Diagnostic Accuracy of Chest Radiograph, and When Concomitantly Studied Lung Ultrasound, in Critically Ill Patients With Respiratory Symptoms: A Systematic Review and Meta-Analysis

Objectives: Chest radiograph is considered the first-line diagnostic imaging modality for patients presenting with pulmonary symptoms in the ICU. In this meta-analysis, we aim to evaluate the diagnostic accuracy of chest radiograph, and when concomitantly studied lung ultrasound, in comparison with the gold-standard CT for adult critically ill patients with respiratory symptoms. Data Sources: PubMed, EMBASE, and Gray literature. Study Selection: Studies comparing chest radiograph, and if performed lung ultrasound, with CT for adult ICU patients with respiratory symptoms. Data Extraction: Quality was scored with Quality Assessment of Diagnostic Accuracy Studies-2, and study setting, test characteristics, and study design were extracted. Data Synthesis: In the meta-analysis, we included 10 full-text studies, including 543 patients, and found that chest radiograph has an overall sensitivity of 49% (95% CI, 40–58%) and specificity of 92% (86–95%). In seven studies, where also lung ultrasound was studied, lung ultrasound had an overall sensitivity of 95% (92–96%) and specificity of 94% (90–97%). Substantial heterogeneity was found. A planned subgroup analysis for individual pathologies was performed. The results of four abstract-only studies, included in the systematic review, were considered unlikely to significantly influence results of our meta-analysis. Study limitations were that most studies were of low power combined with methodological limitations. Conclusions: This meta-analysis demonstrates that chest radiograph has a low sensitivity and reasonable specificity compared with CT for detecting lung pathology in critically ill patients. The studies also investigating lung ultrasound, showed lung ultrasound to be clearly superior to chest radiograph in terms of sensitivity with similar specificity, thereby opting to be the first-line diagnostic tool in these patients. All authors take responsibility for the integrity of the data interpretation and analysis. All authors contributed substantially in the study design, data interpretation, and the writing of the article. Dr. van de Ven performed statistical analysis and data syntheses. All authors approved the final version of the article. 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 (https://ift.tt/29S62lw). Supported, in part, by Departmental funds. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: p.tuinman@vumc.nl Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Revisited: A Systematic Review of Therapeutic Hypothermia for Adult Patients Following Traumatic Brain Injury

Objectives: Therapeutic hypothermia has been of topical interest for many years and with the publication of two international, multicenter randomized controlled trials, the evidence base now needs updating. The aim of this systematic review of randomized controlled trials is to assess the efficacy of therapeutic hypothermia in adult traumatic brain injury focusing on mortality, poor outcomes, and new pneumonia. Data Sources: The following databases were searched from January 1, 2011, to January 26, 2018: Cochrane Central Register of Controlled Trial, MEDLINE, PubMed, and EMBASE. Study Selection: Only foreign articles published in the English language were included. Only articles that were randomized controlled trials investigating adult traumatic brain injury sustained following an acute, closed head injury were included. Two authors independently assessed at each stage. Data Extraction: Quality was assessed using the Cochrane Collaboration's tool for assessing the risk of bias. All extracted data were combined using the Mantel-Haenszel estimator for pooled risk ratio with 95% CIs. p value of less than 0.05 was considered statistically significant. All statistical analyses were conducted using RevMan 5 (Cochrane Collaboration, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Data Synthesis: Twenty-two studies with 2,346 patients are included. Randomized controlled trials with a low risk of bias show significantly more mortality in the therapeutic hypothermia group (risk ratio, 1.37; 95% CI, 1.04–1.79; p = 0.02), whereas randomized controlled trials with a high risk of bias show the opposite with a higher mortality in the control group (risk ratio, 0.70; 95% CI, 0.60–0.82; p

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Increasing the Number of Medical Emergency Calls Does Not Improve Hospital Mortality

Objectives: Medical emergency teams were established to rescue patients experiencing clinical deterioration thus preventing cardiac arrest and unexpected hospital mortality. Although hospitals are encouraged to increase emergency calling rates to improve in-hospital mortality, there are increasing concerns about the impact these calls have on the workload of the teams and the skill levels on the general wards. We set out to examine the relationship between emergency calling rates and adjusted in-hospital mortality. Design: Retrospective analysis of prospectively collected patient and emergency call data. Setting: Tertiary, metropolitan, and regional hospitals in the State of Victoria, Australia. Patients: Consecutive patients discharged from 1) St Vincent's Hospital Melbourne from January 2008 to June 2016 and 2) 15 Victorian hospitals from July 2010 to June 2015. Measurements and Main Results: We studied 441,029 patients from St Vincent's Hospital Melbourne. Median age was 61.0 years (interquartile range, 45–74 yr), 57.2% were men, and 0.70% died; monthly emergency calling rates varied between 9.21 and 30.69 (median 18.4) per 1,000 discharges. In-hospital mortality adjusted for age, gender, emergency status, same day admission, year of discharge, and Charlson Comorbidity Index was not reduced by higher calling rates in the month of discharge (odds ratio, 1.019; 95% CI, 1.008–1.031). We then examined 3,339,789 discharges from 15 Victorian hospitals with median age 61 years (interquartile range, 43–74 yr), 51.4% men, and hospital mortality 0.83% where yearly emergency calling rates varied from 18.46 to 33.40 (median, 25.75) per 1,000 discharges. Again, adjusted mortality was not reduced by higher calling rates in the year of discharge (odds ratio, 1.003; 95% CI, 1.001–1.006). Conclusions: With adjustment for patient factors, illness, and comorbidities, increased emergency calling rates were not associated with reduced in-hospital mortality. Efforts to increase calling rates do not seem warranted. 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 (https://ift.tt/29S62lw). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: john.santamaria@svha.org.au Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Oral bisphosphonate use and lung cancer incidence among postmenopausal women

Abstract

Background

Bisphosphonates are common medications for the treatment of osteoporosis in older populations. Several studies, including the Women's Health Initiative (WHI), have found inverse associations of bisphosphonate use with risk of breast and endometrial cancer, but little is known about its association with other common malignancies. The objective of this study was to evaluate the association of bisphosphonate use on the incidence of lung cancer in the WHI.

Patients and methods

The association between oral bisphosphonate use and lung cancer risk was examined in 151,432 postmenopausal women enrolled into the WHI in 1993-1998. At baseline and during follow-up, participants completed an inventory of regularly used medications including bisphosphonates.

Results

After a mean follow-up of 13.3 years, 2,511 women were diagnosed with incident lung cancer. There was no evidence of a difference in lung cancer incidence between oral bisphosphonate users and never users (adjusted hazard ratio (HR), 0.91; 95% confidence intervals (CI), 0.80-1.04; P = 0.16). However, an inverse association was observed among those who were never smokers (HR = 0.57, 95% CI, 0.39-0.84; P < 0.01).

Conclusion

In this large prospective cohort of postmenopausal women, oral bisphosphonate use was associated with significantly lower lung cancer risk among never smokers, suggesting bisphosphonates may have a protective effect against lung cancer. Additional studies are needed to confirm our findings.

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Alma Ata y medicina de familia: 40 años de travesía del desierto

Amando Martín Zurro
Aten Primaria.2018;50:203-4

Texto completo - PDF

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Relación entre variables familiares y el ajuste conyugal

Nerea Jiménez-Picón, Joaquín-Salvador Lima-Rodríguez, Marta Lima-Serrano
Aten Primaria.2018;50:205-12

Resumen - Texto completo - PDF

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Insuficiencia cardiaca en atención primaria: actitudes, conocimientos y autocuidado

Cristina Salvadó-Hernández, Pilar Cosculluela-Torres, Carmen Blanes-Monllor, Neus Parellada-Esquius, Carmen Méndez-Galeano, Neus Maroto-Villanova, Rosa Maria García-Cerdán, M. Pilar Núñez-Manrique, Carmen Barrio-Ruiz, Betlem Salvador-González
Aten Primaria.2018;50:213-21

Resumen - Texto completo - PDF

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Hiperfrecuentación en Atención Primaria e hiperfrecuentadores en Urgencias

Cesáreo Fernández Alonso, Juan Mariano Aguilar Mulet, Rodolfo Romero Pareja, Arístides Rivas García, Manuel Enrique Fuentes Ferrer, Juan Jorge González Armengol
Aten Primaria.2018;50:222-7

Resumen - Texto completo - PDF

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Prevalencia en la realización de mamografías en España: análisis por comunidades 2006-2014 y factores que influyen

Juan Manuel Carmona-Torres, Ana Isabel Cobo-Cuenca, Noelia María Martín-Espinosa, Rosa María Piriz-Campos, José Alberto Laredo-Aguilera, María Aurora Rodríguez-Borrego
Aten Primaria.2018;50:228-37

Resumen - Texto completo - PDF

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Influencia de las condiciones de trabajo sobre la incapacidad temporal por contingencias comunes

Manuel Vaquero-Álvarez, Esther Álvarez-Theurer, Manuel Romero Saldaña
Aten Primaria.2018;50:238-46

Resumen - Texto completo - PDF

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Impulsando las directrices de la Ley de Calidad del SNS: modelos computacionales de guías de práctica clínica

Arturo González-Ferrer, María Ángel Valcárcel
Aten Primaria.2018;50:247-55

Resumen - Texto completo - PDF

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Influencia de la alfabetización en salud sobre la anticoagulación oral: un factor aún desconocido

Ana Cristina Cabellos-García, Enrique Castro-Sánchez, Antonio Martínez-Sabater, Vicente Antonio Gea-Caballero
Aten Primaria.2018;50:256-7

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Digoxina: ¿también descansa los fines de semana?

Ana Pareja-Obregón Prieto, Fernando Moreno Obregón, David León Jiménez, Ramón Pérez Temprano
Aten Primaria.2018;50:257-8

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Universidad y sanidad: luces y sombras en Montreal (Canadá)

Salvador Pertusa Martínez
Aten Primaria.2018;50:258-9

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O-3-21. Electrophysiological evaluation of peripheral neuropathy in hereditary spinocerebellar ataxia

Peripheral neuropathy often occurs in hereditary spinocerebellar ataxia (hSCA), but the features of nerve involvement have not been fully investigated. We evaluated the prevalence of peripheral neuropathy in hSCAs and classified the underlying pathologies into length-dependent axonopathy and neuronopathy based on sural/radial amplitude ratio (SRAR). SRAR has been reported as a sensitive indicator to differentiate the pathology of peripheral neuropathy. In this study, we defined SRAR less than 0.3 as length-dependent axonopathy, and SRAR more than 0.3 as neuronopathy.

