Long-term clinical results and scanning electron microscopic analysis of the aspheric, hydrophobic, acrylic intraocular lens CT LUCIA 611P(Y)

https://ift.tt/2KHkqyd

Impact of Energy Drinks on Health and Well-being

Abstract

Purpose of Review

Energy drinks and energy shots are functional supplements with higher caffeine content marketed toward adolescents and young adults with the intention of boosting energy. Parallel to its rising popularity, there are safety concerns with the consumption of these beverages. Herein, we reviewed the impact these supplements produce on health and well-being.

Recent Findings

Most of the promoted benefits of the beverages can be attributed to caffeine. The physiologic effects, if any, of other ingredients such as vitamins and herbal extracts are unclear. The presence of a higher caffeine content as compared to soft drinks may predispose to caffeine intoxication in susceptible individuals. Also, the practice of co-ingestion of these beverages with alcohol is still prevalent and associated with serious consequences.

Summary

Strict regulations (restriction of sales, clear warning labels, capping caffeine levels) and public education may help prevent the adverse outcomes from these beverages.

https://ift.tt/2J02gSz

Risk factors for nonroutine discharge in adult spinal deformity surgery

Publication date: Available online 7 July 2018

Source: The Spine Journal

Author(s): Raj M. Amin, Micheal Raad, Amit Jain, Morsi Khashan, Hamid Hassanzadeh, Steven M. Frank, Khaled M. Kebaish

ABSTRACT

BACKGROUND CONTEXT

Surgery for adult spinal deformity (ASD) is increasingly common. Although outcomes of ASD surgery have been studied extensively, to our knowledge, no data exist regarding factors predicting nonroutine discharge in this population. Nonroutine discharge is defined as discharge to a health care facility after surgery rather than to home.

PURPOSE

To determine which patient and surgical factors predict nonroutine discharge after ASD surgery.

DESIGN

This is a retrospective study.

PATIENTS SAMPLE

We conducted a retrospective single-center study of 303 patients who underwent arthrodesis of 5 or more spinal levels to treat ASD between 2009 and 2014.

OUTCOME MEASURES

Patients were stratified into 2 groups according to discharge disposition: home or nonroutine.

METHODS

Objective preoperative characteristics, intraoperative course, and postoperative recovery were analyzed to identify pre- and perioperative factors associated with nonroutine discharge. Univariate analysis was performed first. All factors with P values < .2 on univariate analysis were included in a logistic regression model. Additionally, to understand the relationship between subjective patient-reported outcome (PRO) measures and nonroutine discharge, we compared the 2 groups with respect to mean Oswestry Disability Index and Scoliosis Research Society (SRS)-22r domains using Student t-tests.

RESULTS

On univariate analysis, objective measures that differed significantly (P < .05) between the 2 cohorts were age (≥65 years), osteoporosis, Charlson Comorbidity Index score of ≥2, prolonged hospital stay (>8 days), and blood transfusion. Given the above logistic regression inclusion criteria, we controlled for the performance, and type, of osteotomy (P = .055). On multivariate analysis, older age, osteoporosis, prolonged hospital stay, blood transfusion, and 3-column osteotomy were independently associated with nonroutine discharge. Subjective PRO measures, including Oswestry Disability Index and SRS-22r physical function and pain domain scores, were significantly worse in the nonroutine discharge cohort (P < .05).

CONCLUSION

To our knowledge, this is the first study to evaluate pre- and perioperative factors associated with nonroutine discharge after ASD surgery. Elderly patients who undergo complex surgery and receive blood transfusions are at particularly high risk of nonroutine discharge. Surgeons should consider these factors during surgical planning and preoperative patient counseling.

https://ift.tt/2zfFKWb

Effect of Human Wnt10b Transgene Overexpression on Peri-Implant Osteogenesis in Ovariectomized Rats

Human Gene Therapy, Ahead of Print.


https://ift.tt/2u7J1BZ

Incidence of rotator cuff tears in the setting of calcific tendinopathy on MRI: a case controlled comparison

Abstract

Objective

To compare the incidence of rotator cuff tears on shoulder MRI in patients who have rotator cuff calcific tendinopathy with that in patients without calcific tendinopathy in a frequency-matched case–control study.

Materials and methods

Retrospective review shoulder MRIs of 86 patients with rotator cuff calcific tendinopathy and an 86-patient age-, gender-, and laterality-matched control group using frequency matching.

Results

No statistically significant difference (odds ratio: 0.72, 95% confidence interval: 0.38–1.38, p = 0.32) was found in the incidence of rotator cuff tear in the calcific tendinopathy (27.9%) and control groups (34.9%). A significant (p < 0.001) difference in the size of rotator cuff tear was seen between the two groups, with 12.5% of tears being full-thickness in the calcific tendinopathy group and 63.3% of tears being full-thickness in the control group. Only 3 of the 24 (12.5%) rotator cuff tears present in the calcific tendinopathy group occurred at the site of tendon calcification.

Conclusion

Patients presenting with indeterminate shoulder pain and rotator cuff calcific tendinopathy are not at increased risk for having a rotator cuff tear compared with similar demographic patients without calcific tendinopathy presenting with shoulder pain. Calcific tendinopathy and rotator cuff tears likely arise from different pathological processes.

https://ift.tt/2J0PK53

Impact of long-term androgen deprivation therapy on PSMA ligand PET/CT in patients with castration-sensitive prostate cancer

Abstract

Purpose

Since the introduction of PSMA PET/CT with ⁶⁸Ga-PSMA-11, this modality for imaging prostate cancer (PC) has spread worldwide. Preclinical studies have demonstrated that short-term androgen deprivation therapy (ADT) can significantly increase PSMA expression on PC cells. Additionally, retrospective clinical data in large patient cohorts suggest a positive association between ongoing ADT and a pathological PSMA PET/CT scan. The present evaluation was conducted to further analyse the influence of long-term ADT on PSMA PET/CT findings.

Methods

A retrospective analysis was performed of all 1,704 patients who underwent a ⁶⁸Ga-PSMA-11 PET/CT scan at our institution from 2011 to 2017 to detect PC. Of 306 patients scanned at least twice, 10 had started and continued ADT with a continuous clinical response between the two PSMA PET/CT scans. These ten patients were included in the current analysis which compared the tracer uptake intensity and volume of PC lesions on PSMA PET/CT before and during ongoing ADT.

Results

Overall, 31 PC lesions were visible in all ten patients before initiation of ADT. However, during ongoing ADT (duration 42–369 days, median 230 days), only 14 lesions were visible in eight of the ten patients. The average tracer uptake values decreased in 71% and increased in 12.9% of the PC lesions. Of all lesions, 33.3% were still visible in six patients with a complete PSA response (≤0.1 ng/ml).

Conclusion

Continuous long-term ADT significantly reduces the visibility of castration-sensitive PC on PSMA PET/CT. If the objective is visualization of the maximum possible extent of disease, we recommend referring patients for PSMA PET/CT before starting ADT.

https://ift.tt/2J1G0aN

Second-Site IDH2 Mutations Confer Resistance to Enasidenib In Trans [Research Watch]

Two patients with IDH2^R140Q AML acquired resistance to an IDH2 inhibitor via secondary IDH2 mutations.

https://ift.tt/2MTOMda

CBF{beta}-SMMHC Activates MYC Enhancers to Promote Leukemogenesis [Research Watch]

CBFβ–SMMHC inhibition induces RUNX1-mediated repression of MYC to induce apoptosis in inv(16) AML cells.

https://ift.tt/2KEqbN2

IL23 Produced by MDSCs Promotes Castration-Resistant Prostate Cancer [Research Watch]

In patients with CRPC an increase in tumor-infiltrating MDSCs that secrete IL23 upregulates AR.

https://ift.tt/2MUNcYt

Paralog Dependency May Be Exploitable in Tumors Lacking Chromosome 1p [Research Watch]

Cells with chromosome 1p loss and hemizygous deletion of MAGOH are dependent on its paralog, MAGOHB.

https://ift.tt/2KAvEUS

Positive Results for Tazemetostat in Follicular Lymphoma [News in Brief]

Phase II study finds drug effective in patients with EZH2 mutations.

https://ift.tt/2KC30mq

Forestalling BRAF-inhibitor resistance in a shocking way

Targeting BRAF in BRAF-mutant melanoma is highly effective, but most patients develop resistance. Heat shock protein 90 (HSP90) has been implicated and identified as a therapeutic target. Ultimately, early stage clinical investigation will be necessary to provide proof-of-principle of this approach, and if appropriate randomized trials to confirm promising findings.

https://ift.tt/2KSaFcf

Functions and mechanisms of tumor necrosis factor-{alpha} and noncoding RNAs in bone-invasive pituitary adenomas

Purpose-To explore the molecular mechanism and prognosis of bone-invasive pituitary adenomas (BIPAs). Experimental Design-A total of 274 patients with pituitary adenomas were followed up. Transcriptomic microarrays analysis was performed on 10 pituitary adenomas, including 5 BIPAs and 5 nonbone-invasive pituitary adenomas (NBIPAs). The targeted molecular markers were validated by qRT-PCR, immunohistochemistry, elisa and osteoclast differentiation. Results-Clinical variable analyses revealed a significant correlation between bone invasion and female sex, large tumor volume, non-gross total resection (NGTR) and tumor regrowth. BIPAs had worse PFS (progression free survival) than did NBIPAs in the NGTR and NFPA (nonfunctional pituitary adenoma) groups. GO functional and KEGG pathway analyses showed that the biological processes and pathways were primarily immune and inflammatory pathways. Pathway act work showed that osteoclast differentiation pathway was significantly implicated in the pathway network. BIPAs had higher expression of TNF-α than that of NBIPAs on immunohistochemistry. In vitro, TNF-α could induce RAW264.7 cells to differentiate into mature osteoclasts, leading to bone destruction. NR_033258, lncRNA SNHG24, miR-181c-5p and miR-454-3p can regulate TNF-α expression. Conclusions-BIPAs had worse PFS than did NBIPAs in the NGTR and NFPA groups. Inflammatory and immune factors play an important role in BIPAs. TNF-α can directly induce osteoclast differentiation in BIPAs. NR_033258, lncRNA SNHG24, miR-181c-5p and miR-454-3p can regulate TNF-α expression. TNF-α and its related lncRNAs and miRNAs represent potential therapeutic targets for bone-invasive pituitary adenomas in the future.

https://ift.tt/2KNLScz

ERCC2 Helicase Domain Mutations Confer Nucleotide Excision Repair Deficiency and Drive Cisplatin Sensitivity in Muscle-Invasive Bladder Cancer

