bluuebunny/crossref_metadata_2025 huggingface dataset:
Similar effects of low to moderate-intensity exercise program vs moderate-intensity continuous exercise program on depressive disorder in heart failure patients
Authors: Abdelbasset Walid Kamal , Alqahtani Bader A. , Alrawaili Saud M. , Ahmed Ahmed S. , Elnegamy Tamer E. , Ibrahim Ahmed A. , Soliman Gaber S.
Published: August 2019

Background:

Heart failure related depression is recently increased worldwide. Heart failure (HF) disease is identified as a critical cause of increasing morbidity, hospital readmission, and mortality. The most important purpose of treatment of HF disease is to relief disease problems, improve functional performance, and achieve better quality of life.

Objectives:

This study was proposed to evaluate the effects of low to moderate-intensity exercise program vs moderate-intensity continuous exercise program on the level of depressive disorder in heart failure patients.

Study design:

12-week randomized controlled trial.

Methods:

Sixty nine HF patients with mild to moderate level of depression and ejection fraction <40% were examined before and after 12-week intervention. Their age was ranged from 40 to 60 years. Patients were randomly classified into 3 groups. Group I (n = 23) received low to moderate intensity exercise program (LMIEP), group II (n = 23) received moderate-intensity exercise program (MICEP), and group III (n = 23) did not receive any exercise program (Non-exercised group). All patients were instructed to conduct home-based exercise with their pharmacological therapy. The level of depression was evaluated before and after 12 weeks of the intervention program.

Results:

The 3 study groups were associated with significant decrease of depression level (P < .05). Significant differences were exhibited between the 3 groups in favor to both exercise programs (P < .05) with non-significant differences between the 2 exercise programs (P > .05).

Conclusions:

Both exercise programs had positive effects in reducing the severity of depression in HF patients. Low to moderate and moderate-intensity exercise programs should be proposed for depression illness specially patients with heart failure.
Childhood obesity leads to adult type 2 diabetes and coronary artery diseases
Authors: Fang Xuqian , Zuo Junli , Zhou Jingqi , Cai Jialin , Chen Changqiang , Xiang Enfei , Li Haibo , Cheng Xiaoyan , Chen Peizhan
Published: August 2019

Observational studies have reported that childhood obesity is positively associated with risks of type 2 diabetes (T2D) and coronary artery disease (CAD) in adults; however, whether this association is causal is still unclear. In the present study, we conducted the 2-sample Mendelian randomization (MR) studies to investigate whether childhood obesity is causally associated with T2D and CAD in adults.

Seven single-nucleotide polymorphisms (SNPs) that significantly associated with childhood obesity were used as instrumental variables. The 2-sample MR analyses were performed with the summary-level data of large-sample genome-wide association studies to evaluate the causal effects of childhood obesity on adult T2D and CAD and the levels of cardiometabolic traits.

The 2-sample MR analyses suggested that each 1-unit increase in the log-odds of having childhood obesity was causally associated with an increased risk of adult T2D (odds ratio [OR] = 1.16, 95% confidential interval [CI] = 1.06–1.28; P = 1.0 × 10–3) and CAD (OR = 1.07, 95% CI = 1.02–1.12; P = 4.0 × 10–3) based on the inverse-variance weighted method. The MR analyses also suggested that childhood obesity was positively associated with the levels of adult body mass index, waist circumference, hip circumference, waist and hip ratio, log-transformed fasting glucose, log-transformed homeostatic model assessment (HOMA) of insulin resistance (%), and triglycerides. The childhood obesity was negatively associated with the adult high-density lipoprotein cholesterol level; however, there was no evidence of a causal association between childhood obesity and the levels of fasting glucose, 2-hour glucose, HbA1c (%), log-transformed HOMA of ß-cell function (%), low-density lipoprotein cholesterol, or total cholesterol in adults.

In conclusion, a genetic predisposition to childhood obesity was associated with an increased risk of adult T2D and CAD, providing causal relations between childhood obesity and the risks of T2D and CAD in adults; however, the results need to be validated with larger-scale intervention studies.
Auxiliary living donor liver transplantation combined with two-stage hepatectomy for unresectable colorectal liver metastases
Authors: Nadalin Silvio , Königsrainer Alfred , Capobianco Ivan , Settmacher Utz , Rauchfuss Falk
Published: August 2019

Purpose of review

To review the role of liver transplantation for unresectable colorectal liver metastases (u-CRLM) and to describe the intial experience with auxiliary living donor liver transplantation combined with two-stage hepatectomy for u-CRLM (i.e. living donor RAPID).

Recent findings

Patients affected with u-CRLM have a poor prognosis with 5 years overall survival (OS) rate less than 10% under standard modern chemotherapy.There is an actual international consensus that liver transplantation for u-CRLM represents a viable option in highly selected patients with OS rate at 5 years up to 80% notwithstanding high recurrence rates. Due to the scarcity of whole liver graft from deceased donors, the RAPID procedure (i.e. resection and partial liver segment 2–3 transplantation from deceased donors with delayed total hepatectomy) has been introduced as possible alternative. The RAPID procedure represents the most actual and modern fusion of the two most challenging procedures of modern hepatobiliary and liver transplant surgery: that is auxiliary partial orthotopic liver transplantation and associating liver partition and portal vein ligation for staged hepatectomy. Although the deceased donor-RAPID procedure may show promising results, the basic problem of scarcity of organs from deceased donors and mainly the lack of splittable organs still remains.

