Πέμπτη 7 Ιουνίου 2018
18 F-PSMA-1007 PET/CT at 60 and 120 minutes in patients with prostate cancer: biodistribution, tumour detection and activity kinetics
Abstract
Purpose
PSMA-targeted PET in patients with prostate cancer (PCa) has a significant impact on treatment decisions. By far the most frequently used PSMA ligand is 68Ga-labelled PSMA-11. However, due to the availability of larger amounts of activity, 18F-labelled PSMA ligands are of major interest. The aim of the present study was to evaluate the biodistribution and performance of the novel 18F-labelled ligand PSMA-1007 at two different time points.
Methods
This retrospective analysis included 40 consecutive patients (mean age 68.7 ± 8.1 years) referred for PSMA PET/CT. 18F-PSMA-1007 PET/CT was performed for localization of biochemical relapse, primary staging or therapy follow-up. Circular regions of interest were placed on representative slices of the liver, spleen, kidney, abdominal aortic blood pool, bone marrow (fourth lumbar vertebral body), urinary bladder and gluteus muscle at 60 and 120 min after injection. In malignant lesions the maximum standardized uptake (SUVmax) was measured within volumes of interest at both time points. All SUVs at 60 min were compared with those at 120 min after injection.
Results
The activity in the blood pool, urinary bladder and gluteus muscle was very low and decreased significantly over time (P < 0.001). Uptake in the liver, spleen and kidney showed a significant increase over time and uptake in the bone marrow remained stable. Overall, 135 PCa lesions were detected at 60 min and 136 lesions at 120 min after injection. The median SUVmax increased significantly (P < 0.001) from 10.98 to 15.51 between 60 and 120 min.
Conclusion
PCa lesions show a significant increase in 18F-PSMA-1007 uptake at 120 min compared with 60 min after injection. In addition, accumulation of the tracer in the urinary bladder was very low leading to improved contrast of adjacent PCa lesions. Increasing accumulation in the liver may limit the sensitivity of the tracer in detecting liver metastases.
https://ift.tt/2sH2mZL
The role of interim 18 F-FDG PET/CT in prediction of response to ipilimumab treatment in metastatic melanoma
Abstract
Purpose
The aim of the present study was to assess the value of interim 18F-FDG PET/CT performed after the first two cycles of ipilimumab treatment in the prediction of the final clinical response to this type of immunotherapy.
Methods
The study group comprised 41 patients with unresectable metastatic melanoma scheduled for ipilimumab therapy. Whole-body 18F-FDG PET/CT was performed before the start of ipilimumab treatment (baseline PET/CT) and after the initial two cycles of ipilimumab treatment (interim PET/CT). Evaluation of patient response to treatment was based on the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria for PET as well as the recently proposed PET Response Evaluation Criteria for Immunotherapy (PERCIMT). The patients' best clinical response, assessed at a median of 21.4 months (range 6.3–41.9 months) was used as reference.
Results
According to their best clinical response, the patients were divided into two groups: those showing clinical benefit (CB) including stable disease, partial response and complete response (31 patients), and those showing no clinical benefit (no-CB including progressive disease (10 patients). According to the EORTC criteria, interim PET/CT demonstrated progressive metabolic disease (PMD) in 20 patients, stable metabolic disease (SMD) in 11 patients, partial metabolic response (PMR) in 8 patients, and complete metabolic response (CMR) in 2 patients. According to the PERCIMT, interim PET/CT demonstrated PMD in 9 patients, SMD in 24 patients, PMR in 6 patients and CMR in 2 patients. On the basis of the interim PET, the patients were divided in a similar manner to the division according to clinical response into those showing metabolic benefit (MB) including SMD, PMR and CMR, and those showing no metabolic benefit (no-MB) including PMD. According to this dichotomization, the EORTC criteria showed a sensitivity (correctly predicting CB) of 64.5%, a specificity (correctly predicting no-CB) of 90.0%, a positive predictive value (PPV) of 95.2%, a negative predictive value (NPV) of 45.0% and an accuracy of 70.7% in predicting best clinical response. The PERCIMT showed a sensitivity of 93.6%, a specificity of 70.0%, a PPV of 90.6%, a NPV of 77.8% and an accuracy of 87.8%. The McNemar test showed that the PERCIMT had a significantly higher sensitivity than EORTC criteria (p = 0.004), while there was no significant difference in specificity (p = 0.5). The agreement between the two sets of criteria was poor (McNemar test p = 0.001, and accordingly kappa = 0.46).
Conclusion
The application of the recently proposed PERCIMT to interim 18F-FDG PET/CT provides a more sensitive predictor of final clinical response to immunotherapy than the application of the EORTC criteria in patients with metastatic melanoma.
https://ift.tt/2Hvd8qF
Correction to: 18 F-FDG PET in drug-resistant epilepsy due to focal cortical dysplasia type 2: additional value of electroclinical data and coregistration with MRI
The original version of this article has added numbers in the text which are unnecessary. Correct line should be: "We also performed PET/MRI based surgical resections in an increasing number of MRI negative/ doubtful cases with favourable outcome."
https://ift.tt/2JEdJLI
Amyloid load but not regional glucose metabolism predicts conversion to Alzheimer’s dementia in a memory clinic population
Abstract
Purpose
The value of imaging regional glucose metabolism with [18F]FDG PET for the prediction of progression from mild cognitive impairment (MCI) to Alzheimer's dementia (AD) is controversial. The predictive value of imaging with [18F]FDG PET was therefore tested and compared with that of imaging beta-amyloid load with [11C]PIB PET in the same memory clinic population of MCI patients.
Methods
Thirty-nine patients with MCI who had undergone [18F]FDG as well as [11C]PIB PET were identified from a single-centre clinical registry. [18F]FDG and [11C]PIB PET images were rated as positive or negative for the presence of regional hypometabolism typical of AD and beta-amyloid deposition, respectively. Raters were blinded to the clinical information. Patients were followed clinically for 2.7 ± 1.2 years after PET. Cox proportional hazards models, adjusted for age and sex, were used to test the predictive value of [18F]FDG PET, [11C]PIB PET, and both in combination.
Results
[18F]FDG PET did not significantly predict conversion to AD (p > 0.1). By contrast, models including [11C]PIB PET only (p < 0.05) or both [18F]FDG and [11C]PIB PET (p < 0.05) significantly predicted conversion to AD. The hazard ratio for AD in patients with a positive [11C]PIB scan was 10.2 (95% confidence interval 1.3–78.1). The results were confirmed by analysis of semiquantitative measures using normalized [18F]FDG uptake and [11C]PIB standardized uptake value ratios in AD-typical regions as continuous predictors.
Conclusion
In contrast to [11C]PIB PET, [18F]FDG PET did not predict conversion from MCI to AD in this clinical patient sample. Therefore, amyloid PET should be preferred for individual prediction and patient counselling in clinical practice.
https://ift.tt/2sGbwpv
The central zone has increased 68 Ga-PSMA-11 uptake: “Mickey Mouse ears” can be hot on 68 Ga-PSMA-11 PET
Abstract
Purpose
Given the good correlation between PSMA expression and intraglandular tumour aggressiveness based on immunohistochemistry, there is increasing interest in 68Ga-PSMA-11 PET/MRI for staging prostate cancer (PCA). Therefore, accurate knowledge of prostate anatomy as well as normal distribution of PSMA within the prostate gland is becoming essential. The aim of this study was to investigate the physiological intraprostatic distribution of 68Ga-PSMA-11.
Methods
We retrospectively analysed all patients who underwent a staging 68Ga-PSMA-11 PET/MRI scan between June 2016 and January 2018 for high-risk PCA, underwent radical prostatectomy in our institution, and gave written consent for further data analysis. In each patient, standardized volumes of interest (VOIs) were placed bilaterally in the central, transition and peripheral zones within the zonal anatomy according to T2 weighted sequences in the axial and coronal planes. VOIs were only placed if they were safely within healthy tissue without spillover from the PCA. SUVmax and SUVmean were determined and their differences among the regions were assessed using the Wilcoxon signed-ranks test.
Results
Of 283 consecutive patients scanned with 68Ga-PSMA-11 PET/MR, 31 were analysed. A total of 133 VOIs were placed, 46 in the central zone, 41 in the transition zone and 46 in the peripheral zone. Differences in SUVmax between the central zone (mean 3.9 ± 0.58) and transition zone (mean 3.2 ± 0.59) and between the central zone and peripheral zone (mean 2.7 ± 0.54) were statistically significant (both p < 0.001).
Conclusion
Our results suggest that higher 68Ga-PSMA-11 accumulation in the central zone than in the transition and peripheral zones is normal, and leads to a pattern resembling "Mickey Mouse ears" on 68Ga-PSMA-11 PET. This pattern could be helpful in avoiding false-positive interpretations of PET scans.
https://ift.tt/2sFRnjt
Preoperative [ 18 F]FDG PET/CT tumour heterogeneity index in patients with uterine leiomyosarcoma: a multicentre retrospective study
Abstract
Purpose
We investigated the prognostic value of the tumour heterogeneity index determined on preoperative [18F]FDG PET/CT in patients with uterine leiomyosarcoma (LMS).
Methods
We retrospectively reviewed patients with uterine LMS who underwent preoperative [18F]FDG PET/CT scans at three tertiary referral hospitals. The PET/CT parameters maximum standardized uptake value of the primary tumour (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis were assessed. The negative values of the MTV linear regression slope (nMLRS) according to the SUV thresholds of 2.5 and 3.0 were determined as the tumour heterogeneity index. The value of PET/CT-derived parameters in predicting progression-free survival (PFS) and overall survival (OS) were determined in regression analyses.
Results
Clinicopathological and PET/CT data from 16 patients were reviewed. The median postsurgical follow-up was 21 months (range 4–82 months), and 12 patients (75.0%) experienced recurrence. Tumour size (P = 0.017), SUVmax (P = 0.019), MTV (P = 0.016) and nMLRS (P = 0.008) were significant prognostic factors for recurrence. MTV (P = 0.048) and nMLRS (P = 0.045) were significant prognostic factors for patient survival. nMLRS was correlated with clinicopathological parameters including tumour size (Pearson's correlation coefficient γ = 0.825, P < 0.001) and lymph node metastasis (γ = 0.721, P = 0.004). Patient groups categorized according to the nMLRS cut-off value showed significant differences in PFS (P = 0.033) and OS (P = 0.044).
