bluuebunny/crossref_metadata_2025_split huggingface dataset:
International Consensus Definition of Low Anterior Resection Syndrome
Authors: Keane Celia , Fearnhead Nicola S. , Bordeianou Liliana G. , Christensen Peter , Basany Eloy Espin , Laurberg Søren , Mellgren Anders , Messick Craig , Orangio Guy R. , Verjee Azmina , Wing Kirsty , Bissett Ian 
Published: February 2020

BACKGROUND:
Low anterior resection syndrome is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The low anterior resection syndrome score was designed as a simple tool for clinical evaluation of low anterior resection syndrome. Although the low anterior resection syndrome score has good clinical utility, it may not capture all important aspects that patients may experience.

OBJECTIVE:
The aim of this collaboration was to develop an international consensus definition of low anterior resection syndrome that encompasses all aspects of the condition and is informed by all stakeholders.

DESIGN:
This international patient-provider initiative used an online Delphi survey, regional patient consultation meetings, and an international consensus meeting.

PARTICIPANTS:
Three expert groups participated: patients, surgeons, and other health professionals from 5 regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in 3 languages (English, Spanish, and Danish).

MAIN OUTCOME MEASURE:
The primary outcome measured was the priorities for the definition of low anterior resection syndrome.

RESULTS:
Three hundred twenty-five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96%, and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to 8 symptoms and 8 consequences that capture essential aspects of the syndrome.

LIMITATIONS:
Sampling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this.

CONCLUSIONS:
This is the first definition of low anterior resection syndrome developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of low anterior resection syndrome. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in low anterior resection syndrome over time and with intervention.
Pulmonary Delivery of Antiarrhythmic Drugs for Rapid Conversion of New-Onset Atrial Fibrillation
Authors: Verrier Richard L. , Belardinelli Luiz 
Published: February 2020

Abstract:
Pharmacologic management of atrial fibrillation (AF) is a pressing problem. This arrhythmia afflicts >5 million individuals in the United States and prevalence is estimated to rise to 12 million by 2050. Although the pill-in-the-pocket regimen for self-administered AF cardioversion introduced over a decade ago has proven useful, significant drawbacks exist. Among these are the relatively long latency of effects in the range of hours along with potential for hypotension and other adverse effects. This experience prompted development of a new strategy for increasing plasma concentrations of antiarrhythmic drugs rapidly and for a limited time, namely, pulmonary delivery. In preclinical studies in Yorkshire pigs, intratracheal administration of flecainide was shown to cause a rapid, reproducible increase in plasma drug levels. Moreover, pulmonary delivery of flecainide converted AF to normal sinus rhythm by prolonging atrial depolarization, which slows intra-atrial conduction and seems to be directly correlated with efficacy in converting AF. The rapid rise in plasma flecainide levels optimizes its anti-AF effects while minimizing adverse influences on ventricular depolarization and contractility. A more concentrated and soluble formulation of flecainide using a novel cyclodextrin complex excipient reduced net drug delivery for AF conversion when compared to the acetate formulation. Inhalation of the beta-adrenergic blocking agent metoprolol slows ventricular rate and can also terminate AF. In human subjects, oral inhalation of flecainide acetate with a hand-held, breath-actuated nebulizer results in signature prolongation of the QRS complex without serious adverse events. Thus, pulmonary delivery is a promising advance in pharmacologic approach to management of AF.
Urinary Tract Infections With Extended-spectrum-β-lactamase-producing Bacteria
Authors: Amin Omayma , Prestel Christopher , Gonzalez Mark D. , Lyon Tabitha , Shane Andi , Jaggi Preeti , Tippett Ashley , Yildirim Inci 
Published: February 2020

Background:
Urinary tract infections (UTI) are the most common bacterial infections among infants and young children with fever without a source. Extended-spectrum β-lactamases (ESBLs) have emerged as emerging cause of UTI globally; however, data about risk factors and clinical features of children with ESBL-UTI have been scarce.

Objective:
To describe the predisposing risk factors, clinical and microbiologic features associated with pediatric UTIs caused by ESBL-producing bacteria (ESBL-PB).

