A New EBV Related Technologies of T Cells in Treating Malignant Tumors and Clinical Application

Condition:   Nasopharyngeal Neoplasms
Intervention:   Other: CAR-T cells
Sponsor:   The Second Hospital of Nanjing Medical University
Recruiting - verified November 2016

http://ift.tt/2gv76MT

Improvement of Outcomes in Draf III/Endoscopic Modified Lothrop Procedure

Conditions:   Chronic Sinusitis;   Frontal Sinusitis
Intervention:   Device: Porcine Intestinal submucosal xenograft
Sponsor:   University of California, Los Angeles
Recruiting - verified November 2016

http://ift.tt/2ghlqpe

The Use of Integra in Coverage of Radial Forearm Free Flap Donor Site Defect

Condition:   Head and Neck Cancer
Interventions:   Device: Integra plus STSG;   Procedure: STSG
Sponsor:   Comprehensive Cancer Center of Wake Forest University
Recruiting - verified November 2016

http://ift.tt/2gv6oPE

Dual Inhibition of EGFR With Afatinib and Cetuximab in the Treatment of Recurrent or Metastatic Squamous Cell Cancers of the Head and Neck

Condition:   Squamous Cell Cancers of the Head and Neck
Interventions:   Drug: cetuximab;   Drug: afatinib
Sponsors:   Aarti Bhatia;   National Comprehensive Cancer Network;   Boehringer Ingelheim
Not yet recruiting - verified November 2016

http://ift.tt/2ghi8SM

Phase II/III Study Comparing Chemoradiotherapy With Radiotherapy in Elderly Patients With Esophageal or Esophagogastric Cancer

Conditions:   Esophagus Cancer;   Esophagogastric Junction Cancer;   Radiotherapy; Complications;   Chemoradiation
Interventions:   Radiation: SIB-IMRT;   Drug: S-1
Sponsors:   Chinese Academy of Medical Sciences;   Hebei Medical University Fourth Hospital;   Tianjin Medical University Cancer Institute and Hospital;   Anyang Tumor Hospital;   The First Affiliated Hospital with Nanjing Medical University;   Affiliated Hospital of Hebei University;   Fujian Cancer Hospital
Recruiting - verified December 2016

http://ift.tt/2gvbyep

Megestrol Acetate Against Cancer-related Critical Body Weight Loss in Patients With H&N Cancer Who Receiving CCRT

Condition:   Head and Neck Cancer
Intervention:   Drug: Megestrol acetate (MA) 400 mg/day
Sponsors:   TTY Biopharm;   Chang Gung Memorial Hospital
Recruiting - verified July 2016

http://ift.tt/2ghfcG9

Modulation of a Circulating Uremic Solute via Rational Genetic Manipulation of the Gut Microbiota

Publication date: Available online 1 December 2016
Source:Cell Host & Microbe
Author(s): A. Sloan Devlin, Angela Marcobal, Dylan Dodd, Stephen Nayfach, Natalie Plummer, Tim Meyer, Katherine S. Pollard, Justin L. Sonnenburg, Michael A. Fischbach
Renal disease is growing in prevalence and has striking co-morbidities with metabolic and cardiovascular disease. Indoxyl sulfate (IS) is a toxin that accumulates in plasma when kidney function declines and contributes to the progression of chronic kidney disease. IS derives exclusively from the gut microbiota. Bacterial tryptophanases convert tryptophan to indole, which is absorbed and modified by the host to produce IS. Here, we identify a widely distributed family of tryptophanases in the gut commensal Bacteroides and find that deleting this gene eliminates the production of indole in vitro. By altering the status or abundance of the Bacteroides tryptophanase, we can modulate IS levels in gnotobiotic mice and in the background of a conventional murine gut community. Our results demonstrate that it is possible to control host IS levels by targeting the microbiota and suggest a possible strategy for treating renal disease.

Graphical abstract

Teaser

Devlin et al. identify a widely distributed family of indole-producing tryptophanases in commensal gut bacteria. Using this information, they engineer bacteria to control in vivo production of the downstream product, the uremic toxin indoxyl sulfate. These results suggest a new strategy for treating chronic kidney disease by targeting the microbiome.


http://ift.tt/2fP7Qx2

Genesis, Evolution and Prevalence of H5N6 Avian Influenza Viruses in China

Publication date: Available online 1 December 2016
Source:Cell Host & Microbe
Author(s): Yuhai Bi, Quanjiao Chen, Qianli Wang, Jianjun Chen, Tao Jin, Gary Wong, Chuansong Quan, Jun Liu, Jun Wu, Renfu Yin, Lihua Zhao, Mingxin Li, Zhuang Ding, Rongrong Zou, Wen Xu, Hong Li, Huijun Wang, Kegong Tian, Guanghua Fu, Yu Huang, Alexander Shestopalov, Shoujun Li, Bing Xu, Hongjie Yu, Tingrong Luo, Lin Lu, Xun Xu, Yang Luo, Yingxia Liu, Weifeng Shi, Di Liu, George Fu Gao
Constant surveillance of live poultry markets (LPMs) is currently the best way to predict and identify emerging avian influenza viruses (AIVs) that pose a potential threat to public health. Through surveillance of LPMs from 16 provinces and municipalities in China during 2014–2016, we identified 3,174 AIV-positive samples and isolated and sequenced 1,135 AIVs covering 31 subtypes. Our analysis shows that H5N6 has replaced H5N1 as one of the dominant AIV subtypes in southern China, especially in ducks. Phylogenetic analysis reveals that H5N6 arose from reassortments of H5 and H6N6 viruses, with the hemagglutinin and neuraminidase combinations being strongly lineage specific. H5N6 viruses constitute at least 34 distinct genotypes derived from various evolutionary pathways. Notably, genotype G1.2 virus, with internal genes from the chicken H9N2/H7N9 gene pool, was responsible for at least five human H5N6 infections. Our findings highlight H5N6 AIVs as potential threats to public health and agriculture.

