Αρχειοθήκη ιστολογίου

Τρίτη 5 Ιουλίου 2016

Treatment of complex anterior cerebral artery aneurysms with Pipeline flow diversion: mid-term results

Background

The off-label use of flow diverters in the treatment of distal aneurysms continues to be debated.

Objective

To report our multicenter experience in the treatment of complex anterior cerebral artery aneurysms with the Pipeline embolization device (PED).

Methods

The neurointerventional databases of the four participating institutions were retrospectively reviewed for aneurysms treated with PED between October 2011 and January of 2016. All patients treated for anterior cerebral artery aneurysms were included in the analysis. Clinical presentation, location, type, vessel size, procedural complications, clinical and imaging follow-up were included in the analysis.

Results

Twenty patients (13 female) with 20 aneurysms met the inclusion criteria in our study. Fifteen aneurysms were classified as saccular and five as fusiform (mean size 7.3 mm). Thirteen aneurysms were located in the anterior communicating region (ACOM or A1/2 junction), six were A2-pericallosal, and one was located in the A1 segment. Six patients had presented previously with subarachnoid hemorrhage and had their aneurysms initially clipped or coiled. There was one minor event (a small caudate infarct) and one major event (intraparenchymal hemorrhage). Sixteen of the 20 patients had angiographic follow-up (mean 10 months). Eleven aneurysms were completely occluded, one had residual neck, and four had residual aneurysm filling.

Conclusions

The treatment of complex anterior cerebral artery aneurysms with the PED as an alternative for patients who are not good candidates for conventional methods is technically feasible and safe. Mid-term results are promising but larger series with long-term follow-up are required to assess its effectiveness.



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Is intensive care monitoring necessary after coil embolization of unruptured intracranial aneurysms?

Introduction

Patients with an unruptured intracranial aneurysm treated with coil embolization are routinely admitted to the intensive care unit (ICU) after the procedure; however, this practice is questionable. The purpose of this study was to determine if routine admission to the ICU is necessary for patients undergoing coil embolization of an unruptured intracranial aneurysm.

Methods

We conducted a retrospective cohort study of all patients undergoing elective endovascular treatment of an unruptured intracranial aneurysm between 2005 and 2012 at our institution. Multivariate regression analysis was performed to identify predictors of outcome. Cost savings analysis compared ICU admission to step-down or telemetry unit admission.

Results

311 unruptured intracranial aneurysms were treated by coil embolization (190), balloon remodeling (13), or stent-assisted coiling (108). Eleven (3.5%) neurologic complications were noted; 5 (1.6%) of these were permanent. Multivariate regression analysis identified female sex (p=0.028), hypercoagulability (p=0.021), aneurysm size >2 cm (p=0.003), and intraoperative rupture (p<0.001) as predictors of a post-procedural neurologic complication. Cost savings were 57% for admission to a step-down unit and 32% for admission to a telemetry unit compared with ICU admission.

Conclusions

Neurologic complications are rare in the treatment of unruptured intracranial aneurysms, suggesting that routine ICU admission after treatment may not be necessary. Female sex, history of hypercoagulability, aneurysm size >2 cm, and an intraprocedural rupture were predictive of a postoperative complication. ICU monitoring in these subgroups may therefore be warranted.



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18 F-FDG PET/MRI evaluation of retroperitoneal fibrosis: a simultaneous multiparametric approach for diagnosing active disease

Abstract

Purpose

The aim of this study was to evaluate integrated 18F-FDG PET/MRI as a one-stop diagnostic procedure in the assessment of (active) idiopathic retroperitoneal fibrosis (RPF)

Methods

A total of 22 examinations comprising a PET/CT scan followed by a PET/MRI scan in 17 patients (13 men, 4 women, age 58 ± 11 years) with histopathologically confirmed RPF at diagnosis or during follow-up under steroid therapy were analysed in correlation with laboratory inflammation markers (ESR, CRP). The patient cohort was subdivided into two groups: 6 examinations in untreated and 16 in treated patients. Tissue formations in typically periaortic localization suggestive of RPF were visually and quantitatively evaluated. The PET analysis included the assessment of SUVmax and a qualitative score for FDG uptake in RPF tissue in relation to the uptake in the liver. MRI analysis included evaluation of the T2-weighted image signal intensity, contrast enhancement and diffusion restriction (ADC values). Mean values were compared using the Mann-Whitney U test. ADC, SUVmax and ESR values were correlated using Pearson's correlation.

Results

MRI analysis revealed restricted diffusion in 100 % and 56 %, hyperintense T2 signal in 100 % and 31 %, and contrast enhancement in the periaortic tissue formation suggestive of RPF in 100 % and 62.5 % in the untreated and treated patients, respectively. In the qualitative and quantitative PET analysis, statistically significant differences were found for mean FDG uptake scores (2.5 ± 0.8 in untreated patients and 1.1 ± 0.9 in treated patients) and mean SUVmax (7.8 ± 3.5 and 4.1 ± 2.2, respectively). A strong correlation was found between the ADC values and SUVmax (Pearson r   −0.65, P = 0.0019), and between ESR and CRP values and SUVmax (both r = 0.45, P = 0.061).

Conclusion

Integrated 18F-FDG PET/MRI shows high diagnostic potential as a one-stop diagnostic procedure for the assessment of (active) RPF providing multiparametric supportive information.



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Radiation dosimetry of 68 Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing

Abstract

Purpose

The clinical introduction of 68Ga-PSMA-11 ("HBED-CC") ligand targeting the prostate-specific membrane antigen (PSMA) has been regarded as a significant step forward in the diagnosis of prostate cancer (PCa). In this study, we provide human dosimetry and data on optimal timing of PET imaging after injection.

Methods

Four patients with recurrent PCa were referred for 68Ga-PSMA-11 PET/CT. Whole-body PET/CTlow-dose scans were conducted at 5 min, and 1, 2, 3, 4 and 5 h after injection of 152–198 MBq 68Ga-PSMA-11. Organs of moderate to high uptake were used as source organs; their total activity was determined at all measured time points. Time–activity curves were created for each source organ as well as for the remainder. The radiation exposure of a 68Ga-PSMA-11 PET was identified using the OLINDA-EXM software. In addition, tracer uptake was measured in 16 sites of metastases.

Results

The highest tracer uptake was observed in the kidneys, liver, upper large intestine, and the urinary bladder. Mean organ doses were: kidneys 0.262 ± 0.098 mGy/MBq, liver 0.031 ± 0.004 mGy/MBq, upper large intestine 0.054 ± 0.041 mGy/MBq, urinary bladder 0.13 ± 0.059 mGy/MBq. The calculated mean effective dose was 0.023 ± 0.004 mSv/MBq (=0.085 ± 0.015 rem/mCi). Most tumor lesions (n = 16) were visible at 3 h p.i., while at all other time points many were not qualitatively present (10/16 visible at 1 h p.i.).

Conclusions

The mean effective dose of a 68Ga-PSMA-11 PET is 0.023 mSv/MBq. A 3-h delay after injection was optimal timing for 68Ga-PSMA-11 PET/CT in this patient cohort.



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Andreas Engert and Anas Younes (Eds), Hodgkin Lymphoma: A Comprehensive Overview



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In vivo PET imaging of the neuroinflammatory response in rat spinal cord injury using the TSPO tracer [ 18 F]GE-180 and effect of docosahexaenoic acid

Abstract

Purpose

Traumatic spinal cord injury (SCI) is a devastating condition which affects millions of people worldwide causing major disability and substantial socioeconomic burden. There are currently no effective treatments. Modulating the neuroinflammatory (NI) response after SCI has evolved as a major therapeutic strategy. PET can be used to detect the upregulation of the 18-kDa translocator protein (TSPO), a hallmark of activated microglia in the CNS. We investigated whether PET imaging using the novel TSPO tracer [18F]GE-180 can be used as a clinically relevant biomarker for NI in a contusion SCI rat model, and we present data on the modulation of NI by the lipid docosahexaenoic acid (DHA).