Purpose: DNA damaging agents comprise the backbone of systemic treatment for many tumor types; however, few reliable predictive biomarkers are available to guide use of these agents. In muscle-invasive bladder cancer (MIBC), cisplatin-based chemotherapy improves survival, yet response varies widely among patients. Here, we sought to define the role of the nucleotide excision repair (NER) gene ERCC2 as a biomarker predictive of response to cisplatin in MIBC. Experimental Design: Somatic missense mutations in ERCC2 are associated with improved response to cisplatin-based chemotherapy; however, clinically identified ERCC2 mutations are distributed throughout the gene and the impact of individual ERCC2 variants on NER capacity and cisplatin sensitivity is unknown. We developed a microscopy-based NER assay to profile ERCC2 mutations observed retrospectively in prior studies and prospectively within the context of an institution-wide tumor profiling initiative. In addition, we created the first ERCC2-deficient bladder cancer preclinical model for studying the impact of ERCC2 loss-of-function. Results: We used our functional assay to test the NER capacity of clinically observed ERCC2 mutations and found that most ERCC2 helicase domain mutations cannot support NER. Further, we show that introducing an ERCC2 mutation into a bladder cancer cell line abrogates NER activity and is sufficient to drive cisplatin sensitivity in an orthotopic xenograft model. Conclusions: Our data support a direct role for ERCC2 mutations in driving cisplatin response, define the functional landscape of ERCC2 mutations in bladder cancer, and provide an opportunity to apply combined genomic and functional approaches to prospectively guide therapy decisions in bladder cancer.

https://ift.tt/2J03sFv

Molecular Imaging of Radiolabeled Bispecific T-cell Engager 89Zr-AMG211 Targeting CEA-positive Tumors

Background: AMG 211, a bispecific T-cell engager (BiTE) antibody construct, targets carcinoembryonic antigen (CEA) and the CD3 epsilon subunit of the human T-cell receptor. AMG 211 was labeled with zirconium-89 (89Zr) or fluorescent dye to evaluate the tumor targeting properties. Experimental Design: 89Zr-AMG211 was administered to mice bearing CEA-positive xenograft tumors of LS174T colorectal adenocarcinoma or BT474 breast cancer cells, as well as CEA-negative HL-60 promyelocytic leukemia xenografts. Biodistribution studies with 2-10 µg 89Zr-AMG211 supplemented with unlabeled AMG 211 up to 500 µg protein dose were performed. A BiTE® that does not bind CEA, 89Zr-Mec14, served as a negative control. 89Zr-AMG211 integrity was determined in tumor lysates ex vivo. Intratumoral distribution was studied with IRDye800CW-AMG211. Moreover, 89Zr-AMG211 was manufactured according to Good Manufacturing Practice (GMP) guidelines for clinical trial NCT02760199. Results: 89Zr-AMG211 demonstrated dose-dependent tumor uptake at 6 hours. The highest tumor uptake was observed with 2 μg dose, and the lowest tumor uptake was observed with 500 μg dose. After 24 hours, higher uptake of 10 μg 89Zr-AMG211 occurred in CEA-positive xenografts, compared to CEA-negative xenografts. Although the blood half-life of 89Zr-AMG211 was ~1 hour, tumor retention persisted for at least 24 hours. 89Zr-Mec14 showed no tumor accumulation beyond background level. Ex vivo autoradiography revealed time-dependent disintegration of 89Zr-AMG211. 800CW-AMG211 was specifically localized in CEA-expressing viable tumor tissue. GMP-manufactured 89Zr-AMG211 fulfilled release specifications. Conclusions: 89Zr-AMG211 showed dose-dependent CEA-specific tumor targeting and localization in viable tumor tissue. Our data enabled its use to clinically evaluate AMG 211 in vivo behavior.

https://ift.tt/2NtnN9s

Neoantigens in ovarian cancer: embarrassment of riches or needles in a haystack?

Comprehensive genomic and transcriptomic analysis demonstrates that tumor-infiltrating T lymphocytes that react to mutated neo-epitopes could be identified in recurrent ovarian cancer. Two of these T cell populations reacted against TP53 hotspot missense mutations that are present in a wide variety of malignancies.

https://ift.tt/2J03qNT

High-energy trauma patients with pelvic fractures: management trends in Ontario, Canada

Publication date: Available online 6 July 2018

Source: Injury

Author(s): Stephen M. Mann, Daniel Banaszek, Katherine Lajkosz, Susan B. Brogly, Shelby M. Stanojev, Chris Evans, Davide D. Bardana, Jeff Yach, Stephen Hall

Abstract

Introduction

Although fractures of the pelvic ring account for only 2-3% of all fractures, they are present in approximately 7-20% of patients with high-energy polytrauma. High-energy pelvic fractures are life-threatening injuries, with mortality estimates ranging from 6-35%. The purpose of this study was to examine trends in the incidence, diagnosis, treatment, and mortality rates of high-energy pelvic fractures in Ontario, Canada over a 10-year period.

Methods

A cohort of 3915 patients who sustained a high-energy pelvic fracture in Ontario between 01 April 2005 and 31 March 2015 was identified using the Ontario Trauma Registry and administrative healthcare data linked by the Institute for Clinical Evaluative Science (ICES). Severely injured patients (defined as having an Injury Severity Score (ISS) of ≥16) with pelvic fractures following high-velocity mechanisms of injury were identified using applicable ICD-10 codes. Trends were assessed statistically using the Poisson and the Cochrane-Armitage tests for trend. Modified Poisson regression was used to model the adjusted risk ratio of mortality by pelvic fracture treatment.

Results

The incidence of pelvic fracture remained constant at approximately 4.6 cases per 100,000 population annually between 2005 and 2011. From 2012, there was a decrease in patients with ISS ≥ 16 due to changes in the calculation of the ISS. The proportion of patients presenting with ISS > 50 increased from 8.2% to 14.1% (p = 0.008) over the study period. Automobile collisions or pedestrians struck by vehicles accounted for over half of injuries. Approximately 6% of patients underwent angioembolisation. Treatment with external fixation (15.5% to 20.2%) or no surgical intervention (46.2% to 61.3%) increased from 2005 to 2015. Mortality remained constant (11% at 30 days), and laparotomy was the only major intervention not associated with decreased risk of death.

Conclusions

Stable mortality despite increasing injury severity suggests that the quality of care provided to patients with high-energy pelvic fractures has improved over time. However, unchanged incidence suggests the need for ongoing efforts aimed towards injury prevention. ISS at presentation was the most significant predictor of mortality in this patient population.

https://ift.tt/2u7rrOv

Erbin suppresses KSR1-mediated RAS/RAF signaling and tumorigenesis in colorectal cancer

Erbin belongs to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that plays important roles in orchestrating cell signaling. Here we show that Erbin functions as a tumor suppressor in colorectal cancer (CRC). Analysis of Erbin expression in CRC patient specimens revealed that Erbin was downregulated at both mRNA and protein levels in tumor tissues. Knockdown of Erbin disrupted epithelial cell polarity and increased cell proliferation in 3D culture. In addition, silencing Erbin resulted in increased amplitude and duration of signaling through Akt and RAS/RAF pathways. Erbin loss induced epithelial-mesenchymal transition (EMT), which coincided with a significant increase in cell migration and invasion. Erbin interacted with kinase suppressor of Ras 1 (KSR1) and displaced it from the RAF/MEK/ERK complex to prevent signal propagation. Furthermore, genetic deletion of Erbin in Apc knockout mice promoted tumorigenesis and significantly reduced survival. Tumor organoids derived from Erbin/Apc double knockout mice displayed increased tumor initiation potential and activation of Wnt signaling. Results from gene set enrichment analysis (GSEA) revealed that Erbin expression associated positively with the E-cadherin adherens junction pathway and negatively with Wnt signaling in human CRC. Taken together, our study identifies Erbin as a negative regulator of tumor initiation and progression by suppressing Akt and RAS/RAF signaling in vivo.

https://ift.tt/2u91RYz

Shisha microbiota: the good, the bad and the not so ugly

Over the last decade, there has been a rapid expansion of the trendy water pipe smoking around the world especially among younger adults. The initial objective of this study was to identify the microbiota of t...

https://ift.tt/2zogVXQ

Partners in anti-crime: how interferon-inducible GTPases and autophagy proteins team up in cell-intrinsic host defense

Jörn Coers | Hailey M Brown | Seungmin Hwang | Gregory A Taylor

https://ift.tt/2u0MamW

Risk-Stratified Breast Cancer Screening Ups Cost-Effectiveness

FRIDAY, July 6, 2018 -- Risk-stratified breast screening improves the cost-effectiveness of screening, according to a study published online July 5 in JAMA Oncology. Nora Pashayan, M.D., Ph.D., from University College London, and colleagues used...

https://ift.tt/2Nvj5Ik

IT Solutions for Easier EHRs Save Physicians Time, Burnout

FRIDAY, July 6, 2018 -- Yale Medicine is effectively targeting electronic health record (EHR) use and functionality as a way to improve physician job satisfaction and reduce burnout, according to an article published in the American Medical...

https://ift.tt/2KUotD6

Occupational Exposure Limits for Heat Stress Often Exceeded: CDC

FRIDAY, July 6, 2018 -- Based on recommendations from the U.S. Centers for Disease Control and Prevention's National Institute for Occupational Safety and Health and the American Conference of Governmental Industrial Hygienists, occupational...

https://ift.tt/2NwjOsT

Tick-Caused Meat Allergy on the Rise in the United States

FRIDAY, July 6, 2018 -- Red meat allergy caused by a bite from the lone star tick appears to be on the rise in the United States, a researcher says. More than 5,000 cases have been reported in the United States, up from 3,500 two years ago,...

https://ift.tt/2J2Ak0b

FDA: Zephyr Endobronchial Valve Approved for Severe Emphysema

FRIDAY, July 6, 2018 -- A new device, the Zephyr Endobronchial Valve (Zephyr Valve), has been approved by the U.S. Food and Drug Administration for the treatment of breathing difficulties associated with severe emphysema. During a procedure in a...

https://ift.tt/2KRaIs4

The ER – Glycogen Particle – Phagophore Triangle: A Hub Connecting Glycogenolysis and Glycophagy?