Graphical abstract

Teaser

Live poultry market (LPM) surveillance helps identify emerging avian influenza viruses. By surveillance of Chinese LPMs in 2014–2016, Bi et al. discover that H5N6 has become a dominant AIV subtype in southern China, especially in ducks. At least 34 distinct H5N6 genotypes were noted, four responsible for human infections.


http://ift.tt/2fP2Qc6

Twenty years of triptans in the United States Medicaid programs: Utilization and reimbursement trends from 1993 to 2013

Objective

After sumatriptan was approved by the Food and Drug Administration in 1992, triptans became first-line anti-migraine therapies. Rapidly rising triptan expenditures, however, led payers, including Medicaid, to implement cost-containment policies. We describe triptan utilization and reimbursement trends in Medicaid.

Methods

Using national summary files for outpatient drug utilization, utilization and expenditure data from 1993 to 2013 were extracted and summed for all triptan national drug codes reimbursed by Medicaid. Data were collected separately for tablets, injections and sprays.

Results

The number of triptan prescriptions increased from 87,348 in 1993 to 0.9 million in 2004; fell to 0.4 million in 2009; rose to 1 million in 2011; and rose 1.2 million in 2013. In 2013, Medicaid spent $96.8 million on triptans: 74.4%, 18.4% and 7.2% for tablets, injections and sprays, respectively. Average reimbursement per prescription was $54 for tablets, $351 for injections and $235 for sprays in 2013. From 1993 to 2013, sumatriptan was the most widely prescribed among the triptans.

Conclusions

The substantial increase in triptan prescriptions from 2009 to 2011, without being convincingly explained by either rising migraine prevalence or rising Medicaid enrollment, is suggestive of reduced access to these medications prior to 2009. Cost-containment policies may have inadvertently prevented Medicaid migraineurs from obtaining appropriate pharmacotherapy.

Prior presentations

An earlier version of this paper was presented as a poster at the Annual Meeting of the International Society for Pharmacoeconomics and Outcomes Research, Philadelphia, PA, May 2015, where it received a finalist award.

http://ift.tt/2fP6eUn

Cardiac monitoring of high-dose verapamil in cluster headache: An international Delphi study

Background

In many patients, high-dose verapamil (HDV) is the only effective prophylactic treatment for cluster headache. Although cardiac adverse events and EKG abnormalities are relatively common, evidence-based guidelines for screening and monitoring patients on HDV are lacking.

Goal and methods

Using the Delphi approach, we interviewed 22 international clinical experts in cardiac rhythm disorders to formulate EKG guidelines for the pretreatment screening and monitoring of cluster headache patients using HDV.

Results

The panel agreed only on performing pretreatment EKG to screen for pre-existing cardiac arrhythmia. Pretreatment EKG was deemed not necessary by most panel members for patients who did not have cardiac adverse events during a previous period of cluster headache attacks treated with HDV. Half the panel advised Holter EKG for patients on verapamil ≥ 480 mg/day. The highest recommended daily doses varied between 240 and 960 mg. Contraindications for use of verapamil largely followed FDA guidelines.

Discussion

Experts in cardiac rhythm disorders agreed on pretreatment EKG monitoring, but no consensus was reached on EKG monitoring during HDV treatment and around dose adjustments.

http://ift.tt/2gVi0IQ

Migraine is related to an increased risk of Parkinsons disease: A population-based, propensity score-matched, longitudinal follow-up study

Background

The association between migraine and Parkinson's disease (PD) remains controversial. The purpose of the present population-based, propensity score-matched follow-up study was to investigate whether migraineurs are at a higher risk of developing PD.

Methods

A total of 41,019 subjects aged between 40 and 90 years with at least two ambulatory visits with a diagnosis of migraine in 2001 were enrolled in the migraine group. A logistic regression model that included age, sex, pre-existing comorbidities and socioeconomic status as covariates was used to compute the propensity score. The non-migraine group consisted of 41,019 propensity score-matched, randomly sampled subjects without migraine. The PD-free survival rate were estimated using the Kaplan–Meier method. Stratified Cox proportional hazard regression was used to estimate the effect of migraine on the risk of developing PD.

Results

During follow-up, 148 subjects in the migraine group and 101 in the non-migraine group developed PD. Compared to the non-migraine group, the hazard ratio of PD for the migraine group was 1.64 (95% confidence interval: 1.25–2.14, p = 0.0004). The PD-free survival rate for the migraine group was significantly lower than that for the non-migraine group (p = 0.0041).

Conclusions

This study showed an increased risk of developing PD in patients with migraine.

http://ift.tt/2fP0SIF

Dynamics of a haemodynamic headache: A case report and literature review of headache secondary to flow inversion of the internal jugular vein

Background

Haemodialysis arteriovenous fistulas have common local and regional complications, but are rarely associated with neurological symptoms.

Case report

A 43-year-old woman presented with short acute episodes of unilateral, non-throbbing, severe headache, vertigo and left lateropulsion. She had undergone renal transplantation and had a still-functioning left brachial arteriovenous fistula. No abnormality was detected on neurological examination or on brain parenchymal imaging. Colour Doppler ultrasonography showed a subclavian steal syndrome of the left vertebral artery and reversed flow in the left internal jugular vein. Ligation of the arteriovenous fistula had to be delayed as a result of renal graft dysfunction. Six months later she developed a headache attributed to intracranial hypertension. All symptoms subsided after ligation of the arteriovenous fistula.

Literature review

We identified 16 case reports of central neurological complications attributed to haemodialysis brachial fistulas. Headache descriptions were scarce and were not fully detailed.

Conclusions

The case of our patient suggests that unilateral, episodic, non-throbbing, non-postural headache with transient neurological symptoms can be caused by combined arterial and venous flow abnormalities secondary to a high-flow arteriovenous brachial fistula. In this setting, this pattern of headache may precede overt signs of intracranial hypertension and may be used as a warning sign of cerebral venous congestion.

http://ift.tt/2gVfjXv

Gray matter changes related to medication overuse in patients with chronic migraine

Objective

The objective of this article is to investigate the neurological substrates associated with medication overuse (MO) in patients with chronic migraine (CM).