Methods

A total of 22 adult male Wistar rats were subjected to controlled spinal cord contusion at the T10 spinal cord level. Six non-injured and ten T10 laminectomy only (LAM) animals were used as controls. A subset of six SCI animals were treated with a single intravenous dose of 250 nmol/kg DHA (SCI-DHA group) 30 min after injury; a saline-injected group of six animals was used as an injection control. PET and CT imaging was carried out 7 days after injury using the [18F]GE-180 radiotracer. After imaging, the animals were killed and the spinal cord dissected out for biodistribution and autoradiography studies. In vivo data were correlated with ex vivo immunohistochemistry for TSPO.

Results

In vivo dynamic PET imaging revealed an increase in tracer uptake in the spinal cord of the SCI animals compared with the non-injured and LAM animals from 35 min after injection (P < 0.0001; SCI vs. LAM vs. non-injured). Biodistribution and autoradiography studies confirmed the high affinity and specific [18F]GE-180 binding in the injured spinal cord compared with the binding in the control groups. Furthermore, they also showed decreased tracer uptake in the T10 SCI area in relation to the non-injured remainder of the spinal cord in the SCI-DHA group compared with the SCI-saline group (P < 0.05), supporting a NI modulatory effect of DHA. Immunohistochemistry showed a high level of TSPO expression (38 %) at the T10 injury site in SCI animals compared with that in the non-injured animals (6 %).

Conclusion

[18F]GE-180 PET imaging can reveal areas of increased TSPO expression that can be visualized and quantified in vivo after SCI, offering a minimally invasive approach to the monitoring of NI in SCI models and providing a translatable clinical readout for the testing of new therapies.



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Severe early basal ganglia hypometabolism in neurodegeneration with brain iron accumulation



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Is 18 FDG uptake useful to decide on chemotherapy in ER+/HER2- breast cancer?



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William T. O’Brien Sr. (Ed.), Top 3 Differentials in Neuroradiology: A Case Review. Thieme Medical Publishers, Inc., 2015. ISBN 978-1- 60406-723-1



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FDG-PET/ceCT is useful to predict recurrence of Pseudomyxoma peritonei

Abstract

Purpose

Pseudomyxoma peritonei (PMP) is a rare peritoneal neoplasm originating from appendicular tumours. There is no consolidated data available in the literature about the precise role of [18F] fluorodesoxy-D-glucose Positron Emission Tomography / contrast enhanced Computed Tomography (FDG-PET/ceCT). The aim of this study was to evaluate the correlation between preoperative FDG-PET/ceCT (qualitative and semi-quantitative assessment) and progression free survival (PFS) of patients treated for PMP.

Methods

All patients scheduled for PMP treatment by cytoreductive unicentric surgery, intraperitoneal chemotherapy (HIPEC), and who underwent a FDG-PET/ceCT between February 2008 and January 2014, were included. No previous treatment was performed (except biopsy or appendectomy). FDG-PET/ceCT was interpreted by two nuclear physicians in consensus. Positive FDG-PET/ceCT scans were further labelled in diffuse disease and poly/mono focal disease. SUVmax was measured based on post-operative reports. The Peritoneal Cancer Index (PCI) and Completeness of CytoReduction Score (CCR) were assessed after surgery.

Results

Fifty-six patients were included in this study, with a mean age of 56-years-old and a mean follow-up of 29.3 months. SUVmax, with a cut-off at 2.02, was predictive for the PFS on multivariate analysis. No differences were observed between diffuse disease and focal disease on PFS for progression free survival, PCI, and SUVmax (p = 0.1). Post-operative CCR was not significantly correlated with SUVmax or FDG-PET/ceCT qualitative assessment.

Conclusion

SUVmax on preoperative FDG-PET/ceCT was an independent predictive factor for PFS in PMP. Further studies are needed to explore if FDG-PET/ceCT could potentially predict post-operative CCR.



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Erratum to: Dual-phase amyloid PET: hitting two birds with one stone



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Andrew M. Evens and Kristie A. Blum (Eds), Non-Hodgkin Lymphoma. Pathology, Imaging, and Current Therapy



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18 F-FDG PET/CT in patients with idiopathic retroperitoneal and mediastinal fibrosis



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Prognostic value of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with Barcelona Clinic Liver Cancer stages 0 and A hepatocellular carcinomas: a multicenter retrospective cohort study

Abstract

Purpose

We evaluated the prognostic value of pretreatment 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT) in patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A hepatocellular carcinoma (HCC) who had received curative treatment or transarterial chemoembolization (TACE).

Methods

Between 2009 and 2010, 317 patients diagnosed with HCC at seven hospitals were enrolled. Among these, 195 patients underwent curative treatments including resection, liver transplantation, and radiofrequency ablation. TACE was performed in 122 patients. The tumor-to-normal liver standardized uptake value ratio (TLR) of the primary tumor was measured using pretreatment FDG PET/CT. The prognostic significance of TLR and other clinical variables was assessed using Cox regression models. Differences in the overall survival (OS) associated with TLR or other significant clinical factors were examined using the Kaplan-Meier method.

Results

Over a median follow-up period of 46 months, 77 patients died from cancer. In the curative cohort, higher TLR (≥2) was significantly associated with death (hazard ratio [HR] = 2.68; 95 % CI, 1.16–6.15; P = 0.020) in multivariable analysis. Patients with a higher TLR had significantly worse OS than patients with a lower TLR (5-year overall survival, 61 % vs. 79.4 %; P = 0.006). In the TACE cohort, the Model for End-Stage Liver Disease (MELD) score (≥8) was a significant independent prognostic factor for OS (HR = 3.34; 95 % CI, 1.49–7.48; P = 0.003), whereas TLR was not associated with OS. The Kaplan-Meier curves showed significantly poorer OS in patients with higher MELD scores (≥8) than in those with lower MELD scores (5-year survival rate, 33.1 % vs. 79.6 %; P < 0.001).

Conclusions

Pretreatment TLR measured using FDG PET/CT was an independent prognostic factor for OS in patients with BCLC stage 0 or A HCC undergoing curative treatment. In contrast, underlying liver function appeared to be important in predicting the prognosis of patients undergoing TACE.



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Tau PET and tauopathies



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Role of 68 Ga somatostatin receptor PET/CT in the detection of endogenous hyperinsulinaemic focus: an explorative study

Abstract

Purpose

To explore the role of 68Ga-DOTATATE/DOTATOC PET/CT (SR PET/CT) in patients with suspicion of or histopathologically proven pancreatogenic hyperinsulinaemic hypoglycaemia.

Methods

We included 13 patients with histopathologically proven or a high clinical suspicion of pancreatogenic hyperinsulinaemia. All the patients underwent a SR PET/CT scan. The results were correlated with histopathological findings. Normalization of blood glucose levels after resection of the pancreatic lesion, as well as a cytological and/or pathological diagnosis of insulinoma, was considered the diagnostic gold standard for insulinoma. The diagnosis of nesidioblastosis was based on exclusion of an insulinoma and conclusive pathological examination of a segment of the pancreas. Malignant insulinoma was defined as the presence of locoregional or distant metastases.

Results

Based on histopathology, 13 patients were found to have pancreatic hyperinsulinaemia: two patients had malignant insulinoma, eight had nonmetastasized insulinoma, and three had nesidioblastosis. SR PET was positive in 11 of the 13 patients (84.6 %) with a final diagnosis of endogenous pancreatic hypoglycaemia. Histopathological staining confirmed 16 foci of hyperinsulinism (insulin positivity). SR PET detected 14 of the 16 lesions, resulting in a sensitivity of 87 %. One intrapancreatic spleen was falsely diagnosed as insulinoma focus on SR PET, resulting in positive predictive value of 93.3 %. Immunohistochemical staining of somatostatin receptor (SSR) subtype 2a was available in ten specimens: two nesidioblastosis, and seven benign and one malignant insulinoma. Eight out of the ten specimens (80 %) stained strongly to moderately positive. Seven of the eight SSR2a-positive lesions were picked up on SR PET. Based on the results of SR PET/CT, nine patients achieved complete remission of the hypoglycaemic events during follow-up.

Conclusion

This explorative study suggests that SR PET in combination with CT may play a significant role in the detection and management of patients with pancreatogenic hyperinsulinaemic hypoglycaemia. A large proportion of insulinomas express SSR2a, and a larger study is needed to fully assess the diagnostic accuracy of SR PET in patients with insulinoma and nesidioblastosis compared with current localizing studies used in clinical practice.