Abstract

Glycogen particle is an intracellular organelle, which serves as a carbohydrate reserve in various cells. The function of glycogen is not entirely known in several cell types. Glycogen can be mobilized for different purposes, which can be related to cellular metabolic needs, intracellular redox state, metabolic state of the whole organism depending on regulatory aspects and also on cell functions. Essentially there are two different ways of glycogen degradation localized in different cellular organelles: glycogenolysis or lysosomal breakdown by acid alpha-glucosidase. While glycogenolysis occurs in glycogen particles connected to endoplasmic reticulum membrane, glycogen particles can be also combined with phagophores forming autophagosomes. A subdomain of the endoplasmic reticulum membrane - omegasomes - are the sites for phagophore formation. Thus, three organelles, the endoplasmic reticulum, the phagophore and the glycogen particle forms a triangle in which glycogen degradation occurs. The physiological significance, molecular logic and regulation of the two different catabolic paths are summarized and discussed with special aspect on the role of glycogen particles in intracellular organelle homeostasis and on molecular pathology of the cell. Pathological aspects and some diseases connected to the two different degradation pathways of glycogen particles are also detailed.

https://ift.tt/2KGTMFp

Quantitative Analysis on Ex Vivo Nonlinear Microscopy Images of Basal Cell Carcinoma Samples in Comparison to Healthy Skin

Abstract

Basal cell carcinoma (BCC) is the most frequent malignant neoplasm in the Caucasian population. There are several therapeutic options for BCC, but surgical excision is considered gold standard treatment. As BCCs often have poorly defined borders, the clinical assessment of the tumor margins can be challenging. Therefore, there is an increasing demand for efficient in vivo imaging techniques for the evaluation of tumor borders prior to and during surgeries. In the near future, nonlinear microscopy techniques might meet this demand. We measured the two-photon excitation fluorescence (TPEF) signal of nicotinamide adenine dinucleotide hydride (NADH) and elastin and second harmonic generation (SHG) signal of collagen on 10 ex vivo healthy control and BCC skin samples and compared the images by different quantitative image analysis methods. These included integrated optical density (IOD) measurements on TPEF and SHG images and application of fast Fourier transform (FFT), CT-FIRE and CurveAlign algorithms on SHG images to evaluate the collagen structure. In the BCC samples, we found significantly lower IOD of both the TPEF and SHG signals and higher collagen orientation index utilizing FFT. CT-FIRE algorithm revealed increased collagen fiber length and decreased fiber angle while CurveAlign detected higher fiber alignment of collagen fibers in BCC. These results are in line with previous findings which describe pronounced changes in the collagen structure of BCC. In the future, these novel image analysis methods could be integrated in handheld nonlinear microscope systems, for sensitive and specific identification of BCC.

https://ift.tt/2MSxPA4

Accuracy of Photogrammetry for Detecting Adolescent Idiopathic Scoliosis Progression

Publication date: Available online 6 July 2018

Source: The Spine Journal

Author(s): Jefferson Soares Leal, Rozilene Maria Cota Aroeira, Vinicius Gressler, Marcelo Greco, Antônio Eustáquio. M. Pertence, Joel Alves Lamounier

Abstract

Background Context

The gold standard method of monitoring the evolution of scoliosis has been serial standing, posteroanterior, full-length spine radiographs with curvature measurements using the Cobb method. However, over the course of follow-up, patients can receive high radiation doses. Various studies have shown that repeated exposure to radiation in children and adolescents can be harmful to their health.

Purpose

To determine the accuracy of photogrammetry in evaluating the progression of adolescent idiopathic scoliosis in comparison with radiography.

Study Design

Diagnostic study

Patient Sample

Ninety adolescents subjected to radiographic follow-up of idiopathic scoliosis.

Outcome Measures

The angle of scoliotic curvature was measured using the Cobb radiographic method and photogrammetry. An increase of five degrees or more between two radiographic exams was considered a progression of the curvature and was defined as the standard for calculations of sensitivity, specificity, predictive value and accuracy of the photogrammetric method for measuring scoliosis progression.

Methods

Patients were subjected to radiographic and photogrammetric exams concomitantly and were reevaluated after an average of 8.6 months. The exams were analyzed separately and independently by two examiners for progression of scoliosis.

Results

The measurements of the curves at the beginning of the study were 39.5 ± 16.7 degrees and 39.5 ± 14.3 degrees for radiographic and photogrammetric exams, respectively (p=1.0). At the end of the study, the measurements of the curves were 40.2 ± 16.2 degrees and 41.3 ± 15.1 degrees for the radiographic and photogrammetric exams, respectively (p=0.310). The photogrammetric method had an accuracy of 89% (CI 95% = 82.5–95.5) for the detection of scoliosis progression, with a sensitivity of 94.4% (CI 95% = 89.6–99.2), a specificity of 86.7% (CI 95% = 79.7–93.7), a positive predictive value of 75.5% (CI 95% = 66.6–84.4), a negative predictive value of 97.2% (CI 95% = 93.8–100) and a Kappa index of 0.75 (CI 95% = 66.1–83.9). The interclass correlation coefficient (ICC) between the two methods was 0.74 (CI 95% = 0.65–0.81; p=0).

Conclusion

The photogrammetric method showed good performance for detecting the progression of adolescent idiopathic scoliosis in comparison with the radiographic exam method.

https://ift.tt/2zhtzbh

Enhancement and bilateral synchronization of ripples in atypical benign epilepsy of childhood with centrotemporal spikes

Benign epilepsy in childhood with centrotemporal spikes (BECTS), or Rolandic epilepsy is the most common childhood epilepsy syndrome, and it is often described clinically as "benign" drug-sensitive epilepsy (Fejerman, 2008). The seizures occur during sleep in most children. Atypical clinical presentations of BECTS have been reported in some patients (Fejerman, 2009). One such presentation includes frequent drug-resistant seizures (Datta, 2007) that could result in permanent learning and behavioral disabilities (Hahn, 2001; Uliel-Sibony, 2015); this presentation is termed "atypical forms" of BECTS (ABECTS, atypical Rolandic epilepsy; Fejerman 2009).

https://ift.tt/2m0abGp

Perceptions of traditional Chinese medicine for chronic disease care and prevention: a cross-sectional study of Chinese hospital-based health care professionals

In China, demands for disease prevention and health care and the prevalence of chronic non-communicable diseases have increased. TCM and general hospitals are increasingly utilizing TCM strategies for chronic ...

https://ift.tt/2KSatgg

Water extract of Clinacanthus nutans leaves exhibits in vitro, ex vivo and in vivo anti-angiogenic activities in endothelial cell via suppression of cell proliferation

Clinacanthus nutans (Burm. f.) Lindau. has traditionally been using in South East Asia countries to manage cancer. However, scientific evidence is generally lacking to support this traditional claim. This study a...

https://ift.tt/2IXXWmx

Clinical characteristics and short-term prognosis of LGI1 antibody encephalitis: a retrospective case study

Recently, most reports of Leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis are from Europe and the US, while the short term outcome and clinical characteristics of Chinese patients are rarely rep...

https://ift.tt/2KNnyrf

TPL2, a therapeutic potential target for cancer

Dear Editor,

https://ift.tt/2KE7Wr2

Immune checkpoint blockade as a potential therapeutic strategy for undifferentiated malignancies

Undifferentiated malignancies (UMs) encompass a diverse set of aggressive tumors that pose not only a diagnostic challenge but also a challenge for clinical management. Most tumors in this category are currently treated empirically with nonspecific chemotherapeutic agents that yield extremely poor clinical responses. Given that UMs are inherently genetically unstable neoplasms with the potential for immune dysregulation and increased neoantigen production, they are likely to be particularly amenable to immune checkpoint inhibitors, which target programmed cell death protein 1 (PD-1) or its ligands, PD-L1 and PD-L2, to promote T-cell antitumor activity.

https://ift.tt/2MW3UHc

Repairing the human esophagus with tissue engineering

https://ift.tt/2lYxiB9

Managing underperformance in endoscopy: a pragmatic approach

GI endoscopy is increasingly the procedure of choice for the investigation and management of upper and lower GI symptoms. Internationally, key performance indicators (KPIs) are often used to provide key data points and auditable outcomes for endoscopists and endoscopy services with published standards existing for colonoscopy, bowel cancer screening, flexible sigmoidoscopy, ERCP and upper GI endoscopy. Quality assurance (QA) and training programs aim to ensure high skill levels of endoscopists and, supported by quality improvement programs (QI), aim to raise the quality of endoscopy service provision.

https://ift.tt/2zj5twO

Technical feasibility of endoscopic submucosal dissection for local failure after chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma

Salvage endoscopic submucosal dissection (ESD) after chemoradiotherapy might be technically difficult due to radiation-induced fibrosis. We aimed to evaluate the technical feasibility of ESD for local failure after chemoradiotherapy for esophageal squamous cell carcinoma (ESCC), and for other primary lesions within the irradiation field.

https://ift.tt/2lYxfoX

The association among diet, dietary fiber, and bowel preparation at colonoscopy

Pre-colonoscopy dietary restrictions vary widely and lack evidence-based guidance. We investigated whether fiber and various other foods/macronutrients consumed during the 3 days before colonoscopy are associated with bowel preparation quality.

https://ift.tt/2ud4f0n

A prospective multicenter study using a new multiband mucosectomy device for endoscopic resection of early neoplasia in Barrett’s esophagus

Early neoplasia in Barrett's esophagus (BE) can be effectively and safely removed by endoscopic resection (ER) using multi-band mucosectomy (MBM). This study aimed to document performance of a novel MBM device designed for improved visualization, easier passage of accessories, and better suction power compared with other marketed MBM devices.

https://ift.tt/2lVP4Vw

Effects of Delayed Cord Clamping on Four-Month Ferritin Levels, Brain Myelin Content, and Neurodevelopment: A Randomized Controlled Trial

To evaluate whether placental transfusion influences brain myelination at 4 months of age.

https://ift.tt/2tY99iA

Preterm Infant Outcomes after Randomization to Initial Resuscitation with FiO2 0.21 or 1.0

To determine rates of death or neurodevelopmental impairment (NDI) at 2 years corrected age (primary outcome) in children <32 weeks' gestation randomized to initial resuscitation with a fraction of inspired oxygen (FiO2) value of 0.21 or 1.0.

https://ift.tt/2ucciKP

Low Interleukin-7 Receptor Messenger RNA Expression Is Independently Associated With Day 28 Mortality in Septic Shock Patients

Objectives: Septic shock is the primary cause of death in ICUs. A better comprehension of its pathophysiology, in particular, the immune alteration mechanisms, opened new therapeutic perspectives such as the recombinant interleukin-7. The use of biomarkers could improve the identification of eligible patients for this therapy. The soluble form of the interleukin-7 appears as a promising candidate in this regard since an association between its high plasmatic level and mortality in critically ill patients has been demonstrated. Because there are no data available on the transcriptional regulation of the interleukin-7 receptor in such patients, this study aimed to explore the expression level of different interleukin-7 receptor transcripts after septic shock and evaluate their association with mortality. Design: Retrospective discovery cohort (30 patients) and validation cohort (177 patients). Setting: Two French ICUs (discovery study) and six French ICUs (validation study). Patients: Adult septic shock patients. Interventions: None. Measurements and Main Results: The quantification of several interleukin-7 receptor transcripts using specific reverse transcription quantitative polymerase chain reaction designs allowed for global evaluation of interleukin-7 receptor gene expression in whole blood. In the discovery cohort, all interleukin-7 receptor transcripts studied were expressed at lower levels in septic shock patients than in healthy volunteers. Interleukin-7 receptor gene expression at day 3 after septic shock diagnosis was associated with day 28 mortality. Patients at a lower risk of death showed higher expression levels. These results were confirmed in the independent validation cohort. Interestingly, using a threshold obtained on the discovery cohort, we observed in the validation cohort a high negative predictive value for day 28 mortality for the transcript encoding the membrane form of interleukin-7 receptor (0.86; 95% CI, 0.79–0.93). Conclusions: Interleukin-7 receptor transcripts appear as biomarkers of impaired adaptive immune response in septic shock patients and as a promising tool for patient stratification in clinical trials evaluating immunoadjuvant therapies. 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. The experimental work was performed at the Hospices Civils de Lyon – bioMérieux - Université Claude Bernard Lyon 1, Joint Research Unit, Lyon, France. Supported, in part, by grants from bioMérieux and Hospices Civils de Lyon, and was part of Advanced Diagnostic for New Therapeutic Approaches, a program dedicated to personalized medicine, coordinated by Institut Mérieux and supported by French public agency BPI France. Dr. Delwarde and Peronnet contributed equally to this work. 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). All authors work in a Joint Research Unit cofunded by the Hospices Civils de Lyon, bioMérieux, and Université Claude Bernard Lyon 1. Drs. Delwarde and Venet, Mr. Meunier, and Drs. Lepape, Rimmelé, and Monneret are employees of Hospices Civils de Lyon. Dr. Peronnet, Ms. Cerrato, and Drs. Mouillaux, Pachot, and Textoris are employees of bioMérieux. This study was part of Advanced Diagnostic for New Therapeutic Approaches (ADNA), a program dedicated to personalized medicine, coordinated by Institut Mérieux, and supported by the French public agency Banque Publique d'Investissement (BPI) France. Drs. Delwarde, Peronnet, and Venet, Ms. Cerrato, and Drs. Lepape, Monneret, and Textoris are coinventors on three patent families covering interleukin-7 receptor biomarkers. This does not alter the authors' adherence to all Critical Care Medicine policies on sharing data and materials. Dr. Peronnet disclosed that she is a coinventor on the pending patent WO2017093672, and that this study was part of ADNA. Dr. Venet's institution received funding from bioMerieux (he works in a joint research unit between bioMerieux and the Hospices Civils de Lyon, but does not receive any financial retribution from bioMerieux based on this collaboration). Dr. Lepape disclosed that he is a coinventors of patents WO2013140103 and WO2015040328. Drs. Pachot and Textoris' institution received funding from ADNA. Dr. Pachot received funding from bioMérieux as an employee of bioMérieux; he received support for article research from ADNA, and he disclosed government work. Dr. Textoris disclosed that he is an employee of bioMeriaux and Hospices Civils de Lyon, and he is listed as an inventor of patent WO2017093672 (pending), for which he does not own rights. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: estelle.peronnet@biomerieux.com Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Features of Adult Hyperammonemia Not Due to Liver Failure in the ICU