Conclusion
The preoperative tumour heterogeneity index obtained using the MTV linear regression slope may be a novel and useful prognostic marker in uterine LMS.
https://ift.tt/2HtJguS
The effect of aging and contextual information on manual asymmetry in tool use
Abstract
Healthy aging affects manual asymmetries in simple motor tasks, such as unilateral reaching and aiming. The effects of aging on manual asymmetries in the performance of a complex, naturalistic task are unknown, but are relevant for investigating the praxis system. This study examined how aging influences manual asymmetry in different contexts in a tool manipulation task. Fifty healthy, right-hand-dominant young (N = 29; 21.41 ± 2.87 years), and elderly (N = 21; mean: 74.14 ± 6.64 years) participants performed a 'slicing' gesture in response to a verbal command in two contexts: with (tool) and without the tool (pantomime). For interjoint relationships between shoulder plane of elevation and elbow flexion, a HAND × AGE × CONTEXT interaction existed (F1,43 = 4.746, p = 0.035). In pantomime, interjoint control deviated more in the left (non-dominant) than the right (dominant) limb in the elderly adult group (Wilcoxon, p = 0.010). No such differences existed in the young adult group (Wilcoxon, p = 0.471). Furthermore, contextual information reduced interjoint deviation in young adults when the task was performed with the right (dominant) hand (Wilcoxon, p = 0.001) and in the elderly adults when the task was performed with the left (non-dominant) hand (Wilcoxon, p = 0.012). The presence of the tool did not reduce interjoint deviation for the right hand in the elderly group (Wilcoxon, p = 0.064) or the left hand in the young group (Wilcoxon, p = 0.044). Deviation within trials (i.e., intrasubject deviation) in elbow flexion was higher in the elderly relative to the young adult group (p = 0.003). Finally, resultant peak velocities were smaller (p = 0.002) and cycle duration longer (p < 0.0001) in the elderly adult group. This study provides novel evidence that aging affects manual asymmetries and sensorimotor control in a naturalistic task and warrants that aging research considers the context in which the task is performed.
https://ift.tt/2sR80YJ
Remote dwelling Aboriginal Australian women and birthing: A critical review of literature
Publication date: Available online 7 June 2018
Source:Women and Birth
Author(s): Catrina Felton-Busch, Sarah Larkins
ProblemAustralian Aboriginal women's aspirations for birthing on country (having our babies born on our traditional land) are increasingly being reported in Australian scholarly and policy literature. However given the paucity of publications authored by Aboriginal Australians from remote areas of Australia, how well can the current knowledge base in Australia inform the development of culturally appropriate maternity services for our communities?ObjectiveThe aim of this literature review is to critically analyse the policy documents informing maternity services policy and scholarly literature on the birthing experiences (including the provision of maternity services) of Aboriginal Australian women from remote communities from an Indigenous standpoint.MethodPolicy documents and scholarly literature were critically analysed to identify who the authors were, their background, approaches and perspectives; and emergent themes. A further analysis of the literature drew on Fairclough's ideas on discourse, power and hegemony.FindingsA critical discourse analysis of this literature exposed how these texts are ideologically shaped to give voice (and power) to the medical fraternity, maternity care services practitioners and policy makers (whose knowledge is valued) while simultaneously silencing the voices of Aboriginal Australians that pose a challenge to that power.ConclusionThis critical review of current literature highlights the importance of ongoing critique of maternity services policy and practice discourse necessary to combat western medical hegemony that maintains the disenfranchisement of Aboriginal Australians.
https://ift.tt/2sQWFHZ
How Australian dual registrants identified as midwives to meet national registration-renewal requirements
Publication date: Available online 7 June 2018
Source:Women and Birth
Author(s): Michelle Gray
AimA theoretical discussion using categorisation theory to discuss the final analysis of findings from research which investigated midwives' responses to the changed registration-renewal requirements in Australia after the introduction of national registration.BackgroundIn 2010 the Health Practitioner Regulation National Law Act introduced national registration to standardise the regulation of health professionals in Australia. Annual registration-renewal standards required all health professionals to meet the same standards of clear police check, insurance for scope of practice, Continuing Professional Development (CPD) and Recency of Practice (ROP).QuestionHow did dual registered midwives respond to the changed registration-renewal requirements when national registration was introduced?MethodsA longitudinal single case study was conducted in two phases between 2011–2013 with a purposive sample of 24 midwives from five states of Australia to perform individual or group interviews.FindingsParticipants used inclusion and exclusion criteria to create boundaries around practice to illustrate how they met the registration-renewal standards. Accentuation (exaggeration) of practice helped them define their separate professional registrations. Boundaries included the type of person being cared for, practice activities. and place of practice.ConclusionThe theory of categorisation helped explain the dual registrants' behaviour and rationalise their midwifery responses.
https://ift.tt/2kWTg6S
Editorial
Publication date: June 2018
Source:Women and Birth, Volume 31, Issue 3
https://ift.tt/2kUyJQs
Publisher's Note
Publication date: June 2018
Source:Women and Birth, Volume 31, Issue 3
https://ift.tt/2xTcdRh
Low socioeconomic status increases effects of negative life events on antenatal anxiety and depression
Publication date: Available online 7 June 2018
Source:Women and Birth
Author(s): Tjitte Verbeek, Claudi L.H. Bockting, Chantal Beijers, Judith L. Meijer, Mariëlle G. van Pampus, Huibert Burger
ProblemLow socioeconomic status and prior negative life events are documented risk factors for antenatal anxiety and depression, preterm birth and birth weight. We aimed to asses whether the adverse effects of prior negative life events increase with lower socioeconomic status and which aspects of socioeconomic status are most relevant.MethodsWe performed a population-based cohort study in the Netherlands including 5398 women in their first trimester of pregnancy. We assessed the number of negative life events prior to pregnancy, aspects of paternal and maternal socio-economic position and symptoms of anxiety and depression. Associations of the number of prior negative life events with anxiety, depression, low birth weight and gestational age were quantified.FindingsThe number of prior negative life events, particularly when they had occurred in the two years before pregnancy and maternal aspects of low socioeconomic status (educational level, unemployment and income) were associated with antenatal anxiety and depression. Furthermore, low socioeconomic status increased the adverse effects of prior negative life events. Obstetric outcomes showed similar trends, although mostly not statistically significant.DiscussionLow socioeconomic status and prior negative life events both have an adverse effect on antenatal anxiety and depression. Furthermore, low socioeconomic status increases the adverse impact of prior negative life events on anxiety and depressive symptoms in pregnancy.ConclusionInterventions for anxiety and depression during pregnancy should be targeted particularly to unemployed, less-educated or low-income women who recently experienced negative life events.
https://ift.tt/2kWMa2v
Cancers, Vol. 10, Pages 189: The Roles of p53 in Mitochondrial Dynamics and Cancer Metabolism: The Pendulum between Survival and Death in Breast Cancer?
Cancers, Vol. 10, Pages 189: The Roles of p53 in Mitochondrial Dynamics and Cancer Metabolism: The Pendulum between Survival and Death in Breast Cancer?
Cancers doi: 10.3390/cancers10060189
Authors: David E. Moulder Diana Hatoum Enoch Tay Yiguang Lin Eileen M. McGowan
Cancer research has been heavily geared towards genomic events in the development and progression of cancer. In contrast, metabolic regulation, such as aberrant metabolism in cancer, is poorly understood. Alteration in cellular metabolism was once regarded simply as a consequence of cancer rather than as playing a primary role in cancer promotion and maintenance. Resurgence of cancer metabolism research has identified critical metabolic reprogramming events within biosynthetic and bioenergetic pathways needed to fulfill the requirements of cancer cell growth and maintenance. The tumor suppressor protein p53 is emerging as a key regulator of metabolic processes and metabolic reprogramming in cancer cells—balancing the pendulum between cell death and survival. This review provides an overview of the classical and emerging non-classical tumor suppressor roles of p53 in regulating mitochondrial dynamics: mitochondrial engagement in cell death processes in the prevention of cancer. On the other hand, we discuss p53 as a key metabolic switch in cellular function and survival. The focus is then on the conceivable roles of p53 in breast cancer metabolism. Understanding the metabolic functions of p53 within breast cancer metabolism will, in due course, reveal critical metabolic hotspots that cancers advantageously re-engineer for sustenance. Illustration of these events will pave the way for finding novel therapeutics that target cancer metabolism and serve to overcome the breast cancer burden.
https://ift.tt/2sR5zFz
Cost–effectiveness of afatinib and erlotinib as second-line treatments for advanced squamous cell carcinoma of the lung
Future Oncology, Ahead of Print.
https://ift.tt/2kSyB3U
Long QT syndrome KCNH2 mutation with sequential fetal and maternal sudden death
Abstract
We report a case of a woman who experienced intrauterine fetal death at full term pregnancy, and then died suddenly soon after learning about the death of her fetus. At autopsy, previously undiagnosed neurofibromatosis and an adrenal gland pheochromocytoma were discovered in the mother. Genetic screening also revealed a novel KCNH2mutation in both fetus and mother indicating type 2 congenital long-QT syndrome (LQTS). A catecholamine surge was suspected as the precipitating event of fetal cardiac arrhythmia and sudden fetal death, while the addition of emotional stress provoked a lethal cardiac event in the mother. This case illustrates the potential for lethal interactions between two occult diseases (pheochromocytoma, LQTS).