The living donor RAPID, based on transplantation of left lateral segments from living donor, may represent the way out to this problem. It is feasible and safe (for both donor and recipient), but characterized by a very challenging high-end transplantological procedure.
Variation of Gut Mucosal Microbiome With Anti‐Saccharomyces cerevisiae Antibody Status in Pediatric Crohn Disease
Authors: Kansal Shivani , Catto‐Smith Anthony G. , Boniface Karen , Thomas Sarah , Cameron Donald J. , Oliver Mark , Alex George , Kirkwood Carl D. , Wagner Josef
Published: August 2019

Objectives:

Crohn disease (CD) is a chronic relapsing condition possibly caused by a dysbiotic microbiome. Approximately 30% to 60% of patients with CD have anti‐Saccharomyces cerevisiae antibody (ASCA), but any association with gut microbiota is unexplored. We hypothesized that ASCA positivity would predict a signature microbial status and clinical phenotype.

Methods:

Ileocolonic mucosal biopsies were obtained from children with CD (n = 135), and controls without inflammatory bowel disease (n = 45). Comparison was made between ASCA status, microbial diversity, and clinical characteristics.

Results:

ASCA was highly specific but poorly sensitive for the diagnosis of CD. In patients with CD, ASCA positivity was associated with older age (≥10 years), ileocolonic disease, and long‐term risk of surgery. Microbial alpha and beta diversity were similar in patients with CD with or without ASCA, but significantly less when compared to noninflammatory bowel disease controls. Microbial richness was similar across all 3 groups. Fourteen bacterial species were associated with ASCA‐positive patients with CD and 14 species with ASCA‐negative patients (P < 0.05). After using a false discovery rate correction Ruminococcus torques and bacterium Yersinia enterocolitica 61 remained significantly associated with CD ASCA positivity (P = 0.0178), whereas Enterobacter cloacae and Faecalibacterium prausnitzii were significantly associated with CD ASCA negativity (P = 0.0178 and 0.0342).

Conclusion:

ASCA‐positive and ASCA‐negative patients with CD have significant differences in gut microbiome composition, which could possibly be influencing the phenotype of the disease.
Pilot Study of the Mastery Lifestyle Intervention
Authors: Ruiz R. Jeanne , Newman Matt , Records Kathie , Wommack Joel C. , Stowe Raymond P. , Pasillas Rebecca M.
Published: August 2019

Background

Recognizing the effects of acculturation on quality of life and emotional health, especially during pregnancy, we developed an intervention that would target these factors in order to improve maternal well-being during the prenatal period and potentially improve infant outcomes, particularly preterm birth for Mexican-American women (Latinas).

Objective

The purpose of these pilot studies was to test the acceptability, feasibility, and preliminary efficacy of the mastery lifestyle intervention (MLI) to decrease depressive and anxiety symptoms and improve coping as implemented in prenatal clinics with culturally homogenous groups of Latinas.

Methods

The MLI was tested in three small pilot studies (n = 15), one in El Paso, Texas (an urban area), and two in Bastrop, Texas (a rural area outside Austin), for acceptability and feasibility. A pretest/posttest, quasi-experimental design was used with pregnant self-identified Mexican-American Latinas at 14–20 weeks' gestation. Measures of anxiety, depressive symptoms, and positive and negative coping were used.

Results

Feasibility was a success in terms of implementation of the MLI in an active prenatal clinic setting and the use of electronic tablets for data collection and entry of data into REDcap. Satisfaction was high, with the location of the MLI being at their primary OB/GYN clinic. Participants reported that six intervention sessions appear to be ideal as was the class length of 1.5 to 2 hours. On Cohen's d, there were medium to large effect size decreases in depressive and anxiety symptoms and small to medium effect size decreases in the use of negative coping strategies and small effect sizes for increases in positive coping strategies.

Discussion

Pilot testing of the MLI indicated that it was well accepted from the participants and feasible as a culturally tailored behavioral therapy administered in a group setting by nurse practitioners. Our initial pilot results also suggest preliminary efficacy as indicated by moderate to large Cohen's d effect sizes for depression and anxiety.
Immune Thrombocytopenic Purpura in Pregnancy
Authors: Baucom Amanda M. , Kuller Jeffrey A. , Dotters-Katz Sarah
Published: August 2019

Importance

Immune thrombocytopenia purpura (ITP), an autoimmune disease characterized by destruction of platelets, is a hematological disorder that can present in both pregnant and nonpregnant patients. Although thrombocytopenia in pregnancy can be caused by more common pathologies such as gestational thrombocytopenia and preeclampsia, ITP can present initially during pregnancy, further complicating diagnosis. Management must be considerate of both the pregnancy itself and the fetus.

Objective

Review the diagnosis, treatment, and management of ITP in pregnancy based on current recommendations.

Evidence Acquisition

Review articles, original research, and case studies were utilized.

Results

Throughout pregnancy, patients are screened for a variety of conditions or disorders of pregnancy. Thrombocytopenia is a common pathology of pregnancy, but ITP is a rare condition that a provider needs to be aware of. After ruling out secondary causes of thrombocytopenia or more common causes such as gestational thrombocytopenia or preeclampsia, ITP should be considered. After diagnosis, treatment options should be discussed and initiated to provide safety for both the mother and fetus.