Objectives: To evaluate the epidemiology of hyperammonemia unrelated to liver failure in the critical care setting. Design: Retrospective case series. Setting: Critically ill patients admitted to ICUs at Mayo Clinic, Rochester, MN (medical ICU, two mixed medical-surgical ICUs, coronary care unit, or the cardiosurgical ICU) between July 1, 2004, and October 31, 2015. Patients: Adult critically ill patients with hyperammonemia not related to acute or chronic liver failure. We excluded patients with diagnosis of moderate or severe liver disease, hyperbilirubinemia, and patients who denied the use of their medical records. Interventions: None. Measurements and Main Results: Of 3,908 ICU patients with hyperammonemia, 167 (4.5%) had no evidence of acute or chronic liver failure. One-hundred one patients (60.5%) were male with median age of 65.7 years (interquartile range, 50–74.5 yr) and median serum ammonia level of 68 µg/dL (interquartile range, 58–87 µg/dL). Acute encephalopathy was present in 119 patients (71%). Predisposing conditions included malnutrition 27 (16%), gastric bypass six (3.6%), total parenteral nutrition four (2.4%); exposure to valproic acid 17 (10%); status epilepticus 11 (6.6%), high tumour burden 19 (11.3%), and renal failure 82 (49.1%). Urea cycle defects were diagnosed in seven patients (4.1%). Hospital mortality was high (30%), and median ammonia level was higher among the nonsurvivors (74 vs 67 µg/dL; p = 0.05). Deaths were more likely in hyperammonemic patients who were older (p = 0.016), had greater illness severity (higher Acute Physiology and Chronic Health Evaluation III score, p

https://ift.tt/2KS0NlW

Double Cycling During Mechanical Ventilation: Frequency, Mechanisms, and Physiologic Implications

Objectives: Double cycling generates larger than expected tidal volumes that contribute to lung injury. We analyzed the incidence, mechanisms, and physiologic implications of double cycling during volume- and pressure-targeted mechanical ventilation in critically ill patients. Design: Prospective, observational study. Setting: Three general ICUs in Spain. Patients: Sixty-seven continuously monitored adult patients undergoing volume control-continuous mandatory ventilation with constant flow, volume control-continuous mandatory ventilation with decelerated flow, or pressure control-continuous mandatory mechanical ventilation for longer than 24 hours. Interventions: None. Measurements and Main Results: We analyzed 9,251 hours of mechanical ventilation corresponding to 9,694,573 breaths. Double cycling occurred in 0.6%. All patients had double cycling; however, the distribution of double cycling varied over time. The mean percentage (95% CI) of double cycling was higher in pressure control-continuous mandatory ventilation 0.54 (0.34–0.87) than in volume control-continuous mandatory ventilation with constant flow 0.27 (0.19–0.38) or volume control-continuous mandatory ventilation with decelerated flow 0.11 (0.06–0.20). Tidal volume in double-cycled breaths was higher in volume control-continuous mandatory ventilation with constant flow and volume control-continuous mandatory ventilation with decelerated flow than in pressure control-continuous mandatory ventilation. Double-cycled breaths were patient triggered in 65.4% and reverse triggered (diaphragmatic contraction stimulated by a previous passive ventilator breath) in 34.6% of cases; the difference was largest in volume control-continuous mandatory ventilation with decelerated flow (80.7% patient triggered and 19.3% reverse triggered). Peak pressure of the second stacked breath was highest in volume control-continuous mandatory ventilation with constant flow regardless of trigger type. Various physiologic factors, none mutually exclusive, were associated with double cycling. Conclusions: Double cycling is uncommon but occurs in all patients. Periods without double cycling alternate with periods with clusters of double cycling. The volume of the stacked breaths can double the set tidal volume in volume control-continuous mandatory ventilation with constant flow. Gas delivery must be tailored to neuroventilatory demand because interdependent ventilator setting–related physiologic factors can contribute to double cycling. One third of double-cycled breaths were reverse triggered, suggesting that repeated respiratory muscle activation after time-initiated ventilator breaths occurs more often than expected. Additional investigators from the Asynchronies in the Intensive Care Unit (ASYNICU) Group are listed in Appendix 1. 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 projects PI09/91074 and PI13/02204, integrated in the Plan Nacional de R+D+I, and cofunded by the Instituto de Salud Carlos III Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional, Centro de Investigación Biomédica en Red en Enfermedades Respiratorias, Fundación Mapfre, Fundació Parc Taulí, Plan Avanza TSI-020302-2008-38, Ministerio de Ciencia e Innovación, and Ministerio de Industria, Turismo y Comercio (Spain). Mr. Montanya and Drs. Blanch, Murias, and Lucangelo own stock options of Better Care SL, which is a research and development spinoff of Corporació Sanitària Parc Taulí (Spain). Dr. Subirà disclosed work for hire. Drs. Murias and Blanch disclosed that they are inventors of one Corporació Sanitaria Parc Taulí owned US patent: "Method and system for managed related patient parameters provided by a monitoring device," U.S. Patent No. 12/538,940. Dr. Kacmarek is a consultant for Medtronic and Orange Medical and has received research grants from Medtronic and Venner Medical. His institution received funding from Medtronic and Venner Medical, and he received funding from Medtronic, Orange Medical, and Teleflex. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: lblanch@tauli.cat Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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The Impact of Early Adequate Treatment on Extubation and Discharge Alive of Patients With Pseudomonas aeruginosa-Related Ventilator-Associated Pneumonia

Objectives: We aim to examine the effect of early adequate treatment in comparison with inadequate or delayed treatment on being extubated or discharged alive over time, in patients with Pseudomonas aeruginosa-related ventilator-associated pneumonia. Design: Retrospective analyses of a prospective observational multicenter cohort study. Setting: ICU. Patients: Patients of the French prospective database (OUTCOMEREA) were included if they acquired a ventilator-associated pneumonia due to P. aeruginosa between 1997 and 2014 and were mechanically ventilated for more than 48 hours. Interventions: Early adequate treatment in comparison with inadequate or delayed adequate treatment. Measurements and Main Results: Multistate models were applied to estimate the time-dependent probability of being extubated or discharged alive, and separate Cox regression analyses were used to assess the treatment effect on all important events that influence the outcome of interest. A propensity score-adjusted innovative regression technique was used for a combined and comprehensive patient-relevant summary effect measure. No evidence was found for a difference between adequate and inadequate or delayed treatment on being extubated or discharged alive. However, for all patients, the probability of being extubated or discharged alive remains low and does not exceed 50% even 40 days after a P. aeruginosa-related ventilator-associated pneumonia. Conclusions: Early adequate treatment does not seem to be associated with an improved prognosis. Its potential benefit requires further investigation in larger observational studies. 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). Drs. Sommer and Timsit and Ms. von Cube were supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement n [115737-2 – COMBACTE-MAGNET], resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies. Dr. Wolkewitz received funding from the German Research Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: sommer@imbi.uni-freiburg.de Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Outcomes in Patients With Severe West Nile Neuroinvasive Disease

Objective: To assess the long-term outcomes of patients hospitalized with severe West Nile neuroinvasive disease. Design: Retrospective cohort. Setting: Patients admitted to a referral center (Saint Mary's Hospital, Mayo Clinic). Participants: Twenty-six patients with West Nile neuroinvasive disease were identified by retrospective search of electronic database of Saint Mary's Hospital from January 1999 to November 2016. Interventions: Retrospective electronic medical records review and prospective telephone follow-up. Measurements and Main Results: Functional disability and cognitive outcomes were evaluated with the modified Rankin Scale and the Telephone Interview for Cognitive Status scores. Data on the time that the patient returned home after the hospitalization for West Nile neuroinvasive disease and the time of return to work were also collected. We identified 26 patients (81% males), 59 ± 17 years old. After a median hospital stay of 14.5 days (3–126), four patients died and 90% of survivors had a modified Rankin Scale of 3–5. Two additional patients died, and 80% of survivors had a modified Rankin Scale of 0–2 after a median follow-up of 73 months (1–144). Seven patients had cognitive impairment, which was severe in two of them. The combination of encephalitis and acute flaccid paralysis at presentation was associated with lower likelihood of returning home within 1 month after discharge (p

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Deresuscitation of Patients With Iatrogenic Fluid Overload Is Associated With Reduced Mortality in Critical Illness