https://ift.tt/2JgkFzg
RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors
RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors
RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors, Published online: 07 June 2018; doi:10.1038/s41419-018-0714-7
RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitorshttps://ift.tt/2sJWAG2
Loss of Drosha underlies dopaminergic neuron toxicity in models of Parkinson’s disease
Loss of Drosha underlies dopaminergic neuron toxicity in models of Parkinson's disease
Loss of Drosha underlies dopaminergic neuron toxicity in models of Parkinson's disease, Published online: 07 June 2018; doi:10.1038/s41419-018-0716-5
Loss of Drosha underlies dopaminergic neuron toxicity in models of Parkinson's diseasehttps://ift.tt/2kWVofa
Challenging tumor resistance with less toxic, more effective drug combinations: an example from neuroblastoma
Challenging tumor resistance with less toxic, more effective drug combinations: an example from neuroblastoma
Challenging tumor resistance with less toxic, more effective drug combinations: an example from neuroblastoma, Published online: 07 June 2018; doi:10.1038/s41419-018-0728-1
Challenging tumor resistance with less toxic, more effective drug combinations: an example from neuroblastomahttps://ift.tt/2sQjjjB
miR-16-5p inhibits chordoma cell proliferation, invasion and metastasis by targeting Smad3
miR-16-5p inhibits chordoma cell proliferation, invasion and metastasis by targeting Smad3
miR-16-5p inhibits chordoma cell proliferation, invasion and metastasis by targeting Smad3, Published online: 07 June 2018; doi:10.1038/s41419-018-0738-z
miR-16-5p inhibits chordoma cell proliferation, invasion and metastasis by targeting Smad3https://ift.tt/2kUwxsb
Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis
Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis
Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis, Published online: 07 June 2018; doi:10.1038/s41419-018-0723-6
Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosishttps://ift.tt/2sQjhZ1
Inflammation, neurodegeneration and protein aggregation in the retina as ocular biomarkers for Alzheimer’s disease in the 3xTg-AD mouse model
Inflammation, neurodegeneration and protein aggregation in the retina as ocular biomarkers for Alzheimer's disease in the 3xTg-AD mouse model
Inflammation, neurodegeneration and protein aggregation in the retina as ocular biomarkers for Alzheimer's disease in the 3xTg-AD mouse model, Published online: 07 June 2018; doi:10.1038/s41419-018-0740-5
Inflammation, neurodegeneration and protein aggregation in the retina as ocular biomarkers for Alzheimer's disease in the 3xTg-AD mouse modelhttps://ift.tt/2kUwufZ
Role of neutrophils in allergic asthma
Coraline Radermecker | Renaud Louis | Fabrice Bureau | Thomas Marichal
https://ift.tt/2JzFoxs
Enhancing the potency and specificity of engineered T cells for cancer treatment [Research Articles]
The adoptive transfer of chimeric antigen receptor (CAR)-modified T cells has produced tumor responses even in patients with refractory diseases. However, the paucity of antigens that are tumor selective has resulted, on occasion, in "on-target, off-tumor" toxicities. To address this issue, we developed an approach to render T cells responsive to an expression pattern present exclusively at the tumor by using a trio of novel chimeric receptors. Using pancreatic cancer as a model, we demonstrate how T cells engineered with receptors that recognize PSCA, TGFβ, and IL4, and whose endodomains recapitulate physiologic T cell signaling by providing signals for activation, co-stimulation and cytokine support, produce potent anti-tumor effects selectively at the tumor site. In addition, this strategy has the benefit of rendering our cells resistant to otherwise immunosuppressive cytokines (TGFβ and IL4) and can be readily extended to other inhibitory molecules present at the tumor site (e.g. PD-L1, IL10, IL13).
https://ift.tt/2xUwBkY
MACROD2 Haploinsufficiency Impairs Catalytic Activity of PARP1 and Promotes Chromosome Instability and Growth of Intestinal Tumors [Research Articles]
ADP-ribosylation is an important post-translational protein modification that regulates diverse biological processes, controlled by dedicated transferases and hydrolases. Here we show that frequent deletions (~30%) of the MACROD2 mono-ADP-ribosylhydrolase locus in human colorectal cancer (CRC) cause impaired PARP1 transferase activity in a gene dosage-dependent manner. MACROD2 haploinsufficiency alters DNA repair and sensitivity to DNA damage, and results in chromosome instability. Heterozygous and homozygous depletion of Macrod2 enhances intestinal tumorigenesis in ApcMin/+ mice and the growth of human CRC xenografts. MACROD2 deletion in sporadic CRC is associated with the extent of chromosome instability, independent of clinical parameters and other known genetic drivers. We conclude that MACROD2 acts as a haploinsufficient tumor suppressor, with loss of function promoting chromosome instability thereby driving cancer evolution.
https://ift.tt/2xUwA0o
Maintenance Chemo Improves Pediatric RMS [News in Brief]
Following standard therapy, low-dose cyclophosphamide plus vinorelbine extends rhabdomyosarcoma survival.
https://ift.tt/2xS5qXY
President Signs STAR Act for Kids' Cancers [News in Brief]
Legislation aims to expand collection of biospecimens, improve surveillance, and support research on survivorship.
https://ift.tt/2JiEgyN
Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3K{gamma} to promote pancreatic cancer metastasis
Exosomes are emerging as important mediators of the crosstalk between tumor cells and the microenvironment. However, the mechanisms by which exosomes modulate tumor development under hypoxia in pancreatic cancer (PC) remain largely unknown. Here we found that hypoxic exosomes derived from PC cells activate macrophages to the M2 phenotype in a HIF-1a or HIF-2a-dependent manner, which then facilitates the migration, invasion, and EMT of PC cells. Given that exosomes have been shown to transport miRNAs to alter cellular functions, we discovered that miR-301a-3p was highly expressed in hypoxic PC cells and enriched in hypoxic PC cells-derived exosomes. Circulating exosomal miR-301a-3p levels positively associated with depth of invasion, lymph node metastasis, late TNM stage, and poor prognosis of PC. Hypoxic exosomal miR-301a-3p induced the M2 polarization of macrophages via activation of the PTEN/PI3Kγ signaling pathway. Co-culturing of PC cells with macrophages in which miR-301a-3p was upregulated or treated with hypoxic exosomes enhanced their metastatic capacity. Collectively, these data indicate that PC cells generate miR-301a-3p-rich exosomes in a hypoxic microenvironment, which then polarize macrophages to promote malignant behaviors of PC cells. Targeting exosomal miR-301a-3p may provide a potential diagnosis and treatment strategy for PC.
https://ift.tt/2kT0U22
Macrophages Promote Circulating Tumor Cell-Mediated Local Recurrence Following Radiation Therapy in Immunosuppressed Patients
Although radiation therapy (RT) decreases the incidence of locoregional recurrence in breast cancer, patients with triple-negative breast cancer (TNBC) have increased risk of local recurrence following breast-conserving therapy (BCT). The relationship between RT and local recurrence is unknown. Here we tested the hypothesis that recurrence in some instances is due to the attraction of circulating tumor cells to irradiated tissues. To evaluate the effect of absolute lymphocyte count on local recurrence after RT in TNBC patients, we analyzed radiation effects on tumor and immune cell recruitment to tissues in an orthotopic breast cancer model. Recurrent patients exhibited a prolonged low absolute lymphocyte count when compared to non-recurrent patients following RT. Recruitment of tumor cells to irradiated normal tissues was enhanced in the absence of CD8+ T cells. Macrophages (CD11b+F480+) preceded tumor cell infiltration and were recruited to tissues following RT. Tumor cell recruitment was mitigated by inhibiting macrophage infiltration using maraviroc, an FDA-approved CCR5 receptor antagonist. Our work poses the intriguing possibility that excessive macrophage infiltration in the absence of lymphocytes promotes local recurrence after RT. This combination thus defines a high-risk group of TNBC patients.
https://ift.tt/2sOZwRF
Hexavalent Chromium-Induced Chromosome Instability Drives Permanent and Heritable Numerical and Structural Changes and a DNA Repair-Deficient Phenotype
A key hypothesis for how hexavalent chromium (Cr(VI)) causes cancer is that it drives chromosome instability (CIN), which leads to neoplastic transformation. Studies show chronic Cr(VI) can impact DNA repair and induce centrosome amplification, which can lead to structural and numerical CIN. However, no studies have considered whether these outcomes are transient or permanent. In this study, we exposed human lung cells to particulate Cr(VI) for three sequential 24-hour periods, each separated by about a month. After each treatment, cells were seeded at colony forming density, cloned, expanded and retreated, creating 3 generations of clonal cell lines. Each generation of clones was tested for chromium sensitivity, chromosome complement, DNA repair capacity, centrosome amplification, and the ability to grow in soft agar. After the first treatment, Cr(VI)-treated clones exhibited a normal chromosome complement, but some clones showed a repair-deficient phenotype and amplified centrosomes. After the second exposure, more than half of the treated clones acquired an abnormal karyotype including numerical and structural alterations, with many exhibiting deficient DNA double strand break repair and amplified centrosomes. The third treatment produced new abnormal clones, with previously abnormal clones acquiring additional abnormalities and most clones exhibiting repair deficiency. CIN, repair deficiency, and amplified centrosomes were all permanent and heritable phenotypes of repeated Cr(VI) exposure. These outcomes support the hypothesis that CIN is a key mechanism of Cr(VI)-induced carcinogenesis.
https://ift.tt/2kT0NUa
Reciprocally Regulation of DUSP9 and DUSP16 Expression by HIF-1 Controls ERK and p38 MAP Kinase Activity and Mediates Chemotherapy-Induced Breast Cancer Stem Cell Enrichment
Triple-negative breast cancer (TNBC) has a poor prognosis due to its aggressive characteristics and lack of targeted therapies. Cytotoxic chemotherapy may reduce tumor bulk, but leaves residual disease due to the persistence of chemotherapy-resistant breast cancer stem cells (BCSCs), which are critical for tumor recurrence and metastasis. Here we demonstrate that hypoxia-inducible factor (HIF)-1-dependent regulation of mitogen-activated protein kinase (MAPK) signaling pathways contributes to chemotherapy-induced BCSC enrichment. Chemotherapy increased DUSP9 expression and decreased DUSP16 expression in a HIF-1-dependent manner, leading to inhibition of ERK and activation of p38 signaling pathways, respectively. Inhibition of ERK caused transcriptional induction of the pluripotency factor Nanog through decreased inactivating phosphorylation of FoxO3, while activation of p38 stabilized Nanog and Klf4 mRNA through increased inactivating phosphorylation of RNA binding protein ZFP36L1, both of which promoted specification of the BCSC phenotype. Inhibition of HIF-1 or p38 signaling blocked chemotherapy-induced pluripotency factor expression and BCSC enrichment. These surprising results delineate a mechanism by which a transcription factor switches cells from ERK to p38 signaling in response to chemotherapy and suggest that therapeutic targeting of HIF-1 or the p38 pathway in combination with chemotherapy will block BCSC enrichment and improve outcome in TNBC.
https://ift.tt/2xPgJQR
gQTL: A Web Application for QTL Analysis Using the Collaborative Cross Mouse Genetic Reference Population
Multi-parental recombinant inbred populations, such as the Collaborative Cross (CC) mouse genetic reference population, are increasingly being used for analysis of quantitative trait loci (QTL). However specialized analytic software for these complex populations is typically built in R that works only on command-line, which limits the utility of these powerful resources for many users. To overcome analytic limitations, we developed gQTL, a web accessible, simple graphical user interface application based on the DOQTL platform in R to perform QTL mapping using data from CC mice.
https://ift.tt/2LuLUCU
Auxin-Mediated Sterility Induction System for Longevity and Mating Studies in Caenorhabditis elegans
The ability to control both the means and timing of sexual reproduction provides a powerful tool to understand not only fertilization but also life history trade-offs resulting from sexual reproduction. However, precisely controlling fertilization has proved a major challenge across model systems. An ideal sterility induction system should be external, non-toxic, and reversible. Using the auxin-inducible degradation system targeting the spe-44 gene within the nematode Caenorhabditis elegans, we designed a means of externally inducing spermatogenesis arrest. We show that exposure to auxin during larval development induces both hermaphrodite self-sterility and male sterility. Moreover, male sterility can be reversed upon cessation of auxin exposure. The sterility induction system developed here has multiple applications in the fields of spermatogenesis and mating systems evolution. Importantly, this system is also a highly applicable tool for aging studies. In particular, we show that auxin-induced self-sterility is comparable to the commonly used chemically-induced FUdR sterility, while offering multiple benefits, including being less labor intensive, being non-toxic, and avoiding compound interactions with other experimental treatments.