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P3-3-1. Features of the correlation between the sites of EEG based on the difference in duration of epileptiform discharges

To investigate differences in the duration of epileptiform discharges, wavelet-crosscorrelation analysis was performed to identify correlations and time-lags between sites of the brain. Electroencephalography recordings were categorized into two time spans according to the duration of the epileptiform discharge: short run, 2–3 s; and long run, ⩾3 s. Both runs were subcategorized into before, during, and after epileptiform discharge groups. The EEG was divided into 2-s segments. In all patients, wavelet-crosscorrelation coefficients (WCC) and time-lag (LAG) at 6 Hz were calculated between all electrodes, and between all electrodes and the temporal region electrodes for each segment.

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SP-2. What dose TMS stimulate?

Transcranial magnetic stimulation (TMS) is a technique to stimulate the nervous system non-invasively through the intact scalp and skin. The TMS machine delivers a short pulse of electric current into a TMS coil to generate a quick changing magnetic field surrounding the coil as an example of Ampere's law. TMS stimulates the neuronal circuits with the eddy current induced by the changing magnetic field, not the magnetic field its self, based on Faraday's law. To generate enough power for stimulating human's brain, a TMS machine is generally built to generate a current of around 8000 A for a 2.5–4 Tesla output, although it may vary between machine types and manufacturers.

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Shimazono-Lecture-1. What I have done using TMS techniques

CMCT, CTX-BST CT, BST-Cv CT, CCCT, CECT: Using brainstem and conus medullaris stimulation in combination with the motor cortical and spinal nerve stimulation, we estimated conduction delays at several segments in CSTs.Cerebellar inhibition of the motor cortex (CBI): Purkinje cell activation by TMS induced a transient motor cortical inhibition. Mechanisms underlying ataxia was studied with this method.Shor interval intracortical inhibition (SICI): We showed the dependency of SICI on the motor cortical TMS pulse directions, which gave us a hint about the mechanisms of SICI.

https://ift.tt/2E6j0VI

P3-6-03. Visualization of nerve impulse traveling along the brachial plexus after ulnar nerve stimulation using 132ch SQUID magnetoneurography system

Using 132ch superconducting quantum interference device (SQUID) magnetoneurography sensor system, we succeeded in visualizing nerve impulse traveling along the brachial plexus (BP) after median nerve stimulation and propagating into the C5–C8 intervertebral foramen with participant's X-ray imaging. Here we analyzed the nerve impulse traveling along BP following ulnar nerve stimulation at the wrist.Magnetoneurogram following wrist stimulation were measured over BP from 5 healthy volunteers. Somatosensory evoked potential (SEP) was simultaneously measured at Erb's point for making sure to deliver supramaximal stimulation.

https://ift.tt/2GV1dnd

Shourei Prize 2. Utility of TMS for neuroscience of speech

Transcranial magnetic stimulation (TMS) has widely been accepted as a useful method of non-invasive brain stimulation in neuroscience. Compared with neuroimaging and intraoperative mapping, the number of speech experiments using TMS has, however, still been small. Here, an introduction to recent TMS studies that explored speech perception and imitation is presented. Single-pulse TMS of the primary motor cortex (M1) showed a speech specific and topographically specific increase of excitability in the M1 lip area during speech perception.

https://ift.tt/2uxoau7

P2-3-8. Change of cross frequency coupling by symptom provocation in Obsessive Compulsive Disorder (OCD) based on sLORETA

We investigated the changes in directional cross frequency interactions between theta and alpha oscillations, across six cortical regions, induced by a symptom provocation procedure, in patients with OCD, and in normal controls. Nine OCD outpatients and nine controls participated in this study. Eyes closed EEG was recorded before and under the instruction to imagine that the towel placed on their hands is contaminated (symptom provocation, SP). Cortical electric neuronal activity were calculated with sLORETA at medial-prefrontal, precuneus, inferior-parietal, and dorsolateral-prefrontal cortices.

https://ift.tt/2GWoSUB

A-19. Visual evoked potentials: Basic technology and clinical applications

Visual information is processed simultaneously via multiple parallel channels and each channel constitutes a set of sequential processes. The visual evoked potentials (VEPs) are the evoked electrophysiological potential that can be extracted, using signal averaging, from the electroencephalographic activity recorded at the scalp. VEPs can provide important diagnostic information regarding the functional integrity of the visual pathways and the visual cortex. Commonly used visual stimuli are flashing lights or pattern reversal (checkerboards or gratings) on the TV monitor or video screen.

https://ift.tt/2uxzKWq

S11-3. Three points to remember when you conduct research using event-related potentials

Event-related potentials (ERP) are a part of the electroencephalogram (EEG) that is time-locked to a certain event, such as stimulus presentation or movement onset. As recent advances in electronics bring inexpensive and easy-to-use EEG amplifiers to the market, more and more people are interested in also recording ERPs. However, easy-to-use does not mean easy-to-succeed. In this talk, I will make three practical recommendations for conducting ERP research. First, make sure that the timings of events are precisely registered with the EEG data.

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B-2. Clinical application of patterned DC stimulation

In addition to conventional surgical and pharmacological methods, electromagnetic interventions to the human brain have been developed for testing and treating neuropsychiatric disorders. Considering that the central principle of brain coding is based on neural firings and cell membrane potentials, that is electrical phenomena, electromagnetic intervention to the brain can be useful and effective for modulating brain functions.Among various electromagnetic methods, the most advanced one is the transcranial magnetic stimulation (TMS) which was put into practical use in 1985.

https://ift.tt/2uwrDJB

S14-2. F wave and spinal excitability; masseteric contraction or motor imagery enhances ulnar nerve F wave

We tested the validity of instructing patients to clench the teeth to facilitate F-waves recorded from a limb muscle in clinical practice. We explored to study effect of motor imagery and voluntary contraction of the masseter muscles on F waves recorded from the first dorsal interosseous muscle in healthy subjects. F waves were recorded at rest, during motor imagery and during voluntary contraction monitored by a force transducer to maintain the level at 10% of maximal effort. F-wave persistence increased from at rest to during motor imagery, and during voluntary contraction.

https://ift.tt/2GVzGSS

B-3. Electroencephalography and seizures learned from ictal recording

Experience on ictal video electroencephalography (EEG) recording enriches knowledge on EEG and seizures. Following five fundamentals are important for correct interpretation of EEG during focal epileptic seizures.Epileptic seizures never happen without EEG changes.Epileptic seizure propagates.EEG changes are not necessarily visible.EEG changes occur as a remote effect.EEG seizure explains clinical symptoms.Focal epileptic seizure starts with several patterns such as low voltage fast activity or repetitive spikes, followed by ictal rhythm that evolves spatially from focal to diffuse area, and temporally from low amplitude fast to high amplitude slow waves.

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P3-4-8. Utility of diaphragm ultrasound and phrenic nerve conduction in myopathy

Respiratory dysfunction in myopathy such as muscular dystrophy is extremely important because it is directly related to life prognosis, and appropriate evaluation and management is necessary. For objective assessment of respiratory muscle strength in myopathy, we study the usefulness of diaphragm ultrasonography and phrenic nerve study. Nineteen myopathy patients who were confirmed by genetic testing or muscle biopsy during our hospital visit were included. In both cases, respiratory function test, phrenic nerve conduction test, diaphragm ultrasonic examination were performed.

https://ift.tt/2GVHKD9

B-4. Neurophysiology of sleep in humans

Studies on EEG slowing in the progression of sleep since the discovery of electroencephalogram (EEG) in the 1920s, and identification of rapid eye movement (REM) sleep in the 1950s lead to the current principle that human sleep consists of REM and non-REM (NREM) sleep cycles. In this lecture, I will review sleep-wake homeostasis. Quantitative analysis of sleep EEG has revealed that delta EEG activity is enhanced according to the length of prior wakefulness, and achieved the recovery of the brain.

https://ift.tt/2E6vAnJ

P3-1-2. Assessment of the atypical cortico-cortical evoked potentials

Cortico-cortical evoked potential (CCEP) has been widely used to probe brain network.Typically CCEP waveform consists of two negative potentials, N1 (peak: 10–50 ms) and N2 (peak: 100–500 ms). We, however, occasionally encounter atypical responses, such as those with prolonged N1 peak latency. We attempt to classify these atypical patterns and clarify their anatomical distribution. We retrospectively reviewed CCEP responses in two patients with intractable focal epilepsy, in whom CCEPs were obtained bystimulating all the implanted subdural electrodes (IRB#443).

https://ift.tt/2GUFhbX

B-7. Electrodiagnostic criteria for ALD: Current state and perspectives

The diagnosis of amyotrophic lateral sclerosis (ALS) requires (1) evidence for extensive upper and lower motor neuron dysfunction, (2) progressive course, and (3) exclusion of other causes of motor neuronal loss. So far, a number of diagnostic criteria for ALS have been proposed, such as El Escorial (1990), revised El Escorial (1998), Awaji (2008), and updated Awaji (2015). According to the frequent revision/proposal criteria, electrodiagnostic criteria for ALS are somewhat confusing. In these criteria, the body motor system are divided into 4 regions; cranial, cervical, thoracic, and lumbosacral, and evidence for upper and lower motor neuron signs in the two or more regions are required for the diagnosis of "probable" ALS.

https://ift.tt/2uwwjiu

P1-5-02. Evaluation of facial muscle elasticity with real-time tissue elastography – Examination in cases with synkinesis following peripheral facial nerve paresis

The study was performed to clarify the relationship between facial muscle elasticity measured by real-time tissue elastography (RTE) and the clinical phenotypes of peripheral facial nerve paresis (PFP). We examined the orbicularis oculi muscles of nine PFP patients with synkinesis by RTE. The strain ratio (SR) of the muscle to an acoustic coupler was calculated as an index of muscle elasticity. We also recorded and integrated electromyograms of left and right orbicularis oculi muscles, respectively.

https://ift.tt/2GXOsbR

Cancers, Vol. 10, Pages 97: Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1 Mouse Breast Cancer: A Review

Cancers, Vol. 10, Pages 97: Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1 Mouse Breast Cancer: A Review

Cancers doi: 10.3390/cancers10040097

Authors: Stephen Beebe Brittany Lassiter Siqi Guo

Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD). With lower electric fields, like those peripheral to the primary treatment zone, NPS can activate dendritic cells (DCs). The activation of DCs by dead/dying cells leads to increases in memory effector and central memory T-lymphocytes in the blood and spleen. NPS also eliminates immunosuppressive cells in the tumor microenvironment and blood. Finally, NPS treatment of 4T1 breast cancer exhibits an abscopal effect and largely prevents spontaneous metastases to distant organs. NPS with fast rise–fall times and pulse durations near the plasma membrane charging time constant, which exhibits transient, high-frequency components (1/time = Hz), induce responses from mitochondria, endoplasmic reticulum, and nucleus. Such effects may be responsible for release of danger-associated molecular patterns, including ATP, calreticulin, and high mobility group box 1 (HMBG1) from 4T1-Luc cells to induce immunogenic cell death (ICD). This likely leads to immunity and the vaccine-like response. In this way, NPS acts as a unique onco-immunotherapy providing distinct therapeutic advantages showing possible clinical utility for breast cancers as well as for other malignancies.

