Multigeneration family with dominant SPG30 hereditary spastic paraplegia

Abstract

Autosomal recessive KIF1A missense mutations cause hereditary spastic paraplegia (HSP) type SPG30, while recessive truncations lead to sensory and autonomic neuropathy (HSN2C) and many de novo missense mutations are associated with cognitive impairment. Here, we describe family members across three generations with pure HSP. A heterozygous p.Ser69Leu KIF1A mutation segregates with those afflicted. The same variant was previously reported in a Finnish father and son with pure HSP as well as four members of a Sicilian kindred with more intrafamilial phenotypic variability. This further validates the pathogenicity of the p.Ser69Leu mutation and suggests that it may represent a mutation hot spot.

http://ift.tt/2gFVhTt

Improved plan quality with automated radiotherapy planning for whole brain with hippocampus sparing: a comparison to the RTOG 0933 trial

Abstract

Background

Whole-brain radiation therapy (WBRT) with hippocampus sparing (HS) has been investigated by the radiation oncology working group (RTOG) 0933 trial for patients with multiple brain metastases. They showed a decrease of adverse neurocognitive effects with HS WBRT compared to WBRT alone. With the development of automated treatment planning system (aTPS) in the last years, a standardization of the plan quality at a high level was achieved. The goal of this study was to evaluate the feasibility of using an aTPS for the treatment of HS WBRT and see if the RTOG 0933 dose constraints could be achieved and improved.

Methods

Ten consecutive patients treated with HS WBRT were enrolled in this study. 10 × 3 Gy was prescribed according to the RTOG 0933 protocol to 92% of the target volume (whole-brain excluding the hippocampus expanded by 5 mm in 3-dimensions). In contrast to RTOG 0933, the maximum allowed point dose to normal brain was significantly lowered and restricted to 36.5 Gy. All patients were planned with volumetric modulated arc therapy (VMAT) technique using four arcs. Plans were optimized using Auto-Planning (AP) (Philips Radiation Oncology Systems) with one single AP template and optimization.

Results

All the constraints from the RTOG 0933 trial were achieved. A significant improvement for the maximal dose to 2% of the brain with a reduction of 4 Gy was achieved (33.5 Gy vs. RTOG 37.5 Gy) and the minimum hippocampus dose was reduced by 10% (8.1 Gy vs. RTOG 9 Gy). A steep dose gradient around the hippocampus was achieved with a mean dose of 27.3 Gy at a distance between 0.5 cm and 1 cm from the hippocampus. The effective working time to optimize a plan was kept below 6′.

Conclusion

Automated treatment planning for HS WBRT was able to fulfil all the recommendations from the RTOG 0933 study while significantly improving dose homogeneity and decreasing unnecessary hot spot in the normal brain. With this approach, a standardization of plan quality was achieved and the effective time required for plan optimization was minimized.

http://ift.tt/2yoVu6I

Exclusion of emphysematous lung from dose-volume estimates of risk improves prediction of radiation pneumonitis

Abstract

Background

The risk factors for radiation pneumonitis (RP) in patients with chronic obstructive pulmonary disease (COPD) are unclear. Mean lung dose (MLD) and percentage of irradiated lung volume are common predictors of RP, but the most accurate dosimetric parameter has not been established. We hypothesized that the total lung volume irradiated without emphysema would influence the onset of RP.

Methods

We retrospectively evaluated 100 patients who received radiotherapy for lung cancer. RP was graded according to the Common Terminology Criteria for Adverse Events (version 4.03). We quantified low attenuation volume (LAV) using quantitative computed tomography analysis. The association between RP and traditional dosimetric parameters including MLD, volume of the lung receiving a dose of ≥2 Gy, ≥ 5 Gy, ≥ 10 Gy, ≥ 20 Gy, and ≥30 Gy, and counterpart measurements of the lung without LAV, were analyzed by logistic regression. We compared each dosimetric parameter for RP using multiple predictive performance measures including area under the receiver operating characteristic curve (AUC) and integrated discrimination improvement (IDI).

