Retrospective comparison of S-1 plus cisplatin versus S-1 monotherapy for the treatment of advanced gastric cancer patients with positive peritoneal cytology but without gross peritoneal metastasis

Abstract

Background

Peritoneal cytology positive for carcinoma cells (CY+) is an independent poor prognostic factor in gastric cancer, and patients with CY+ are diagnosed with stage IV disease. However, there is no standard treatment strategy for CY+ gastric cancer, whereas combination chemotherapy with fluoropyrimidine and platinum has been established as the standard treatment for unresectable advanced gastric cancer or after R2 resection. Herein, we assessed whether adding cisplatin to S-1 (SP) could improve the outcome of CY+ gastric cancer patients, as compared to S-1 monotherapy.

Methods

This retrospective study was conducted at a single Japanese institute between June 2005 and March 2014. Patients diagnosed with CY+ advanced gastric cancer and treated with S-1-based therapy were enrolled. Patients with incurable factors other than CY+ were excluded.

Results

Forty-four patients were enrolled; 25 and 19 were administered S-1 and SP, respectively. The 2-year survival rates were 52.0% [95% confidence interval (CI), 31.2–69.2%] and 52.6% (28.7–71.9%) in the S-1 and SP groups, respectively. The median overall survival (OS) and progression-free survival (PFS) were 28.2 and 15.6 months in the S-1 group and 24.0 and 18.8 months in the SP group, respectively; they were not significantly different. The relative dose intensities were 0.79 (S-1) in the S-1 group and 0.69 (S-1)/0.70 (cisplatin) in the SP group.

Conclusion

Adding cisplatin to long-term S-1 monotherapy did not significantly improve the outcome of CY+ advanced gastric cancer patients.

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Structure-function relationships in the visual system in multiple sclerosis: an MEG and OCT study

Abstract

Background

We conducted a multi-modal optical coherence tomography (OCT) and magnetoencephalography (MEG) study to test whether there is a relationship between retinal layer integrity and electrophysiological activity and connectivity (FC) in the visual network influenced by optic neuritis (ON) in patients with multiple sclerosis (MS).

Methods

One hundred and two MS patients were included in this MEG/OCT study. Retinal OCT data were collected from the optic discs, macular region, and segmented. Neuronal activity and FC in the visual cortex was estimated from source-reconstructed resting-state MEG data by computing relative power and the phase lag index (PLI). Generalized estimating equations (GEE) were used to account for intereye within-patient dependencies.

Results

There was a significant relationship for both relative power and FC in the visual cortex with retinal layer thicknesses. The findings were influenced by the presence of MSON, particularly for connectivity in the alpha bands and the outer macular layers. In the absence of MSON, this relationship was dominated by the lower frequency bands (theta, delta) and inner and outer retinal layers.

Conclusion

These results suggest that visual cortex FC more than activity alters in the presence of MSON, which may guide the understanding of FC plasticity effects following MSON.

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Central Retinal Vein Occlusion in 2 Patients Using Antipsychotic Drugs

Purpose: To report our findings in 2 patients who developed a central retinal vein occlusion (CRVO) and were chronic users of antipsychotic medications. Case Presentation: Case 1 was a 62-year-old woman who had a sudden reduction of vision in her right eye to 20/2,000. Her fundus showed signs of an impending CRVO with marked macular edema. She had been taking antipsychotic drugs (quetiapine fumarate and risperidone) for about 2 years. She refused anti-VEGF therapy for her macular edema but selected systemic kallidinogenase. Two days later, the macular edema was significantly reduced but the number of cotton wool spots (CWS) was increased. Ten days later, the macular edema was resolved and her BCVA improved to 20/60. The CWS gradually disappeared, and her BCVA improved to 20/20. Case 2 was a 43-year-old man who presented with vision reduction in his right eye of 1 week's duration. His BCVA was 20/50 and his fundus showed signs of a CRVO-related macular edema with CWS in the peripapillary area. He had been taking sulpiride (Dogmatyl^TM) for depression for 1 year, and his blood test showed an increase in red blood cells and hematocrit. Anti-VEGF therapy was performed, and the macular edema was resolved with vision improving to 20/20. There has been no recurrence to date in both cases. Conclusions: These results indicate that a CRVO can be a complication of chronic use of antipsychotic medications. However, early treatment can lead to good outcomes. Clinicians should question patients who develop a sudden CRVO whether they are using antipsychotic medications.
Case Rep Ophthalmol 2017;8:410–415

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Fundus Findings in Wernicke Encephalopathy

Wernicke encephalopathy (WE) is an acute neuropsychiatric syndrome resulting from thiamine (vitamin B₁) deficiency, classically characterized by the triad of ophthalmoplegia, confusion, and ataxia. While commonly associated with chronic alcoholism, WE may also occur in the setting of poor nutrition or absorption. We present a 37-year-old woman who underwent laparoscopic sleeve gastrectomy and presented with visual disturbance with bilateral horizontal nystagmus, confusion, and postural imbalance. Fundus examination revealed bilateral optic disc edema with a retinal hemorrhage in the left eye. Metabolic workup demonstrated thiamine deficiency. Her symptoms resolved after thiamine treatment. This case raises the awareness of the possibility of posterior segment findings in WE, which are underreported in WE.
Case Rep Ophthalmol 2017;8:406–409

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Neuroanesthesiology: the ineludible path toward super-specialty.

No abstract available

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Inverse estimation of cardiac activation times via gradient-based optimisation

Summary

Computational modeling may provide a quantitative framework for integrating multi-scale data to gain insight into mechanisms of heart disease, identify and test pharmacological and electrical therapy and interventions, and support clinical decisions. Patient-specific computational cardiac models can help guide such procedures, and cardiac inverse modelling is a promising alternative to adequately personalize these models. Indeed, full cardiac inverse modelling is currently becoming computationally feasible; however, fundamental work to assess the feasibility of emerging techniques is still needed. In this study, we use a PDE-constrained optimal control approach to numerically investigate the identifiability of an initial activation sequence from synthetic (partial) observations of the extracellular potential using the bidomain approximation and 2D representations of cardiac tissue. Our results demonstrate that activation times and duration of several stimuli can be recovered even with high levels of noise, that it is sufficient to sample the observations at the ECG-relevant sampling frequency of 1 kHz, and that spatial resolutions that are coarser than the standard in electrophysiological simulations can be used. The optimization of activation times is still effective when synthetic data are generated with a different cell membrane kinetics model than optimized for. The findings thus indicate that the presented approach has potential for finding activation sequences from clinical data modalities, as an extension to existing cardiac imaging approaches. This article is protected by copyright. All rights reserved.

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Internal carotid, external carotid and vertebral artery blood flow responses to a 3-day of head-out dry immersion

Abstract

We have recently demonstrated that heterogeneous cerebral blood flow (CBF) response in each cerebral artery may contribute to the maintenance of circulatory homeostasis in the brain. However, to what extent weightlessness associated with fluid shift from peripheral to central circulations influences distribution of CBF in each cerebral artery remains unknown. We hypothesised that dry immersion-induced fluid shift (weightlessness condition) would cause heterogeneous CBF response in each cerebral artery. During and after a 3-day dry immersion, internal carotid (ICA), external carotid (ECA) and vertebral arteries (VA) blood flows were measured by Doppler ultrasonography using an 8-MHz linear transducer. Although the 3-day dry immersion and the 2-day recovery period did not change blood flow in each cerebral artery, both ICA and VA conductance decreased during dry immersion on day 2 and day 3 (ICA, 2.95 and 3.23 ml min⁻¹ mmHg⁻¹; VA, 1.10 and 1.05 ml min⁻¹ mmHg⁻¹) from the baseline (ICA, 3.47 ml min⁻¹ mmHg⁻¹, P = 0.027; VA, 1.23 ml min⁻¹ mmHg⁻¹, P = 0.004). In addition, Pearson correlation analysis demonstrated that the 3-day dry immersion-induced a decrease in cardiac output (P = 0.004) was associated with changes in ICA (P = 0.046) and VA blood flow (P = 0.021), but not ECA blood flow (P = 0.466). These findings suggest that short exposures to weightlessness via a cephalad redistribution of fluid volume and blood flow in the human body influenced cerebral vasculature in each cerebral artery but did not cause heterogeneous CBF response in each cerebral artery.

This article is protected by copyright. All rights reserved

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Simple methods to reduce major allergens Ara h 1 and Ana o 1/2 in peanut and cashew extracts

Abstract

Whole peanut or cashew extracts are usually used in immunotherapy. Reducing major allergen(s) in the extracts may lessen their side effects. Three methods were evaluated to reduce major allergens in peanut extracts: (1) p-aminobenzamidine; (2) magnetic agarose beads; and (3) extraction of a commercial peanut flour at pH 7, respectively. The first two methods were also used to reduce major allergens in cashew extracts. After treatments, samples were evaluated by SDS-PAGE. pABA-treated samples were also analyzed for IgE binding in western blot. We found that the methods resulted in peanut extracts lacking detectable Ara h 1 but containing Ara h 2/6 and cashew extract lacking Ana o 1/2, but containing Ana o 3. Consequently, reduced IgE binding was observed. We conclude that the methods are useful for producing peanut or cashew extract with little Ara h 1 or Ana o 1/2.

We successfully reduced a major allergen in peanut or cashew extract, using simple methods such as magnetic beads, a chemical, and pH extraction.

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Oxidative changes in lipids, proteins, and antioxidants in yogurt during the shelf life

Abstract

Oxidation processes in milk and yogurt during the shelf life can result in an alteration of protein and lipid constituents. Therefore, the antioxidant properties of yogurt in standard conditions of preservation were evaluated. Total phenols, free radical scavenger activity, degree of lipid peroxidation, and protein oxidation were determined in plain and skim yogurts with or without fruit puree. After production, plain, skim, plain berries, and skim berries yogurts were compared during the shelf life up to 9 weeks. All types of yogurts revealed a basal antioxidant activity that was higher when a fruit puree was present but gradually decreased during the shelf life. However, after 5–8 weeks, antioxidant activity increased again. Both in plain and berries yogurts lipid peroxidation increased until the seventh week of shelf life and after decreased, whereas protein oxidation of all yogurts was similar either in the absence or presence of berries and increased during shelf life. During the shelf life, a different behavior between lipid and protein oxidation takes place and the presence of berries determines a protection only against lipid peroxidation.

The antioxidant power in various types of yogurt was investigated. The total phenolic content especially depends on the type of fruit puree added. Increased lipid peroxidation was followed by a decrease during the shelf life. Protein oxidation is similar either in the absence or in the presence of berries.

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High Antimetastatic Activity of Platin Liposomal Form after Lyophilization and Storage

Antimetastatic activity of Platin in lyophilized liposomes stored for 7 years after fabrication was evaluated. The main flaw of liposomes as vehicles for drug delivery to the tumors is their high affinity for the liver, which accumulates a great amount thereof. This property of liposomes can be used for adjuvant therapy of operable primary tumors metastasizing to the liver. It is shown on the model of mouse GA-1 tumor metastases in the liver that platinum(II) complex compound Platin in phosphatidylcholine-cholesterol liposomes, stored for 7 years after lyophilization, causes complete cure of 40% animals, while free Platin prolongs the lifespan of mice with tumors by only 31.7% vs. control (no treatment).