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Small Cells, Big Problems

A 55-year-old man presented to his family doctor with a chronic cough and recurrent pneumonia. Chest X ray indicated an abnormality in the left upper lung zone. A subsequent computed tomography scan of the thorax demonstrated a left upper lobe mass measuring 4 × 7 cm with mediastinal adenopathy (Fig. 1A). Endobronchial ultrasound-guided biopsy showed small cell carcinoma. On pulmonary function testing, forced expiratory volume in 1 second was 83% of predicted, forced expiratory volume in 1 second/forced vital capacity was 0.75, and corrected diffusing capacity of the lungs for carbon monoxide was 86% of predicted.

https://ift.tt/2GI9zRB

In Regard to Churilla et al

To the Editor: I read with interest the scientific letter presenting a secondary analysis of North Central Treatment Group N0574 in the December 1, 2017, issue (1, 2). The authors should be commended for this important work on a common clinical problem. In the secondary analysis, they sought to determine whether whole-brain radiation therapy (WBRT) provides a benefit to non-small cell lung cancer patients with 1 to 3 brain metastases and favorable prognoses as defined by the Diagnosis-Specific Graded Prognostic Assessment (GPA) (2).

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A Small Window of Opportunity When Disease Is Limited in Extensive-Stage Small Cell Lung Cancer?

Prophylactic cranial irradiation (PCI) and consolidative chest radiation therapy (RT) improve survival in extensive-stage small cell lung cancer (SCLC) patients who have responded to standard platinum/etoposide-based chemotherapy. Because these RT-based additions represent the only advances in this disease over the last decade, the appropriateness of more-aggressive strategies that also preserve quality of life is of considerable interest.

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In Regard to Seibert et al

To the Editor: I would like to congratulate the team of Seibert et al (1) for their study. I would like to add some suggestions.

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Genomics Reloaded: Rise of the Expression Profiles

In this issue of Oncology Scan, similar to previous head and neck cancer Oncology Scans (1-7), we examine the use of genomic signatures to predict response to head and neck cancer therapy (8-10). In the past decade and a half, multiple teams have identified and developed gene expression profile signatures capable of subclassifying head and neck cancer, prognosticating outcome, and predicting treatment response. We discuss the implications of these genomic signatures for head and neck cancer patients, how these signatures can be applied to other therapies, their use to assist in preclinical studies, and suggestions on how this work can move the field forward, not just for head and neck cancer but potentially for all types of cancers.

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Select Patients With “Limited” Extensive-Stage Small Cell Lung Cancer Should Be Treated Aggressively

In this case, with an excellent response to chemotherapy, I recommend prophylactic cranial irradiation (PCI) to 25 Gy at 250 cGy per fraction. Supporting data include a decrease in brain metastases and improvement in survival with PCI for extensive-stage small cell lung cancer (1, 2).

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Not All Nails Need a Hammer

In this case of metastatic small cell lung cancer, we should be first reminded that this is a noncurable scenario (1). As nicely shown in the summary table contained in the Radiation Therapy Oncology Group (RTOG) 0937 publication, the best reported 5-year survival was less than 10% in the Jeremic study from 1999 (2, 3). In fact, neither RTOG 0937 nor the CREST trial was able to meet their primary endpoints (4). The CREST trial has a much ballyhooed 7% survival benefit at 2 years. Equally important, RTOG 0937 showed a doubling of grade 3 toxicity when adding thoracic radiation therapy to prophylactic cranial irradiation (PCI).

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In Reply to El Majjaoui et al

To the Editor: We thank the authors for their interest in our publication and appreciate the opportunity to respond to this commentary (1, 2).

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In Reply to Cihan

To the Editor: We welcome discussion on this important topic and thank Dr Cihan for her comments and useful further review of the literature on hippocampal damage. Moreover, we absolutely agree that radiation therapy is not the only cause of reduction in hippocampal volume. The purpose of our study (1, 2) was to determine whether radiation therapy in brain tumor patients was associated with hippocampal atrophy and whether there was, additionally, a dose-dependent effect. Indeed, we did find radiation dose–dependent atrophy in brain tumor patients.

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Issue Highlights

Gan and Kimple

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In Reply to Gultekin et al

To the Editor: The management options for recurrent pediatric central nervous system (CNS) malignancies include systemic therapy, surgical resection, radiation therapy, or a combination thereof. We reported our multi-institutional experience of the clinical outcomes of 67 pediatric patients treated who underwent reirradiation in the CNS (1, 2). Median overall survival from the end of reirradiation was 12.8 months in the entire cohort and 20.5 months and 8.4 months for patients with recurrent ependymoma and medulloblastoma, respectively.

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Meetings

May 2-4, 2018

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In Regard to Pasquier et al

To the Editor: Pasquier et al (1) analyzed a large data set in their retrospective Multicenter Rare Cancer Network Study, on management of small cell carcinoma of the bladder (SCCB).

https://ift.tt/2GEEEpj

National Cancer Institute Workshop on Proton Therapy for Children: Considerations Regarding Brainstem Injury

Proton therapy can allow for superior avoidance of normal tissues. A widespread consensus has been reached that proton therapy should be used for patients with curable pediatric brain tumor to avoid critical central nervous system structures. Brainstem necrosis is a potentially devastating, but rare, complication of radiation. Recent reports of brainstem necrosis after proton therapy have raised concerns over the potential biological differences among radiation modalities. We have summarized findings from the National Cancer Institute Workshop on Proton Therapy for Children convened in May 2016 to examine brainstem injury.

https://ift.tt/2IhU9Rj

Radiation-induced edema after single or multi-fraction stereotactic radiosurgery for meningioma: A critical review

Potential dosimetric and clinico-pathological predictors of radiation-induced brain edema after single- or multi-fraction stereotactic radiosurgery (SRS) for non-base of skull (non-BOS) meningiomas are summarized based upon a systematic review of the published literature.

https://ift.tt/2Gpnvwj

Risk of Radiation Vasculopathy and Stroke in Pediatric Patients Treated with Proton Therapy for Brain and Skull Base Tumors

Childhood cancer survivors are at risk of vasculopathy. This review of 651 children treated with proton therapy estimates the rate of serious vasculopathy is 2.6% at 3 years following treatment. Young age and doses ≥54 CGE to the suprasellar region are the dominant risk factors.

https://ift.tt/2GHBCR9

Phosphatidylinositol-3-kinase mutations are associated with increased local failure in brain metastases treated with radiation

We retrospectively reviewed 259 patients with brain metastases treated with whole brain radiation (WBRT) or stereotactic radiosurgery (SRS). Patients with PIK3 mutations were found to be at higher risk for LF following WBRT, while PIK3 mutations were not significantly associated with LF following SRS. Novel therapeutic strategies to improve outcomes in patients with PIK3 mutations undergoing WBRT should be considered.

https://ift.tt/2GmWxFH

Patients undergoing radiation therapy at risk for financial toxicity: A patient-based prospective survey study

Little is known about the financial burden experienced by patients receiving radiation therapy. Furthermore, there are currently no financial toxicity screening tools validated for use in radiation oncology.

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Accelerating drug development in pediatric cancer: a novel Phase I study design of venetoclax in relapsed/refractory malignancies

Future Oncology, Ahead of Print.


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Ensemble Docking in Drug Discovery

Ensemble docking corresponds to the generation of an "ensemble" of drug target conformations in computational structure-based drug discovery, often obtained by using molecular dynamics simulation, that is used in docking candidate ligands. This approach is now well established in the field of early-stage drug discovery. This review gives a historical account of the development of ensemble docking and discusses some pertinent methodological advances in conformational sampling.

https://ift.tt/2pUlAJ4

Transketolase regulates the metabolic switch to control breast cancer cell metastasis via the alpha-ketoglutarate signaling pathway

Although metabolic reprogramming is recognized as a hallmark of tumorigenesis and progression, little is known about metabolic enzymes and oncometabolites that regulate breast cancer metastasis, and very few metabolic molecules have been identified as potential therapeutic targets. In this study, the transketolase (TKT) expression correlated with tumor size in the 4T1/BALB/c syngeneic model. In addition, TKT expression was higher in lymph node metastases compared with primary tumor or normal tissues of patients, and high TKT levels were associated with poor survival. Depletion of TKT or addition of alpha-ketoglutarate (α-KG) enhanced the levels of tumor suppressors succinate dehydrogenase (SDH) and fumarate hydratase (FH), decreasing oncometabolites succinate and fumarate and further stabilizing HIF prolyl hydroxylase 2 (PHD2) and decreasing HIF-1α, ultimately suppressing breast cancer metastasis. Reduced TKT or addition of α-KG mediated a dynamic switch of glucose metabolism from glycolysis to oxidative phosphorylation. Various combinations of the TKT inhibitor oxythiamine, docetaxel, and doxorubicin enhanced cell death in triple-negative breast cancer (TNBC) cells. Furthermore, oxythiamine treatment led to increased levels of α-KG in TNBC cells. Together, our study has identified a novel TKT-mediated α-KG signaling pathway that regulates breast cancer oncogenesis and can be exploited as a modality for improving therapy.

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Hyperpolarized [1-13C]-pyruvate magnetic resonance spectroscopic imaging of prostate cancer in vivo predicts efficacy of targeting the Warburg effect

Purpose:  To evaluate the potential of hyperpolarized [1-¹³C]-pyruvate magnetic resonance spectroscopic imaging (MRSI) of prostate cancer as a predictive biomarker for targeting the Warburg effect. Experimental Design:  Two human prostate cancer cell lines (DU145 and PC3) were grown as xenografts.  The conversion of pyruvate to lactate in xenografts was measured with hyperpolarized [1-¹³C]-pyruvate MRSI after systemic delivery of [1-¹³C] pyruvic acid.  Steady state metabolomic analysis of xenograft tumors was performed with mass spectrometry and steady state lactate concentrations were measured with proton (¹H) MRS.  Perfusion and oxygenation of xenografts was measured with electron paramagnetic resonance (EPR) imaging with OX063. Tumor growth was assessed after lactate dehydrogenase (LDH) inhibition with FX-11 (42 µg/mouse/day for 5 days x 2 weekly cycles).  Lactate production, pyruvate uptake, extracellular acidification rates and oxygen consumption of the prostate cancer cell lines was analyzed in vitro.  LDH activity was assessed in tumor homogenates.Results: DU145 tumors demonstrated an enhanced conversion of pyruvate to lactate with hyperpolarized [1-¹³C]-pyruvate MRSI compared to PC3, and a corresponding greater sensitivity to LDH inhibition.  No difference was observed between PC3 and DU145 xenografts in steady state measures of pyruvate fermentation, oxygenation, or perfusion.  The two cell lines exhibited similar sensitivity to FX-11 in vitro.  LDH activity correlated to FX-11 sensitivity. Conclusions: Hyperpolarized [1-¹³C]-pyruvate MRSI of prostate cancer predicts efficacy of targeting the Warburg effect.

