bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare Neurosurgical Complications of Epidural Injections: An 8-Yr Single-Institution Experience
Authors: Smith Gabriel A. , Pace Jonathan , Strohl Madeleine , Kaul Anand , Hayek Salim , Miller Jonathan P.
Published: March 2017

BACKGROUND: Neurosurgical complications from epidural injections have rarely been reported.

OBJECTIVE: To define the spectrum of complications from these procedures in order to identify risk factors and strategies for prevention.

METHODS: A prospectively maintained database of 14 247 neurosurgical admissions over 8 yr was screened to identify patients who had suffered procedural complications associated with 1182 cervical and 4617 lumbar interlaminar epidural injection procedures performed at a single institution. Patients who developed new neurological symptoms or deficits were included. A retrospective analysis of demographic and procedural features was performed.

RESULTS: Thirteen patients experienced complications requiring neurosurgical treatment, accounting for an overall procedural complication rate of 0.22% (0.51% and 0.15% for cervical and lumbar injections, respectively), and representing 0.09% of all neurosurgical admissions over 8 yr. There were 3 categories: hemorrhage (n = 7), infection (n = 3), and inadvertent dural penetration (n = 3). There was significant association with anticoagulation use among patients with hemorrhagic vs nonhemorrhagic complications (P < .01, Fisher's exact test). Six patients who developed epidural hematoma had been managed in accordance with current guidelines, either after prolonged cessation of anticoagulation (n = 3) or taking only aspirin (n = 3); all were decompressed promptly with good long-term outcome. All infections were associated with lumbar injection. Dural penetration resulted in diffuse pneumocephalus (n = 1), intramedullary air at the site of injection (n = 1), and acutely symptomatic colloid cyst (n = 1).

CONCLUSION: A majority of neurosurgical complications from epidural injections are hemorrhagic and associated with anticoagulation, although infection and inadvertent dural penetration also occur. Prompt treatment of compressive lesions is associated with good outcome.
Reduced Sufentanil Doses are Effective for Postoperative Analgesia After Ductal Closure in Extremely Premature Infants
Authors: Soreze Yohan , Audureau Etienne , Decobert Fabrice , Jaby Olivier , Blary Sabine , Danan Claude , Durrmeyer Xavier
Published: March 2017

Objectives:

The objective of the study was to assess the efficacy of reduced sufentanil doses for postoperative analgesia following surgical ductal closure in extremely premature infants.

Methods:

This was a retrospective, single-center, cohort study comparing 2 sufentanil dosing regimens used between 2001 and 2010 and included all infants born at <28 weeks of gestation with surgical ductal closure. Sufentanil doses were reduced in 2007 as a standard of care. Time was divided into 3 epochs to distinguish the effects of practice changes over time from the effects of sufentanil dose change: epoch 1 (2001 to 2004), epoch 2 (May 2005 to 2007), and epoch 3 (June 2007 to 2010).

Results:

A total of 109 of 114 eligible infants were analyzed (mean [±SD], gestational age: 25.1 [±1.1] wk; mean [±SD], birth weight: 756 [±144] g). Median sufentanil doses were significantly higher during epochs 1 and 2 (0.1 to 0.2 µg/kg/h) than during epoch 3 (0.03 to 0.04 µg/kg/h) (P<0.0001). EDIN (Echelle de Douleur et d’Inconfort du Nouveau-né) pain scores were mostly ≤4 throughout the study period and their changes over time were not contemporaneous with the reduction in sufentanil doses; they were lower during epoch 1 versus epochs 2 and 3 (P<0.0001) and comparable between epochs 2 and 3. Midazolam doses and paracetamol use were not higher during epoch 3 as compared with epochs 1 and 2. No difference in opioid-related adverse events was observed between the 3 epochs.

Conclusion:

Our study supports the use of low continuous intravenous sufentanil doses, consistent with morphine doses currently recommended in this population.
Lumbar Tactile Acuity in Patients With Low Back Pain and Healthy Controls
Authors: Adamczyk Wacław , Luedtke Kerstin , Saulicz Edward
Published: March 2017

Objective:

Diminished tactile acuity in chronic non-neuropathic pain syndromes has been attributed to central pain processing and cortical reorganization. The latter was recently targeted in clinical trials that demonstrated no clear advantages over traditional approaches for the reduction of nonspecific low back pain (LBP). The aim of this systematic review and meta-analysis was to summarize the current evidence on tactile acuity in LBP and pain-free controls.

Methods:

Six databases were independently searched by 2 researchers. Nineteen studies with either case-control, cross-sectional, or baseline lumbar tactile acuity data collected before an intervention were included in the qualitative and quantitative synthesis. All pooled analyses were based on random effects models. Risk of bias was assessed using the Downs and Black scale and selection criteria were verified independently by 2 assessors.

Results:

Data on patients (n=547) and controls (n=346) were summarized. Studies on patients included data on nonspecific chronic LBP only; no data on acute LBP were identified. There was a significant mean difference between patients and controls for lumbar tactile acuity including (11.74 mm; 95% confidence interval, 8.61-14.87) and excluding (9.49 mm; 95% confidence interval, 3.64-15.34) higher risk of bias studies.

