bluuebunny/crossref_metadata_2025 huggingface dataset:
Periprocedural Management of Direct Oral Anticoagulants Surrounding Cardioversion and Invasive Electrophysiological Procedures
Authors: Finks Shannon W. , Dobesh Paul P. , Trujillo Toby C. , Crossley George H.
Published: April 2018

As direct oral anticoagulants (DOACs) have demonstrated favorable efficacy and safety outcomes compared with vitamin K antagonists for the treatment and prevention of venous thromboembolism and the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, their role in the management of anticoagulation during electrophysiological procedures continues to evolve. At present, guidelines are limited regarding specific recommendations for the use of DOACs in these clinical settings. Here, we review available data regarding the risks and benefits associated with various periprocedural anticoagulation management approaches when patients receiving DOACs undergo electrophysiologic procedures including cardioversion, ablation, and device implantation. This discussion is intended to provide clinicians with an overview of available evidence and best practices to minimize the risk of both thromboembolic and bleeding events in the periprocedural setting.
Phase II Clinical Trial to Evaluate the Efficacy of Transanal Endoscopic Total Mesorectal Excision for Rectal Cancer
Authors: Park Sung Chan , Sohn Dae Kyung , Kim Min Jung , Chang Hee Jin , Han Kyung Su , Hyun Jong Hee , Joo Jungnam , Oh Jae Hwan
Published: April 2018

BACKGROUND:

Total mesorectal excision has become the standard treatment for rectal cancer, and several investigators have shown that a transanal approach is a feasible option.

OBJECTIVE:

This study aimed to evaluate the efficacy of transanal endoscopic total mesorectal excision in patients with rectal cancer.

DESIGN:

This study was a prospective, single-arm phase II trial. It was registered on clinicaltrials.gov under identifier NCT02406118.

SETTINGS:

Inpatients at a hospital specializing in oncology were selected.

PATIENTS:

This prospective study enrolled 49 patients with rectal cancer located 3 to 12 cm from the anal verge who were scheduled to undergo radical surgery.

INTERVENTIONS:

Laparoscopy-assisted transanal total mesorectal excision was performed.

MAIN OUTCOME MEASURES:

The primary end point was total mesorectal excision quality and circumferential resection margin. Secondary end points included the number of harvested lymph nodes, operation time, and 30-day postoperative complications.

RESULTS:

From March 2015 to April 2016, 32 men and 17 women with rectal cancer were enrolled. The mean age was 61.2 years, and mean BMI was 23.3 kg/m2. The mean operating time was 158 minutes, and the mean estimated blood loss was 89.3 mL. There were no intraoperative complications and no conversions to open surgery. Successful treatment based on total mesorectal excision quality and circumferential resection margin was achieved in 45 patients (91.8%). Fifteen patients (30.6%) had 30-day postoperative complications, including 7 (14.3%) with anastomotic dehiscence, 5 (10.2%) with urinary retention, 2 (4.1%) with abdominal wound complications, and 1 (2.0%) with ileus. There was no postoperative mortality.

LIMITATIONS:

This was a noncomparative single-arm trial conducted at a single institution.

CONCLUSIONS:

Transanal endoscopic total mesorectal excision showed acceptable results based on perioperative and short-term oncologic outcomes. Further investigations are necessary to show the benefits and long-term outcomes of this procedure. See Video Abstract at http://links.lww.com/DCR/A563.
Associations Between Ambient Nitrogen Dioxide and Daily Cause-specific Mortality
Authors: Chen Renjie , Yin Peng , Meng Xia , Wang Lijun , Liu Cong , Niu Yue , Lin Zhijing , Liu Yunning , Liu Jiangmei , Qi Jinlei , You Jinling , Kan Haidong , Zhou Maigeng
Published: April 2018

Background:

There has been a long history of debate regarding whether ambient nitrogen dioxide (NO2) directly affects human health.

Methods:

We conducted a nationwide time-series analysis in 272 major Chinese cities (2013–2015) to evaluate the associations between short-term exposure to NO2 and cause-specific mortality. We used the overdispersed generalized linear model together with the Bayesian hierarchical model to estimate the associations between NO2 and mortality at the national and regional levels. We examined two-pollutant models with adjustment of fine particles, sulfur dioxide, carbon monoxide, and ozone to evaluate robustness for the effects of NO2.

Results:

At the national-average level, we observed linear and positive associations between NO2 and mortality from all causes and main cardiorespiratory diseases. A 10 μg/m3 increase in 2-day average concentrations of NO2 would lead to increments of 0.9% (95% posterial interval [PI], 0.7%, 1.1%) in mortality from total nonaccidental causes, 0.9% (95% PI, 0.7%, 1.2%) from total cardiovascular disease, 1.4% (95% PI, 0.8%, 2.0%) from hypertension, 0.9% (95% PI, 0.6%, 1.2%) from coronary heart disease, 0.9% (95% PI, 0.5%, 1.2%) from stroke, 1.2% (95% PI, 0.9%, 1.5%) from total respiratory diseases, and 1.6% (95% PI, 1.1%, 2.0%) from chronic obstructive pulmonary disease. There were no appreciable differences in estimates from single-pollutant and two-pollutant models. The associations were stronger in the south of China, in the elderly, and in females.