Conclusions

After reading this article, the reader will understand the current recommendations regarding the diagnosis, treatment, and management of ITP in pregnancy.

Relevance

The practitioner will be comfortable treating this condition during pregnancy.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the obstetrician/gynecologist should be better able to describe thrombocytopenia in pregnancy and identify common manifestations; select appropriate tests for evaluation of thrombocytopenia; and explain treatment options for management of ITP during pregnancy and delivery considerations for women with this condition.
The Effect of Body Mass Index on Retropubic Midurethral Slings
Authors: Bach Fiona , Hill Simon , Toozs-Hobson Philip
Published: August 2019

(Abstracted from Am J Obstet Gynecol 2019;220:371.e1–371.e9)

The prevalence of obesity during the past 2 decades in England has risen by approximately 40% and is continuing to rise as it has in other developed countries. There is a well-recognized association between stress urinary incontinence (SUI) and increasing body mass index (BMI).
Prenatal Diagnosis of Vasa Previa: Outpatient Versus Inpatient Management
Authors: Bartal Michal Fishel , Sibai Baha M. , Ilan Hadas , Katz Sharon , Eisen Irit Schushan , Kassif Eran , Yoeli Rakefet , Yinon Yoav , Mazaki-Tovi Shali
Published: August 2019

(Abstracted from Am J Perinatol 2019;36:422–427)

Vasa previa is defined as fetal vessels that run through the fetal membranes, over or within 2-cm distance from the endocervical os and unprotected by the placenta or umbilical cord. Vasa previa is associated with a high fetal or neonatal mortality rate due to risk of fetal exsanguination resulting from the fetal vessels tearing when rupture of membranes occurs.
RELA Fusion in Supratentorial Extraventricular Ependymomas: A Morphologic, Immunohistochemical, and Molecular Study of 43 Cases
Authors: Wang Leiming , Liu Lina , Li Hainan , Wang PeiPei , Hu Zeliang , Wei Yukui , Zhang Ming , Wen Wenjuan , Li Zhi , Liu Li , Zhao Lihong , Lu Dehong , Teng Lianghong
Published: August 2019

Supratentorial extraventricular ependymomas (STEEs) are relatively rare ependymomas, and their pathologic and genetic characteristics are still poorly understood. The aim of this study was to determine the histologic, immunohistochemical, and RELA fusion features, as well as to clarify in more detail the clinical courses of STEEs. Data from a total of 43 patients with STEEs was analyzed retrospectively. The status of RELA fusion was evaluated using fluorescence in situ hybridization. The expression levels of L1CAM, p65, cyclin D1, and p53 were assessed using immunohistochemistry. Progression-free survival and overall survival were calculated via Kaplan-Meier estimation using the log-rank test. Among all 43 STEEs, 65.1% (28/43) are positive for RELA fusion. Interestingly, almost half of the patients with RELA fusion–positive ependymomas are adults (13/28), and 89.3% (25/28) cases are anaplastic ependymomas, which suggests that RELA fusion testing is necessary in adults with STEEs. We investigated the immunohistochemical status of p65, L1CAM and CCND1 protein expression for their ability to predict RELA fusion status. RELA fusion–positive STEEs are frequently associated with expression of p65 (85.2%), L1CAM (85.2%), and CCND1 (81.5%). The accuracy of predicting RELA fusion status was much higher when the expression of p65 and L1CAM was combined, that is, when both were immunopositive. The status of RELA fusion, p53 overexpression, and extent of tumor resection are significantly associated with prognosis.
Prediction of Nonelective Central Venous Catheter Removal in Medically Complex Neonates
Authors: Beard Lauren , Levek Claire , Hwang Sunah , Grover Theresa
Published: August 2019

Introduction:

Central venous catheters (CVCs) are essential to neonatal care but associated with significant morbidity. Nonelective CVC removal (NER) is an inadequately studied outcome associated with increased morbidity, infant and family stress, and cost. This study describes prevalence and predictors of NER in infants admitted to a level IV neonatal intensive care unit and NER variation between peripherally inserted central catheters (PICCs), cutdown PICCs, and surgical CVCs.

Methods:

In this study, we include patient and catheter data for infants admitted to a level IV neonatal intensive care unit (2010–2015). Demographic and clinical characteristics were compared using 1-way analysis of variance (ANOVA), Kruskal-Wallis, and chi-square tests for continuous, non-normally distributed continuous, and categorical variables, respectively. The association between NER due to complication and infant and catheter characteristics was assessed using generalized linear mixed models.

Results:

Patient and catheter characteristics vary significantly by catheter type. The overall rate of NER is 15% (17% PICCs, 13% cutdown PICCs, and 19% surgical CVCs). The most common indications for NER are catheter breakage, blood stream infection(BSI)/central line-associated blood stream infection(CLABSI), catheter malposition, mechanical obstruction, and extravasation. Birth weight, patient diagnosis, catheter dwell time, and concurrent catheters are associated with increased odds of NER.