Discussion:

A gap of knowledge regarding tactile acuity in populations with acute and chronic non-neuropathic LBP needs to be addressed in future research as this may significantly help the understanding of the causality of tactile acuity alterations.
The Fear-Avoidance Components Scale (FACS)
Authors: Neblett Randy , Mayer Tom G. , Williams Mark J. , Asih Sali , Cuesta-Vargas Antonio I. , Hartzell Meredith M. , Gatchel Robert J.
Published: March 2017

Objectives:

To assess the clinical validity and factor structure of the Fear-Avoidance Components Scale (FACS), a new fear-avoidance measure.

Materials and Methods:

In this study, 426 chronic musculoskeletal pain disorder patients were admitted to a Functional Restoration Program (FRP). They were categorized into 5 FACS severity levels, from subclinical to extreme, at admission, and again at discharge. Associations with objective lifting performance and other patient-reported psychosocial measures were determined at admission and discharge, and objective work outcomes for this predominantly disabled cohort, were assessed 1 year later.

Results:

Those patients in the severe and extreme FACS severity groups at admission were more likely to “drop out” of treatment than those in the lower severity groups (P=0.05). At both admission and discharge, the FACS severity groups were highly and inversely correlated with objective lifting performance and patient-reported fear-avoidance–related psychosocial variables, including kinesiophobia, pain intensity, depressive symptoms, perceived disability, perceived injustice, and insomnia (Ps<0.001). All variables showed improvement at FRP discharge. Patients in the extreme FACS severity group at discharge were less likely to return to, or retain, work 1 year later (P≤0.02). A factor analysis identified a 2-factor solution.

Discussion:

Strong associations were found among FACS scores and other patient-reported psychosocial and objective lifting performance variables at both admission and discharge. High discharge-FACS scores were associated with worse work outcomes 1 year after discharge. The FACS seems to be a valid and clinically useful measure for predicting attendance, physical performance, distress, and relevant work outcomes in FRP treatment of chronic musculoskeletal pain disorder patients.
Somatosensory Functions in Survivors of Critical Illness
Authors: Baumbach Philipp , Götz Theresa , Günther Albrecht , Weiss Thomas , Meissner Winfried
Published: March 2017

Objectives:

There is growing evidence for increased levels of pain and reduced health-related quality of life in survivors of critical illness. Recent studies showed marked small nerve fiber pathology in critically ill patients, which may contribute to chronic pain states and reduced physical recovery after ICU discharge. Primary objective of this study was the comparison of somatosensory functions between survivors of critical illness 6 months after ICU discharge and controls. In post hoc analyses, we aimed to identify associations between small fiber deficits, pain, health-related quality of life, and clinical data.

Design:

Cross-sectional study.

Setting:

Study in critical illness survivors.

Patients:

Critical illness survivors (n = 84) and controls (n = 44).

Interventions:

None.

Measurements and Main Results:

Somatosensory functions were assessed with validated quantitative sensory testing. Pain and pain-related disability were assessed with the chronic pain grade questionnaire. Health-related quality of life was assessed by means of the Short Form-36. Compared with controls, former patients showed significantly increased thermal detection thresholds and more abnormal values in thermal testing, indicating reduced small fiber functioning. In addition, compared to patients without significant small fiber deficits (n = 46, 54.8%), patients with significant small fiber deficits (n = 38, 45.2%) reported higher average pain intensity, pain-related disability, and reduced physical health-related quality of life in the SF-36.

Conclusions:

A large portion of former critically ill patients show small fiber deficits which seem to be associated with increased pain and reduced physical health-related quality of life. Screening of somatosensory functions in the (post-) acute setting could possibly help to identify patients at risk of long-term impairments.
Quantifying the Mortality Impact of Do-Not-Resuscitate Orders in the ICU*
Authors: Fuchs Lior , Anstey Matthew , Feng Mengling , Toledano Ronen , Kogan Slava , Howell Michael D. , Clardy Peter , Celi Leo , Talmor Daniel , Novack Victor
Published: March 2017

Objectives:

We quantified the 28-day mortality effect of preexisting do-not-resuscitate orders in ICUs.

Design:

Longitudinal, retrospective study of patients admitted to five ICUs at a tertiary university medical center (Beth Israel Deaconess Medical Center, BIDMC, Boston, MA) between 2001 and 2008.

Intervention:

None.

Patients:

Two cohorts were defined: patients with do not resuscitate advance directives on day 1 of ICU admission and a control group comprising patients with no limitations of level of care on ICU day 1 (full code).

Measurements and Main Results:

The primary outcome was mortality at 28 days after ICU admission. Of 19,007 ICU patients, 1,239 patients (6.5%) had a do-not-resuscitate order on the first day of ICU admission and survived 48 hours in the ICU. We matched those do-not-resuscitate patients with 2,402 patients with full-code status. Twenty-eight day and 1-year mortality were both significantly higher in the do-not-resuscitate group (33.9% vs 18.4% and 60.7% vs 40.2%; p < 0.001, respectively).