Results

Of 100 patients, RP of Grades 1, 2, 3, 4, and 5 was diagnosed in 24, 12, 13, 1, and 1 patients, respectively. Compared with traditional dosimetric parameters, counterpart measurements without LAV improved risk prediction of symptomatic RP. The ratio of the lung without LAV receiving ≥30 Gy to the total lung volume without LAV most accurately predicted symptomatic RP (AUC, 0.894; IDI, 0.064).

Conclusion

Irradiated lung volume without LAV predicted RP more accurately than traditional dosimetric parameters.

http://ift.tt/2gm9V5b

Comparative study of the effects of different radiation qualities on normal human breast cells

Abstract

Background

As there is a growing number of long-term cancer survivors, the incidence of carcinogenesis as a late effect of radiotherapy is getting more and more into the focus. The risk for the development of secondary malignant neoplasms might be significantly increased due to exposure of healthy tissue outside of the target field to secondary neutrons, in particular in proton therapy. Thus far, the radiobiological effects of these neutrons and a comparison with photons on normal breast cells have not been sufficiently characterised.

Methods

MCF10A cells were irradiated with doses of up to 2 Gy with neutrons of different energy spectra and X-rays for comparison. The biological effects of neutrons with a broad energy distribution (<E _n > = 5.8 MeV), monoenergetic neutrons (1.2 MeV, 0.56 MeV) and of the mixed field of gamma's and secondary neutrons (<E _n > = 70.5 MeV) produced by 190 MeV protons impinging on a water phantom, were analysed. The clonogenic survival and the DNA repair capacity were determined and values of relative biological effectiveness were compared. Furthermore, the influence of radiation on the sphere formation was observed to examine the radiation response of the potential fraction of stem like cells within the MCF10A cell population.

Results

X-rays and neutrons caused dose-dependent decreases of survival fractions after irradiations with up to 2 Gy. Monoenergetic neutrons with an energy of 0.56 MeV had a higher effectiveness on the survival fraction with respect to neutrons with higher energies and to the mixed gamma - secondary neutron field induced by proton interactions in water. Similar effects were observed for the DNA repair capacity after exposure to ionising radiation (IR). Both experimental endpoints provided comparable values of the relative biological effectiveness. Significant changes in the sphere formation were notable following the various radiation qualities.

Conclusion

The present study compared the radiation response of MCF10A cells after IR with neutrons and photons. For the first time it was shown that monoenergetic neutrons with energies around 1 MeV have stronger radiobiological effects on normal human breast cells with respect to X rays, to neutrons with a broad energy distribution (<E _n > = 5.8 MeV), and to the mixed gamma - secondary neutron field given by interactions of 190 MeV protons in water. The results of the present study are highly relevant for further investigations of radiation-induced carcinogenesis and are very important in perspective for a better risk assessment after secondary neutron exposure in the field of conventional and proton radiotherapy.

http://ift.tt/2yoYq3g

CT imaging features associated with recurrence in non-small cell lung cancer patients after stereotactic body radiotherapy

Abstract

Background

Predicting recurrence after stereotactic body radiotherapy (SBRT) in non-small cell lung cancer (NSCLC) patients is problematic, but critical for the decision of following treatment. This study aims to investigate the association of imaging features derived from the first follow-up computed tomography (CT) on lung cancer patient outcomes following SBRT, and identify patients at high risk of recurrence.

Methods

Fifty nine biopsy-proven non-small cell lung cancer patients were qualified for this study. The first follow-up CTs were performed about 3 months after SBRT (median time: 91 days). Imaging features included 34 manually scored radiological features (semantics) describing the lesion, lung and thorax and 219 quantitative imaging features (radiomics) extracted automatically after delineation of the lesion. Cox proportional hazard models and Harrel's C-index were used to explore predictors of overall survival (OS), recurrence-free survival (RFS), and loco-regional recurrence-free survival (LR-RFS). Five-fold cross validation was performed on the final prognostic model.

