Αρχειοθήκη ιστολογίου

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Παρασκευή 18 Ιανουαρίου 2019

Periventricular white matter changes in idiopathic intracranial hypertension

Abstract

Objective

To evaluate whether increased cerebrospinal fluid (CSF) pressure causes alteration of periventricular white matter (WM) microstructure in patients with idiopathic intracranial hypertension (IIH).

Methods

In a prospective study, patients with refractory chronic headache with and without IIH performed a neuroimaging study including 3T MRI, 3D Phase Contrast MR venography, and diffusion tensor imaging (DTI) of the brain. Whole‐brain voxel‐wise comparisons of DTI abnormalities of WM were performed using tract‐based spatial statistics. A correlation analysis between DTI indices and CSF opening pressure, highest peak, and mean pressure was also performed in patients with IIH.

Results

We enrolled 62 consecutive patients with refractory chronic headaches. Thirty‐five patients with IIH, and 27 patients without increased intracranial pressure. DTI analysis revealed no fractional anisotropy changes, but decreased mean, axial, and radial diffusivity in body (IIHMD = 0.80 ± 0.04, non‐IIHMD = 0.84 ± 0.4, IIHAD = 1.67 ± 0.07, non‐IIHAD = 1.74 ± 0.05, IIHRD = 0.38 ± 0.04, non‐IIHRD = 0.42 ± 0.05 [mm2/sec × 10−3]) of corpus callosum, and in right superior corona radiata (IIHMD = 0.75 ± 0.04, non‐IIHMD = 0.79 ± 0.05, IIHAD = 1.19 ± 0.07, non‐IIHAD = 1.28 ± 0.09, IIHRD = 0.59 ± 0.03, non‐IIHRD = 0.53 ± 0.03 [mm2/sec × 10−3]) of 35 patients with IIH compared with 27 patients without increased intracranial pressure. DTI indices were negatively correlated with high CSF pressures (< 0.05). After medical treatment, eight patients showed incremented MD in anterior corona radiata left and right and superior corona radiata right.

Conclusions

There is significant DTI alteration in periventricular WM microstructure of patients with IIH suggesting tissue compaction correlated with high CSF pressure. This periventricular WM change may be partially reversible after medical treatment.



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The Development of Chronic Critical Illness Determines Physical Function, Quality of Life, and Long-Term Survival Among Early Survivors of Sepsis in Surgical ICUs

Objectives: This study sought to examine mortality, health-related quality of life, and physical function among sepsis survivors who developed chronic critical illness. Design: Single-institution, prospective, longitudinal, observational cohort study assessing 12-month outcomes. Setting: Two surgical/trauma ICUs at an academic tertiary medical and level 1 trauma center. Patients: Adult critically ill patients that survived 14 days or longer after sepsis onset. Interventions: None. Measurements and Main Results: Baseline patient characteristics and function, sepsis severity, and clinical outcomes of the index hospitalization were collected. Follow-up physical function (short physical performance battery; Zubrod; hand grip strength) and health-related quality of life (EuroQol-5D-3L, Short Form-36) were measured at 3, 6, and 12 months. Hospital-free days and mortality were determined at 12 months. We compared differences in long-term outcomes between subjects who developed chronic critical illness (≥ 14 ICU days with persistent organ dysfunction) versus those with rapid recovery. The cohort consisted of 173 sepsis patients; 63 (36%) developed chronic critical illness and 110 (64%) exhibited rapid recovery. Baseline physical function and health-related quality of life did not differ between groups. Those who developed chronic critical illness had significantly fewer hospital-free days (196 ± 148 vs 321 ± 65; p

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Validation and Critical Evaluation of the Effective Arterial Elastance in Critically Ill Patients

Objectives: First, to validate bedside estimates of effective arterial elastance = end-systolic pressure/stroke volume in critically ill patients. Second, to document the added value of effective arterial elastance, which is increasingly used as an index of left ventricular afterload. Design: Prospective study. Setting: Medical ICU. Patients: Fifty hemodynamically stable and spontaneously breathing patients equipped with a femoral (n = 21) or radial (n = 29) catheter were entered in a "comparison" study. Thirty ventilated patients with invasive hemodynamic monitoring (PiCCO-2; Pulsion Medical Systems, Feldkirchen, Germany), in whom fluid administration was planned were entered in a "dynamic" study. Interventions: In the "dynamic" study, data were obtained before/after a 500 mL saline administration. Measurements and Main Results: According to the "cardiocentric" view, end-systolic pressure was considered the classic index of left ventricular afterload. End-systolic pressure was calculated as 0.9 × systolic arterial pressure at the carotid, femoral, and radial artery level. In the "comparison" study, carotid tonometry allowed the calculation of the reference effective arterial elastance value (1.73 ± 0.62 mm Hg/mL). The femoral estimate of effective arterial elastance was more accurate and precise than the radial estimate. In the "dynamic" study, fluid administration increased stroke volume and end-systolic pressure, whereas effective arterial elastance (femoral estimate) and systemic vascular resistance did not change. Effective arterial elastance was related to systemic vascular resistance at baseline (r = 0.89) and fluid-induced changes in effective arterial elastance and systemic vascular resistance were correlated (r = 0.88). In the 15 fluid responders (cardiac index increases ≥ 15%), fluid administration increased end-systolic pressure and decreased effective arterial elastance and systemic vascular resistance (each p

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The Cost-Effectiveness of Interventions to Increase Utilization of Prone Positioning for Severe Acute Respiratory Distress Syndrome

Objectives: Despite strong evidence supporting proning in acute respiratory distress syndrome, few eligible patients receive it. This study determines the cost-effectiveness of interventions to increase utilization of proning for severe acute respiratory distress syndrome. Design: We created decision trees to model severe acute respiratory distress syndrome from ICU admission through death (societal perspective) and hospital discharge (hospital perspective). We assumed patients received low tidal volume ventilation. We used short-term outcome estimates from the PROSEVA trial and longitudinal cost and benefit data from cohort studies. In probabilistic sensitivity analyses, we used distributions for each input that included the fifth to 95th percentile of its CI. Setting: ICUs that care for patients with acute respiratory distress syndrome. Subjects: Patients with moderate to severe acute respiratory distress syndrome. Interventions: The implementation of a hypothetical intervention to increase the appropriate utilization of prone positioning. Measurements and Main Results: In the societal perspective model, an intervention that increased proning utilization from 16% to 65% yielded an additional 0.779 (95% CI, 0.088–1.714) quality-adjusted life years at an additional long-term cost of $31,156 (95% CI, –$158 to $92,179) (incremental cost-effectiveness ratio = $38,648 per quality-adjusted life year [95% CI, $1,695–$98,522]). If society was willing to pay $100,000 per quality-adjusted life year, any intervention costing less than $51,328 per patient with moderate to severe acute respiratory distress syndrome would represent good value. From a hospital perspective, the intervention yielded 0.072 (95% CI, 0.008–0.147) more survivals-to-discharge at a cost of $5,242 (95% CI, –$19,035 to $41,019) (incremental cost-effectiveness ratio = $44,615 per extra survival [95% CI, –$250,912 to $558,222]). If hospitals were willing to pay $100,000 per survival-to-discharge, any intervention costing less than $5,140 per patient would represent good value. Conclusions: Interventions that increase utilization of proning would be cost-effective from both societal and hospital perspectives under many plausible cost and benefit assumptions. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://bit.ly/29S62lw). Dr. Baston received financial support from the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute T32 HL-007891, and he received support for article research from the NIH. Dr. Mancebo received funding from Faron, Medtronic, and IMTmedical (travel and accommodation), and Fisher Paykel, General Electric, and A-Lung provided equipment to conduct clinical research. The remaining authors have not disclosed any potential conflicts of interest. This work was performed at the University of Pennsylvania. Address requests for reprints to: Cameron M Baston, 3400 Spruce St, Philadelphia, PA 19104. E-mail: cbass@alum.mit.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Incidence and Risk Factors for Cannula-Related Venous Thrombosis After Venovenous Extracorporeal Membrane Oxygenation in Adult Patients With Acute Respiratory Failure

Objectives: Venovenous extracorporeal membrane oxygenation is indicated in patients with severe refractory acute respiratory failure. Venous thrombosis due to indwelling catheters is a frequent complication. The aim of this study was to analyze the incidence of cannula-related thrombosis and its risk factors after venovenous extracorporeal membrane oxygenation. Design: Retrospective observational study. Setting: A medical ICU at the University Hospital Regensburg. Patients: We analyzed consecutive patients with severe respiratory failure (PaO2/FIO2

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A Fate Worse Than Death: Prognostication of Devastating Brain Injury

Objectives: To describe the sources of uncertainty in prognosticating devastating brain injury, the role of the intensivist in prognostication, and ethical considerations in prognosticating devastating brain injury in the ICU. Data Sources: A PubMed literature review was performed. Study Selection: Articles relevant to prognosis in intracerebral hemorrhage, acute ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and postcardiac arrest anoxic encephalopathy were selected. Data Extraction: Data regarding definition and prognosis of devastating brain injury were extracted. Themes related to how clinicians perform prognostication and their accuracy were reviewed and extracted. Data Synthesis: Although there are differences in pathophysiology and therefore prognosis in the various etiologies of devastating brain injury, some common themes emerge. Physicians tend to have fairly good prognostic accuracy, especially in severe cases with poor prognosis. Full supportive care is recommended for at least 72 hours from initial presentation to maximize the potential for recovery and minimize secondary injury. However, physician approaches to the timing of and recommendations for withdrawal of life-sustaining therapy have a significant impact on mortality from devastating brain injury. Conclusions: Intensivists should consider the modern literature describing prognosis for devastating brain injury and provide appropriate time for patient recovery and for discussions with the patient's surrogates. Surrogates wish to have a prognosis enumerated even when uncertainty exists. These discussions must be handled with care and include admission of uncertainty when it exists. Respect for patient autonomy remains paramount, although physicians are not required to provide inappropriate medical therapies. The authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Alexandra K. Pratt, MD, Department of Critical Care, MedStar Washington Hospital Center, 110 Irving St NW, Suite 4B-42, Washington, DC 20010. E-mail: akapratt@gmail.com Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Respiratory Variability of Pulmonary Velocity-Time Integral As a New Gauge of Fluid Responsiveness For Mechanically Ventilated Patients in the ICU

Objectives: To evaluate reliability and feasibility of the respiratory variability of pulmonary velocity-time integral as a new dynamic marker of fluid responsiveness in mechanically ventilated patients. Design: Prospective observational study. Setting: Medical-surgical ICU of a general hospital. Patients: Fifty mechanically ventilated patients with acute circulatory failure. Interventions: Transthoracic echocardiography was performed at inclusion (transthoracic echocardiography baseline). Fluid therapy was prescribed to patients exhibiting one value greater than or equal to 13% among commonly used variables of fluid responsiveness: respiratory variability of aortic velocity-time integral, respiratory variability of inferior vena cava diameter, or pulse pressure variation. Measurements and Main Results: Respiratory variability of pulmonary velocity-time integral was assessed at baseline. Respiratory variability of pulmonary velocity-time integral was significantly greater in patients who received fluid therapy (26.9 ± 12.5% vs 6.2 ± 4.3%; p