Conclusion:

Do-not-resuscitate status is an independent risk factor for ICU mortality. This may reflect severity of illness not captured by other clinical factors, but the perceptions of the treating team related to do-not-resuscitate status could also be causally responsible for increased mortality in patients with do-not-resuscitate status.
Exosomes in Critical Illness
Authors: Terrasini Nora , Lionetti Vincenzo
Published: March 2017

Objective:

Exosomes are small, cell-released vesicles (40–100 nm in size) with the potential to transfer proteins, lipids, small RNAs, messenger RNAs, or DNA between cells via interstitial fluids. Due to their role in tissue homeostasis, exosomes have emerged as a new type of therapeutic and diagnostic (theranostic) tool in the noninvasive assessment of organ response to injury or treatment and in the development of reliable organ-protective intensive therapy. Our review provides current insights into the role of exosomes in the personalized management of injury and repair responses in critical illness.

Data Source:

Data were obtained from a PubMed search of the most recent medical literature, including the PubMed “related articles” search methodology.

Study Selection:

Articles considered include original articles, review articles and conference proceedings.

Data Extraction:

A detailed review of scientific, peer-reviewed data was performed. Relevant pre-clinical and clinical studies were included and summarized.

Data Synthesis:

Current scientific evidence is focused on the following: 1) Frontiers in the management of critical illness; 2) Biogenesis, characterization, and function of circulating exosomes; 3) The role of exosomes in acute lung injury; 4) The role of exosomes in acute cardiac injury; 5) The role of exosomes in acute kidney injury; 6) The role of exosomes in sepsis; 7) Limitations of exosome isolation protocols; and 8) Perspectives in the theranostic use of exosomes.

Conclusions:

Circulating levels of exosomes are associated with the onset and clinical course of critical illness. Exosomes released from cells with different phenotypes exert different functions in order to protect tissue and preserve organ function. Therefore, multifunctional exosomes with combined diagnostic and therapeutic functions show great promise in terms of personalized nanomedicine for patient-specific diagnosis and treatment of critical illness.
In Development—A New Paradigm for Understanding Vascular Disease
Authors: Flavahan Nicholas A.
Published: March 2017

Under physiological conditions, the arterial endothelium exerts a powerful protective influence to maintain vascular homeostasis. However, during the development of vascular disease, these protective activities are lost, and dysfunctional endothelial cells actually promote disease pathogenesis. Numerous investigations have analyzed the characteristics of dysfunctional endothelium with a view to understanding the processes responsible for the dysfunction and to determining their role in vascular pathology. This review adopts an alternate approach: reviewing the mechanisms that contribute to the initial formation of a healthy protective endothelium and on how those mechanisms may be disrupted, precipitating the appearance of dysfunctional endothelial cells and the progression of vascular disease. This approach, which highlights the role of endothelial adherens junctions and vascular endothelial–cadherin in endothelial maturation and endothelial dysfunction, provides new insight into the remarkable biology of this important cell layer and its role in vascular protection and vascular disease.
Predictors and social consequences of daily pain expectancy among adults with chronic pain
Authors: Mun Chung Jung , Thummala Kirti , Davis Mary C. , Karoly Paul , Tennen Howard , Zautra Alex J.
Published: March 2017

Previous research suggests that for people living with chronic pain, pain expectancy can undermine access to adaptive resources and functioning. We tested and replicated the unique effect of pain expectancy on subsequent pain through 2 daily diary studies. We also extended previous findings by examining cognitive and affective antecedents of pain expectancy and the consequences of pain expectancy for daily social enjoyment and stress. In study 1, 231 individuals with rheumatoid arthritis completed 30 end-of-day diaries. Results of multilevel structural equation model showed that controlling for today's pain, pain expectancy predicted next day pain. In study 2, diary assessments of affective, cognitive, and social factors were collected during the morning, afternoon, and evening for 21 days from a sample of 220 individuals with fibromyalgia. Results showed that both positive affect and the extent to which pain interfered with daily activities in the afternoon predicted evening pain expectancy in the expected direction. However, negative affect and pain coping efficacy were not associated with pain expectancy. Consistent with study 1, more than usual evening pain expectancy was related to greater next morning pain. We also found that next morning pain predicted next afternoon social enjoyment but not social stress. The findings of these 2 studies point to the importance of promoting positive affect and reducing pain expectancy as a way of decreasing the detrimental effect of chronic pain on enjoyable social experiences.
A Single US Center Experience of Transbronchial Lung Cryobiopsy for Diagnosing Interstitial Lung Disease With a 2-Scope Technique
Authors: Sriprasart Thitiwat , Aragaki Alejandro , Baughman Robert , Wikenheiser-Brokamp Kathryn , Khanna Gaurav , Tanase Daniel , Kirschner Michelle , Benzaquen Sadia
Published: March 2017

Background:

Transbronchial lung cryobiopsy (TBLC) has been used to establish the diagnosis of interstitial lung disease (ILD) in recent years. The technique and diagnostic yield vary among institutions. We report a new 2-scope technique and the results of TBLC in our institution.

Methods:

This is a retrospective chart review of patients who underwent TBLC for evaluation of ILD. Bronchoscopy with TBLC was performed by a board-certified interventional pulmonologist with a 2-scope technique under general anesthesia.

Results:

A total of 74 patients underwent TBLC with a 2-scope technique. Their mean age was 54±14 years. The mean tissue surface area was 63.54±6.76 mm2. The average anesthesia time was 80.66 minutes. The diagnostic yield was 87.84%. The most common diagnosis was sarcoidosis pneumothorax, which occurred in 5 cases (7%). There was 1 case with bronchoscopic-related respiratory failure associated with significant bleeding. Death occurred in 3 cases (4%), which is comparable to recent mortality data for “elective” surgical lung biopsy for ILD (1.7% to 4.2%).