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RGD-K5 PET/CT in patients with advanced head and neck cancer treated with concurrent chemoradiotherapy: Results from a pilot study

Abstract

Background/Aim

We prospectively investigated the potential usefulness of PET using a new tracer targeting integrin αvβ3 (termed RGD-K5) in patients with head and neck cancer (HNC) undergoing definitive concurrent chemoradiotherapy (CCRT).

Patients and Methods

Newly diagnosed patients with locally advanced HNC scheduled for definitive CCRT were eligible. RDG-K5 PET and FDG PET scans were performed at three different time points (baseline, 2 weeks, and 3 months post-treatment).

Results

Nine patients completed all of the three scans, whereas two patients withdrew after two scans only. Uptake of both RGD-K5 and FDG generally decreased following CCRT. However, the observed decrease did not differ significantly between complete responders and non-responders. At 3 months post-treatment, the uptake of both RGD-K5 and FDG at the main tumors was significantly lower in those who achieved complete responses than in those with residual tumors.

Conclusion

RGD-K5 PET has the potential to identify patients with incomplete responses to CCRT.



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Accounting for treatment by center interaction in sample size determinations and the use of surrogate outcomes in the pessary for the prevention of preterm birth trial: a simulation study

The Pessary for the Prevention of Preterm Birth Study (PS3) is an international, multicenter, randomized clinical trial designed to examine the effectiveness of the Arabin pessary in preventing preterm birth i...

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Serotonin-Exacerbated DSS-Induced Colitis Is Associated with Increase in MMP-3 and MMP-9 Expression in the Mouse Colon

Background. 5-HT enhances dextran sulfate sodium- (DSS-) induced colitis and is involved in inflammatory bowel disease (IBD). Matrix metalloproteinases (MMPs) play roles in the process of intestinal inflammation. Aims. To examine whether 5-HT induces MMPs expression in mouse colon to enhance DSS-induced colitis. Materials and Methods. C57BL/6J (B6) mice were treated with either low-dose (1.0 mg/kg) or high-dose (2.0 mg/kg) 5-HT by enema, low-dose (1.0%) or high-dose (2.5%) DSS, or combined low-dose (1.0%) DSS and (1.0 mg/kg) 5-HT. Mouse colitis was analyzed. MMPs and tissue inhibitors of MMPs (TIMPs) mRNA were measured by real-time quantitative RT-PCR in mouse colon and in human Caco-2 cells and neutrophils. MMP-3 and MMP-9 protein levels were quantified from immunohistochemistry (IHC) images of mouse colons. Results. 5-HT exacerbated DSS-induced colitis, low-dose 5-HT induces both MMP-3 and MMP-9, and high-dose 5-HT only increased MMP-3 mRNA expression in mouse colon. Mouse colon MMP-3 and MMP-9 protein levels were also elevated by 5-HT treatment. The MMP-2, TIMP-1, and TIMP-2 mRNA levels were increased in the inflamed colon. 5-HT induced MMP-3 and MMP-9 mRNA expression in Caco-2 and human neutrophils, respectively, in vitro. Conclusion. 5-HT induced MMP-3 and MMP-9 expression in mouse colon; these elevated MMPs may contribute to DSS-induced colitis.

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Effects of Traumeel (Tr14) on Exercise-Induced Muscle Damage Response in Healthy Subjects: A Double-Blind RCT

The present double-blind, randomized, placebo-controlled clinical trial intended to test whether ingestion of a natural combination medicine (Tr14 tablets) affects serum muscle damage and inflammatory immune response after downhill running. 96 male subjects received Tr14 tablets, which consist of 14 diluted biological and mineral components, or a placebo for 72 h after the exercise test, respectively. Changes in postexercise levels of various serum muscle damage and immunological markers were investigated. The area under the curve with respect to the increase () of perceived pain score and creatine kinase (CK) were defined as primary outcome measures. While for CK the value of the difference between the two groups is borderline, the pain score and muscle strength were not statistically significant. However, a trend towards lower levels of muscle damage (CK, ; LDH, ) in the Tr14 group was shown. Less pronounced lymphopenia (), a trend towards a lower expression of CD69 count (), and antigen-stimulated ICAM-1 () were found in the verum group. The Tr14 group showed a tendentially lower increase of neutrophils (), BDNF (), stem cell factor (), and GM-CSF () to higher levels. The results of the current study indicate that Tr14 seems to limit exercise-induced muscle damage most likely via attenuation of both innate and adaptive immune responses. This study was registered with ClinicalTrials.gov (NCT01912469).

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Impact of aspirin use on morbidity and mortality in massively transfused cardiac surgery patients: a propensity score matched cohort study

Abstract

Purpose

Aspirin may prevent organ dysfunction in critically ill patients and mitigate transfusion associated acute lung injury. We hypothesized that aspirin use might be associated with decreased morbidity and mortality in massively transfused cardiac surgery patients.

Methods

A single center retrospective cohort study was performed using data from an 8.5-year period (2006–2014). Massive transfusion was defined as receiving at least 2400 ml (8 units) of red blood cell units intraoperatively. A propensity score model was created to account for the likelihood of receiving aspirin and matched pairs were identified using global optimal matching. The primary endpoint, in-hospital mortality, was compared between aspirin users and non-users. Secondary outcomes including: ICU hours, mechanical lung ventilation hours, prolonged mechanical lung ventilation (>24 h), pneumonia, stroke, acute renal failure, atrial fibrillation, deep sternal wound infection, and multiple organ dysfunction syndrome were also compared.

Results

Of 7492 cardiac surgery patients, 452 (6 %) were massively transfused and mortality was 30.6 %. There were 346 patients included in the matched cohort. No significant association was found between preoperative aspirin use and in-hospital mortality; absolute risk reduction with aspirin = 7.5 % (95 % CI −2.0 to 16.9 %, p = 0.12). Preoperative aspirin use was associated with fewer total mechanical lung ventilation hours (p = 0.02) and less prolonged mechanical lung ventilation; absolute risk reduction = 11.0 % (95 % CI 1.1–20.5 %, p = 0.02).

Conclusions

Preoperative aspirin use is not associated with decreased in-hospital mortality in massively transfused cardiac surgery patients, but may be associated with less mechanical lung ventilation time.



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Girl's hand amputated after fireworks blast

Associated Press

COMPTON, Calif. — Investigators say a 9-year-old girl in Compton lost her left hand and fingers on her right hand in an explosion that was likely caused by the use of illegal fireworks.

The Los Angeles County Sheriff's Department says the girl also sustained blast injuries to her face following the explosion at a city park Saturday afternoon.

Authorities say she was taken to a hospital where her left hand was amputated.

She is listed in stable condition.

The incident is under investigation.



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The effects of direct hemoperfusion using a polymyxin B-immobilized column in a pig model of severe Pseudomonas aeruginosa pneumonia

Hemoperfusion through a column containing polymyxin B-immobilized fiber (PMX-HP) is beneficial in abdominal sepsis. We assessed the effects of PMX-HP in a model of severe Pseudomonas aeruginosa pneumonia.

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FGFR2 overexpression predicts survival outcome in patients with metastatic papillary renal cell carcinoma

Abstract

Background

Up to date, there are no data about FGFR2 expression and its predictive role in papillary RCC (pRCC) patients. The aim of the present study was to test FGFR2 expression and mutations for association with survival outcome in patients with pRCC.

Methods

Specimens of removed primary tumors from 214 untreated metastatic pRCC patients were evaluated by immunohistochemistry with FGFR2 antibody. FGFR2 mutations were assessed by PCR and direct sequencing, with DNA obtained from 62 paraffin-embedded pRCC samples. FGFR2 expression was tested for associations with progression-free survival (PFS), overall survival (OS) and best objective response.

Results

Expression of FGFR2 was observed in 23 % (49/214) of primary pRCC, mostly in cytoplasm of tumor cells. Expression of FGFR2 was significant lower in normal tissue of kidney (1 %, P = 0.001). FGFR2 S252W mutation was found in one patient (1.6 %), and no N549K mutation was detected. FGFR2 expression was strongly associated with a number of metastatic sites, type 2 of pRCC, lower nucleolar grade (P < 0.001). FGFR2-positive patients had significantly shorter OS and PFS (P < 0.05). On multivariate analysis, FGFR2 expression, MSKCC risk group and type of pRCC were found to be independent predictors of survival.