Conclusions:

Patient risk factors and potentially modifiable catheter characteristics, including catheter dwell time and concurrent catheters, are associated with increased NER. As NER is associated with a broad spectrum of adverse outcomes, we propose a quality improvement strategy to risk stratify patients and reduce exposure to high-risk, modifiable catheter characteristics.
Differentiating trait pain from state pain: a window into brain mechanisms underlying how we experience and cope with pain
Authors: Davis Karen D. , Cheng Joshua C.
Published: August 2019

Across various biological and psychological attributes, individuals have a set point around which they can fluctuate transiently into various states. However, if one remains in a different state other than their set point for a considerable period (eg, induced by a disease), this different state can be considered to be a new set point that also has associated surrounding states. This concept is instructive for understanding chronic pain, where an individual's set point may maladaptively shift such that they become stuck at a new set point of pain (trait pain), from which pain can fluctuate on different timescales (ie, pain states). Here, we discuss the importance of considering trait and state pains in neuroimaging studies of brain structure and function to gain an understanding of not only an individual's current pain state but also more broadly to their trait pain, which may be more reflective of their general condition.
Brainstem neuroimaging of nociception and pain circuitries
Authors: Napadow Vitaly , Sclocco Roberta , Henderson Luke A.
Published: August 2019

The brainstem is known to be an important brain area for nociception and pain processing, and both relaying and coordinating signaling between the cerebrum, cerebellum, and spinal cord. Although preclinical models of pain have characterized the many roles that brainstem nuclei play in nociceptive processing, the degree to which these circuitries extend to humans is not as well known. Unfortunately, the brainstem is also a very challenging region to evaluate in humans with neuroimaging. The challenges for human brainstem imaging arise from the location of this elongated brain structure, proximity to cardiorespiratory noise sources, and the size of its constituent nuclei. These challenges can require dedicated approaches to brainstem imaging, which should be adopted when study hypotheses are focused on brainstem processing of nociception or modulation of pain perception. In fact, our review will highlight many pain neuroimaging studies that have reported some brainstem involvement in nociceptive processing and chronic pain pathology. However, we note that with recent advances in neuroimaging leading to improved spatial and temporal resolution, more studies are needed that take advantage of data collection and analysis methods focused on the challenges of brainstem neuroimaging.
Imaging clinically relevant pain states using arterial spin labeling
Authors: Loggia Marco Luciano , Segerdahl Andrew Reilly , Howard Matthew Alexander , Tracey Irene
Published: August 2019

Arterial spin labeling (ASL) is a perfusion-based functional magnetic resonance imaging technique that uses water in arterial blood as a freely diffusible tracer to measure regional cerebral blood flow noninvasively. To date, its application to the study of pain has been relatively limited. Yet, ASL possesses key features that make it uniquely positioned to study pain in certain paradigms. For instance, ASL is sensitive to very slowly fluctuating brain signals (in the order of minutes or longer). This characteristic makes ASL particularly suitable for the evaluation of brain mechanisms of tonic experimental, postsurgical, and ongoing/or continuously varying pain in chronic or acute pain conditions (whereas blood-oxygen level–dependent functional magnetic resonance is better suited to detect brain responses to short-lasting or phasic/evoked pain). Unlike positron emission tomography or other perfusion techniques, ASL allows the estimation of regional cerebral blood flow without requiring the administration of radioligands or contrast agents. Thus, ASL is well suited for within-subject longitudinal designs (eg, to study evolution of pain states over time, or of treatment effects in clinical trials). Arterial spin labeling is also highly versatile, allowing for novel paradigms exploring a flexible array of pain states, plus it can be used to simultaneously estimate not only pain-related alterations in perfusion but also functional connectivity. In conclusion, ASL can be successfully applied in pain paradigms that would be either challenging or impossible to implement using other techniques. Particularly when used in concert with other neuroimaging techniques, ASL can be a powerful tool in the pain imager's toolbox.
The neural mechanisms of mindfulness-based pain relief: a functional magnetic resonance imaging-based review and primer
Authors: Zeidan Fadel , Baumgartner Jennifer N. , Coghill Robert C.
Published: August 2019

The advent of neuroimaging methodologies, such as functional magnetic resonance imaging (fMRI), has significantly advanced our understanding of the neurophysiological processes supporting a wide spectrum of mind–body approaches to treat pain. A promising self-regulatory practice, mindfulness meditation, reliably alleviates experimentally induced and clinical pain. Yet, the neural mechanisms supporting mindfulness-based pain relief remain poorly characterized. The present review delineates evidence from a spectrum of fMRI studies showing that the neural mechanisms supporting mindfulness-induced pain attenuation differ across varying levels of meditative experience. After brief mindfulness-based mental training (ie, less than 10 hours of practice), mindfulness-based pain relief is associated with higher order (orbitofrontal cortex and rostral anterior cingulate cortex) regulation of low-level nociceptive neural targets (thalamus and primary somatosensory cortex), suggesting an engagement of unique, reappraisal mechanisms. By contrast, mindfulness-based pain relief after extensive training (greater than 1000 hours of practice) is associated with deactivation of prefrontal and greater activation of somatosensory cortical regions, demonstrating an ability to reduce appraisals of arising sensory events. We also describe recent findings showing that higher levels of dispositional mindfulness, in meditation-naïve individuals, are associated with lower pain and greater deactivation of the posterior cingulate cortex, a neural mechanism implicated in self-referential processes. A brief fMRI primer is presented describing appropriate steps and considerations to conduct studies combining mindfulness, pain, and fMRI. We postulate that the identification of the active analgesic neural substrates involved in mindfulness can be used to inform the development and optimization of behavioral therapies to specifically target pain, an important consideration for the ongoing opioid and chronic pain epidemic.
The “virtual lesion” approach to transcranial magnetic stimulation: studying the brain–behavioral relationships in experimental pain
Authors: Weissman-Fogel Irit , Granovsky Yelena
Published: August 2019