Conclusions:

The present study provided robust epidemiologic evidence of associations between day-to-day NO2 and mortality from total natural causes and main cardiorespiratory diseases that might be independent of other criteria air pollutants.
Using Search Engine Data as a Tool to Predict Syphilis
Authors: Young Sean D. , Torrone Elizabeth A. , Urata John , Aral Sevgi O.
Published: April 2018

Background:

Researchers have suggested that social media and online search data might be used to monitor and predict syphilis and other sexually transmitted diseases. Because people at risk for syphilis might seek sexual health and risk-related information on the internet, we investigated associations between internet state-level search query data (e.g., Google Trends) and reported weekly syphilis cases.

Methods:

We obtained weekly counts of reported primary and secondary syphilis for 50 states from 2012 to 2014 from the US Centers for Disease Control and Prevention. We collected weekly internet search query data regarding 25 risk-related keywords from 2012 to 2014 for 50 states using Google Trends. We joined 155 weeks of Google Trends data with 1-week lag to weekly syphilis data for a total of 7750 data points. Using the least absolute shrinkage and selection operator, we trained three linear mixed models on the first 10 weeks of each year. We validated models for 2012 and 2014 for the following 52 weeks and the 2014 model for the following 42 weeks.

Results:

The models, consisting of different sets of keyword predictors for each year, accurately predicted 144 weeks of primary and secondary syphilis counts for each state, with an overall averageR2of 0.9 and overall average root mean squared error of 4.9.

Conclusions:

We used Google Trends search data from the prior week to predict cases of syphilis in the following weeks for each state. Further research could explore how search data could be integrated into public health monitoring systems.
Therapeutic Drug Monitoring of Methotrexate in Plasma Using Ultra High-Performance Liquid Chromatography–Electrospray Ionization–Tandem Mass Spectrometry: Necessary After Administration of Glucarpidase in Methotrexate Intoxications
Authors: Mulder Midas B. , Huisman Ruud , Engels Frederike K. , van der Sluis Inge M. , Koch Birgit C. P.
Published: April 2018

High-dose methotrexate (HD-MTX) is used to treat a variety of cancers. In all patients receiving HD-MTX, plasma MTX levels are monitored mainly to anticipate rescue therapy to prevent adverse events. We present 2 children treated with HD-MTX and afterward treated with glucarpidase at different time-points after their HD-MTX infusions. After the administration of glucarpidase, a nontoxic metabolite of MTX cross-reacts with MTX in the standard immunoassay (Abbott Diagnostics, Hoofddorp, the Netherlands) resulting in an artificially elevated MTX level. An artificially elevated MTX level results in unnecessarily long folinic acid administration, which decreases the effectivity of MTX. This grand round highlights the importance of measuring plasma MTX levels after the administration of glucarpidase with an ultra high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry method instead of with an immunoassay.
Development and Validation of an Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry Method for the Concurrent Measurement of Gabapentin, Lamotrigine, Levetiracetam, Monohydroxy Derivative of Oxcarbazepine, and Zonisamide Concentrations in Serum in a Clinical Setting
Authors: Palte Michael J. , Basu Sankha S. , Dahlin Jameson L. , Gencheva Ralitsa , Mason Donald , Jarolim Petr , Petrides Athena K.
Published: April 2018

Background:

Therapeutic drug monitoring of antiepileptic drugs (AEDs) is often necessary to prevent associated destructive toxicities. Tandem mass spectrometry (MS/MS) with stable-isotope–labeled internal standards is considered the gold standard for the measurement of AEDs. This study presents the development and validation of a clinical ultra-performance liquid chromatography–MS/MS method for the concurrent measurement of gabapentin, lamotrigine, levetiracetam, monohydroxy derivative of oxcarbazepine, and zonisamide in human serum.

Methods:

To determine the optimal assay analyte range, one year of AED therapeutic drug monitoring results (n = 1825) were evaluated. Simple protein precipitation with acetonitrile containing isotopically labeled internal standards was used. Reverse-phase ultra-performance liquid chromatography chromatographic separation was used, having a total run time of 3 minutes. Quantification of analytes was accomplished using electrospray ionization in positive ion mode and collision-induced dissociation MS. Assay parameters were evaluated per Food and Drug Administration bioanalytical guidelines.

Results:

After evaluating internal patient data, the analytical measuring range (AMR) of the assay was established as 0.1–100 mcg/mL. All AEDs were linear across the AMR, with R2 values ranging from 0.9988 to 0.9999. Imprecision (% coefficient of variation) and inaccuracy (% difference) were calculated to be <20% for the lower limit of quantitation and <15% for the low, mid, and high levels of quality controls across the AMR. All AEDs demonstrated acceptable assay parameters for carryover, stability under relevant storage conditions, matrix effects, recovery, and extraction and processing efficiency. In addition, the assay displayed acceptable concordance to results obtained from a national reference laboratory, with Deming regression R2 of 0.99 and slope values ranging from 0.89 to 1.17.