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Electrophysiological Features of Single Store-Operated Calcium Channels in HEK S4 Cell Line with Stable STIM1 Protein Knockdown

An important role in intracellular calcium signaling is played by store-operated channels activated by STIM proteins, calcium sensors of the endoplasmic reticulum. In stable STIM1 knockdown HEK S4 cells, single channels activated by depletion of intracellular calcium stores were detected by cell-attached patch-clamp technique and their electrophysiological parameters were described. Comparison of the properties of single channels in HEK293 and HEK S4 cells revealed no significant differences in their current-voltage curves, while regulation of store-operated calcium channels in these cell lines depended on the level of STIM1 expression. We can conclude that electrophysiological peculiarities of store-regulated calcium entry observed in different cells can be explained by differences in STIM1 expression.

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Dynamics of the Development of Depressive-Like State in Rats Stressed by Chronic Exposure of Ultrasound of Variable Frequency

We studied the effect of ultrasonic waves with a frequency of 20-45 kHz on behavioral reactions of rats after 7, 14 and 21 days of continuous exposure. A decrease in the number of social contacts in the social interest test was recorded in all groups, while lengthening of immobility time in Porsolt test was found only in the groups exposed to ultrasound for 2 and 3 weeks. Memory impairment in the new object recognition test was recorded only after 21 days of stressing. Chronic exposure to ultrasound of variable frequencies leads to the development of a depressive-like state in rats and the duration of exposure affects the specificity of the observed disorders. Different protocols of using of this model help to determine the stages of depressive-like condition in rats that can serve as a basis for the development of new methods of depressive disorders treatment.

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Lipoxygenase Inhibitors Nordihydroguaiaretic Acid and Fungus Lecanicillum lecanii Extract Induce Death of Lymphoid Leukemia Cells

We studied the effect of lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA) and fungus Lecanicillum lecanii extract on lymphatic leukemia P388 cells. The cells grown in the abdominal cavity of DBA2 mice for 7 days were transferred into a nutrient medium. The effect of lipoxygenase inhibitors was evaluated by changes in cell number, trypan blue staining, nucleus damage, and changes in cell distribution by DNA content after 22-h incubation. NDGA and fungus extract induced apoptotic death of lymphatic leukemia cells, which was seen from nucleus damage and reduced DNA content in cells. IC₅₀ for NDGA and fungus extract was 0.66 and 5.5 μg/ml, respectively.

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Antioxidant and Antiamnestic Effects of Potassium Comenate and Comenic Acid under Conditions of Normobaric Hypoxia with Hypercapnia

Potassium comenate and comenic acid exhibit manifest and virtually identical antioxidant activity under conditions of hypoxia with hypercapnia. The effects of these drugs on conditioned reflex training with positive reinforcement differ significantly. Potassium comenate promotes retention of the learning capacity and memory in hypoxic rats at the level of intact control, that is, exhibits a pronounced protective antiamnestic effect, while comenic acid only facilitates training of the conditioned reflex with positive reinforcement.

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Effects of Chitosan Derivative N-[(2-Hydroxy-3-Trimethylammonium)Propyl]Chloride on Anticoagulant Activity of Guinea Pig Plasma

Intravenous injection of protamine sulfate or quarternized chitosan derivative to guinea pigs after injection of 70 aIIa U/kg non-fractionated heparin shortened plasma clotting time (shown by partial activated thromboplastin time, thrombin time, and prothrombin time). Intravenous injection of protamine sulfate or quarternized chitosan derivative to guinea pigs after injection of 1 mg/kg (100 aXa U/kg) low-molecular-weight heparin (clexane) led to shortening of plasma clotting time in the ReaClot Heparin test and to prolongation of plasma amidolytic activity in the factor Xa chromogenic substrate test.

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Metabolic Restructuring in the Liver under Conditions of Endogenous Intoxication

Significant metabolic alterations in the liver were observed in dogs with modeled acute peritonitis. These changes significantly impaired detoxification function of the liver, which was seen from the increase in the titer of toxic products in the early post-surgery period not only in the lymph, but also in the blood plasma. The key pathogenic mechanism leading to acute liver failure is destabilization of cell membrane resulting from LPO, phospholipase activity, and tissue hypoxia. Activation of LPO and increase in phospholipase activity in the liver tissues were observed within 12 h after peritonitis modeling.

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Role of NF-κB, PI3K, MAPK/ERK 1/2, and p38 in Erythropoietin Production by Bone Marrow Nuclears under Conditions of Immobilization Stress

The involvement of the studied signal cascades in the regulation of erythropoietin production by bone marrow nuclears under conditions of immobilization stress depends on the type of the hemopoiesis-inducing microenvironment cells and the period of blood system reaction to stress exposure. Secretory activity of monocytes is regulated mainly by PI3K improving cell resistance to disturbances. The functional role of signal cascades involved in the production of erythropoietin by T cells is determined by the stage of the common adaptation syndrome.

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Benchmark problems for numerical treatment of backflow at open boundaries

Summary

In computational fluid dynamics, incoming velocity at open boundaries, or backflow, often yields to unphysical instabilities already for moderate Reynolds numbers. Several treatments to overcome these backflow instabilities have been proposed in the literature. However, these approaches have not yet been compared in detail in terms of accuracy in different physiological regimes, in particular due to the difficulty to generate stable reference solutions apart from analytical forms. In this work, we present a set of benchmark problems in order to compare different methods in different backflow regimes (with a full reversal flow and with propagating vortices after a stenosis). The examples are implemented in FreeFem++ and the source code is openly available, making them a solid basis for future method developments. This article is protected by copyright. All rights reserved.

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The Stress-Inducible Peroxidase TSA2 Underlies a Conditionally Beneficial Chromosomal Duplication in Saccharomyces cerevisiae

Although chromosomal duplications are often deleterious, in some cases they enhance cells' abilities to tolerate specific genetic or environmental challenges. Identifying the genes that confer these conditionally beneficial effects to particular chromosomal duplications can improve our understanding of the genetic and molecular mechanisms that enable certain aneuploidies to persist in cell populations and contribute to disease and evolution. Here, we perform a screen for spontaneous mutations that improve the tolerance of haploid Saccharomyces cerevisiae to hydrogen peroxide. Chromosome IV duplication is the most frequent mutation, as well as the only change in chromosomal copy number, seen in the screen. Using a genetic mapping strategy that involves systematically deleting segments of a duplicated chromosome, we show that the Chromosome IV duplication's effect is largely due to the generation of a second copy of the stress-inducible cytoplasmic thioredoxin peroxidase TSA2. Our findings add to a growing literature that shows the conditionally beneficial effects of chromosomal duplication are typically mediated by a small numbers of genes that enhance tolerance to specific stresses when their copy numbers are increased.

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Genome-Wide Screen for Genes Involved in Caenorhabditis elegans Developmentally Timed Sleep

In Caenorhabditis elegans, Notch signaling regulates developmentally timed sleep during the transition from L4 larval stage to adulthood (L4/A). To identify core sleep pathways and to find genes acting downstream of Notch signaling, we undertook the first genome-wide, classical genetic screen focused on C. elegans developmentally timed sleep. To increase screen efficiency, we first looked for mutations that suppressed inappropriate anachronistic sleep in adult hsp::osm-11 animals over-expressing the Notch co-ligand OSM-11 after heat shock. We retained suppressor lines that also had defects in L4/A developmentally timed sleep, without heat-shock over-expression of the Notch co-ligand. Sixteen suppressor lines with defects in developmentally timed sleep were identified. One line carried a new allele of goa-1; loss of GOA-1 Gα_o decreased C. elegans sleep. Another line carried a new allele of gpb-2, encoding a G-beta₅ (Gβ₅) protein; Gβ₅ proteins have not been previously implicated in sleep. In other scenarios, Gβ₅ GPB-2 acts with regulators of G protein signaling (RGS proteins) EAT-16 and EGL-10 to terminate either EGL-30 Gα_q signaling or GOA-1 Gα_o signaling, respectively. We found that loss of Gβ₅ GPB-2 or RGS EAT-16 decreased L4/A sleep. By contrast, EGL-10 loss had no impact. Instead, loss of RGS-1 and RGS-2 increased sleep. Combined, our results suggest that, in the context of L4/A sleep, GPB-2 predominantly acts with EAT-16 RGS to inhibit EGL-30 Gαq signaling. These results confirm the importance of G protein signaling in sleep and demonstrate that these core sleep pathways function genetically downstream of the Notch signaling events promoting sleep.

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Immunological recovery in tuberculosis/HIV co-infected patients on antiretroviral therapy: implication for tuberculosis preventive therapy

Understanding the immune response to combination antiretroviral therapy (cART) is essential for a clear approach to tuberculosis (TB) preventive therapy. We investigated the immunological recovery in cART-trea...

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A cross-sectional sero-survey on preoperative HBV vaccination policy in Poland

A two-dose preoperative vaccination schedule against HBV has been the widely accepted policy in Poland. However, its effectiveness has not yet been assessed.

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A comparison study between GeXP-based multiplex-PCR and serology assay for Mycoplasma pneumoniae detection in children with community acquired pneumonia

Diagnosis of community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae (Mp) in children has been hampered by difficulty in obtaining convalescent serum and time constraints. In this study, the two diagno...

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Magnetic hyperthermia enhance the treatment efficacy of peri-implant osteomyelitis

When bacteria colony persist within a biofilm, suitable drugs are not yet available for the eradication of biofilm-producing bacteria. The aim of this study is to study the effect of magnetic nano-particles-in...

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Sterile Drug Products by Cantrell Drug Company: Recall - Lack of Sterility Assurance

Audience: Health Professional, Risk Manager [Posted 07/25/2017] ISSUE: Cantrell Drug Company is voluntarily recalling all lots of unexpired sterile drug products to the hospital and user level due to lack of sterility assurance. The recalled...

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Impact of Electronic Acute Kidney Injury (AKI) Alerts With Automated Nephrologist Consultation on Detection and Severity of AKI: A Quality Improvement Study

Several electronic alert systems for acute kidney injury (AKI) have been introduced. However, their clinical benefits require further investigation.