https://ift.tt/2Jg7qyy
The Doubletime Homolog KIN-20 Mainly Regulates let-7 Independently of Its Effects on the Period Homolog LIN-42 in Caenorhabditis elegans
The Caenorhabditis elegans (C. elegans) heterochronic pathway, which regulates developmental timing, is thought to be an ancestral form of the circadian clock in other organisms. An essential member of this clock is the Period protein whose homolog, lin-42, in C. elegans is an important heterochronic gene. LIN-42 functions as a transcriptional repressor of multiple genes including the conserved lin-4 and let-7 microRNAs. Like other Period proteins, levels of LIN-42 oscillate throughout development. In other organisms this cycling is controlled in part by phosphorylation. KIN-20 is the C. elegans homolog of the Drosophila Period protein kinase Doubletime. Worms containing a large deletion in kin-20 have a significantly smaller brood size and develop slower than wild type C. elegans. Here we analyze the effect of kin-20 on lin-42 phenotypes and microRNA expression. We find that kin-20 RNAi enhances loss-of-function lin-42 mutant phenotypes and that kin-20 mutant worms express lower levels of LIN-42. We also show that kin-20 is important for post-transcriptional regulation of mature let-7 and lin-4 microRNA expression. In addition, the increased level of let-7 found in lin-42(n1089) mutant worms is not maintained after kin-20 RNAi treatment. Instead, let-7 is further repressed when levels of kin-20 and lin-42 are both decreased. Altogether these results suggest that though kin-20 regulates lin-42 and let-7 microRNA, it mainly affects let-7 microRNA expression independently of lin-42. These findings further our understanding of the mechanisms by which these conserved circadian rhythmic genes interact to ultimately regulate rhythmic processes, developmental timing and microRNA biogenesis in C. elegans.
https://ift.tt/2xRPHYZ
Digestive Disease Week, June 2-5
Digestive Disease Week 2018 The Digestive Disease Week annual meeting sponsored by the American Association for the Study of Liver Diseases, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and Society for...
https://ift.tt/2sNhgx1
NCI Cancer Centers Endorse Goal of Eliminating HPV Cancers
THURSDAY, June 7, 2018 -- National Cancer Institute (NCI)-designated cancer centers are endorsing the goal of eliminating cancers caused by the human papillomavirus (HPV) through HPV vaccination and evidence-based cancer screening, according to a...
https://ift.tt/2sHaGJ5
1999 to 2016 Saw Increase in Suicide Rates Across Most States
THURSDAY, June 7, 2018 -- From 1999 to 2016 there was a significant increase in suicide rates across 44 states, according to research published in the June 8 issue of the U.S. Centers for Disease Control and Prevention's Morbidity and Mortality...
https://ift.tt/2M5uZb8
Adjusting for Novel Therapy Use Key to Value-Based Programs
THURSDAY, June 7, 2018 -- Medicare's approach to adjust for use of novel oncology therapies in value-based oncology programs provides financial protection for some high-use practices, according to a report published in the May issue of Health...
https://ift.tt/2sOyXfv
Prognostic value of androgen receptor and FOXA1 co-expression in non-metastatic triple negative breast cancer and correlation with other biomarkers
Prognostic value of androgen receptor and FOXA1 co-expression in non-metastatic triple negative breast cancer and correlation with other biomarkers
Prognostic value of androgen receptor and FOXA1 co-expression in non-metastatic triple negative breast cancer and correlation with other biomarkers, Published online: 08 June 2018; doi:10.1038/s41416-018-0142-6
Prognostic value of androgen receptor and FOXA1 co-expression in non-metastatic triple negative breast cancer and correlation with other biomarkershttps://ift.tt/2LwhgsV
Carcinoma Cuniculatum: A Rare Cause of a Gastroesophageal Junction Mass
A 68-year-old man presented with several months of progressive dysphagia and 50-pound weight loss. Endoscopy revealed a firm mass at the gastroesophageal junction (Figure A). Multiple biopsies including fine-needle biopsy returned atypical squamous proliferation, most consistent with reactive changes (Figure B). Endoscopic ultrasound and cross-sectional imaging, including a positron emission tomography scan demonstrating a highly positron emission tomography avid mass with no evidence of spread, suggested a T3 lesion.
https://ift.tt/2Jq77xd
The forkhead domain hinge-loop plays a pivotal role in DNA binding and transcriptional activity of FOXP2
Journal Name: Biological Chemistry
Issue: Ahead of print
https://ift.tt/2M7jIqT
Ischaemic cardiomyopathy and embolic stroke in a young adult with suspected synthetic cannabinoid use
The incidence of cardiovascular disease is increasing in young adults. We are reporting a case of acute stroke in a young patient with severe ischaemic cardiomyopathy in the absence of traditional risk factors. After ruling out atherosclerotic disease, his presentation was attributed to synthetic cannabinoid use. We then discussed the typical barriers in early diagnosis and limitations of laboratory testing in this condition. Due to the increase in abuse of these synthetic drugs among young adults, there is a need for high clinical suspicion which can help with early recognition and improve morbidity and mortality associated with these chemicals.
https://ift.tt/2M6OMXC
Correction: A Meta-Analysis of the Associations Between the ATP-Binding Cassette Transporter ABCA1 R219K (rs2230806) Polymorphism and the Risk of Type 2 Diabetes in Asians
Horm Metab Res 2018; 50: e4-e4
DOI: 10.1055/a-0634-7904
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Lymphoblastic Lymphoma: Guidelines from the International Lymphoma Radiation Oncology Group (ILROG)
Presentation with a large mediastinal mass is a hallmark of acute lymphoblastic lymphoma, a disease that is treated in the same way as acute lymphoblastic leukemia even in the absence of marrow involvement. The role of mediastinal radiation for patients who achieve complete remission after chemotherapy has been overlooked and controversial. This document presents current knowledge on the role of radiation for lymphoblastic lymphoma and best practices for addressing how to deliver mediastinal radiation with modern technology.
https://ift.tt/2kT6pOu
A prospective comparison of computerized-tomography (CT) based with trans-rectal-ultrasonography (TRUS) assistance and magnetic-resonance imaging (MRI) based target-volume definition during image guided adaptive brachytherapy for cervical cancers
Target volume definition and delineation (high risk) at the time of brachytherapy (BT) is an important step in image guided adaptive brachytherapy for cervical cancers. We present the first prospective study comparing CT-based target delineation with incorporation of trans-rectal ultrasonography at BT and gold standard approach of MR-based target delineation and report comparable results. These findings have a potential impact on brachytherapy practice for cervical cancers across the globe.
https://ift.tt/2sN0VIH
Clinical applications of quantitative three-dimensional MRI analysis for pediatric embryonal brain tumors
The relationship between clinical outcomes and imaging characteristics of pediatric embryonal brain tumors is poorly understood. Here, we analyze embryonal brain tumor magnetic resonance images to identify quantitative radiomic features associated with clinical outcomes. Our results demonstrate that features quantifying primary tumor size and heterogeneity are associated with patient age, neuraxis metastases, histology and recurrence. These data suggest that 3D MRI analysis has the non-invasive potential to identify radiomic risk features for pediatric embryonal brain tumor patients.
https://ift.tt/2sN0Swv
Timing and Causes of Common Pediatric Readmissions
To evaluate and compare readmission causes and timing within the first 30 days after hospitalization for 3 acute and 3 chronic common pediatric conditions.
https://ift.tt/2sEh4kq
Parathyroidectomy in the Management of Secondary Hyperparathyroidism
Secondary hyperparathyroidism develops in CKD due to a combination of vitamin D deficiency, hypocalcemia, and hyperphosphatemia, and it exists in nearly all patients at the time of dialysis initiation. There is insufficient data on whether to prefer vitamin D analogs compared with calcimimetics, but the available evidence suggests advantages with combination therapy. Calcium derangements, patient adherence, side effects, and cost limit the use of these agents. When parathyroid hormone level persists >800 pg/ml for >6 months, despite exhaustive medical interventions, monoclonal proliferation with nodular hyperplasia is likely present along with decreased expression of vitamin D and calcium-sensing receptors. Hence, surgical parathyroidectomy should be considered, especially if concomitant disorders exist, such as persistent hypercalcemia or hyperphosphatemia, tissue or vascular calcification including calciphylaxis, and/or worsening osteodystrophy. Parathyroidectomy is associated with 15%–57% greater survival in patients on dialysis, and it also improves hypercalcemia, hyperphosphatemia, tissue calcification, bone mineral density, and health-related quality of life. The parathyroidectomy rate in the United States declined to approximately seven per 1000 dialysis patient-years between 2002 and 2011 despite an increase in average parathyroid hormone levels, reflecting calcimimetics introduction and uncertainty regarding optimal parathyroid hormone targets. Hospitalization rates are 39% higher in the first postoperative year. Hungry bone syndrome occurs in approximately 25% of patients on dialysis, and profound hypocalcemia requires high doses of oral and intravenous calcium along with calcitriol supplementation. Total parathyroidectomy with autotransplantation carries a higher risk of permanent hypocalcemia, whereas risk of hyperparathyroidism recurrence is higher with subtotal parathyroidectomy. Given favorable long-term outcomes from observational parathyroidectomy cohorts, despite surgical risk and postoperative challenges, it is reasonable to consider parathyroidectomy in more patients with medically refractory secondary hyperparathyroidism.
https://ift.tt/2xQtGtD
Concentrations of Trace Elements and Clinical Outcomes in Hemodialysis Patients: A Prospective Cohort Study
Background and objectives
Deficiency of essential trace elements and excess of potentially toxic trace elements are common in patients on hemodialysis. Whether these abnormalities are associated with poor outcomes is unknown but worth investigating, because they are potentially treatable.
Design, setting, participants, & measurementsWe did a prospective longitudinal study of 1278 patients on incident hemodialysis, assessing blood concentrations of 25 trace elements at baseline. We used adjusted logistic regression to evaluate the association between trace element status and four outcomes (death, cardiovascular events, systemic infection, and hospitalization). A priori hypotheses concerned (1) deficiency of zinc, selenium, and manganese and (2) excess of lead, arsenic, and mercury. Concentrations of the other 19 elements were tested in hypothesis-generating analyses.