Conclusions:

A simple, cost-effective, and robust ultra-performance liquid chromatography–tandem mass spectrometry method for monitoring multiple AEDs was developed and validated to address the clinical needs of patients at our institution.
Survival Time to Biopsy-Proven Acute Rejection and Tacrolimus Adverse Drug Reactions in Pediatric Liver Transplantation
Authors: Riva Natalia , Dip Marcelo , Halac Esteban , Cáceres Guido Paulo , Woillard Jean B. , Licciardone Nieves , Chan Debora , Buendía Jefferson , Borgnia Daniela , Bosaleh Andrea , de Davila María T. , Imventarza Oscar , Schaiquevich Paula
Published: April 2018

Background:

Despite advances in surgical procedures and the optimization of immunosuppressive therapies in pediatric liver transplantation, acute rejection (AR) and serious adverse drug reaction (ADR) to tacrolimus still contribute to morbidity and mortality. Identifying risk factors of safety and efficacy parameters may help in optimizing individual immunosuppressive therapies. This study aimed to identify peritransplant predictors of AR and factors related to the risk of ADR to tacrolimus in a large Latin American cohort of pediatric liver transplant patients.

Methods:

We performed a retrospective cohort study in a pediatric liver transplant population (n = 72). Peritransplant variables were collected retrospectively including demographic, clinical, laboratory parameters, genomic (CYP3A5 donor and recipients polymorphism), and tacrolimus trough concentrations (C0) over a 2-year follow-up period. Variability in tacrolimus C0 was calculated using percent coefficient of variation and tortuosity. ADR- and AR-free survival rates were calculated using the Kaplan–Meier method, and risk factors were identified by multivariate Cox regression models.

Results:

Cox-proportional hazard models identified that high tortuosity in tacrolimus C0 was associated with an 80% increased risk of AR [hazard ratio (HR), 1.80; 95% confidence interval (CI), 1.01–3.22; P < 0.05], whereas steroid in maintenance doses decreased this risk (HR, 0.56; 95% CI, 0.31–0.99; P < 0.05). Forty-six patients experienced at least one ADR including hypomagnesemia, nephrotoxicity, hypertension, malignancies, and tremor as a first event. Multivariate analysis showed that C0 values 10 days before the event (HR, 1.25; 95% CI, 1.21–1.39; P < 0.0001) and CYP3A5 expresser recipients (HR, 2.05; 95% CI, 1.03–4.06; P < 0.05) were independent predictors of ADR.

Conclusions:

Tacrolimus C0 values, its variability, and CYP3A5 polymorphisms were identified as risk factors of AR and tacrolimus ADR. This knowledge may help to control and reduce their incidence in pediatric liver transplant patients. Prospective studies are important to validate these results.
The Impact of Microsurgery on Congenital Hand Anomalies Associated with Amniotic Band Syndrome
Authors: Chiu David T. W. , Patel Anup , Sakamoto Sara , Chu Alice
Published: April 2018

Background:

Amniotic Band Syndrome is a clinical constellation of congenital anomalies characterized by constricting rings, tissue synechiae and amputation of body parts distal to the constriction bands. Involvement of the hand with loss of multiple digits not only leads to devastating deformities but also loss of functionality.

Methods:

In this series, utilizing microvascular transfer of the second toe from both feet, along with local tissue reconfiguration, a tetra-digital hand with simile of normal cascade was reconstructed. A consecutive series of eight children with Amniotic Band Syndrome, younger than two years in age operated on by single surgeon over a twenty five year interval was reviewed.

Results:

There was no flap loss. The hands were sensate with effective simple prehensile function.

Conclusion:

Application of Microvascular toe-to-hand transfer for well selected, albeit severe hand deformity in Amniotic Band Syndrome is a valid surgical concept.
Plastic Surgeons’ Perceptions of Financial Conflicts of Interest and the Sunshine Act
Authors: Purvis Taylor E. , Lopez Joseph , Milton Jacqueline , May James W. , Dorafshar Amir H.
Published: April 2018

Background:

It is unknown whether recent legislation known as the Physician Payments Sunshine Act has affected plastic surgeons’ views of conflicts of interest (COI). The purpose of this study was to evaluate plastic surgeons’ beliefs about COI and their comprehension of the government-mandated Sunshine Act.

Methods:

Plastic surgeon members of the American Society of Plastic Surgeons were invited to complete an electronic survey. The survey contained 27 questions that assessed respondents’ past and future receipt of financial gifts from industry, awareness of the Sunshine Act, and beliefs surrounding the influence of COI on surgical practice.

Results:

A total of 322 individuals completed the survey. A majority had previously accepted gifts from industry (n = 236; 75%) and would accept future gifts (n = 181; 58%). Most respondents believed that COI would affect their colleagues’ medical practice (n = 190; 61%) but not their own (n = 165; 51%). A majority was aware of the Sunshine Act (n = 272; 89%) and supported data collection on surgeon COI (n = 224; 73%). A larger proportion of young surgeons believed patients would benefit from knowing their surgeon’s COI (P = 0.0366). Surgeons who did not expect COI in the future believed financial COI could affect their own clinical practice (P = 0.0221).