Conclusions

In this study, we described immunohistochemical expression of FGFR2 in a large series of pRCC specimens. FGFR2 expression was found to be prognostic factor for survival in patients with metastatic pRCC. FGFR2 mutations are rare across papillary types of RCC.



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Risk of second primary malignancies among cancer survivors in the United States, 1992 through 2008

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BACKGROUND

In the current study, the authors attempted to describe the incidence, most common sites, and mortality of second primary malignancies among survivors of common cancers.

METHODS

The authors identified patients aged ≥18 years who were diagnosed with a primary malignancy from the 10 most common cancer sites (prostate, breast, lung, colon, rectum, bladder, uterus, kidney, melanoma, and non-Hodgkin lymphoma) between 1992 and 2008 from Surveillance, Epidemiology, and End Results data. Factors associated with the incidence of second primary malignancies were explored using bivariable and multivariable models, and mortality attributable to first and second primary malignancies was examined.

RESULTS

A cohort of 2,116,163 patients was identified, 170,865 of whom (8.1%) developed a second primary malignancy. Survivors of bladder cancer had the highest risk of developing a second cancer. In a multivariable model controlling for age, race, tumor grade, stage of disease, marital status, educational level, and income, a history of non-Hodgkin lymphoma (hazard ratios of 2.70 and 2.88, respectively, for men and women) and bladder cancer (hazard ratios of 1.88 and 1.66, respectively, for men and women) predicted the highest risk of developing a second cancer. For patients with 2 incident cancers, 13% died of their initial cancer, but greater than one-half (55%) died of their second primary malignancy. Lung cancer was the cause of death in 12% of patients with 2 incident cancers.

CONCLUSIONS

Nearly 1 in 12 patients diagnosed with a common cancer developed a second malignancy, the most common of which was lung cancer. Greater than one-half of patients with 2 incident cancers died of their secondary malignancy. The findings from the current study may inform care strategies among cancer survivors. Cancer 2016. © 2016 American Cancer Society.



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What should EMS providers know about, besides EMS?

We asked EMS1 readers three poll questions about what EMTs and paramedic should know besides EMS. Here is some demographic information for the 612 people who responded to the survey:

  • Half are 30-50 years old.
  • Two-thirds are male.
  • Half are paramedics.
  • A third have less than five years' experience.
  • Most (59%) have at least an Associate's degree.
  • About half are married with children.

Here is what we learned.

1. Small talk with patients is about family and work
The first question asked, "Which of the following non-medical topics do you most often discuss with your patients?"

Family (83 percent) and occupation/employment (60 percent) were the most common subjects by far, with sports a distant third (32 percent) among caregivers 50 or younger.

Occupation/employment small talk was particularly popular among the under-30 age group. Men were much more likely than women to talk sports; women made up that gap by discussing family with patients more often.

According to our respondents, money, religion and politics are rarely raised with patients.

2. Back to school for psychiatry and science training
The second question asked, "What academic subjects should EMS providers be most familiar with?"

Psychology (75 percent) and science (60 percent), mentioned most often, seem like good subjects for further study by paramedics and EMTs. Psychology isn't covered much in EMS courses despite its relevance to patient care, and sciences such as physics, chemistry and biology can help EMS providers better understand why therapies work the way they do.

Also popular, at 41 percent each, were foreign languages and math.

Although foreign languages are more often electives than requirements in U.S. public schools, it would be hard to argue the advantage American EMS providers gain by mastering simple conversation in common languages other than English.

Fractions, decimals, the metric system and basic algebra are everyday skills which are particularly useful to paramedics. Caregivers with a solid foundation in math are presumably less likely to make medication errors.

Foreign languages and science were mentioned much more frequently by caregivers under 30 than those over 50. The opposite was true of history.

Math and history were significantly more popular with the most experienced caregivers who responded. Foreign languages drew many more responses from relative newcomers to EMS.

Psychology was more popular with women, while men preferred history.

3. EMS providers worry about money, sleep and getting hurt
The final question asked, "What are your top EMS job-related concerns?"

There was no clear winner for this question. Fatigue, finances and injury/disability were each mentioned by approximately half the respondents, although finances wasn't as big an issue for caregivers older than 50. Professional or career advancement was also less important to that age group.

A serious discussion about reducing fatigue would have to weigh the convenience of 24-hour or even 48-hour shifts against the danger of dispatching drowsy crews to critical calls.

The concern about finances could be just as much about managing money as having more of it. Living within one's means — a no-brainer for some — can be a challenge for folks who've never learned to set and stick to simple budgets.

Minor injuries may be inevitable in EMS, but the chances of long-term, disabling injuries can be reduced through continued ergonomic improvements like powered stretchers, equipment miniaturization and more logical ambulance layouts. Also important is judicious use of speed and other defensive driving skills during response and transport.

Paramedics, particularly those married and over 50, were twice as preoccupied with retirement as EMTs.

Advancement and continued employment were mentioned much more frequently by men, while women were more concerned about violence and coworker behavior.



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Indications, applications, and outcomes of inferior vena cava filters for venous thromboembolism in Japanese patients

Abstract

A recent multicenter registry study of venous thromboembolism (VTE) patients in Japan demonstrated a high prevalence of inferior vena cava (IVC) filter placement. However, data regarding indications, applications, and outcomes of IVC filters in Japanese patients are quite limited. This study was an observational, single-center, retrospective cohort study of all consecutive patients with acute VTE treated between March 2006 and February 2014. Data extracted included patient demographics, indications, applications, and complications of IVC filters, as well as VTE recurrence and death. A total of 257 consecutive patients were analyzed. Seventy-eight patients (30 %) received IVC filters. The proportions of IVC filter placement were 26 % for deep-vein thrombosis (DVT) alone, 10 % for pulmonary embolism (PE) alone, and 46 % for both DVT and PE. There was no significant difference in patient demographics between the IVC filter group and no-IVC filter group. Stated indications for filter placement were 24 cases (30 %) of DVT in intrapelvic veins, 16 cases (20 %) of DVT in proximal veins, and 11 cases (14 %) of contraindication to anticoagulant therapy. In the IVC filter group, cases of class I indication (guidelines: JCS 75:1258–1281, 2009) numbered only 6 (8 %). Many of the retrievable IVC filters were not removed and placed permanently and the retrieval rate was 42 %. We found complications of IVC filters in 8 cases (10 %). IVC filter placement was significantly associated with a better survival rate and a higher incidence of DVT recurrence during a mean observation period of 541 days. Our research suggests the frequent use of IVC filters for VTE treatment, combined with a low retrieval rate. Most of the stated indications of IVC filter placement for VTE in Japanese patients were cases of DVT in intrapelvic veins or proximal veins, not cases of contraindication to anticoagulant therapy.



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Predictors of persistent pulmonary hypertension after mitral valve replacement

Abstract

Persistent pulmonary hypertension (P-PH) after mitral valve replacement (MVR) leads to an increased risk of morbidity and mortality. We sought to determine which factors were involved in its occurrence. Patients undergoing MVR for a 3-year period were collected in a retrospective way. We excluded those with an available follow-up shorter than 3 months. Sample size was 111 patients. PH was diagnosed if systolic pulmonary artery pressure (sPAP) estimated by Doppler echocardiography was >40 mmHg. Clinical, echocardiographic, and surgical factors were analyzed. P-PH was present in 42.3 % of patients after 12.6 months of mean follow-up. P-PH was more frequently observed in elderly and female patients, in those with severe degrees of PH before surgery, and significant tricuspid regurgitation (TR). On multivariable analysis, significant TR (OR 1.739; p = 0.01) and more severe degrees of PH before surgery (OR 1.761; p = 0.03) were significantly associated with the presence of P-PH after MVR. Surgical factors related to P-PH were prosthesis size and tricuspid annuloplasty: no need for the performing of tricuspid annuloplasty (OR 0.345; p = 0.025) and the implantation of a smaller prosthesis (OR 0.656; p = 0.004) were related to higher rates of P-PH after MVR. MVR was associated with high prevalence of P-PH after mid-term follow-up. Both PH and significant TR before surgery were associated with P-PH. Our data point out that MVR should be planned before the development of PH and greater TR. Smaller prosthetic size is also a risk factor for P-PH and bigger prostheses are desirable when possible.