Methods

We recruited age- and sex-matched CM patients with MO (CMwMO), CM patients without MO (CMwoMO), and healthy controls (HCs). Magnetic resonance T1-weighted images were processed by voxel-based morphometry, and the findings were correlated with clinical variables and treatment responses.

Results

A total of 66 patients with CM (half with MO) and 33 HCs completed the study. Patients with CMwMO compared to the patients with CMwoMO showed gray matter volume (GMV) decrease in the orbitofrontal cortex and left middle occipital gyrus as well as GMV increase in the left temporal pole/parahippocampus. The GMV changes explained 31.1% variance of the analgesics use frequency. The patients who responded to treatment had greater GMV in the orbitofrontal cortex (p = 0.028). Patients with CM (with and without MO), compared with HCs, had decreased GMV at multiple brain areas including the frontal, temporal and occipital lobes, precuneus and cerebellum.

Conclusions

Our study showed GMV changes in CMwMO patients compared to the CMwoMO patients. These three cerebral regions accounted for significant variance in analgesics use frequency. Moreover, the GMV of the orbitofrontal cortex was predictive of the response to MO treatments.

http://ift.tt/2fP2iTg

Cryopyrin-associated periodic fever syndrome manifesting as Tolosa-Hunt syndrome

Background

Tolosa-Hunt syndrome (THS) is characterized by unilateral orbital pain, ipsilateral oculomotor paresis and a prompt response to treatment with corticosteroids. Several reports have demonstrated that the clinical features of THS are not specific to one causal aetiology and can lead to misdiagnosis.

Case report

We report the case of a patient diagnosed with THS after an episode of unilateral orbital pain and diplopia with demonstration of granulomatous inflammation of both cavernous sinus on cerebral magnetic resonance imaging and an immediate response to treatment with corticosteroids. Progression of the disease over the following years, accompanied by increasing signs of inflammation on cerebral magnetic resonance imaging and cerebrospinal fluid pleocytosis, led to further diagnostic tests. Genetic analyses revealed a heterozygote low-penetrance mutation (Q703K) of the cryopyrin/NLRP3 gene compatible with a cryopyrin-associated periodic fever syndrome.

Discussion

This case report demonstrates that THS can be a central nervous system manifestation of cryopyrin-associated periodic fever syndrome, which therefore represents a differential diagnosis of THS, even in elderly patients.

http://ift.tt/2gVa8Hk

The phenotype of migraine with unilateral cranial autonomic symptoms documents increased peripheral and central trigeminal sensitization. A case series of 757 patients

Background

Migraine with unilateral cranial autonomic symptoms (UAS) is a putative migraine endophenotype with convincing response to trigeminal-targeted treatments that still needs a thorough characterization.

Objective

The objective of this article is to carefully investigate the clinical phenotype of migraine with UAS in a large group of patients for more accurate migraine diagnoses, improved clinical management, and better outcome prediction.

Methods

We studied 757 consecutive episodic and chronic migraineurs in a tertiary headache clinic with face-to-face interviews, detailing in depth their lifestyle, sociodemographic and headache characteristics.

Results

Migraineurs with UAS (37.4%) differed from the general migraine population with respect to longer attack duration (OR = 2.47, p < 0.02, having >72-hour long attacks), more strictly unilateral (OR = 3.18, p < 0.001) and severe headache (OR = 1.72, p = 0.011), more frequent allodynia (OR = 3.03, p < 0.001) and photophobia (OR = 1.87, p = 0.019).

Conclusions

Migraine patients with UAS are characterized not only by symptoms due to intense peripheral trigeminal activation but also to central sensitization. Our study broadens the knowledge on the clinical and phenotypic characteristics of migraine with UAS, suggests pathophysiological implications, and supports the need for future prospective clinical studies.

http://ift.tt/2fP5y1a

Vanishing calcification associated with a spontaneous ventral spinal cerebrospinal fluid leak

Background

Some patients with spontaneous intracranial hypotension have a ventral spinal cerebrospinal fluid (CSF) leak and these CSF leaks may be associated with calcified disk herniations. Identifying these calcifications is helpful in directing treatment. We report here the unusual case of a patient with a ventral CSF leak in whom the associated calcification absorbed over a five-month period.

Case report

A 42-year-old woman developed orthostatic headaches and bilateral abducens nerve palsies. Magnetic resonance imaging of her brain showed typical findings of spontaneous intracranial hypotension. Magnetic resonance imaging of her spine showed an extensive cervicothoracic CSF leak. Computed tomographic myelography showed calcification at the Th1–2 disk space. Three epidural blood patches were performed, but her symptoms persisted. Digital subtraction myelography performed five months later showed an upper thoracic ventral CSF, but the calcification was no longer present. A dural tear, found at surgery at the Th1–2 level, was repaired and the patient made an uneventful recovery.

Discussion

The resorption of calcifications at the level of a ventral spinal CSF leak could explain the absence of any calcifications in at least some patients with such leaks and demonstrates the usefulness of reviewing previous imaging in patients with ventral CSF leaks if the exact site of the leak remains unknown.

http://ift.tt/2gVevCb

Migraine and endothelial function: The HUNT3 Study

Background

Reduced endothelial function is associated with elevated risk of cardiovascular disease, but evidence on the association between migraine and endothelial function is conflicting. The aim of this population-based study was to examine the relationship between flow-mediated dilatation (FMD) and migraine with aura, migraine without aura and tension-type headache.

Methods

In the third Nord-Trøndelag Healthy Study (HUNT3) FMD was measured by ultrasound during reactive hyperaemia of the brachial artery in a sample of 4739 healthy adult participants, 3929 of whom answered headache questions. The cross-sectional association between different headache diagnoses and FMD was evaluated by logistic regression, using a categorical approach.

Results

Mean FMD did not differ between the headache groups and headache-free controls. In multi-adjusted analyses, no consistent association was found between FMD quintiles and headache groups.