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PinX1 Is a Potential Prognostic Factor for Non-Small-Cell Lung Cancer and Inhibits Cell Proliferation and Migration

PinX1 has been identified as a suppressor of telomerase enzymatic activity. However, the tumour-suppressive roles of PinX1 in different types of human cancers are unclear. PinX1 expression status and its correlation with clinicopathological features in non-small-cell lung cancer (NSCLC) have not been investigated. Accordingly, in this study, we aimed to evaluate the roles of PinX1 in NSCLC. PinX1 expression status was examined by immunohistochemistry using tissue microarray from a total of 158 patients. Correlations among PinX1 expression, clinicopathological variables, and patient survival were analysed. Furthermore, we overexpressed PinX1 in NSCLC cells and tested telomerase activity using real-time quantitative telomeric repeat amplification protocol (qTRAP) assays. Proliferation and migration of NSCLC cells were examined using the MTS method, wound healing assays, and transwell assays, respectively. Our results showed that negative PinX1 expression was associated with a poor prognosis in NSCLC. Sex, smoking status, lymph gland status, subcarinal lymph node status, pathological stage, and PinX1 expression were related to survival. PinX1 was not an independent prognostic factor in NSCLC. PinX1 overexpression inhibited proliferation and migration in NSCLC cells by suppressing telomerase activity. Our findings suggested that PinX1 could be a potential tumour suppressor in NSCLC and that loss of PinX1 promoted NSCLC progression.

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Survey of Provider Preferences Regarding the Route of Misoprostol for Induction of Labor at Term

AJP Rep 2017; 07: e158-e162
DOI: 10.1055/s-0037-1603954

Objective To survey obstetrical provider preferences regarding use of misoprostol for induction of labor (IOL). Methods An anonymous 25-question survey was distributed at an American College of Obstetricians and Gynecologists (ACOG) joint District V and VII Meeting in 2014 to obstetrics providers. The same survey was sent electronically to local providers. A separate survey was emailed to the labor and delivery nurses at two of the teaching hospitals in Indianapolis. The surveys queried provider demographics, dosing practice for misoprostol, opinions regarding different dosing strategies, and instructions on buccal administration. Results A total of 113 (46.5%) providers responded. Of these, 92.9% used misoprostol for IOL, 73% preferred the vaginal route, 20% preferred buccal administration, and 7% oral administration. Only resident physician and midwife providers endorsed buccal route preference. Being a midwife independently predicted a preference for using buccal misoprostol (odds ratio [OR]: 125.8, 95% confidence interval [CI]: 7.9–1992.3). Additionally, 44 nurses completed the survey regarding administration techniques of buccal misoprostol. Also, 54.5% of nurses correctly instructed their patients on buccal administration techniques. Conclusion Although not extensively studied, one-fifth of providers, particularly nurse midwives, prefer buccal administration of misoprostol for IOL. The majority of nurses correctly administered buccal misoprostol. There may be a need for further study and education about buccal administration of misoprostol for IOL.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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MAGEA4 expression in bone and soft tissue tumors: its utility as a target for immunotherapy and diagnostic marker combined with NY-ESO-1

Abstract

Cancer-testis (CT) antigens have promise as targets for immunotherapy, because of their restricted expression in tumor or testis tissue. MAGEA4 is both a MAGE family member and a CT antigen, and has attracted attention as a potential immunotherapeutic target. We investigated MAGEA4 expression by immunohistochemistry in bone and soft tissue tumor specimens that consisted of 35 malignant or intermediate and 24 benign histological subtypes, in order to evaluate its possible utility as an immunotherapy target and its potential use as a diagnostic marker when combined with another CT antigen, NY-ESO-1. Among these tumors, MAGEA4 was detected in 82.2% of synovial sarcomas, 67.7% of myxoid liposarcomas, 43.8% of osteosarcomas, 41.4% of angiosarcomas, 24.6% of malignant peripheral nerve sheath tumors (MPNSTs), and 21.4% of chondrosarcomas. NY-ESO-1 expression was found in 88.2% of myxoid liposarcomas, 61.1% of synovial sarcomas, 31.3% of osteosarcomas, 21.4% of pleomorphic liposarcomas, 16.7% of desmoplastic small round cell tumors, and 14.3% of chondrosarcomas. Benign tumors and non-tumorous tissue, except for testis tissue, did not express MAGEA4 or NY-ESO-1. Combined use of MAGEA4 and NY-ESO-1 increased the sensitivity, specificity, positive predictive values, and negative predictive values for distinguishing synovial sarcoma from spindle cell tumors and other mimicking tumors, compared to individual use of MAGEA4 or NY-ESO-1. Our results support the immunotherapy targeting MAGEA4 or NY-ESO-1 can be an ancillary therapy in the above-mentioned tumors, and the potential utility of MAGEA4 as an ancillary diagnostic marker for synovial sarcoma combined with NY-ESO-1.

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Sterile Drug Products by Cantrell Drug Company: Recall - Lack of Sterility Assurance

Audience: Health Professional, Risk Manager [Posted 07/25/2017] ISSUE: Cantrell Drug Company is voluntarily recalling all lots of unexpired sterile drug products to the hospital and user level due to lack of sterility assurance. The recalled...

http://ift.tt/2uVmytj

To intubate or not to intubate: emergency medicine physicians' perspective on intubating critically ill, terminal cancer patients

Emergency Physicians (EPs) often need to make a decision whether or not to intubate a terminal cancer patient.

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Supply-Side Differences Only Modestly Associated with Inpatient Hospitalizations among Medicare Beneficiaries in the Last 6 Months of Life

Inpatient hospitalizations are a driver of expenditures at the end of life and are a useful proxy for the intensity of care at that time.

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Altered Biodistribution of 99m Tc-DPD on Bone Scan After Intravenous Iron Supplement

Abstract

We report a case with altered biodistribution of ^99mTc-dicarboxypropane diphosphonate (^99mTc-DPD) on whole body bone scan after intravenous iron supplement therapy. A 47-year-old male patient who had recently been detected with a hepatic mass suggestive of hepatocellular carcinoma underwent bone scan as staging work-up before surgery. Bone scan images at 3 h after injection of ^99mTc-DPD demonstrated unusually increased blood pool activities in the heart, liver, and spleen with usual skeletal uptakes. The patient had been treated for severe anemia from hemorrhoid with two intravenous administration of ferric hydroxide carboxymaltose complex at approximately 22 h and 2 h prior to the ^99mTc-DPD injection, which we consider as the most probable cause of altered biodistribution of ^99mTc-DPD.

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Readmissions for Recurrent Sepsis: New or Relapsed Infection?.

Objectives: Sepsis hospitalizations are frequently followed by hospital readmissions, often for recurrent sepsis. However, it is unclear how often sepsis readmissions are for relapsed/recrudescent versus new infections. The aim of this study was to assess the extent to which 90-day readmissions for recurrent sepsis are due to infection of the same site and same pathogen as the initial episode. Design: Retrospective cohort study. Setting: University of Michigan Health System. Patients: All hospitalizations (May 15, 2013 to May 14, 2015) with a principal International Classification of Diseases, Ninth revision, Clinical Modification diagnosis of septicemia (038.x), severe sepsis (995.92), or septic shock (785.52), as well as all subsequent hospitalizations and sepsis readmissions within 90 days. We determined organism and site of sepsis through manual chart abstraction. Interventions: None. Measurements and Main Results: We identified 472 readmissions within 90 days of sepsis, of which 137 (29.1%) were for sepsis. In sepsis readmissions, the site and organisms were most commonly urinary (29.2%), gastrointestinal (20.4%), Gram negative (29.9%), Gram positive (16.8%), and culture negative (30.7%). Ninety-four readmissions (68.6%) were for infection at the same site as initial sepsis hospitalization. Nineteen percent of readmissions were confirmed to be same site and same organism. However, accounting for the uncertainty from culture-negative sepsis, as many as 53.2% of readmissions could plausibly due to infections with both the same organism and same site. Conclusions: Of the patients readmitted with sepsis within 90 days, two thirds had infection at the same site as their initial admission. Just 19% had infection confirmed to be from the same site and organism as the initial sepsis hospitalization. Half of readmissions were definitively for new infections, whereas an additional 34% were unclear since cultures were negative in one of the hospitalizations. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2uvtD2M

Can Concurrent Abnormalities in Free Light Chains and Immunoglobulin Concentrations Identify a Target Population for Immunoglobulin Trials in Sepsis?.

Objectives: Light chains [kappa] and [lambda] are immunoglobulin constituents but also circulate independently in blood as free light chains. We investigated whether a concomitant abnormality in free light chain and immunoglobulin levels could identify a high risk of death sepsis subpopulation to inform future IV immunoglobulin trials. We tested whether light chain allelic inclusion occurs in circulating B cells. Design: Prospective cohort study. Setting: Adult general ICUs. Patients: Adult sepsis patients without any documented immune comorbidity. Interventions: None. Measurements and Main Results: Serum total free light chain, immunoglobulin G, immunoglobulin A, and immunoglobulin M were measured on ICU days 1, 3, and 7. Population normal ranges defined normal and abnormal categories. Logistic regression models tested any independent relationship between high free light chain, immunoglobulins and hospital mortality. CD19 B-cell subsets expressing cell surface [kappa] and [lambda] were quantified by flow cytometry; their frequencies were compared against healthy subjects and correlation assessed against free light chain concentrations. On ICU day 1, high free light chain [lambda] and high free light chain [kappa] were seen in 46.5% and 75.3% of the study cohort (n = 101). Low immunoglobulin levels were commonplace (45.5%) at ICU admission. ICU admission day free light chain and immunoglobulin concentrations were significantly correlated. Septic patients had significantly more CD19 B cells expressing both [kappa] and [lambda] compared with healthy controls (median [interquartile range] 4.1% [2.4-11.0] vs 1.3% [1.2-2.9], respectively; p = 0.0001); these correlated with free light chain concentrations. Conclusions: To our knowledge, abnormalities and associations of free light chain in critically ill adults with sepsis have not been previously reported. The additional prognostic value of free light chain [lambda] and the significance of allelic inclusion in B cells in sepsis require further investigation. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Association Between Survival and Time of Day for Rapid Response Team Calls in a National Registry.

Objectives: Decreased staffing at nighttime is associated with worse outcomes in hospitalized patients. Rapid response teams were developed to decrease preventable harm by providing additional critical care resources to patients with clinical deterioration. We sought to determine whether rapid response team call frequency suffers from decreased utilization at night and how this is associated with patient outcomes. Design: Retrospective analysis of a prospectively collected registry database. Setting: National registry database of inpatient rapid response team calls. Patients: Index rapid response team calls occurring on the general wards in the American Heart Association Get With The Guidelines-Medical Emergency Team database between 2005 and 2015 were analyzed. Interventions: None. Measurements and Main Results: The primary outcome was inhospital mortality. Patient and event characteristics between the hours with the highest and lowest mortality were compared, and multivariable models adjusting for patient characteristics were fit. A total of 282,710 rapid response team calls from 274 hospitals were included. The lowest frequency of calls occurred in the consecutive 1 AM to 6:59 AM period, with 266 of 274 (97%) hospitals having lower than expected call volumes during those hours. Mortality was highest during the 7 AM hour and lowest during the noon hour (18.8% vs 13.8%; adjusted odds ratio, 1.41 [1.31-1.52]; p

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Reduced Functional Connectivity between Ventromedial Prefrontal Cortex and Insula Relates to Longer Corrected QT Interval in HIV+ and HIV- Individuals

Despite the widespread availability of antiretroviral therapy, mortality from cardiovascular disease (CVD) has increased for persons infected with human immunodeficiency virus (HIV) (Enakpene et al., 2015). A large proportion of this CVD comorbidity has been attributed to sudden cardiac death (Tseng et al., 2012). The QT interval reflects the latency between the initiation of the QRS-complex and end of the T-wave and is used as a general marker of ventricular repolarization (Drew et al., 2010). Clinical presentation of ventricular arrhythmias (i.e., torsade de pointes) is partially attributed to prolongation of the QT interval (Viskin, 1999).