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A case of interferon-α-induced pulmonary arterial hypertension after living donor liver transplantation

Abstract

Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease characterized by elevated pulmonary vascular resistance, which results in right-heart failure. We present a case of interferon (IFN)-α-induced PAH developed after living donor liver transplantation. Although IFN is categorized as a "possible" risk factor for PAH in the current international classification, it is still under recognized. Moreover, the prognosis of IFN-induced PAH is poor in the limited number of published cases. In our case, we achieved good outcome by the withdrawal of IFN and administration of combination therapy using tadalafil, beraprost, and treprostinil. Since IFN is an important treatment option in current medical therapy, its contribution to the pathogenesis of PAH should be taken into consideration. In conclusion, our case suggests the importance of PAH screening in patients treated with IFN.



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Axillary artery cannulation provides balanced cerebral oxygenation

Abstract

Deterioration of cerebral performance remains a major problem after cardiac surgery. Axillary artery cannulation can improve clinical outcome, but some experimental series show a malperfusion of the right hemisphere. The aim of our clinical study was to analyze the intraoperative investigation of cerebral oxygenation in two different arterial cannulation sites by use of near-infrared spectroscopic oximetry (NIRO). We compared retrospectively the cerebral saturation of 20 patients with aortic cannulation (group AoC) and 20 patients with right axillary artery cannulation (group AxC) during either valve, coronary artery bypass graft (CABG), combined procedures, or aortic surgery. Patients were monitored with bihemispheric NIRO (NIRO-200, Hamamatsu, Herrsching, Germany). The oxygenation data were calculated as tissue oxygenation index (TOI). And the cardiopulmonary bypass time was considered with special regard to potentially dangerous phases for cerebral desaturation like the starting of the extracorporeal circulation (ECC), cross-clamping, rewarming phase, aortic declamping, and stopping of ECC. Patients were then postoperatively evaluated by a standardized neurological examination. During the entire CPB time and the specific phases potentially at risk for cerebral desaturation, no statistically significant drop of cerebral oxygenation (>20 % for >60 s) was detected after aortic and right axillary artery cannulation, respectively. Furthermore, no significant difference in TOI was found comparing the left and right hemisphere in each group. Postoperatively 2 transient confusional syndromes (CS) were observed after aortic and 3 CS after axillary artery cannulation. Right axillary artery cannulation provides balanced cerebral oxygenation in both hemispheres during extracorporeal circulation and its specific phases potentially at risk for cerebral malperfusion. It might therefore reduce the risk of neurological injury by reduction of solid embolization and maintenance of balanced cerebral oxygenation.



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Relationship between diastolic ventricular dysfunction and subclinical sleep-disordered breathing in atrial fibrillation ablation candidates

Abstract

Sleep-disordered breathing (SDB) is recognized as a primary factor or mediator of atrial fibrillation (AF). We hypothesized that the severity of SDB among AF ablation candidates would be associated with left ventricular diastolic dysfunction (LVDD) even for subclinical SDB. A total of 246 patients hospitalized for initial pulmonary vein isolation (PVI) were analyzed. Known SDB cases were excluded. We measured the oxygen desaturation index (ODI) by pulse oximetry overnight as an indicator of SDB, and classified SDB severity by 3 % ODI as normal (ODI < 5 events/h), mild (ODI ≤ 5 to <15 events/h), or moderate-to-severe (ODI ≥15 events/h). The LVDD was assessed by echocardiography using combined categories with tissue Doppler imaging and left atrial (LA) volume measurement. Among the participants, 42 patients (17.1 %) had LVDD. The prevalence of LVDD increased with the SDB severity from 8.6 % (normal) to 12.7 % (mild) to 40.0 % (moderate-to-severe SDB) (p < 0.0001). In the multivariate logistic regression analysis, the odds ratio of having LVDD in the moderate-to-severe SDB group (ODI ≥ 15) vs. normal group (ODI < 5) was 5.96 (95 % CI, 2.10–19.00, P = 0.006). The presence of moderate-to-severe SDB in AF ablation candidates adversely affected LV diastolic function even during a subclinical state of SDB.



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Linkage of sleep-disordered breathing and acute aortic dissection with patent false lumen

Abstract

Sleep-disordered breathing (SDB) is known as a cardiovascular risk factor and has high prevalence in hypertension, which is a major risk factor of aortic dissection (AD). However, the impact of SDB on AD has not been fully clarified. The aim of this study is to elucidate the impact of SDB on AD, especially on the type of false lumen in AD. We enrolled twenty-three consecutive patients with acute AD (mean age: 66 ± 13 years). All subjects were evaluated by an ambulatory polygraphic sleep monitoring within 1 month from the onset. AD was evaluated by axial images of computed tomography. We comparatively analyzed SDB and AD. 35 % of the subjects presented severe OSA (apnea–hypopnea index: AHI ≥30). The patent false lumen group showed significantly higher systolic and diastolic blood pressure (BP) on arrival and AHI, and lower percutaneous oxygen saturation (SaO2) compared with those in the thrombosed false lumen group. The prevalence of severe SDB was higher in the patent false lumen group (60 vs 15 %, p = 0.039). Systolic BP on arrival was significantly correlated with AHI (r = 0.457, p = 0.033) and the minimum SaO2 (r = −0.537, p = 0.010). The present study revealed close linkage between SDB and AD, and a high prevalence of SDB among AD patients. Severe SDB was related to the development of AD, especially for the patent false lumen type through highly elevated BP which might be easily evoked in the presence of severe SDB. Repetitive occurrence of intrathoracic negative pressure also might influence the repair or closure of false lumen of AD, although the present analysis did not reach statistical significance.



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Prognostic significance of beta-blocker up-titration in conjunction with cardiac resynchronization therapy in heart failure management

Abstract

Clinical practice guidelines emphasize that optimal pharmacotherapy, including beta-blockers (BB), is a prerequisite before receiving cardiac resynchronization therapy (CRT) in eligible patients with heart failure (HF). However, the optimal dose of BB before CRT implantation cannot be tolerated in a number of patients. Sixty-three consecutive patients who underwent CRT in 2006–2013 were retrospectively investigated. Before receiving CRT, BB could not be introduced in 20 patients (32 %); the daily carvedilol-equivalent dose in other 43 patients was 5.6 ± 7.0 mg because of significant HF and bradycardia. After receiving CRT, BB could be introduced in almost all patients (n = 61, 97 %), and the daily BB dose increased from 5.6 ± 7.0 to 13.2 ± 7.8 mg (P < 0.001). Multivariate analysis indicated that the change of BB dose after CRT was independently associated with improved left ventricular end-systolic volume (LVESV) [β = −0.36; 95 % confidence interval (CI) −2.13 to −0.45; P < 0.01] after 6-months follow-up. Furthermore, Cox proportional hazard analysis also showed that the change in the BB dose (hazard ratio, 0.92; 95 % CI, 0.87–0.98; P < 0.01) as well as the New York Heart Association functional classification was an independent predictor of cardiac events. After initiating CRT, BB therapy can be introduced and up-titrated in intolerant HF patients. The up-titrated dose of BB after CRT was an independent predictor for the improvement of LVESV and HF prognosis.