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Evolution and Impact of Thrombocytopenia in Septic Shock: A Retrospective Cohort Study

Objectives: To characterize the prevalence, incidence, and temporal evolution of thrombocytopenia (platelets

http://bit.ly/2FLobi4

How and Whom to Monitor for Seizures in an ICU: A Systematic Review and Meta-Analysis

Objectives: To pool prevalence of nonconvulsive seizure, nonconvulsive status epilepticus, and epileptiform activity detected by different electroencephalography types in critically ills and to compare detection rates among them. Data Sources: MEDLINE (via PubMed) and SCOPUS (via Scopus) Study Selection: Any type of study was eligible if studies were done in adult critically ill, applied any type of electroencephalography, and reported seizure rates. Case reports and case series were excluded. Data Extraction: Data were extracted independently by two investigators. Separated pooling of prevalence of nonconvulsive seizure/nonconvulsive status epilepticus/epileptiform activity and odds ratio of detecting outcomes among different types of electroencephalography was performed using random-effect models. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and also adhered to the Meta-analyses Of Observational Studies in Epidemiology guidelines. Quality of evidence was assessed with the Newcastle-Ottawa Quality Assessment Scale for observational studies and Cochrane methods for randomized controlled trial studies. Data Synthesis: A total of 78 (16,707 patients) and eight studies (4,894 patients) were eligible for pooling prevalence and odds ratios. For patients with mixed cause of admission, the pooled prevalence of nonconvulsive seizure, nonconvulsive status epilepticus, either nonconvulsive seizure or nonconvulsive status epilepticus detected by routine electroencephalography was 3.1%, 6.2%, and 6.3%, respectively. The corresponding prevalence detected by continuous electroencephalography monitoring was 17.9%, 9.1%, and 15.6%, respectively. In addition, the corresponding prevalence was high in post convulsive status epilepticus (33.5%, 20.2%, and 32.9%), CNS infection (23.9%, 18.1%, and 23.9%), and post cardiac arrest (20.0%, 17.3%, and 22.6%). The pooled conditional log odds ratios of nonconvulsive seizure/nonconvulsive status epilepticus detected by continuous electroencephalography versus routine electroencephalography from studies with paired data 2.57 (95% CI, 1.11–5.96) and pooled odds ratios from studies with independent data was 1.57 (95% CI, 1.00–2.47). Conclusions: Prevalence of seizures detected by continuous electroencephalography was significantly higher than with routine electroencephalography. Prevalence was particularly high in post convulsive status epilepticus, CNS infection, and post cardiac arrest. Dr. Limotai had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs. Limotai and Thakkinstian contributed to drafting of the article and statistical analysis. Drs. Limotai, Ingsathit, and Thakkinstian contributed to study concept or design, administrative, technical, or material support. Drs. Ingsathit, McEvoy, Attia, and Thakkinstian contributed to study supervision. Drs. Limotai, Ingsathit, McEvoy, Attia, and Thakkinstian contributed to critical revision of the article for important intellectual content. All authors contributed to the acquisition, analysis, or interpretation of data. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://bit.ly/29S62lw). This article is an integral part of training for Dr. Limotai who is a PhD candidate in Clinical Epidemiology and Biostatistics in the Faculty of Medicine Ramathibodi Hospital and Faculty of Graduate Studies, Mahidol University, Bangkok, Thailand. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: atiporning@gmail.com; atiporn.ing@mahidol.ac.th; chusak.l@chula.ac.th Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Lipidomics Detection of Brain Cardiolipins in Plasma Is Associated With Outcome After Cardiac Arrest

Objectives: Brain mitochondrial dysfunction limits neurologic recovery after cardiac arrest. Brain polyunsaturated cardiolipins, mitochondria-unique and functionally essential phospholipids, have unprecedented diversification. Since brain cardiolipins are not present in plasma normally, we hypothesized their appearance would correlate with brain injury severity early after cardiac arrest and return of spontaneous circulation. Design: Observational case-control study. Setting: Two medical centers within one city. Participants (Subjects): We enrolled 41 adult cardiac arrest patients in whom blood could be obtained within 6 hours of resuscitation. Two subjects were excluded following outlier analysis. Ten healthy subjects were controls. Sprague-Dawley rats were used in asphyxial cardiac arrest studies. Interventions: None. Measurements and Main Results: We developed a high-resolution liquid chromatography/mass spectrometry method and determined cardiolipins speciation in human brain, heart, and plasma within 6 hours of (return of spontaneous circulation) from 39 patients with cardiac arrest, 5 with myocardial infarction, and 10 healthy controls. Cerebral score was derived from brain-specific cardiolipins identified in plasma of patients with varying neurologic injury and outcome. Using a rat model of cardiac arrest, cardiolipins were quantified in plasma, brain, and heart. Human brain exhibited a highly diverse cardiolipinome compared with heart that allowed the identification of brain-specific cardiolipins. Nine of 26 brain-specific cardiolipins were detected in plasma and correlated with brain injury. The cerebral score correlated with early neurologic injury and predicted discharge neurologic/functional outcome. Cardiolipin (70:5) emerged as a potential point-of-care marker predicting injury severity and outcome. In rat cardiac arrest, a significant reduction in hippocampal cardiolipins corresponded to their release from the brain into systemic circulation. Cerebral score was significantly increased in 10 minutes versus 5 minutes no-flow cardiac arrest and naïve controls. Conclusions: Brain-specific cardiolipins accumulate in plasma early after return of spontaneous circulation and proportional to neurologic injury representing a promising novel biomarker. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://bit.ly/29S62lw). Supported, in part, by the National Institutes of Health (NS084604, HL114453, U19AI068021, NS076511, NS061817, K08NS069817, HL133864, HL 128304, UL1 TR001857, and HL142130). Mr. Lamade and Drs. Kagan, Dezfulian, and Bayir received support for article research form the National Institutes of Health. Dr. Kagan disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: dezfulianc@upmc.edu; bayihx@ccm.upmc.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://bit.ly/2FMbzar

Evaluation of Medication Errors at the Transition of Care From an ICU to Non-ICU Location

Objectives: To determine the point prevalence of medication errors at the time of transition of care from an ICU to non-ICU location and assess error types and risk factors for medication errors during transition of care. Design: This was a multicenter, retrospective, 7-day point prevalence study. Setting: Fifty-eight ICUs within 34 institutions in the United States and two in the Netherlands. Patients: Nine-hundred eighty-five patients transferred from an ICU to non-ICU location. Interventions: None. Measurements and Main Results: Of 985 patients transferred, 450 (45.7%) had a medication error occur during transition of care. Among patients with a medication error, an average of 1.88 errors per patient (SD, 1.30; range, 1–9) occurred. The most common types of errors were continuation of medication with ICU-only indication (28.4%), untreated condition (19.4%), and pharmacotherapy without indication (11.9%). Seventy-five percent of errors reached the patient but did not cause harm. The occurrence of errors varied by type and size of institution and ICU. Renal replacement therapy during ICU stay and number of medications ordered following transfer were identified as factors associated with occurrence of error (odds ratio, 2.93; 95% CI, 1.42–6.05; odds ratio 1.08, 95% CI, 1.02–1.14, respectively). Orders for anti-infective (odds ratio, 1.66; 95% CI, 1.19–2.32), hematologic agents (1.75; 95% CI, 1.17–2.62), and IV fluids, electrolytes, or diuretics (odds ratio, 1.73; 95% CI, 1.21–2.48) at transition of care were associated with an increased odds of error. Factors associated with decreased odds of error included daily patient care rounds in the ICU (odds ratio, 0.15; 95% CI, 0.07–0.34) and orders discontinued and rewritten at the time of transfer from the ICU (odds ratio, 0.36; 95% CI, 0.17–0.73). Conclusions: Nearly half of patients experienced medication errors at the time of transition of care from an ICU to non-ICU location. Most errors reached the patient but did not cause harm. This study identified risk factors upon which risk mitigation strategies should be focused. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://bit.ly/29S62lw). Dr. Jarrell received funding from Intensive Care On-line Network (presenting education webinars) and Living Legacy Foundation (grant to conduct a pharmacokinetic study in solid organ transplant patients). The remaining authors have disclosed that they do not have any potential conflicts of interest. This work was performed at the Blount Memorial Hospital; Cape Coral Hospital; Chambersburg Hospital; Christiana Care Health System; ErasmusMC University Medical Center Rotterdam, Netherlands; Eskenazi Health; Florida Hospital Orlando; Florida Hospital East Orlando; Gulf Coast Medical Center; Health Park Medical Center; Johns Hopkins Bayview Medical Center; Loma Linda University Children's Hospital; Loma Linda University Medical Center; Lee Memorial Hospital; Mary Washington Hospital; Mayo Clinic Hospital—Rochester; Memorial Hermann-Texas Medical Center; Mercy Health St. Charles Hospital; Sharp Grossmont Hospital; Southwest General Health Center; St. Mary Medical Center; Stanford Health Care; The Hospital of Central Connecticut; The Johns Hopkins Hospital; University Hospitals Cleveland Medical Center; University Hospitals Geauga Medical Center; University Hospitals Parma Medical Center; University Hospitals St. John Medical Center; University Medical Center Groningen, Netherlands; University of Alabama at Birmingham Hospital; University of Arkansas for Medical Sciences; University of California San Diego Health; University of Kentucky HealthCare; University of Virginia Health System; Vanderbilt University Medical Center; and Wake Forest Baptist Medical Center. Address requests for reprints to: Rachel M. Kruer, PharmD, Department of Pharmacy, The Johns Hopkins Hospital, 600 North Wolfe Street—Carnegie Bldg Room 180, Baltimore, MD 21287. E-mail: rmbkruer@gmail.com; rkruer1@jhmi.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Towards Gender Equity in Critical Care Medicine: A Qualitative Study of Perceived Drivers, Implications, and Strategies

Objectives: Critical care medicine is a medical specialty where women remain underrepresented relative to men. The purpose of this study was to explore perceived drivers (i.e., influencing factors) and implications (i.e., associated consequences) of gender inequity in critical care medicine and determine strategies to attract and retain women. Design: Qualitative interview-based study. Setting: We recruited participants from the 13 Canadian Universities with adult critical care medicine training programs. Participants: We invited all faculty members (clinical and academic) and trainees to participate in a semistructured telephone interview and purposely aimed to recruit two faculty members (one woman and one man) and one trainee from each site. Interviews were transcribed verbatim, and two investigators conducted thematic analysis. Interventions: Not applicable. Measurements and Main Results: Three-hundred seventy-one faculty members (20% women, 80% men) and 105 trainees (28% women, 72% men) were invited to participate, 48 participants were required to achieve saturation. Participants unanimously described critical care medicine as a specialty practiced predominantly by men. Most women described experiences of being personally or professionally impacted by gender inequity in their group. Postulated drivers of the gender gap included institutional and interpersonal factors. Mentorship programs that span institutions, targeted policies to support family planning, and opportunities for modified role descriptions were common strategies suggested to attract and retain women. Conclusions: Participants identified a gender gap in critical care medicine and provided important insight into the impact for personal, professional, and group dynamics. Recommended improvement strategies are feasible, map broadly onto reported drivers and implications, and are applicable to critical care medicine and more broadly throughout medical specialties. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://bit.ly/29S62lw). Dr. Straus disclosed that she is funded by a Tier 1 Canada Research Chair. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: jeanna.parsonsleigh@uwo.ca Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Prinston Pharmaceutical Inc. Issues Voluntary Nationwide Recall of Irbesartan and Irbesartan HCTZ Tablets Due to Detection of a Trace Amount of Unexpected Impurity, N-Nitrosodiethylamine (NDEA) in the Products

Audience: Consumer, Health Professional, Pharmacy Prinston Pharmaceutical Inc., dba Solco Healthcare LLC., has initiated a voluntary recall of one (1) lot of Irbesartan and seven (7) lots of Irbesartan HCTZ Tablets to the consumer level due to the...