Objectives: To characterize current practice in fluid administration and deresuscitation (removal of fluid using diuretics or renal replacement therapy), the relationship between fluid balance, deresuscitative measures, and outcomes and to identify risk factors for positive fluid balance in critical illness. Design: Retrospective cohort study. Setting: Ten ICUs in the United Kingdom and Canada. Patients: Adults receiving invasive mechanical ventilation for a minimum of 24 hours. Interventions: None. Measurements and Main Results: Four-hundred patients were included. Positive cumulative fluid balance (fluid input greater than output) occurred in 87.3%: the largest contributions to fluid input were from medications and maintenance fluids rather than resuscitative IV fluids. In a multivariate logistic regression model, fluid balance on day 3 was an independent risk factor for 30-day mortality (odds ratio 1.26/L [95% CI, 1.07–1.46]), whereas negative fluid balance achieved in the context of deresuscitative measures was associated with lower mortality. Independent predictors of greater fluid balance included treatment in a Canadian site. Conclusions: Fluid balance is a practice-dependent and potentially modifiable risk factor for adverse outcomes in critical illness. Negative fluid balance achieved with deresuscitation on day 3 of ICU stay is associated with improved patient outcomes. Minimization of day 3 fluid balance by limiting maintenance fluid intake and drug diluents, and using deresuscitative measures, represents a potentially beneficial therapeutic strategy which merits investigation in randomized trials. A full list of Role of Active Deresuscitation After Resuscitation (RADAR) Investigators is listed in Appendix 1. 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 a doctoral fellowship award to Dr. Silversides from the Northern Ireland Health and Social Care Research and Development Division. Dr. Silversides' institution received funding from British Journal of Anaesthesia (BJA)/Royal College of Anaesthetists (RCoA) project grant WKR0-2017-0019. Dr. Lapinsky received other support from research grants from the Chest Foundation and Ontario Lung Association for an unrelated research project. Dr. McAuley's institution received funding from v Division (Doctoral Fellowship grant for Dr. Silversides), BJA/RCoA Project Grant WKR0-2017-0019, National Institute of Health Research Health Technology Assessment grant application pending, and GlaxoSmithKline, and he received other funding from Bayer, Boehringer Ingelheim, Peptinnovate. Dr. Marshall received funding from the Data and Safety Monitoring Board of Asahi-Kasei Pharma, Bristol-Myers Squibb (Advisory Board), and Regeneron. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: jon.silversides@belfasttrust.hscni.net Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Benzodiazepine Use and Neuropsychiatric Outcomes in the ICU: A Systematic Review

Objectives: A systematic assessment of the role of benzodiazepine use during ICU stay as a risk factor for neuropsychiatric outcomes during and after ICU admission. Data Sources: PubMed/Medline, EMBASE, The Cochrane Library, CINAHL, and PsychINFO. Study Selection: Databases were searched independently by two reviewers for studies in adult (former) ICU patients, reporting benzodiazepine use, and neuropsychiatric outcomes of delirium, posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction. Data Extraction: Data were extracted using a piloted extraction form; methodological quality of eligible studies was assessed by applying the Quality Index checklist. Data Synthesis: Forty-nine of 3,066 unique studies identified were included. Thirty-five studies reported on neuropsychiatric outcome during hospitalization, 12 after discharge, and two at both time points. Twenty-four studies identified benzodiazepine use as a risk factor for delirium, whereas seven studies on delirium or related outcomes did not; six studies reported mixed findings. Studies with high methodological quality generally found benzodiazepine use to be a risk factor for the development of delirium. Five studies reported an association between benzodiazepine use and symptoms of posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction after ICU admission; five studies reported mixed findings, and in four studies, no association was found. No association was found with methodological quality and sample size for these findings. Meta-analysis was not feasible due to major differences in study methods. Conclusions: The majority of included studies indicated that benzodiazepine use in the ICU is associated with delirium, symptoms of posttraumatic stress disorder, anxiety, depression, and cognitive dysfunction. Future well-designed studies and randomized controlled trials are necessary to rule out confounding by indication. 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. Hillegers's institution received funding from Fonds Psychische Gezondhei, and she received support for article research from Fonds Psychische Gezondhei. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: L.Kok@umcutrecht.nl Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Methodologic Innovation in Creating Clinical Practice Guidelines: Insights From the 2018 Society of Critical Care Medicine Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption Guideline Effort

Objectives: To describe novel guideline development strategies created and implemented as part of the Society of Critical Care Medicine's 2018 clinical practice guidelines for pain, agitation (sedation), delirium, immobility (rehabilitation/mobility), and sleep (disruption) in critically ill adults. Design: We involved critical illness survivors from start to finish, used and expanded upon Grading of Recommendations, Assessment, Development and Evaluation methodology for making recommendations, identified evidence gaps, and developed communication strategies to mitigate challenges. Setting/Subjects: Thirty-two experts from five countries, across five topic-specific sections; four methodologists, two medical librarians, four critical illness survivors, and two Society of Critical Care Medicine support staff. Interventions: Unique approaches included the following: 1) critical illness survivor involvement to help ensure patient-centered questions and recommendations; 2) qualitative and semiquantitative approaches for developing descriptive statements; 3) operationalizing a three-step approach to generating final recommendations; and 4) systematic identification of evidence gaps. Measurements and Main Results: Critical illness survivors contributed to prioritizing topics, questions, and outcomes, evidence interpretation, recommendation formulation, and article review to ensure that their values and preferences were considered in the guidelines. Qualitative and semiquantitative approaches supported formulating descriptive statements using comprehensive literature reviews, summaries, and large-group discussion. Experts (including the methodologists and guideline chairs) developed and refined guideline recommendations through monthly topic-specific section conference calls. Recommendations were precirculated to all members, presented to, and vetted by, most members at a live meeting. Final electronic voting provided links to all forest plots, evidence summaries, and "evidence to decision" frameworks. Written comments during voting captured dissenting views and were integrated into evidence to decision frameworks and the guideline article. Evidence gaps, reflecting clinical uncertainty in the literature, were identified during the evidence to decision process, live meeting, and voting and formally incorporated into all written recommendation rationales. Frequent scheduled "check-ins" mitigated communication gaps. Conclusions: Our multifaceted, interdisciplinary approach and novel methodologic strategies can help inform the development of future critical care clinical practice guidelines. 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). Mr. Devlin has received research funding from the National Institute of Aging, National Heart, Lung and Blood Institute, and AstraZeneca Pharmaceuticals, is on the editorial board of Critical Care Medicine, and is the president of the American Delirium Society. Dr. Skrobik participates in the American Thoracic Society (ATS) and the American College of Chest Physicians, and she is on the editorial board for Intensive Care Medicine and Chest. Dr. Rochwerg participates as a guideline methodologist for other organizations (i.e., ATS and Canadian Blood Service) in addition to Society of Critical Care Medicine. Dr. Nunnally participates in the Society of Critical Care Anesthesiologists, International Anesthesia Research Society, and American Society of Anesthesiology (ASA). Dr. Needham is a principal investigator on a National Institutes of Health (NIH)-funded, multicentered randomized trial (R01HL132887) evaluating nutrition and exercise in acute respiratory failure and, related to this trial, is currently in receipt of an unrestricted research grant and donated amino acid product from Baxter Healthcare and an equipment loan from Reck Medical Devices to two of the participating study sites, external to his institution. Dr. Pandharipande's institution received funding from Hospira (research grant to purchase study drug [dexmedetomidine] in collaboration with a NIH-funded RO1 study) and disclosed that he is the past president of the American Delirium Society. Dr. Slooter has disclosed that he is involved in the development of an electroencephalography-based delirium monitor, where any (future) profits from electroencephalography-based delirium monitoring will be used for future scientific research only. Dr. Kho received funding from Restorative Therapies (Baltimore, MD) (loaned two supine cycle ergometers for ongoing research). Ms. Price has disclosed that she is a medical librarian working at Johns Hopkins University, and she consults as an information specialist to the Cochrane Urology Review Group. Dr. Flood participates on the Society of Obstetric Anesthesia and Perinatology research committee and the ASA Chronic Pain Committee. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: j.devlin@neu.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Association between Medicaid Expansion under the Affordable Care Act and Preemptive Listings for Kidney Transplantation

Background and objectives

Before 2014, low-income individuals in the United States with non–dialysis-dependent CKD had fewer options to attain health insurance, limiting their opportunities to be preemptively wait-listed for kidney transplantation. We examined whether expanding Medicaid under the Affordable Care Act was associated with differences in the number of individuals who were pre-emptively wait-listed with Medicaid coverage.

Design, setting, participants, & measurements

Using the United Network of Organ Sharing database, we performed a retrospective observational study of adults (age≥18 years) listed for kidney transplantation before dialysis dependence between January 1, 2011–December 31, 2013 (pre-Medicaid expansion) and January 1, 2014–December 31, 2016 (post-Medicaid expansion). In multinomial logistic regression models, we compared trends in insurance types used for pre-emptive wait-listing in states that did and did not expand Medicaid with a difference-in-differences approach.

Results

States that fully implemented Medicaid expansion on January 1, 2014 ("expansion states," n=24 and the District of Columbia) had a 59% relative increase in Medicaid-covered pre-emptive listings from the pre-expansion to postexpansion period (from 1094 to 1737 listings), compared with an 8.8% relative increase (from 330 to 359 listings) among 19 Medicaid nonexpansion states (P<0.001). From the pre- to postexpansion period, the adjusted proportion of listings with Medicaid coverage decreased by 0.3 percentage points among nonexpansion states (from 4.0% to 3.7%, P=0.09), and increased by 3.0 percentage points among expansion states (from 7.0% to 10.0%, P<0.001). Medicaid expansion was associated with absolute increases in Medicaid coverage by 1.4 percentage points among white listings, 4.0 percentage points among black listings, 5.9 percentage points among Hispanic listings, and 5.3 percentage points among other listings (P<0.001 for all comparisons).

Conclusions

Medicaid expansion was associated with an increase in the proportion of new pre-emptive listings for kidney transplantation with Medicaid coverage, with larger increases in Medicaid coverage among racial and ethnic minority listings than among white listings.

https://ift.tt/2KFY4gg

BP Measurement Techniques: What They Mean for Patients with Kidney Disease

Patients with CKD typically have hypertension. Manual BP measurement in the office setting was used to define hypertension, establish eligibility, and assess BP targets in the epidemiologic studies and early randomized, controlled trials that inform current management of hypertension. Use of automated oscillometric devices has largely replaced manual BP measurement in the office and clinical trials. These newer devices may reduce the white coat effect and facilitate guideline-adherent measurement protocols. Obtaining BP measurements outside of the office with home and ambulatory BP monitoring is now more common. Out of office BPs are especially important in patients with CKD, because reduced GFR and proteinuria are associated with masked hypertension (normal office BP and elevated BP outside of the office), elevated nighttime BP, and abnormal diurnal variation in BP, all of which are associated with higher risk for target organ damage and adverse outcomes. Also, it is now feasible to routinely measure central BP and central hemodynamics. These measures are of greater importance to patients with CKD given the higher prevalence of increased sympathetic tone, arteriosclerosis, and inflammation as well as impaired sodium excretion and endothelial dysfunction, which lead to alterations in central BPs in this population. In this review, we describe various BP measurement techniques and how they apply to the care of patients with CKD.

https://ift.tt/2KFXXRK

Overcoming Translational Barriers in Acute Kidney Injury: A Report from an NIDDK Workshop

AKI is a complex clinical condition associated with high mortality, morbidity, and health care costs. Despite improvements in methodology and design of clinical trials, and advances in understanding the underlying pathophysiology of rodent AKI, no pharmacologic agent exists for the prevention or treatment of AKI in humans. To address the barriers that affect successful clinical translation of drug targets identified and validated in preclinical animal models of AKI in this patient population, the National Institute of Diabetes and Digestive and Kidney Diseases convened the "AKI Outcomes: Overcoming Barriers in AKI" workshop on February 10–12, 2015. The workshop used a reverse translational medicine approach to identify steps necessary to achieve clinical success. During the workshop, breakout groups were charged first to design feasible, phase 2, proof-of-concept clinical trials for delayed transplant graft function, prevention of AKI (primary prevention), and treatment of AKI (secondary prevention and recovery). Breakout groups then were responsible for identification of preclinical animal models that would replicate the pathophysiology of the phase 2 proof-of-concept patient population, including primary and secondary end points. Breakout groups identified considerable gaps in knowledge regarding human AKI, our understanding of the pathophysiology of AKI in preclinical animal models, and the fidelity of cellular and molecular targets that have been evaluated preclinically to provide information regarding human AKI of various etiologies. The workshop concluded with attendees defining a new path forward to a better understanding of the etiology, pathology, and pathophysiology of human AKI.