Conclusions:

Most plastic surgeons have a history of accepting industry gifts but refute their influence on personal clinical practice. Surgeon age and anticipation of future COI affected beliefs about the benefits of COI disclosure to patients and the influence of COI on surgical practice.
Exertional Medial Compartment Syndrome of the Foot—Referred Pain and Sequelae of Delayed Diagnosis: A Case Report
Authors: Park Young Hwan , Ahn Jeong Hwan , Choi Gi Won , Kim Hak Jun
Published: April 2018

In a 31-year-old man, the diagnosis of medial compartment syndrome of foot was delayed for 8 days. In contrast to previously reported cases, the patient presented with mainly bilateral lateral thigh-referred pain rather than foot pain. Although delayed decompression of the medial compartment provided dramatic relief of the referred pain, the patient complained of sensory deficit at the medial side of the foot and flexion deformity of the great toe at the final follow-up visit. Medial compartment syndrome of the foot can cause referred pain, and delayed or missed diagnosis can cause irreversible damage. Therefore, prompt diagnosis of compartment syndrome is crucial, and clinicians must consider the possibility of referred pain when the origin of pain is uncertain.
Applying DDX3X Biomarker to Discriminate Atypical from Benign Meningiomas in Tissue Microarray
Authors: Tsai Wen-Chiuan , Hueng Dueng-Yuan , Lin Chii-Ruey , Yang Thomas C. K. , Nieh Shin , Gao Hong-Wei
Published: April 2018

Patients with atypical meningiomas have a higher recurrence rate and poorer prognosis than patients with benign meningeal tumors. However, differentiating atypical from benign meningiomas based on fragmented specimens from brain tumor biopsy is complicated. We tested the association of DDX3X cytoplasmic expression and World Health Organization grading system in various subtypes of meningiomas. In our study, DDX3X expression was evaluated immunohistochemically in 10 non-neoplastic brain tissues and 71 meningiomas. The immunostaining scores were calculated as the product of cytoplasmic DDX3X intensity and the percentage of positively stained cells. Our results revealed most of the non-neoplastic brain tissues were immunonegative for DDX3X. The average DDX3X immunostaining score was significantly higher in meningiomas than non-neoplastic brain tissues and significantly higher in atypical meningiomas than in various subtypes of benign meningiomas. In conclusion, DDX3X immunohistochemistry combined with hematoxylin and eosin staining may help differentiate atypical meningiomas from benign meningeal tumors.
Persistent Physical Symptoms as Perceptual Dysregulation: A Neuropsychobehavioral Model and Its Clinical Implications
Authors: Henningsen Peter , Gündel Harald , Kop Willem J. , Löwe Bernd , Martin Alexandra , Rief Winfried , Rosmalen Judith G.M. , Schröder Andreas , van der Feltz-Cornelis Christina , Van den Bergh Omer
Published: April 2018

Objective

The mechanisms underlying the perception and experience of persistent physical symptoms are not well understood, and in the models, the specific relevance of peripheral input versus central processing, or of neurobiological versus psychosocial factors in general, is not clear. In this article, we proposed a model for this clinical phenomenon that is designed to be coherent with an underlying, relatively new model of the normal brain functions involved in the experience of bodily signals.

Methods

Based on a review of recent literature, we describe central elements of this model and its clinical implications.

Results

In the model, the brain is seen as an active predictive processing or inferential device rather than one that is passively waiting for sensory input. A central aspect of the model is the attempt of the brain to minimize prediction errors that result from constant comparisons of predictions and sensory input. Two possibilities exist: adaptation of the generative model underlying the predictions or alteration of the sensory input via autonomic nervous activation (in the case of interoception). Following this model, persistent physical symptoms can be described as “failures of inference” and clinically well-known factors such as expectation are assigned a role, not only in the later amplification of bodily signals but also in the very basis of symptom perception.

Conclusions

We discuss therapeutic implications of such a model including new interpretations for established treatments as well as new options such as virtual reality techniques combining exteroceptive and interoceptive information.
Smoking Is a Risk Factor for Relapse of Antimyeloperoxidase Antibodies–Associated Vasculitis
Authors: Yamaguchi Makoto , Ando Masahiko , Katsuno Takayuki , Tsuboi Naotake , Maruyama Shoichi
Published: April 2018

Background/Objective

Several studies have identified predictors of relapse in antineutrophil cytoplasmic antibody–associated small-vessel vasculitis. However, the role of smoking as a risk factor of relapse has not been elucidated. Therefore, this study aimed to evaluate whether a history of smoking is a dose-dependent independent risk factor for antineutrophil cytoplasmic antibody–associated small-vessel vasculitis relapse.

Methods

This multicenter retrospective cohort study included 122 patients with granulomatosis with polyangiitis and microscopic polyangiitis (MPA) from 9 nephrology centers in Japan. Dose-response relationships between cigarette smoking and outcomes were assessed using multivariate Cox proportional hazards models, adjusted for clinically relevant factors. The primary outcome was the time from remission to first relapse.

Results

During the observation period (median, 41 months; interquartile range, 23–66 months), 118 (95.8%) and 34 (21.7%) patients experienced at least 1 remission and 1 relapse, respectively. A log-rank test showed that smoking was significantly associated with relapse (p = 0.003). Multivariate Cox proportional hazards models found current smoking to be associated with relapse (adjusted hazard ratio, 7.48; 95% confidence interval, 2.73–21.0). An association between the risk of relapse and cumulative pack-years of smoking was also noted (p = 0.004). Smoking, however, was not associated with remission.

Conclusions

Smoking is a significant and dose-dependent risk factor for relapse of MPA. All patients with MPA who smoke should be encouraged to quit.
Comparison of Incidence and Severity of Chronic Postsurgical Pain Following Ear Surgery
Authors: Güven Mehmet , Kara Ahmet , Yilmaz Mahmut Sinan , Demir Deniz , Güven Ebru Mihriban
Published: April 2018

Objectives:

Literature review shows a limited number of studies investigating chronic pain following ear surgeries. The effect of mastoidectomy on chronic postsurgical pain, however, has never been investigated. The present study investigates not only the incidence and severity of chronic pain following ear surgeries with and without mastoidectomy, but also predisposing diseases for pain.