Results

The median follow-up time was 42 months. The model for OS contained Eastern Cooperative Oncology Group (ECOG) performance status (HR = 3.13, 95% CI: 1.17–8.41), vascular involvement (HR = 3.21, 95% CI: 1.29–8.03), lymphadenopathy (HR = 3.59, 95% CI: 1.58–8.16) and the 1st principle component of radiomic features (HR = 1.24, 95% CI: 1.02–1.51). The model for RFS contained vascular involvement (HR = 3.06, 95% CI: 1.40–6.70), vessel attachment (HR = 3.46, 95% CI: 1.65–7.25), pleural retraction (HR = 3.24, 95% CI: 1.41–7.42), lymphadenopathy (HR = 6.41, 95% CI: 2.58–15.90) and relative enhancement (HR = 1.40, 95% CI: 1.00–1.96). The model for LR-RFS contained vascular involvement (HR = 4.96, 95% CI: 2.23–11.03), lymphadenopathy (HR = 2.64, 95% CI: 1.19–5.82), circularity (F13, HR = 1.60, 95% CI: 1.10–2.32) and 3D Laws feature (F92, HR = 1.96, 95% CI: 1.35–2.83). Five-fold cross-validated the areas under the receiver operating characteristic curves (AUC) of these three models were all above 0.8.

Conclusions

Our analysis reveals disease progression could be prognosticated as early as 3 months after SBRT using CT imaging features, and these features would be helpful in clinical decision-making.

http://ift.tt/2giy5xt

Combined high dose radiation and pazopanib in metastatic renal cell carcinoma: a phase I dose escalation trial

Abstract

Background

The primary objective was to determine maximum tolerated radiation dose in patients with metastatic renal cell carcinoma on pazopanib treatment.

Methods

Treatment-naïve patients received pazopanib according to standard of care. Stereotactic body radiotherapy (SBRT) was delivered concurrently to the largest metastatic lesion at day 8, 10 and 12. SBRT doses were escalated in 3 dose levels (24 Gy/3, 30 Gy/3 and 36 Gy/3). Dose level was assigned using Time-to-Event Continual Reassessment Method with the target dose-limiting toxicity rate set to 0.25.

Results

Thirteen patients were included. One patient experienced dose limiting toxicity (DLT) at dose level 3 (grade 4 hypoglycemia). Maximum tolerated dose was not reached with a recommended dose of 36 Gy/3 having a probability of DLT of 11%. One-year local control was 83% (95% confidence interval 61–100) and 1-year progression-free survival was 28% (95% confidence interval 1–55).

Conclusions

SBRT in combination with pazopanib is well tolerated with good local control and response rates outside the radiation field.

Trial registration

This trial was retrospectively registered on clinicaltrials.gov(NCT02334709) on January 6th, 2015.

http://ift.tt/2yoTUBJ

Comparison of volumetric-modulated arc therapy using simultaneous integrated boosts (SIB-VMAT) of 45 Gy/55 Gy in 25 fractions with conventional radiotherapy in preoperative chemoradiation for rectal cancers: a propensity score case-matched analysis

Abstract

Background and purpose

The aim of this retrospective study was to compare volumetric-modulated arc therapy using simultaneous integrated boosts (SIB-VMAT) of 45 Gy/55 Gy in 25 fractions with three-dimensional conformal radiotherapy (3D–CRT) in preoperative chemoradiation for rectal cancers.

Methods and materials

In the propensity score-matching analysis of 1:2, we selected 60 patients from the SIB-VMAT group and 120patients from the 3D–CRT group matched pairings out of 145 patients between 2005 and 2015. The regimen of concurrent combined chemotherapy was oral uracil/tegafur plus leucovorin with/without irinotecan.

Results

There were no significant differences between the two groups, in pathological complete response rates (pCR) (11% in the 3D–CRT group vs. 17% in the SIB-VMAT group, P = 0.39), pathological response rates (44% vs. 60%, P = 0.77), disease-free survival (P = 0.32), or local control (P = 0.52). The SIB-VMAT method marginally improved the rate of pathological grade 2–3 effects and the OS was significantly better in patients with grade 2–3 effects. Recurrence was seen in 36 patients (30%) in the 3D–CRT group and 19 patients (32%) in the SIB-VMAT group. The first distant recurrence site in the SIB-VMAT group was liver in 6 patients and lung in 8 patients. The obvious radiation-induced late toxicity in the SIB-VMAT group was recto-vesical fistula in two patients.