Methods:
Our nested case-control study ran from January 1, 2012 to December 31, 2016. Pediatric patients with ESBL-PB UTI were compared with patients with non-ESBL-PB UTI matched for age and year of diagnosis.

Results:
A total of 720 children were enrolled (240 cases and 480 controls). Patients with ESBL-PB UTI were more likely to have a history of prior intensive care unit (ICU) admission (22.5% vs. 12.3%, P < 0.001), at least one underlying comorbidity (19.2% vs. 5.8%, P < 0.001), prior hospitalization (47.1% vs. 32.9%, P < 0.001), exposure to a cephalosporin antibiotic within 30 days before culture (7.5% vs. 4.2%, P = 0.035), and to have cystostomy (7.9% vs. 1.5%, P < 0.001) compared with those with non-ESBL-PB UTI. Patients with ESBL-PB UTI were more likely to present with hypothermia (48.8% vs. 38.5%, P = 0.009); had significantly longer average hospital stays {8.7 days [95% confidence interval (CI): 3.2–14.3] vs. 4.0 days (95% CI: 2.5–5.5)} and were more likely to be admitted to the ICU [odds ratio (OR) 1.8; 95% CI: 1.1-2.9). Multivariate analysis determined that only having cystostomy (OR 3.7; 95% CI: 1.4–9.4] and at least one underlying comorbidity (OR 2.4; 95% CI: 1.3–4.3) were the independent risk factors for ESBL-PB UTI. All ESBL-PB isolates tested against meropenem were susceptible, majority were resistant to multiple non-beta-lactam antibiotics.

Conclusions:
Children with underlying comorbidities and cystostomy are at higher risk for ESBL-PB UTI, but majority of ESBL cases were patients without any known risk factors. Clinical signs/symptoms and commonly used biochemical markers were unreliable to differentiate cases caused by ESBL-PB from those caused by non-ESBL-PB. Further research is needed to elucidate the conditions most associated with ESBL-PB UTIs among children to properly guide empirical therapy in patients at-risk for these infections, to improve the outcomes, and finally, to determine strategies for rational antimicrobial use.
Neonatal Outcomes Following Culture-negative Late-onset Sepsis Among Preterm Infants
Authors: Jiang Siyuan , Yang Zuming , Shan Ruobing , Zhang Yi , Yan Weili , Yang Yi , Shah Prakesh S. , Lee Shoo K. , Cao Yun 
Published: February 2020

Background:
Culture-negative late-onset sepsis (LOS) is commonly diagnosed in neonatal intensive care units, while the outcomes of neonatal culture-negative LOS are not reported for large cohorts. This study aimed to examine the incidence and neonatal outcomes for culture-negative LOS in a contemporary multicenter cohort of preterm infants.

Methods:
We performed a retrospective analysis of data from a cluster-randomized controlled study. Infants <34 weeks of gestation and admitted to 25 neonatal intensive care units between May 1, 2015, and April 30, 2018, were included. Culture-negative LOS was diagnosed if infants had abnormal manifestations and laboratory tests but negative blood cultures. The primary outcome was a composite of mortality or morbidities including periventricular leukomalacia (PVL), retinopathy of prematurity (ROP) ≥ stage 3 or bronchopulmonary dysplasia (BPD).

Results:
Of 22,346 eligible infants, 1505 (6.7%) infants had culture-negative and 761 (3.4%) infants had culture-positive LOS. Compared with infants without LOS, infants with culture-negative LOS had higher rates of composite outcome (24.1% vs. 9.6%), death (3.8% vs. 1.8%), PVL (4.8% vs. 2.2%), severe ROP (3.3% vs. 1.1%) and BPD (18.1% vs. 7.0%). After adjustment, culture-negative LOS was independently associated with increased risk of composite outcome {adjusted odds ratio [aOR]: 1.8 [95% confidence interval (CI): 1.5–2.1]}, PVL [aOR: 2.0 (95% CI: 1.4–2.8)] and BPD [aOR: 1.8 (95% CI: 1.5–2.2)] relative to the absence of LOS.