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Non-linear effects of cathodal transcranial direct current stimulation (tDCS) of the primary motor cortex on implicit motor learning

Abstract

Transcranial direct current stimulation (tDCS) of 1 mA for 13 min was reported to create a linear inter-dependency between the intensity and duration of the current and the effects of the stimulation. tDCS on the primary motor cortex (M1) has been shown to have an effect on both motor-evoked potential (MEP) and motor learning. However, recent findings have shown that the known linear effect is invalid in a 2 mA stimulation for 20 min, where cathodal stimulation led to excitability, rather than inhibition, as measured by MEP changes. Here we aim to replicate the non-linear effect of cathodal stimulation over the M1, using a cognitive task. Twenty-two healthy subjects participated in three sessions, where they were administered with a 2 mA anodal and cathodal stimulation for 20 min over the left M1, and a sham stimulation, while performing the serial reaction time task (SRTT). The overall analysis failed to show any effects of either polarity of tDCS on SRTT performance and hence did not replicate previous findings. However, given our goal to replicate the previously reported reversed polarity effects on MEP, we conducted an exploratory analysis to see whether there were any more subtle signs of a change in sign of the cathodal effect compared with anodal. Anodal stimulation led to faster performance than cathodal stimulation before 13 min of stimulation have passed, however, after 13 min, the pattern had switched, and performance under cathodal stimulation was faster. We conclude that cathodal tDCS has a non-linear effect, and the known polarity-dependent effects of tDCS shift after 13 min of stimulation, leading to an increased, rather than decreased, excitability.



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Oncocytic cyst of the larynx: a rare finding

A 75-year-old woman presented with an 18-month history of severe, slowly worsening dysphonia. She was a smoker and known to have multiple benign cystic thyroid lesions. She reported no associated symptoms and other medical and social history was unremarkable. Fibreoptic nasendoscopy revealed a right-sided supraglottic cyst appearing to arise from the right false vocal cord. Further bedside examination was unremarkable. She underwent microlaryngoscopy and biopsy which showed a cyst originating from the right anterior ventricle, successfully removed without rupture using cold steel. Formal histopathology revealed a 14x10x7 mm unilocular, completely excised cyst lined by oncocytic epithelium and composed of columnar cells with darkly stained nuclei and abundant granular, eosinophilic cytoplasm. Three weeks postoperatively the patient's voice had returned to normal. To date, 11 months postoperatively, there is no evidence of recurrence, and she will continue long-term follow-up.



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Inguinal hernia containing a native orthotopic kidney

We report a rare case of an inguinal hernia containing part of a native kidney and present a review of the literature with regard to urological findings in patients with inguinal hernias. This case involves an elderly man with known bilateral inguinal hernias with an incidental radiographic finding of a large right inguinal hernia containing the inferior pole of the right kidney. The patient was not symptomatic from the hernia and given his overall frailty, no surgical intervention was offered.



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Hypokalaemic metabolic alkalosis, hypertension and diabetes: what is the link

Two years after diagnosis of a metastatic neuroendocrine gastrin-secreting tumour and after several cycles of chemotherapy and peptide receptor radionuclide therapy, a 56-year-old woman presented with hypokalaemic metabolic alkalosis, hypertension, leg oedema and new-onset diabetes mellitus. Further investigations revealed renal potassium loss confirmed by a transtubular potassium gradient of 16, fully suppressed serum aldosterone, but instead highly elevated blood levels of morning cortisol and adrenocorticotropic hormone as well as increased urinary excretion of glucocorticoid and mineralocorticoid metabolites. Ruling out other causes, paraneoplastic hypercortisolism was diagnosed. Pharmacological inhibition of the steroid 11β-hydroxylase with metyrapone resulted in complete resolution of metabolic alkalosis, hypokalaemia, hypertension, hyperglycaemia and leg oedema within 1 week.



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Early diagnosis of cutaneous mastocytosis in an infant: the importance of a clinical sign



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Monocytopenia in clozapine-induced agranulocytosis: insights into pathophysiology and treatment

A 26-year-old man with history of schizophrenia was admitted for neutropaenia. He was started on clozapine 3 months prior to admission. As a result he had weekly monitoring of his blood counts and on day of admission was noted to have an absolute neutrophil count (ANC) of 450 cells/μL. He was admitted for clozapine-induced agranulocytosis. Clozapine was held and the patient was started on granulocyte colony-stimulating factor (G-CSF) filgrastim and received two doses without any signs of ANC recovery. On further review, it was noted that the absolute monocyte count (AMC) was also low and tracked with the trend of ANC. We then theorised that the impact of clozapine was on a haematopoietic precursor (colony-forming unit granulocyte-macrophage, CFU-GM) which gives rise to both monocytic and myeloid lineages. Therefore, sargramostim GM-CSF was started. After two doses, the ANC and AMC started trending up and by the third dose, both counts had fully recovered. He was discharged from the hospital and there are no plans to rechallenge with clozapine. Thus, we demonstrate a case of monocytopenia accompanying clozapine-induced agranulocytosis with successful use of GM-CSF. At least in this case, the target of the clozapine injury appears to be the CFU-GM, explaining the rapid and full response to GM-CSF after lack of response to G-CSF.



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Focal myositis and contracture secondary to amiodarone extravasation from a peripheral cannula

A 63-year-old man underwent cardioversion of atrial fibrillation with intravenous amiodarone through an antecubital fossa cannula. Mid-infusion, the cannula tissued. He developed immediate pain and swelling. At 3 weeks, he continued to have significant pain and had developed a fixed flexion deformity. MRI demonstrated focal myositis of the biceps and brachialis muscles. Treatment included physiotherapy and plastic surgery but sadly in spite of this, the patient has had minimal symptomatic improvement at 1 year. Amiodarone extravasation is well recognised to cause local injection site reactions. Involvement of deeper tissues is rare. To our knowledge, this is only the second description of a consequent focal myositis in the literature.



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Rare case of bladder chondroma causing lower urinary tract symptoms

An extraosseous or soft tissue chondroma is a rare, benign cartilaginous tumour characterised by the formation of mature hyaline cartilage. The majority of osseous chondromas are located within the medullary cavity of long bones. Soft tissue chondromas are extremely rare with only five cases affecting the bladder being reported in the literature. Soft tissue chondroma of the bladder is a rare cause of lower urinary tract symptoms and abdominopelvic pain. All reported cases of soft tissue chondromas of the bladder have occurred in women in their fifth to seventh decades of life. We describe the case of a 65-year-old woman diagnosed with a soft tissue chondroma of her bladder while being investigated for lower urinary tract symptoms.



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Urothelial carcinoma with villoglandular differentiation (UCVGD) with small cell neuroendocrine carcinoma of urinary bladder

Urothelial carcinoma with villoglandular differentiation (UCVGD) is a rare aggressive variant of urothelial carcinoma. It is usually associated with high-grade urothelial carcinoma or rarely adenocarcinoma. There is only one other previous report of UCVGD associated with small cell neuroendocrine carcinoma of urinary bladder. We report the second case of UCVGD with small cell neuroendocrine carcinoma of urinary bladder in a 74-year-old non-smoker male patient. The mass was muscle invasive and also invaded the prostate. This entity needs to be confidently diagnosed due to its prognostic and therapeutic implications.



http://bit.ly/2FA9mQh

Spontaneous anterior dislocation of lens in a case of ectopia lentis et pupillae: a rare entity treated by a novel technique of microscope integrated optical coherence tomography (MIOCT) guided intralenticular lens aspiration

A 7-year-old girl presented with watering and redness in the left eye for 2 months. Her parents reported poor vision in both eyes for 4 years. Visual acuity was finger counting at 1 m and finger counting close to face in the right and left eyes, respectively. Slit lamp examination of the right eye revealed corectopia, aphakia in the pupillary area, temporally subluxated clear crystalline lens, persistent pupillary membrane, irido-hyaloidal adhesion and poorly dilating pupil. Left eye revealed central corneal oedema with descemet scarring, anteriorly dislocated clear crystalline lens with lenticulo-corneal touch. Ultrasound examination of the left eye was normal. Hence a diagnosis of ectopia lentis et pupillae with left eye spontaneous anterior dislocation of the lens along with corneal decompensation was made. The child underwent microscope integrated intraoperative optical coherence tomography guided intralenticular lens aspiration with optical iridectomy in the left eye. Postoperative visual rehabilitation was done with aphakic glasses.



http://bit.ly/2FKEps3

Mandibular Contour Surgery Training System Beneficial

FRIDAY, Jan. 18, 2019 -- An intraoral mandibular contour surgery (MCS) training system is effective for improving clinical surgery time and accuracy, according to a study published online Jan. 17 in JAMA Facial Plastic Surgery. Jia Qiao, M.D., from...

http://bit.ly/2sBM4B4

Assessing Symptoms After 4 Weeks of Psychotherapy Helpful in Teens

FRIDAY, Jan. 18, 2019 -- Therapists implementing interpersonal psychotherapy for depressed adolescents (IPT-A) should routinely monitor depression symptoms and consider augmenting treatment for insufficient responders as early as week 4 of...

http://bit.ly/2Mh6Qii

Wait Times Have Improved in VA Health Care System

FRIDAY, Jan. 18, 2019 -- From 2014 to 2017, there were improvements in wait times in the Department of Veterans Affairs (VA) health care system, resulting in reduced wait times versus the private sector (PS) in 2017, according to a study published...

http://bit.ly/2szTTHB

Medication Treatment for Substance Abuse Up in Facilities

FRIDAY, Jan. 18, 2019 -- From 2007 to 2016, there was an increase in the proportion of substance use treatment facilities offering medication treatment (MT), according to a study published in the January issue of Health Affairs. Using data from...

http://bit.ly/2Mj1e7l

Mindfulness, Stress Linked to Menopausal Symptoms

FRIDAY, Jan. 18, 2019 -- Higher mindfulness and lower stress are independently associated with lower menopausal symptom scores among midlife women, according to a study published online Jan. 17 in Climacteric. Richa Sood, M.D., from the Mayo Clinic...