Conclusions

The SIB-VMAT may be a promising method for preoperative CRT of rectal cancer.

http://ift.tt/2yodwG2

Single-unit activity of the anterior globus pallidus internus in Tourette patients and posterior globus pallidus internus in Dystonic patients

Dystonia is a movement disorder characterised by involuntary sustained muscle contractions that lead to twisting, repetitive movements and abnormal postures. Two types of Dystonia can be distinguished: Primary Dystonia has no evidence of other pathological abnormalities, and secondary Dystonia which is associated with neurological lesions, either degenerative or traumatic (Albanese et al. 2013). Tourette's Syndrome (TS) is a neuropsychiatric disorder that is chronic and typically characterised by motor and vocal tics.

http://ift.tt/2gkmn5k

Local changes in computational non-rapid eye movement sleep depth in infants

Newborns and young infants spend most of their time sleeping, and the quality of sleep has been found to be important for their development. Although the contribution of each sleep stage is different, both REM and NREM sleep have important functional roles in brain maturation and in normal synaptic development (Graven, 2006). As for NREM, deep NREM is considered to be the most important sleep stage for infants. In adults, slow wave sleep and slow wave activity (SWA) of NREM sleep are homeostatically regulated and considered a measure of sleep pressure (Borbély and Achermann, 1999).

http://ift.tt/2yrlPl7

Disease-Modifying Therapies for Multiple Sclerosis: A Systematic Literature Review of Cost-Effectiveness Studies

Abstract

Introduction and objective

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. MS is considered incurable; however, disease treatment has advanced significantly over the past several decades with the introduction of disease-modifying therapies (DMTs). The current study reviewed the cost-effectiveness analyses of DMTs in relapsing–remitting MS (RRMS) patients.

Methods

A systematic literature search of bibliographic databases was conducted to identify economic evaluations published after 2007. The relevant population, intervention, comparators, outcomes, and study design (PICOS) were considered. The outcomes of interest were incremental cost-effectiveness ratios (ICERs), net monetary benefits, incremental benefits, and incremental costs. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement was used to assess the reporting quality of published studies.

Results

A total of 1370 potentially relevant citations were identified, of which 33 published articles and four Health Technology Assessment (HTA) reports prepared for the UK were included in the final analysis. Almost all studies were based on a health economic model and considered RRMS as the phase of disease at study entry. The studies were conducted in 10 different countries, with approximately 50% based in the US. Study outcomes were rarely comparable due to the different settings, input data, and assumptions. Even within the same country, the discrepancy between study criteria was considerable. The compliance with reporting standards of the CHEERS statement was generally high.

Conclusions

Internationally, a large number of health economic assessments of DMTs in RRMS were available, yielding difficult to compare, and at times conflicting, results.

http://ift.tt/2ibv828

The Modular Design and Production of an Intelligent Robot Based on a Closed-Loop Control Strategy

We present a protocol on modular design and production of intelligent robots to help scientific and technical workers design intelligent robots with special production tasks based on personal needs and individualized design.

http://ift.tt/2xFdrz7

Vascular Endothelial Mitochondrial Function Predicts Death or Pulmonary Outcomes in Preterm Infants

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1040-1049, October 15, 2017.


http://ift.tt/2yo0p80

Effects of Omalizumab on Rhinovirus Infections, Illnesses, and Exacerbations of Asthma

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 985-992, October 15, 2017.


http://ift.tt/2gjTeaG

Combined Impact of Smoking and Early-Life Exposures on Adult Lung Function Trajectories

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1021-1030, October 15, 2017.


http://ift.tt/2yocnyq

Carbon Monoxide Exposure in Workplaces, Including Coffee Processing Facilities

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1080-1081, October 15, 2017.


http://ift.tt/2gjT4A6

Comparing Drivers and Dynamics of Tuberculosis in California, Florida, New York, and Texas