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Spatial constraints evoke increased number of steps during turning in Parkinsońs disease

A hallmark of parkinsonian gait phenomenology is the patients' difficulty to perform standing or walking turns. Turns require the patients to repeatedly shift their weight, and this frequently contributes to falls (Robinovitch et al., 2013). A recent project evaluated objective home-recorded data which demonstrated that people with Parkinson's disease (PwP) showed reduced performance in turning while the overall activity was similar compared to healthy controls (Mancini et al., 2015). Independently from turning, progressive deterioration of stepping, i.e.

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Impact of novel miR-145-3p regulatory networks on survival in patients with castration-resistant prostate cancer

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Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

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Mitochondria on the move: emerging paradigms of organelle trafficking in tumour plasticity and metastasis

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Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study

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Extreme assay sensitivity in molecular diagnostics further unveils intratumour heterogeneity in metastatic colorectal cancer as well as artifactual low-frequency mutations in the KRAS gene

http://ift.tt/2tI1KFT

Embracing model-based designs for dose-finding trials

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Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma

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Post-translational regulation contributes to the loss of LKB1 expression through SIRT1 deacetylase in osteosarcomas

http://ift.tt/2tI3e2I

Comprehensive analysis of copy number aberrations in microsatellite stable colon cancer in view of stromal component

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Characterisation of blood-derived exosomal hTERT mRNA secretion in cancer patients: a potential pan-cancer marker

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A cancer geography paradox? Poorer cancer outcomes with longer travelling times to healthcare facilities despite prompter diagnosis and treatment: a data-linkage study

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Examining the Relationship Between Nursing Informatics Competency and the Quality of Information Processing.

The purpose of this study was to examine nursing informatics competency and the quality of information processing among nurses in Jordan. The study was conducted in a large hospital with 380 registered nurses. The hospital introduced the electronic health record in 2010. The measures used in this study were personal and job characteristics, self-efficacy, Self-Assessment Nursing Informatics Competencies, and Health Information System Monitoring Questionnaire. The convenience sample consisted of 99 nurses who used the electronic health record for at least 3 months. The analysis showed that nine predictors explained 22% of the variance in the quality of information processing, whereas the statistically significant predictors were nursing informatics competency, clinical specialty, and years of nursing experience. There is a need for policies that advocate for every nurse to be educated in nursing informatics and the quality of information processing. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2uyOnFd

"Anonymous Meltdown": Content Themes Emerging in a Nonfacilitated, Peer-only, Unstructured, Asynchronous Online Support Group for Family Caregivers.

By providing care for loved ones in the home, family caregivers save millions of dollars for our overtaxed healthcare system. Support groups can lighten the psychological burden of caregiving. Nonprofessionally facilitated (or peer) online caregiver support groups can help meet a critical need in healthcare as a low-cost resource for caregivers. Online caregiver peer support groups can promote the health and well-being of family caregivers and, by extension, the patients themselves, resulting in cost-savings for society. A better understanding of these types of groups is of critical importance, given the unrelenting pace of demographic shift in the United States. The purpose of this study was to examine content themes emerging from an unstructured, asynchronous online peer support group for family caregivers of people with chronic illness. Qualitative content analysis was used, yielding six themes: "experiencing the emotional toll," "need for catharsis/venting," "finding the silver linings," "seeking specific advice/problem solving," "realizing home is no longer a haven," and "adapting to the caregiver role." The themes reflect what emerged organically in an online support group that was not professionally facilitated or structured in any way. Heterogeneity in the relationship between caregivers and care recipients may negatively affect outcomes and requires further study. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2uVazvR

Ultrasound Imaging for Dorsal Ulnar Cutaneous Neuropathy With Extensor Carpi Ulnaris Tendinopathy.

No abstract available

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Role of Transesophageal Echocardiography in Surgery for Hemitruncus Arteriosus.

No abstract available

http://ift.tt/2vYiHsj

Medication Errors in Pediatric Anesthesia: A Report From the Wake Up Safe Quality Improvement Initiative.

BACKGROUND: Wake Up Safe is a quality improvement initiative of the Society for Pediatric Anesthesia that contains a deidentified registry of serious adverse events occurring in pediatric anesthesia. The aim of this study was to describe and characterize reported medication errors to find common patterns amenable to preventative strategies. METHODS: In September 2016, we analyzed approximately 6 years' worth of medication error events reported to Wake Up Safe. Medication errors were classified by: (1) medication category; (2) error type by phase of administration: prescribing, preparation, or administration; (3) bolus or infusion error; (4) provider type and level of training; (5) harm as defined by the National Coordinating Council for Medication Error Reporting and Prevention; and (6) perceived preventability. RESULTS: From 2010 to the time of our data analysis in September 2016, 32 institutions had joined and submitted data on 2087 adverse events during 2,316,635 anesthetics. These reports contained details of 276 medication errors, which comprised the third highest category of events behind cardiac and respiratory related events. Medication errors most commonly involved opioids and sedative/hypnotics. When categorized by phase of handling, 30 events occurred during preparation, 67 during prescribing, and 179 during administration. The most common error type was accidental administration of the wrong dose (N = 84), followed by syringe swap (accidental administration of the wrong syringe, N = 49). Fifty-seven (21%) reported medication errors involved medications prepared as infusions as opposed to 1 time bolus administrations. Medication errors were committed by all types of anesthesia providers, most commonly by attendings. Over 80% of reported medication errors reached the patient and more than half of these events caused patient harm. Fifteen events (5%) required a life sustaining intervention. Nearly all cases (97%) were judged to be either likely or certainly preventable. CONCLUSIONS: Our findings characterize the most common types of medication errors in pediatric anesthesia practice and provide guidance on future preventative strategies. Many of these errors will be almost entirely preventable with the use of prefilled medication syringes to avoid accidental ampule swap, bar-coding at the point of medication administration to prevent syringe swap and to confirm the proper dose, and 2-person checking of medication infusions for accuracy. (C) 2017 International Anesthesia Research Society

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Improving Adherence to Intraoperative Lung-Protective Ventilation Strategies at a University Medical Center.

BACKGROUND: Intraoperative lung-protective ventilation (ILPV) is defined as tidal volumes 65 kg. Surveyed providers demonstrated stronger agreement to having knowledge and practice consistent with ILPV after interventions. CONCLUSIONS: Our interventions improved anesthesia provider adherence to low tidal volume ILPV. IBW was found to be an important factor related to provider adherence to ILPV. Provider attitudes about their knowledge and practice consistent with ILPV also changed with our interventions. (C) 2017 International Anesthesia Research Society

http://ift.tt/2v6fNWb

Estimation of Stroke Volume and Stroke Volume Changes by Electrical Impedance Tomography.

BACKGROUND: Electrical impedance tomography (EIT) is a noninvasive imaging method that identifies changes in air and blood volume based on thoracic impedance changes. Recently, there has been growing interest in EIT to measure stroke volume (SV). The objectives of this study are as follows: (1) to evaluate the ability of systolic impedance variations ([DELTA]Zsys) to track changes in SV in relation to a baseline condition; (2) to assess the relationship of [DELTA]Zsys and SV in experimental subjects; and (3) to identify the influence of body dimensions on the relationship between [DELTA]Zsys and SV. METHODS: Twelve Agroceres pigs were instrumented with transpulmonary thermodilution catheter and EIT and were mechanically ventilated in a random order using different settings of tidal volume (VT) and positive end-expiratory pressure (PEEP): VT 10 mL[middle dot]kg-1 and PEEP 10 cm H2O, VT 10 mL[middle dot]kg-1 and PEEP 5 cm H2O, VT 6 mL[middle dot]kg-1 and PEEP 10 cm H2O, and VT 6 mL[middle dot]kg-1 and PEEP 5 cm H2O. After baseline data collection, subjects were submitted to hemorrhagic shock and successive fluid challenges. RESULTS: A total of 204 paired measurements of SV and [DELTA]Zsys were obtained. The 4-quadrant plot showed acceptable trending ability with a concordance rate of 91.2%. Changes in [DELTA]Zsys after fluid challenges presented an area under the curve of 0.83 (95% confidence interval, 0.74-0.92) to evaluate SV changes. Conversely, the linear association between [DELTA]Zsys and SV was poor, with R2 from linear mixed model of 0.35. Adding information on body dimensions improved the linear association between [DELTA]Zsys and SV up to R2 from linear mixed model of 0.85. CONCLUSIONS: EIT showed good trending ability and is a promising hemodynamic monitoring tool. Measurements of absolute SV require that body dimensions be taken into account. (C) 2017 International Anesthesia Research Society

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Venovenous Bypass Is Associated With a Lower Incidence of Acute Kidney Injury After Liver Transplantation in Patients With Compromised Pretransplant Renal Function.

BACKGROUND: Although the hemodynamic benefits of venovenous bypass (VVB) during liver transplantation (LT) are well appreciated, the impact of VVB on posttransplant renal function is uncertain. The aim of this study was to determine if VVB was associated with a lower incidence of posttransplant acute kidney injury (AKI). METHODS: Medical records of adult (>=18 years) patients who underwent primary LT between 2004 and 2014 at a tertiary hospital were reviewed. Patients who required pretransplant renal replacement therapy and intraoperative piggyback technique were excluded. Patients were divided into 2 groups, VVB and non-VVB. AKI, determined by the Acute Kidney Injury Network criteria, was compared between the 2 groups. Propensity match was used to control selection bias that occurred before VVB and multivariable logistic regression was used to control confounding factors during and after VVB. RESULTS: Of 1037 adult patients who met the study inclusion criteria, 247 (23.8%) received VVB. A total of 442 patients (221 patients in each group) were matched. Aftermatch patients were further divided according to a predicted probability AKI model using preoperative creatinine (Cr), VVB, and intraoperative variables into 2 subgroups: normal and compromised pretransplant renal functions. In patients with compromised pretransplant renal function (Cr >=1.2 mg/dL), the incidence of AKI was significantly lower in the VVB group compared with the non-VVB group (37.2% vs 50.8%; P = .033). VVB was an independent risk factor negatively associated with AKI (odds ratio, 0.1; 95% confidence interval, 0.1-0.4; P = .001). Renal replacement in 30 days and 1-year recipient mortality were not significantly different between the 2 groups. The incidence of posttransplant AKI was not significantly different between the 2 groups in patients with normal pretransplant renal function (Cr

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Lack of Association Between the Use of Nerve Blockade and the Risk of Persistent Opioid Use Among Patients Undergoing Shoulder Arthroplasty: Evidence From the Marketscan Database.