ResultsOver 2 years of follow-up, 260 (20%) patients died, 285 (24%) experienced a cardiovascular event, 117 (10%) were hospitalized for systemic infection, and 928 (77%) were hospitalized for any cause. Lower concentrations of zinc or manganese and higher concentrations of lead, arsenic, or mercury were not independently associated with higher risk of clinical outcomes. Lower concentrations of selenium were strongly and independently associated with death (odds ratio, 0.86 per decile; 99.2% confidence interval, 0.80 to 0.93) and all-cause hospitalization (odds ratio, 0.92 per decile; 99.2% confidence interval, 0.86 to 0.98). In exploratory analyses, higher copper concentrations were significantly associated with higher risk of death (odds ratio, 1.07 per decile; 99.2% confidence interval, 1.00 to 1.15), and cadmium levels in the highest decile were associated with higher risk of death (odds ratio, 1.89; 99.2% confidence interval, 1.06 to 3.38).
ConclusionsLower levels of zinc or manganese and higher concentrations of lead, arsenic, or mercury were not associated with higher risk of clinical outcomes, but lower concentrations of selenium were strongly and independently associated with the risks of death and hospitalization.
https://ift.tt/2xSvUsz
Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events
Background and objectives
AKI in the hospital is common and is associated with excess mortality. We examined whether AKI is also independently associated with a higher risk of different cardiovascular events in the first year after discharge.
Design, setting, participants, & measurementsWe conducted a retrospective analysis of a cohort between 2006 and 2013 with follow-up through 2014, within Kaiser Permanente Northern California. We identified all adults admitted to 21 hospitals who had one or more in-hospital serum creatinine test result and survived to discharge. Occurrence of AKI was on the basis of Kidney Disease: Improving Global Outcomes diagnostic criteria. Potential confounders were identified from comprehensive inpatient and outpatient, laboratory, and pharmacy electronic medical records. During the 365 days after discharge, we ascertained occurrence of heart failure, acute coronary syndromes, peripheral artery disease, and ischemic stroke events from electronic medical records.
ResultsAmong a matched cohort of 146,941 hospitalized adults, 31,245 experienced AKI. At 365 days postdischarge, AKI was independently associated with higher rates of the composite outcome of hospitalization for heart failure and atherosclerotic events (adjusted hazard ratio [aHR], 1.18; 95% confidence interval [95% CI], 1.13 to 1.25) even after adjustment for demographics, comorbidities, preadmission eGFR and proteinuria, heart failure and sepsis complicating the hospitalization, intensive care unit (ICU) admission, length of stay, and predicted in-hospital mortality. This was driven by an excess risk of subsequent heart failure (aHR, 1.44; 95% CI, 1.33 to 1.56), whereas there was no significant association with follow-up atherosclerotic events (aHR, 1.05; 95% CI, 0.98 to 1.12).
ConclusionsAKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge.
https://ift.tt/2JjTVOy
Family Consultation to Reduce Early Hospital Readmissions among Patients with End Stage Kidney Disease: A Randomized Controlled Trial
Background and objectives
The US Centers for Medicare and Medicaid Services have mandated reducing early (30-day) hospital readmissions to improve patient care and reduce costs. Patients with ESKD have elevated early readmission rates, due in part to complex medical regimens but also cognitive impairment, literacy difficulties, low social support, and mood problems. We developed a brief family consultation intervention to address these risk factors and tested whether it would reduce early readmissions.
Design, setting, participants, & measurementsOne hundred twenty hospitalized adults with ESKD (mean age=58 years; 50% men; 86% black, 14% white) were recruited from an urban, inpatient nephrology unit. Patients were randomized to the family consultation (n=60) or treatment-as-usual control (n=60) condition. Family consultations, conducted before discharge at bedside or via telephone, educated the family about the patient's cognitive and behavioral risk factors for readmission, particularly cognitive impairment, and how to compensate for them. Blinded medical record reviews were conducted 30 days later to determine readmission status (primary outcome) and any hospital return visit (readmission, emergency department, or observation; secondary outcome). Logistic regressions tested the effects of the consultation versus control on these outcomes.
ResultsPrimary analyses were intent-to-treat. The risk of a 30-day readmission after family consultation (n=12, 20%) was 0.54 compared with treatment-as-usual controls (n=19, 32%), although this effect was not statistically significant (odds ratio, 0.54; 95% confidence interval, 0.23 to 1.24; P=0.15). A similar magnitude, nonsignificant result was observed for any 30-day hospital return visit: family consultation (n=19, 32%) versus controls (n=28, 47%; odds ratio, 0.53; 95% confidence interval, 0.25 to 1.1; P=0.09). Per protocol analyses (excluding three patients who did not receive the assigned consultation) revealed similar results.
ConclusionsA brief consultation with family members about the patient's cognitive and psychosocial risk factors had no significant effect on 30-day hospital readmission in patients with ESKD.
https://ift.tt/2JlfDl0
Identifying Outcomes that Are Important to Living Kidney Donors: A Nominal Group Technique Study
Background and objectives
Living kidney donor candidates accept a range of risks and benefits when they decide to proceed with nephrectomy. Informed consent around this decision assumes they receive reliable data about outcomes they regard as critical to their decision making. We identified the outcomes most important to living kidney donors and described the reasons for their choices.
Design, setting, participants, & measurementsPrevious donors were purposively sampled from three transplant units in Australia (Sydney and Melbourne) and Canada (Vancouver). In focus groups using the nominal group technique, participants identified outcomes of donation, ranked them in order of importance, and discussed the reasons for their preferences. An importance score was calculated for each outcome. Qualitative data were analyzed thematically.
ResultsAcross 14 groups, 123 donors aged 27–78 years identified 35 outcomes. Across all participants, the ten highest ranked outcomes were kidney function (importance=0.40, scale 0–1), time to recovery (0.27), surgical complications (0.24), effect on family (0.22), donor-recipient relationship (0.21), life satisfaction (0.18), lifestyle restrictions (0.18), kidney failure (0.14), mortality (0.13), and acute pain/discomfort (0.12). Kidney function and kidney failure were more important to Canadian participants, compared with Australian donors. The themes identified included worthwhile sacrifice, insignificance of risks and harms, confidence and empowerment, unfulfilled expectations, and heightened susceptibility.
ConclusionsLiving kidney donors prioritized a range of outcomes, with the most important being kidney health and the surgical, lifestyle, functional, and psychosocial effects of donation. Donors also valued improvements to their family life and donor-recipient relationship. There were clear regional differences in the rankings.
https://ift.tt/2Lx27rm
Changes in Glomerular Filtration Rate and Impact on Long-Term Survival among Adults after Hematopoietic Cell Transplantation: A Prospective Cohort Study
Background and objectives
Kidney injury is a significant complication for patients undergoing hematopoietic cell transplantation (HCT), but few studies have prospectively examined changes in GFR in long-term survivors of HCT. We described the association between changes in GFR and all-cause mortality in patients up to 10 years after HCT.
Design, setting, participants, & measurementsWe conducted a prospective, observational cohort study of adult patients undergoing HCT at the Fred Hutchinson Cancer Center in Seattle, Washington from 2003 to 2015. Patients were followed from baseline, before conditioning therapy, until a maximum of 10 years after transplant. We used Cox proportional hazard models to examine the association between creatinine eGFR and all-cause mortality. We used time-dependent generalized estimating equations to examine risk factors for decreases in eGFR.
ResultsA total of 434 patients (median age, 52 years; range, 18–76 years; 64% were men; 87% were white) were followed for a median 5.3 years after HCT. The largest decreases in eGFR occurred within the first year post-transplant, with the eGFR decreasing from a median of 98 ml/min per 1.73 m2 at baseline to 78 ml/min per 1.73 m2 by 1 year post-HCT. Two thirds of patients had an eGFR<90 ml/min per 1.73 m2 at 1 year after transplant. When modeled as a continuous variable, as eGFR declined from approximately 60 ml/min per 1.73 m2, the hazard of mortality progressively increased relative to a normal eGFR of 90 ml/min per 1.73 m2 (P<0.001). For example, when compared with an eGFR of 90 ml/min per 1.73 m2, the hazard ratios for eGFR of 60, 50, and 40 ml/min per 1.73 m2 are 1.15 (95% confidence interval, 0.87 to 1.53), 1.68 (95% confidence interval, 1.26 to 2.24), and 2.67 (95% confidence interval, 1.99 to 3.60), respectively. Diabetes, hypertension, acute graft versus host disease, and cytomegalovirus infection were independently associated with a decline in GFR, whereas calcineurin inhibitor levels, chronic graft versus host disease, and albuminuria were not.
ConclusionsAdult HCT recipients have a high risk of decreased eGFR by 1 year after HCT. Although eGFR remains fairly stable thereafter, a decreased eGFR is significantly associated with higher risk of mortality, with a progressively increased risk as eGFR declines.
https://ift.tt/2Jk3gWE
Prevalence of Hypertension in Children with Early-Stage ADPKD
Background and objectives
Autosomal dominant polycystic kidney disease is the most common inheritable kidney disease, frequently thought to become symptomatic in adulthood. However, patients with autosomal dominant polycystic kidney disease may develop signs or symptoms during childhood, in particular hypertension. Although ambulatory BP monitoring is the preferred method to diagnose hypertension in pediatrics, data in children with autosomal dominant polycystic kidney disease are limited.
Design, setting, participants, & measurementsOur retrospective multicenter study was conducted to collect ambulatory BP monitoring recordings from patients with autosomal dominant polycystic kidney disease age <18 years old. Basic anthropometric parameters as well as data on kidney function, BP treatment, and kidney ultrasound were also collected.
ResultsData from 310 children with autosomal dominant polycystic kidney disease with a mean age of 11.5±4.1 years old were collected at 22 European centers. At the time when ambulatory BP monitoring was performed, 95% of children had normal kidney function. Reference data for ambulatory BP monitoring were available for 292 patients. The prevalence rates of children with hypertension and/or those who were treated with antihypertensive drugs were 31%, 42%, and 35% during daytime, nighttime, or the entire 24-hour cycle, respectively. In addition, 52% of participants lacked a physiologic nocturnal BP dipping, and 18% had isolated nocturnal hypertension. Logistic regression analysis showed a significant association between a categorical cyst score that was calculated on the basis of the number of cysts >1 cm per kidney and daytime hypertension (odds ratio, 1.70; 95% confidence interval, 1.21 to 2.4; P=0.002), nighttime hypertension (odds ratio, 1.31; 95% confidence interval, 1.05 to 1.63; P=0.02), or 24-hour hypertension (odds ratio, 1.39; 95% confidence interval, 1.08 to 1.81; P=0.01). Kidney length, expressed as SD score, was also significantly associated with nighttime hypertension (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.42; P=0.10).
ConclusionsThese data indicate high prevalence of hypertension in children with autosomal dominant polycystic kidney disease starting at young ages.
https://ift.tt/2Jkwg0j
Incidence and Progression of Chronic Kidney Disease in Black and White Individuals with Type 2 Diabetes
Background and objectives
Type 2 diabetes and associated CKD disproportionately affect blacks. It is uncertain if racial disparities in type 2 diabetes-associated CKD are driven by biologic factors that influence propensity to CKD or by differences in type 2 diabetes care.