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1050-1059, October 15, 2017.


http://ift.tt/2gh1KHm

FULFIL an Unmet Need in Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1082-1082, October 15, 2017.


http://ift.tt/2ynmKlR

The Use of Modeling to Compare Tuberculosis Dynamics in Four U.S. States

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 953-954, October 15, 2017.


http://ift.tt/2giZuQ2

Exposure Interaction: A Lifelong Phenomenon with Relevance to Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 947-948, October 15, 2017.


http://ift.tt/2ynEWvG

Cell-free DNA noninvasive prenatal screening for aneuploidy versus conventional screening: a systematic review of economic evaluations

Abstract

Although non-invasive prenatal testing (NIPT) for aneuploidies using cell free fetal DNA in maternal blood has been reported to have a high accuracy, only little evidence about its cost effectiveness is available. We systematically reviewed and assessed quality of economic evaluation studies published between 1st January 2009 and 1st January 2016 where NIPT was compared to the current screening practices consisting of biochemical markers with or without nuchal translucency (NT) and/or maternal age). We included 16 studies and we found that, at current level of NIPT prices, contingent NIPT provide the best value for money, especially for publicly funded screening programs. NIPT as first-line test was found not cost-effective in the majority of studies. The NIPT unit cost, the risk cut-offs for current screening practice, the screening uptake rates (first and second line screening) as well as the costs and uptake rates of invasive diagnostic screening were the most common uncertain variables. The overall quality of included studies was fair. Considering a possible drop in prices and an ongoing NIPT expansion to include other chromosomes abnormalities other than T21, T18, T13 and sex chromosomes aneuploidies, future research are needed to examine the potential cost effectiveness of implementing NIPT as first-line test.

http://ift.tt/2yKuXlH

Cancers, Vol. 9, Pages 137: STAT3 but Not HIF-1α Is Important in Mediating Hypoxia-Induced Chemoresistance in MDA-MB-231, a Triple Negative Breast Cancer Cell Line

Cancers, Vol. 9, Pages 137: STAT3 but Not HIF-1α Is Important in Mediating Hypoxia-Induced Chemoresistance in MDA-MB-231, a Triple Negative Breast Cancer Cell Line

Cancers doi: 10.3390/cancers9100137

Authors: Hoda Soleymani Abyaneh Nidhi Gupta Aneta Radziwon-Balicka Paul Jurasz John Seubert Raymond Lai Afsaneh Lavasanifar

Hypoxia-induced chemoresistance (HICR) is a well-recognized phenomenon, and in many experimental models, hypoxia inducible factor-1α (HIF-1α) is believed to be a key player. We aimed to better understand the mechanism underlying HICR in a triple negative breast cancer cell line, MDA-MB-231, with a focus on the role of HIF-1α. In this context, the effect of hypoxia on the sensitivity of MDA-MB-231 cells to cisplatin and their stem-like features was evaluated and the role of HIF-1α in both phenomena was assessed. Our results showed that hypoxia significantly increased MDA-MB-231 resistance to cisplatin. Correlating with this, intracellular uptake of cisplatin was significantly reduced under hypoxia. Furthermore, the stem-like features of MDA-MB-231 cells increased as evidenced by the significant increases in the expression of ATP-binding cassette (ABC) drug transporters, the proportion of CD44+/CD24− cells, clonogenic survival and cisplatin chemoresistance. Under hypoxia, both the protein level and DNA binding of HIF-1α was dramatically increased. Surprisingly, siRNA knockdown of HIF-1α did not result in an appreciable change to HICR. Instead, signal transducer and activator of transcription 3 (STAT3) activation was found to be important. STAT3 activation may confer HICR by upregulating ABC transporters, particularly ABCC2 and ABCC6. This study has demonstrated that, in MDA-MB-231 cells, STAT3 rather than HIF-1α is important in mediating HICR to cisplatin.

http://ift.tt/2xEGApm

Characteristics of spontaneous coagulase-negative staphylococcal spondylodiscitis: a retrospective comparative study versus Staphylococcus aureus spondylodiscitis