https://ift.tt/2IhBpkR

Clinical utility of cell-free DNA for the detection of ALK fusions and genomic mechanisms of ALK inhibitor resistance in non-small cell lung cancer

Purpose: Patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor anaplastic lymphoma kinase ALK gene fusions benefit from treatment with ALK inhibitors (ALKi). Analysis of cell-free circulating tumor DNA (cfDNA) may provide a non-invasive way to identify ALK fusions and actionable resistance mechanisms without biopsy. Experimental Design: The Guardant360 (G360) de-identified database of NSCLC cases was queried to identify 88 consecutive patients with 96 plasma-detected ALK fusions. G360 is a clinical cfDNA next-generation sequencing (NGS) test that detects point mutations, select copy number gains, fusions, insertions, and deletions in plasma. Results: Identified fusion partners included EML4 (85.4%), STRN (6%), and KCNQ,KLC1, KIF5B, PPM1B, and TGF (totaling 8.3%). Forty-two ALK positive patients had no history of targeted therapy (cohort 1) with tissue ALK molecular testing attempted in 21 (5 negative, 5 positive, 11 tissue insufficient). Follow-up of 3 of the 5 tissue negative patients showed responses to ALKi. Thirty-one patients were tested at known or presumed ALKi progression (cohort 2); 16 samples (53%) contained 1 - 3 ALK resistance mutations. In 13 patients, clinical status was unknown (cohort 3), and no resistance mutations or bypass pathways were identified. In 6 patients with known EGFR activating mutations, an ALK fusion was identified on progression (cohort 4) (4 STRN, 1 EML4; one both STRN and EML4), five harbored EGFR T790M. Conclusions: In this cohort of cfDNA detected ALK fusions, we demonstrate that comprehensive cfDNA NGS provides a non-invasive means of detecting targetable alterations, and characterizing resistance mechanisms on progression.

https://ift.tt/2pPBYM1

Functional precision medicine identifies novel druggable targets and therapeutic options in head and neck cancer

Purpose: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with high mortality and a lack of targeted therapies. To identify and prioritize druggable targets, we performed genome analysis together with genome-scale siRNA and oncology drug profiling using low passage tumor cells derived from a patient with a treatmentresistant HPV-negative HNSCC. Experimental design: A tumor cell culture was established and subjected to whole exome sequencing, RNA sequencing, comparative genome hybridization, and high-throughput phenotyping with siRNA library covering the druggable genome and an oncology drug library. Secondary screens of candidate target genes were performed on the primary tumor cells and two non-tumorigenic keratinocyte cell cultures for validation and to assess cancer-specificity. siRNA screens of the kinome on two isogenic pairs of p53-mutated HNSCC cell lines were used to determine generalizability. Clinical utility was addressed by performing drug screens on two additional HNSCC cell cultures derived from patients enrolled in a clinical trial. Results: Many of the identified copy number aberrations and somatic mutations in the primary tumor were typical of HPV(-) HNSCC, but none pointed to obvious therapeutic choices. In contrast, siRNA profiling identified 391 candidate target genes, 35 of which were preferentially lethal to cancer cells, most of which were not genomically altered. Chemotherapies and targeted agents with strong tumor specific activities corroborated the siRNA profiling results and included drugs that targeted the mitotic spindle, the proteasome and G2/M kinases WEE1 and CHK1. We also show the feasibility of ex-vivo drug profiling for patients enrolled in a clinical trial. Conclusions: High-throughput phenotyping with siRNA and drug libraries using patient derived tumor cells prioritizes mutated driver genes and identifies novel drug targets not revealed by genomic profiling. Functional profiling is a promising adjunct to DNA sequencing for precision oncology.

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Combinatorial effects of VEGFR kinase inhibitor axitinib and oncolytic virotherapy in mouse and human glioblastoma stem-like cell models

Purpose: Glioblastoma (GBM), a fatal brain cancer, contains a subpopulation of GBM stem-like cells (GSCs) that contribute to resistance to current therapy. Angiogenesis also plays a key role in GBM progression. Therefore, we developed a strategy to target the complex GBM microenvironment, including GSCs and tumor vasculature. Experimental design: We evaluated the cytotoxic effects of VEFGR tyrosine kinase inhibitor (TKI) axitinib in vitro and then tested anti-tumor efficacy of axitinib in combination with oncolytic herpes simplex virus (oHSV) expressing anti-angiogenic cytokine murine IL12 (G47-mIL12) in two orthotopic GSC-derived GBM models: patientderived recurrent MGG123 GSCs, forming vascular xenografts in immune-deficient mice, and mouse 005 GSCs, forming syngeneic tumors in immune-competent mice. Results: GSCs form endothelial-like tubes and were sensitive to axitinib. G47-mIL12 significantly improved survival, as did axitinib, while dual combinations further extended survival significantly compared to single therapies alone in both models. In MGG123 tumors, axitinib was effective only at high doses (50 mg/kg), alone and in combination with G47-mIL12, and this was associated with greatly decreased vascularity, increased macrophage infiltration, extensive tumor necrosis and PDGFR/ERK pathway inhibition. In the mouse 005 model, anti-glioma activity, after single and combination therapy, was only observed in immune-competent mice and not T cell-deficient athymic mice. Interestingly, immune checkpoint inhibition did not improve efficacy. Conclusions: Systemic TKI (axitinib) beneficially combines with G47-mIL12 to enhance anti-tumor efficacy in both immune-deficient and immune-competent orthotopic Saha et al 4 GBM models. Our results support further investigation of TKIs in combination with oHSV for GBM treatment.

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CD103+ tumor-resident CD8+ T cells are associated with improved survival in immunotherapy naive melanoma patients and expand significantly during anti-PD1 treatment.

Purpose: Therapeutic blockade of immune checkpoints has revolutionized cancer treatment. Durable responses however, occur in less than half of those treated and efforts to improve treatment efficacy are confounded by a lack of understanding of the characteristics of the cells that initiate anti-tumor immune response. Experimental Design: We performed multi-parameter flow cytometry and quantitative multiplex immunofluorescence staining on tumor specimens from immunotherapy-naïve melanoma patients and longitudinal biopsy specimen obtained from patients undergoing anti-PD-1 therapy. Results: Increased numbers of CD69+CD103+ tumor-resident CD8+ T cells was associated with improved melanoma-specific survival in immunotherapy-naive melanoma patients. Local IL-15 expression levels strongly correlated with these tumor-resident T cell numbers. The expression of several immune checkpoints including PD-1 and LAG3 was highly enriched in this subset and these cells significantly expanded early during anti-PD-1 immunotherapy. Conclusions: Tumor-resident CD8+ T cell numbers are more prognostic than total CD8+ T cells in metastatic melanoma. In addition, they are likely to initiate response to anti-PD-1 and anti-LAG-3 treatments. We propose that the immune profile of these cells prior to treatment could inform strategies for immune checkpoint blockade.

https://ift.tt/2GpOO9N

Toward universal influenza virus vaccines: from natural infection to vaccination strategy

Chen Zhao | Jianqing Xu

https://ift.tt/2GXlXLp

H3K4 Methylation Dependent and Independent Chromatin Regulation by JHD2 and SET1 in Budding Yeast

Set1 and Jhd2 regulate the methylation state of histone H3 lysine-4 (H3K4me) through their opposing methyltransferase and demethylase activities in the budding yeast Saccharomyces cerevisiae. H3K4me associates with actively transcribed genes and, like both SET1 and JHD2 themselves, is known to regulate gene expression diversely. It remains unclear, however, if Set1 and Jhd2 act solely through H3K4me. Relevantly, Set1 methylates lysine residues in the kinetochore protein Dam1 while genetic studies of the S. pombe SET1 ortholog suggest the existence of non-H3K4 Set1 targets relevant to gene regulation. We interrogated genetic interactions of JHD2 and SET1 with essential genes involved in varied aspects of the transcription cycle. Our findings implicate JHD2 in genetic inhibition of the histone chaperone complexes Spt16-Pob3 (FACT) and Spt6-Spn1. This targeted screen also revealed that JHD2 inhibits the Nrd1-Nab3-Sen1 (NNS) transcription termination complex. We find that while Jhd2's impact on these transcription regulatory complexes likely acts via H3K4me, Set1 governs the roles of FACT and NNS through opposing H3K4-dependent and -independent functions. We also identify diametrically opposing consequences for mutation of H3K4 to alanine or arginine, illuminating that caution must be taken in interpreting histone mutation studies. Unlike FACT and NNS, detailed genetic studies suggest an H3K4me-centric mode of Spt6-Spn1 regulation by JHD2 and SET1. Chromatin immunoprecipitation and transcript quantification experiments show that Jhd2 opposes the positioning of a Spt6-deposited nucleosome near the transcription start site of SER3, a Spt6-Spn1 regulated gene, leading to hyper-induction of SER3. In addition to confirming and extending an emerging role for Jhd2 in the control of nucleosome occupancy near transcription start sites, our findings suggest some of the chromatin regulatory functions of Set1 are independent of H3K4 methylation.

https://ift.tt/2uwZVMT

Pharmacists Have Responsibility to Check Opioid Rx Are Legitimate

THURSDAY, March 29, 2018 -- Pharmacists should be aware that they are expected to take steps to make sure opioid prescriptions are written for legitimate medical purposes, and should document these efforts, according to a report published in Drug...

https://ift.tt/2E4D0bl

Scale of Online Marketplace for Marijuana Increasing

THURSDAY, March 29, 2018 -- The scale of the online marketplace for marijuana increased from 2005 to 2017, according to a study published online March 22 in the American Journal of Preventive Medicine. Theodore L. Caputi, from the University College...

https://ift.tt/2Gm3ATi

Nurse Education Improves Post-Op Survival in Dementia Patients

THURSDAY, March 29, 2018 -- Having more nurses in the hospital with at least a bachelor of science degree in nursing (BSN) is tied to lower post-surgical mortality among patients with Alzheimer's disease and related dementias (ADRD), according to a...

https://ift.tt/2uC6BJG

Non-Invasive Test Can Detect Urothelial Cancer

THURSDAY, March 29, 2018 -- UroSEEK, which uses DNA recovered from cells shed into urine, can detect urothelial cancer, according to a study published online March 20 in eLife. Simeon U. Springer, from the Ludwig Center for Cancer Genetics and...

https://ift.tt/2GjkTUS

Change in BMI During Puberty Tied to Later Heart Failure Risk

THURSDAY, March 29, 2018 -- Change in body mass index (BMI) to overweight during puberty significantly increases men's risk of heart failure later in life, according to a study published online March 12 in the Journal of Internal Medicine. Jenny M....

https://ift.tt/2uwa8ZM

Efficacy of EUS- and ERCP-guided biliary drainage for malignant biliary obstruction: prospective randomized controlled study