Conclusions

There was no relationship between FMD and migraine or other headache diagnoses in this large cross-sectional study of otherwise healthy respondents including freedom from pulmonary and cardiovascular diseases.

http://ift.tt/2fP6bIb

Decreased levels of aquaporin-4 in the cerebrospinal fluid of patients with idiopathic intracranial hypertension

Background

Idiopathic intracranial hypertension is characterized by increased intracranial pressure. Its pathogenesis is largely unknown. Aquaporins may play a role in the homeostasis of cerebrospinal fluid.

Methods

We aimed to elucidate the role of aquaporins in idiopathic intracranial hypertension by measuring the level of aquaporin-1 and aquaporin-4 in the cerebrospinal fluid and plasma of 28 patients and 29 controls by enzyme-linked immunosorbent assay. The adipokines leptin and retinol-binding protein 4 were also measured.

Results

We found a reduction in aquaporin-4 in the cerebrospinal fluid of patients. Leptin levels were increased in the cerebrospinal fluid and plasma of patients and were correlated with weight, body mass index and body fat. There was no difference between patients and controls in the levels of aquaporin-4 and retinol-binding protein 4.

Conclusion

Our data suggest that an imbalance of aquaporin-4 in the cerebrospinal fluid of patients with idiopathic intracranial hypertension may contribute to the pathogenesis of this disorder.

http://ift.tt/2gV7fWI

Headache of neurally mediated syncope

Background

Neurally mediated syncope and migraine have a complex relationship.

Aim

The aim of this study was to investigate whether patients developing syncope in the laboratory would experience migraine.

Methods

Thirty-one consecutive patients were evaluated for precipitation of headache during head-up tilt (HUT)-induced syncope (reduction of systolic blood pressure [SBP] >20 mmHg and prodromal symptoms with or without loss of consciousness). Autonomic functions were assessed using heart rate response to deep breathing (HRDB), Valsalva maneuver and HUT. Blood pressure and heart rate (via electrocardiography) were continuously monitored. Headache diagnosis was based on ICHD-3 criteria.

Results

Eighteen patients (58%) experienced syncope without headache and 13 (42%) had syncope and headache (SH). No difference was observed in time of syncope onset, reduction in SBP, Valsalva ratio, HRDB or tachycardia during initial 10 minutes of HUT. Of the 13 SH patients, 11 (85%) had a past history of migraine. Two reported headache just before tilt, eight developed headache during tilt and three developed headache only after tilt. Headache resolved within 1–15 minutes in 10 out of 13 patients. No patient experienced migraine.

Conclusions

Syncope did not precipitate migraine. Headache during syncope may be due to cerebral hypoperfusion, and cerebral hyperperfusion may cause post-syncopal headache.

http://ift.tt/2fP2eD6

Case report: Epicranial pain after radiotherapy for skull base meningioma - the first symptomatic epicrania fugax?

Background

To date, no symptomatic forms of epicrania fugax (EF) have been reported. Here, we describe the first EF-type pain to be probably caused by an underlying disorder.

Case report

A 77-year-old woman started suffering from left V1–V2 trigeminal neuralgia at 72 years of age. Neurologic examination was normal. Magnetic resonance imaging (MRI) showed a left middle sphenoid wing meningioma compressing the left trigeminal nerve medially. After trying several neuromodulators, she received stereotactic radiotherapy. One month later, the episodes of facial pain were significantly diminished, but she started feeling brief electric paroxysms across her left hemicranium that were clinically identical to those of backwards EF. Serial MRI showed persistence of the meningioma without changes.

Conclusion

Although the pathogenesis of EF remains uncertain, this case is consistent with a symptomatic origin in the trigeminal root/pathway. The onset of the EF-like pain could have been caused by the compressive effect of the tumour or, most likely, by the radiation.

http://ift.tt/2gV7XU9

Psychological factors associated with failure of detoxification treatment in chronic headache associated with medication overuse

Aim

The aim of this study was to evaluate the psychological factors associated with a negative outcome following detoxification in a 2-month follow-up in medication-overuse headache.

Methods

All consecutive patients entering the detoxification program were analysed in a prospective, non-randomised fashion. Psychiatric conditions and personality characteristics were assessed using the Structured Clinical Interview for DSM-IV Disorders (SCID-I) and the Minnesota Multiphasic Personality Inventory (MMPI)-2. ² tests, one-way analyses of variance, and odds ratios (ORs) were used.

Results

A total of 248 patients completed the follow-up: 156 stopped overuse and their headaches reverted to an episodic pattern (Group A); 23 kept overusing without any benefit on headache frequency (Group B); and 51 stopped overuse without any benefit on headache frequency (Group C). The prognostic factors for the outcome of Group B were higher scores on the correction (OR 1.128; p = 0.036), depression (OR 1.071; p = 0.05), hysteria (OR 1.106; p = 0.023), and overcontrolled hostility (OR 1.182; p = 0.04) MMPI-2 scales, whereas those for Group C were psychiatric comorbidities (OR 1.502; p = 0.021) and higher scores on the hysteria scale (OR 1.125; p = 0.004).

Conclusions

The outcome of detoxification is influenced by psychological factors that should be considered when considering treatment strategies.

http://ift.tt/2fP4nie

Recurrent painful ophthalmoplegia in a patient with diabetes mellitus: Is ophthalmoplegia associated with diabetes mellitus?

http://ift.tt/2gVkruM

A Review of the Recent Advances in Antimicrobial Coatings for Urinary Catheters

Publication date: Available online 1 December 2016
Source:Acta Biomaterialia
Author(s): Priyadarshini Singha, Jason Locklin, Hitesh Handa
More than 75% of hospital-acquired or nosocomial urinary tract infections are initiated by urinary catheters, which are used during the treatment of 15-25% of hospitalized patients. Among other purposes, urinary catheters are primarily used for draining urine after surgeries and for urinary incontinence. During catheter-associated urinary tract infections, bacteria travel up to the bladder and cause infection. A major cause of catheter-associated urinary tract infection is attributed to the use of non-ideal materials in the fabrication of urinary catheters. Such materials allow for the colonization of microorganisms, leading to bacteriuria and infection, depending on the severity of symptoms. The ideal urinary catheter is made out of materials that are biocompatible, antimicrobial, and antifouling. Although an abundance of research has been conducted over the last forty-five years on the subject, the ideal biomaterial, especially for long-term catheterization of more than a month, has yet to be developed. The aim of this review is to highlight the recent advances (over the past 10 years) in developing antimicrobial materials for urinary catheters and to outline future requirements and prospects that guide catheter materials selec tion and design.Statement of SignificanceThis review article intends to provide an expansive insight into the various antimicrobial agents currently being researched for urinary catheter coatings. According to CDC, approximately 75% of urinary tract infections are caused by urinary catheters and 15-25% of hospitalized patients undergo catheterization. In addition to these alarming statistics, the increasing cost and health related complications associated with Catheter Associated UTIs make the research for antimicrobial urinary catheter coatings even more pertinent. This review provides a comprehensive summary of the history, the latest progress in development of the coatings and a brief conjecture on what the future entails for each of the antimicrobial agents discussed.