Conclusion:

TBLC with a 2-scope technique could be an alternative method for diagnosing various types of ILD in patients unfit for surgical lung biopsy. Further prospective studies should clarify its role in the diagnostic armamentarium for undiagnosed ILDs.
Febrile infant update
Authors: Dorney Kate , Bachur Richard G.
Published: March 2017

Purpose of review

The approach to febrile young infants remains challenging. This review serves as an update on the care of febrile infants less than 90 days of age with a focus on the changing epidemiology of serious bacterial infection (SBI), refinement of management strategies based on biomarkers, and the development of novel diagnostics.

Recent findings

There is high variability in the emergency department management of febrile young infants without significant differences in outcomes. C-reactive protein (CRP) and procalcitonin have emerged as valuable risk-stratification tests to identify high-risk infants. When interpreting automated urinalyses for suspected urinary tract infection (UTI), urine concentration influences the diagnostic value of pyuria. Novel diagnostics including RNA biosignatures and protein signatures show promise in better identifying young febrile infants at risk of serious infection.

The majority of febrile infants with an SBI will have a UTI but the diagnosis of invasive bacterial infection in infants continues to be challenging. The use of procalcitonin and CRP as biomarkers in prediction algorithms facilitates identification of low-risk infants.
Multilevel Factors Associated With Injurious Falls in Acute Care Hospitals
Authors: Zhao Yunchuan (Lucy) , Bott Marjorie , He Jianghua , Kim Heejung , Park Shin Hye , Dunton Nancy
Published: March 2017

Using National Database of Nursing Quality Indicators data from July 2013 to June 2014, this correlational study examined the associations of injurious falls among all patient falls with multilevel factors in hospitals. The sample included all falls recorded in adult medical, surgical, combined medical-surgical, and step-down units (N = 2299) in participating hospitals (N = 488). Hierarchical negative binominal regression analyses were performed. Results revealed hospital and unit organizational factors associated with inpatient injurious falls.
Suicidal Ideation and Psychological Strain Among Patients Diagnosed With Stomach Cancer
Authors: Zhang Xuekun , Zhang Jie , Procter Nicholas , Chen Xiaoyun , Su Yonggang , Lou Fenglan , Cao Fenglin
Published: March 2017

Patients with stomach cancer are at high risk to experience suicidal ideation. Strain theory of suicide assumes that suicide is preceded by psychological strain. Despite wide international acceptance of the theory, its use with a sample of patients with stomach cancer has not previously been reported. The aims were to examine the relationship between psychological strain and suicidal ideation among patients with stomach cancer and to determine whether psychopathological factors act as mediators. A cross-sectional study was undertaken involving subjects with no history of mental disorder, and questionnaires were administered by face-to-face interview. Patients who experienced more psychological strain, especially coping strain, are more likely to experience suicidal ideation. The mediation effects of hopelessness and psychological distress are significant. Psychological strain, hopelessness, and psychological distress may be the vital factors among patients with stomach cancer in the suicide-risk assessment interview and for care planning and psychological intervention.
Factors Associated With Discharge Home After Transfer to a Pediatric Emergency Department
Authors: Peebles Erin R. , Miller Michael R. , Lynch Tim P. , Tijssen Janice A.
Published: March 2017

Objectives

The transfer of children from community emergency departments (EDs) to tertiary care pediatric EDs for investigations, interventions, or a second opinion is common. In order to improve health care system efficiency, we must have a better understanding of this population and identify areas for education and capacity building.

Methods

We conducted a retrospective chart review of all patients (aged 0–17 years) who were transferred from community ED to a pediatric ED from November 2013 to November 2014. The primary outcome was the frequency of referred patients who were discharged home from the pediatric ED.

Results

Two hundred four patients were transferred from community EDs in the study period. One hundred thirteen children (55.4%) were discharged home from the pediatric ED. Presence of inpatient pediatric services (P = 0.04) at the referral hospital and a respiratory diagnosis (P = 0.03) were independently associated with admission to the children’s hospital. In addition, 74 patients (36.5%) had no critically abnormal vital signs at the referral hospital and did not require any special tests, interventions, consultations, or admission to the children’s hospital. Younger age (P = 0.03), lack of inpatient pediatric services (P = 0.04), and a diagnosis change (P = 0.03) were independently associated with this outcome.

Conclusions

More than half of patients transferred to the pediatric tertiary care ED did not require admission, and more than one third did not require special tests, interventions, consults, or admission. Many of these patients were likely transferred for a second opinion from a pediatric emergency medicine specialist. Education and real-time videoconferencing consultations using telemedicine may help to reduce the frequency of transfers for a second opinion and contribute to cost savings over the long term.
Experience With a Care Process Model in the Evaluation of Pediatric Musculoskeletal Infections in a Pediatric Emergency Department
Authors: Patel Lina , Michael Jeff , Allen Nancy , Schroeder Lisa , Berglund Lisa , Newland Jason G.
Published: March 2017

Objectives

Care process models (CPMs) for certain conditions have improved clinical outcomes in children. This study describes the implementation and impact of a CPM for the evaluation of musculoskeletal infections in a pediatric emergency department (ED).