ERCP-guided biliary drainage (ERCP-BD is a criterion standard treatment for malignant biliary obstruction when curative surgery is not an option. Alternative methods such as PTBD would significantly lower the quality of life. EUS-guided biliary drainage (EUS-BD) has been developed and performed by experienced endoscopists. Therefore, the aims of this study were to evaluate the efficacy and safety of EUS-BD compared with ERCP in malignant biliary obstruction.

https://ift.tt/2uBFjTs

Stability Analysis of CT Radiomics Features With Respect to the Variation of Manual Segmentation in Oropharyngeal Cancer

Accurate segmentation of tumors and quantification of tumor features are important for cancer detection, diagnosis, monitoring, and planning therapeutic intervention. Due to inherent noise components in multiparametric imaging and inter-observer variations, it is common that various segmentation methods, including both manual segmentation and computer-aided segmentation methods, may produce large segmentation errors in tumor volumes and their associated radiomics features. Such errors may eventually lead to large prediction errors.

https://ift.tt/2GSQ5Y1

Discrimination of Epstein-Barr Virus Status in NPC Using CT-Derived Radiomics Features: Linking Imaging Phenotypes to Tumor Biology

This study aims at employing computed tomography (CT)–based radiomics analysis within the primary tumor among NPC patients for the selection of candidate features, which can be correlated to EBV status.

https://ift.tt/2E4kXC7

Advanced dynamic statistical parametric mapping with MEG in localizing epileptogenicity of the bottom of sulcus dysplasia

Focal cortical dysplasia at bottom of sulcus (FCDB) is defined as a focal cortical dyplasia (FCD) type II located at the bottom of a sulcus. FCDB is intrinsically epileptogenic and provokes early onset focal seizures, with a high frequency of seizures during active periods, and occasionally with hospitalization for severe exacerbation (Harvey et al., 2015). Complete resection of FCDB, however, results in seizure freedom in up to 90% of selected cases (Chassoux et al., 2010).

https://ift.tt/2pPzKME

The role of EEG localized activation and central nervous system arousal in executive function performance in children with Attention-Deficit/Hyperactivity Disorder

Resting-state electroencephalogram (RS-EEG) provides a window to understand spontaneous brain activity in children with Attention-Deficit/Hyperactivity Disorder (AD/HD) (Barry et al., 2003). Its measures (e.g. the theta to beta ratio) have been considered as candidate biomarkers to diagnose AD/HD (Thome et al., 2012; Faraone et al., 2014); however, the diagnostic reliability of RS-EEG measures is controversial (Arns et al., 2013; Faraone et al., 2014). Instead, it has also been proposed that RS-EEG measures have prognostic value in AD/HD (Arns et al., 2013; Arns and Gordon, 2014; Olbrich et al., 2015), based on evidence that RS-EEG profiles are heterogeneous (Clarke et al., 2001, 2011) and different RS-EEG profiles are associated with different responses to medication-based treatment (Clarke et al., 2002; Arns et al., 2008, 2013; Arns, 2012).

https://ift.tt/2GotqSF

212 Bovine Dental Graft as a Cause of Secondary Membranous Nephropathy

https://ift.tt/2pRbB7l

319 Ventricular Assist Devices in Medicare Beneficiaries with ESRD

https://ift.tt/2J7s8gn

317 Icosapent Ethyl Reduces Potentially Atherogenic Lipid and Inflammatory Markers in High-Risk Statin-Treated Patients with Persistent High Triglycerides, EGFR <90 Ml/Min/1.73 M^2, and Elevated Highsensitivity C-Reactive Protein ≥2.0 Mg/L

https://ift.tt/2pRbrNh

Title: Impact of ambiguous and restrictive regulations on opioid-prescribing practice in Georgia

Chronic pain management with opioids in incurable patients remains a challenge of modern medicine regardless of the evidence-based effectiveness of opioids and recommendations of authorities such as the World Health Organization (WHO) and International Narcotics Control Board (INCB). Many countries, including Georgia, maintain overly restrictive regulations that contribute to inadequate pain management.

https://ift.tt/2J3TjZv

Racial and Ethnic Disparities and Bias in the Evaluation and Reporting of Abusive Head Trauma

To characterize racial and ethnic disparities in the evaluation and reporting of suspected abusive head trauma (AHT) across the 18 participating sites of the Pediatric Brain Injury Research Network (PediBIRN). We hypothesized that such disparities would be confirmed at multiple sites and occur more frequently in patients with a lower risk for AHT.

http://bit.ly/2J0dVSx

Whole-mount Confocal Microscopy for Adult Ear Skin: A Model System to Study Neuro-vascular Branching Morphogenesis and Immune Cell Distribution

Here, we describe a high resolution whole-mount imaging method in the entire adult mouse ear skin, which enables us to visualize branching morphogenesis and patterning of peripheral nerves and blood vessels, as well as immune cell distribution.

http://bit.ly/2uwlZar

Non-Targeted HIV Testing in ER Acceptable to Patients

THURSDAY, March 29, 2018 -- A non-targeted HIV testing approach in a South African emergency department is acceptable to patients and reveals a high HIV prevalence, including undiagnosed cases, according to a study published online March 13 in PLOS...

http://bit.ly/2J4RTy6

CDC: Many Adults Not Receiving Sexual Risk Assessments

THURSDAY, March 29, 2018 -- Less than half of women and a quarter of men with recent sexual activity receive sexual risk assessment, according to a March data brief published by the U.S. Centers for Disease Control and Prevention's National Center...

https://ift.tt/2pMEO3s

Duration of Antibiotics Often Exceeds Guidelines for Sinusitis

THURSDAY, March 29, 2018 -- The durations of most courses of antibiotic therapy for adult outpatients with sinusitis exceed guideline recommendations, according to a research letter published online March 26 in JAMA Internal Medicine. Laura M. King,...

https://ift.tt/2pSeXaj

Bariatric Surgery Can Lead to Changes in Relationship Status

THURSDAY, March 29, 2018 -- Bariatric surgery is associated with changes in relationship status, according to a study published online March 28 in JAMA Surgery. Gustave Bruze, Ph.D., from the Karolinska Institute in Stockholm, and colleagues...

http://bit.ly/2J5lxTV

Traumatic Brain Injury Rare for Children With Isolated Vomiting

THURSDAY, March 29, 2018 -- Children presenting with head injury with isolated vomiting rarely have clinically important traumatic brain injury (ci-TBI) or traumatic brain injury on computed tomography (TBI-CT), according to a study published online...

https://ift.tt/2pTrNF8

Relapse in Major Depression Linked to Brain Cortical Changes

THURSDAY, March 29, 2018 -- For patients with major depressive disorder (MDD), relapse is associated with brain cortical changes over two years, according to a study published online March 28 in JAMA Psychiatry. Dario Zaremba, from the University of...

http://bit.ly/2J4RNGK

Lower Thromboembolic Risk With New A-Fib After CABG Versus NVAF

THURSDAY, March 29, 2018 -- For patients post coronary artery bypass graft (CABG) surgery, new-onset postoperative atrial fibrillation (POAF) is associated with lower long-term thromboembolic risk than that seen among patients with nonvalvular...

https://ift.tt/2pTrKZY

Three-dimensional Rendering and Analysis of Immunolabeled, Clarified Human Placental Villous Vascular Networks

This study presents a protocol for the reversible tissue clearing, immunostaining, 3D-rendering and analysis of vascular networks in human placenta villi samples on the order of 1 - 2 mm3.

https://ift.tt/2GnvPgf

Molecular cloning, expression, and functional characterization of the β-agarase AgaB-4 from Paenibacillus agarexedens

In this study, a β-agarase gene, agaB-4, was isolated for the first time from the agar-degrading bacterium Paenibacillus agarexedens BCRC 17346 by using next-generation sequencing. agaB-4 consists of 2652 bp and ...

https://ift.tt/2pRfxoS

Micro-dissection of Enamel Organ from Mandibular Incisor of Rats Exposed to Environmental Toxicants

Understanding enamel formation and possible alterations requires the study of ameloblast activity. Here, we describe a reliable and consistent method to micro-dissect enamel organs containing secretion- and maturation-stage ameloblasts that may be used for further quantitative and qualitative experimental procedures.

https://ift.tt/2E5Cgm2

Site-Directed Immobilization of Bone Morphogenetic Protein 2 to Solid Surfaces by Click Chemistry

Biomaterials doped with Bone Morphogenetic Protein 2 (BMP2) have been used as a new therapeutic strategy to heal non-union bone fractures. To overcome side effects resulting from an uncontrollable release of the factor, we propose a new strategy to site-directly immobilize the factor, thus creating materials with improved osteogenic capabilities.

https://ift.tt/2GWfZKz

Preparation and High-temperature Anti-adhesion Behavior of a Slippery Surface on Stainless Steel

Slippery surfaces provide a new way to solve the adhesion problem. This protocol describes how to fabricate slippery surfaces at high temperatures. The results demonstrate that the slippery surfaces showed anti-wetting for liquids and a remarkable anti-adhesion effect on soft tissues at high temperatures.

https://ift.tt/2E4SV9p

Refusal of recommended maternity care: Time to make a pact with women?

Publication date: Available online 28 March 2018
Source:Women and Birth
Author(s): Bec Jenkinson, Sue Kruske, Sue Kildea
BackgroundThe right to refuse medical treatment can be contentious in maternity care. Professional guidance for midwives and obstetricians emphasises informed consent and respect for patient autonomy, but there is little guidance available to clinicians about the appropriate clinical responses when women decline recommended care.ObjectivesWe propose a comprehensive, woman-centred, systems-level framework for documentation and communication with the goal of supporting women, clinicians and health services in situations of maternal refusal. We term this the Personalised Alternative Care and Treatment framework.DiscussionThe Personalised Alternative Care and Treatment framework addresses Australian policy, practice, education and professional issues to underpin woman-centred care in the context of maternal refusal. It embeds Respectful Maternity Care in system-level maternity care policy; highlights the woman's role as decision maker about her maternity care; documents information exchanged with women; creates a 'living' plan that respects the woman's birth intentions and can be reviewed as circumstances change; enables communication between clinicians; permits flexible initiation pathways; provides for professional education for clinicians, and incorporates a mediation role to act as a failsafe.ConclusionThe Personalised Alternative Care and Treatment framework has the potential to meet the needs of women, clinicians and health services when pregnant women decline recommended maternity care.



https://ift.tt/2GWfPCX

Paclitaxel as Albumin-Bound Nanoparticles with Gemcitabine for Untreated Metastatic Pancreatic Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Abstract