Patients and Methods:

The study was performed in a total of 150 patients who underwent tympanoplasty or tympanomastoidectomy through a retroauricular incision in a single tertiary health care center. During the routine postoperative 3rd-month examination, the patients were questioned for the presence and severity of chronic pain, as well as the diseases that might predispose the pain.

Results:

The difference between the visual analog scale scores of the groups was not statistically significant. Comparison of pain character revealed that neuropathic pain is more prevalent in both the groups. Evaluating the relationship between concomitant diseases and chronic pain, it was observed that migraine, cervical pathology, and acute postsurgical pain were closely associated with chronic pain.

Conclusion:

It was demonstrated that mastoidectomy does not pose an additional risk for chronic postsurgical pain. However, patients with migraine, cervical pathology, and acute postsurgical pain are at risk for chronic postsurgical pain.
A Patient With Severe Lower Face Degloving Injury
Authors: Cavalcante Pita Neto Ivo , Martins Pereira Lucena Franco Jéferson , Chaves Moreno Eduardo , Pita Pablo , Aurelio Lucchesi Sandrini Francisco , Gomes de Alencar Gondim David
Published: April 2018

Avulsions of mandible are among the most devastating lesions observed in cranio-maxillofacial traumas. They present an important health problem because of the high risk of morbidity related to deformities that cause functional limitations and esthetic changes. The avulsions commonly result from high-energy effects, which cause complete or partial separation of the mandibular bone of the face. As a result of the intense aggression, the skin and subcutaneous tissues of the bone are usually removed, affecting muscles, fascia, blood vessels, and the surrounding nerves. This article aimed to present a case of partial avulsion of mandible caused by car accident. Here, we emphasize the importance of correctly performing patient stabilization and maintenance of the airways, damage control, and facial reconstruction. Finally, we proceeded with a literature review to discuss standard protocols and controversies in the treatment of these lesions.
Comparison of Osseointegration of Five Different Surfaced Titanium Implants
Authors: Dundar Serkan , Yaman Ferhan , Bozoglan Alihan , Yildirim Tuba Talo , Kirtay Mustafa , Ozupek Muhammet Fatih , Artas Gokhan
Published: April 2018

The topography, chemical features, surface charge, and hydrophilic nature of titanium implant surfaces are crucial factors for successful osseointegration. This study aimed to investigate the bone implant contact (BIC) ratio of titanium dental implants with different surface modification techniques using the rat femoral bone model. Sandblasted and acid washed (SL-AW), sandblasted (SL), resorbable blast material (RBM), microarc (MA), and sandblasted and microarc (SL-MA) surfaces were compared in this study. Forty male Sprague–Dawley rats were used in this study. The rats were divided into 5 equal groups (n = 8), and totally 40 implants were integrated into the right femoral bones of the rats. The rats were sacrificed 12 weeks after the surgical integration of the implants. The implant surface–bone tissue interaction was directly observed by a light microscope, and BIC ratios were measured after the nondecalcified histological procedures. Bone implant contact ratios were determined as follows: SL-AW: 59.26 ± 14.36%, SL: 66.01 ± 9.63%, RBM: 63.53 ± 11.23%, MA: 65.51 ± 10.3%, and SL-MA: 68.62 ± 6.6%. No statistically significant differences were found among the 5 different surfaced titanium implant groups (P > 0.05). Our results show that various implant surface modification techniques can provide favorable bone responses to the BIC of dental implants.
Treatment of Facial Infantile Hemangioma: Comparative Study Between Propranolol and Ethanolamine Oleate
Authors: Lameiro Thais Miguel do Monte , Denadai Rafael , Pereira-Filho João Carlos , Raposo-Amaral Cesar Augusto , Raposo-Amaral Cassio Eduardo
Published: April 2018

Background:

Infantile hemangiomas (IH) are the most common benign vascular tumors in childhood. Approximately 10% to 15% of these tumors require drug or surgical intervention. There are many options for IH treatment, of which propranolol is currently considered the gold standard. This study aims to compare the therapeutic results of 2 distinct drugs (ethanolamine oleate and propranolol), in order to increase the available therapeutic arsenal for the treatment of IH, thereby benefiting a larger group of patients.

Methods:

A retrospective observational study was conducted to assess 16 patients with facial IH, allocated into 2 groups (n = 8). All patients met the same inclusion and exclusion criteria. The resulting evolution assessment was based on photographic documentation produced in a professional setting, and was performed before, during, and after treatment. Two measurement scales, photographic-based assessment of infantile hemangioma characteristics, and outcomes were used for comparison between the 2 therapeutic methods.

Results:

Both assessment methods did not present any significant statistical difference (P > 0.05) at 1 year of follow-up.