BACKGROUND: Persistent opioid use following surgery has received increasing attention from policymakers, researchers, and clinicians. Perioperative nerve blockade has been hypothesized to decrease the risk of persistent opioid use. We examined whether nerve blockade was associated with a decreased risk of persistent opioid use among patients undergoing shoulder arthroplasty, a procedure with high rates of persistent postoperative pain. METHODS: Using health care claims data, we constructed a sample of 6695 patients undergoing shoulder arthroplasty between 2002 and 2012 and used billing data to identify the utilization of nerve blockade. We then used a multivariable logistic regression to estimate the association between nerve blockade and 2 measures of opioid use: having filled at least 1 prescription for an opioid between postoperative days (PODs) 0 and 90, and between POD 91 and 365. This regression adjusted for a variety of potential confounders, such as preoperative opioid use and medical history. RESULTS: There was no association between nerve blockade and our 2 measures of persistent opioid use: adjusted odds ratio, 1.12 (97.5% confidence interval, 0.939-1.34; P = .15) for opioid use between POD 0 and 90, and adjusted odds ratio, 0.997 (97.5% confidence interval, 0.875-1.14; P = .95) for opioid use between POD 91 and 365. CONCLUSIONS: Although the use of perioperative nerve blockade may offer short-term benefits, in this study, it was not associated with a reduction in the risk of persistent opioid use for patients undergoing shoulder arthroplasty. (C) 2017 International Anesthesia Research Society

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Quality and Safety in Anesthesia and Perioperative Care.

No abstract available

http://ift.tt/2v64mOd

Absent Pulmonary Valve in a Case of Tetralogy of Fallot: An Incidental Discovery on Intraoperative Transesophageal Echocardiography.

No abstract available

http://ift.tt/2v63KIs

Do Not Fear the Difficult IV.

No abstract available

http://ift.tt/2vYtItv

End-Expiratory Occlusion Test Predicts Fluid Responsiveness in Patients With Protective Ventilation in the Operating Room.

BACKGROUND: End-expiratory occlusion test (EEOT) has been proposed to predict fluid responsiveness in mechanically ventilated intensive care unit patients. The utility of this test during low-tidal-volume ventilation remains uncertain. This study aimed to determine whether hemodynamic variations induced by EEOT could predict the effect of volume expansion in patients with protective ventilation in the operating room. METHODS: Forty-one patients undergoing neurosurgery were included. Stroke volume and pulse pressure variations were continuously recorded using pulse contour analysis before and immediately after a 30-second EEOT and after volume expansion (250 mL saline 0.9% given over 10 minutes). Patients with an increase in stroke volume >= 10% after volume expansion were defined as responders. RESULTS: Twenty patients were responders to fluid administration. EEOT induced a significant increase in stroke volume, which was correlated with the stroke volume changes induced by volume expansion (r2 = 0.55, P

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Erratum

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Erratum

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Erratum

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Current trends in patient enrollment for robotic-assisted laparoscopic prostatectomy in Belgium

BACKGROUND

During the last decade, an inverse stage migration has been observed in radical prostatectomy series at tertiary centers. However, it remains unclear whether similar trends can also be observed in solely robotic practices, including nonreferral centers. The aim of this study was to investigate the clinical and pathological trends in robotic-assisted laparoscopic prostatectomy (RALP) enrollment in Belgium over a period of 6 years through an analysis of a prospective registry.

METHODS

A prospective, multicenter database was constructed: consecutive patients undergoing RALP in Belgium from 2010 to 2015 were enrolled, and 7366 men were analyzed. Variations in clinical and pathological variables were explored as a function of the enrollment year with proportional odds for categorical variables and with linear regressions for continuous variables.

RESULTS

Net increases were observed in the prostate-specific antigen levels, cT stage, and biopsy Gleason scores across the study years (P < .001). The rate of low-risk prostate cancer (PCa) decreased from 36% in 2010 to 21% in 2015, whereas the rate of intermediate-risk PCa rose from 47% to 58%, and the rate of high-risk PCa rose from 17% to 21%. In parallel, the pT2 stage rate decreased from 76% to 64%, and the rate of Gleason 6 (3 + 3) cases was reduced from 45% to 23% (P < .001). Conversely, the pT3a stage rate rose from 16% to 24%, the pT3b stage rate rose from 7% to 11%, and the rate of Gleason 7 (4 + 3) cases rose from 7% to 21% (P < .0001). Finally, more patients underwent node dissection, and positive lymph nodes were increasingly diagnosed (from 3% in 2010 to 7% in 2015).

CONCLUSIONS

During the last 6 years of RALP implementation in Belgium, there was a significant increase in the enrollment of intermediate- and high-risk PCa patients. This yielded a significant increase in adverse pathological characteristics. These results suggest a paradigm shift in PCa treatment, with radical robotic surgery increasing for intermediate- and high-risk patients. Cancer 2017. © 2017 American Cancer Society.

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HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium

BACKGROUND

Human epidermal growth factor receptor 2 (HER2) mutations have been reported in lung adenocarcinomas. Herein, the authors describe the prevalence, clinical features, and outcomes associated with HER2 mutations in 1007 patients in the Lung Cancer Mutation Consortium (LCMC).

METHODS

Patients with advanced-stage lung adenocarcinomas were enrolled to the LCMC. Tumor specimens were assessed for diagnosis and adequacy; multiplexed genotyping was performed in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories to examine 10 oncogenic drivers. The LCMC database was queried for patients with HER2 mutations to access demographic data, treatment history, and vital status. An exploratory analysis was performed to evaluate the survival of patients with HER2 mutations who were treated with HER2-directed therapies.

RESULTS

A total of 920 patients were tested for HER2 mutations; 24 patients (3%) harbored exon 20 insertion mutations (95% confidence interval, 2%-4%). One patient had a concurrent mesenchymal-epithelial transition factor (MET) amplification. The median age of the patients was 62 years, with a slight predominance of females over males (14 females vs 10 males). The majority of the patients were never-smokers (71%) and presented with advanced disease at the time of diagnosis. The median survival for patients who received HER2-targeted therapies (12 patients) was 2.1 years compared with 1.4 years for those who did not (12 patients) (P = .48). Patients with HER2 mutations were found to have inferior survival compared with the rest of the LCMC cohort with other mutations: the median survival was 3.5 years in the LCMC population receiving targeted therapy and 2.4 years for patients not receiving targeted therapy.

CONCLUSIONS

HER2 mutations were detected in 3% of patients with lung adenocarcinoma in the LCMC. HER2-directed therapies should be investigated in this subgroup of patients. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2h1osmh

Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era: Cohort study of 477 patients

BACKGROUND

Outcomes in patients with chronic myeloid leukemia in blast phase (CML-BP) are historically dismal. Herein, the authors sought to analyze the characteristics, prognostic factors, and survival outcomes in patients with CML-BP in the tyrosine kinase inhibitor (TKI) era.

METHODS

A total of 477 patients with CML-BP were treated with a TKI at some point during the course of their CML. Cox proportional hazard models identified characteristics that were predictive of survival. Overall survival and failure-free survival were assessed. Optimal cutoff points for specific parameters were identified using classification and regression tree (CART) analysis.

RESULTS

The median age of the patients was 53 years (range, 16-84 years) and 64% were male. Approximately 80% of patients initially were diagnosed in the chronic phase of CML at a median of 41 months (range, 0.7-298 months) before transformation to CML-BP. De novo CML-BP occurred in 71 patients. Approximately 72% of patients received TKI therapy before CML-BP. The initial therapy for CML-BP included a TKI alone (35%), a TKI with chemotherapy (46%), and non-TKI therapies (19%). The median overall survival was 12 months and the median failure-free survival was 5 months. In multivariate analysis, myeloid immunophenotype, prior TKI, age ≥58 years, lactate dehydrogenase level ≥1227 IU/L, platelet count < 102 K/μL, no history of stem cell transplantation, transition to BP from chronic phase/accelerated phase, and the presence of chromosome 15 aberrations predicted for a significantly increased risk of death. Achievement of major hematologic response and/or complete cytogenetic response to first-line treatment was found to be predictive of better survival. The combination of a TKI with intensive chemotherapy followed by stem cell transplantation appeared to confer the best outcome.

CONCLUSIONS

Patients with CML-BP continue to pose a therapeutic challenge, have dismal outcomes, and require newer treatment approaches. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2eLY4vY

Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic myeloid leukemia

BACKGROUND

Several studies have demonstrated that approximately one-half of patients with chronic myeloid leukemia (CML) who receive treatment with tyrosine kinase inhibitors (TKIs) and achieve and maintain a deep molecular response (DMR) are able to successfully discontinue therapy. In patients who have a molecular relapse, a DMR is rapidly regained upon treatment re-initiation.

METHODS

The authors report the results from RE-STIM, a French observational, multicenter study that evaluated treatment-free remission (TFR) in 70 patients who re-attempted TKI discontinuation after a first unsuccessful attempt. After the second TKI discontinuation attempt, the trigger for treatment re-introduction was the loss of a major molecular response in all patients.

RESULTS

The median follow-up was 38.3 months (range, 4.7-117 months), and 45 patients (64.3%) lost a major molecular response after a median time off therapy of 5.3 months (range, 2-42 months). TFR rates at 12, 24, and 36 months were 48% (95% confidence interval [CI], 37.6%-61.5%), 42% (95% CI, 31.5%-55.4%), and 35% (95% CI, 24.4%-49.4%), respectively. No progression toward advanced-phase CML occurred, and no efficacy issue was observed upon TKI re-introduction. In univariate analysis, the speed of molecular relapse after the first TKI discontinuation attempt was the only factor significantly associated with outcome. The TFR rate at 24 months was 72% (95% CI, 48.8%-100%) in patients who remained in DMR within the first 3 months after the first TKI discontinuation and 36% (95% CI, 25.8%-51.3%) for others.

CONCLUSIONS

This study is the first to demonstrate that a second TKI discontinuation attempt is safe and that a first failed attempt at discontinuing TKI does not preclude a second successful attempt. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2h17dlp

Chronic hepatitis C virus infection and neurocognitive function in adult survivors of childhood cancer

BACKGROUND

Cancer survivors transfused with blood products before reliable screening for hepatitis C virus (HCV) are at risk for infection. This study examined the impact of HCV on neurocognitive function and health-related quality of life (HRQOL) among adult survivors of childhood cancer.

METHODS

Neurocognitive testing was conducted for 836 adult survivors of childhood cancer (mean age, 35 years [standard deviation, 7.4 years]; time since diagnosis, 29 years [standard deviation, 6.2 years]) who received blood products before universal HCV screening. No differences were observed between confirmed HCV-seropositive survivors (n = 79) and HCV-seronegative survivors (n = 757) in the primary diagnosis or neurotoxic therapies. Multivariate regression models were used to compare functional outcomes between seropositive and seronegative survivors.