Graphical abstract

http://ift.tt/2gQjWUe

Management of metastatic thyroid cancer in pregnancy: risk and uncertainty

Metastatic thyroid cancer is an uncommon condition to be present at the time of pregnancy, but presents a challenging paradigm of care. Clinicians must balance the competing interests of long-term maternal health, best achieved by iatrogenic hyperthyroidism, regular radioiodine therapy and avoidance of dietary iodine, against the priority to care for the developing foetus, with inevitable compromise. Additionally, epidemiological and cellular data support the role of oestrogen as a growth factor for benign and malignant thyrocytes, although communicating the magnitude of this risk to patients and caregivers, as well as the uncertain impact of any pregnancy on long-term prognosis, remains challenging. Evidence to support treatment decisions in this uncommon situation is presented in the context of a case of a pregnant teenager with known metastatic papillary thyroid cancer and recent radioiodine therapy.

Learning points:

Pregnancy is associated with the growth of thyroid nodules due to stimulation from oestrogen receptors on thyrocytes and HCG cross-stimulation of the TSH receptor.

Thyroid cancer diagnosed during pregnancy has not been shown to be associated with increased rates of persistent or recurrent disease in most studies.

There is little evidence to guide the management of metastatic thyroid cancer in pregnancy, where both maternal and foetal wellbeing must be carefully balanced.

http://ift.tt/2g0LxTO

Age-Related Differences in Clinical Characteristics and Esophageal Motility in Patients with Dysphagia

Abstract

Dysphagia in elderly patients has a major effect on nutrition and quality of life (QOL). Although several studies have shown that aging itself is associated with changes in esophageal motility, the impact of these changes on dysphagia symptoms and QOL is unknown. This study assessed the manometric diagnoses of elderly patients with dysphagia compared with diagnoses in younger counterparts. Participants included 116 consecutive patients examined for dysphagia from 2007 to 2014. We divided patients into three groups by age: Group A, 66 years and older (24 men, 23 women); Group B, 45–65 years (18 men, 24 women); and Group C, 44 years and younger (15 men, 12 women). The three groups were compared in regard to symptoms, esophageal motility, and health-related QOL (HRQOL). All patients underwent esophageal manometry examination and completed a self-administered questionnaire concerning their symptoms; HRQOL assessment was based on results of the Short Form-8 General Health Survey. Symptoms rated ≥4 points on the Likert scale were defined as significant. Although all patients had dysphagia as a major symptom, more elderly patients reported globus sensation, whereas more young patients reported heartburn as the primary symptom. Manometric diagnoses were generally similar across the three groups. Ineffective esophageal motility was more prevalent in Groups A and C than in Group B, although the difference was not statistically significant. No significant differences in manometric parameters or HRQOL were detected among the three groups. Despite differences in symptom patterns, broad manometric diagnoses and impairment of HRQOL in elderly patients with dysphagia are similar to those in younger counterparts.

http://ift.tt/2gIplfx

Development of International Terminology and Definitions for Texture-Modified Foods and Thickened Fluids Used in Dysphagia Management: The IDDSI Framework

Abstract

Dysphagia is estimated to affect ~8% of the world's population (~590 million people). Texture-modified foods and thickened drinks are commonly used to reduce the risks of choking and aspiration. The International Dysphagia Diet Standardisation Initiative (IDDSI) was founded with the goal of developing globally standardized terminology and definitions for texture-modified foods and liquids applicable to individuals with dysphagia of all ages, in all care settings, and all cultures. A multi-professional volunteer committee developed a dysphagia diet framework through systematic review and stakeholder consultation. First, a survey of existing national terminologies and current practice was conducted, receiving 2050 responses from 33 countries. Respondents included individuals with dysphagia; their caregivers; organizations supporting individuals with dysphagia; healthcare professionals; food service providers; researchers; and industry. The results revealed common use of 3–4 levels of food texture (54 different names) and ≥3 levels of liquid thickness (27 different names). Substantial support was expressed for international standardization. Next, a systematic review regarding the impact of food texture and liquid consistency on swallowing was completed. A meeting was then convened to review data from previous phases, and develop a draft framework. A further international stakeholder survey sought feedback to guide framework refinement; 3190 responses were received from 57 countries. The IDDSI Framework (released in November, 2015) involves a continuum of 8 levels (0–7) identified by numbers, text labels, color codes, definitions, and measurement methods. The IDDSI Framework is recommended for implementation throughout the world.

http://ift.tt/2g0Hgjb

Congenital absence of internal carotid artery: an unsuspected diagnosis

Description

A man aged 56 years, with a history of moderate sensorineural hearing loss, presented with a fast progressing loss of hearing discrimination in his right ear. The audiogram confirmed the moderate sensorineural hearing loss with a speech discrimination drop from 90% on the previous audiogram to 30%.