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Mandating Staffing Ratios in Hemodialysis Facilities: California SB 349 and Unintended Consequences

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Burden of Proof for Tolvaptan in ADPKD: Did REPRISE Provide the Answer?

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Introduction to Nephropharmacology for the Clinician: A New CJASN Series

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The Affordable Care Act, Kidney Transplant Access, and Kidney Disease Care in the United States

https://ift.tt/2MVhNp2

Prevalence of Central Vein Stenosis in Patients Referred for Vein Mapping

Background and objectives

Central vein stenosis is considered to be common in patients on hemodialysis but its exact prevalence is not known. In this study, we report the prevalence of central vein stenosis in patients with CKD referred for vein mapping.

Design, setting, participants, & measurements

We conducted a retrospective study of adult patients who had bilateral upper extremity venographic vein mapping from September 1, 2011 to December 31, 2015. Patients with and without stenosis were compared for differences in clinical or demographic characteristics. Multiple logistic regression was used to identify independent associations between patient characteristics and central vein stenosis.

Results

There were 525 patients who underwent venographic vein mapping during the study period, 27% of whom were referred before initiation of hemodialysis. The mean age (±SD) and body mass index were 59 (±15) years and 28 (±7), respectively. Women accounted for 45% of patients; 82% were black. The prevalence of central vein stenosis was 10% (95% confidence interval [95% CI], 8% to 13%) for the whole group, and 13% (95% CI, 10% to 17%) among patients with tunneled central venous dialysis catheters. Current use of tunneled hemodialysis catheters (odds ratio [OR], 14.5; 95% CI, 3.25 to 65.1), presence of cardiac rhythm devices (OR, 5.07; 95% CI, 1.82 to 14.11), previous history of fistula or graft (OR, 3.28; 95% CI, 1.58 to 6.7), and history of previous kidney transplant (OR, 18; 95% CI, 4.7 to 68.8) were independently associated with central vein stenosis.

Conclusions

In this population, the prevalence of central vein stenosis was 10% and was clustered among those with tunneled hemodialysis catheters, cardiac rhythm device, and previous history of dialysis access or transplant.

https://ift.tt/2KEoOhd

Risk Factors and Outcomes of Rapid Correction of Severe Hyponatremia

Background and objectives

Rapid correction of severe hyponatremia can result in serious neurologic complications, including osmotic demyelination. Few data exist on incidence and risk factors of rapid correction or osmotic demyelination.

Design, setting, participants, & measurements

In a retrospective cohort of 1490 patients admitted with serum sodium <120 mEq/L to seven hospitals in the Geisinger Health System from 2001 to 2017, we examined the incidence and risk factors of rapid correction and osmotic demyelination. Rapid correction was defined as serum sodium increase of >8 mEq/L at 24 hours. Osmotic demyelination was determined by manual chart review of all available brain magnetic resonance imaging reports.

Results

Mean age was 66 years old (SD=15), 55% were women, and 67% had prior hyponatremia (last outpatient sodium <135 mEq/L). Median change in serum sodium at 24 hours was 6.8 mEq/L (interquartile range, 3.4–10.2), and 606 patients (41%) had rapid correction at 24 hours. Younger age, being a woman, schizophrenia, lower Charlson comorbidity index, lower presentation serum sodium, and urine sodium <30 mEq/L were associated with greater risk of rapid correction. Prior hyponatremia, outpatient aldosterone antagonist use, and treatment at an academic center were associated with lower risk of rapid correction. A total of 295 (20%) patients underwent brain magnetic resonance imaging on or after admission, with nine (0.6%) patients showing radiologic evidence of osmotic demyelination. Eight (0.5%) patients had incident osmotic demyelination, of whom five (63%) had beer potomania, five (63%) had hypokalemia, and seven (88%) had sodium increase >8 mEq/L over a 24-hour period before magnetic resonance imaging. Five patients with osmotic demyelination had apparent neurologic recovery.

Conclusions

Among patients presenting with severe hyponatremia, rapid correction occurred in 41%; nearly all patients with incident osmotic demyelination had a documented episode of rapid correction.

Podcast

This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_06_05_CJASNPodcast_18_7_G.mp3

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Training Nephrology Fellows in Temporary Hemodialysis Catheters and Kidney Biopsies Is Not Needed and Should Not Be Required

https://ift.tt/2KFg62j

Self-Reported Tobacco, Alcohol, and Illicit Drug Use and Progression of Chronic Kidney Disease

Background and objectives

Previous studies suggest that tobacco, alcohol, and illicit drug use is associated with CKD. We examined the associations of substance use with CKD progression and all-cause mortality among patients with CKD.

Design, setting, participants, & measurements

The Chronic Renal Insufficiency Cohort Study is a prospective, longitudinal cohort study among 3939 participants with CKD in the United States. Self-reported tobacco smoking, alcohol drinking, marijuana use, and hard illicit drug (cocaine, heroin, or methamphetamine) use were obtained at baseline and annual follow-up visits. CKD progression was defined as incident ESKD or halving of eGFR. Substance use was modeled as the cumulative average exposure to capture both recent and long-term use in multivariable time-dependent Cox regression.

Results

Over a median 5.5-year follow-up, 1287 participants developed CKD progression, and 1001 died. Baseline proportions of tobacco smoking, alcohol drinking, marijuana use, and hard illicit drug use were 13%, 20%, 33%, and 12%, respectively. Compared with nonsmoking throughout follow-up, multivariable-adjusted hazard ratios for persistent tobacco smoking were 1.02 (95% confidence interval, 0.86 to 1.21) for CKD progression and 1.86 (95% confidence interval, 1.54 to 2.24) for all-cause mortality. Compared with nondrinking throughout follow-up, multivariable-adjusted hazard ratios for persistent alcohol drinking were 1.06 (95% confidence interval, 0.88 to 1.29) for CKD progression and 0.73 (95% confidence interval, 0.58 to 0.91) for all-cause mortality. Compared with nonuse throughout follow-up, multivariable-adjusted hazard ratios for persistent marijuana use were 0.94 (95% confidence interval, 0.82 to 1.07) for CKD progression and 1.11 (95% confidence interval, 0.96 to 1.30) for all-cause mortality. Compared with nonuse throughout follow-up, multivariable-adjusted hazard ratios for persistent hard illicit drug use were 1.25 (95% confidence interval, 1.00 to 1.55) for CKD progression and 1.41 (95% confidence interval, 1.10 to 1.81) for all-cause mortality.

Conclusions

Hard illicit drug use is associated with higher risk of CKD progression and all-cause mortality, tobacco smoking is associated with higher risk of all-cause mortality, and alcohol drinking is associated with lower risk of all-cause mortality among patients with CKD.

https://ift.tt/2MS6spO

Correction

https://ift.tt/2KGxFzb

Twenty-Four-Hour Urine Phosphorus as a Biomarker of Dietary Phosphorus Intake and Absorption in CKD: A Secondary Analysis from a Controlled Diet Balance Study

Background and objectives

Twenty-four-hour urine phosphorus is commonly used as a surrogate measure for phosphorus intake and absorption in research studies, but its reliability and accuracy are unproven in health or CKD. This secondary analysis sought to determine the reliability and accuracy of 24-hour urine phosphorus as a biomarker of phosphorus intake and absorption in moderate CKD.

Design, setting, participants, & measurements

Eight patients with stage 3–4 CKD participated in 2-week balance studies with tightly controlled phosphorus and calcium intakes. Thirteen 24-hour urine collections per patient were analyzed for variability and reliability of 24-hour urine phosphorus and phosphorus-to-creatinine ratio. The accuracy of 24-hour urine phosphorus to predict phosphorus intake was determined using a published equation. The relationships of 24-hour urine phosphorus with phosphorus intake, net absorption, and retention were determined.

Results

There was wide day-to-day variation in 24-hour urine phosphorus within and among subjects (coefficient of variation of 30% and 37%, respectively). Two 24-hour urine measures were needed to achieve ≥75% reliability. Estimating dietary phosphorus intake from a single 24-hour urine resulted in underestimation up to 98% in some patients and overestimation up to 79% in others. Twenty-four-hour urine phosphorus negatively correlated with whole-body retention but was not related to net absorption.

Conclusions

From a sample of eight patients with moderate CKD on a tightly controlled dietary intake, 24-hour urine phosphorus was highly variable and did not relate to dietary phosphorus intake or absorption, rather it inversely related to phosphorus retention.

https://ift.tt/2MU82r6

Requirements for Procedural Skills in Nephrology Training Programs: Framing the Conversation

https://ift.tt/2KFYm6Q

Soluble Urokinase-Type Plasminogen Activator Receptor in Black Americans with CKD

Background and objectives

Black Americans with and without APOL1 kidney disease risk variants face high risk of ESKD. Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, constitutes a promising biomarker of CKD-associated risks. We aimed to quantify the associations between serum suPAR concentration and adverse outcomes in Black Americans with and without APOL1 kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria.

Design, setting, participants, & measurements

Using data from the African-American Study of Kidney Disease and Hypertension, a multicenter clinical trial followed by a cohort phase with a median total follow-up of 9.7 years (interquartile range, 6.5–10.9 years), we examined the associations of suPAR with CKD progression (defined as doubling of serum creatinine or ESKD), ESKD, worsening proteinuria (defined as pre-ESKD doubling of 24-hour urine protein-to-creatinine ratio to ≥220 mg/g), and all-cause death.

Results

At baseline, the median suPAR was 4462 pg/ml, mean measured GFR was 46 ml/min per 1.73 m², and median 24-hour urine protein-to-creatinine ratio was 80 mg/g. After controlling for baseline demographics, randomization arm, GFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.26-times higher risk for CKD progression per SD higher baseline log-transformed suPAR (hazard ratio [HR], 1.26; 95% confidence interval [95% CI], 1.11 to 1.43; P<0.001). Higher suPAR was also independently associated with risk of ESKD (HR, 1.36; 95% CI, 1.17 to 1.58; P<0.001) and death (HR, 1.25; 95% CI, 1.08 to 1.45; P=0.003). suPAR was only associated with worsening proteinuria in patients with two APOLI risk alleles (HR, 1.46; 95% CI, 1.08 to 1.99; P=0.02).

Conclusions

Higher suPAR was associated with various adverse outcomes in Black Americans with CKD, with and without APOL1 kidney disease risk variants, independently of proteinuria and GFR.

https://ift.tt/2MS6r5e

Site of Care and Health Outcomes of Veterans Undergoing Maintenance Dialysis

https://ift.tt/2KGxAeR

Emotional Impact of Illness and Care on Patients with Advanced Kidney Disease

Background and objectives

The highly specialized and technologically focused approach to care inherent to many health systems can adversely affect patients' emotional experiences of illness, while also obscuring these effects from the clinician's view. We describe what we learned from patients with advanced kidney disease about the emotional impact of illness and care.