Conclusion:

Both therapeutic modalities are able to offer the patient similar and satisfactory final esthetic results.
Absences of Endothelial Microvesicle Changes in the Presence of the Endotheliopathy of Trauma
Authors: Wade Charles E. , Matijevic Nena , Wang Yao-Wei W. , Rodriguez Erika G. , Lopez Ernesto , Ostrowski Sisse R. , Cardenas Jessica C. , Baer Lisa A. , Chen Tzu-An , Tomasek Jeffrey S. , Henriksen Hanne H. , Stensballe Jakob , Cotton Bryan A. , Holcomb John B. , Johansson Pär I.
Published: April 2018

Introduction:

Severe trauma is accompanied by endothelial glycocalyx disruption, which drives coagulopathy, increasing transfusion requirements and death. This syndrome has been termed endotheliopathy of trauma (EOT). Some have suggested EOT results from endothelial cellular damage and apoptosis. Endothelial microvesicles (EMVs) represent cellular damage. We hypothesized that EOT is associated with endothelial damage and apoptosis resulting in an increase in circulating EMVs.

Methods:

Prospective, observational study enrolling severely injured patients. Twelve patients with EOT, based on elevated Syndecan-1 levels, were matched with 12 patients with lower levels, based on Injury Severity Score (ISS), abbreviated injury scale profile, and age. Thrombelastography and plasma levels of biomarkers indicative of cellular damage were measured from blood samples collected on admission. EMVs were determined by flow cytometry using varied monoclonal antibodies associated with endothelial cells. Significance was set at P < 0.05.

Results:

Admission physiology and ISS (29 vs. 28) were similar between groups. Patients with EOT had higher Syndecan-1, 230 (158, 293) vs. 19 (14, 25) ng/mL, epinephrine, and soluble thrombomodulin levels. Based on thrombelastography, EOT had reductions in clot initiation, amplification, propagation and strength, and a greater frequency of transfusion, 92% vs. 33%. There were no differences in EMVs irrespective of the antibody used. Plasma norepinephrine, sE-selectin, sVE-cadherin, and histone-complexed DNA fragments levels were similar.

Conclusion:

In trauma patients presenting with EOT, endothelial cellular damage or apoptosis does not seem to occur based on the absence of an increase in EMVs and other biomarkers. Thus, this suggests endothelial glycocalyx disruption is the underlying primary cause of EOT.
Bone Marrow Cells Transplant in Septic Mice Modulates Systemic Inflammatory Response via Cell–Cell Contact
Authors: Lorigados Clara B. , Ariga Suely K.K. , de Lima Thais M. , Barbeiro Denise F. , Krieger Jose E. , Soriano Francisco G.
Published: April 2018

Sepsis is a dynamic disease, displaying an inflammatory profile that varies over time and for each organ. Controlling the inflammatory response based in targeting a single molecule has been proved useless. We hypothesized that treatment with bone marrow-derived mononuclear cells (BMDMCs) may be more efficient to modulate the systemic inflammatory response to infection. Adult male Balb/c mice were subjected to cecal ligation and puncture (CLP) or endotoxemia model of experimental sepsis. BMDMCs were separated under Ficoll gradient and injected intravenously 1 h after the procedures. Cytokines concentration was quantified in plasma, lungs, heart, and gut. Spleens, lymph nodes, and thymus were used for lymphocytes isolation and cell death assessment. All measurements were performed 2 h after BMDMCs injection. RAW264.7 macrophages and BMDMCs were cocultivated in vitro to investigate the mechanisms involved. Our data showed that an early single intravenous injection of BMDMCs in animals submitted to the murine model of endotoxemia led to the improvement of survival rate; BMDMCs persistency in lung, liver, and spleen after 24 h; decreased necrosis and apoptosis of mononuclear cells; lower TNF-α, but increased IL-10 concentration in plasma; and tissue-specific cytokine profile. In vitro experiments demonstrated that IL-6, IL-10, and nitric oxide production depends on direct contact of BMDMCs to macrophages and that TNF-α production is negatively regulated by PGE2. BMDMCs are efficient in protecting animals from endotoxemia and sepsis, reducing systemic inflammation as well as specifically modulating tissue inflammation, producing the necessary immune regulation to re-equilibrate the inflammatory response.
Optimizing Live Kidney Donor Workup: A Decision Analysis Approach
Authors: Cheng Jian Y. , Martin Andrew , Ramanathan Ganesh , Cooper Bruce A.
Published: April 2018

Background

Screening potential live kidney donors is an intense process for both candidates and the healthcare system. It is conventionally implemented using a standard generic protocol. Efficiencies in this process could potentially be achieved using personalized protocols that are optimized for a given candidate. Aim: To create personalized protocols (by age, sex, and paired exchange status) and evaluate them relative to the standard generic protocol.

Methods

Two personalized protocols were created. One sequenced tests according to probability (high to low) of excluding a given candidate. The other sequenced tests according to the expected cost (low to high) per exclusion. Test costs and exclusion probabilities were extracted predominantly from Australian sources. These were integrated into a decision analysis incorporating Markov processes. This estimated the expected financial cost and expected number of tests performed to exclude an ineligible candidate in the standard generic and personalized protocols.

Results

The standard generic protocol consistently ranked poorest in terms of expected costs and expected tests per exclusion across all ages, sexes, and paired exchange status. Compared with the most efficient personalized protocol, the standard generic protocol was on average A$1767.49 more expensive and required 3.53 more tests.