Coagulase-negative staphylococci (CoNS) are increasingly implicated in recent patient series of spondylodiscitis, but there are no series of CoNS-spondylodiscitis available. The objective of this study was to ...

http://ift.tt/2zmA0Wz

Infection by and genotype characteristics of Enterocytozoon bieneusi in HIV/AIDS patients from Guangxi Zhuang autonomous region, China

Enterocytozoon bieneusi has been increasingly reported to infect humans and various mammals. Microsporidia cause diarrhea in HIV-infected patients worldwide. PCR amplification and sequ...

http://ift.tt/2z7eB2x

Prevalence of urinary tract infections mimicking respiratory infections and risk factors associated

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http://ift.tt/2g9Puom

A tale of two pregnancies: A Critical Interpretive Synthesis of women’s perceptions about delayed initiation of antenatal care

Publication date: Available online 14 October 2017
Source:Women and Birth
Author(s): Rosalind Haddrill
BackgroundDelayed access to antenatal care in high income countries is associated with poor maternal, fetal and neonatal outcomes. The aim was to synthesise the diverse body of evidence around women's views of early antenatal care and barriers to attendance in such countries. Critical Interpretive Synthesis integrates the process of systematic review with the qualitative methods of meta-ethnography and grounded theory, with a focus on theory generation to inform policy, practice and future research.MethodsDatabase searches were conducted, supplemented with reference and citation tracking and website searching between February 2014 and April 2016. Qualitative data analysis methods were used to extract and summarise the key themes from each study. A taxonomy of constructs was created, with the synthesis developed to thread these together. Fifty-four papers were synthesised, including qualitative, quantitative, mixed method and systematic review, published between 1987 and 2016.FindingsSeventeen constructs around the core concept of 'acceptance of personal and public pregnancies' were produced. Acceptance of the 'personal' pregnancy considers the contribution of mindset in the recognition and acceptance of pregnancy, influenced by knowledge of pregnancy symptoms, pregnancy planning and desire. Acceptance of the 'public' pregnancy considers women's assessment of the social consequences of pregnancy, and the relevance and priority of antenatal care.ConclusionCritical Interpretive Synthesis offers a systematic yet creative approach to the synthesis of diverse evidence. The findings offer new perspectives on women's perceptions of early pregnancy and attendance for care, which may be used to facilitate timely antenatal provision for all pregnant women.



http://ift.tt/2yidznS

Australian midwives views and experiences of practice and politics related to water immersion for labour and birth: A web based survey

Publication date: Available online 13 October 2017
Source:Women and Birth
Author(s): Megan Cooper, Jane Warland, Helen McCutcheon
BackgroundThere is little published research that has examined practitioners' views and experiences of pain relieving measures commonly used during labour and birth, particularly for non-pharmacological measures such as water immersion. Furthermore, there is minimal published research examining the process of policy and guideline development, that is, the translation of published research to usable practice guidance.AimsThe aims of phase three of a larger study were to explore midwives knowledge, experiences and support for the option of water immersion for labour and birth in practice and their involvement, if any, in development of policy and guidelines pertaining to the option.MethodsPhase three of a three phased mixed methods study included a web based survey of 234 Australian midwives who had facilitated and/or been involved in the development of policies and/or guidelines relating to the practice of water immersion.FindingsMidwives who participated in this study were supportive of both water immersion for labour and birth reiterating documented benefits of reduced pain, maternal relaxation and a positive birth experience. The most significant concerns were maternal collapse, the difficulty of estimating blood loss and postpartum haemorrhage whilst barriers included lack of accredited staff, lifting equipment and negative attitudes. Midwives indicated that policy/guideline documents limited their ability to facilitate water immersion and did not always to support women's informed choice.ConclusionMidwives who participated in this study supported the practice of water immersion reiterating the benefits documented in the literature and minimal risk to the woman and baby.Ethical considerationsThe Human Research Ethics Committee of the University of South Australia approved the research.



http://ift.tt/2g9Dnrh

A research method to explore midwives’ views of national maternity service reforms