Conclusion:
Culture-negative LOS was frequently diagnosed in preterm infants and was associated with increased risks of adverse outcomes. There is an emerging need for more precise diagnosis and treatment strategies for culture-negative LOS.
Preclinical Detection of Non-catheter Related Late-onset Sepsis in Preterm Infants by Fecal Volatile Compounds Analysis
Authors: Berkhout Daniel J.C. , Niemarkt Hendrik J. , Andriessen Peter , Vijlbrief Daniel C. , Bomers Marije K. , Cossey Veerle , Hulzebos Christian V. , van Kaam Anton H. , Kramer Boris W. , van Lingen Richard A. , Wicaksono Alfian N. , Covington James A. , van Weissenbruch Mirjam M. , Benninga Marc A. , de Boer Nanne K.H. , de Meij Tim G.J. 
Published: February 2020

Background:
Late onset sepsis (LOS) in preterm infants is preceded by fecal volatile organic compound (VOC) alterations, suggesting an etiologic role of gut microbiota in LOS rather than being primarily caused by central venous catheters (CVC). To increase our knowledge about the involvement of the gut microbiota in LOS, we analyzed fecal samples from septic infants without a CVC.

Methods:
In this prospective multicenter study, fecal samples were collected daily from all infants born at ≤30 weeks gestation. Fecal VOC profiles up to 3 days prior to sepsis onset from infants with non-catheter–related LOS were compared with profiles from non-septic controls by means of High-Field Asymmetric Waveform Ion Mobility Spectrometry.

Results:
In total, 104 fecal samples were analyzed. Fecal VOC profiles allowed for discrimination between non-catheter–related LOS cases (n = 24) and matched controls (n = 25). Discriminative accuracy increased after focusing on center of origin (area under the curve, sensitivity, specificity; 0.95, 100%, 83%) and after focusing on LOS cases caused by Staphylococcus epidermidis (0.95, 100%, 78%), the most cultured pathogen (n = 11).

Conclusions:
Fecal VOC profiles of preterm LOS infants without a CVC differed from matched controls underlining the increasing notion that aberrations in gut microbiota composition and activity may play a role in LOS etiology.
Burden of Injury and Illness in the Road Race Medical Tent: A Narrative Review
Authors: Breslow Rebecca G. , Giberson-Chen Carew C. , Roberts William O. 
Published: February 2020

Objective:
To summarize the literature relating to prehospital care at 5 km through marathon distance road races and present the epidemiology of common medical encounters, significant medical complications, and medical outcomes.

Data Sources:
We searched PubMed and Google Scholar for the published literature pertaining to road race medical tent encounters at 5 km through marathon distance road races from 2000 to 2018. We included English-language, original articles reporting on injury and illness incidence.

Main Results:
Standard medical encounter definitions have recently been formulated in response to the previous lack of uniform definitions. The incidence of medical complications at road races may be influenced by environmental conditions and race distance. Minor and moderate medical encounters, such as dermatologic injuries, musculoskeletal injuries, and exercise-associated collapse, are common. Serious and life-threatening medical complications, including exertional heat stroke, exercise-associated hyponatremia, and cardiac arrest, are less frequent. Fatalities are also rare, with rates of 0.3 to 5 per 100 000 participants reported at marathons. The ratio of hospital transports to medical encounters is low.

Conclusions:
On-site medical services play a key role in the safety of both runners and the community. Future research and care initiatives in this field should focus on optimizing treatment protocols, promoting injury prevention efforts and reducing host community costs.
Short-Term Outcome Predictors in Patients With Primary Adhesive Capsulitis Treated With Ultrasound-Guided Hydrodilatation With Corticosteroids
Authors: Yang Chen-Ya , Fu Li-Heng , Lee Chao-Chung , Wang Kevin A. , Chou Chen-Liang , Wang Jia-Chi 
Published: February 2020

Objective
Glenohumeral joint hydrodilatation with corticosteroids has been proposed as an effective secondary therapeutic procedure for primary adhesive capsulitis. However, little is known about which subgroup of patients would benefit from this procedure. This study aimed to identify covariates associated with improved prognosis in patients receiving ultrasound-guided hydrodilatation with corticosteroid injection.