http://bit.ly/2sBM18m

MNK1/NODAL signaling promotes invasive progression of breast ductal carcinoma in situ

The mechanisms by which breast cancers progress from relatively indolent ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) are not well understood. However, this process is critical to the acquisition of metastatic potential. MAP kinase-interacting serine/threonine-protein kinase 1 (MNK1) signaling can promote cell invasion. NODAL, a morphogen essential for embryogenic patterning, is often re-expressed in breast cancer. Here we describe a MNK1/NODAL signaling axis that promotes DCIS progression to IDC. We generated MNK1 knockout (KO) or constitutively active MNK1 (caMNK1)-expressing human MCF-10A-derived DCIS cell lines, which were orthotopically injected into the mammary glands of mice. Loss of MNK1 repressed NODAL expression, inhibited DCIS to IDC conversion, and decreased tumor relapse and metastasis. Conversely, caMNK1 induced NODAL expression and promoted IDC. The MNK1/NODAL axis promoted cancer stem cell properties and invasion in vitro. The MNK1/2 inhibitor SEL201 blocked DCIS progression to invasive disease in vivo. In clinical samples, IDC and DCIS with microinvasion expressed higher levels of phospho-MNK1 and NODAL versus low grade (invasion-free) DCIS. Cumulatively, our data support further development of MNK1 inhibitors as therapeutics for preventing invasive disease.

http://bit.ly/2FAQjFp

Blockade of a laminin-411 - Notch axis with CRISPR/Cas9 or a nanobioconjugate inhibits glioblastoma growth through tumor-microenvironment crosstalk

There is an unmet need for the treatment of glioblastoma multiforme (GBM). The extracellular matrix (ECM), including laminins, in the tumor microenvironment is important for tumor invasion and progression. In a panel of 226 patient brain glioma samples, we found a clinical correlation between the expression of tumor vascular laminin-411 (α4β1γ1) with higher tumor grade and with expression of cancer stem cell (CSC) markers including Notch pathway members, CD133, Nestin, and c-Myc. Laminin-411 overexpression also correlated with higher recurrence rate and shorter survival of GBM patients. We also showed that depletion of laminin-411 α4 and β1 chains with CRISPR/Cas9 in human GBM cells led to reduced growth of resultant intracranial tumors in mice, and significantly increased survival of host animals compared to mice with untreated cells. Inhibition of laminin-411 suppressed Notch pathway in normal and malignant human brain cell types. A nanobioconjugate potentially suitable for clinical use and capable of crossing blood-brain barrier was designed to block laminin-411 expression. Nanobioconjugate treatment of mice carrying intracranial GBM significantly increased animal survival and inhibited multiple CSC markers including the Notch axis. This study describes an efficient strategy for GBM treatment via targeting a critical component of the tumor microenvironment largely independent of heterogeneous genetic mutations in glioblastoma.

http://bit.ly/2FKomKz

Mitochondrial miRNA determines chemoresistance by reprogramming metabolism and regulating mitochondrial transcription

MicroRNAs (miRNA) that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNAs (mitomiR). mitomiR have been shown to modulate the translational activity of the mitochondrial genome, yet their role in mitochondrial DNA(mtDNA) transcription remains to be determined. Here we report that the mitomiR-2392 regulates chemoresistance in tongue squamous cell carcinoma (TSCC) cells by reprogramming metabolism via downregulation of oxidative phosphorylation (OXPHOS) and upregulation of glycolysis. These effects were mediated through partial inhibition of mtDNA transcription by mitomiR-2392 rather than through translational regulation. This repression required specific miRNA-mtDNA base pairing and Argonaute 2 (AGO2). mitomiR-2392 recognized target sequences in the H-strand and partially inhibited polycistronic mtDNA transcription in a cell-specific manner. A retrospective analysis of TSCC patient tumors revealed a significant association of miR-2392 and regulated mitochondrial gene expression with chemosensitivity and overall survival. The clinical relevance of targeted mitochondrial genes was consistently validated by TCGA RNA sequencing in multiple types of cancer. Our study revealed for the first time the role of mitomiR in mtDNA transcription and its contribution to the molecular basis of tumor cell metabolism and chemoresistance.

http://bit.ly/2FCboiG

Dynamic Interactions Between the Genome and an Endogenous Retrovirus: Tirant in Drosophila simulans Wild-Type Strains

All genomes contain repeated sequences that are known as transposable elements (TEs). Among these are endogenous retroviruses (ERVs), which are sequences similar to retroviruses and are transmitted across generations from parent to progeny. These sequences are controlled in genomes through epigenetic mechanisms. At the center of the epigenetic control of TEs are small interfering RNAs of the piRNA class, which trigger heterochromatinization of TE sequences. The tirant ERV of Drosophila simulans displays intra-specific variability in copy numbers, insertion sites, and transcription levels, providing us with a well-suited model to study the dynamic relationship between a TE family and the host genome through epigenetic mechanisms. We show that tirant transcript amounts and piRNA amounts are positively correlated in ovaries in normal conditions, unlike what was previously described following divergent crosses. In addition, we describe tirant insertion polymorphism in the genomes of three D. simulans wild-type strains, which reveals a limited number of insertions that may be associated with gene transcript level changes through heterochromatin spreading and have phenotypic impacts. Taken together, our results participate in the understanding of the equilibrium between the host genome and its TEs.



http://bit.ly/2QZNrDe

Colon Cancer in Young Adults: Trends and Their Implications

Abstract

Purpose of Review

The recent rise of young individuals under age 50 with colorectal cancer (CRC) is a startling trend in need of greater focus and research. The etiology of young-onset CRC is unexplained as efforts to blame obesity or diabetes as causative factors are simplistic and inadequate.

Recent Findings

We describe the epidemiologic shifts of CRC incidence and mortality across age groups as well as the differences in clinicopathologic, molecular, treatment, and survival characteristics between young and older patients. Novel studies of the microbiome may elucidate bacterial causes of CRC carcinogenesis in younger individuals. Moving up the colonoscopy screening to age 45 in normal-risk individuals should prove beneficial in detecting more patients with early-onset CRC.

Summary

We favor the development of risk-adaptive screening decision algorithms and flexible sigmoidoscopy screening at age 40 given the predilection for left-sided primaries in this age group. More awareness and attention to young-onset CRC will be critical to improve outcomes in this patient population.



http://bit.ly/2W1EGwa

Indoleamine Dioxygenase Inhibitors: Clinical Rationale and Current Development

Abstract

Purpose of Review

This review focuses on the recent clinical development of indolamine-2,3-dioxygenase-1 (IDO-1) inhibitors.

Recent Findings

IDO-1 alters tryptophan metabolism in a manner enhancing T-regulatory cell activity, but pre-clinical data show that its role in tumorigenesis is context-dependent on host and tumor interaction, highlighting some challenges in understanding the molecular oncology of this enzymatic drug target. Because results from phase I/II trials of IDO-1 inhibitor monotherapy have been disappointing, current clinical trials employ IDO-1 inhibitors in combination strategies with other immunotherapy agents or with chemotherapy ± radiation. Combinations with anti-PD-1/PD-L1 antibodies are already showing promise, and related strategies are under active evaluation.

Summary

While further research is needed to elucidate the precise role of IDO-1 in tumor development, its mechanisms of action appear sufficiently distinct from other immunotherapy targets to warrant inclusion in combination immunotherapy regimens, an approach where multiple clinical trials are currently underway.



http://bit.ly/2QYzBkA

Effect of the JAK2/STAT3 signaling pathway on nerve cell apoptosis in rats with white matter injury

OBJECTIVE: The Janus activated kinase 2 (JAK2)/signal transducer and the activator of transcription 3 (STAT3) pathway are involved in many physiological processes, such as cell survival, inflammation, development, proliferation and differentiation. Increasing evidence has shown that this pathway also has neuron-specific functions in the central nervous system. In this study, the functional significance of the JAK2/STAT3 signaling pathway in nerve cell apoptosis in rats with white matter injury was evaluated.

MATERIALS AND METHODS: The rat model of white matter injury was established by ligating bilateral common carotid arteries, and the changes of the JAK2 and STAT3 phosphorylation in hippocampal neurons were evaluated using the immunohistochemistry. In addition, the effects of JAK2 inhibitor AG490 and STAT3 small interfering ribonucleic acids (siRNAs) on the expression of phosphorylated-JAK2 (pJAK2), STAT3 messenger RNAs (mRNAs) and pSTAT3 in hippocampal neurons of white matter injury rats were studied. The effects of both on cerebral infarction volume and neuron apoptosis in white matter injury rats were also investigated.

RESULTS: The expression of pJAK2 and pSTAT3 were significantly increased after white matter injury in rats (p<0.05). JAK2 inhibitor AG490 markedly decreased the phosphorylation of JAK2 and STAT3 in hippocampal neurons in the model group (p<0.05). STAT3 siRNAs remarkably reduced the expression levels of STAT3 mRNA and protein in hippocampus neurons in the model group (p<0.05), while having no effect on the expression level of pJAK2 protein. AG490 and STAT3 siRNAs notably attenuated the volume of cerebral infarction in the model group, as well as reduced neuron apoptosis after white matter injury.

CONCLUSIONS: The inhibition of the JAK2/STAT3 signaling pathway contributed to reducing the volume of cerebral infarction and neuron apoptosis in rats with white matter injury.

L'articolo Effect of the JAK2/STAT3 signaling pathway on nerve cell apoptosis in rats with white matter injury sembra essere il primo su European Review.



http://bit.ly/2DhYAM4

Correlations between the level of antibody against peptide of glutamate receptor NR3B subunit in the CSF and cognitive comorbidities of patients with epilepsy

OBJECTIVE: Autoimmune epilepsy is an under-recognized condition, and the mechanisms of antibody-mediated epileptogenesis are unknown. The N-methyl-D-aspartate (NMDA) receptor subunit 3 peptide B (NR3B) modulates Mg2+ sensitivity and Ca2+ mobilization of glutamate responses in the central nervous system (CNS). The levels of antibodies against NR3B (NR3B Ab's) in the cerebrospinal fluid (CSF) and the correlations between NR3B Ab's and cognitive comorbidities of epilepsy patients remain unclear.

PATIENTS AND METHODS: CSF samples were collected from 36 patients with consecutive epilepsy and 17 healthy controls. The levels of NR3B Ab's in the CSF were measured by ELISA. The cognitive function was assessed by Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE).

RESULTS: The results showed that the levels of NR3B Ab's were significantly higher in patients with epilepsy than those in the controls (p<0.01). Thirteen of 36 patients had higher levels of NR3B Ab's exceeding mean+ 2SD of all patients, and the scores of MMSE and MoCA of these 13 patients were significantly lower than the other 23 patients and controls (p<0.01; p<0.001). However, there were no significant differences in the scores of MMSE and MoCA between the 23 patients and the controls. Correlation analysis indicated a significant negative correlation between the levels of NR3B Ab's and the scores of MMSE (correlation coefficient: r=-0.543; p<0.01) or the scores of MoCA (correlation coefficient: r=-0.548; p<0.01).