Design, setting, participants, & measurementsWe conducted a post hoc analysis of 1937 black and 6372 white participants of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to examine associations of black race with change in eGFR and risks of developing microalbuminuria, macroalbuminuria, incident CKD (eGFR<60 ml/min per 1.73m2, ≥25% decrease from baseline eGFR, and eGFR slope <–1.6 ml/min per 1.73 m2 per year), and kidney failure or serum creatinine >3.3 mg/dl.
ResultsDuring a median follow-up that ranged between 4.4 and 4.7 years, 278 black participants (58 per 1000 person-years) and 981 white participants (55 per 1000 person-years) developed microalbuminuria, 122 black participants (16 per 1000 person-years) and 374 white participants (14 per 1000 person-years) developed macroalbuminuria, 111 black participants (21 per 1000 person-years) and 499 white participants (28 per 1000 person-years) developed incident CKD, and 59 black participants (seven per 1000 person-years) and 178 white participants (six per 1000 person-years) developed kidney failure or serum creatinine >3.3 mg/dl. Compared with white participants, black participants had lower risks of incident CKD (hazard ratio, 0.73; 95% confidence intervals, 0.57 to 0.92). There were no significant differences by race in eGFR decline or in risks of microalbuminuria, macroalbuminuria, and kidney failure or of serum creatinine >3.3 mg/dl.
ConclusionsBlack participants enrolled in a randomized controlled trial had lower rates of incident CKD compared with white participants. Rates of eGFR decline, microalbuminuria, macroalbuminuria, and kidney failure did not vary by race.
https://ift.tt/2Jkwh4n
Elimination of Mycoplasma contamination in Chlamydia stocks as a result of in vivo passage or plaque isolation
This study aims to eliminate Mycoplasma spp. contamination from laboratory stocks of Chlamydia spp. by in vivo passage or by plaque assay.
https://ift.tt/2M6RCvX
Multiplex PCR for the simultaneous detection of the Enterobacterial gene wecA, the Shiga Toxin genes (stx1 and stx2) and the Intimin gene (eae)
The aetiology of several human diarrhoeas has been increasingly associated with the presence of virulence factors rather than with the bacterial species hosting the virulence genes, exemplified by the sporadic...
https://ift.tt/2Jpv1ZG
Urinary exosomal expression of activator of G protein signaling 3 in polycystic kidney disease
PKD is a genetic disease that is characterized by abnormally proliferative epithelial cells in the kidney and liver. Urinary exosomes have been previously examined as a source of unique proteins that may be us...
https://ift.tt/2M90q4j
Challenges to achieving low palatal fistula rates following primary cleft palate repair: experience of an institution in Uganda
To determine frequency of palatal fistula following primary cleft palate repair and the associated factors as a measure of cleft palate repair outcome and its challenges at a cleft centre in Uganda.
https://ift.tt/2sPQFzc
Emergency Department Utilization Among the Uninsured During Insurance Expansion in Maryland
We analyzed the effect of insurance expansion on emergency department (ED) utilization among the uninsured in Maryland, which expanded Medicaid eligibility and created health insurance exchanges in 2014.
https://ift.tt/2Jps9vS
iRhoms: A Potential Path to More Specific Therapeutic Targeting of Lupus Nephritis
Lupus nephritis (LN) affects 30% to 60% of patients with systemic lupus erythematosus (SLE) and remains an intractable problem. Despite modern immunosuppressive strategies, <50% of patients reach complete remission. Many of the newer biologic agents tried to date have had no significant effect (reviewed in1). Novel treatments are clearly needed to protect kidneys against podocyte, endothelial, and tubule cell injury in SLE, which mainly occurs as a response to immune complex deposition.
https://ift.tt/2M5867I
Significance of serum ferritin as a prognostic factor in advanced hepatobiliary cancer patients treated with Korean medicine: a retrospective cohort study
Advanced hepatobiliary cancers are highly lethal cancers that require precise prediction in clinical practice. Serum ferritin level increases in malignancy and high serum ferritin level is associated with poor...
https://ift.tt/2sPTKz8
Transcriptome–pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS
Abstract
Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression. After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology. Transcriptome–pathology correlation identified casein kinase 1ε (CSNK1E) mRNA as tightly correlated to levels of pTDP-43 in sALS patients. Enhanced crosslinking and immunoprecipitation in human sALS patient- and healthy control-derived frontal cortex, revealed that TDP-43 binds directly to and regulates the expression of CSNK1E mRNA. Additionally, we were able to show that pTDP-43 itself binds RNA. CK1E, the protein product of CSNK1E, in turn interacts with TDP-43 and promotes cytoplasmic accumulation of pTDP-43 in human stem-cell-derived MNs. Pathological TDP-43 phosphorylation is therefore, reciprocally regulated by CK1E activity and TDP-43 RNA binding. Our framework of transcriptome–pathology correlations identifies candidate genes with relevance to novel mechanisms of neurodegeneration.
https://ift.tt/2xYnYGm
Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry
One of the most challenging stress conditions that organisms encounter during their lifetime involves the accumulation of oxidants. During oxidative stress, cells heavily rely on molecular chaperones. Here, we present methods used to investigate the redox-regulated anti-aggregation activity, as well as to monitor structural changes governing the chaperone function using HDX-MS.
https://ift.tt/2LvYDoT
Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
https://ift.tt/2JmvIXC
Label-free Neutrophil Enrichment from Patient-derived Airway Secretion Using Closed-loop Inertial Microfluidics
In this research, we demonstrate a label-free neutrophil separation method from clinical airway secretions using closed-loop operation of spiral inertial microfluidics. The proposed method would expand the clinical in vitro assays for various respiratory diseases.
https://ift.tt/2LvYD8n
Highly selective SGLT2 inhibitor dapagliflozin reduces seizure activity in pentylenetetrazol-induced murine model of epilepsy
Worldwide, over 10 million individuals suffer from drug-resistant epilepsy. New therapeutic strategies are needed to address this debilitating disease. Inhibition of sodium-glucose linked transporters (SGLTs),...
https://ift.tt/2kWAUmI
Mortality and associated factors of patients with extensive drug-resistant tuberculosis: an emerging public health crisis in China
Limited treatment options of extensive drug-resistant tuberculosis (XDR-TB) have led to its high mortality worldwide. Relevant data about mortality of XDR-TB patients in literature are limited and likely under...
https://ift.tt/2Jjz4uK
Seroprevalence of transfusion-transmissible infections among blood donors at National Blood Transfusion Service, Eritrea: a seven-year retrospective study
Blood transfusion is associated with several risks particularly exposure to blood transfusion-transmissible infections (TTI), including: Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human immunodeficiency...
https://ift.tt/2LvS7yw
Tuberculosis case finding using population-based disease surveillance platforms in urban and rural Kenya
Tuberculosis (TB) case finding is an important component of TB control because it can reduce transmission of Mycobacterium tuberculosis (MTB) through prompt detection and treatment of infectious patients.
https://ift.tt/2JjhDu3
Feco-prevalence and risk factors of Helicobacter pylori infection among symptomatic patients at Dessie Referral Hospital, Ethiopia
Helicobacter pylori (H. pylori) infection is the most common chronic bacterial infection in the world. It can result in various upper gastroduodenal diseases. The prevalence varies among countries, population gro...
https://ift.tt/2LxFmnb
Recurrence of tuberculosis in a low-incidence setting: a retrospective cross-sectional study augmented by whole genome sequencing
The recurrence of tuberculosis (TB) disease in treated patients can serve as a marker of the efficacy of TB control programs. Recurrent disease represents either endogenous reactivation with the same strain of My...
https://ift.tt/2JmZsUn
Methods of Ex Situ and In Situ Investigations of Structural Transformations: The Case of Crystallization of Metallic Glasses
https://ift.tt/2JijNu6
A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
A method to generate a doxorubicin-induced cardiomyopathy model in adult zebrafish (Danio rerio) is described here. Two alternative ways of intraperitoneal injection are presented and conditions to reduce variations among different experimental groups are discussed.
https://ift.tt/2Ls16kj
Respiratory Pathogens May Up Treatment Failure Risk in Asthma
THURSDAY, June 7, 2018 -- Respiratory pathogens are associated with increased risk of treatment failure in children with asthma exacerbations, according to a study published online June 4 in Pediatrics. Joanna Merckx, M.D., from Montreal Children's...
https://ift.tt/2JmG3mN
HIV Pre-Exposure Prophylaxis Linked to Drop in Condom Use
THURSDAY, June 7, 2018 -- For gay and bisexual men, an increase in HIV pre-exposure prophylaxis (PrEP) is associated with a reduction in condom use, according to a study published online June 6 in The Lancet HIV. Martin Holt, Ph.D., from the...
https://ift.tt/2LvRlS8
More Rapid Decline in Kidney Function for Diagnosed Diabetes
THURSDAY, June 7, 2018 -- Individuals with diagnosed diabetes have more rapid kidney function decline than those without diabetes, according to a study published online June 1 in Diabetes Care. Bethany Warren, from Johns Hopkins Bloomberg School of...
https://ift.tt/2Jio80h
Intellectual Activities in Later Life May Cut Dementia Risk
THURSDAY, June 7, 2018 -- Active participation in intellectual activities among adults aged 65 years or older is associated with reduced risk of dementia, according to a study published online May 30 in JAMA Psychiatry. Allen T.C. Lee, M.B.Ch.B.,...
https://ift.tt/2LvPcpt
Skin Cancer Examinations More Likely for Indoor Tanning Users
THURSDAY, June 7, 2018 -- Engaging in ultraviolet (UV) indoor tanning is associated with increased use of skin cancer examinations, according to a research letter published online May 30 in JAMA Dermatology. Kasey L. Morris, Ph.D., from the National...
https://ift.tt/2JhQZ4J
ASCO: Overall Survival Up for African-American Men With mCRPC
THURSDAY, June 7, 2018 -- Overall survival is increased for African-American men with metastatic castration resistant prostate cancer (mCRPC) versus Caucasian men treated with docetaxel/prednisone (DP) or a DP-containing regimen, according to a...
https://ift.tt/2y17GMX
ASCO: Undertreatment Seen for Women With Head & Neck Cancer
THURSDAY, June 7, 2018 -- Females with head and neck cancer (HNC) are less likely to receive intensive chemotherapy and radiation, and have an increased relative risk for death from HNC versus other causes, according to a study presented at the...
https://ift.tt/2JjHJNO
Compression + Early Ablation Tied to Faster Leg Ulcer Healing
THURSDAY, June 7, 2018 -- Early endovenous ablation of superficial venous reflux results in faster healing of venous leg ulcers and more time free from ulcers, compared with deferring endovenous ablation until after ulcer healing, according to a...
https://ift.tt/2y17w8j
Factors ID'd for Persistent Opioid Use After Pediatric Surgery
THURSDAY, June 7, 2018 -- Higher daily average inpatient pain scores and higher postoperative opioid consumption are associated with a subsequent persistent opioid use of up to six months among pediatric patients undergoing major oncologic surgery,...