Design, setting, participants, & measurements

As part of an ongoing study on advance care planning, we conducted semistructured interviews at the VA Puget Sound Healthcare System in Seattle, Washington, with 27 patients with advanced kidney disease between April of 2014 and May of 2016. Of these, ten (37%) were receiving center hemodialysis, five (19%) were receiving peritoneal dialysis, and 12 (44%) had an eGFR≤20 ml/min per 1.73 m² and had not started dialysis. Interviews were audiotaped, transcribed, and analyzed inductively using grounded theory methods.

Results

We here describe three emergent themes related to patients' emotional experiences of care and illness: (1) emotional impact of interactions with individual providers: when providers seemed to lack insight into the patient's experience of illness and treatment, this could engender a sense of mistrust, abandonment, isolation, and/or alienation; (2) emotional impact of encounters with the health care system: just as they could be affected emotionally by interactions with individual providers, patients could also be affected by how care was organized, which could similarly lead to feelings of mistrust, abandonment, isolation, and/or alienation; and (3) emotional impact of meaning-making: patients struggled to make sense of their illness experience, worked to apportion blame, and were often quick to blame themselves and to assume that their illness could have been prevented.

Conclusions

Interactions with individual providers and with the wider health system coupled with patients' own struggles to make meaning of their illness can take a large emotional toll. A deeper appreciation of patients' emotional experiences may offer important opportunities to improve care.

https://ift.tt/2MVMTNk

Heroin Use Is Associated with AA-Type Kidney Amyloidosis in the Pacific Northwest

Background and objectives

AA-type kidney amyloidosis is classically associated with chronic autoimmune or inflammatory disorders. However, some urban centers have reported a high prevalence of injection drug use among patients with kidney AA amyloidosis. Previous reports lack control groups to quantify associations and most predate the opioid epidemic in the United States.

Design, setting, participants, & measurements

We conducted a case–control study of 38 patients with biopsy-confirmed kidney AA amyloidosis and 72 matched control individuals without this condition from two large hospital systems in Seattle, Washington. We ascertained the pattern and duration of heroin use by medical chart review and determined associations using logistic regression.

Results

Among case patients, 95% had a prior history of heroin use, 87% had skin abscesses, and 76% and 27% had evidence of muscling and skin popping, respectively. After adjustment for age, race, sex, site, and year of biopsy, any heroin use (past or current) was associated with an estimated 170-times higher risk of kidney AA amyloidosis compared with no heroin use (95% confidence interval, 28 to 1018 times higher; P<0.001). Chronic autoimmune disorders were uncommon among case patients in this study. The median time to ESKD among patients with AA amyloidosis was 2.4 years (interquartile range, 0.5–7.5 years).

Conclusions

Injection heroin use is strongly associated with kidney AA amyloidosis in the Pacific Northwest. Unique aspects of heroin use, in particular geographic regions or frequent associated soft-tissue infections, may be an important cause of this progressive kidney disease.

https://ift.tt/2MQFVZR

Management of Nonadherence in ESKD Patients

https://ift.tt/2KFXQ8U

Kidney Involvement of Patients with Waldenström Macroglobulinemia and Other IgM-Producing B Cell Lymphoproliferative Disorders

Background and objectives

Kidney involvement in Waldenström macroglobulinemia is less well described compared with kidney manifestations in multiple myeloma.

Design, setting, participants, & measurements

Of the 1363 patients seen with Waldenström macroglobulinemia and other IgM-secreting B cell lymphoproliferative disorders seen at the Mayo Clinic between 1996 and 2015, 57 kidney biopsies were retrospectively studied. The biopsy findings were correlated with clinical, kidney, and hematologic characteristics. Criteria for inclusion were evidence of a monoclonal IgM protein and availability of a kidney and a bone marrow biopsy for review. Glomerular and tubulointerstitial pathologies were categorized according to whether they were related to the monoclonal IgM.

Results

Of the 57 patients identified, monoclonal gammopathy–related kidney lesions were identified in 82% (47 of 57 biopsies), whereas nonmonoclonal gammopathy–related kidney lesions were seen in 18% (ten of 57). Monoclonal gammopathy–related kidney lesions included monoclonal Ig–related amyloidosis (n=19; 33%), nonamyloid glomerulopathy (n=20, 35%), and tubulointerstitial nephropathies (n=8; 14%). The most common monoclonal gammopathy–related kidney lesion was monoclonal Ig–related amyloidosis (n=19; 33%) followed by cryoglobulinemic GN (n=13; 28%). Lymphoma infiltration was the most common tubulointerstitial lesion (n=4; 9%). The hematologic diagnosis was Waldenström macroglobulinemia in 74% (n=42), monoclonal gammopathy of renal significance in 16% (n=9), and marginal zone lymphoma (n=2), chronic lymphocytic leukemia (n=2), and low-grade B cell lymphoma (n=2) in 4% each.

Conclusions

Our study confirms a diverse variety of kidney lesions in patients with monoclonal IgM gammopathy.

https://ift.tt/2MTVwYv

A pharmacist-led medication switch protocol in an academic HIV clinic: patient knowledge and satisfaction

Tenofovir alafenamide (TAF) is associated with less renal and bone toxicity compared with tenofovir disoproxil (TDF). TAF's recent FDA approval has spurred HIV providers to consider switching antiretroviral th...

https://ift.tt/2m0Gtkx

Epidemiology of Ventilator-Associated Pneumonia, microbiological diagnostics and the length of antimicrobial treatment in the Polish Intensive Care Units in the years 2013-2015

Ventilator-associated pneumonia (VAP) is a common nosocomial infection in intensive care units (ICUs). The objective of this study was to describe the epidemiology and microbiology of VAP in Polish ICUs from 2...

https://ift.tt/2zrh2lR

Unlocking pandemic potential: prevalence and spatial patterns of key substitutions in avian influenza H5N1 in Egyptian isolates

Avian influenza H5N1 has a high human case fatality rate, but is not yet well-adapted to human hosts. Amino acid substitutions currently circulating in avian populations may enhance viral fitness in, and thus ...

https://ift.tt/2lXt64z

Late-onset paradoxical reactions 10 years after treatment for tuberculous meningitis in an HIV-negative patient: a case report

Although paradoxical reactions (PRs) to anti-tuberculosis (anti-TB) therapy during treatment are well-established occurrences, PRs presenting as a new lesion after the completion of treatment are extremely rar...

https://ift.tt/2zhGbiH

Knowledge and attitude towards antimicrobial resistance among final year undergraduate paramedical students at University of Gondar, Ethiopia

Globally, antimicrobial resistance (AMR) is a complex public problem, which is mainly fuelled by inappropriate use of antimicrobials. Rational use of antimicrobials is the main strategy for the prevention of A...

https://ift.tt/2m01Nqa

How useful are hemoglobin concentration and its variations to predict significant hemorrhage in the early phase of trauma? A multicentric cohort study

The diagnostic value of hemoglobin (Hb) for detecting a significant hemorrhage (SH) in the early phase of trauma remains controversial. The present study aimed to assess the abilities of Hb measurements taken ...

https://ift.tt/2lXpUpB

Large-volume paracentesis effects plasma disappearance rate of indo-cyanine green in critically ill patients with decompensated liver cirrhosis and intraabdominal hypertension

Ascites is a major complication of decompensated liver cirrhosis. Intraabdominal hypertension and structural alterations of parenchyma involve decisive changes in hepatosplanchnic blood flow. Clearance of indo...

https://ift.tt/2zdJeIM

Prediction of chronic kidney disease after acute kidney injury in ICU patients: study protocol for the PREDICT multicenter prospective observational study

Acute kidney injury (AKI) is frequent and associated with poor outcome in intensive care unit (ICU) patients. Besides the association with short- and long-term mortality, the increased risk of chronic kidney ...

https://ift.tt/2lXpRKr

Does zoledronate therapy make mandibular bone susceptible to fracture? A radiographical and biomechanical study in rats

Publication date: Available online 6 July 2018

Source: Injury

Author(s): Mohammad Zandi, Abbas Shokri, Maryam Mousavi, Sanaz Rajaei, Naser Mohammad Gholi Mezerji

Abstract

Introduction

The aim of this study was to evaluate the effect of zoledronate therapy on susceptibility of mandibular bone to fracture in rats.

Methods

Fifty rats were randomly allocated to two groups of 25 animals. The rats in group Z received monthly intravenous infusion of 0.06 mg/kg zoledronate for 6 months. The rats in the group C were injected with an equal volume of saline in the same manner. A month after the last zoledronate/saline administration, all 50 rats were euthanized. Using a cone beam computed tomography, the cortical thickness of inferior border of mandible and the mandibular bone mineral density were calculated, and using a three-point bending test, the peak load failure and the ultimate stress of mandibular bone were determined.

Results

The mean mandibular inferior cortical bone thickness and the mean bone mineral density were significantly larger in zoledronate-treated rats (0.30 ± 0.02 mm and 1045.00 ± 185.79, respectively) compared to control rats (0.21 ± 0.01 mm and 878.66 ± 166.53, respectively). The peak load and the ultimate stress were lower in the zoledronate-treated hemimandibles (84.61 ± 33.62 N and 1.76 ± 0.72 MPa, respectively) compared to the control hemimandibles (98.36 ± 16.5 9 N and 2.03 ± 0.44 MPa, respectively).