Design
This was a cohort study. Data on baseline demographic characteristics, disease status, past medical conditions, and initial ultrasonographic findings were collected. Linear and logistic regression analyses were performed to determine the prognostic factors associated with better clinical outcomes.

Results
Fifty-three patients (54 shoulders) were included. Linear regression analysis showed that coracohumeral ligament thickness of less than 3 mm, use of analgesics before hydrodilatation, and female sex were associated with good improvement in the Shoulder Pain and Disability Index score. Multivariate logistic regression analysis showed that coracohumeral ligament thickness of less than 3 mm on ultrasound was associated with a strong tendency (P = 0.054) of reaching the minimal detectable change. In addition, capsule rupture did not play a role in determining the clinical efficacy of hydrodilatation.

Conclusions
In patients with primary adhesive capsulitis, coracohumeral ligament thickness of less than 3 mm is correlated with greater short-term improvement in the Shoulder Pain and Disability Index score after ultrasound-guided hydrodilatation with steroid injection is performed.
Persistent Immune Activation in HIV-1–Infected Ex Vivo Model Tissues Subjected to Antiretroviral Therapy: Soluble and Extracellular Vesicle-Associated Cytokines
Authors: Mercurio Vincenzo , Fitzgerald Wendy , Molodtsov Ivan , Margolis Leonid 
Published: February 2020

Background:
Residual immune activation after successful antiretroviral therapy (ART) in HIV-1–infected patients is associated with the increased risk of complications. Cytokines, both soluble and extracellular vesicle (EV)-associated, may play an important role in this immune activation.

Setting:

Ex vivo tissues were infected with X4LAI04 or R5SF162 HIV-1. Virus replicated for 16 days, or tissues were treated with the anti-retroviral drug ritonavir.

Methods:
Viral replication and production of 33 cytokines in soluble and EV-associated forms were measured with multiplexed bead-based assays.

Results:
Both variants of HIV-1 efficiently replicated in tissues and triggered upregulation of soluble cytokines, including IL-1β, IL-7, IL-18, IFN-γ, MIP-1α, MIP-1β, and RANTES. A similar pattern was observed in EV-associated cytokine release by HIV-infected tissues. In addition, TNF-α and RANTES demonstrated a significant shift to a more soluble form compared with EV-associated cytokines. Ritonavir treatment efficiently suppressed viral replication; however, both soluble and EV-associated cytokines remained largely upregulated after 13 days of treatment. EV-associated cytokines were more likely to remain elevated after ART. Treatment of uninfected tissues with ritonavir itself did not affect cytokine release.

Conclusions:
We demonstrated that HIV-1 infection of ex vivo lymphoid tissues resulted in their immune activation as evaluated by upregulation of various cytokines, both soluble and EV-associated. This upregulation persisted despite inhibition of viral replication by ART. Thus, similar to in vivo, HIV-1–infected human tissues ex vivo continue to be immune-activated after viral suppression, providing a new laboratory model to study this phenomenon.
Surgical Prevention of Anastomotic Recurrence by Excluding Mesentery in Crohn's Disease: The SuPREMe-CD Study - A Randomized Clinical Trial
Authors: Luglio Gaetano , Rispo Antonio , Imperatore Nicola , Giglio Mariano Cesare , Amendola Alfonso , Tropeano Francesca Paola , Peltrini Roberto , Castiglione Fabiana , De Palma Giovanni Domenico , Bucci Luigi 
Published: February 2020

Objective:
This trial aimed to provide randomized controlled data comparing Kono-S anastomosis and stapled ileocolic side-to-side anastomosis.

Background:
Recently, a new antimesenteric, functional, end-to-end, hand-sewn ileocolic anastomosis (Kono-S) has shown a significant reduction in endoscopic recurrence score and surgical recurrence rate in Crohn disease (CD).

Methods:
Randomized controlled trial (RCT) at a tertiary referral institution. Primary endpoint: endoscopic recurrence (ER) (Rutgeerts score ≥i2) after 6 months. Secondary endpoints: clinical recurrence (CR) after 12 and 24 months, ER after 18 months, and surgical recurrence (SR) after 24 months.