Transcranial magnetic stimulation (TMS) can be used to create a temporary “virtual lesion” (VL) of a target cortical area, disrupting its function and associated behavior. Transcranial magnetic stimulation can therefore test the functional role of specific brain areas. This scoping review aims at investigating the current literature of the “online” TMS-evoked VL approach to studying brain–behavioral relationships during experimental pain in healthy subjects. Ovid-Medline, Embase, and Web of Science electronic databases were searched. Included studies tested different TMS-based VLs of various pain brain areas during continuous experimental pain or when time-locked to a noxious stimulus. Outcome measures assessed different pain measurements. Initial screening resulted in a total of 403 studies, of which 17 studies were included in the review. The VLs were directed to the prefrontal, primary and secondary somatosensory, primary motor, and parietal cortices through single/double/triple/sequence of five-TMS pulses or through repeated TMS during mechanical, electrical contact, radiant heat, or capsaicin-evoked noxious stimulation. Despite a wide variability among the VL protocols, outcome measures, and study designs, a behavioral VL effect (decrease or increase in pain responses) was achieved in the majority of the studies. However, such findings on the relationships between the modified brain activity and the manifested pain characteristics were often mixed. To conclude, TMS–elicited VLs during experimental pain empower our understanding of brain–behavior relationships at specific time points during pain processing. The mixed findings of these relationships call for an obligatory standard of all pain-related TMS protocols for clearly determining the magnitude and direction of TMS-induced behavioral effects.
Osseous Transformation with Facial Feminization Surgery: Improved Anatomical Accuracy with Virtual Planning
Authors: Gray Rachel , Nguyen Khang , Lee Justine C. , Deschamps-Braly Jordan , Bastidas Nicholas , Tanna Neil , Bradley James P.
Published: August 2019

Background:

Facial feminization surgery entails a series of surgical procedures that help the transwoman pass as their affirmed gender. Although virtual surgical planning, with intraoperative cutting guides, and custom plates have been shown to be helpful for craniomaxillofacial reconstruction, they have not yet been studied for facial feminization surgery. The authors used cadaveric analysis for morphologic typing and to demonstrate the utility of virtual surgical planning in facial feminization surgery procedures.

Methods:

Male cadaveric heads underwent morphologic typing analysis of the frontal brow, lateral brow, mandibular angle, and chin regions (n = 50). Subsequently, the cadavers were split into two groups: (1) virtual surgical planning intraoperative cutting guides and (2) no preoperative planning. Both groups underwent (1) anterior frontal sinus wall setback, (2) lateral supraorbital recontouring, (3) mandibular angle reduction, and (4) osseous genioplasty narrowing. Efficiency (measured as operative time), safety (determined by dural or nerve injury), and accuracy (scored with three-dimensional computed tomographic preoperative plan versus postoperative result) were compared between groups, with significance being p < 0.05.

Results:

For frontal brow and lateral lower face, morphologic type 3 (severe) predominated; for lateral brow and chin, type 2 (moderate) predominated. For frontal sinus wall setback, virtual surgical planning improved efficiency (19 minutes versus 44 minutes; p < 0.05), safety (100 percent versus 88 percent; p < 0.05; less intracranial entry), and accuracy (97 percent versus 79 percent; p < 0.05) compared with no preoperative planning. For mandibular angle reduction, virtual surgical planning improved safety (100 percent versus 88 percent; p < 0.05; less inferior alveolar nerve injury) and accuracy (95 percent versus 58 percent; p < 0.05).

Conclusions:

Preoperative planning for facial feminization surgery is helpful to determine morphologic typing. Virtual surgical planning with the use of cutting guides/custom plates improved efficiency, safety, and accuracy when performing four key craniofacial techniques for facial feminization.
Algorithm for Free Perforator Flap Selection in Lower Extremity Reconstruction Based on 563 Cases
Authors: Abdelfattah Usama , Power Hollie A. , Song Sinyoung , Min Kyunghyun , Suh Hyunsuk Peter , Hong Joon Pio
Published: August 2019

Background:

Microsurgical lower extremity reconstruction remains a challenge. The use of perforator flaps in lower extremity reconstruction is expanding. The authors present an algorithm to guide in the selection of the ideal free perforator flap that can be tailored to each lower extremity defect.

Methods:

The authors conducted a retrospective review of lower extremity reconstruction using free perforator flaps over a 7-year period. Demographics, comorbidities, defect characteristics, operative details, complications, and secondary procedures were documented. Pairwise comparisons of flap types were performed to differentiate flaps on the basis of flap size, thickness, and pedicle length.