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Increased p -cresyl sulfate level is independently associated with poor outcomes in patients with heart failure

Abstract

Amino acid-derived metabolites, including protein-bound uremic toxins, may have prognostic value for patients with heart failure (HF). The aim of this study was to investigate whether p-cresyl sulfate (PCS), indoxyl sulfate (IS), and arginine metabolites provided prognostic values in addition to the traditional biomarker, B-type natriuretic peptide (BNP), in patients with HF. Chromatography mass spectrometry was performed to measure tyrosine, tryptophan, arginine, PCS, IS, and asymmetric (ADMA) and symmetric dimethylarginine (SDMA) in the plasma from 51 normal controls and 136 HF patients. Compared to the normal controls, PCS levels significantly increased in HF patients (p = 0.003). During the follow-up (2.3 ± 1.1 years), 35 (25.7 %) patients experienced a composite event of death or HF-related re-hospitalization. In univariable analysis, PCS, estimated glomerular filtration rate (eGFR), BNP, DMA/arginine ratio, and ADMA/arginine ratio were associated with a higher rate of composite events. In the multivariable analysis, PCS was the only independent predictor of composite events [hazard ratio (HR) 1.06 (per 10 μM), 95 % confidence interval (CI) 1.01–1.11, p = 0.02]. Kaplan–Meier curves showed that a PCS level of ≥50 μM was significantly associated with a higher composite event rate than those with a PCS level of <50 μM (Log rank = 5.11, p = 0.024; HR 2.13, 95 % CI 1.09–4.16, p = 0.02). In conclusion, among protein-bound uremic toxins, eGFR, and DMA metabolites, increased PCS is the only independent predictor of HF-related events in patients with HF. A combination of PCS and BNP should better risk-stratify patients with HF.



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Does reducing ischemia time justify to catheterize firstly the culprit artery in every primary PCI?

Abstract

No consensus exists about which coronary artery should be firstly catheterized in primary PCIs. Initial catheterization of the "culprit artery" could reduce reperfusion time. However, complete knowledge of coronary anatomy could modify revascularization strategy. The objective of the study was to analyze this issue in ST-elevation myocardial infarction patients undergoing primary PCI. PCIs were performed in 384 consecutive patients. Choice of ipsilateral approach (IA): starting with a guiding catheter for the angiography and PCI of the "culprit artery", or contralateral approach (CA): starting with a diagnostic catheter for the "non-culprit artery" and completing the angiography and PCI of the culprit with a guiding catheter was left to the operator. Differences between two approaches regarding reperfusion time, acute events or revascularization strategies were analyzed. There were no differences between two approaches regarding reperfusion time or clinical events. When the left coronary artery was responsible, IA was more frequent (76.4 vs 22.6 %), but when it was the right coronary artery, CA was preferred (20 vs 80 %); p < 0.0001. With CA, bare metal stents (BMS) were more used than drug eluting (DES) (60.8 vs 39.2 %) inversely than with IA (BMS 41.3 vs DES 59.7 %; p < 0.0001). With CA there were more patients with left main or multivessel disease in which revascularization was completed with non-urgent surgery (4.13 vs 2.4 %, p < 0.0001). Initial CA does not involve higher reperfusion time. Furthermore, overall knowledge of coronary anatomy offers more options in revascularization strategy and may imply a change in management. Despite the need to individualize each case, contralateral approach may be the first option with the exception of unstable patients.



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Progression from stenosis to occlusion in the proximal native coronary artery after coronary artery bypass grafting

Abstract

Coronary artery bypass grafting (CABG) is an established treatment for multivessel coronary artery disease. However, problematic situations are occasionally encountered after CABG, such as disease progression in the native coronary artery with graft occlusion, which causes difficulty in revascularization. The purpose of this study was to evaluate changes in the native coronary artery after CABG. Between 2009 and 2012 in our institution, 351 patients underwent CABG, and 768 bypass grafts were anastomosed to non-occluded coronary arteries. Of these, 489 bypass grafts had available early postoperative angiographic results (≤6 months) suitable for assessment in this study. We defined malignant graft failure after CABG to be bypass graft occlusion and de novo complete occlusion of the target native coronary artery proximal to the graft anastomosis site. In the early angiographic results, 17 grafts were occluded (17/489; 3.5 %). Two of the grafts displayed malignant graft failure (a saphenous vein graft to the right coronary artery and a saphenous vein graft to the diagonal branch) (2 of 17 occluded grafts, and 2 of 489 studied grafts). Of the patent bypass grafts, 24 involved progression to occlusion in the proximal native coronary artery (19 saphenous vein grafts, 4 left internal thoracic artery grafts, and 1 right internal thoracic artery graft). Malignant graft failure was uncommon during short-term follow-up after CABG. At the same time, disease progression in the proximal native coronary artery from stenosis to occlusion following patent bypass grafting was relatively common, especially for vein grafts.



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Relationship between abdominal aortic and coronary artery calcification as detected by computed tomography in chronic kidney disease patients

Abstract

The purpose of this study was to investigate the relationship between abdominal aortic calcification (AAC) and coronary artery calcification (CAC) in chronic kidney disease (CKD) patients. We evaluated 126 asymptomatic CKD patients (mean estimated glomerular filtration rate: 36.1 ± 14.1 mL/min/1.73 m2, mean age 70.3 ± 10.1 years). A non-contrast computed tomography scan was used to determine the abdominal aortic calcification index (ACI) and CAC score, and this relationship was investigated. Among the subjects, AAC was present in 109 patients (86.5 %) as defined by ACI >0 and median ACI was 11.7 %. ACI increased in accordance with advances in CAC score grades (3.0, 5.2, 17.2, and 32.8 % for CAC score 0, 1–100, 101–400, and 401 or more, respectively, p < 0.001). Even after multivariate adjustment, ACI was independently associated with severe CAC score as defined by CAC score >400 [odds ratio 1.08, 95 % confidence interval (CI) 1.04–1.12, p < 0.001]. Receiver-operating curve analysis showed that the ACI optimal cut-off value predicting severe CAC score was 16.5 % (area under the curve = 0.79, 95 % CI 0.69–0.90, p < 0.001). The C statics for predicting CAC score was significantly increased by adding ACI values to the model including other risk factors (0.853 versus 0.737, p = 0.023). In conclusion, the ACI value of 16.5 % allows us to predict the presence of severe CAC in CKD patients, and that the addition of ACI to the model with traditional risk factors significantly improves the predictive ability of severe CAC score. These data reinforce the utility of ACI as a screening tool in clinical practice.



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Outcomes in children with advanced heart failure in Japan: importance of mechanical circulatory support

Abstract

The Japanese organ transplant law was revised in July 2010 in order to enable children aged <15 years to donate organs. However, the waiting time for orthotopic heart transplantation (HTx) is as long as 636 days in children due to a shortage of organ donors. Ventricular assist devices (VADs) have been widely used as a bridge to transplantation in Western countries, whereas experience with VADs is limited in Japan due to a lack of device availability for small children. This study aimed to clarify the clinical profiles and outcomes of children with advanced heart failure in Japan and to investigate the importance of mechanical circulatory support (MCS), VADs, and extracorporeal membrane oxygenation (ECMO) in children. A retrospective chart review of patients with advanced heart failure who were eligible for HTx between January 2006 and May 2015 was performed at the Department of Pediatric Cardiology, Tokyo Woman's Medical University, Japan. Patients were divided into two groups based on need for MCS. Clinical data pre- and post-revision of the Japanese organ transplant law were compared. Preoperative clinical conditions were evaluated based on Interagency Registry for Mechanically Circulatory Support (INTERMACS) profiles. Twenty-two patients were included in the study, 12 of whom required MCS. VADs were implanted in nine patients and ECMO was needed in seven patients. Of the MCS group, 5 deaths occurred in patients with a preoperative INTERMACS profile-1. High total bilirubin was found to be associated with mortality by multivariate logistic regression analysis (OR 7.8, p = 0.02). Wait list mortality was 32 % and no difference in clinical profiles pre- and post-revision of the Japanese organ transplant law was observed. Approximately 55 % of pediatric patients with advanced heart failure required MCS support. Preoperative conditions such as INTERMACS profile-1 and high total bilirubin were associated with poor outcomes. The Japanese organ transplant law revision had no significant influence on patient profiles or outcomes.



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Association between smoking habits and severity of coronary stenosis as assessed by coronary computed tomography angiography

Abstract

Smoking promotes arteriosclerosis and is one of the most important coronary risk factors. However, few studies have investigated the association between smoking habits and the severity of coronary stenosis as assessed by coronary computed tomography angiography (CTA). We enrolled 416 patients [165/251 = smoker (past and current)/non-smoker)]. They had all undergone CTA and either were clinically suspected of having coronary artery disease (CAD) or had at least one cardiovascular risk factor. We divided the patients into smoking and non-smoking groups, and evaluated the presence of CAD, the number of significantly stenosed coronary vessels (VD), and the Gensini score as assessed by CTA in the two groups. The incidence of CAD, VD, the Gensini score, and coronary calcification score in the smoking group were all significantly greater than those in the non-smoking group (CAD, p = 0.009; VD, p = 0.003; Gensini score, p = 0.007; coronary calcification score, p = 0.01). Pack-year was significantly associated with VD and the Gensini score, and was strongly associated with multi-vessel disease (2- and 3-VD) (p < 0.05), whereas the duration of cessation in past smokers was not associated with VD or the Gensini score. Pack-year, but not the duration of cessation, may be the most important factor that was associated with the severity of coronary stenosis in terms of VD and the Gensini score.