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Time Spent in Education Is Causal Risk Factor for Myopia
THURSDAY, June 7, 2018 -- More time spent in education seems to be a causal risk factor for myopia, according to a study published online June 6 in The BMJ. Edward Mountjoy, Ph.D., from the University of Bristol in the United Kingdom, and colleagues...
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Volume of interest delineation techniques for 18 F-FDG PET-CT scans during neoadjuvant extremity soft tissue sarcoma treatment in adults: a feasibility study
Abstract
Background
This study explores various volume of interest (VOI) delineation techniques for fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT) scans during neoadjuvant extremity soft tissue sarcoma (ESTS) treatment.
Results
During neoadjuvant treatment, hyperthermic isolated limb perfusion (HILP) and preoperative external beam radiotherapy (EBRT), 11 patients underwent three 18F-FDG PET-CT scans. The first scan was made prior to the HILP, the second after the HILP but prior to the start of the EBRT, and the third prior to surgical resection. An automatically drawn VOIauto, a manually drawn VOIman, and two gradient-based semi-automatically drawn VOIs (VOIgrad and VOIgrad+) were obtained. Maximum standardized uptake value (SUVmax), SUVpeak, SUVmean, metabolically active tumor volume (MATV), and total lesion glycolysis (TLG) were calculated from each VOI. The correlation and level of agreement between VOI delineation techniques was explored. Lastly, the changes in metabolic tumor activity were related to the histopathologic response. The strongest correlation and an acceptable level of agreement was found between the VOIman and the VOIgrad+ delineation techniques. A decline (VOIman) in SUVmax, SUVpeak, SUVmean, TLG, and MATV (all p < 0.05) was found between the three scans. A > 75% decline in TLG between scan 1 and scan 3 possibly identifies histopathologic response.
Conclusions
The VOIgrad+ delineation technique was identified as most reliable considering reproducibility when compared with the other VOI delineation techniques during the multimodality neoadjuvant treatment of locally advanced ESTS. A significant decline in metabolic tumor activity during the treatment was found. TLG deserves further exploration as predictor for histopathologic response after multimodality ESTS treatment.
https://ift.tt/2JDgoWa
Measuring In-Hospital Recovery After Colorectal Surgery Within a Well-Established Enhanced Recovery Pathway: A Comparison Between Hospital Length of Stay and Time to Readiness for Discharge
BACKGROUND: Hospital length of stay is often used as a measure of in-hospital recovery but may be confounded by organizational factors. Time to readiness for discharge may provide a superior index of recovery. OBJECTIVE: The purpose of this study was to contribute evidence for the construct validity of time to readiness for discharge and length of stay as measures of in-hospital recovery after colorectal surgery in the context of a well-established enhanced recovery pathway. DESIGN: This was an observational validation study designed according to the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. SETTINGS: The study was conducted at a university-affiliated tertiary hospital. PATIENTS: A total of 100 consecutive patients undergoing elective colorectal resection (mean age = 65 y; 57% men; 81% laparoscopic) who participated in a randomized controlled trial were included. MAIN OUTCOME MEASURES: We tested a priori hypotheses that length of stay and time-to-readiness for discharge are longer in patients undergoing open surgery, with lower physical status, with severe comorbidities, with postoperative complications, undergoing rectal surgery, who are older (≥75 y), who have a new stoma, and who have inflammatory bowel disease. RESULTS: Median time-to-readiness for discharge and length of stay were both 3 days. For both measures, 6 of 8 construct validity hypotheses were supported (hypotheses 1 and 4–8). LIMITATIONS: The use of secondary data from a randomized controlled trial (risk of selection bias) was a limitation. Results may not be generalizable to institutions where patient care is not equally structured. CONCLUSIONS: This study contributes evidence to the construct validity of time-to-readiness for discharge and length of stay as measures of in-hospital recovery within enhanced recovery pathways. Our findings suggest that length of stay can be a less resource-intensive and equally construct-valid index of in-hospital recovery compared with time-to-readiness for discharge. Enhanced recovery pathways may decrease process-of-care variances that impact length of stay, allowing more timely discharge once discharge criteria are achieved. See Video Abstract at https://ift.tt/2sEnLmB.https://ift.tt/2sPbvi6
The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for Anal Squamous Cell Cancers (Revised 2018)
No abstract availablehttps://ift.tt/2M7XdSP
Expert Commentary on Pilonidal Disease: Management and Definitive Treatment
No abstract availablehttps://ift.tt/2M4IdVA
Detection Rate of High-Grade Squamous Intraepithelial Lesions as a Quality Assurance Metric for High-Resolution Anoscopy in HIV-Positive Men
BACKGROUND: High-resolution anoscopy-guided biopsies are the gold standard for identifying anal intraepithelial neoplasia, but diagnosing high-grade squamous intraepithelial lesions depends on the skills of the anoscopist. OBJECTIVE: This study aims to validate the high-grade squamous intraepithelial lesion detection rate as a quality assurance metric for high-resolution anoscopy in HIV-positive men. DESIGN: This is a retrospective study. SETTING: This study was conducted at 3 HIV outpatient clinics in Amsterdam, The Netherlands. PATIENTS: HIV-positive men who have sex with men were selected for this study. MAIN OUTCOME MEASURES: We analyzed the high-grade squamous intraepithelial lesion detection rate per high-resolution anoscopy, the mean number of biopsies taken, and the mean high-grade squamous intraepithelial lesion rate per biopsy in time-subsequent groups for 7 anoscopists performing high-resolution anoscopy. RESULTS: Seven anoscopists performed high-resolution anoscopy in 1340 HIV-positive men who have sex with men. The overall high-grade squamous intraepithelial lesion detection rate for all 7 anoscopists combined increased significantly over time, from 27% to 40% (phttps://ift.tt/2sDjLTa
A Population-Based Cohort Analysis of Chemoradiation Versus Radiation Alone for Definitive Treatment of Stage I Anal Cancer in Older Patients
BACKGROUND: Although the benefit of chemoradiation over radiation therapy alone has been shown in randomized trials for stage II to III squamous cell of the anus, this benefit is not clear for patients with stage I cancer. Nevertheless, most societal recommendations endorse chemoradiation for patients with stage I squamous cell carcinoma of the anus despite the lack of proven benefit and potential increase in toxicity. OBJECTIVE: The purpose of this study was to determine whether outcomes are improved with the addition of chemotherapy versus radiation alone for stage I squamous cell carcinoma of the anus. DESIGN: This was a cohort analysis using Surveillance, Epidemiology and End Results registry linked to Medicare from 1996 to 2011. Propensity-score methods were used to control for potential confounding. SETTINGS: This was a population-based study. PATIENTS: Medicare eligible patients (age >65 y or with an eligible disability) with stage I squamous cell carcinoma of the anus treated with either definitive radiation alone or chemoradiation were included. INTERVENTIONS: Radiation or chemoradiation was the intervention. MAIN OUTCOME MEASURES: Overall survival, disease-free survival, cause-specific survival, colostomy-free survival, and acute or late toxicities were measured. RESULTS: A total of 200 patients with squamous cell carcinoma of the anus were identified who received chemoradiation versus 99 treated with lone radiotherapy. Median age was 72 years and did not differ by treatment (p = 0.6). Patients receiving chemoradiation had improved unadjusted overall survival compared with lone radiotherapy, but after adjustment using propensity-score methods there was no difference in overall survival (HR = 0.7 (95% CI, 0.4–1.0)), cause-specific survival (HR = 0.7 (95% CI, 0.3–1.6)), colostomy-free survival (HR = 1.1 (95% CI, 0.5–2.5)), or disease-free survival (HR = 0.9 (95% CI, 0.6–1.4)). Chemoradiation was associated with an increased risk of select early and late toxicities. LIMITATIONS: This is a retrospective series from an anonymous database. The data might not be relevant for younger, healthier patients. CONCLUSIONS: Lone radiation may be associated with adequate oncologic outcomes when used to treat older and sicker patients with stage I anal cancer. Physicians should discuss the potential benefits and harms of adding chemotherapy for the treatment of these patients. See Video Abstract at https://ift.tt/2sPfaMP.https://ift.tt/2sERj3c
Predicting Survival After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Appendix Adenocarcinoma
BACKGROUND: Appendix adenocarcinomas are rare tumors with propensity for peritoneal metastasis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is an established treatment with curative intent, but, to date, studies reporting survival have been heterogeneous with regard to their patient groups (including other tumor types), interventions (not all patients receiving intraperitoneal chemotherapy), and follow-up (varying surveillance protocols). OBJECTIVE: The aim of this study is to quantify the impact of this intervention on survival in a homogeneous group of patients with appendix adenocarcinoma receiving standardized treatment and follow-up, and to determine the impact of prognostic indicators on survival. DESIGN: This is a retrospective analysis of a prospective database at a national peritoneal tumor center where all patients had their appendix pathology reviewed and management planned by a specialized peritoneal tumor multidisciplinary team. MAIN OUTCOME MEASURES: Data were extracted on prognostic indicators including peritoneal cancer index, completeness of cytoreduction score, preoperative tumor markers, and histological features. Overall and disease event-free survival from the date of intervention were evaluated using Kaplan Meier curves and univariate Cox proportional hazards regression analysis. RESULTS: A total of 65 patients underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for appendix adenocarcinoma between 2005 and 2015. Median follow-up was 44.3 months. The overall survival was 55.5% and disease event-free survival was 36.1% (5-year rate). Peritoneal Cancer Indexhttps://ift.tt/2sODVcb
Risk Factors for Peritoneal Recurrence in Stage II to III Colon Cancer
BACKGROUND: Most previous reports to analyze risk factors for peritoneal recurrence in patients with colon cancer have been observational studies of a population-based cohort. OBJECTIVE: This study aimed to determine the risk factors for peritoneal recurrence in patients with stage II to III colon cancer who underwent curative resection. DESIGN: This was a pooled analysis using a combined database obtained from 3 large phase III randomized trials (N = 3714). SETTINGS: Individual patient data were collected from the Japanese Foundation for Multidisciplinary Treatment of Cancer clinical trials 7, 15, and 33, which evaluated the benefits of postoperative 5-fluorouracil–based adjuvant therapies in patients with locally advanced colorectal cancer. PATIENTS: We included patients who had stage II to III colon cancer and underwent curative resection with over D2 lymph node dissection. MAIN OUTCOME MEASURES: Main outcomes measured were risk factors for peritoneal recurrence without other organ metastasis after curative surgery. RESULTS: Peritoneal recurrence occurred in 2.3% (86/3714) of all patients undergoing curative resection. Mean duration from operation to peritoneal recurrence was 17.0 ± 10.3 months. Of these patients with peritoneal recurrence, 29 patients (34%) had recurrence in ≥1 other organ. Multivariate analysis showed that age (≥60 y: HR = 0.531; p = 0.0182), pathological T4 (HR = 3.802; phttps://ift.tt/2sOqxVC