Results:
In all, 79 ileocolic CD patients were randomized in Kono group (36) and Conventional group (43). After 6 months, 22.2% in the Kono group and 62.8% in the Conventional group presented an ER [P < 0.001, odds ratio (OR) 5.91]. A severe postoperative ER (Rutgeerts score ≥i3) was found in 13.8% of Kono versus 34.8% of Conventional group patients (P = 0.03, OR 3.32). CR rate was 8% in the Kono group versus 18% in the Conventional group after 12 months (P = 0.2), and 18% versus 30.2% after 24 months (P = 0.04, OR 3.47). SR rate after 24 months was 0% in the Kono group versus 4.6% in the Conventional group (P = 0.3). Patients with Kono-S anastomosis presented a longer time until CR than patients with side-to-side anastomosis (hazard ratio 0.36, P = 0.037). On binary logistic regression analysis, the Kono-S anastomosis was the only variable significantly associated with a reduced risk of ER (OR 0.19, P < 0.001). There were no differences in postoperative outcomes.

Conclusions:
This is the first RCT comparing Kono-S anastomosis and standard anastomosis in CD. The results demonstrate a significant reduction in postoperative endoscopic and clinical recurrence rate for patients who underwent Kono-S anastomosis, and no safety issues.
ClinicalTrials.gov ID NCT02631967.
Lateralised cerebral processing of abstract linguistic structure in clear and degraded speech
Authors: Meng Qingqing , Hegner Yiwen Li , Giblin Iain , McMahon Catherine , Johnson Blake W 
Published: February 2020

AbstractProviding a plausible neural substrate of speech processing and language comprehension, cortical activity has been shown to track different levels of linguistic structure in connected speech (syllables, phrases and sentences), independent of the physical regularities of the acoustic stimulus. In the current study, we investigated the effect of speech intelligibility on this brain activity as well as the underlying neural sources. Using magnetoencephalography (MEG), brain responses to natural speech and noise-vocoded (spectrally-degraded) speech in nineteen normal hearing participants were measured. Results showed that cortical MEG coherence to linguistic structure changed parametrically with the intelligibility of the speech signal. Cortical responses coherent with phrase and sentence structures were lefthemisphere lateralized, whereas responses coherent to syllable/word structure were bilateral. The enhancement of coherence to intelligible compared to unintelligible speech was also left lateralized and localized to the parasylvian cortex. These results demonstrate that cortical responses to higher level linguistics structures (phrase and sentence level) are sensitive to speech intelligibility. Since the noise-vocoded sentences simulate the auditory input provided by a cochlear implant, such objective neurophysiological measures have potential clinical utility for assessment of cochlear implant performance.
Parallel lemniscal and non-lemniscal sources control auditory responses in the orbitofrontal cortex (OFC)
Authors: Srivastava Hemant K , Bandyopadhyay Sharba 
Published: February 2020

AbstractThe orbitofrontal cortex (OFC), controls flexible behavior through stimulus value updating based on stimulus outcome associations, allowing seamless navigation in dynamic sensory environments with changing contingencies. Sensory cue driven responses, primarily studied through behavior, exist in the OFC. However, OFC neurons’ sensory response properties, particularly auditory, are unknown, in the mouse, a genetically tractable animal. We show that mouse OFC single neurons have unique auditory response properties showing pure deviance detection and long timescales of adaptation resulting in stimulus-history dependence. Further, we show that OFC auditory responses are shaped by two parallel sources in the auditory thalamus, lemniscal and non-lemniscal. The latter underlies a large component of the observed deviance detection and additionally controls persistent activity in the OFC through the amygdala. The deviant selectivity can serve as a signal for important changes in the auditory environment. Such signals if coupled with persistent activity, obtained by disinhibitory control from the non-lemniscal auditory thalamus or the amygdala, will allow for associations with a delayed outcome related signal, like reward prediction error, and potentially forms the basis of updating stimulus outcome associations in the OFC. Thus the baseline sensory responses allow the behavioral requirement based response modification through relevant inputs from other structures related to reward, punishment, or memory. Thus, alterations in these responses in neurological disorders can lead to behavioral deficits.