As part of the single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited Celgene Ltd to submit clinical and cost-effectiveness evidence for paclitaxel as albumin-bound nanoparticles (Nab-Pac) in combination with gemcitabine (Nab-Pac + Gem) for patients with untreated metastatic pancreatic cancer. The STA was a review of NICE's 2015 guidance (TA360) in which Nab-Pac + Gem was not recommended for patients with untreated metastatic pancreatic cancer. The review was prompted by a proposed Patient Access Scheme (PAS) discount on the price of Nab-Pac and new evidence that might lead to a change in the guidance. The Liverpool Reviews and Implementation Group at the University of Liverpool was the Evidence Review Group (ERG). This article summarises the ERG's review of the company's evidence submission for Nab-Pac + Gem, and the Appraisal Committee (AC) decision. The final scope issued by NICE listed three comparators: gemcitabine monotherapy (Gem), gemcitabine in combination with capecitabine (Gem + Cap), and a combination of oxaliplatin, irinotecan, leucovorin and fluorouracil (FOLFIRINOX). Clinical evidence for the comparison of Nab-Pac + Gem versus Gem was from the phase III CA046 randomized controlled trial. Analysis of progression-free survival (PFS) and overall survival (OS) showed statistically significant improvement for patients treated with Nab-Pac + Gem versus Gem. Clinical evidence for the comparison of Nab-Pac + Gem versus FOLFIRINOX and versus Gem + Cap was derived from a network meta-analysis (NMA). Results of the NMA did not indicate a statistically significant difference in OS or PFS for the comparison of Nab-Pac + Gem versus either Gem + Cap or FOLFIRINOX. The ERG's main concerns with the clinical effectiveness evidence were difficulties in identifying the patient population for whom treatment with Nab-Pac + Gem is most appropriate, and violation of the proportional hazards (PH) assumption in the CA046 trial. The ERG highlighted methodological issues in the cost-effectiveness analysis pertaining to the modelling of survival outcomes, estimation of drug costs and double counting of adverse-event disutilities. The AC accepted all the ERG's amendments to the company's cost-effectiveness model; however, these did not make important differences to the incremental cost-effectiveness ratios (ICERs). The company's base-case ICER was £46,932 per quality-adjusted life-year (QALY) gained for the comparison of Nab-Pac + Gem versus Gem. Treatment with Nab-Pac + Gem was dominated both by treatment with Gem + Cap and with FOLFIRINOX in the company's base case. The AC concluded that the most plausible ICER for treatment with Nab-Pac + Gem versus Gem was in the range of £41,000–£46,000 per QALY gained. The AC concluded that Nab-Pac + Gem was not cost effective compared with Gem + Cap or FOLFIRINOX, and accepted that treatment with Nab-Pac + Gem met the end-of-life criteria versus Gem but did not consider Nab-Pac + Gem to meet the end-of-life criteria compared with Gem + Cap or FOLFIRINOX. The AC also concluded that although patients who would receive Nab-Pac + Gem rather than FOLFIRINOX or Gem + Cap were difficult to distinguish, they were identifiable in clinical practice. The AC recommended treatment with Nab-Pac + Gem for patients with untreated metastatic pancreatic cancer for whom other combination chemotherapies were unsuitable and who would otherwise receive Gem.

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The Impact of Postreperfusion Syndrome on Acute Kidney Injury in Living Donor Liver Transplantation: A Propensity Score Analysis

BACKGROUND: Postreperfusion syndrome (PRS) has been shown to be related to postoperative morbidity and graft failure in orthotopic liver transplantation. To date, little is known about the impact of PRS on the prevalence of postoperative acute kidney injury (AKI) and the postoperative outcomes after living donor liver transplantation (LDLT). The purpose of our study was to determine the impact of PRS on AKI and postoperative outcomes after LDLT surgery. METHODS: Between January 2008 and October 2015, we retrospectively collected and evaluated the records of 1865 patients who underwent LDLT surgery. We divided the patients into 2 groups according to the development of PRS: PRS group (n = 715) versus no PRS group (n = 1150). Risk factors for AKI and mortality were investigated by multivariable logistic and Cox proportional hazards regression model analysis. Propensity score (PS) analysis (PS matching and inverse probability of treatment weighting analysis) was designed to compare the outcomes between the 2 groups. RESULTS: The prevalence of PRS and the mortality rate were 38% and 7%, respectively. In unadjusted analyses, the PRS group showed more frequent development of AKI (P

https://ift.tt/2GkOGsc

Anesthetics Influence Mortality in a Drosophila Model of Blunt Trauma With Traumatic Brain Injury

Background: Exposure to anesthetics is common in the majority of early survivors of life-threatening injuries. Whether and to what degree general anesthetics influence outcomes from major trauma is unknown. Potential confounding effects of general anesthetics on outcome measures are usually disregarded. We hypothesized that exposure to isoflurane or sevoflurane modulates the outcome from blunt trauma with traumatic brain injury (bTBI). Methods: We tested the hypothesis in a novel model of bTBI implemented in Drosophila melanogaster. Fruit flies of the standard laboratory strain w1118 were cultured under standard conditions. We titrated the severity of bTBI to a mortality index at 24 hours (MI24) of approximately 20% under control conditions. We administered standard doses of isoflurane and sevoflurane before, before and during, or after bTBI and measured the resulting MI24. We report the MI24 as mean ± standard deviation. Results: Isoflurane or sevoflurane administered for 2 hours before bTBI reduced the MI24 from 22.3 ± 2.6 to 10.4 ± 1.8 (P

https://ift.tt/2GET7S8

Database Quality and Access Issues Relevant to Research Using Anesthesia Information Management System Data

For this special article, we reviewed the computer code, used to extract the data, and the text of all 47 studies published between January 2006 and August 2017 using anesthesia information management system (AIMS) data from Thomas Jefferson University Hospital (TJUH). Data from this institution were used in the largest number (P = .0007) of papers describing the use of AIMS published in this time frame. The AIMS was replaced in April 2017, making this finite sample finite. The objective of the current article was to identify factors that made TJUH successful in publishing anesthesia informatics studies. We examined the structured query language used for each study to examine the extent to which databases outside of the AIMS were used. We examined data quality from the perspectives of completeness, correctness, concordance, plausibility, and currency. Our results were that most could not have been completed without external database sources (36/47, 76.6%; P = .0003 compared with 50%). The operating room management system was linked to the AIMS and was used significantly more frequently (26/36, 72%) than other external sources. Access to these external data sources was provided, allowing exploration of data quality. The TJUH AIMS used high-resolution timestamps (to the nearest 3 milliseconds) and created audit tables to track changes to clinical documentation. Automatic data were recorded at 1-minute intervals and were not editable; data cleaning occurred during analysis. Few paired events with an expected order were out of sequence. Although most data elements were of high quality, there were notable exceptions, such as frequent missing values for estimated blood loss, height, and weight. Some values were duplicated with different units, and others were stored in varying locations. Our conclusions are that linking the TJUH AIMS to the operating room management system was a critical step in enabling publication of multiple studies using AIMS data. Access to this and other external databases by analysts with a high degree of anesthesia domain knowledge was necessary to be able to assess the quality of the AIMS data and ensure that the data pulled for studies were appropriate. For anesthesia departments seeking to increase their academic productivity using their AIMS as a data source, our experiences may provide helpful guidance. Accepted for publication January 29, 2018. Funding: None. The authors declare no conflicts of interest. 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 (https://ift.tt/KegmMq). Data from this study were presented, in part, at the 2017 Annual Meeting of the American Society of Anesthesiologists, October 21–25, 2017, Boston, MA. Reprints will not be available from the authors. Address correspondence to Richard H. Epstein, MD, Department of Anesthesiology, Perioperative Medicine & Pain Management, University of Miami, Miller School of Medicine, 1400 NW 12th Ave, Suite 3075, Miami, FL 33136. Address e-mail to repstein@med.miami.edu. © 2018 International Anesthesia Research Society

https://ift.tt/2E5a42I

Dexamethasone as an Adjuvant for Caudal Blockade in Pediatric Surgical Patients: A Systematic Review and Meta-analysis

BACKGROUND: Caudal block is commonly used to provide postoperative analgesia after pediatric surgery in the lower abdomen. Typically administered as a single-shot technique, 1 limitation of this block is the short duration of analgesia. To overcome this, dexamethasone has been used as an adjuvant to prolong block duration. However, there are concerns about steroid-related morbidity and the optimal route of dexamethasone administration (eg, caudal or intravenous) is unknown. METHODS: We conducted a systematic review and random-effects meta-analysis of randomized controlled trials recruiting pediatric surgical patients receiving a caudal block for surgical anesthesia or postoperative analgesia. Included studies compared dexamethasone (caudal, intravenous, or both) to control. Duration of analgesia was the primary outcome. Database sources were Medline, Embase, the Cochrane Library, and Google Scholar searched up to August 18, 2017, without language restriction. Screening of studies, data extraction, and risk of bias assessment were performed independently and in duplicate by 2 authors. Risk of bias was assessed using Cochrane methodology and the strength of evidence was scored using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: The initial search retrieved 93 articles. Fourteen randomized controlled trials that comprised 1315 pediatric patients met the inclusion criteria. All but 1 study involved lower abdominal operations (orchidopexy, inguinal hernia repair, and hypospadias repair). The caudal and intravenous dose of dexamethasone ranged from 0.1 to 0.2 mg/kg and 0.5 to 1.5 mg/kg, respectively, and all studies were pooled in the main analysis. Dexamethasone prolonged the duration of analgesia by both the caudal route (5.43 hours, 95% confidence interval [CI], 3.52–7.35; P

https://ift.tt/2GAJkwx

Time for a Fresh Approach to Examining Factors Associated With Red Blood Cell Transfusion Outcome

No abstract available

https://ift.tt/2E3FDdt

Repeated Morphine Prolongs Postoperative Pain in Male Rats

BACKGROUND: Opioids are effective postoperative analgesics. Disturbingly, we have previously reported that opioids such as morphine can worsen inflammatory pain and peripheral and central neuropathic pain. These deleterious effects are mediated by immune mediators that promote neuronal hyperexcitability in the spinal dorsal horn. Herein, we tested whether perioperative morphine could similarly prolong postoperative pain in male rats. METHODS: Rats were treated with morphine for 7 days, beginning immediately after laparotomy, while the morphine was tapered in a second group. Expression of genes for inflammatory mediators was quantified in the spinal dorsal horn. In the final experiment, morphine was administered before laparotomy for 7 days. RESULTS: We found that morphine treatment after laparotomy extended postoperative pain by more than 3 weeks (time × treatment: P

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A Dedicated Acute Pain Service Is Associated With Reduced Postoperative Opioid Requirements in Patients Undergoing Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy

BACKGROUND: The Acute Pain Service (APS) was initially introduced to optimize multimodal postoperative pain control. The aim of this study was to evaluate the association between the implementation of an APS and postoperative pain management and outcomes for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: In this propensity-matched retrospective cohort study, we performed a before-after study without a concurrent control group. Outcomes were compared among patients undergoing CRS-HIPEC when APS was implemented versus historical controls (non-APS). The primary objective was to determine if there was a decrease in median total opioid consumption during postoperative days 0–3 among patients managed by the APS. Secondary outcomes included opioid consumption on each postoperative day (0–6), time to ambulation, time to solid intake, and hospital length of stay. RESULTS: After exclusion, there were a total of 122 patients, of which 51 and 71 were in the APS and non-APS cohort, respectively. Between propensity-matched groups, the median (quartiles) total opioid consumption during postoperative days 0–3 was 27.5 mg intravenous morphine equivalents (MEQs) (7.6–106.3 mg MEQs) versus 144.0 mg MEQs (68.9–238.3 mg MEQs), respectively. The median difference was 80.8 mg MEQs (95% confidence interval, 46.1– 124.0; P 50%, as well as shorter time to ambulation and time to solid intake. Implementation of an APS may improve outcomes in CRS-HIPEC patients. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Accepted for publication February 2, 2018. E. T. Said and J. F. Sztain contributed equally to this manuscript. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. This work has been presented, in part, as an oral presentation at the Enhanced Recovery After Surgery US Conference, November 10, 2017, Dallas, TX. Reprints will not be available from the authors. Address correspondence to Engy T. Said, MD, Department of Anesthesiology, University of California, 200 W Arbor Dr, MC 8770, San Diego, CA 92103. Address e-mail to esaid@ucsd.edu. © 2018 International Anesthesia Research Society

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Evidence Basis for Regional Anesthesia in Ambulatory Anterior Cruciate Ligament Reconstruction: Part I—Femoral Nerve Block

The optimal management of pain after ambulatory anterior cruciate ligament reconstruction (ACLR) is unclear. Femoral nerve block (FNB) is purported to enhance postoperative analgesia, but its effectiveness in the setting of modern multimodal analgesia is unclear. This systematic review examines the effect of adding FNB to multimodal analgesia on analgesic outcomes after ACLR, whether or not the analgesic regimen used included local instillation analgesia (LIA). We retrieved randomized controlled trials evaluating the effects of adding FNB to multimodal analgesia on analgesic outcomes after ACLR, compared to multimodal analgesia alone (control). We designated postoperative opioid consumption at 24 hours as our primary outcome. Secondary outcomes included postoperative opioid consumption at 24–48 hours, rest, and dynamic pain severity between 0 and 48 hours, time to analgesic request, postanesthesia care unit and hospital stay durations, patient satisfaction, postoperative nausea and vomiting, functional outcomes, and long-term (>1 month) quadriceps strength. Eight randomized controlled trials (716 patients) were identified. Five trials compared FNB administration to control, and another 3 compared the combination of FNB and LIA to LIA alone. Compared to control, adding FNB resulted in modest reductions in 24-hour opioid consumption in 2 of 3 trials, and improvements in rest pain at 1 hour in 1 trial and up to 24 hours in another. In contrast, the combination of FNB and LIA, compared to LIA alone, did not reduce opioid consumption in any of the trials, but it did improve pain scores at 20 minutes only in 1 trial. The effect of FNB on long-term quadriceps strength or function after ACLR was not evaluated in the reviewed trials. Contemporary evidence suggests that the benefits of adding FNB to multimodal analgesia for ACLR are modest and conflicting, but there is no incremental analgesic benefit if the multimodal analgesic regimen included LIA. Our findings do not support the routine use of FNB for analgesia in patients having ACLR. Accepted for publication January 10, 2018. Funding: Departmental. Both F. W. Abdallah and R. Brull are supported by the Merit Award Program, Department of Anesthesia, University of Toronto. R. Brull receives research support from the Evelyn Bateman Cara Operations Endowed Chair in Ambulatory Anesthesia and Women's Health, Women's College Hospital, Toronto. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Faraj W. Abdallah, MD, Department of Anesthesia, St Michael's Hospital, 30 Bond St, Toronto, ON M5B 1W8, Canada. Address e-mail to abdallahf@smh.ca. © 2018 International Anesthesia Research Society

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Determination of Geolocations for Anesthesia Specialty Coverage and Standby Call Allowing Return to the Hospital Within a Specified Amount of Time

BACKGROUND: For emergent procedures, in-house teams are required for immediate patient care. However, for many procedures, there is time to bring in a call team from home without increasing patient morbidity. Anesthesia providers taking subspecialty or backup call from home are required to return to the hospital within a designated number of minutes. Driving times to the hospital during the hours of call need to be considered when deciding where to live or to visit during such calls. Distance alone is an insufficient criterion because of variable traffic congestion and differences in highway access. We desired to develop a simple, inexpensive method to determine postal codes surrounding hospitals allowing a timely return during the hours of standby call. METHODS: Pessimistic travel times and driving distances were calculated using the Google distance matrix application programming interface for all N= 136 postal codes within 60 great circle ("straight line") miles of the University of Miami Hospital (Miami, FL) during all 108 weekly standby call hours. A postal code was acceptable if the estimated longest driving time to return to the hospital was ≤60 minutes (the anesthesia department's service commitment to start an urgent case during standby call). Linear regression (with intercept = 0) minimizing the mean absolute percentage difference between the distances (great circle and driving) and the pessimistic driving times to return to the hospital was performed among all 136 postal codes. Implementation software written in Python is provided. RESULTS: Postal codes allowing return to the studied hospital within the specified interval were identified. The linear regression showed that driving distances correlated poorly with the longest driving time to return to the hospital among the 108 weekly call hours (mean absolute percentage error = 25.1% ± 1.7% standard error [SE]; N = 136 postal codes). Great circle distances also correlated poorly (mean absolute percentage error = 28.3% ± 1.9% SE; N = 136). Generalizability of the method was determined by successful application to a different hospital in a rural state (University of Iowa Hospital). CONCLUSIONS: The described method allows identification of postal codes surrounding a hospital in which personnel taking standby call could be located and be able to return to the hospital during call hours on every day of the week within any specified amount of time. For areas at the perimeter of the acceptability, online distance mapping applications can be used to check driving times during the hours of standby call. Accepted for publication January 9, 2018. Funding: None. The authors declare no conflicts of interest. 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 (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Richard H. Epstein, MD, Department of Anesthesiology, Perioperative Medicine & Pain Management, University of Miami, Miller School of Medicine, 1400 NW 12th Ave, Suite 3075, Miami, FL 33136. Address e-mail to repstein@med.miami.edu. © 2018 International Anesthesia Research Society

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Intravenous Acetaminophen Does Not Reduce Inpatient Opioid Prescription or Opioid-Related Adverse Events Among Patients Undergoing Spine Surgery

BACKGROUND: Having entered the US market relatively recently, the perioperative role of intravenous acetaminophen (ivAPAP) remains to be established for several surgeries. Using national data, we therefore assessed current utilization and whether it reduces inpatient opioid prescription and opioid-related side effects in a procedure with relatively high opioid utilization. METHODS: Patients undergoing a lumbar/lumbosacral spinal fusion (n = 117,269; 2011–2014) were retrospectively identified in a nationwide database and categorized by the amount and timing of ivAPAP administration (1 or >1 dose on postoperative day [POD] 0, 1, or 1+). Multivariable models measured associations between ivAPAP utilization categories and opioid prescription and perioperative complications; odds ratios (or % change) and 95% confidence intervals are reported. RESULTS: Overall, ivAPAP was used in 18.9% (n = 22,208) of cases of which 1 dose on POD 0 was the most common (73.6%; n = 16,335). After covariate adjustment, use of ivAPAP on POD 0 and 1 was associated with minimal changes in opioid prescription, length and cost of hospitalization particularly favoring >1 ivAPAP dose with a modestly (-5.2%, confidence interval, -7.2% to -3.1%; P

https://ift.tt/2Gn5v5Z

Clonidine Effect on Pain After Cesarean Delivery: A Randomized Controlled Trial of Different Routes of Administration

BACKGROUND: Intrathecal clonidine prolongs spinal anesthesia. We evaluated the effects of the addition of intrathecal or intravenous clonidine (75 µg) to standard cesarean delivery spinal anesthesia on postoperative pain and neonatal outcomes. METHODS: In a randomized, placebo-controlled, double-blind trial, 64 women scheduled for elective cesarean delivery under spinal anesthesia were randomly allocated and compared among 3 groups: intrathecal clonidine 75 µg, intravenous clonidine 75 µg, and placebo. The primary outcome was acute postoperative pain. A sample size of 26 individuals per group (N = 78) was planned. RESULTS: From April 2015 to April 2016, 64 women were analyzed (14 excluded). No differences in postoperative pain scores were found (Numerical Verbal Scale for pain at movement at 24 hours of postcesarean delivery: 4.53 ± 3.0 vs 4.45 ± 2.73 vs 3.93 ± 3.07 for control, intrathecal, and intravenous, respectively, P = .771). Intrathecal and intravenous clonidine led to more sedation, in comparison to the control group, during the intraoperative period (Richmond Agitation and Sedation Scale: −0.3 ± 0.47 vs −1 ± 0.53 vs −0.73 ± 0.45 for control, intrathecal, and intravenous, respectively, overall P

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Changes in International Normalized Ratios After Plasma Transfusion of Varying Doses in Unique Clinical Environments

BACKGROUND: Plasma transfusion is commonly performed for the correction of abnormal coagulation screening tests. The goal of this investigation was to assess the relationship between the dose of plasma administered and changes in coagulation test results in a large and diverse cohort of patients with varying levels of coagulation abnormalities and comorbid disease and in a variety of clinical settings. METHODS: In this single-center historical cohort study, all plasma transfusion episodes in adult patients with abnormal coagulation screening tests were extracted between 2011 and 2015. The primary outcome was the proportion of patients attaining normal posttransfusion international normalized ratio (INR ≤1.1) with secondary outcomes including the proportion of patients attaining partial normalization of INR (INR ≤1.5) or at least 50% normalization in pretransfusion values with respect to an INR of 1.1. RESULTS: In total, 6779 unique patients received plasma with a median (quartiles) pretransfusion INR of 1.9 (1.6–2.5) and a median transfusion volume of 2 (2–3) units. The majority (85%) of transfusions occurred perioperatively, with 20% of transfusions administered prophylactically before a procedure. The median decrease in INR was 0.4 (0.2–0.8). Complete INR normalization was obtained in 12%. Reductions in INR were modest with pretransfusion INR values

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Presence of Aedes and Anopheles mosquito larvae is correlated to bacteria found in domestic water-storage containers

Abstract

Water-storage containers are common in households where access to water is scarce, and often act as breeding sites for vector mosquitoes. Bacteria in these containers may be important for attracting or repelling ovipositing mosquitoes. We hypothesized that bacterial community composition in water-storage containers would represent either inhibitory or suitable environmental conditions for mosquito larvae. To investigate this, we characterized the bacterial community composition in water-storage containers and correlated these communities to Aedes and Anopheles larval densities. Water samples were collected over two years from 13 containers in an Indian village and analyzed by high throughput 16S rRNA gene amplicon sequencing. Comparisons of bacterial community composition between water with and without mosquito larvae showed that Xanthomonadaceae, Comamonadaceae and Burkholderiaceae were more common (p < 0.05) in absence of larvae, while Lachnospiraceae, Synechococcaceae, Alcaligenaceae and Cryomorphaceae were more common (p < 0.05) in presence of larvae. Indicator analysis identified operational taxonomic units designated as CL500–29 marine group (Acidimicrobiaceae) and FukuN101 (Microbacteriaceae) for absence and presence of larvae, respectively. These results contribute to the understanding of which bacteria, directly or indirectly, can be linked to absence or presence of mosquitoes around households and set the basis for potential measures to be taken against these vector mosquitoes.