An MRI of the brain revealed an absence of the right internal carotid artery (ICA). No signs of acute or chronic ischaemic changes were found in the brain parenchyma. Subsequently, a cervical and intracranial MR angiogram was performed, which revealed a complete absence of the right ICA and the first segment (A1) of the anterior cerebral artery (ACA) from ICA to the anterior communicating artery (figure 1). Both ACA arise from the left ICA. A CT scan of the brain and a CT angiogram of the supra-aortic arteries revealed a thinner common CA ending at the external CA (

http://ift.tt/2gOE8It

Saddle pulmonary embolism as the initial presentation of prothrombin gene mutation G20210A

Description

A Hispanic man aged 28 years with intermittent tobacco and cocaine use presented to the emergency department with acute shortness of breath for 2 days duration in addition to brief calf pain a few days prior that had resolved. He had sustained tachycardia 120–130 bpm but otherwise unremarkable examination, chest X-ray (figure 1) and EKG. D-dimer was elevated at 2586 ng/mL. CT angiogram revealed extensive thrombus burden, including saddle emboli (figure 2), and segmental and subsegmental emboli (figure 3). Echocardiogram showed severely enlarged right ventricle (figure 4) with markedly elevated right systolic ventricular pressure of 54 mm Hg (figure 5). Owing to concern of impending cardiovascular collapse, catheter-guided thrombolysis of pulmonary embolism (PE) was carried out. During the angiogram, a near occlusive right popliteal vein thrombus with extension to femoral vein was identified and treated with thrombectomy followed by inferior vena cava filter...

http://ift.tt/2fThfPt

Traumatic haemopneumothorax and 'whole-body subcutaneous emphysema: successful use of a small-bore chest drain

A 56-year-old man presented having had two falls at home. He had a background of multiple sclerosis. After his second fall, during which he had fallen onto the toilet injuring his right chest, he was brought into the emergency department reporting pleuritic chest discomfort. Immediately evident was extensive swelling from his forehead to his thighs, which on palpation was found to be subcutaneous emphysema. A chest X-ray showed a large right-sided pneumothorax for which a chest drain was inserted. A CT revealed extensive surgical emphysema, pneumomediastinum, pneumoperitoneum and gas within the spinal canal. It also showed right-sided rib fractures and associated haemothorax. He was managed conservatively with a 12-French (F), small-bore, chest drain and made a complete recovery without complication. This case challenges the widely held, but poorly evidenced, opinion that traumatic haemopneumothorax needs to be managed with a large-bore surgical chest drain.

http://ift.tt/2gOCGWo

Aseptic inflammation of prosthetic knee in a patient affected by rheumatoid arthritis

Description

A woman aged 40 years affected by an aggressive and active form of rheumatoid arthritis (RA) underwent total knee arthroplasty (TKA) of the left knee for persistent synovitis after several therapeutic lines, the last one included methotrexate and a TNF-inhibitor.

Two months after the surgical procedure, the patient reported mild fever and persistent swelling of the left knee. On examination, there were signs of inflammation but no effusion to drain. Ultrasonography only showed oedema of the tissues surrounding the knee, and therefore, suspecting a prosthetic infection, antibiotic therapy was immediately started.

A subsequent scintigraphy with 99mTC-HmPAO (hexamethylpropylene-amine-oxime)-labelled leucocytes demonstrated the presence of early and persistent accumulation of labelled leucocytes in the femoral and tibial periprosthetic soft tissues, supporting the hypothesis of prosthetic infection (figure 1A).

Figure 1

(A) Images of the scintigraphy with 99mTC-HmPAO (hexamethylpropylene-amine-oxime)-labelled leucocytes, showing early and persistent (after 4 hours) accumulation (black...

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Effects of dexmedetomidine administered for postoperative analgesia on sleep quality in patients undergoing abdominal hysterectomy

To evaluate the effects of postoperative dexmedetomidine infusion on sleep quality in patients undergoing abdominal hysterectomy.

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Sevoflurane preserves regional cerebral oxygen saturation better than propofol: Randomized controlled trial

To investigate possible effects of volatile induction and maintenance anesthesia with sevoflurane (VIMA) and total intravenous anesthesia with propofol (TIVA) on regional cerebral oxygen saturation (rcSo2) during laparoscopic cholecystectomy.

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Hypocapnia measured by end-tidal carbon dioxide tension during anesthesia is associated with increased 30-day mortality rate

To evaluate the relationship between intraoperative end-tidal carbon dioxide (etco2) values and clinical outcomes with special attention on 30-day postoperative mortality and secondarily on hospital length of stay (LOS).

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Airway management for glossopexy in infants with micrognathia and obstructive breathing

To identify airway management and tracheal intubation techniques for glossopexy in infants with preexisting airway obstruction under general anesthesia.

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Total intravenous anesthesia without muscle relaxant in a parturient with amyotrophic lateral sclerosis undergoing cesarean section: a case report

Cases of amyotrophic lateral sclerosis with pregnancy are quite rare. The aim of this case report is to present the successful use of total intravenous anesthesia without muscle relaxant for cesarean section in a parturient with amyotrophic lateral sclerosis at 35 weeks' gestation. The parturient presented with impaired neuromuscular function. Titrated general anesthesia with short-acting anesthetics was applied. During the procedure, no muscle relaxant was used. This strategy helped avoid prolonged ventilation and prevent maternal respiratory complications.

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Cerebral air embolism after ERCP

Digestive endoscopic procedures have become increasingly common diagnostic and therapeutic procedures in hospitals. Generally they are safe procedures and complications, though infrequent, can occur and are potentially lethal. As the number of procedures performed increases, the complications arising are likely to become more frequent, so it is advisable to bear this in mind when establishing early diagnosis and treatment.Cerebral air embolism is a rare complication after a digestive endoscopic procedure, although in the case of endoscopic retrograde cholangiopancreatography (ERCP), may be as high as 10%.