Methods

A retrospective pre-post intervention study was performed to analyze the impact of a musculoskeletal infection CPM. Patients were identified retrospectively through electronic order history for imaging of an extremity or joint and recommended laboratory tests. Clinical outcomes evaluated included hospital length of stay (LOS), time to magnetic resonance imaging (MRI), time to administration of antibiotics, hospital admission rate, and 30-day readmission rate.

Results

Musculoskeletal infection evaluations completed in the ED were reviewed from 1 year before implementation (n = 383) and 2 years after implementation (n = 1219) of the CPM. A significant improvement in the time to antibiotic administration for all patients (4.3 vs 3.7 hours, P < 0.05) and for patients with confirmed musculoskeletal infections (9.5 vs 4.9 hours, P < 0.05) was observed after the implementation of the CPM. The overall time to MRI (13.2 vs 10.3 hours, P = 0.29) and hospital LOS (4.7 vs 3.7 days, P = 0.11) were improved for all patients but were not statistically significant. The admission rate and 30-day readmission were similar before and after the implementation of the CPM.

Conclusions

The implementation of a musculoskeletal infection CPM has standardized the approach to the evaluation and diagnosis of musculoskeletal infections resulting in a significant decrease in the time to administer antibiotics and a downward trend in time to MRI and hospital LOS.
Acute Painless Lower Gastrointestinal Bleed That Mimics Meckel Diverticulum
Authors: Gourishankar Anand , Tsao KuoJen
Published: March 2017

Objective

We describe a case of gastrointestinal duplication cyst with heterotopic gastric mucosa presenting with hematochezia.

Case

The patient was a previously healthy 2-month-old girl presenting with passing fresh blood in the diaper without distress or abdominal discomfort. She was evaluated for colic prior to this episode and discharged home. Meckel scan was positive, and surgeons performed an exploratory laparotomy to identify a jejunal duplication cyst. The infant had an uneventful recovery and was discharged home.

Conclusions

Gastrointestinal duplication cyst is an uncommon condition and can rarely present with lower gastrointestinal bleed with heterotopic gastric mucosa.
Mindfulness Meditation Training and Executive Control Network Resting State Functional Connectivity: A Randomized Controlled Trial
Authors: Taren Adrienne A. , Gianaros Peter J. , Greco Carol M. , Lindsay Emily K. , Fairgrieve April , Brown Kirk Warren , Rosen Rhonda K. , Ferris Jennifer L. , Julson Erica , Marsland Anna L. , Creswell J. David
Published: March 2017

Objective

Mindfulness meditation training has been previously shown to enhance behavioral measures of executive control (e.g., attention, working memory, cognitive control), but the neural mechanisms underlying these improvements are largely unknown. Here, we test whether mindfulness training interventions foster executive control by strengthening functional connections between dorsolateral prefrontal cortex (dlPFC)—a hub of the executive control network—and frontoparietal regions that coordinate executive function.

Methods

Thirty-five adults with elevated levels of psychological distress participated in a 3-day randomized controlled trial of intensive mindfulness meditation or relaxation training. Participants completed a resting state functional magnetic resonance imaging scan before and after the intervention. We tested whether mindfulness meditation training increased resting state functional connectivity (rsFC) between dlPFC and frontoparietal control network regions.

Results

Left dlPFC showed increased connectivity to the right inferior frontal gyrus (T = 3.74), right middle frontal gyrus (MFG) (T = 3.98), right supplementary eye field (T = 4.29), right parietal cortex (T = 4.44), and left middle temporal gyrus (T = 3.97, all p < .05) after mindfulness training relative to the relaxation control. Right dlPFC showed increased connectivity to right MFG (T = 4.97, p < .05).

Conclusions

We report that mindfulness training increases rsFC between dlPFC and dorsal network (superior parietal lobule, supplementary eye field, MFG) and ventral network (right IFG, middle temporal/angular gyrus) regions. These findings extend previous work showing increased functional connectivity among brain regions associated with executive function during active meditation by identifying specific neural circuits in which rsFC is enhanced by a mindfulness intervention in individuals with high levels of psychological distress.

Clinical Trial Registration

Clinicaltrials.gov, NCT01628809.
Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT
Authors: Sivay Mariya V. , Li Maoji , Piwowar-Manning Estelle , Zhang Yinfeng , Hudelson Sarah E. , Marzinke Mark A. , Amico Rivet K. , Redd Andrew , Hendrix Craig W. , Anderson Peter L. , Bokoch Kevin , Bekker Linda-Gail , van Griensven Frits , Mannheimer Sharon , Hughes James P. , Grant Robert , Eshleman Susan H.
Published: March 2017

Background:

HIV Prevention Trials Network (HPTN) 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed therapy (DOT) of TDF/FTC, and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial.

Methods:

HIV rapid testing was performed at study sites. Retrospective testing included fourth generation assays, HIV RNA testing, Western blot, an HIV-1/2 discriminatory assay, resistance testing, and antiretroviral drug testing.