Results:

A total of 563 free perforator flaps were performed. The most common causes were trauma (36.5 percent) and diabetes (24.4 percent). Nine flaps were used, with the most common being superficial circumflex iliac perforator (51.2 percent) and anterolateral thigh (33.2 percent). Size differed significantly between flap types (p < 0.05), with the exception of thoracodorsal artery perforator versus gluteal artery perforator flaps (p = 0.26). The thinnest flaps were posterior interosseous artery perforator (3.7 ± 0.5 mm) and superficial circumflex iliac perforator (5.4 ± 0.8 mm). The thickest flaps were deep inferior epigastric perforator (11.1 ± 3.9 mm) and anterolateral thigh (9.0 ± 1.5 mm). The shortest pedicles were in posterior interosseous artery perforator (3.3 ± 0.3 cm) and superficial circumflex iliac perforator flaps (5.2 ± 0.8 cm). The longest pedicles were in deep inferior epigastric perforator (11.7 ± 1.4 cm), thoracodorsal artery perforator (9.3 ± 1.4 cm), and anterolateral thigh flaps (9.2 ± 0.8 cm).

Conclusions:

Free perforator flaps are reliable in lower extremity reconstruction. The authors believe their algorithm for flap selection helps to optimize form and function, decrease operative time, and minimize donor-site morbidity and secondary procedures.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Using Quantitative Computed Tomographic Imaging to Understand Chronic Obstructive Pulmonary Disease and Fibrotic Interstitial Lung Disease
Authors: Castillo-Saldana Daniela , Hague Cameron J. , Coxson Harvey O. , Ryerson Christopher J.
Published: August 2019

Computed tomography (CT) is commonly used in the evaluation and management of patients with diffuse lung pathologies, including chronic obstructive pulmonary disease (COPD) and fibrotic interstitial lung disease (ILD). In clinical practice, the qualitative (visual) assessment of CT images by a radiologist provides insight into the diagnosis of diffuse lung disease, estimates disease severity, and supports the identification of complications. Quantitative CT (qCT) is an emerging technique that provides some advantages over qualitative assessment. qCT can allow early and accurate detection of emphysema and airway disease, as well as aiding the evaluation of disease burden in both COPD and ILD. This approach is starting to be used as a surrogate biomarker in clinical trials to assess response to therapy. Artificial intelligence techniques have recently been incorporated into qCT, with such rapid evolution that it is currently difficult to determine the exact role it will eventually play in evaluating patients with COPD or pulmonary fibrosis. This article reviews the current state of the art for qualitative and qCT assessment of both COPD and fibrotic ILD. Current areas of controversy and limitations of these techniques are discussed, along with the potential future role of artificial intelligence. Recommendations are provided with regard to the current use of these techniques in the management of patients with diffuse lung disease.
Immunosuppression and Reproductive Health After Kidney Transplantation
Authors: Chandra Anupam , Midtvedt Karsten , Åsberg Anders , Eide Ivar Anders
Published: August 2019

Following successful kidney transplantation, recipients usually regain fertility. Post-engraftment pregnancies should be planned and the teratogenic mycophenolic acid should be replaced with azathioprine before conception. To avoid unintentional pregnancies, pre-conception counseling is mandatory in women of reproductive age who are scheduled for a kidney transplant. Counseling should be repeated after transplantation. Female recipients should receive advice to use long-acting reversible contraception and avoid pregnancy for a minimum of 1 year following transplantation. Conception should be deferred even longer in female recipients with moderate to severe proteinuria, uncontrolled hypertension or reduced graft function and be very carefully discussed in highly HLA-sensitized patients. The recipient wishes, values and acceptance of pregnancy-related risk should receive attention. Assisted fertilization increases the risk of pre-eclampsia, but still result in live births. Pregnancy management in kidney transplant recipients should be provided by a multidisciplinary team consisting of a nephrologist, a midwife and an obstetrician with expertise in high-risk pregnancies. Until measurement of unbound fraction of calcineurin inhibitors becomes clinically available, we recommend to adjust calcineurin inhibitor dose according to whole blood trough level, even though it overestimates the effective drug concentration during pregnancy. If nephrotoxicity is suspected, the calcineurin inhibitor dose should be reduced. Breastfeeding should be accepted after kidney transplantation since infant immunosuppressive drug exposure via breastmilk is extremely low. The prevalence of congenital malformations in children fathered by male recipients, including patients on mycophenolic acid therapy at the time of conception, is at level with the general population.
Cold Pulsatile Machine Perfusion Versus Static Cold Storage for Kidneys Donated After Circulatory Death: A Multicenter Randomized Controlled Trial
Authors: Summers Dominic M. , Ahmad Niaz , Randle Lucy V. , O’Sullivan Ann-Marie , Johnson Rachel J. , Collett David , Attia Magdy , Clancy Marc , Tavakoli Afshin , Akyol Murat , Jamieson Neville V. , Bradley J. Andrew , J.E. Watson Christopher
Published: August 2019

Background.

The benefits of cold pulsatile machine perfusion (MP) for the storage and transportation of kidneys donated after circulatory death are disputed. We conducted a UK-based multicenter, randomized controlled trial to compare outcomes of kidneys stored with MP versus static cold storage (CS).

Methods.

Fifty-one pairs of kidneys donated after circulatory death were randomly allocated to receive static CS or cold pulsatile MP. The primary endpoint, delayed graft function, was analyzed by “intention-to-treat” evaluation.

Results.

There was no difference in the incidence of delayed graft function between CS and MP (32/51 (62.8%) and 30/51 (58.8%) P = 0.69, respectively), although the trial stopped early due to difficulty with recruitment. There was no difference in the incidence of acute rejection, or in graft or patient survival between the CS and MP groups. Median estimated glomerular filtration rate at 3 months following transplantation was significantly lower in the CS group compared with MP (CS 34 mL/min IQR 26–44 vs MP 45 mL/min IQR 36–60, P = 0.006), although there was no significant difference in estimated glomerular filtration rate between CS and MP at 12 months posttransplant.