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Splice site identification in human genome using random forest

Abstract

Gene identification has been an increasingly important task due to developments of Human Genome Project. Splice site prediction lies at the heart of identifying human genes, thus development of new methods which detect the splice site accurately is crucial. Machine learning classifiers are utilized to detect the splice sites. Performance of those classifiers mainly depends on DNA encoding methods (feature extraction) and feature selection. The feature extraction methods try to capture as much information as the DNA sequences have, while the feature selection methods provide useful biological knowledge by cleaning out the redundant information. According to the literature, Markovian models are popular encoding methods and the support vector machine (SVM) is known as the best algorithm for classification of splice sites. However, random forest (RF) may outperform the SVM in this domain using those Markovian encoding methods. In this study, performance of RF has been investigated as feature selection and classification in splice site domain. We proposed three methods, namely MM1-RF, MM2-RF and MCM-RF by combining RF with first order Markov Model (MM1), second order Markov model (MM2), and Markov Chain Model (MCM). We compared the performance of the RF with the SVM competitively on HS3D and NN269 benchmark datasets. Also, we evaluated the efficiency of the proposed methods with other current state of arts methods such as Reduced MM1-SVM, SVM-B and LVMM2. The experimental results show that the RF outperforms the SVM when the same Markovian encoding methods are used on both donor and acceptor datasets. Furthermore, the RF classifier performs much faster than the SVM classifier in detecting the splice sites.

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The effects of coenzyme Q10 supplementation on glucose metabolism and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial

Summary

Background

Data on the effects of coenzyme Q10 (CoQ10) supplementation on metabolic profiles among subjects with polycystic ovary syndrome (PCOS) are scarce.

Objective

This study was done to evaluate the effects of CoQ10 supplementation on glucose metabolism and lipid profiles in subjects with PCOS.

Design, Patients and Measurements

This randomized double-blind, placebo-controlled trial was conducted on 60 women diagnosed with PCOS. Subjects were randomly assigned into two groups to intake either 100 mg CoQ10 supplements (N=30) or placebo (N=30) per day for 12 weeks. Markers of insulin metabolism and lipid profiles were assessed at first and 12 weeks after the intervention.

Results

After 12 weeks of intervention, compared to the placebo, subjects who CoQ10 supplements had significantly decreased fasting plasma glucose (-0.24±0.51 vs. +0.01±0.44 mmol/L, P=0.04), serum insulin concentrations (-7.8±14.4 vs. +6.0±15.0 pmol/L, P<0.001), the homeostasis model of assessment-estimated insulin resistance (-0.3±0.6 vs. +0.2±0.6, P=0.001), the homeostasis model of assessment-estimated B cell function (-5.4±9.5 vs. +4.5±9.9, P<0.001) and increased the quantitative insulin sensitivity check index (+0.006±0.009 vs. -0.006±0.01, P<0.001). In addition, changes in serum total- (-0.10±0.48 vs. +0.19±0.50 mmol/L, P=0.02) and LDL-cholesterol concentrations (-0.15±0.40 vs. +0.14±0.49 mmol/L, P=0.01) in supplemented women were significantly different from those of women in the placebo group. When we adjusted the analysis for baseline values of biochemical parameters, age and baseline BMI, serum LDL-cholesterol (P=0.05) became non-significant, other findings did not alter.

Conclusions

Overall, CoQ10 supplementation for 12 weeks among subjects with PCOS had beneficial effects on glucose metabolism, serum total- and LDL-cholesterol levels.

This article is protected by copyright. All rights reserved.

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Table of Contents

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Author Index

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Subject Index

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Calendar

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Calendar Listings

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Editorial Board

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Instructions for Contributors

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Development and External Validation of a Model Predicting Death After Surgery in Patients With a Ruptured Abdominal Aortic Aneurysm: The Dutch Aneurysm Score

Publication date: Available online 1 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): G.C.I. von Meijenfeldt, S.C. van Beek, F. Bastos Gonçalves, H.J.M. Verhagen, C.J. Zeebregts, A.C. Vahl, W. Wisselink, M.J. van der Laan, R. Balm
ObjectiveThe decision whether or not to proceed with surgical intervention of a patient with a ruptured abdominal aortic aneurysm (rAAA) is very difficult in daily practice. The primary objective of the present study was to develop and to externally validate a new prediction model: the Dutch Aneurysm Score (DAS).MethodsWith a prospective cohort of 10 hospitals (n = 508) the DAS was developed using a multivariate logistic regression model. Two retrospective cohorts with rAAA patients from two hospitals (n = 373) were used for external validation. The primary outcome was the combined 30 day and in-hospital death rate. Discrimination (AUC), calibration plots, and the ability to identify high risk patients were compared with the more commonly used Glasgow Aneurysm Score (GAS).ResultsAfter multivariate logistic regression, four pre-operative variables were identified: age, lowest in hospital systolic blood pressure, cardiopulmonary resuscitation, and haemoglobin level. The area under the receiver operating curve (AUC) for the DAS was 0.77 (95% CI 0.72–0.82) compared with the GAS with an AUC of 0.72 (95% CI 0.67–0.77). The DAS showed a death rate in patients with a predicted death rate ≥80% of 83%.ConclusionsThe present study shows that the DAS has a higher discriminative performance (AUC) compared with the GAS. All clinical variables used for the DAS are easy to obtain. Identification of low risk patients with the DAS can potentially reduce turndown rates. The DAS can reliably be used by clinicians to make a more informed decision in dialogue with the patient and their family whether or not to proceed with surgical intervention.



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Activation of GPER ameliorates experimental pulmonary hypertension in male rats

Publication date: 15 January 2017
Source:European Journal of Pharmaceutical Sciences, Volume 97
Author(s): Allan K. Alencar, Guilherme C. Montes, Tadeu Montagnoli, Ananssa M. Silva, Sabrina T. Martinez, Aline G. Fraga, Hao Wang, Leanne Groban, Roberto T. Sudo, Gisele Zapata-Sudo
RationalePulmonary hypertension (PH) is characterized by pulmonary vascular remodeling that leads to pulmonary congestion, uncompensated right-ventricle (RV) failure, and premature death. Preclinical studies have demonstrated that the G protein-coupled estrogen receptor (GPER) is cardioprotective in male rats and that its activation elicits vascular relaxation in rats of either sex.ObjectivesTo study the effects of GPER on the cardiopulmonary system by the administration of its selective agonist G1 in male rats with monocrotaline (MCT)-induced PH.MethodsRats received a single intraperitoneal injection of MCT (60mg/kg) for PH induction. Experimental groups were as follows: control, MCT+vehicle, and MCT+G1 (400μg/kg/daysubcutaneous). Animals (n=5pergroup) were treated with vehicle or G1 for 14days after disease onset.Measurements and Main ResultsActivation of GPER attenuated exercise intolerance and reduced RV overload in PH rats. Rats with PH exhibited echocardiographic alterations, such as reduced pulmonary flow, RV hypertrophy, and left-ventricle dysfunction, by the end of protocol. G1 treatment reversed these PH-related abnormalities of cardiopulmonary function and structure, in part by promoting pulmonary endothelial nitric oxide synthesis, Ca²⁺ handling regulation and reduction of inflammation in cardiomyocytes, and a decrease of collagen deposition by acting in pulmonary and cardiac fibroblasts.ConclusionsG1 was effective to reverse PH-induced RV dysfunction and exercise intolerance in male rats, a finding that have important implications for ongoing clinical evaluation of new cardioprotective and vasodilator drugs for the treatment of the disease.