Conclusions

Personalized protocols enhance the ability of a kidney transplant unit to effectively exclude live kidney donor candidates more quickly and cost effectively compared with the conventional standard generic protocol.
Campylobacter fetus prosthetic valve endocarditis presenting as a stroke
Authors: Petridou Christina , Strakova Lenka , Simpson Ruan
Published: April 2018

Introduction.Campylobacteris a common pathogen of the gastrointestinal tract, but invasive disease is rare.Campylobacter fetuscan play a role in osteomyelitis, meningitis and joint infection and has a prediliction for the vascular endothelium, causing mycotic aneurysms, thrombophlebitis and endocarditis. Here we present a case of prosthetic valve endocarditis caused byC. fetusand a review of the literature.

Case presentation.An 85-year-old woman with a tissue aortic valve replacement and atrial fibrillation was admitted to hospital with tonic-clonic seizures, right-sided hemiparesis, facial droop and hemianopia. Multiple cerebral emboli were seen on magnetic resonance imaging of the brain. Blood cultures grewC. fetusand an echocardiogram showed thickening and restricted movement of the aortic valve, a significant difference from an echocardiogram done 2 months before when the same organism was again isolated in blood cultures. She improved after treatment with 6 weeks of amoxicillin and 2 weeks of synergistic gentamicin for prosthetic valve endocarditis.

Conclusion.There have only been five previously reported cases ofC. fetusprosthetic valve endocarditis and this is the only patient who presented as a stroke. The majority of surviving patients required replacement of the affected valve with only one other patient surviving in the absence of surgery. No guidelines exist on the optimum treatment ofC. fetusendocarditis and this case reports adds to the growing literature on the appropriate management for this rare and potentially devastating disease.
Decline in pneumococcal disease in unimmunized adults is associated with vaccine-associated protection against colonization in toddlers and preschool-aged children
Authors: Weinberger Daniel M. , Pitzer Virginia E. , Regev-Yochay Gili , Givon-Lavi Noga , Dagan Ron
Published: April 2018

Vaccinating children with pneumococcal conjugate vaccines disrupts transmission, reducing disease rates in unvaccinated adults. When considering changes in vaccination strategies (e.g., removing doses), it is critical to understand which groups of children contribute most to transmission. We used data from Israel to evaluate how the build-up of vaccine-associated immunity in children was associated with declines in IPD due to vaccine-targeted serotypes in unimmunized adults. Data on vaccine uptake and prevalence of colonization with PCV-targeted serotypes were obtained from a unique study conducted among children visiting an emergency department in southern Israel and from surveys of colonization from central Israel. Data on invasive pneumococcal disease in adults were obtained from a nationwide surveillance study. We compared the trajectory of decline of IPD due to PCV-targeted serotypes in adults with the trajectory of decline of colonization prevalence and trajectory of increase in vaccine-derived protection against pneumococcal carriage among different age groupings of children. The declines in IPD in adults were most closely associated with the declines in colonization and increased vaccination coverage in children in the range of 36-59 months of age. This suggests that preschool-aged children, rather than infants, are responsible for maintaining the indirect benefits of PCVs.
Terrestriality and bacterial transfer: A comparative study of gut microbiomes in sympatric Malagasy mammals
Authors: Perofsky Amanda C. , Lewis Rebecca J. , Meyers Lauren Ancel
Published: April 2018

The gut microbiomes of mammals appear to mirror their hosts’ phylogeny, suggesting a shared history of co-speciation. Yet, much of this evidence stems from comparative studies of distinct wild or captive populations that lack data for disentangling the relative influences of shared phylogeny and environment. Here, we present phylogenetic and multivariate analyses of gut microbiomes from six sympatric (i.e., co-occurring) mammal species inhabiting a 1-km2area in western Madagascar—three lemur and three non-primate species—that consider genetic, dietary, and ecological predictors of microbiome functionality and composition. Host evolutionary history, indeed, appears to drive gut microbial patterns among distantly related species. However, we also find that diet—reliance on leaves versus fruit—is the best predictor of microbiome similarity among closely related lemur species, and that host substrate preference—ground versus tree— constrains horizontal transmission via incidental contact with feces, with arboreal species harboring far more distinct communities than those of their terrestrial and semi-terrestrial counterparts.
mCSEA: Detecting subtle differentially methylated regions
Authors: Martorell-Marugán Jordi , González-Rumayor Víctor , Carmona-Sáez Pedro
Published: April 2018

Motivation

The identification of differentially methylated regions (DMRs) among phenotypes is one of the main goals of epigenetic analysis. Although there are several methods developed to detect DMRs, most of them are focused on detecting relatively large differences in methylation levels and fail to detect moderate, but consistent, methylation changes that might be associated to complex disorders.

Results

We present mCSEA, an R package that implements a Gene Set Enrichment Analysis method to identify differentially methylated regions from Illumina 450K and EPIC array data. It is especially useful for detecting subtle, but consistent, methylation differences in complex phenotypes. mCSEA also implements functions to integrate gene expression data and to detect genes with significant correlations among methylation and gene expression patterns. Using simulated datasets, we show that mCSEA outperforms other tools in detecting DMRs. In addition, we applied mCSEA to a previously published dataset of sibling pairs discordant for intrauterine hyperglycemia exposure. We found several differentially methylated promoters in genes related to metabolic disorders like obesity and diabetes, demonstrating the potential of mCSEA to identify differentially methylated regions not detected by other methods.

Availability

mCSEA is freely available from the Bioconductor repository.