CONCLUSIONS: We suggest that some patients with epilepsy may have immune process after onset and the presence of NR3B Ab's may be associated with cognitive comorbidities in patients with epilepsy.

L'articolo Correlations between the level of antibody against peptide of glutamate receptor NR3B subunit in the CSF and cognitive comorbidities of patients with epilepsy sembra essere il primo su European Review.



http://bit.ly/2TYA7RC

Effects of Medical Cannabis on Use of Opioids and Hospital Visits by Patients With Painful Chronic Pancreatitis



http://bit.ly/2RD4ZKy

Short Disease Duration Does Not Always Indicate Early Crohn’s Disease



http://bit.ly/2Cw0WFL

Increasing ESKD in Diabetes in the Land Down Under: What Can Be Done, We Must Wonder

Globally, kidney disease in diabetes is the leading cause of end-stage kidney disease (ESKD) and is associated with increased morbidity and mortality due to cardiovascular complications. Since 1990, national registries such as the US Renal Data System have provided data on the alarming increases in the number of people treated for ESKD due to diabetes.1 This has been partly due to the increasing number of individuals with type 1 and, in particular, type 2 diabetes. The number of people around the world with diabetes was estimated to be 415 million in 2015 and is expected to grow to more than 640 million people by 2040, according to the International Diabetes Federation.

http://bit.ly/2U6Monh

Minor Blunt Thoracic Trauma in the Emergency Department: Sensitivity and Specificity of Chest Ultralow-Dose Computed Tomography Compared With Conventional Radiography

To evaluate the diagnostic performance of chest ultralow-dose computed tomography (CT) compared with chest radiograph for minor blunt thoracic trauma.

http://bit.ly/2szHKCn

Imaging of Progressive Neuropathic Arthropathy of the Shoulder

imageNo abstract available

http://bit.ly/2RToOga

Evidence in Rehabilitation Medicine: Between Facts and Prejudices

imageThe relationship between evidence-based medicine and rehabilitation medicine is somewhat controversial. The motto "there is no evidence in rehabilitation medicine" is at times a real burden on the shoulders of rehabilitation medicine. There are many ideas around evidence in rehabilitation medicine; some are correct, whereas others are probably prejudices only. In this article, it is first discussed what evidence is, its origin and meaning, giving some notes about Cochrane—arguably, the criterion standard of evidence medicine. The relationship between rehabilitation medicine and evidence is then faced, to try to understand why these difficulties exist; it is considered what rehabilitation medicine is, comparing rehabilitation medicine with the other "classical" medical specialties; the problems with evidence generation and the actual state of research in rehabilitation medicine. The implementation of evidence in rehabilitation medicine is also introduced, including a brief discussion of knowledge translation, what it is, and why it is important, paying particular attention to Cochrane Rehabilitation—the new global rehabilitation medicine body that is facing these issues. Finally, some solutions for evidence in rehabilitation medicine are proposed.

http://bit.ly/2HlSnTv

Is Aerobic Exercise Training Beneficial for Adults With Fibromyalgia?: A Cochrane Review Summary with Commentary

No abstract available

http://bit.ly/2RUfit1

A Controlled Clinical Trial on the Effects of Exercise on Cognition and Mobility in Adults With Multiple Sclerosis

imageObjective The aim of the study was to investigate the effects of a 6-mo exercise program on cognition and mobility in participants with multiple sclerosis. Design This is a prospective, single-blind, controlled clinical trial. Setting A community rehabilitation program within a large metropolitan health service. Participants Twenty-eight patients with multiple sclerosis were referred for outpatient rehabilitation. Interventions Participants were allocated to one of two groups and undertook a cognitive-motor exercise program or monitoring (control group). Main Outcome Measures Cognition and mobility were the main outcome measures. Cognition was evaluated using the Mini-Mental State Examination and the Frontal Assessment Battery. Mobility was assessed with the Timed Get Up and Go test, applied with and without dual task distractors. Results The findings showed benefits provided by exercise on cognition and mobility. Differently, participants of the control group did not have significant changes in cognition scores after 6 mos of follow-up and had a worse performance in mobility tests. Conclusion Six months of exercise provided benefits to cognition and mobility in adults with multiple sclerosis. This trial was registered prospectively with the Brazilian Clinical Trials Register, ID: RBR-9gh4km (http://bit.ly/2HkNN86). To Claim CME Credits Complete the self-assessment activity and evaluation online at http://bit.ly/1l80W45 CME Objectives Upon completion of this article, the reader should be able to: (1) Recognize the physical and cognitive decline in multiple sclerosis; (2) Identify the importance of exercise on cognition and mobility in patients with multiple sclerosis; and (3) Appreciate the potential benefit of dual tasking in the rehabilitation of individuals with multiple sclerosis. Level: Advanced Accreditation The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

http://bit.ly/2HkNKZY

Integrated Rehabilitation for Breast Cancer Survivors

imageThe physical and psychological side effects of breast cancer therapies can have substantial impact on survivors' physical and social functioning. Roughly half of the more than 3 million Americans alive with a history of breast cancer report adverse, function-degrading sequelae related to their oncologic treatments. Care delivery models for the timely delivery of rehabilitation services have been proposed yet limitedly vetted or implemented. These include the prospective surveillance model, procedure-linked referrals, survivorship care plans, and risk stratification. Patients' capacity to engage in the rehabilitative process varies during cancer therapy and into survivorship. Perioperative attention generally focuses on managing premorbid impairments and normalizing shoulder function. In contrast, during chemotherapy and radiation therapy, symptom control, constructive coping, and role preservation may become more salient. Risk-stratified, individualized screening and prevention activities for specific impairments have become increasingly feasible through predictive models and analytics. Impairments' severity deleterious impact can be mitigated, as has been established for lymphedema, shoulder dysfunction, chemotherapy-induced peripheral neuropathy, cognitive dysfunction, fatigue, and sexual side effects. Integrated rehabilitative programs, often initiated after the completion of cancer treatment, are available in some countries outside of the United States and may offer survivors vital vocation- and avocation-directed services.

http://bit.ly/2RZssVG

Effect of Exercise on Risk Factors of Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis

imageThe objectives of this study were to examine the effectiveness of different types of exercise on risk factors of diabetic foot ulcers, including glycated hemoglobin, peripheral arterial disease, and diabetic peripheral neuropathy, in people with type 2 diabetes mellitus. PubMed, Web of Science, Cochrane Library, Scopus, and CINAHL were searched from inception to January 2018 for relevant articles. Eligible studies were randomized controlled trials that examined effects of exercise on the selected risk factors. Twenty randomized controlled trials with 1357 participants were included in the meta-analyses. The differences in postintervention values of glycated hemoglobin and ankle brachial index between exercise and control groups were synthesized, yielding mean differences of −0.45% (P

http://bit.ly/2HhMMNR

Comment on “Efficacy of Armeo Robotic Therapy Versus Conventional Therapy on Upper Limb Function in Children With Hemiplegic Cerebral Palsy”

No abstract available

http://bit.ly/2RQQDG1

Morphological Differences in the Upper Trapezius Muscle Between Female Office Workers With and Without Trapezius Myalgia: Facts or Fiction?: A Cross-Sectional Study

imageObjective Work-related trapezius myalgia is a common musculoskeletal disorder in office workers. Prolonged low-level muscle activity during office work may lead to morphological changes in the muscle tissue, causing pain and fatigue. The aim of the present study was to investigate differences in muscle morphology between office workers with and without trapezius myalgia. Design Muscle biopsy samples were obtained from the upper trapezius of female office workers with trapezius myalgia (n = 17) and healthy controls (n = 15). Myosin heavy chain immunohistochemistry and Gomori trichrome stainings were performed to identify differences in muscle fiber type proportion, Feret's diameter, and internal nuclear proportion. Results The myalgia group showed significantly more type IIA and IIA/IIX fibers and less type I and IIX fibers, compared with the control group (P 0.05). However, a significantly higher Feret's diameter was found for type I fibers, compared with type II fibers in both groups (P

http://bit.ly/2HlSkHj

Cochrane Corners to Enhance Access to Evidence-Based Physiatry

No abstract available

http://bit.ly/2RQQD8Z

Functional Outcome Scores With Standard Myoelectric Prostheses in Below-Elbow Amputees

imageObjective The aim of the study was to report normative outcome data of prosthetic hand function in below-elbow amputees using four different objective measurements closely related to activities of daily living. Design Seventeen patients who underwent prosthetic fitting after unilateral below-elbow amputation were enrolled in this study. Global upper extremity function was evaluated using the Action Research Arm Test, Southampton Hand Assessment Procedure, the Clothespin-Relocation Test, and the Box and Block Test, which monitor hand and extremity function. Results The patients achieved a mean ± SD Action Research Arm Test score of 35.06 ± 4.42 of 57. The mean ± SD Southampton Hand Assessment Procedure score was 65.12 ± 13.95 points. The mean ± SD time for the Clothespin-Relocation Test was 22.57 ± 7.50 secs, and the mean ± SD score in the Box and Block Test was 20.90 ± 5.74. Conclusions In the current economic situation of health care systems, demonstrating the effectiveness and necessity of rehabilitation interventions is of major importance. This study reports outcome data of below-elbow amputees and provides a useful guide for expected prosthetic user performance.

http://bit.ly/2HkNABQ

The Incidence of Physiatry-Relevant Complications in Trauma Patients Admitted to an Urban Canadian Trauma Center

imageThe objective of this study was to describe the incidence of complications in trauma patients that could be prevented, diagnosed, or managed by a consulting acute care physiatrist. Demographic and complication data were extracted by chart review of adult trauma patients admitted to a Canadian academic trauma center. Subjects were included if they had a diagnosis of traumatic brain injury, spinal cord injury, or multiple injuries resulting in an Injury Severity Score greater than 15. Means and standard deviations were calculated for continuous variables and frequencies for categorical data. Secondary analyses involved using Spearman's ρ and χ2 analysis to examine relationships between the development of complications and various patient factors. A total of 286 individuals were included. The overall incidence of a physical medicine & rehabilitation-relevant complication was 32.9%. The complications with the highest incidence were pneumonia (15.5%), delirium (14.1%), and urinary tract infection (13.4%). Secondary analyses demonstrated associations between the development of complications with older age, the presence of comorbidities, having both a traumatic brain injury and spinal cord injury, and length of stay. This study demonstrated that trauma patients may experience multiple complications that are of relevance to the consulting physiatrist.