Conclusions.

This study is underpowered, which limits definitive conclusions about the use of MP, as an alternative to static CS. It did not demonstrate that the use of MP reduces the incidence of delayed graft function in donation after circulatory death kidney transplantation.
Listening difficulties in children: Behavior and brain activation produced by dichotic listening of CV syllables
Authors: Moore David R. , Hugdahl Kenneth , Stewart Hannah J. , Vannest Jennifer , Perdew Audrey J. , Sloat Nicholette T. , Cash Erin , Hunter Lisa L
Published: August 2019

Listening difficulties (LiD), also known as auditory processing disorders, are common in children with and without hearing loss. Impaired interactions between the two ears have been proposed as an important component of LiD. Previous studies have focused on testing using multiple sequential dichotic digits that carry a substantial memory load and executive control demands. We examined the ability of 6-13 year old children with normal audiometric thresholds to identify and selectively attend to dichotically presented CV syllables using the Bergen Dichotic Listening Test (BDLT;www.dichoticlistening.com). Children were recruited as typically developing (TD; n=39) or having LiD (n=35) based primarily on composite score of the ECLiPS caregiver report. Different single syllables (ba, da, ga, pa, ta, ka) were presented simultaneously to each ear (6×36 trials). Children reported the syllable heard most clearly (non-forced, NF) or the syllable presented to the right (forced, FR) or left (FL) ear. Interaural level differences (ILDs) manipulated bottom-up perceptual salience. Dichotic listening data (correct responses, Laterality Index) were analyzed initially by group (LiD, TD), age, report method (NF, FR, FL) and ILD (0, ± 15 dB) and compared with speech-in-noise thresholds (LiSN-S) and cognitive performance (NIH Toolbox). fMRI measured brain activation produced by a receptive speech task that segregated speech, phonetic and intelligibility components. Some activated areas (planum temporale, inferior frontal gyrus and orbitofrontal cortex) were correlated with dichotic results in TD children only.

Neither group, age nor report method affected the Laterality Index of right/left recall. However, a significant interaction was found between ear, group and ILD. Children with LiD were more influenced by large ILDs, especially favoring the left ear, than were TD children. Neural activity associated with Speech, Phonetic and Intelligibility sentence cues did not significantly differ between groups. Significant correlations between brain activity level and BDLT were found in several frontal and temporal locations for the TD but not for the LiD group.

Children with LiD were more influenced by large ILDs, especially favoring the left ear, than were TD children and were thus less able to modulate performance through attention, and more driven by the physical properties of the acoustic stimuli.
Genetic and molecular mechanism for distinct clinical phenotypes conveyed by allelic truncating mutations implicated in FBN1
Authors: Lin Mao , Liu Zhenlei , Liu Gang , Zhao Sen , Li Chao , Chen Weisheng , Akdemir Zeynep Coban , Lin Jiachen , Song Xiaofei , Wang Shengru , Xu Qiming , Zhao Yanxue , Wang Lianlei , Zhang Yuanqiang , Yan Zihui , Liu Sen , Liu Jiaqi , Chen Yixin , Yang Xu , Sun Tianshu , Yang Xin-Zhuang , Niu Yuchen , Li Xiaoxin , You Wesley , Qiu Bintao , Ding Chen , Liu Pengfei , Zhang Shuyang , Carvalho Claudia M. B. , Posey Jennifer E. , Qiu Guixing , Lupski James R. , Wu Zhihong , Zhang Jianguo , Wu Nan ,   on behalf of the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study
Published: August 2019

The molecular and genetic mechanisms by which different single nucleotide variant (SNV) alleles in specific genes, or at the same genetic locus, bring about distinct disease phenotypes often remain unclear. Allelic truncating mutations of fibrillin-1(FBN1) cause either classical Marfan syndrome (MFS) or a more severe phenotype associated with Marfanoid-progeroid-lipodystrophy syndrome (MPLS). A total of three Marfan syndrome/Marfanoid patients (2 singletons and 1 parent-offspring trio) were recruited. Targeted next-generation sequencing was performed on all the participants. We analyzed the molecular diagnosis, patient clinical features, and the potential molecular mechanism involved in the MPLS subject in our cohort. We investigated a small cohort, consisting of two classical MFS and one MPLS patient from China, whose clinical presentation included scoliosis potentially requiring surgical intervention. We provide evidence that most nonsense and frameshift mutations lead to FBN1 null alleles due to mutant mRNA transcript degradation. In contrast, the more severe disease phenotype, MPLS, is caused by mutant mRNAs that are predicted to escape the nonsense mediated decay (NMD) surveillance pathway, making a mutant protein that exerts a dominant negative interference effect to FBN1 thus generating a gain-of-function (GoF) rather than a loss-of-function (LoF) allele as in MFS. Overall, we provide direct evidence that a dominant negative interaction of FBN1 potentially explains the distinct clinical phenotype in MPLS patients through genetic and functional analysis of the first Chinese patient with MPLS. Moreover, our study expands the mutation spectrum of FBN1 and highlights the potential molecular mechanism for MPLS patients.
An altered metabolism could contribute to the low activation of neonatal CD8+T cells
Authors: Antonio Sánchez-Villanueva José , Otoniel Rodríguez-Jorge , Oscar Ramírez-Pliego , Gabriela Rosas Salgado , Wassim Abou-Jaoudé , Céline Hernandez , Aurélien Naldi , Denis Thieffry , Angélica Santana María
Published: August 2019

