Conclusions:
The nonlesion group had a better prognosis with shorter treatment duration. This group was more limited in head tilting than in head rotation, and the pattern of head rotation/tilting in the same direction was observed only in this group. These findings suggest that pathophysiological mechanisms and clinical characteristics may differ between CMT patients with and without SCM lesions.

Level of Evidence:
Level II—prognostic studies, retrospective study.
Recovery of Motor Nerve Injuries Associated With Displaced, Extension-type Pediatric Supracondylar Humerus Fractures
Authors: Shore Benjamin J. , Gillespie Bryce T. , Miller Patricia E. , Bae Donald S. , Waters Peter M. 
Published: August 2017

Background:
Nerve injuries occur in approximately 11% of pediatric extension supracondylar humerus fractures (SCHF), yet there is scarce literature to guide clinicians on management. The primary goal of this study was to report the presentation, treatment, and outcome of motor nerve injuries associated with extension SCHF. Our secondary goal was to determine which injury and treatment factors were associated with prolonged motor nerve recovery.

Methods:
Two hundred forty-four traumatic nerve injuries associated with extension SCHF treated at a single institution between 1996 and 2012 were reviewed. Patients with iatrogenic nerve injuries or subjective paresthesias without motor deficit were excluded. Univariable and multivariable general linear modeling were used to compare recovery times across nerve injury types and to determine the effect of injury and treatment characteristics on recovery time.

Results:
Patients were a mean age of 6.7 years, with 89% presenting with a single nerve injury and 29% of the cohort experiencing a concurrent vascular injury. The majority of injuries (62%) were to the median nerve. Forty-three (18%) cases had acute nerve decompression at the time of fracture fixation. Five cases required subsequent surgery for poor nerve recovery; none of which underwent initial nerve decompression. Thirty-one patients were lost to follow-up after injury. Median time to nerve recovery was 2.3 months (IQR 1.4 to 3.7 mo); 60% of injuries had nerve recovery by 3 months and 196 (92%) patients had complete nerve recovery at final follow-up. A greater percentage of isolated median nerve (70%) injuries recovered within 3 months compared with radial nerve (42%) injuries (P=0.01). Multivariable analysis demonstrated that multiple nerve injuries took 54% longer to recover than single median nerve injuries (P=0.01), and single radial nerve injuries took 30% longer to recover than single median nerve injuries (P=0.04).

Conclusions:
The majority of nerve injuries associated with pediatric extension SCHF recover within 6 months without acute nerve decompression. The presence of either an isolated radial nerve injury or multiple nerve injuries is associated with prolonged motor recovery.

Level of Evidence:
Level IV.
Neuroprotective Effects of C-terminal Domain of Tetanus Toxin on Rat Brain Against Motorneuron Damages After Experimental Spinal Cord Injury
Authors: Sozbilen Murat Celal , Ozturk Murat , Kaftan Gizem , Dagci Taner , Ozyalcin Halit , Armagan Guliz 
Published: August 2017

Study Design.
Experimental animal study investigating the efficacy of C-terminal domain of tetanus toxin application as neuroprotective effects on rat brain in a model of spinal cord injury (SCI).

Objective.
The aim of the present study was to investigate the possible role of C-terminal domain of tetanus toxin (Hc-TeTx) on cell death mechanisms including apoptosis and autophagy following SCI.

Summary of Background Data.
Traumatic SCI can lead to posttraumatic inflammation, oxidative stress, motor neuron apoptosis, necrosis, and autophagy of tissue. To promote and enhance recovery after SCI, recent development of devices and therapeutic interventions are needed.

Methods.
Twenty-eight adult rats were divided into four groups (n = 7 each) as follows: sham, trauma (SCI), SCI + Hc-TeTx, and SCI + methylprednisolone groups. The functional neurological deficits due to the SCI were assessed by behavioral analysis using the Basso, Beattie and Bresnahan (BBB) open-field locomotor test. The alterations in pro-/anti-apoptotic and autophagy related-protein levels were measured by Western blotting technique.

Results.
In this study, Hc-TeTx promotes locomotor recovery and motor neuron survival of SCI rats. Hc-TeTx also decreased expression of bax, bad, bak, cleaved caspase-3, Ask1, and autophagy-related proteins including Atg5 and LC3II in brain. Our study provides an evidence that cell death mechanisms play critical roles in SCI and that the nontoxic peptides including Hc-TeTx may exert protective effect and decrease cell death following SCI.

Conclusion.
Our preliminary findings suggest a possible therapeutic agent to improve survival after spinal cord trauma, but further analysis are still needed to evaluate the difference between acute and chronic injuries.

Level of Evidence: N/A