Publication date: Available online 14 October 2017
Source:Women and Birth
Author(s): Bridget Roache, Jennifer Kelly
BackgroundPriorities of the National Maternity Services Plan (NMSP) are a significant contrast to current standard hospital maternity service provision. This paper demonstrates the applicability of case study methods to explore the views of midwives during a period of midwifery reform.AimThis research aims to highlight key findings and insights surrounding recommended changes facing midwives that can be shared with education providers to incorporate strategies into education programs to ensure contemporary midwifery practice.MethodsExploratory Case Study methodology was employed using ethical processes and designing semi-structured interview questions to explore participants' views. Purposive sampling ensured participants were currently practicing midwives in order to reflect the perspective and intent of this study. Data were analysed and findings presented in categories and subcategories.ResultsCase Study methodology enables an in-depth understanding of a phenomenon to be explored within a natural context. The participants of this study formed a single unit of analysis to ensure the research makes a worthwhile contribution to the profession of midwifery.ConclusionThis paper demonstrates that Case Study methodology is a valid research approach to exploring the views of midwives employed in standard care settings during a period of national reform. The rigorous processes and versatility of Case Study methodology ensured a systematic, critical enquiry was undertaken to gain understanding of the views of participants in implementing the NMSP. This understanding is reflective of the real life contexts of midwives to promote understanding and provide a body of knowledge where there is ambiguity and uncertainty.



http://ift.tt/2ygxN14

Microvesicles releasing by oral cancer cells enhance endothelial cell angiogenesis via Shh/RhoA signaling pathway

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http://ift.tt/2ynODu7

Expression of SESN1, UHRF1BP1, and miR-377-3p as prognostic markers in mutated TP53 squamous cell carcinoma of the head and neck

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http://ift.tt/2xEQyqv

Leptomeningeal carcinomatosis from gastric cancer successfully treated by the intrathecal methotrexate plus temozolomide and simultaneous radiotherapy: Case report and literatures review

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http://ift.tt/2ynxb96

MALAT1/miR-124/Capn4 axis regulates proliferation, invasion and EMT in nasopharyngeal carcinoma cells

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http://ift.tt/2xF8OA2

Prognostication and Initiation of Therapy in Polycythemia Vera: Do We Have it Right?

Abstract

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http://ift.tt/2hGD1cb

Clinical performance of 68 Ga-PSMA-11 PET/MRI for the detection of recurrent prostate cancer following radical prostatectomy

Abstract

Purpose

Sensitive visualization of recurrent prostate cancer foci is a challenge in patients with early biochemical recurrence (EBR). The recently established ⁶⁸Ga-PSMA-11 PET/CT has significantly improved the detection rate with published values of up to 55% for patients with a serum PSA concentration between 0.2–0.5 ng/mL. The increased soft tissue contrast in the pelvis using simultaneous ⁶⁸Ga-PSMA-11 PET/MRI might further improve the detection rate in patients with EBR and low PSA values over PET/CT.

Methods

We retrospectively analyzed a cohort of 56 consecutive patients who underwent a ⁶⁸Ga-PSMA-11 PET/MRI for biochemical recurrence in our institution between April and December 2016 with three readers. Median PSA level was 0.99 ng/mL (interquartile range: 3.1 ng/mL). Detection of PSMA-positive lesions within the prostate fossa, local and distant lymph nodes, bones, or visceral organs was recorded. Agreement among observers was evaluated with Fleiss's kappa (k).

Results

Overall, in 44 of 56 patients (78.6%) PSMA-positive lesions were detected. In four of nine patients (44.4%) with a PSA < 0.2 ng/mL, suspicious lesions were detected (two pelvic and one paraaortic lymph nodes, and two bone metastases). In eight of 11 patients (72.7%) with a PSA between 0.2 and < 0.5 ng/mL, suspicious lesions were detected (two local recurrences, six lymph nodes, and one bone metastasis). Five out of 20 patients with a PSA < 0.5 ng/mL had extrapelvic disease. In 12 of 15 patients (80.0%) with a PSA between 0.5 and < 2.0 ng/mL, suspicious lesions were detected (four local recurrences, nine lymph nodes, and four bone metastases). In 20 of 21 patients (95.2%) with a PSA >2.0 ng/mL, suspicious lesions were detected. The overall interreader agreement for cancer detection was excellent (κ = 0.796, CI 0.645–0.947).