RESULTS

Compared with seronegative survivors, seropositive survivors demonstrated lower performance on measures of attention (P < .001), processing speed (P = .008), long-term verbal memory (P = .01), and executive function (P = .001). After adjustments for sex, age at diagnosis, and treatment exposures, seropositive survivors had a higher prevalence of impairment in processing speed (prevalence ratio [PR], 1.3; 95% confidence interval [CI], 1.1-1.6) and executive functioning (PR, 1.3; 95% CI, 1.1-1.6). Differences were not associated with the treatment of HCV or the presence of liver cirrhosis. Seropositive survivors reported worse general HRQOL (PR, 1.6; 95% CI, 1.2-2.1), which was associated with the presence of liver cirrhosis (P = .001).

CONCLUSIONS

Survivors of childhood cancer with a history of HCV infection are at risk for neurocognitive impairment and reduced HRQOL beyond the known risks associated with neurotoxic cancer therapies. Cancer 2017. © 2017 American Cancer Society.

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Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology

BACKGROUND

Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, to the authors' knowledge, it is unknown whether this benefit persists in histological variants. The objective of the current study was to assess the effect of neoadjuvant chemotherapy on the probability of non-organ-confined disease and overall survival after radical cystectomy (RC) in patients with histological variants.

METHODS

Querying the National Cancer Data Base, the authors identified 2018 patients with histological variants who were undergoing RC for bladder cancer between 2003 and 2012. Variants were categorized as micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, neuroendocrine tumors, and other histology. Logistic regression models estimated the odds of non-organ-confined disease at the time of RC for each histological variant, stratified by the receipt of neoadjuvant chemotherapy. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup.

RESULTS

Patients with neuroendocrine tumors (odds ratio [OR], 0.16; 95% confidence interval [95% CI], 0.08-0.32 [P<.001]), micropapillary differentiation (OR, 0.30; 95% CI, 0.10-0.95 [P=.041]), sarcomatoid urothelial carcinoma (OR, 0.40; 95% CI, 0.17-0.94 [P=.035]), and adenocarcinoma (OR, 0.24; 95% CI, 0.06-0.91 [P=.035]) were less likely to harbor non-organ-confined disease at the time of RC when treated with neoadjuvant chemotherapy. An overall survival benefit for neoadjuvant chemotherapy was only found in patients with neuroendocrine tumors (hazard ratio, 0.49; 95% CI, 0.33-0.74 [P=.001]).

CONCLUSIONS

Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better overall survival and lower rates of non-organ-confined disease at the time of RC. For tumors with micropapillary differentiation, sarcomatoid differentiation, or adenocarcinoma, neoadjuvant chemotherapy decreased the frequency of non-organ-confined disease at the time of RC. However, this favorable effect did not translate into a statistically significant overall survival benefit for these patients, potentially due to the aggressive tumor biology. Cancer 2017;000:000-000. © 2017 American Cancer Society.

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Propper 4PV Armor records first save

ST. CHARLES, Mo. — Troup County (GA) Sheriff's Deputy Michael Hockett, 24 years old and newly married, recently became the best kind of statistic – a survivor – thanks in part to his Propper 4PV concealable armor. According to the sheriff's office, Hockett was responding just before noon on January 9 to a welfare check call in the rural community when he was allegedly shot ...

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Firefighters treat colleague for an hour after he collapses at barbecue

Firefighter-paramedics gave Steve Sawatzky CPR for nearly an hour while waiting for an ambulance at a company outing

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ALK and ROS1 testing on lung cancer cytologic samples: Perspectives

Cytologic sampling is the mainstay of diagnosing advanced lung cancer. Moreover, to select patients for personalized first-line or second-line treatment, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangements are tested on cytologic preparations. Commercially available fluorescence in situ hybridization (FISH) and immunocytochemistry (ICC) assays have primarily been used for the identification of cells harboring ALK or ROS1 gene fusions on histologic rather than cytologic preparations. However, it is now recognized that FISH and ICC also can be applied on cytologic samples provided the cytopathologist is aware that FISH and ICC results are not always concordant and that the performance of ICC largely depends on antibody clones, signal detection systems, and scoring systems. Notably, the routine clinical use of FISH and ICC may be replaced by emerging next-generation sequencing and digital, color-coded barcode technologies, which have the advantage of simultaneously evaluating ALK, ROS1, and EGFR alterations in a single analysis. Although their use in clinical cytologic practice remains to be fully established, it is conceivable that this technology will replace both FISH and ICC analyses in future diagnostic algorithms. Here, the authors review studies devoted to testing ALK and ROS1 on cytology specimens in an attempt to provide an update for the cytopathologist regarding current and evolving practice. Cancer (Cancer Cytopathol) 2017. © 2017 American Cancer Society.

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Morbidity in the Mountainous Province of Kyrgyzstan: Results from a Population-Based Cross-Sectional Study

High Altitude Medicine & Biology , Vol. 0, No. 0.


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Particle rejuvenation of Rao-Blackwellized sequential Monte Carlo smoothers for conditionally linear and Gaussian models

This paper focuses on sequential Monte Carlo approximations of smoothing distributions in conditionally linear and Gaussian state spaces. To reduce Monte Carlo variance of smoothers, it is typical in these mod...

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Cancer-associated fibroblasts promote bone invasion in oral squamous cell carcinoma

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Leukocyte telomere length and renal cell carcinoma survival in two studies

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The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

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Intracrine VEGF signalling mediates colorectal cancer cell migration and invasion

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Evidence for genetic association between chromosome 1q loci and predisposition to colorectal neoplasia

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Ambulance hit by bullets on way to call

One paramedic was treated at the hospital after getting hit by shards of glass when the bullet passed through the windshield

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Outcome of oscillating saw open osteotomy in two-stage lower extremity bone transport with monolateral frame

Publication date: Available online 25 July 2017
Source:Injury
Author(s): Pablo S. Corona, Luis Ramírez Nuñez, Carles Amat, Luis Carrera
IntroductionBone transport techniques have been widely used to solve massive bone defects due to trauma, osteomyelitis or bone tumors. The technique of bone interruption to achieve better new bone formation is a subject of debate. Low-energy osteotomy (LEO) techniques have been proposed as the gold standard. Some authors reject open osteotomy with an oscillating saw (OOS osteotomy), based on the danger of bone tissue thermal necrosis and periosteal damage. To date, however, there is no strong clinical evidence to discourage this high-energy (HEO) bone interruption technique.MethodsThe aim of this study was to determine outcomes in using OOS osteotomy in a series of patients, where monolateral-frame bone transport has been used to resolve segmental bone defects of the lower extremity. The minimum accepted follow-up was 1year. The primary endpoints were radiographic evidence of regenerated bone quality (Li classification) and final outcome (Cattaneo clinical system assessment). Further, we analyzed associated complications, and compared results with other published series. We hypothesized that OOS osteotomy produces results no less favorable than those achieved with other, low-energy techniques.ResultsA total of 54 patients, with an average bone defect of 8.58cm (CI95% 7.01–10.16), were enrolled in the study. In terms of regeneration quality, 84% of the regenerated segment shapes were associated with good outcomes; only 16% exhibited a shape (hypotrophic) predictive of a poor outcome. Regarding functional assessment, following the Cattaneo system, we found a total of 90% good or excellent results. Finally, the Bone Healing Index (BHI) in our series averaged 21.09days per cm. The main complication observed was pin-track infection, occurring in 45% of the cases.ConclusionAccording our data, the superiority of an LEO technique over HEO techniques is yet to be confirmed; it appears that any open osteotomy is effective, performed well and in a proper clinical setting, and that many factors other than choice of osteotomy technique must play important roles.



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Generating Stability in Elderly Acetabular Fractures − A Biomechanical Assessment

Publication date: Available online 24 July 2017
Source:Injury
Author(s): Clay A. Spitler, Dirk Kiner, Rachel Swafford, Daniel Doty, Ron Goulet, LaRita C. Jones, Josie Hydrick, Peter Nowotarski
Background & objectivesAs the overall health and life expectancy increases in the United States, the incidence of fragility fractures in elderly patients also continues to increase. Given their medical comorbidities and decreased bone mineral density, acetabular fractures in the elderly population present a significant challenge to the orthopaedic trauma surgeon. The anterior column posterior hemitransverse (ACPHT) fracture pattern is a common fracture pattern in this population, and is often associated with central subluxation/dislocation of the femoral head with articular impaction. This study sought to delineate the most stable fixation construct in ACPHT fracture patterns in the elderly population.Materials and methodsThe sample consisted of 3 groups of synthetic hemipelves (N=15), which were tested in order to compare stiffness by measuring motion at fracture lines under applied loads. The three groups of unique quadrilateral plate fixation were as follows: a specialty quadrilateral surface plate; 4 long peri-articular screws parallel to the quadrilateral surface into the ischium,; and an 8 hole infrapectineal buttress plate. Digital imaging system measured construct motion under load. Construct stiffness was estimated by linear regression of load between 50 and 850N versus average relative motion (average of relative motion at 200 points along the line of the osteotomy). Permanent deformation was estimated as the magnitude of relative motion upon unloading.ResultsUsing ANOVA with Tukey's test to determine construct stiffness in loading, the group long peri-articular screws was found to have significantly higher stiffness than either of the other groups. Maximal fracture displacement was located at the intersection of the low transverse fracture line in the posterior column and the free quadrilateral surface fragment.



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Effectiveness of Controlled Telescoping System for Lateral Hip Pain Caused by Sliding of Blade following Intramedullary Nailing of Trochanteric Fracture

Publication date: Available online 25 July 2017
Source:Injury
Author(s): Suk Kyu Choo, Hyoung-Keun Oh, Hyeong Tak Ko, Dong-Uk Min, Youngwoo Kim
IntroductionThe purpose of this study was to demonstrate the effectiveness of controlled telescoping system for lateral hip pain caused by sliding of the blade following intramedullary nailing of trochanteric fractures.Materials and MethodsA retrospective cohort study was performed to compare the controlled telescoping system (Compression Hip Nail; CHN) with the conventional sliding system (Proximal Femoral Nail Antirotation; PFNA) for trochanteric fractures. 74 cases in the PFNA group and 77 cases in the CHN group were included from two university hospitals in this study. All patients had a minimum of 12-month follow up period. Lateral hip pain was evaluated and operation time and blood loss during the surgery were measured. The fracture classification was evaluated. The quality of postoperative reduction and other complications after surgery were also evaluated and tip-apex distance (TAD), telescoping and lateral protrusion of the blade and lag screw were measured.ResultsThe mean age was 78.5 years in the PFNA group and 74.7 years in the CHN group (p=0.25). The mean telescoping was 19.2mm in the PFNA group and 10.7mm in the CHN group (p<0.001). The mean length of lateral protrusion was 10.5mm in the PFNA group and 2.5mm in the CHN group (p<0.001). Twenty-eight patients in the PFNA group complained of lateral hip pain, whereas 12 patients in the CHN group did (p=0.002). These four variables showed statistically significant differences between the PFNA and CHN groups (p<0.05). The length of lateral protrusion was the only variable significantly related to lateral hip pain through multivariate logistic regression analysis (p=0.045).ConclusionsThe degree of lateral protrusion was mainly related to lateral hip pain. Therefore, controlled telescoping would help to decrease lateral hip pain by decreasing the lateral protrusion beyond the lateral femoral cortex.



http://ift.tt/2h0eW34

FDA Grants Full Approval to Blinatumomab for Acute Lymphoblastic Leukemia

FDA changed its accelerated approval of blinatumomab (Blincyto) for some patients with acute lymphoblastic leukemia to a full approval and expanded the approved indications for its use.