https://ift.tt/2Gp63Ig

Activity and Diversity of Methane-Oxidizing Bacteria along a Norwegian sub-Arctic Glacier Forefield

Abstract

Methane (CH₄) is one of the most abundant greenhouse gases in the atmosphere and identification of its sources and sinks is crucial for the reliability of climate model outputs. Although CH₄ production and consumption rates have been reported from a broad spectrum of environments, data obtained from glacier forefields are restricted to a few locations. We report the activities of methanotrophic communities and their diversity along a chronosequence in front of a sub-Arctic glacier using high-throughput sequencing and gas flux measurements. CH₄ oxidation rates were measured in the field throughout the growing season during three sampling times at eight different sampling points in combination with laboratory incubation experiments. The overall results showed that the methanotrophic community had similar trends of increased CH₄ consumption and increased abundance as a function of soil development and time of year. Sequencing results revealed that the methanotrophic community was dominated by a few OTUs and that a short-term increase in CH₄ concentration, as performed in the field measurements, altered slightly the relative abundance of the OTUs.

https://ift.tt/2Gyz08j

Fermentation products in the cystic fibrosis airways induce aggregation and dormancy-associated expression profiles in a CF clinical isolate of Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa is a well-known dominant opportunistic pathogen in cystic fibrosis (CF) with a wide range of metabolic capacities. However, P. aeruginosa does not colonize the airways alone, and benefits from the metabolic products of neighboring cells—especially volatile molecules that can travel between different parts of the airways easily. Here, we present a study that investigates the metabolic, gene expression profiles, and phenotypic responses of a P. aeruginosa clinical isolate to fermentation products lactic acid and 2,3-butanediol, metabolites that are produced by facultative anaerobic members of the CF polymicrobial community and potential biomarkers of disease progression. Although previous studies have successfully investigated the metabolic and transcriptional profiles of P. aeruginosa, most have used common lab reference strains that may differ in important ways from clinical isolates. Using transcriptomics and metabolomics with gas chromatography time of flight mass spectrometry (GCTOF-MS), we observe that fermentation products induce pyocyanin production along with expression of genes involved in P. aeruginosa amino acid utilization, dormancy and aggregative or biofilm modes of growth. These findings have important implications for how interactions within the diverse CF microbial community influence microbial physiology, with potential clinical consequences.

https://ift.tt/2uAjHqW

Effect of clarification pH of sorghum juice on the composition of essential nutrients for fermentation

Abstract

The growing demand to replace fossil fuels with renewable alternatives has generated an urgent and imminent global need to find new non-fossil sources. Sweet sorghum is widely recognized as a highly promising biomass energy crop with particular potential to complement sugarcane for ethanol production. Our aim in this study was to evaluate the influence of pH during the clarification method on the composition of essential nutrients in the sorghum juice and how this affects the efficiency of the ethanol fermentation process. We found that a higher pH directly affected residual concentrations of key nutrients (P, Ca, Zn, Mn) and as a consequence the efficiency of ethanol fermentation. In conclusion we recommend a clarification procedure at pH 6–6.5 in order not to significantly affect nutritional parameters important for the yeast fermentation process.

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Effect of ethanol and butanol on autotrophic growth of model homoacetogens

Abstract

Research efforts aimed at increasing ethanol and butanol productivity from syngas are currently gaining attention. For most model carboxydotrophic bacteria, production rates, yields and maximum product titers have been studied in detail, but little is known on alcohol toxicity in these bacteria. The aim of this work was to investigate the inhibitory effects of ethanol and butanol on the growth of Clostridium ljungdahlii PETC, Clostridium carboxidivorans P7, and 'Butyribacterium methylotrophicum DSM3468'. Experiments to determine inhibitory effects due to product accumulation were carried out using a synthetic mixture of CO:CO₂:H₂ as a substrate. These conditions were chosen to mimic gaseous effluents of biomass and waste gasification plants. Inhibition effects were recorded as changes in growth parameters. No significant inhibition was observed for ethanol at concentrations below 15 g/L. The three species exhibited higher sensitivity to butanol. Half inhibition constants for butanol could be estimated for P7 (IC₅₀ = 4.12 g/L), DSM3468 (IC₅₀ = 1.79 g/L), and PETC (IC₅₀ = 9.75 g/L). In conclusion, at least for the tested strains, there is no urgent need to overcome alcohol inhibition in eventual industrial production of alcohols from syngas fermentation.

https://ift.tt/2uwoVUh

The Development of a Machine Learning Inpatient Acute Kidney Injury Prediction Model

Objectives: To develop an acute kidney injury risk prediction model using electronic health record data for longitudinal use in hospitalized patients. Design: Observational cohort study. Setting: Tertiary, urban, academic medical center from November 2008 to January 2016. Patients: All adult inpatients without pre-existing renal failure at admission, defined as first serum creatinine greater than or equal to 3.0 mg/dL, International Classification of Diseases, 9th Edition, code for chronic kidney disease stage 4 or higher or having received renal replacement therapy within 48 hours of first serum creatinine measurement. Interventions: None. Measurements and Main Results: Demographics, vital signs, diagnostics, and interventions were used in a Gradient Boosting Machine algorithm to predict serum creatinine–based Kidney Disease Improving Global Outcomes stage 2 acute kidney injury, with 60% of the data used for derivation and 40% for validation. Area under the receiver operator characteristic curve (AUC) was calculated in the validation cohort, and subgroup analyses were conducted across admission serum creatinine, acute kidney injury severity, and hospital location. Among the 121,158 included patients, 17,482 (14.4%) developed any Kidney Disease Improving Global Outcomes acute kidney injury, with 4,251 (3.5%) developing stage 2. The AUC (95% CI) was 0.90 (0.90–0.90) for predicting stage 2 acute kidney injury within 24 hours and 0.87 (0.87–0.87) within 48 hours. The AUC was 0.96 (0.96–0.96) for receipt of renal replacement therapy (n = 821) in the next 48 hours. Accuracy was similar across hospital settings (ICU, wards, and emergency department) and admitting serum creatinine groupings. At a probability threshold of greater than or equal to 0.022, the algorithm had a sensitivity of 84% and a specificity of 85% for stage 2 acute kidney injury and predicted the development of stage 2 a median of 41 hours (interquartile range, 12–141 hr) prior to the development of stage 2 acute kidney injury. Conclusions: Readily available electronic health record data can be used to predict impending acute kidney injury prior to changes in serum creatinine with excellent accuracy across different patient locations and admission serum creatinine. Real-time use of this model would allow early interventions for those at high risk of acute kidney injury. 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 (https://ift.tt/29S62lw). Dr. Koyner has received research funding from Satellite Healthcare. Drs. Edelson and Churpek have a patent pending (ARCD. P0535US.P2) for risk stratification algorithms for hospitalized patients. Dr. Edelson has received research funding from Philips Healthcare and Early Sense and has ownership interests in Quant HC, which is developing products for risk stratification of hospitalized patients. Mr. Carey has disclosed that he does not have any potential conflicts of interest. For information regarding this article, E-mail: jkoyner@uchicago.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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The Speaker Gender Gap at Critical Care Conferences

Objectives: To review women's participation as faculty at five critical care conferences over 7 years. Design: Retrospective analysis of five scientific programs to identify the proportion of females and each speaker's profession based on conference conveners, program documents, or internet research. Setting: Three international (European Society of Intensive Care Medicine, International Symposium on Intensive Care and Emergency Medicine, Society of Critical Care Medicine) and two national (Critical Care Canada Forum, U.K. Intensive Care Society State of the Art Meeting) annual critical care conferences held between 2010 and 2016. Subjects: Female faculty speakers. Interventions: None. Measurements and Main Results: Male speakers outnumbered female speakers at all five conferences, in all 7 years. Overall, women represented 5–31% of speakers, and female physicians represented 5–26% of speakers. Nursing and allied health professional faculty represented 0–25% of speakers; in general, more than 50% of allied health professionals were women. Over the 7 years, Society of Critical Care Medicine had the highest representation of female (27% overall) and nursing/allied health professional (16–25%) speakers; notably, male physicians substantially outnumbered female physicians in all years (62–70% vs 10–19%, respectively). Women's representation on conference program committees ranged from 0% to 40%, with Society of Critical Care Medicine having the highest representation of women (26–40%). The female proportions of speakers, physician speakers, and program committee members increased significantly over time at the Society of Critical Care Medicine and U.K. Intensive Care Society State of the Art Meeting conferences (p

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Which safety standards should your ambulance remount meet?

With more safety data available, ambulance remounts may be the next to receive significant upgrades to minimum quality standards

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Biomaterial Scaffolds as Pre‐metastatic Niche Mimics Systemically Alter the Primary Tumor and Tumor Microenvironment

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2I75QKC

A Cascade‐Targeting Nanocapsule for Enhanced Photothermal Tumor Therapy with Aid of Autophagy Inhibition

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2utmcel

Regenerative Medicine: Hierarchical Design of Tissue Regenerative Constructs (Adv. Healthcare Mater. 6/2018)

Advanced Healthcare Materials, Volume 7, Issue 6, March 21, 2018.


https://ift.tt/2Gha7yr

Toward Immunocompetent 3D Skin Models

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2I3mzyi

Carbon‐Dot‐Decorated TiO2 Nanotubes toward Photodynamic Therapy Based on Water‐Splitting Mechanism

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2I75ZxE

Wearable Biosensors: Disposable Morpho menelaus Based Flexible Microfluidic and Electronic Sensor for the Diagnosis of Neurodegenerative Disease (Adv. Healthcare Mater. 5/2018)

Advanced Healthcare Materials, Volume 7, Issue 5, March 7, 2018.


https://ift.tt/2pFvy0Y

Advances and Opportunities in Nanoparticle‐ and Nanomaterial‐Based Vaccines against Bacterial Infections

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2Grmc3b

Surface‐Enhanced Raman Scattering for Rapid Detection and Characterization of Antibiotic‐Resistant Bacteria

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2Gqxbdj

Novel 3D Hybrid Nanofiber Aerogels Coupled with BMP‐2 Peptides for Cranial Bone Regeneration

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2pHg8tc

A Capsule‐Type Microrobot with Pick‐and‐Drop Motion for Targeted Drug and Cell Delivery

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2IevrB4

Tropoelastin Implants That Accelerate Wound Repair

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2pQvKLG

Tough Composite Hydrogels with High Loading and Local Release of Biological Drugs

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2Igf8Ux