Recurrence of Rectal Prolapse After Surgical Repair in Women With Pelvic Organ Prolapse
BACKGROUND: Pelvic organ prolapse is prevalent among women with rectal prolapse. OBJECTIVE: This study aimed to determine whether clinically significant pelvic organ prolapse impacts rectal prolapse recurrence after surgical repair. DESIGN: A retrospective cohort. SETTING: This study was performed at a single managed-care institution. PATIENTS: Consecutive women undergoing rectal prolapse repair between 2008 and 2016 were included. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Full-thickness rectal prolapse recurrence was compared between 4 groups: abdominal repair without pelvic organ prolapse (AR−POP); abdominal repair with pelvic organ prolapse (AR+POP); perineal repair without pelvic organ prolapse PR−POP; and perineal repair with pelvic organ prolapse (PR+POP). Recurrence-free period and hazard of recurrence were compared using Kaplan-Meier and Cox proportional hazards methods. To identify potential confounding risk factors for rectal prolapse recurrence, the characteristics of subjects with/without recurrence were compared with univariable and multivariable analyses. RESULTS: Overall, pelvic organ prolapse was present in 33% of 112 women and was more prevalent among subjects with rectal prolapse recurrence (52.4% vs 28.6%, p = 0.04). Median follow-up was 42.5 months; rectal prolapse recurrence occurred in 18.8% at a median of 9 months. The rate of recurrence and the recurrence-free period differed significantly between groups: AR−POP 3.8%, 95.7 months; AR+POP 13.0%, 86.9 months; PR−POP 34.8%, 42.1 months; PR+POP 57.1%, 23.7 months (phttps://ift.tt/2M6rhye
Transanal Total Mesorectal Excision vs Laparoscopic Total Mesorectal Excision in the Treatment of Low and Middle Rectal Cancer: A Propensity Score Matching Analysis
BACKGROUND: Transanal total mesorectal excision is a novel and promising technique in the treatment of low and middle rectal cancer. OBJECTIVE: This study aimed to compare the safety and feasibility of transanal total mesorectal excision versus laparoscopic total mesorectal excision. DESIGN: This was a retrospective study using propensity score matching analysis. SETTINGS: This study was conducted in a single high-volume university hospital. PATIENTS: Patients with low and middle rectal cancer who underwent total mesorectal excision with curative intent between 2007 and 2017 were recruited. INTERVENTIONS: Laparoscopic total mesorectal excision and transanal total mesorectal excision had been performed. MAIN OUTCOME MEASURES: Intraoperative, pathological, and 30-day postoperative outcomes were compared between the transanal and laparoscopic groups. RESULTS: Overall, 105 patients were selected from the whole sample of 316 patients with rectal cancer. After propensity score matching analysis, 46 patients for each group were compared. Laparoscopic total mesorectal excision was associated with a higher conversion rate to open surgery (19.6% vs 0%, p = 0.002). Transanal total mesorectal excision showed a longer distal resection margin (15 mm vs 25 mm; phttps://ift.tt/2sPzcH0
Robotic Platform for an IPAA
INTRODUCTION: An IPAA is the preferred operative approach for restoration of intestinal continuity in patients with ulcerative colitis and familial adenomatous polyposis. As minimally invasive approaches have become more widely adopted, their use in IPAA has also become increasingly commonplace. Laparoscopy has the same limitations during the proctectomy portion as seen in operations for rectal cancer, including dissection in the mid-to-lower rectum attributed to angles created by bony confines of the deep pelvis and lack of visibility when constructing the anastomosis. Robotic surgery provides improved 3-dimensional and high-definition visualization of the pelvis and multiple degrees of freedom, which greatly enhance performance during the proctectomy and construction of the anastomosis. TECHNIQUE: In the setting of a previous subtotal colectomy, the ileostomy site is taken down and stapled across. A 15-mm balloon trocar is placed in the site to achieve insufflation, and the robotic ports are placed horizontally just above the umbilicus. The lateral mesenteric attachments are mobilized laparoscopically, then the J-pouch is constructed through the ostomy site. The J-pouch is placed back into the abdomen with the anvil in place, and the proctectomy is performed after docking the robot. The rectum is stapled with the robotic stapler and exteriorized from the ileostomy site, and the anastomosis is constructed under direct robotic visualization. RESULTS: In addition to the potential ergonomic advantages, the maneuverability and visualization in the pelvis during the proctectomy and construction of the anastomosis are reported by many surgeons to be improved as compared with laparoscopy, especially in male or obese patients. CONCLUSIONS: A robotic approach during the proctectomy and IPAA offers significant advantages to a laparoscopic approach, expanding our armamentarium of minimally invasive surgical techniques to IPAA.https://ift.tt/2sCdszs
The Effect of Peer Support on Colorectal Cancer Patients’ Adherence to Guideline-Concordant Multidisciplinary Care
BACKGROUND: Multidisciplinary care is critical for the successful treatment of stage III colorectal cancer, yet receipt of adjuvant chemotherapy remains unacceptably low. Peer support, or exposure to others treated for colorectal cancer, has been proposed as a means to improve patient acceptance of cancer care. OBJECTIVE: The purpose of our study was to evaluate the effect of peer support on the attitudes of patients with colorectal cancer toward chemotherapy and their adherence to it. DESIGN: We conducted a population-based survey of patients with sage III colorectal cancer and compared demographics and adjuvant chemotherapy adherence after patient-reported exposure to peer support. SETTINGS: Patients were identified by using Surveillance, Epidemiology, and End Results Program cancer registries and were recruited 3 to 12 months after cancer resection. PATIENTS: All patients with stage III colorectal cancer who underwent colorectal resection between 2011 and 2013 and were located in the Detroit and Georgia regions were included. MAIN OUTCOME MEASURES: The main outcome measure was adjuvant chemotherapy adherence. Exposure to peer support was an intermediate outcome. RESULTS: Among 1301 patient respondents (68% response rate), 48% reported exposure to peer support. Exposure to peer support was associated with younger age, higher income, and having a spouse or domestic partner. Exposure to peer support was significantly associated with receipt of adjuvant chemotherapy (OR, 2.94; 95% CI, 1.89–4.55). Those exposed to peer support reported positive effects on attitudes toward chemotherapy. LIMITATIONS: This study has limitations inherent to survey research including the potential lack of generalizability and responses that are subject to recall bias. Additionally, the survey results do not allow for determination of the temporal relationship between peer support exposure and receipt of chemotherapy. CONCLUSION: Our study demonstrates that exposure to peer support is associated with higher adjuvant chemotherapy adherence. These data suggest that facilitated peer support programs could positively influence patient expectations and coping with diagnosis and treatment, thereby affecting the uptake of postoperative chemotherapy. See Video Abstract at https://ift.tt/2M8oG6O.https://ift.tt/2sV0H2j
The Dantastic Mr. Tox & Howard Episode 7 – Life is a High-Way
https://ift.tt/2JhVDQl Addiction beyond dopamine with Dr. Andy Chambers Join Dan (@drusyniak) &howard (@heshiegreshie) as they explore the neurobehavioral underpinnings of addiction. Learn about the Google Maps of the motivational system of the brain and gain insight into why psychiatric patients and adolescents are such vulnerable populations. And make sure that you check out Dr. Andy […]
EMCrit Project by Tox & Hound.
https://ift.tt/2xPyP5b
Reinstatement of Drug-seeking in Mice Using the Conditioned Place Preference Paradigm
https://ift.tt/2M7Qdp2
CMAP Scan MUNE (MScan) - A Novel Motor Unit Number Estimation (MUNE) Method
This protocol describes a new method to estimate the number of functioning motor units in a muscle, by fitting a model to a detailed stimulus-response curve of the compound muscle action potential. It is quick and easy to perform and analyze and has excellent reproducibility.
https://ift.tt/2JmExgd
A Technology Intervention for Nurses Engaged in Preventing Catheter-Associated Urinary Tract Infections
Catheter-associated urinary tract infections account for 40% of healthcare-acquired infections. This study explored the addition of cloud-based software technology to an established nursing quality improvement program to reduce catheter-associated urinary tract infections. Unit-based nurse champions evaluated peers' evidence-based catheter-associated urinary tract infection prevention practices using manual, paper-based feedback. That process achieved reduced rates of catheter-associated urinary tract infection over 18 months. However, it was resource intensive. Cloud-based software technology was introduced to replace the paper. Nurse champions' satisfaction, catheter-associated urinary tract infection and indwelling urinary catheter utilization, and prevention practices were compared before and after the technology intervention. Compliance with the provision of a chlorhexidine bath demonstrated improvement (P = .003), while other practice measures did not significantly change. The indwelling urinary catheter utilization ratio was lower (P = .01), yet the intervention yielded no change in catheter-associated urinary tract infection rates. The short time interval of the intervention was potentially a contributing factor in no significant rate change. Nurse champions (N = 14) were more satisfied with the cloud-based technology (P = .004), the clarity of improvement targets (P = .004), and the speed of sharing data (P = .001). Their time to share data decreased from 4 days or more to 1 hour or less. Nurse champions readily adopted the cloud-based technology. These findings suggest additional research on technology innovations for nursing quality improvement is needed.https://ift.tt/2Lr1Ndq
The Role of the Electronic Medical Record in the Intensive Care Unit Nurse's Detection of Patient Deterioration: A Qualitative Study
Failure to detect patient deterioration signals leads to longer stays in the hospital, worse functional outcomes, and higher hospital mortality rates. Surveillance, including ongoing acquisition, interpretation, and synthesis of patient data by the nurse, is essential for early risk detection. Electronic medical records promote accessibility and retrievability of patient data and can support patient surveillance. A secondary analysis was performed on interview data from 24 intensive care unit nurses, collected in a study that examined factors influencing nurse responses to alarms. Six themes describing nurses' use of electronic medical record information to understand the patients' norm and seven themes describing electronic medical record design issues were identified. Further work is needed on electronic medical record design to integrate documentation and information presentation with the nursing workflow. Organizations should involve bedside nurses in the design of handoff formats that provide key information common to all intensive care unit patient populations, as well as population-specific information.https://ift.tt/2M8loAh
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