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A Method to Assess Bacteriocin Effects on the Gut Microbiota of Mice

Bacteriocins are believed to play a key role in defining microbial diversity in different ecological niches. Here, we describe an efficient procedure to assess how bacteriocins affect gut microbiota composition in an animal model.

http://ift.tt/2vGoT90

The effects of semantic congruency: a research of audiovisual P300-speller

Over the past few decades, there have been many studies of aspects of brain–computer interface (BCI). Of particular interests are event-related potential (ERP)-based BCI spellers that aim at helping mental typ...

http://ift.tt/2tWKZC5

Impact of major different variants of papillary thyroid microcarcinoma on the clinicopathological characteristics: the study of 1041 cases

Abstract

Background

The incidence of papillary thyroid microcarcinoma (PTMC) has been increasing globally in the past few decades. PTMC does not have a distinctive morphology that results in differences in biological behavior. The aim of this study was to classify PTMCs according to the morphological features and explore the relationship with clinicopathological characteristics. Additionally, we sought to evaluate whether different variants of PTMC can be an independent predictor for lymph mode metastasis when considering other risk factors.

Methods

Between December 2014 and December 2015, 1041 PTMC cases undergoing surgical resection at Tianjin Medical University Cancer Institute and Hospital were reviewed retrospectively. Statistical analysis was performed to investigate the independent factors for lymph node metastasis in PTMC.

Results

Conventional variant PTMC (CPTMC), follicular variant PTMC (FPTMC), and encapsulated variant PTMC (EnPTMC) were major variants in PTMC, collectively accounting for 96.7% of the entire PTMC cohort.There were significant differences in clinicopathological characteristics among the three major variants. The frequency of aggressive parameters was significantly different among the three variants, including tumor size, minimal extrathyroidal extension (minimal ETE), and lymph node metastasis (all P < 0.05), being highest in CPTMC, lowest in EnPTMC, and intermediate in FPTMC. FPTMC (OR = 0.642, P = 0.003) and EnPTMC (OR = 0.540, P = 0.041) were independent protective factors for lymph node metastasis (LNM). In contrast, male gender (OR = 1.836, P = 0.000), age less than 45 years (OR = 1.457, P = 0.009), tumor size greater than 0.5 cm (OR = 1.453, P = 0.007), calcification (OR = 1.465, P = 0.016), minimal ETE (OR = 1.801, P = 0.001), and multifocality (OR = 1.721, P = 0.000) were independent risk factors for LNM.

Conclusions

The present study demonstrates the distinct biological behaviors of the three major PTMC variants and establishes an aggressive order of CPTMC ≫ FPTMC > EnPTMC. It is necessary to take into consideration variant-related risks and other independent predictors for the determination of lymphadenectomy in patients with PTMC.

http://ift.tt/2vG6mcT

Recovery from TBI

A recent study suggests that recovery from TBI (traumatic brain injury) may be different between males and female subjects. Historically, TBI studies have used predominately male subjects, whether they be mice or men. However, investigating the effects of injury, disease, and pharmacological treatments in both male and female subjects has led to significant changes to clinical practice across numerous disciplines.

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Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia

Mosaic clone analysis in Drosophila imaginal disc epithelia is a powerful model system to study the genetic and cellular mechanisms of tumorigenesis. Here we describe a protocol to induce tumors in Drosophila wing imaginal discs using the GAL4-UAS system, and introduce a diagnosis method to classify the tumor phenotypes.

http://ift.tt/2uUaFUh

Canadian firefighters treat colleague after he collapses at barbecue

Firefighter paramedics gave Steve Sawatzky CPR for nearly an hour while waiting for an ambulance at a company outing

http://ift.tt/2eLp4f4

Tubal Cytology of the Fallopian Tube as a Promising Tool for Ovarian Cancer Early Detection

We explored a tubal cytologic method by sampling the fallopian tube directly post-surgical excision as a tool of ovarian cancer early detection. Here, we present a protocol to collect fallopian tube cells from freshly received surgical specimens.

http://ift.tt/2v51yke

Time-lapse Confocal Imaging of Migrating Neurons in Organotypic Slice Culture of Embryonic Mouse Brain Using In Utero Electroporation

This protocol provides instructions for direct observation of radially migrating cortical neurons. In utero electroporation, organotypic slice culture, and time-lapse confocal imaging are combined to directly and dynamically study the effects of overexpression or downregulation of genes of interest in migrating neurons and to analyze their differentiation during development.

http://ift.tt/2v5cDBJ

VEGFA Involves in the Use of Fluvastatin and Zoledronate Against Breast Cancer

Abstract

Our study aimed to identify key genes involved in the use of fluvastatin and zoledronate against breast cancer, as well as to investigate the roles of vascular endothelial growth factor A (VEGFA) in the malignant behaviors of breast cancer cells. The expression data GSE33552 was downloaded from Gene Expression Omnibus database, including mocked-, fluvastatin- and zoledronate-treated MDA-MB-231 cells. Differentially expressed genes (DEGs) were identified in fluvastatin- and zoledronate-treated cells using limma package, respectively. Pathway enrichment analysis and protein-protein interaction (PPI) network analysis were then performed. Then we used shRNA specifically targeting VEGFA (shVEGFA) to knock down the expression of VEGFA in MDA-MB-231 cells. Cell viability assay, scratch wound healing assay, Transwell invasion assay and flow cytometry were performed to explore the effects of VEGFA knockdown on the malignant behaviors of breast cancer cells. VEGFA was up-regulated in both fluvastatin- and zoledronate-treated breast cancer cells. Moreover, VEGFA was a hub node in PPI network. In addition, VEGFA was successfully knocked down in MDA-MB-231 cells by shVEGFA. Suppression of VEGFA promoted the migration and invasion of breast cancer MDA-MB-231 cells. Suppression of VEGFA inhibited the apoptosis of MDA-MB-231 cells. Our results indicate that up-regulation of VEGFA may prevent the progression of breast cancer after fluvastatin and zoledronate treatment via inducing cell apoptosis and inhibiting migration and invasion. VEGFA may serve as a potential prognostic indicator for clinical outcome in the management of breast cancer.

http://ift.tt/2uUe0CT

The effect of frequency-specific sound signals on the germination of maize seeds

The effects of sound treatments on the germination of maize seeds were determined.

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Emergence of fluoroquinolone resistance among drug resistant tuberculosis patients at a tertiary care facility in Karachi, Pakistan

Pakistan is classified as one of the high multi-drug resistant tuberculosis (MDR-TB) burden countries. A poorly regulated private sector, over-prescription of antibiotics and self-medication has led to augment...

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Assessment of inhaled corticosteroids use and associated factors among asthmatic patients attending Tikur Anbessa Specialized Hospital, Ethiopia

Inhaled corticosteroids (ICSs) are cornerstone therapy for persistent asthma. However, underutilization of ICSs is common and little is known about factors contributing toward this undesirable use.

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A hospital based surveillance of metallo-beta-lactamase producing gram negative bacteria in Nepal by imipenem-EDTA disk method

A rising threat of the rapid spread of acquired metallo-beta-lactamases (MBLs) among major Gram-negative pathogens is a matter of public health concern worldwide. Hence, for a low income nation like Nepal, sur...

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Multiorgan eosinophilic infiltration after initiation of clozapine therapy: a case report

The eosinophilic response to clozapine is well described in the literature, causing a variety of responses, from serositis to colitis. However, there are not case reports describing a clozapine-induced marked ...

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Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement

Abstract

Background

Base excision repair (BER) pathway is a DNA repair pathway that is important in carcinogenesis and in response to DNA-damaging chemotherapy. XRCC1 is one of important molecular markers for BER. So far, the role of XRCC1 polymorphisms with clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy is inconclusive. To explore the relationship between XRCC1 polymorphisms and platinum-based chemotherapy in advanced NSCLC patients, we performed this meta-analysis.

Methods

Crude odds ratios (ORs), Cox proportional hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were adopted to assess the strength of association between XRCC1 polymorphisms and response rate, Overall survival (OS) and progression free survival (PFS) of advanced NSCLC treated with platinum-based chemotherapy. Q test and I ² test were used for the assessment of heterogeneity. Subgroup analyses were conducted when heterogeneity exists. Begg's funnel plots and Egger's linear regression test were used to estimate publication bias. Sensitivity analysis was performed to evaluate the stability of the result.

Results

A total of 19 studies including 2815 individuals were eligible for the analysis, results showed XRCC1 194Arg allele was negatively associated with the objective response rate relative to 194Trp, and results of homozygous model, dominant model and heterozygous model suggested a gene dosage effect negative correlation between 194Arg allele and objective response rate(ArgArg vs TrpTrp: OR = 0.64(95%CI: 0.44-0.91); ArgArg + TrpArg vs TrpTrp: OR = 0.79(95%CI: 0.57-1.11); TrpArg vs TrpTrp: OR = 1.05(95%CI: 0.73-1.51)). XRCC1 399Gln may indicate favorable overall survival (GlnGln + GlnArg vs ArgArg: HR = 0.65(95%CI: 0.43–0.98)) and favorable PFS (GlnGln vs ArgArg: HR = 0.72(95%CI: 0.48–0.97)) in Asian patients; while in Caucasian patients, XRCC1 399Gln indicated poorer overall survival (GlnGln vs ArgArg: HR = 2.29(95%CI: 1.25–3.33)).

Conclusions

Our results indicated that in NSCLC patients treated with platinum-based regimen, XRCC1 194Arg allele suggest poor objective response rate, the GlnGln genotype of XRCC1 399 suggest poorer overall survival in Caucasian patients, and longer PFS in Asian patients.

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Detection of 22 common leukemic fusion genes using a single-step multiplex qRT-PCR-based assay

Fusion genes generated from chromosomal translocation play an important role in hematological malignancies. Detection of fusion genes currently employ use of either conventional RT-PCR methods or fluorescent i...