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Incidence and predictors of ischemic stroke during hospitalization for congestive heart failure

Abstract

Heart failure (HF) increases the risk of ischemic stroke. Data regarding the incidence and predictors of ischemic stroke during hospitalization for HF are limited. The study population of this retrospective cohort study consisted of patients with congestive HF, consecutively admitted to our center from October 2010 to April 2014. We excluded patients complicated with acute myocardial infarction, infective endocarditis, and takotsubo cardiomyopathy. We also excluded those with dialysis or mechanical circulatory support. We investigated the incidence of ischemic stroke during hospitalization for HF. Thereafter, we divided the patients without oral anticoagulants at admission into two groups: patients with ischemic stroke and those without it, and explored the predictors of ischemic stroke. A total of 558 patients (287 without atrial fibrillation (AF), 271 with AF) were enrolled. The mean age was 76.8 ± 12.3 years, and 244 patients (44 %) were female. The mean left-ventricular ejection fraction was 47.4 %. Oral anticoagulants were prescribed in 147 patients (8 without AF, 139 with AF). During hospitalization (median length 18 days), symptomatic ischemic stroke (excluding catheter-related) occurred in 15 patients (2.7 % of the total, 8 without AF, 7 with AF). Predictors significantly associated with increased risk of ischemic stroke in patients without oral anticoagulants were as follows; short-term increases in blood urea nitrogen after admission (at day 3; odds ratio (per 1 md/dl): 1.06, 95 % confidence interval (CI) 1.01–1.11, p = 0.02, and at day 7; odds ratio: 1.03, 95 % CI 1.00–1.07, p = 0.03, respectively), and previous stroke (odds ratio; 3.33, 95 % CI 1.01–11.00, p = 0.04). The incidence of ischemic stroke during hospitalization for HF was high, even in patients without AF. Previous stroke and short-term increases in blood urea nitrogen was significantly associated with the incidence of ischemic stroke.



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Incidence of ischemic stroke and systemic embolism in patients with hypertrophic cardiomyopathy, nonvalvular atrial fibrillation, CHA 2 DS 2 -VASc score of ≤1 and without anticoagulant therapy

Abstract

Data on the risk of ischemic stroke and systemic embolism (iSSE) events in patients with nonvalvular atrial fibrillation (NVAF), a CHA2DS2-VASc score of ≤1, hypertrophic cardiomyopathy (HCM), and without anticoagulant therapy are still lacking. The aim of this study was to investigate the incidence of iSSE events in these patients. We consecutively screened medical records of patients with HCM and NVAF referred to Fuwai Hospital between January 1994 and March 2014. The primary end point was iSSE events, defined as a composite of ischemic stroke and systemic embolism. Follow-up was carried out to ascertain end point status. Medical records of 522 patients with NVAF and HCM were screened. A total of 108 patients (20.7 %) with a CHA2DS2-VASc score of ≤1 and without anticoagulant therapy were enrolled and constituted our study population. After a median follow-up of 2.4 years (range 0.6–14.1 years; 376.2 patient-years), ischemic stroke occurred in 2 patients, resulting in death of 1 patient in the first year and paralysis of the other patient in the fourth year. No other iSSE events occurred. The incidence of iSSE was 0.9 % [95 % confidence interval (CI) 0.0–5.0 %] in the first year, and 0.5 % per 100 patient-years (95 % CI 0.1–1.9 %). The risk of iSSE events seems low in patients with NVAF, a CHA2DS2-VASc score of ≤1, HCM, and without anticoagulant therapy. Multicenter studies with sizeable study populations are needed to validate the risk of iSSE events in these patients.



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Paced QRS duration and myocardial scar amount: predictors of long-term outcome of right ventricular apical pacing

Abstract

Long-term right ventricular apical pacing (RVAP) is reportedly associated with heart failure (HF) development. However, the predictors of pacing-induced HF (PHF) remained unclear. We retrospectively enrolled 234 patients without structural heart disease who underwent a permanent pacemaker implantation with RVAP between 1982 and 2004. RVAP-induced HF was defined as left ventricular ejection fraction decrease >5 % with HF symptom without other HF development etiology. The QRS duration of a paced beat (pQRSd) and myocardial scar score were analyzed from each patient's 12-lead ECG. During a mean 15.6 years (range 3.3–30.0 years), 48 patients (20.5 %) patients developed RVAP-induced HF. The PHF group patients had a longer pQRSd (192.4 ± 13.5 vs. 175.7 ± 14.7 ms in non-PHF patients, p < 0.001) and a higher myocardial scar score (5.2 ± 1.9 vs. 2.7 ± 1.9, respectively p < 0.001). In multivariate Cox regression analysis, old age at implantation [Hazard ratio (HR) 1.62, 95 % confidential interval (CI) 1.22–2.16, p = 0.001], a longer pQRSd (HR 1.54, 95 % CI 1.15–2.05, p = 0.003), a higher myocardial scar score (HR 1.23, 95 % CI 1.03–1.49, p = 0.037), and a higher percentage of ventricular pacing (HR 1.31, 95 % CI 1.01–1.49, p = 0.010) were independent predictors of PHF. Based on the results of the receiver-operating characteristic (ROC) curve, the pQRSd cutoff was 185 ms (AUC 0.79, sensitivity 66.7 %, specificity 76.3 %) and myocardial scar score cutoff value was 4 (AUC 0.81, sensitivity 81.3 %, specificity 66.1 %). The pQRSd was positively correlated with scar score (r = 0.70, p < 0.001). pQRSd ≥185 ms and/or myocardial scar score ≥4 might be independent long-term prognostic markers of PHF.



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Adolescent Pregnancy and Smoking in West Virginia: Pregnancy Risk Assessment Monitoring System (PRAMS) 2005–2010

Abstract

Objective The purpose of this study was to examine the association between prenatal smoking and small for gestational age (SGA) infants among adolescent women in West Virginia, taking into account sociodemographic and health-related factors. Methods Secondary data analysis was conducted using the 2005–2010 West Virginia Pregnancy Risk Assessment and Monitoring Systems weighted dataset. The study population using complete case analysis procedure consisted of 886 adolescent women ages 19 and younger who delivered a live singleton infant in West Virginia. Results The prevalence of smoking among adolescents during the last 3 months of pregnancy was 67 %. Nearly a quarter (22.0 %) of the adolescents gave birth to SGA infants. Results from the logistic regression analysis showed that after controlling for sociodemographic and health-related variables, adolescents who smoked during the last 3 months of pregnancy were more likely to have SGA infants than those who did not smoke during the last 3 months of pregnancy (OR = 1.86, 95 % CI 1.06–3.27, P = 0.0307). Conclusion This study highlights the importance of recognizing that prenatal smoking is an issue among West Virginia adolescents and the need for evidence-based, culturally, and developmentally appropriate interventions for this Appalachian population.



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Use of 3D pseudo-continuous arterial spin labeling to characterize sex and age differences in cerebral blood flow

Abstract

Introduction

The aim of the present study is to use 3D pseudo-continuous arterial spin labeling (pCASL) to measure changes in normal cerebral blood flow (CBF) values with sex and age.

Methods

Eighty subjects underwent magnetic resonance imaging study on a 3.0-T scanner. 3D pCASL was used to measure CBF. Estradiol and testosterone levels were also assessed. Based on sex and age, the subjects were divided into four groups for statistical analysis.

Results

CBF was higher in young premenopausal women than in young men (P < 0.01), while there was no difference in CBF between older postmenopausal women and older men. CBF was also significantly decreased in older postmenopausal women compared with young women (P < 0.01), whereas no such age-related effect was present in men.