Results:

Six of the 12 seroconverters received TDF/FTC in the DOT phase, but were not randomized (3 were acutely infected at enrollment; 2 were infected during the DOT phase; 1 was not randomized because of pregnancy). One of the 6 randomized participants had acute infection at randomization but was not diagnosed for 3–4 months because HIV rapid tests were nonreactive; continued daily PrEP use was associated with false-negative antibody tests and low HIV RNA levels. The 5 participants infected after randomization included 4 with low adherence to the PrEP regimen, and one who reported a 7-day period without dosing before infection. Three participants had TDF/FTC resistance (M184I, K65R), including 2 who received only 4 once-weekly TDF/FTC doses; most TDF/FTC mutations were detected by next generation sequencing only.

Conclusions:

In HPTN 067/ADAPT, participants who acquired HIV infection had infrequent PrEP dosing or low/suboptimal adherence. Sensitive assays improved detection of HIV infection and drug resistance. Drug resistance was observed with limited PrEP exposure.
Determinants of HIV Phylogenetic Clustering in Chicago Among Young Black Men Who Have Sex With Men From the uConnect Cohort
Authors: Morgan Ethan , Nyaku Amesika N. , D'Aquila Richard T. , Schneider John A.
Published: March 2017

Introduction:

Phylogenetic analysis determines similarities among HIV genetic sequences from persons infected with HIV, identifying clusters of transmission. We determined characteristics associated with both membership in an HIV transmission cluster and the number of clustered sequences among a cohort of young black men who have sex with men (YBMSM) in Chicago.

Methods:

Pairwise genetic distances of HIV-1 pol sequences were collected during 2013–2016. Potential transmission ties were identified among HIV-infected persons whose sequences were ≤1.5% genetically distant. Putative transmission pairs were defined as ≥1 tie to another sequence. We then determined demographic and risk attributes associated with both membership in an HIV transmission cluster and the number of ties to the sequences from other persons in the cluster.

Results:

Of 86 available sequences, 31 (36.0%) were tied to ≥1 other sequence. Through multivariable analyses, we determined that those who reported symptoms of depression and those who had a higher number of confidants in their network had significantly decreased odds of membership in transmission clusters. We found that those who had unstable housing and who reported heavy marijuana use had significantly more ties to other individuals within transmission clusters, whereas those identifying as bisexual, those participating in group sex, and those with higher numbers of sexual partners had significantly fewer ties.

Conclusions:

This study demonstrates the potential for combining phylogenetic and individual and network attributes to target HIV control efforts to persons with potentially higher transmission risk, as well as suggesting some unappreciated specific predictors of transmission risk among YBMSM in Chicago for future study.
Pediatric multiple sclerosis
Authors: Yeshokumar Anusha K. , Narula Sona , Banwell Brenda
Published: March 2017

Purpose of review

This review discusses the epidemiologic factors involved in the pathogenesis of pediatric multiple sclerosis (MS), which have been the focus of numerous studies in the last several years. We also review the clinical features (including diagnostic evaluation and differential diagnosis) of, treatment approach to, and prognosis of pediatric MS.

Recent findings

Up to 10% of patients with MS have their initial demyelinating before the age of 18 years. Over the past 15 years, international and collaborative studies have identified an increasing number of genetic and environmental risk factors for pediatric MS. Identification of these risks and their interplay allow for better understanding of the pathophysiology of pediatric MS, which may inform subsequent treatment and disease management. Careful attention to the management of relapses and chronic symptoms, including implementation of lifestyle modifications and pharmacologic interventions, enables improved school performance and quality of life.

Ongoing research in the field of pediatric MS aims to better understand the epidemiologic factors involved in the pathobiology, safety and efficacy of disease-modifying treatments, and long-term prognosis, particularly of cognitive development and academic potential. Collaborative, multinational studies will enable the advancements needed to truly optimize clinical care for this population.
Ipsilateral Tremor-Like Grasp Reaction in a Patient With Ischemic Stroke
Authors: Inatomi Yuichiro , Nakajima Makoto , Yonehara Toshiro , Ando Yukio
Published: March 2017

Reports of involuntary ipsilateral movements after a stroke are rare, and none have described a patient with both an instinctive grasp reaction and tremor-like movement ipsilateral to the acute stroke lesion. We here report such a patient. A 76-year-old right-handed woman with a past history of left thalamic hemorrhage developed left hemiparesis, an instinctive grasp reaction, and a peculiar involuntary movement of her right arm. This involuntary movement was stereotyped and sometimes rhythmical, with a groping or picking-like action. The lesion responsible for her motor deficits was a broad infarct in the right internal carotid artery territory. We suggest that her characteristic involuntary tremor-like movement was a variation of the instinctive grasp reaction caused by an ipsilateral ischemic lesion that included the frontal lobe. We illustrate her movements with a video, Supplemental Digital Content 1, http://links.lww.com/CBN/A65.
Genetic Alzheimer Disease and Sporadic Dementia With Lewy Bodies: A Comorbidity Presenting as Primary Progressive Aphasia
Authors: Picková Tereza , Matěj Radoslav , Bezdicek Ondrej , Keller Jiří , van der Zee Julie , Van Broeckhoven Christine , Cséfalvay Zsolt , Rusina Robert
Published: March 2017