Conclusion

Zoledronate therapy reduced the mechanical strength of the mandibles, implying an increased risk of mandibular fracture in rats.

https://ift.tt/2MWRvT5

Combined laparoscopic and perineal approach for the management of recurrent tailgut cyst

Asian Journal of Endoscopic Surgery, EarlyView.


https://ift.tt/2KT906a

Four‐directional approach to the meso‐transverse attachment combined with preoperative radiological vascular simulation facilitates short‐term surgical outcomes in laparoscopic transverse colon cancer surgery

Asian Journal of Endoscopic Surgery, EarlyView.


https://ift.tt/2Nw84GB

Thoracoscopic resection for mediastinal thymolipoma in a child

Asian Journal of Endoscopic Surgery, EarlyView.


https://ift.tt/2KX9ybg

Counting Proteins in Single Cells with Addressable Droplet Microarrays

Here we present addressable droplet microarrays (ADMs), a droplet array based method able to determine absolute protein abundance in single cells. We demonstrate the capability of ADMs to characterize the heterogeneity in expression of the tumor suppressor protein p53 in a human cancer cell line.

https://ift.tt/2KSxuzM

High-frequency stimulation of anterior nucleus of thalamus desynchronizes epileptic network in humans

Abstract

Epilepsy has been classically seen as a brain disorder resulting from abnormally enhanced neuronal excitability and synchronization. Although it has been described since antiquity, there are still significant challenges achieving the therapeutic goal of seizure freedom. Deep brain stimulation of the anterior nucleus of the thalamus has emerged as a promising therapy for focal drug-resistant epilepsy; the basic mechanism of action, however, remains unclear. Here, we show that desynchronization is a potential mechanism of deep brain stimulation of the anterior nucleus of the thalamus by studying local field potentials recordings from the cortex during high-frequency stimulation (130 Hz) of the anterior nucleus of the thalamus in nine patients with drug-resistant focal epilepsy. We demonstrate that high-frequency stimulation applied to the anterior nucleus of the thalamus desynchronizes ipsilateral hippocampal background electrical activity over a broad frequency range, and reduces pathological epileptic discharges including interictal spikes and high-frequency oscillations. Furthermore, high-frequency stimulation of the anterior nucleus of the thalamus is capable of decoupling large-scale neural activity involving the hippocampus and distributed cortical areas. We found that stimulation frequencies ranging from 15 to 45 Hz were associated with synchronization of hippocampal local field potentials, whereas higher frequencies (>45 Hz) promoted desynchronization of ipsilateral hippocampal activity. Moreover, reciprocal effective connectivity between the anterior nucleus of the thalamus and the hippocampus was demonstrated by hippocampal-thalamic evoked potentials and thalamic-hippocampal evoked potentials. In summary, high-frequency stimulation of the anterior nucleus of the thalamus is shown to desynchronize focal and large-scale epileptic networks, and here is proposed as the mechanism for reducing seizure generation and propagation. Our data also demonstrate position-specific correlation between deep brain stimulation applied to the anterior nucleus of the thalamus and patients with temporal lobe epilepsy and seizure onset zone within the Papaz circuit or limbic system. Our observation may prove useful for guiding electrode implantation to increase clinical efficacy.

https://ift.tt/2Nybb0H

TRPA1/NOX in the soma of trigeminal ganglion neurons mediates migraine-related pain of glyceryl trinitrate in mice

Abstract

Glyceryl trinitrate is administered as a provocative test for migraine pain. Glyceryl trinitrate causes prolonged mechanical allodynia in rodents, which temporally correlates with delayed glyceryl trinitrate-evoked migraine attacks in patients. However, the underlying mechanism of the allodynia evoked by glyceryl trinitrate is unknown. The proalgesic transient receptor potential ankyrin 1 (TRPA1) channel, expressed by trigeminal nociceptors, is sensitive to oxidative stress and is targeted by nitric oxide or its by-products. Herein, we explored the role of TRPA1 in glyceryl trinitrate-evoked allodynia. Systemic administration of glyceryl trinitrate elicited in the mouse periorbital area an early and transient vasodilatation and a delayed and prolonged mechanical allodynia. The systemic, intrathecal or local administration of selective enzyme inhibitors revealed that nitric oxide, liberated from the parent drug by aldehyde dehydrogenase 2 (ALDH2), initiates but does not maintain allodynia. The central and the final phases of allodynia were respectively associated with generation of reactive oxygen and carbonyl species within the trigeminal ganglion. Allodynia was absent in TRPA1-deficient mice and was reversed by TRPA1 antagonists. Knockdown of neuronal TRPA1 by intrathecally administered antisense oligonucleotide and selective deletion of TRPA1 from sensory neurons in Advillin-Cre; Trpa1fl/fl mice revealed that nitric oxide-dependent oxidative and carbonylic stress generation is due to TRPA1 stimulation, and resultant NADPH oxidase 1 (NOX1) and NOX2 activation in the soma of trigeminal ganglion neurons. Early periorbital vasodilatation evoked by glyceryl trinitrate was attenuated by ALDH2 inhibition but was unaffected by TRPA1 blockade. Antagonists of the calcitonin gene-related peptide receptor did not affect the vasodilatation but partially inhibited allodynia. Thus, although both periorbital allodynia and vasodilatation evoked by glyceryl trinitrate are initiated by nitric oxide, they are temporally and mechanistically distinct. While vasodilatation is due to a direct nitric oxide action in the vascular smooth muscle, allodynia is a neuronal phenomenon mediated by TRPA1 activation and ensuing oxidative stress. The autocrine pathway, sustained by TRPA1 and NOX1/2 within neuronal cell bodies of trigeminal ganglia, may sensitize meningeal nociceptors and second order trigeminal neurons to elicit periorbital allodynia, and could be of relevance for migraine-like headaches evoked by glyceryl trinitrate in humans.

https://ift.tt/2KUzXqg

Cabozantinib Improves Survival in Advanced Hepatocellular Cancer

FRIDAY, July 6, 2018 -- Cabozantinib results in significantly longer overall and progression-free survival than placebo among patients with advanced hepatocellular carcinoma, according to a study published in the July 5 issue of the New England...

https://ift.tt/2Nv41KU

PCPs Often Not Meeting Needs of Seniors With Chronic Conditions

FRIDAY, July 6, 2018 -- Most primary care physicians (PCPs) report being unable to adequately address the needs of patients with multiple chronic conditions, according to a report published by Quest Diagnostics. A total of 801 PCPs who care for...

https://ift.tt/2ucj578

Travel Costs Are Considerable Part of T2DM Follow-Up Costs

FRIDAY, July 6, 2018 -- For patients with type 2 diabetes mellitus (T2DM), travel costs relating to hemoglobin A1c (HbA1c) screening constitute a substantial cost item, and self-monitoring can reduce costs, according to a study published in the July...

https://ift.tt/2NztvXA

Most Women Who Freeze Eggs Motivated by Lack of Partner

FRIDAY, July 6, 2018 -- Most women undergoing elective egg freezing (EEF) are without partners, reflecting different life circumstances, according to a study presented at the annual meeting of the European Society of Human Reproduction and...

https://ift.tt/2zg8Btr

Decrease in Mean Platelet Counts Seen During Pregnancy

FRIDAY, July 6, 2018 -- All women have a decrease in mean platelet counts during pregnancy, according to a study published in the July 5 issue of the New England Journal of Medicine. Jessica A. Reese, Ph.D., from the University of Oklahoma Health...

https://ift.tt/2NxjNVy

Organic Solvents + Genetics May Increase Risk of Multiple Sclerosis

FRIDAY, July 6, 2018 -- The combination of genetics and exposure to organic solvents in paints and varnishes increases the risk of multiple sclerosis (MS), according to a study published online July 3 in Neurology. Anna Karin Hedstrom, M.D., Ph.D.,...

https://ift.tt/2zg8z4N

IV Acetaminophen Minimally Helpful for Colectomy Pain

FRIDAY, July 6, 2018 -- Intravenous acetaminophen does not decrease opioid utilization to a clinically significant threshold among colectomy patients, according to a study published in the July issue of Anesthesiology. Isaac Wasserman, M.P.H., from...

https://ift.tt/2tZQrqK

Disordered Eating Behaviors Up for Overweight Young Adults

FRIDAY, July 6, 2018 -- Young adults at a weight status classified as overweight or obese have increased prevalence of disordered eating behaviors (DEBs), according to a study published online June 11 in the Journal of General Internal...

https://ift.tt/2ui3DGX

Skin Cancer Risk Higher in Military Personnel

FRIDAY, July 6, 2018 -- There is an increased risk for skin cancer among U.S. active duty service members and veterans, according to a review published in the June issue of the Journal of the American Academy of Dermatology. Kelsie Riemenschneider,...

https://ift.tt/2Nqjjk5

Health Gains, Cost Savings Projected for Sodium Goals

FRIDAY, July 6, 2018 -- Substantial health gains and cost savings could be achieved with implementation and achievement of the U.S. Food and Drug Administration sodium reformulation targets, according to a study recently published in PLOS...

https://ift.tt/2zdcgIc

Assessing the efficacy of peripherally acting {micro}-opioid receptor antagonists (PAMORAs) in the treatment of opioid-induced constipation: authors reply

We thank Chedid and Camilleri for their carefully composed letter,1 and are delighted to have provoked further debate about the relative efficacy of drugs acting on µ-opioid receptors in the treatment of opioid-induced constipation (OIC) with our network meta-analysis.2 In fact, we had also written to another journal concerning a recent network meta-analysis examining this issue,3 which had reported erroneously that subcutaneous methylnaltrexone appeared to perform better than other medications for OIC.4 The authors confirmed in their reply to our letter that they had mistakenly included redundant data from duplicate publications of the same two randomised-controlled trials (RCTs) of methylnaltrexone in this meta-analysis,5 likely accounting for their findings.4

In response to the specific issues raised by Chedid and Camilleri,1 first as we reported in the supplementary materials section of our manuscript there were no significant differences in rates...

https://ift.tt/2KVvHdy

Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study

Objective

IBS is associated with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clinical outcome in patients with IBS.

Design

We performed this study in 52 adult patients with moderate-to-severe IBS. At the screening visit, clinical history and symptoms were assessed and faecal samples were collected. Patients were randomised to FMT or placebo capsules for 12 days and followed for 6 months. Study visits were performed at baseline, 1, 3 and 6 months, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected.

Results

A significant difference in improvement in IBS-SSS score was observed 3 months after treatment (p=0.012) favouring placebo. This was similar for IBS-QoL data after 3 months (p=0.003) favouring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not.

Conclusion

In this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 months. Altering the gut microbiota is not enough to obtain clinical improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS.

Trial registration number

NCT02788071.

https://ift.tt/2J0j9MB

In vitro genomic and proteomic evidence of a type IV pili-like structure in the fish pathogen Piscirickettsia salmonis

Abstract

Piscirickettsia salmonis is an intracellular γ-proteobacteria and the etiological agent of piscirickettsiosis, which causes massive economic losses in the Chilean salmon industry. The type IV pili (T4P) play an important role in adherence to host cell surfaces and bacterial pathogenicity. T4P contains a variable number of components, as predicted in P. salmonis genomes. However, no studies have determined if P. salmonis possesses T4P. The aims of this investigation were to identify T4P components in the P. salmonis type strain LF-89^T, evaluate respective transcript expressions, and analyze the main putative T4P proteins using bioinformatics and proteomic approaches. Two main clusters of P. salmonis T4P genes were found. Expression of the pilA gene was up-regulated at 4 h post-infection (hpi), while pilQ was up-regulated 4 d post-infection. At 16 hpi, pilB and pilD were strongly up-regulated. The PilA amino acid sequence analysis showed a conserved N-terminal domain and sequence motifs critical for T4P biosynthesis. MudPIT analysis revealed PilA in the P. salmonis LF-89^T proteome, and TEM showed pili-like filamentous structures on the P. salmonis surface. These results strongly suggest the presence of a T4P-like structure in P. salmonis.

https://ift.tt/2ua2YHu

https://ift.tt/2KXSWjy

Genetics of congenital eye malformations: insights from chick experimental embryology

Abstract

Embryological manipulations in chick embryos have been pivotal in our understanding of many aspects of vertebrate eye formation. This research was particularly important in uncovering the role of tissue interactions as drivers of eye morphogenesis and to dissect the function of critical genes. Here, we have highlighted a few of these past experiments to endorse their value in searching for hitherto unknown causes of rare congenital eye anomalies, such as microphthalmia, anophthalmia and coloboma. We have also highlighted a number of similarities between the chicken and human eye, which might be exploited to address other eye pathologies, including degenerative ocular diseases.

https://ift.tt/2IXvWzG