Conclusions

Our data show that ⁶⁸Ga-PSMA-11 PET/MRI has a high detection rate for recurrent prostate cancer even at very low PSA levels <0.5 ng/mL. Furthermore, even at those low levels extrapelvic disease can be localized in 25% of the cases and local recurrence alone is seen only in 10%.

http://ift.tt/2yKf0Mg

Clinical Characteristics of Patients Experiencing Pathologic Complete Response Following Neoadjuvant Therapy for Borderline Resectable/Locally Advanced Pancreatic Adenocarcinoma.

Objectives: The purpose of this study is to describe clinical characteristics and outcomes of patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) who achieved pathologic complete response (pCR) following neoadjuvant therapy. Materials and Methods: A single institution clinical database for patients with pancreatic ductal adenocarcinoma was queried. Between 2008 and 2014 patients were identified with BRPC and LAPC, who underwent surgical resection after receiving neoadjuvant treatment. Clinical and pathologic features of the patients who achieved pCR were acquired retrospectively. Results: Six patients were identified to have pCR on pathology of the postoperative specimen. On the basis of pretreatment clinical staging, 2 patients were considered to have BRPC and 4 LAPC. Four patients received gemcitabine-based chemotherapy and 2 patients received FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, and leucovorin). Five of 6 patients received radiation therapy before operative resection. Operative procedures included distal pancreatectomy (n=3) and pancreatoduodenectomy (n=3). Pancreatic intraepithelial neoplasia 1 to 2 was present in 3 cases, and pancreatic intraepithelial neoplasia 3 in 1 case. During a median follow-up of 21.3 months, 2 patients died, with a median survival of 11.0 months (range, 10.4 to 11.6 mo). Four patients are alive and continue to follow-up with median survival of 28.7 months (range, 20.1 to 42.4 mo). Conclusions: Multimodality neoadjuvant therapy may lead to complete pathologic response in a small number of patients with borderline resectable/locally advanced pancreatic adenocarcinoma. pCR to neoadjuvant therapy does not lead to cure in most cases, and the majority of patients appear to relapse locally or systemically. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2gFgkFD

"Lost to Follow-up" Among Adult Cancer Survivors.

Background: Follow-up cancer care is important for patients who have received IV chemotherapy but some patients discontinue their care and are lost to follow-up (LFU) at the cancer center where they were treated. The purpose of this study was to determine what proportion of cancer survivors are LFU at 5 years after treatment, the timing of LFU, and the characteristics of those who do not continue survivorship care. Methods: Adult patients with cancer who were treated with chemotherapy at a large community teaching hospital in 2006 and 2007 were identified and linked with State tumor registry data. Hospital medical records were reviewed to obtain information on demographics, diagnosis, treatment, and date of last follow-up visit. Characteristics of patients with >=5 years of follow-up care were compared with those who were LFU. Results: In total, 487 patients received chemotherapy and 304 died (62%) during the 5-year follow-up period. Among the 183 cancer patients who were known to be alive at 5 years, 92 (50%) were LFU and 50% (46/92) of this LFU group were LFU within 1 year of diagnosis. At 5 years, follow-up care was continuing for 55% of women, compared with 39% of men. The highest proportion of follow-up was observed among lung cancer patients (84%), followed by patients with breast cancers (63%) and gastrointestinal cancers (40%). Patients with hematological cancers had the lowest follow-up proportion at 5 years (29%) (P=5 years beyond their diagnosis but there is little data on oncology follow-up rates. In our retrospective study of 183 patients who were treated with chemotherapy only 49.7% continue to follow-up at their treatment center. LFU has important implications in planning long-term care strategies for cancer survivors and in survivorship research. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2z7Vky4

Bilberry extract administration prevents retinal ganglion cell death in mice via the regulation of chaperone molecules under conditions of endoplasmic reticulum stress

http://ift.tt/2zm7Mez