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Association of combined GIF290T>C heterozygous mutation/FUT2 secretor variant with neural tube defects

Folate and vitamin B12 are needed for the proper embryo-fetal development possibly through their interacting role in the one-carbon metabolism. Folate fortification reduces the prevalence of complex birth defects, and more specifically neural tube defects (NTD). GIF and FUT2 are two genes associated with the uptake and blood level of vitamin B12. We evaluated GIF and FUT2 as predictors of severe birth defects, in 181 aborted fetuses compared to 375 healthy newborns. The GIF290C allele frequency was estimated to 0.4% in healthy newborns and to 8.1% in NTD fetuses (odds ratio 17.8 (95% CI: 4.0-77.6)). The frequency of FUT2 rs601338 secretor variant was not different among groups. The GIF 290C heterozygous /FUT2 rs601338 secretor variant combined genotype was reported in 6 of the 37 NTD fetuses, but not in other fetuses and healthy newborns (P<0.0001). This GIF/FUT2 combined genotype has been previously reported in children with congenital GIF deficiency, with respective consequences on B12 binding activity and GIF secretion. In conclusion, a genotype reported in congenital GIF deficiency produces also severe forms of NTD. This suggests that vitamin B12 delivery to neural tissue by the CUBN/GIF pathway could play a role in the neural tube closure mechanisms.

http://ift.tt/2eL9ksB

Functional movement disorders

Purpose of review: The review highlights the clinical presentation of functional movement disorders (FMDs) and presents current evidence on bedside signs and paraclinical tests to differentiate them from other neurological disorders. Recent findings: FMDs are diagnosed by the presence of positive clinical signs as emphasized in the new Diagnostic and Statistical Manual of Mental Disorders-5 classification criteria. Bedside signs are numerous, and a subset of them has been validated in controlled studies. This review summarizes evidence from the literature on specificity and sensibility of positive clinical signs for FMDs. The value of rule-in paraclinical tests to confirm the diagnosis is also presented. Recent developments in neuroscience with pathophysiological mechanisms and current treatment strategies are also discussed. Summary: FMDs represent a field of neurology that is currently rapidly growing in terms of research. Clinicians should be aware that highly reliable signs exist for the diagnosis and that early multidisciplinary treatment should be offered.

http://ift.tt/2uxjIrT

Sleep-related movement disorders and disturbances of motor control

Purpose of review: Review of the literature pertaining to clinical presentation, classification, epidemiology, pathophysiology, diagnosis, and treatment of sleep-related movement disorders and disturbances of motor control. Recent findings: Sleep-related movement disorders and disturbances of motor control are typically characterized by positive motor symptoms and are often associated with sleep disturbances and consequent daytime symptoms (e.g. fatigue, sleepiness). They often represent the first or main manifestation of underlying disorders of the central nervous system, which require specific work-up and treatment. Diverse and often combined cause factors have been identified. Although recent data provide some evidence regarding abnormal activation and/or disinhibition of motor circuits during sleep, for the majority of these disorders the pathogenetic mechanisms remain speculative. The differential diagnosis is sometimes difficult and misdiagnoses are not infrequent. The diagnosis is based on clinical and video-polysomnographic findings. Treatment of sleep-related motor disturbances with few exceptions (e.g. restless legs/limbs syndrome) are based mainly on anecdotal reports or small series. Summary: More state-of-the-art studies on the cause, pathophysiology, and treatment of sleep-related movement disorders and disturbances of motor control are needed.

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Measuring compensation in neurodegeneration using MRI

Purpose of review: Despite signs of cortical and subcortical loss, patients with prodromal and early-stage neurodegenerative disease are able to perform at a level comparable to the normal population. It is presumed that the onset of compensatory processes, that is changes in brain activation within a function-specific network or in the recruitment of a region outside of the task-network, underlies this maintenance of normal performance. However, in most studies to date, increased brain activity is not correlated with indices of both disease and performance and what appears to be compensation could simply be a symptom of neurodegeneration. Recent findings: MRI studies have explored compensation in neurodegenerative disease, claiming that compensation is evident across a number of disorders, including Alzheimer's and Parkinson's disease, but generally always in early stages; after this point, compensation is generally no longer able to operate under the severe burden of disease. However, none of these studies explicitly adopted a particular model of compensation. Thus, we also discuss our recent attempts to operationalize compensation for empirical testing. Summary: There is clear evidence of compensatory processes in the early stages of neurodegenerative disease. However, for a more complete understanding, this requires more explicit empirical modelling.

http://ift.tt/2uxw975

Editorial introductions

No abstract available

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Neuroimaging in Parkinson's disease: focus on substantia nigra and nigro-striatal projection

Purpose of review: The diagnosis of Parkinson disease is based on clinical features; however, unmet need is an imaging signature for Parkinson disease and the early differential diagnosis with atypical parkinsonisms. A summary of the molecular imaging and MRI recent evidences for Parkinson disease diagnosis will be presented in this review. Recent findings: The nigro-striatal dysfunction explored by dopamine transporter imaging is not a mandatory diagnostic criterion for Parkinson disease, recent evidence supported its utility as in-vivo proof of degenerative parkinsonisms, and there might be compensatory mechanisms leading to an early overestimation. The visualization of abnormalities in substantia nigra by MRI has been recently described as sensitive and specific tool for Parkinson disease diagnosis, even in preclinical conditions, whereas it is not useful for distinguishing between Parkinson disease and atypical parkinsonisms. The relationship between the nigral anatomical changes, evaluated as structural alterations or neuromelanin signal decrease and the dopaminergic nigro-striatal function needs to be further clarified. Summary: With the hopeful advent of potential neuroprotective drugs for PD, it is crucial to have imaging measures that are able to detect at risk subjects. Moreover it is desirable to increase the knowledge about which measure better predicts the probability and the time of clinical conversion to PD.

http://ift.tt/2uxpD09

Neuroimaging as a tool to study the sources of phenotypic heterogeneity in Huntington's disease

Purpose of review: Huntington's disease is a neurodegenerative disorder characterized by a triad of motor, cognitive and psychiatric disturbances. There is great variability regarding the prominence and evolution of each type of clinical sign. One possible source of phenotypic heterogeneity could be the more prominent degeneration of specific brain circuits. The scope of this review is to highlight the most recent neuroimaging studies that have analysed the relationship between brain changes and motor, cognitive and psychiatric alterations in Huntington's disease. Recent findings: The results from recent neuroimaging studies are heterogeneous. Although there is a great overlap between the different regions associated with each symptomatic domain, there is some degree of differentiation. For example, the motor network is associated with motor impairment, whereas the ventral striatum is especially involved in emotional deficits related with psychiatric problems. Summary: Motor, cognitive and psychiatric impairments are associated with structural and functional brain biomarkers. However, the specificity of the regions involved remains unknown, because these studies focused on specific regions and symptoms. In order to tease apart the neural substrates that underlie the phenotypic heterogeneity in Huntington's disease, multivariate approaches combining brain and behavioural measures related to all symptomatic domains should be considered in the future.

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New neurosurgical approaches for tremor and Parkinson's disease

Purpose of review: The objective of this review is to gather the newest advances in the surgical treatment of tremor and Parkinson's disease. We will briefly discuss the potential applications of the new technologies of deep brain stimulation (DBS), and we will focus on MRI-guided focused ultrasound (MRgFUS). Recent findings: Novel DBS devices are being progressively adopted, particularly electrodes allowing a longer stimulating surface (suitable for multiple targets stimulation) and current radial steering (to minimize side effects of stimulation). New implantable pulse generators are also able to record neurons and are generating enough knowledge to advance the implementation of adaptive (closed-loop) DBS. Over the last years, 'minimally-invasive' neurosurgical approaches for the treatment of movement disorders have been developed: gamma knife radiosurgery and MRgFUS. Uncontrolled and recent controlled studies have shown the benefits of MRgFUS targeting the thalamus and pallidus for the treatment of tremor and Parkinson's disease. Summary: The initial clinical data are certainly promising and have expanded the current portfolio of neurosurgical treatments of movement disorders. Many issues are yet to be addressed, particularly safety of MRgFUS-and how these new treatments compare with the existing ones.

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Photo-Cross-Linking of IKs Demonstrates State-Dependent Interactions between KCNE1 and KCNQ1

The slow delayed rectifier potassium current (IKs) is a key repolarizing current during the cardiac action potential. It consists of four KCNQ1 α-subunits and up to four KCNE1 β-subunits, which are thought to reside within external clefts of the channel. The interaction of KCNE1 with KCNQ1 dramatically delays opening of the channel but the mechanisms by which this occur are not yet fully understood. Here, we have used unnatural amino acid photo-cross-linking to investigate the dynamic interactions that occur between KCNQ1 and KCNE1 during activation gating.

http://ift.tt/2uWa9F5

Relieving the Pressure on Tissue Development

Understanding how tissue patterning emerges during embryogenesis is a long-standing goal of developmental biology. In particular, the complex interplay between extracellular and intracellular mechanical forces and biochemical cues that lead to cellular differentiation and ultimately adult tissue remains an active area of investigation. One of the main challenges has been that experimental methods that allow for the simultaneous measurement of mechanical force and biochemical signaling are limited.

http://ift.tt/2uW84Jf

Ions Modulate Stress-Induced Nanotexture in Supported Fluid Lipid Bilayers

Most plasma membranes comprise a large number of different molecules including lipids and proteins. In the standard fluid mosaic model, the membrane function is effected by proteins whereas lipids are largely passive and serve solely in the membrane cohesion. Here we show, using supported 1,2-dioleoyl-sn-glycero-3-phosphocholine lipid bilayers in different saline solutions, that ions can locally induce ordering of the lipid molecules within the otherwise fluid bilayer when the latter is supported.

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Modeling of Biomechanics and Biorheology of Red Blood Cells in Type 2 Diabetes Mellitus

Erythrocytes in patients with type-2 diabetes mellitus (T2DM) are associated with reduced cell deformability and elevated blood viscosity, which contribute to impaired blood flow and other pathophysiological aspects of diabetes-related vascular complications. In this study, by using a two-component red blood cell (RBC) model and systematic parameter variation, we perform detailed computational simulations to probe the alteration of the biomechanical, rheological, and dynamic behavior of T2DM RBCs in response to morphological change and membrane stiffening.

http://ift.tt/2uWnHAe

The Unique Protein-to-Protein Carotenoid Transfer Mechanism

Orange Carotenoid Protein (OCP) is known as an effector and regulator of cyanobacterial photoprotection. This 35 kDa water-soluble protein provides specific environment for blue-green light absorbing keto-carotenoids, which excitation causes dramatic but fully reversible rearrangements of the OCP structure, including carotenoid translocation and separation of C- and N-terminal domains upon transition from the basic orange to photoactivated red OCP form. Although recent studies greatly improved our understanding of the OCP photocycle and interaction with phycobilisomes and the fluorescence recovery protein, the mechanism of OCP assembly remains unclear.

http://ift.tt/2uW1hiV

Death Receptor 5 Activation Is Energetically Coupled to Opening of the Transmembrane Domain Dimer

The precise mechanism by which binding of tumor necrosis factor ligands to the extracellular domain of their corresponding receptors transmits signals across the plasma membrane has remained elusive. Recent studies have proposed that activation of several tumor necrosis factor receptors, including Death Receptor 5, involves a scissorlike opening of the disulfide-linked transmembrane (TM) dimer. Using time-resolved fluorescence resonance energy transfer, we provide, to our knowledge, the first direct biophysical evidence that Death Receptor 5 TM-dimers open in response to ligand binding.

http://ift.tt/2uW5LG4