http://bit.ly/2RZsi0w

Impact of Vascular Disease, Amputation Level, and the Mismatch Between Balance Ability and Balance Confidence in a Cross-Sectional Study of the Likelihood of Falls Among People With Limb Loss: Perception Versus Reality

imageObjective The aim of the study was to investigate the impact of balance ability, activities-specific balance confidence, and other self-reported and clinical factors on incidence of falls among people with lower limb loss. Design This is a cross-sectional study (N = 305) with multivariable logistic regression analysis. Results Participants included 68.3% men with an age of 55.5 ± 14.9, with 50% dysvascular and 56.8% transtibial amputations. The mean ± SD activities-specific balance confidence is 2.1/4 ± 1.1, balance ability is 2.9/4 ± 1.3, and walking speed is 0.766 ± 0.387 m/sec. The final model showed fall risk was heightened for people with vascular comorbidities (odds ratio = 3.46, 95% confidence interval = 1.40–8.54) and better balance (odds ratio = 23.29, confidence interval = 3.19–170.23), but attenuated for people with transfemoral (odds ratio = 0.08, confidence interval = 0.01–0.82) and vascular amputations (odds ratio = 0.38, confidence interval = 0.15–0.95). Significant interactions existed between age and amputation level (odds ratio = 1.06, confidence interval = 1.02–1.11) and between balance confidence and balance ability (odds ratio = 0.27, confidence interval = 0.13–0.57). Conclusions Although people with vascular amputations were less likely to fall than those with nonvascular amputations, people with concurrent vascular comorbidities were more likely to fall than those without. People with transfemoral amputations were less likely to fall; however, fall risk increased with each year of age compared with people with transtibial amputations. People with balance ability of 3.5 or greater fell more often than those with lower ability, but people with lower balance ability and mismatched confidence in their balance ability had 3.7 times greater fall risk.

http://bit.ly/2HkNxWG

When the Injury's Healing Process Meets the Needs of a Top-Level Volleyball Player: A Nonconventional Treatment of a Mallet Fracture Reinjury

imageManaging top-level athlete's recovery after an injury is very complicated because it requires a challenging combination of clinical and social/professional aspects with the need to return as soon as possible to sports play. Herein, we report a top-level volleyball player for whom a finger splint combined with a custom made thermoplastic protection was used for the conservative management of a Mallet fracture reinjury. This way our player continued training and competitions in contrast to conventional rehabilitation protocols, which suggest to avoid new traumas until the healing phase is completed. After 8 wks, we obtained the fracture healing and a complete functional recovery without major medical complications. From our results, we suggest that novel treatment strategies or modification of conventional rehabilitation protocols are worth consideration for the management of high-level sports players' injuries. However, new clinical studies with a larger sample can compare these results with those resulting from both surgical procedures and from immobilization and rest as well.

http://bit.ly/2RUfh8r

The Effect of Static Stretching of Peroneal and Tibialis Anterior Muscles on Reaction Time: A Randomized Controlled Study

imageObjective The aim of this study was to investigate the acute and chronic effects of static stretching on peroneal and tibialis anterior reaction characteristics. Design All 23 participants who volunteered for this study were randomly divided into static (n = 12) and control (n = 11) groups. The subjects in the static stretching group performed stretching exercises for the ankle evertor and dorsiflexor muscles 5 days a week for 6 wks. Peroneal and tibialis anterior muscle reaction characteristics were evaluated at the beginning (2 times for acute effect) and end of this period. Electromyographic activity parameters of the muscles were measured using an ankle inversion tilting platform that simulated a sudden ankle inversion. The following were the four different ankle inversion conditions: (a) ankle-neutral, 15-degree inversion; (b) ankle-neutral, 30-degree inversion; (c) ankle–20-degree plantarflexion, 15-degree inversion; and (d) ankle–20-degree plantarflexion, 30-degree inversion. Results Either in terms of acute or chronic effects, no significant differences were found after static stretching exercises for peroneal and tibialis anterior muscle reaction time, reaction duration, and muscle activity evaluated in four positions on the ankle inversion simulation platform (P > 0.05). Conclusions In light of these results, it is possible to state that the short duration of static stretching exercises can still be applied before sports activities.

http://bit.ly/2Hn5OTc

Predatory Open-Access Medical Publishers “Caveat Emptor”

No abstract available

http://bit.ly/2RZs5KM

Effects of Twitch Contraction Induced by Magnetic Stimulation on Expression of Skeletal Muscle Fibrosis Related Genes and Limited Range of Motion in Rats

imageObjective We examined the effects of twitch contraction induced by lumbar spinal root magnetic stimulation on immobilization-induced limited range of motion and skeletal muscle fibrosis in rat soleus muscle. Design The groups included male Wistar rats (controls), rats with both bilateral ankle joints immobilized with plaster casts for 4 wks (immobilization [IM]), and rats in which twitch contraction of the soleus muscle was induced by lumbar magnetic stimulation for 4 wks of immobilization (twitch contraction [TC]). Group differences in ankle dorsiflexion range of motion, collagen content as determined by hydroxyproline assay, and the expression of fibrosis-related genes as determined by reverse transcription-polymerase chain reaction (hypoxia inducible factor 1α, α-smooth muscle actin, and types I and III collagen) in the soleus muscle were examined after the 4-wk-long experiment. Results Range of motion in the TC group was significantly greater than that in the IM group. The hydroxyproline content and the expressions of fibrosis-related genes decreased significantly in the TC group compared with those in the IM group. No significant differences were seen in the expression of transforming growth factor β mRNA. Conclusions These results suggest that twitch contraction induced by lumbar spinal root magnetic stimulation may reduce immobilization-induced limited range of motion and skeletal muscle fibrosis.

http://bit.ly/2HiNP0f

Ultrasound Imaging for Dorsal Radiolunotriquetral Ligament Possibly Causing Wrist Impingement

imageNo abstract available

http://bit.ly/2RQqvuT

Erlotinib and bevacizumab combination therapy for afatinib-refractory leptomeningeal carcinomatosis from EGFR-mutated lung cancer

Abstract

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors remains the main hurdle in treating EGFR-mutated lung cancer. Besides, when leptomeningeal carcinomatosis occurs during treatment, it often leads to treatment failure. We herein report a case of lung adenocarcinoma involving a patient with an EGFR exon 19 deletion mutation who developed leptomeningeal carcinomatosis after afatinib treatment for post-operative recurrence. He received right lower lobectomy, followed by four cycles of cisplatin and pemetrexed treatment. Follow-up CT/MRI revealed multiple pulmonary metastases and brain metastases at 7 months after surgery, and afatinib (40 mg/day) was administered after stereotactic radiotherapy for brain metastasis. At 28 months after surgery, follow-up MRI revealed asymptomatic leptomeningeal carcinomatosis, which was cytologically proven from the cerebrospinal fluid. Because EGFR T790M was not detected in plasma cell-free DNA or cerebrospinal fluid, erlotinib and bevacizumab combination treatment was administered. He remained asymptomatic and was radiographically clear of LM at 2 months after treatment. In comparison to other EGFR-TKIs, erlotinib shows penetrance into the cerebrospinal fluid. Furthermore, the addition of bevacizumab might enhance the treatment effect, because it is known to relieve brain edema from metastatic brain tumors by normalizing immature vascularity and improving drug penetrance into the cerebrospinal fluid by reducing interstitial fluid pressure.



http://bit.ly/2HmujQk

Prognostic Nomogram for Disease-Specific Survival in Patients with Non-metastatic Ampullary Carcinoma After Surgery

Abstract

Objective

The aim of this study was to establish and validate an individualized nomogram for predicting disease-specific survival (DSS) in patients with non-metastatic ampullary carcinoma after surgery.

Methods

The nomogram was prepared using retrospective data from the Surveillance, Epidemiology, and End Results database, and included 2022 patients (training dataset: 1276; validation dataset: 746 patients) with non-metastatic ampullary carcinoma who were surgically treated between 2004 and 2014. Cox multivariate regression was performed to identify independent risk factors. The predictive accuracy was determined using the concordance index (C-index) and calibration curves. Results were validated internally using bootstrap resampling, and externally against the validation dataset.

Results

The median follow-up for the training dataset was 25.5 months (range 1–143), the median survival time was 52 months [95% confidence interval (CI) 41.67–62.33], and the postoperative 1-, 3-, and 5-year DSS rates were 86.7%, 57.3%, and 47.2%, respectively. Univariate and multivariate regression analysis demonstrated that age, grade, tumor size, lymph node ratio, extension range, and histology were independent risk factors for DSS. The C-index of the internal validation dataset for predicting DSS was 0.70 (95% CI 0.68–0.72), which was superior to that of the American Joint Committee on Cancer staging, i.e. 0.64 (95% CI 0.62–0.66; p < 0.001). The 5-year DSS and median DSS time for the low-risk group were significantly greater than those for the high-risk group (p < 0.001).

Conclusion

Our nomogram reliably and accurately predicted DSS in patients with non-metastatic ampullary carcinoma after surgery. This model may help clinicians in their decision making.



http://bit.ly/2szDK4X

Cell Fractionation of U937 Cells in the Absence of High-speed Centrifugation

59022fig1.jpg

Here, we present a protocol to isolate the plasma membrane, cytoplasm and mitochondria of U937 cells without the use of high-speed centrifugation. This technique can be used to purify subcellular fractions for subsequent examination of protein localization via immunoblotting.

http://bit.ly/2T1aPST

Issue Information



http://bit.ly/2W44ZSo

Repeatability of exercise‐induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle

New Findings

What is the central question of this study?

Are individual changes in exercise‐induced mRNA expression repeatable (i.e. representative of the true response to exercise rather than random error)?

What is the main finding and its importance?

Changes in mRNA expression are not repeatable even under identical experimental conditions.

The lack of repeatability is not explained by technical error arising from major gene analysis steps, highlighting sources of technical error and/or biological variability originating directly within the muscle.

Fibre‐type distribution is highly variable in two portions of the same muscle biopsy.

The substantial random error in exercise‐induced mRNA expression challenges its use as a biomarker of adaptive potential and/or individual responsiveness to exercise.

Abstract

It remains unknown if: 1) the observed change in mRNA expression reflects an individual's true response to exercise or random (technical and/or biological) error, and 2) the individual responsiveness to exercise is protocol‐specific. We examined the repeatability of skeletal muscle PGC‐1α, PDK4, NRF‐1, VEGF‐A, HSP72, and p53 mRNA expression following two identical endurance exercise (END) bouts (END‐1, END‐2; 30 minutes of cycling at 65% of peak work rate [WRpeak], = 11) and inter‐individual variability in PGC‐1α and PDK4 mRNA expression following END and sprint interval training (SIT; 8 × 20‐second cycling intervals at ∼170% WRpeak, = 10) in active young males. The repeatability of key gene analysis steps (RNA extraction, reverse transcription, qPCR) and within‐sample fibre‐type distribution (= 8) was also determined to examine potential sources of technical error in our analyses. Despite highly repeatable exercise bout characteristics (work rate, heart rate, blood lactate; ICCs > 0.71; CVs < 10%; > 0.85, < 0.01), gene analysis steps (ICCs > 0.73; CVs < 24%; > 0.75, < 0.01), and similar group‐level changes in mRNA expression, individual changes in PGC‐1α, PDK4, VEGF‐A, and p53 mRNA expression were not repeatable (ICCs < 0.22; CVs > 20%; < 0.21). Fibre‐type distribution in two portions of the same muscle biopsy was highly variable and not significantly related (ICC = 0.39; CV = 26%; = 0.37, = 0.37). Since individual changes in mRNA expression following identical exercise bouts were not repeatable, inferences regarding individual responsiveness to END or SIT were not made. Substantial random error exists in changes in mRNA expression following acute exercise, thereby challenging the use of mRNA expression for analyzing individual responsiveness to exercise.