A low response of neonatal T cells to infections contributes to a high incidence of morbidity and mortality of neonates. Here we evaluated the impact of the cytoplasmic and mitochondrial levels of Reactive Oxygen Species (ROS) of adult and neonatal CD8+T cells on their activation potential. We further constructed a logical model to decipher the interplay of metabolism and ROS on T cell signaling. Our model captures the interplay between antigen recognition, ROS and metabolic status in T cell responses. This model displays alternative stable states corresponding to different cell fates, i.e. quiescent, activated and anergic states, depending on ROS status. Stochastic simulations with this model further indicate that differences in ROS status at the cell population level tentatively explain the lower activation rate of neonatal compared to adult CD8+T cells upon TCR engagement.
Using Transcriptional Signatures to Find Cancer Drivers with LURE
Authors: Haan David , Tao Ruikang , Friedl Verena , Anastopoulos Ioannis Nikolaos , Wong Christopher K , Weinstein Alana S , Stuart Joshua M
Published: August 2019

Cancer genome projects have produced multidimensional datasets on thousands of samples. Yet, depending on the tumor type, 5-50% of samples have no known driving event. We introduce a semi-supervised method called Learning UnRealized Events (LURE) that uses a progressive label learning framework and minimum spanning analysis to predict cancer drivers based on their altered samples sharing a gene expression signature with the samples of a known event. We demonstrate the utility of the method on the TCGA dataset for which it produced a high-confidence result relating 53 new to 18 known mutation events including alterations in the same gene, family, and pathway. We give examples of predicted drivers involved in TP53, telomere maintenance, and MAPK/RTK signaling pathways. LURE identifies connections between genes with no known prior relationship, some of which may offer clues for targeting specific forms of cancer. Code and Supplemental Material are available on the LURE websitehttps://sysbiowiki.soe.ucsc.edu/lure.
Cortical excitation-inhibition ratio mediates the effect of pre-attentive auditory processing deficits on interpersonal difficulties
Authors: Ford Talitha C. , Woods Will , Enticott Peter G. , Crewther David P.
Published: August 2019

Several lines of evidence identify aberrant excitatory-inhibitory neural processes across autism and schizophrenia spectrum disorders, particularly within the psychosocial domain. Such neural processes include increased excitatory glutamate and reduced inhibitory GABA concentrations, which may affect auditory pre-attentive processing as indexed by the mismatch negativity (MMN); thus, an excitation-inhibition imbalance might lead to aberrant MMN, which might in turn drive the relationship between the MMN and psychosocial difficulties. This research has the potential to enhance the neurochemical understanding of the relationship between electrophysiology (MMN) and behavioural/clinical measures (psychosocial difficulties).

Thirty-eight adults (18 male, 18-40 years) completed the Schizotypal Personality Questionnaire (SPQ) and Autism-Spectrum Quotient (AQ). Glutamate and GABA concentrations in bilateral superior temporal cortex (STC) were quantified using proton magnetic resonance spectroscopy (1H-MRS) while auditory MMN to a duration deviant was measured with magnetoencephalography. Spearman correlations probed the relationships between STC glutamate/GABA ratios, MMN amplitude and latency, and AQ and SPQ dimensions. Mediation effects of glutamate/GABA ratios on the relationship between MMN and AQ-SPQ dimensions were probed using causal mediation analysis.

Only SPQ-interpersonal and AQ-communication were significantly correlated with right hemisphere glutamate/GABA ratios and MMN latency (ps<.05), which were themselves correlated (p=.038). Two mediation models were investigated, with right MMN latency as predictor and SPQ-interpersonal and AQ-communication as outcome variables. Right STC glutamate/GABA ratios significantly mediated the relationship between MMN latency and SPQ-interpersonal scores (ß=86.6, p=.033), but only partially mediated the relationship between MMN latency and AQ-communication scores (ß=21.0, p=.093).

These findings support the growing body of literature pointing toward an excitation-inhibition imbalance that is central to psychosocial functioning across multi-dimensional spectrum disorders, such as autism and schizophrenia, and provides neurochemical indicators of the processes that underlie psychosocial dysfunction.
Impact of global warming on insects: are tropical species more vulnerable than temperate species?
Authors: Johansson Frank , Orizaola Germán , Nilsson-Örtman Viktor
Published: August 2019

The magnitude and ecological impact of climate change varies with latitude. Several recent models have shown that tropical ectotherms face the greatest risk from warming because they currently experience temperatures much closer to their physiological optimum than temperate taxa. Even a small increase in temperature may thus result in steep fitness declines in tropical species but increased fitness in temperate species. This prediction, however, is based on a model that does not account for latitudinal differences in activity periods. Temperate species in particular may often experience considerably higher temperatures than expected during the active season. Here, we integrate data on insect warming tolerance and temperature-dependent development to re-evaluate latitudinal trends in thermal safety margins after accounting for latitudinal trends in insect seasonal activity. Our analyses suggest that temperate and tropical species differ far less in thermal safety margins than commonly assumed, and thus face a similar risk from warming.