Contact

pedro.carmona@genyo.es
Serotonergic regulation of corticoamygdalar neurons in the mouse prelimbic cortex
Authors: Avesar Daniel , Stephens Emily K. , Gulledge Allan T.
Published: April 2018

Neuromodulatory transmitters, such as serotonin (5-HT), selectively regulate the excitability of subpopulations of cortical projection neurons to gate cortical output to specific target regions. For instance, in the mouse prelimbic cortex, 5-HT selectively excites commissurally projecting intratelencephalic (COM) neurons via activation of 5-HT2A (2A) receptors, while simultaneously inhibiting corticofugally projecting pyramidal neurons targeting the pons via 5-HT1A (1A) receptors. Here we characterize the physiology, morphology, and serotonergic regulation of corticoamygdalar (CAm) projection neurons in the mouse prelimbic cortex. Layer 5 CAm neurons shared a number of physiological and morphological characteristics with COM neurons, including higher input resistances, smaller HCN-channel mediated responses, and sparser dendritic arbors than corticopontine neurons. Across cortical lamina, CAm neurons also resembled COM neurons in their serotonergic modulation; focally applied 5-HT (100 µM; 1 s) generated 2A-receptor-mediated excitation, or 1A- and 2A- dependent biphasic responses, in ipsilaterally and contralaterally projecting CAm neurons. Serotonergic excitation depended on extrinsic excitatory drive, as 5-HT failed to depolarize CAm neurons from rest, but could enhance the number of action potentials generated by simulated barrages of synaptic input. Finally, using dual tracer injections, we identified double-labeled CAm/COM neurons that displayed primarily excitatory or biphasic responses to 5-HT. Overall, our findings reveal that prelimbic CAm neurons overlap with COM neurons, and that both neuron subtypes exhibit 2A-dependent serotonergic excitation. Our findings suggest that 5-HT, acting at 2A receptors, will promote cortical output to the amygdala.

Significance Statement

Cortical projections to the amygdala allow for executive “top-down” control of emotional responses. Corticoamygdalar (CAm) neurons in the prelimbic cortex contribute to the learning and expression of conditioned fear responses, processes that may also be regulated by serotonin (5-HT). Our study provides a physiological and morphological characterization of prelimbic CAm neurons, and demonstrates that the excitability of CAm neurons is regulated by 5-HT acting at 5-HT2A receptors alone, or in combination with 5-HT1A receptors. Our results suggest that 5-HT may regulate corticoamygdalar circuits during the learning and expression of conditioned fear.
Effect Size and Power in fMRI Group Analysis
Authors: Geuter Stephan , Qi Guanghao , Welsh Robert C. , Wager Tor D. , Lindquist Martin A.
Published: April 2018

Multi-subject functional magnetic resonance imaging (fMRI) analysis is often concerned with determining whether there exists a significant population-wide ‘activation’ in a comparison between two or more conditions. Typically this is assessed by testing the average value of a contrast of parameter estimates (COPE) against zero in a general linear model (GLM) analysis. In this work we investigate several aspects of this type of analysis. First, we study the effects of sample size on the sensitivity and reliability of the group analysis, allowing us to evaluate the ability of small sampled studies to effectively capture population-level effects of interest. Second, we assess the difference in sensitivity and reliability when using volumetric or surface based data. Third, we investigate potential biases in estimating effect sizes as a function of sample size. To perform this analysis we utilize the task-based fMRI data from the 500-subject release from the Human Connectome Project (HCP). We treat the complete collection of subjects (N = 491) as our population of interest, and perform a single-subject analysis on each subject in the population. We investigate the ability to recover population level effects using a subset of the population and standard analytical techniques. Our study shows that sample sizes of 40 are generally able to detect regions with high effect sizes (Cohen’s d > 0.8), while sample sizes closer to 80 are required to reliably recover regions with medium effect sizes (0.5 < d < 0.8). We find little difference in results when using volumetric or surface based data with respect to standard mass-univariate group analysis. Finally, we conclude that special care is needed when estimating effect sizes, particularly for small sample sizes.
BayesENproteomics: Bayesian elastic nets for quantification of proteoforms in complex samples
Authors: Mallikarjun Venkatesh , Richardson Stephen M. , Swift Joe
Published: April 2018

Multivariate regression modelling provides a statistically powerful means of quantifying the effects of a given treatment while compensating for sources of variation and noise, such as variability between human donors and the behaviour of different peptides during mass spectrometry. However, methods to quantify endogenous post-translational modifications (PTMs) are typically reliant on summary statistical methods that fail to consider sources of variability such as changes in levels of the parent protein. Here, we compare three multivariate regression methods, including a novel Bayesian elastic net algorithm (BayesENproteomics) that enables assessment of relative protein abundances while also quantifying identified PTMs for each protein. We tested the ability of these methods to accurately quantify expression of proteins in a mixed-species benchmark experiment, and to quantify synthetic PTMs induced by stable isotope labelling. Finally, we extended our regression pipeline to calculate fold changes at the pathway level, providing a complement to commonly used enrichment analysis. Our results show that BayesENproteomics can quantify changes to protein levels across a broad dynamic range while also accurately quantifying PTM and pathway-level fold changes. Raw data has been deposited to the ProteomeXchange with identifiers PXD012784, PXD012782 and PXD012772. BayesENproteomics is available for Matlab: www.github.com/VenkMallikarjun/BayesENproteomics and Python3: www.github.com/VenkMallikarjun/BENPPy