This article is protected by copyright. All rights reserved



http://bit.ly/2syU6KP

Simultaneous Electrical and Mechanical Stimulation to Enhance Cells' Cardiomyogenic Potential

58934fig1.jpg

Here we present a protocol for training a cell population using electrical and mechanical stimuli emulating cardiac physiology. This electromechanical stimulation enhances the cardiomyogenic potential of the treated cells and is a promising strategy for further cell therapy, disease modeling, and drug screening.

http://bit.ly/2FyQKQJ

Quantification of Antibody-dependent Enhancement of the Zika Virus in Primary Human Cells

We describe a method to evaluate the effect of pre-existing immunity against dengue virus on the Zika virus infection by using human serum, primary human cells, and infection quantification by quantitative real-time polymerase chain reaction.

http://bit.ly/2FG65hH

FDA Investigating Paclitaxel-Coated Balloons, Paclitaxel-Eluting Stents

FRIDAY, Jan. 18, 2019 -- The U.S. Food and Drug Administration alerted health care providers on Thursday that the agency is investigating the use of paclitaxel-coated balloons and paclitaxel-eluting stents to treat peripheral arterial disease (PAD)...

http://bit.ly/2T112fB

Frailty Could Increase Susceptibility for Dementia

FRIDAY, Jan. 18, 2019 -- Frailty and Alzheimer disease-related brain changes independently contribute to dementia status, according to a study published in the February issue of The Lancet Neurology. Lindsay M.K. Wallace, from the Nova Scotia Health...

http://bit.ly/2ASZ7Tf

Oral Hepatoselective Glucokinase Activator Promising in T2DM

FRIDAY, Jan. 18, 2019 -- Use of the oral hepatoselective glucokinase activator (GKA) TTP399 for type 2 diabetes does not cause hypoglycemia and has no detrimental effect on plasma lipids or liver enzymes, according to a study published online Jan....

http://bit.ly/2T2Eif5

Trained Alert Dogs Can Detect Impending T1DM-Related Events

FRIDAY, Jan. 18, 2019 -- Trained alert dogs can help patients with type 1 diabetes regulate their blood glucose levels, according to a study published online Jan. 15 in PLOS ONE. Nicola J. Rooney, Ph.D., from the University of Bristol in the United...

http://bit.ly/2ASZ6Pb

FDA Panel Has Tie Vote on New Type 1 Diabetes Drug

FRIDAY, Jan. 18, 2019 -- A U.S. Food and Drug Administration advisory panel vote on whether to recommend approval of the first oral medication for type 1 diabetes ended in an 8-8 tie Thursday. Despite that result, the FDA is expected to decide by...

http://bit.ly/2T3STH2

Melanoma Survival Varies Among U.S. States

FRIDAY, Jan. 18, 2019 -- U.S. states with more physicians and a larger percentage of non-Hispanic whites have worse melanoma survival, according to a study published online Jan. 16 in the Journal of the American Academy of Dermatology. Zachary H....

http://bit.ly/2AVxCs9

Inappropriate Antibiotic Rx Common in Privately Insured

FRIDAY, Jan. 18, 2019 -- Less than half of all outpatient antibiotic prescription fills by privately insured nonelderly adults and children in the United States are appropriate or potentially appropriate, according to a study published online Jan....

http://bit.ly/2AOcrYP

Mandated Neonatal Abstinence Reporting Helps Quantify Cases

FRIDAY, Jan. 18, 2019 -- Mandated neonatal abstinence syndrome (NAS) surveillance and reporting allows state health departments to quantify incidence and informs programs and services, according to research published in the Jan. 11 issue of the U.S....

http://bit.ly/2T3SW5G

Variation in Revascularization for Asymptomatic SIHD Unexplained

FRIDAY, Jan. 18, 2019 -- For asymptomatic patients with stable ischemic heart disease (SIHD) and coronary artery disease (CAD), there is considerable variation in revascularization practice that is not explained by known factors, according to a...

http://bit.ly/2ASZ4qx

Radiographic Knee Osteoarthritis Tied to Increased Risk for Death

FRIDAY, Jan. 18, 2019 -- Radiographic knee osteoarthritis (RKOA) is associated with an increased risk for mortality from cardiovascular disease (CVD), diabetes, and renal diseases, but self-reported OA is not, according to a study published in the...

http://bit.ly/2T2u7qK

Access to routinely collected clinical data for research: A process implemented at an academic medical center

Abstract

Electronic health records are valuable for clinical and translational research. Institutions must protect patient privacy and comply with applicable regulations while allowing appropriate access to clinical data for research. The processes that investigators must follow to access clinical data can be substantially different at different institutions. In this paper, we describe the process developed at our institution that has been active for five years and was used to satisfy over 200 requests for access to identified clinical data, usually within one day for internal requests and three days for visiting researchers.

This article is protected by copyright. All rights reserved.



http://bit.ly/2CtAWLe

How to conduct clinical trials in children: a tutorial

Abstract

Despite a growing interest in, and commitment to, implementing pediatric clinical trials, approximately one in every five trials in children fails due to inappropriate study design, suboptimal experiment planning, or inadequate participant enrollment. This tutorial, presented from the perspectives of seasoned pediatric investigators, an experienced research coordinator, and an established pediatric clinical trials network, is designed to provide practical guidance for successfully implementing pediatric clinical trials at an academic center, or another comparable institution.

This article is protected by copyright. All rights reserved.



http://bit.ly/2RzROdj

Antibiotics-induced monodominance of a novel gut bacterial order

Objective

The composition of the healthy human adult gut microbiome is relatively stable over prolonged periods, and representatives of the most highly abundant and prevalent species have been cultured and described. However, microbial abundances can change on perturbations, such as antibiotics intake, enabling the identification and characterisation of otherwise low abundant species.

Design

Analysing gut microbial time-series data, we used shotgun metagenomics to create strain level taxonomic and functional profiles. Community dynamics were modelled postintervention with a focus on conditionally rare taxa and previously unknown bacteria.

Results

In response to a commonly prescribed cephalosporin (ceftriaxone), we observe a strong compositional shift in one subject, in which a previously unknown species, UBorkfalki ceftriaxensis, was identified, blooming to 92% relative abundance. The genome assembly reveals that this species (1) belongs to a so far undescribed order of Firmicutes, (2) is ubiquitously present at low abundances in at least one third of adults, (3) is opportunistically growing, being ecologically similar to typical probiotic species and (4) is stably associated to healthy hosts as determined by single nucleotide variation analysis. It was the first coloniser after the antibiotic intervention that led to a long-lasting microbial community shift and likely permanent loss of nine commensals.

Conclusion

The bloom of UB. ceftriaxensis and a subsequent one of Parabacteroides distasonis demonstrate the existence of monodominance community states in the gut. Our study points to an undiscovered wealth of low abundant but common taxa in the human gut and calls for more highly resolved longitudinal studies, in particular on ecosystem perturbations.



http://bit.ly/2Mho9zO

Unified interpretation of liver stiffness measurement by M and XL probes in non-alcoholic fatty liver disease

Objective

The latest model of vibration-controlled transient elastography (VCTE) automatically selects M or XL probe according to patients' body built. We aim to test the application of a unified interpretation of VCTE results with probes appropriate for the body mass index (BMI) and hypothesise that this approach is not affected by hepatic steatosis.

Design

We prospectively recruited 496 patients with non-alcoholic fatty liver disease who underwent VCTE by both M and XL probes within 1 week before liver biopsy.

Results

391 (78.8%) and 433 (87.3%) patients had reliable liver stiffness measurement (LSM) (10 successful acquisitions and IQR:median ratio ≤0.30) by M and XL probes, respectively (p<0.001). The area under the receiver operating characteristic curves was similar between the two probes (0.75–0.88 for F2–4, 0.83–0.91 for F4). When used in the same patient, LSM by XL probe was lower than that by M probe (mean difference 2.3 kPa). In contrast, patients with BMI ≥30 kg/m2 had higher LSM regardless of the probe used. When M and XL probes were used in patients with BMI <30 and ≥30 kg/m2, respectively, they yielded nearly identical median LSM at each fibrosis stage and similar diagnostic performance. Severe steatosis did not increase LSM or the rate of false-positive diagnosis by XL probe.

Conclusion

High BMI but not severe steatosis increases LSM. The same LSM cut-offs can be used without further adjustment for steatosis when M and XL probes are used according to the appropriate BMI.



http://bit.ly/2szqFbJ

Reduced efficacy of low FODMAPs diet in patients with IBS-D carrying sucrase-isomaltase (SI) hypomorphic variants

Recently in Gut and elsewhere,1–3 rare and common hypomorphic sucrase-isomaltase (SI) gene variants have been linked to an increased risk of IBS. Similar to congenital SI deficiency (a form of carbohydrate malabsorption caused by homozygous SI loss-of-function mutations),4 reduced SI enzymatic activity may trigger IBS symptoms via colonic accumulation of undigested disaccharides from starch and sucrose, resulting in fermentation with gas production and osmotic diarrhoea. This information holds potential for patients' stratification, and the identification of IBS subgroups better suited to benefit from specific dietary restrictions. For instance, diets low in short chain carbohydrates like the FODMAPs (fermentable oligo-, di-, mono-saccharides and polyols that are poorly absorbed in the small intestine) have been shown to be effective in reducing GI symptoms in some patients with IBS,5 6 though this has not been studied in relation to SI genotype and/or...



http://bit.ly/2MkBKX0

Experimental microdissection enables functional harmonisation of pancreatic cancer subtypes

Objective

Pancreatic ductal adenocarcinoma (PDA) has among the highest stromal fractions of any cancer and this has complicated attempts at expression-based molecular classification. The goal of this work is to profile purified samples of human PDA epithelium and stroma and examine their respective contributions to gene expression in bulk PDA samples.

Design

We used laser capture microdissection (LCM) and RNA sequencing to profile the expression of 60 matched pairs of human PDA malignant epithelium and stroma samples. We then used these data to train a computational model that allowed us to infer tissue composition and generate virtual compartment-specific expression profiles from bulk gene expression cohorts.

Results

Our analysis found significant variation in the tissue composition of pancreatic tumours from different public cohorts. Computational removal of stromal gene expression resulted in the reclassification of some tumours, reconciling functional differences between different cohorts. Furthermore, we established a novel classification signature from a total of 110 purified human PDA stroma samples, finding two groups that differ in the extracellular matrix-associated and immune-associated processes. Lastly, a systematic evaluation of cross-compartment subtypes spanning four patient cohorts indicated partial dependence between epithelial and stromal molecular subtypes.