Conclusion

These observations indicate that sex and age differences are important considerations when studying nervous system diseases and that the age range and female-to-male ratio should be considered in the selection of subjects for brain studies in order to eliminate bias. Further, the normal CBF values assessed by pCASL provide a basis for further clinical use of pCASL.



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Software output from semi-automated planimetry can underestimate intracerebral haemorrhage and peri-haematomal oedema volumes by up to 41 %

Abstract

Introduction

Haematoma and oedema size determines outcome after intracerebral haemorrhage (ICH), with each added 10 % volume increasing mortality by 5 %. We assessed the reliability of semi-automated computed tomography planimetry using Analyze and Osirix softwares.

Methods

We randomly selected 100 scans from 1329 ICH patients from two centres. We used Hounsfield Unit thresholds of 5–33 for oedema and 44–100 for ICH. Three raters segmented all scans using both softwares and 20 scans repeated for intra-rater reliability and segmentation timing. Volumes reported by Analyze and Osirix were compared to volume estimates calculated using the best practice method, taking effective individual slice thickness, i.e. voxel depth, into account.

Results

There was excellent overall inter-rater, intra-rater and inter-software reliability, all intraclass correlation coefficients >0.918. Analyze and Osirix produced similar haematoma (mean difference: Analyze − Osirix = 1.5 ± 5.2 mL, 6 %, p ≤ 0.001) and oedema volumes (−0.6 ± 12.6 mL, −3 %, p = 0.377). Compared to a best practice approach to volume calculation, the automated haematoma volume output was 2.6 mL (−11 %) too small with Analyze and 4.0 mL (−18 %) too small with Osirix, whilst the oedema volumes were 2.5 mL (−12 %) and 5.5 mL (−25 %) too small, correspondingly. In scans with variable slice thickness, the volume underestimations were larger, −29%/−36 % for ICH and −29 %/−41 % for oedema. Mean segmentation times were 6:53 ± 4:02 min with Analyze and 9:06 ± 5:24 min with Osirix (p < 0.001).

Conclusion

Our results demonstrate that the method used to determine voxel depth can influence the final volume output markedly. Results of clinical and collaborative studies need to be considered in the context of these methodological differences.



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Implementation of a single quad MS detector in routine QC analysis of peptide drugs

A newly developed single quad mass spectrometry (MS) detector was coupled to a ultra-high performance liquid chromatography (UPLC) system and implemented in the routine quality control (QC) and impurity analysis of four therapeutic peptides, namely bleomycin sulfate, tyrothricin, vancomycin HCl and bacitracin, which were selected given their multi-component drug nature and their closely structurally related impurity profiles. The QC and impurity profiling results obtained using the ultra-high performance liquid chromatography ultraviolet/mass spectrometry (UPLC-UV/MS) detection system were analyzed against the results obtained using traditional high performance liquid chromatography-ultraviolet detection (HPLC-UV) methods derived from pharmacopoeial methods. In general, the used stationary phases of sub-2 µm particle (UPLC) technology resulted in lower limits of detection and higher resolution separations, which resulted in more detected impurities and shorter overall run times contrasting the traditional HPLC columns. Moreover, online coupling with a single quad MS detector allowed direct peak identification of the main compounds as well as small impurities, hereby increasing the information content without the need of reference standards.

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Aerosolized non-viral nucleic acid delivery in the vaginal tract of pigs

PURPOSE: The human pathogen Chlamydia trachomatis is worldwide the leading cause of bacterial sexually transmitted disease. Nasal or vaginal nucleic acid vaccination is a promising strategy for controlling genital Chlamydia trachomatis infections. Since naked nucleic acids are generally not efficiently taken up by cells, they are often complexed with carriers that facilitate their intracellular delivery. METHODS: In the current study, we screened a variety of commonly used non-viral gene delivery carriers for their ability to transfect newborn pig tracheal cells. The effect of aerosolization on the physicochemical properties and transfection efficiency of the complexes was also evaluated in vitro. Subsequently, a pilot experiment was performed in which the selected complexes were aerosolized in the vaginal tract of pigs. RESULTS: Both mRNA and pDNA containing lipofectamine and ADM70 complexes showed promise for protein expression in vitro, before and after aerosolization. In vivo, only lipofectamine/pDNA complexes resulted in high protein expression levels 24 h following aerosolization. This correlates to the unexpected observation that the presence of vaginal mucus increases the efficiency of lipofectamine/pDNA complexes 3-fold, while the efficiency of lipofectamine/mRNA complexes and ADM70/mRNA and ADM70/pDNA complexes decreased. CONCLUSIONS: As aerosolization was an easy and effective method to deliver complexes to the vaginal tract of pigs, we believe this application technique has future potential for both vaginal and perhaps nasal vaccination using non-viral gene delivery vectors.

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Anti-atherosclerotic potential of baicalin mediated by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1/ABCG1 pathway

Publication date: October 2016
Source:Biomedicine & Pharmacotherapy, Volume 83
Author(s): Xin-Wei He, Dan Yu, Wei-Ling Li, Zhou Zheng, Chen-Ling Lv, Cai Li, Peng Liu, Chun-Qiang Xu, Xiao-Fei Hu, Xiao-Ping Jin
BackgroundAtherosclerosis (AS) is associated with severe cardiovascular disease. The anti-inflammatory, anti-oxidation, and lipid regulating properties of baicalin suggest potential as an anti-atherosclerotic agent. We therefore investigated whether baicalin can protect against the development of atherosclerosis in an AS rabbit model and explored the underling mechanisms in THP-1 macrophages.Methods and resultsIn vivo, treatment with baicalin markedly decreased atherosclerotic lesion sizes and lipid accumulation in AS rabbit carotid arteries. Western blotting revealed that the protein expression levels of both peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor alpha (LXRα) were up-regulated in the baicalin group compared with the model group. In vitro, baicalin restricted oxidized-low density lipoprotein (ox-LDL)-induced intracellular lipid accumulation and foam cell formation in THP-1 macrophages. Molecular data showed that baicalin significantly increased the expression levels of PPARγ, LXRα, ATP binding cassette transporters (ABC) A1 and ABCG1. Cell transfection experiments (including PPARγ and LXRα siRNAs) suggested that the effects of baicalin are mediated by the PPARγ-LXRα signalling pathway, which stimulates the expression of ABCA1 and ABCG1.ConclusionThese results suggest that baicalin potentially exerts anti-atherosclerosis effects, possibly through the PPARγ-LXRα-ABCA1/ABCG1 pathway, by promoting efflux of cholesterol from macrophages and delaying the formation of foam cells.



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Detection of Molecular Alterations in Medullary Thyroid Carcinoma Using Next-Generation Sequencing: an Institutional Experience

Abstract

Medullary thyroid carcinoma (MTC) harbors rearranged during transfection (RET) gene and rarely RAS gene mutations. The knowledge of the type of gene mutation in MTC is important to determine the treatment of the patients and the management of their family members. Targeted next-generation sequencing with a panel of 47 genes was performed in a total of 12 cases of sporadic (9/12) and hereditary MTC (3/12). Two of three hereditary MTCs had RET/C634R mutation, while the other one harbored two RET mutations (L790F and S649L). All the sporadic MTC had RET/M918T mutation except one case with HRAS mutation. Next-generation sequencing (NGS) can provide comprehensive analysis of molecular alterations in MTC in a routine clinical setting, which facilitate the management of the patient and the family members.



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SILVERBACK+ : scalable association mining via fast list intersection for columnar social data

Abstract

We present Silverback+, a scalable probabilistic framework for accurate association rule and frequent item-set mining of large-scale social behavioral data. Silverback+ tackles the problem of efficient storage utilization and management via: (1) probabilistic columnar infrastructure and (2) using Bloom filters and sampling techniques. In addition, probabilistic pruning techniques based on Apriori method are developed, for accelerating the mining of frequent item-sets. The proposed target-driven techniques yield a significant reduction of the size of the frequent item-set candidates, as well as the required number of repetitive membership checks through a novel list intersection algorithm. Extensive experimental evaluations demonstrate the benefits of this context-aware consideration and incorporation of the infrastructure limitations when utilizing the corresponding research techniques. When compared to the traditional Hadoop-based approach for improving scalability by straightforwardly adding more hosts, Silverback+ exhibits a much better runtime performance, with negligible loss of accuracy.



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