We report a 44-year-old woman, with a family history of early-onset dementia, presenting with primary progressive aphasia. This clinically variable syndrome has multiple underlying pathologies, and correlations between clinical manifestations and postmortem neuropathologic findings are controversial. Our patient suffered worsening language impairment with major word-finding difficulties but preserved comprehension. She also developed episodic memory impairment. Her condition progressed to dementia with behavioral changes. Magnetic resonance imaging showed early left perisylvian and bitemporal atrophy. The patient died shortly afterward from colon cancer. Neuropathologic examination revealed advanced early-onset Alzheimer and Lewy body disease, plus a clinically nonrelevant metastasis of her colon cancer in her left parietal lobe. Genetic examination revealed a p.Glu184Asp mutation in the presenilin1 gene. Our findings confirm the importance of a thorough appreciation for the clinical and neuropathologic correlations in patients with atypical neurodegenerative dementias.
Shifting Spatial Neglect With Repeated Line Bisections: Possible Role of Lateralized Attentional Fatigue
Authors: Woods Mary , Williamson John B. , White Keith D. , Maitland Charles G. , Heilman Kenneth M.
Published: March 2017

Background and Objective:

Many patients who have signs of neglect immediately after a right hemisphere stroke remain disabled even when they improve on tests of neglect. Few patients are tested for attentional persistence and fatigue despite their importance in many instrumental activities. To investigate whether stimulus repetition might alter the allocation of attention, we repeatedly tested a patient 16 weeks after she developed hemispatial neglect from a right hemisphere stroke.

Methods:

During each of three testing sessions given in 1 day, we asked the patient to bisect 90 lines of two lengths, presented in 30-trial blocks in three locations: left, center, and right of her midsagittal plane, partially counterbalanced across sessions. We adjusted multiple regression analyses and analysis of variance as well as post hoc regression and t tests for persistence in the repeated measures using variance-sample size analysis to estimate self-similarity, a measure related to the fractal correlation dimension.

Results:

In each session, the patient’s line bisections revealed transient leftward bias in her left peripersonal space, and constant rightward bias in her right peripersonal space. Her leftward bias shifted to a rightward bias over repeated trials in her left space.

Conclusions:

The patient’s left-to-right shift with repeated trials suggests either fatigue from an attempted compensation for leftward inattention or habituation of a contralesional spatial attentional attraction, revealing contralesional left-sided neglect in both the left and right spaces. Future studies are needed to learn if other patients show similar or different deficits with repetition, and how best to treat them.
Predictors That a Diagnosis of Mild Cognitive Impairment Will Remain Stable 3 Years Later
Authors: Clem Matthew A. , Holliday Ryan P. , Pandya Seema , Hynan Linda S. , Lacritz Laura H. , Woon Fu L.
Published: March 2017

Background and Objective:

In half to two thirds of patients who are diagnosed with mild cognitive impairment (MCI), the diagnosis neither converts to dementia nor reverts to normal cognition; however, little is known about predictors of MCI stability. Our study aimed to identify those predictors.

Methods:

We obtained 3-year longitudinal data from the National Alzheimer’s Coordinating Center Uniform Data Set for patients with a baseline diagnosis of MCI. To predict MCI stability, we used the patients’ baseline data to conduct three logistic regression models: demographics, global function, and neuropsychological performance.

Results:

Our final sample had 1059 patients. At the end of 3 years, 596 still had MCI and 463 had converted to dementia. The most reliable predictors of stable MCI were higher baseline scores on delayed recall, processing speed, and global function; younger age; and absence of apolipoprotein E4 alleles.

Conclusions:

Not all patients with MCI progress to dementia. Of the protective factors that we identified from demographic, functional, and cognitive data, the absence of apolipoprotein E4 alleles best predicted MCI stability. Our predictors may help clinicians better evaluate and treat patients, and may help researchers recruit more homogeneous samples for clinical trials.
Mitogenomes and relatedness do not predict frequency of tool-use by sea otters
Authors: Ralls Katherine , McInerney Nancy Rotzel , Gagne Roderick B. , Ernest Holly B. , Tinker M. Tim , Fujii Jessica , Maldonado Jesus
Published: March 2017

Many ecological aspects of tool-use in sea otters are similar to those in Indo-Pacific bottlenose dolphins. Within an area, most tool-using dolphins share a single mitochondrial haplotype and are more related to each other than to the population as a whole. We asked whether sea otters in California showed similar genetic patterns by sequencing mitogenomes of 43 otters and genotyping 154 otters at 38 microsatellite loci. There were six variable sites in the mitogenome that yielded three haplotypes, one found in only a single individual. The other two haplotypes contained similar percentages (33 and 36%) of frequent tool-users and a variety of diet types. Microsatellite analyses showed that snail specialists, the diet specialist group that most frequently used tools, were no more related to each other than to the population as a whole. The lack of genetic association among tool-using sea otters compared with dolphins may result from the length of time each species has been using tools. Tool-use in dolphins appears to be a relatively recent innovation (less than 200 years) but sea otters have probably been using tools for many thousands or even millions of years.
When environmental factors become stressors: interactive effects of vermetid gastropods and sedimentation on corals
Authors: Zill Julie A. , Gil Michael A. , Osenberg Craig W.
Published: March 2017