Conclusion

Our findings add clarity to the nature and number of molecular subtypes in PDA, expand our understanding of global transcriptional programmes in the stroma and harmonise the results of molecular subtyping efforts across independent cohorts.



http://bit.ly/2sBVqNf

Macrophage and Fibroblast Interactions in Biomaterial‐Mediated Fibrosis

Advanced Healthcare Materials Macrophage and Fibroblast Interactions in Biomaterial‐Mediated Fibrosis

Macrophages and fibroblasts play major roles in biomaterial‐mediated and pathological fibrosis, but their distinct phenotypes and subsequent crosstalk remain loosely defined. This review discusses the role of macrophage phenotypes in fibrosis in vivo, in vitro models to study biomaterial‐mediated fibrosis, macrophage and fibroblast crosstalk in vitro, along with biomaterial strategies to modulate macrophage and fibroblast behavior for tissue regeneration.


Abstract

Biomaterial‐mediated inflammation and fibrosis remain a prominent challenge in designing materials to support tissue repair and regeneration. Despite the many biomaterial technologies that have been designed to evade or suppress inflammation (i.e., delivery of anti‐inflammatory drugs, hydrophobic coatings, etc.), many materials are still subject to a foreign body response, resulting in encapsulation of dense, scar‐like extracellular matrix. The primary cells involved in biomaterial‐mediated fibrosis are macrophages, which modulate inflammation, and fibroblasts, which primarily lay down new extracellular matrix. While macrophages and fibroblasts are implicated in driving biomaterial‐mediated fibrosis, the signaling pathways and spatiotemporal crosstalk between these cell types remain loosely defined. In this review, the role of M1 and M2 macrophages (and soluble cues) involved in the fibrous encapsulation of biomaterials in vivo is investigated, with additional focus on fibroblast and macrophage crosstalk in vitro along with in vitro models to study the foreign body response. Lastly, several strategies that have been used to specifically modulate macrophage and fibroblast behavior in vitro and in vivo to control biomaterial‐mediated fibrosis are highlighted.



http://bit.ly/2FAEizJ

Immunostimulatory Effects Triggered by Self‐Assembled Microspheres with Tandem Repeats of Polymerized RNA Strands

Advanced Healthcare Materials Immunostimulatory Effects Triggered by Self‐Assembled Microspheres with Tandem Repeats of Polymerized RNA Strands

Immunogenicity of self‐assembled RNA microspheres (RMSs) fabricated via rolling circle transcription is fully investigated depending on rationally designed structures composed of ssRNA or dsRNA. The RMSs are swallowed effectively by immune cells and cause negligible levels of proinflammatory cytokines, suggesting their immunocompatibility in the therapeutic range, while systemic control on release of RNA fragments shows a potential usage for immunomodulation.


Abstract

Self‐assembled RNA particles have been exploited widely to maximize the therapeutic potential of RNA. However, the immune response via RNA particles is not fully understood. In addition, the investigation of the immunogenicity from RNA‐based particles is required owing to inherent immunostimulatory effects of RNA for clinical translation. To examine the immune stimulating potency, rationally designed microsized RNA particles, called RNA microspheres (RMSs), are generated with single or double strands via rolling circle transcription. The RMSs show an exceptional stability in the presence of serum, while they are selectively degraded under endolysosomal conditions. With precisely controlled size, both RMSs are successfully taken up by macrophages. Unlike the nature of RNA fragments, RMSs induce only basal‐level expression of inflammatory cytokines as well as type I interferon from macrophages, suggesting that RMSs are immunocompatible in the therapeutic dose range. Taken together, this study could help accelerate clinical translation and broaden the applicability of the self‐assembled RNA‐based particles without being limited by their potential immunotoxicity, while a systematic controllability study observing the release of RNA fragments from RMSs would provide self‐assembled RNA‐based structures with a great potential for immunomodulation.



http://bit.ly/2FHt1go

Isolation of Glomeruli and In Vivo Labeling of Glomerular Cell Surface Proteins

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Here we present a protocol for murine in vivo labeling of glomerular cell surface proteins with biotin. This protocol contains information on how to perfuse mouse kidneys, isolate glomeruli, and perform endogenous immunoprecipitation of the protein of interest.

http://bit.ly/2T1Exal

Preparation of Acute Spinal Cord Slices for Whole-cell Patch-clamp Recording in Substantia Gelatinosa Neurons

Here, we describe the essential steps for whole-cell patch-clamp recordings made from substantia gelatinosa (SG) neurons in the in vitro spinal cord slice. This method allows the intrinsic membrane properties, synaptic transmission and morphological characterization of SG neurons to be studied.

http://bit.ly/2AUYb0D

Soluble CD93 is an apoptotic cell opsonin recognized by αxβ2

Efferocytosis is essential for homeostasis and prevention of the inflammatory and autoimmune diseases resulting from apoptotic cell lysis. CD93 is a transmembrane glycoprotein previously implicated in efferocytosis, with mutations in CD93 predisposing patients to efferocytosis‐associated diseases. CD93 is a cell surface protein which is proteolytically shed under inflammatory conditions, but it is unknown how CD93 mediates efferocytosis or whether its efferocytic activity is mediated by the soluble or membrane‐bound form. Herein, using cell lines and human monocytes and macrophages, we demonstrate that soluble CD93 potently opsonizes apoptotic cells but not a broad range of microorganisms, whereas membrane bound CD93 has no phagocytic, efferocytic, or tethering activity. Using mass spectrometry, we identified αxβ2 as the receptor which recognizes soluble CD93, and via deletion mutagenesis determined that soluble CD93 binds to apoptotic cells via its C‐Type Lectin‐Like domain and to αxβ2 by its EGF‐like repeats. The bridging of apoptotic cells to αxβ2 markedly enhanced efferocytosis by macrophages and was abrogated by αxβ2 knockdown. Combined, these data elucidate the mechanism by which CD93 regulates efferocytosis and identify a previously unreported opsonin‐receptor system utilized by phagocytes for the efferocytic clearance of apoptotic cells.

This article is protected by copyright. All rights reserved



http://bit.ly/2W4I3CS

New Research From Clinical Psychological Science

Reports of Recovered Memories of Abuse in Therapy in a Large Age-Representative U.S. National Sample: Therapy Type and Decade Comparisons
Lawrence Patihis and Mark H. Pendergrast

Open Data and Open Materials badges

To investigate the prevalence of memories of abuse being recovered in psychotherapy, Patihis and Pendergast surveyed patients about the duration and type of treatment they received, whether their therapists had discussed the possibility that they had repressed memories of abuse in childhood, and whether they had retrieved memories of being abused. Of 1,082 participants, 122 reported having recovered a memory of abuse. They were then asked how, where, and in what form they remember the abuse occurring, and whether they had cut off contact with family members. Twenty percent of the participants reported that their therapist had discussed the possibility of them repressing memories; this occurred in all types of therapies but mostly for those who started therapy in the 1990s. When the therapist had discussed the possibility of repressed memories, participants were 20 times more likely to report the recovery of such memories. The recovered memories most frequently reported involved emotional abuse, followed by physical abuse, and then sexual abuse, recalled as flashbacks both inside and outside of a therapy session. The recovered memory frequently resulted in cutting off contact with family members. The authors discuss the potential hazards of claimed memory recovery.

Reflections on Recovered Memories: Comment on Patihis and Pendergrast (2018)
Steven Jay Lynn, Harald Merckelbach, and Craig P. Polizzi

Patihis and Pendergrast showed that patients' recovered memories increased as therapists discussed with them the possibility of recovering memories. In this comment, Lynn and colleagues agree with Patihis and Pendergrast's skepticism about recovered memories and express concern about their accuracy and aftereffects. Moreover, Lynn et al. add that the assumption of a link between traumatic experiences and dissociative disorders is particularly problematic. They suggest that recovered memories could be studied and classified as a function of how the memories were recovered and interpreted, and that researchers could examine the procedures used by therapists who believe in repressed memories. Lynn and colleagues also recommend that therapists provide their clients with informed consent regarding the potential adverse effects of recovered memories and suggestive techniques.

Invasion of the Mind Snatchers: A Nation Full of Traumatic Memories
Elizabeth F. Loftus and Jennifer Teitcher

Commenting on Patihis and Pendergrast's survey suggesting that millions of people may have recovered memories of traumatic events because of psychotherapy, Loftus and Teitcher highlight the risks of recovering memories that are false and the potential risks of recovering real traumatic memories for patients who had spent most of their lives not thinking about those traumatic experiences. Patients that recover traumatic memories may become suicidal or engage in self-mutilation. The authors also believe that simply giving information about the potential hazards of recovered memories as part of informed consent may harm the patient. Therapists and researchers must consider how to ensure patients are actually better off after remembering traumatic events, even when they indeed happened.

The Recovered Memory Debate Continues in Europe: Evidence From the United Kingdom, the Netherlands, France, and Germany
Julia Shaw and Annelies Vredeveldt

The debate about the reliability of recovered traumatic memories and their effects is not unique to the United States. After Patihis and Pendergrast's American survey, Shaw and Vredeveldt analyzed how prevalent the idea of repressed and recovered memories still is in Europe. In the United Kingdom, charities support individuals who claim they have been falsely accused of a crime on the basis of a false memory recovery, usually during therapy. In the Netherlands, most cases involving memory recovery cannot be taken to court, but there are still many individuals who claim to have recovered traumatic memories in therapy. In countries where psychoanalysis is popular, such as France and Germany, the numbers of repressed and recovered memories reported during therapy are even higher. Despite the fact that the concept of recovered memories has been widely criticized by scientists, memory-recovery techniques are still prevalent in psychotherapy in parts of Europe.

False Memories and True Memories of Childhood Trauma: Balancing the Risks
Gail S. Goodman, Lauren Gonzalves, and Samara Wolpe

In this commentary, Goodman et al. weigh in on the debate about recovery of traumatic memories during therapy. They focus on cases in which the traumatic events actually occurred and thus the memories recovered are true, pointing out that it might be legitimate for therapists to ask about past traumatic experiences that otherwise patients would not remember. To support this idea, they discuss literature showing trauma avoidance and the need for prompts to remember forgotten childhood events. The authors do not dismiss the likelihood of falsely recovering memories. However, they consider the risks of clinicians not asking about childhood trauma to be greater than the risks of creating false memories.

Reports of Recovered Memories in Therapy, Informed Consent, and Generalizability: Response to Commentaries
Lawrence Patihis and Mark H. Pendergrast

Patihis and Pendergrast respond to a series of commentaries on their article on the rates of recovered memories during therapy. They further develop their idea of informing patients about the risks of recovering memories, considering the criticisms of Loftus and Teitcher, and the ideas of Lynn, Merckelbach, and Polizzi. They also address the impact that psychoanalysis might have had on the rise of techniques that involve memory recovery, which would explain why these techniques are more common in European countries where psychoanalysis is popular, as Shaw and Vredeveldt showed in their commentary. They also respond to Goodman et al.'s skepticism regarding the original article and their emphasis on the possible accuracy of recovered traumatic memories. The authors argue that addressing childhood trauma will be more effective when there are as few distortions as possible, and thus researchers and therapists should examine and expand research on problematic memory-recovery practices.



http://bit.ly/2FG6lgB