Graphical abstract

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Prognostic impact of HER3 based on protein and mRNA expression in high-grade serous ovarian carcinoma

Abstract

HER3 is a member of the epidermal growth factor family and was predominantly described as a negative prognostic factor in various solid tumors as well as in ovarian cancer. In this study, we investigated HER3 on protein and mRNA expression in histologically defined subtypes of ovarian cancer looking for an influence on patient's survival. Altogether, we examined HER3 in ovarian high-grade serous (HGSC, n = 320), low-grade serous (LGSC, n = 55), endometrioid (EC, n = 33), and clear cell (CCC, n = 48) carcinomas using immunohistochemistry (IHC) and quantitative real-time reverse transcription PCR (qRT-PCR). Univariate and multivariate analyses were performed to explore the association between HER3 and overall survival (OS) as well as progression-free survival (PFS). In HGSC, high HER3 mRNA expression was a favorable prognostic factor for PFS (P = 0.008) and OS (P = 0.052), while for high HER3 protein expression, a trend towards better survival was seen (OS P = 0.064; PFS P = 0.099). A subgroup of HGSC with negative HER3 staining and negative HER3 mRNA levels showed most unfavorable OS and PFS (P = 0.002 and P = 0.004, respectively). Using the multivariate Cox regression model, HER3 was predictive for prolonged PFS (HR, 0.48; 95% CI, 0.26–0.88; P = 0.018). All in all, we cannot confirm the reported negative prognostic impact of HER3 expression in high-grade serous ovarian carcinoma and moreover find a rather positive prognostic implication of HER3 in this major ovarian cancer histological subtype.

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CXCL12 expression and PD-L1 expression serve as prognostic biomarkers in HCC and are induced by hypoxia

Abstract

Anti-PD-1 treatment increases anti-tumour immune responses in animal models of hepatocellular carcinoma (HCC). Sorafenib, the mainstay of treatment of HCC patients, however, leads to tumour hypoxia and thereby abrogates the efficacy of anti-PD-1 treatment. This served as a rationale to implement CXCR4 inhibition as adjunct to sorafenib and anti-PD-1 treatment in murine HCC models. We studied the relationship between tumour hypoxia, PD-L1 and CXCL12 expression in human HCC, aiming to test the rationale for triple therapy combining sorafenib, PD-1 immune checkpoint inhibitors and CXCR4 inhibitors. Expression of CXCL12, PD-L1 and of surrogate markers for tumour hypoxia was evaluated at messenger RNA (mRNA) level in a cohort of HCC patients from The Cancer Genome Atlas and immunohistochemically in an independent cohort from the University Hospital of Bonn. Retrospective survival analyses were conducted. CXCL12 mRNA level significantly correlated with markers indicating tumour hypoxia in HCC (HIF1-α ρ = 0.104, p = 0.047). PD-L1 expression was significantly increased in tumours with a high number of tumour-infiltrating lymphocytes (ρ = 0.533, p < 0.001). In Cox proportional hazard analyses, high PD-L1 expression and loss of nuclear CXCL12 expression showed significant prognostic value in terms of overall survival (hazard ratio (HR) = 3.35 [95%CI 1.33–8.46], p = 0.011 for PD-L1; HR = 2.64 [95%CI 1.18–5.88], p = 0.018 for CXCL12, respectively). This study supports the rationale to combine CXCR4 inhibitors and PD-1 immune checkpoint inhibitors in patients with HCC, as sorafenib-induced tumour hypoxia leads to upregulation of PD-L1 and CXCL12.

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In phyllodes tumors of the breast expression of SPARC (osteonectin/BM40) mRNA by in situ hybridization correlates with protein expression by immunohistochemistry and is associated with tumor progression

Abstract

Secreted protein acidic and rich in cysteine (SPARC) plays an essential role in tumor invasion and metastasis. The present work was undertaken to detect expression of SPARC mRNA in phyllodes tumors (PTs) and its association with SPARC protein expression. This study also evaluated expression of SPARC mRNA and its correlation between grade and clinical behavior of PTs. In addition, we assessed in PTs the association of expression of SPARC with that of matrix metalloproteinase (MMP)-2 and of MMP-9. SPARC mRNA expression was determined by RNAscope in situ hybridization (ISH) in 50 benign, 22 borderline, and 10 malignant PTs using a tissue microarray. Furthermore, we applied immunohistochemistry (IHC) to examine expression of SPARC, MMP-2, and MMP-9. SPARC mRNA appeared to be concentrated mainly in the stromal compartment of PTs. IHC staining patterns of SPARC protein showed concordance with SPARC mRNA ISH results. Stromal SPARC expression increased continuously as PTs progress from benign through borderline to malignant PTs, both at mRNA (using ISH) (P = 0.044) and protein level (using IHC) (P = 0.000). The recurrence percentage was higher in the stromal SPARC mRNA or protein-positive group than in the SPARC-negative group but this difference was not statistically significant. Stromal SPARC mRNA and protein expression was associated with PT grade and correlated with MMP-2 expression. These results indicate that SPARC-mediated degradation of the extracellular matrix, and its possible association with MMPs, might contribute to progression of PTs.

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