Environmental stressors often interact, but most studies of multiple stressors have focused on combinations of abiotic stressors. Here we examined the potential interaction between a biotic stressor, the vermetid snail
Ceraesignum maximum
, and an abiotic stressor, high sedimentation, on the growth of reef-building corals. In a field experiment, we subjected juvenile massive
Porites
corals to four treatments: (i) neither stressor, (ii) sedimentation, (iii) vermetids or (iv) both stressors. Unexpectedly, we found no effect of either stressor in isolation, but a significant decrease in coral growth in the presence of both stressors. Additionally, seven times more sediment remained on corals in the presence (versus absence) of vermetids, likely owing to adhesion of sediments to corals via vermetid mucus. Thus, vermetid snails and high sedimentation can interact to drive deleterious effects on reef-building corals. More generally, our study illustrates that environmental factors can combine to have negative interactive effects even when individual effects are not detectable. Such ‘ecological surprises' may be easily overlooked, leading to environmental degradation that cannot be anticipated through the study of isolated factors.
Theoretically possible spatial accuracy of geomagnetic maps used by migrating animals
Authors: Komolkin Andrei V. , Kupriyanov Pavel , Chudin Andrei , Bojarinova Julia , Kavokin Kirill , Chernetsov Nikita
Published: March 2017

Many migrating animals, belonging to different taxa, annually move across the globe and cover hundreds and thousands of kilometres. Many of them are able to show site fidelity, i.e. to return to relatively small migratory targets, from distant areas located beyond the possible range of direct sensory perception. One widely debated possibility of how they do it is the use of a magnetic map, based on the dependence of parameters of the geomagnetic field (total field intensity and inclination) on geographical coordinates. We analysed temporal fluctuations of the geomagnetic field intensity as recorded by three geomagnetic observatories located in Europe within the route of many avian migrants, to study the highest theoretically possible spatial resolution of the putative map. If migratory birds measure total field intensity perfectly and take the time of day into account, in northern Europe 81% of them may return to a strip of land of 43 km in width along one of coordinates, whereas in more southern areas such a strip may be narrower than 10 km. However, if measurements are performed with an error of 0.1%, the strip width is increased by approximately 40 km, so that in spring migrating birds are able to return to within 90 km of their intended goal. In this case, migrating birds would probably need another navigation system, e.g. an olfactory map, intermediate between the large-scale geomagnetic map and the local landscape cues, to locate their goal to within several kilometres.
Form–function relationships in dragonfly mandibles under an evolutionary perspective
Authors: Blanke Alexander , Schmitz Helmut , Patera Alessandra , Dutel Hugo , Fagan Michael J.
Published: March 2017

Functional requirements may constrain phenotypic diversification or foster it. For insect mouthparts, the quantification of the relationship between shape and function in an evolutionary framework remained largely unexplored. Here, the question of a functional influence on phenotypic diversification for dragonfly mandibles is assessed with a large-scale biomechanical analysis covering nearly all anisopteran families, using finite element analysis in combination with geometric morphometrics. A constraining effect of phylogeny could be found for shape, the mandibular mechanical advantage (MA), and certain mechanical joint parameters, while stresses and strains, the majority of joint parameters and size are influenced by shared ancestry. Furthermore, joint mechanics are correlated with neither strain nor mandibular MA and size effects have virtually play no role for shape or mechanical variation. The presence of mandibular strengthening ridges shows no phylogenetic signal except for one ridge peculiar to Libelluloidea, and ridge presence is also not correlated with each other. The results suggest that functional traits are more variable at this taxonomic level and that they are not influenced by shared ancestry. At the same time, the results contradict the widespread idea that mandibular morphology mainly reflects functional demands at least at this taxonomic level. The varying functional factors rather lead to the same mandibular performance as expressed by the MA, which suggests a many-to-one mapping of the investigated parameters onto the same narrow mandibular performance space.
Limb flexion-induced twist and associated intramural stresses in the human femoropopliteal artery
Authors: Desyatova Anastasia , Poulson William , Deegan Paul , Lomneth Carol , Seas Andreas , Maleckis Kaspars , MacTaggart Jason , Kamenskiy Alexey
Published: March 2017

High failure rates of femoropopliteal artery (FPA) interventions are often attributed to severe mechanical deformations that occur with limb movement. Torsion of the FPA likely plays a significant role, but is poorly characterized and the associated intramural stresses are currently unknown. FPA torsion in the walking, sitting and gardening postures was characterized in
n
= 28
in situ
FPAs using intra-arterial markers. Principal mechanical stresses and strains were quantified in the superficial femoral artery (SFA), adductor hiatus segment (AH) and the popliteal artery (PA) using analytical modelling. The FPA experienced significant torsion during limb flexion that was most severe in the gardening posture. The associated mechanical stresses were non-uniformly distributed along the length of the artery, increasing distally and achieving maximum values in the PA. Maximum twist in the SFA ranged 10–13° cm
−1
, at the AH 8–16° cm
−1
, and in the PA 14–26° cm
−1
in the walking, sitting and gardening postures. Maximum principal stresses were 30–35 kPa in the SFA, 27–37 kPa at the AH and 39–43 kPa in the PA. Understanding torsional deformations and intramural stresses in the FPA can assist with device selection for peripheral arterial disease interventions and may help guide the development of devices with improved characteristics.