European Journal of Immunology, EarlyView.
https://ift.tt/2rQdv9B
Πέμπτη 17 Μαΐου 2018
Microbial metabolites, short‐chain fatty acids, restrain tissue bacterial load, chronic inflammation, and associated cancer in the colon of mice
A 20‐year Review: The Use of Exception From Informed Consent and Waiver of Informed Consent in Emergency Research
Academic Emergency Medicine, EarlyView.
https://ift.tt/2rQcFKJ
Proximate composition, functional, and pasting properties of wheat and groundnut protein concentrate flour blends
Food Science &Nutrition, EarlyView.
https://ift.tt/2GrvXdS
Cancers, Vol. 10, Pages 145: [18F]FDG-PET/CT in Hodgkin Lymphoma: Current Usefulness and Perspectives
Cancers, Vol. 10, Pages 145: [18F]FDG-PET/CT in Hodgkin Lymphoma: Current Usefulness and Perspectives
Cancers doi: 10.3390/cancers10050145
Authors: Salim Kanoun Cedric Rossi Olivier Casasnovas
Functional imaging using 18-fluorodeoxyglycose ([18F]FDG) positron emission tomography combined with computed tomography (PET/CT) has become a major imaging modality in Hodgkin lymphoma. This imaging modality allows for a significant improvement in staging, increased sensitivity, which involves differentiating residual tumors from fibrosis during assessment, and highly impacts treatment decisions into new PET-driven strategies. This review presents the main scientific data concerning the current applications of [18F]FDG-PET/CT in Hodgkin lymphoma at baseline, interim, and the end of treatment evaluation along with the main PET-driven trials for therapeutic decisions. The emergence of total metabolic tumor volume as a new functional prognostic factor will also be discussed.
https://ift.tt/2rT7FUV
Genetic Analyses of Elys Mutations in Drosophila Show Maternal-Effect Lethality and Interactions with Nucleoporin Genes
ELYS determines the subcellular localizations of Nucleoporins (Nups) during interphase and mitosis. We made loss-of-function mutations of Elys in Drosophila melanogaster and found that ELYS is dispensable for zygotic viability and male fertility but the maternal supply is necessary for embryonic development. Subsequent to fertilization, mitotic progression of the embryos produced by the mutant females is severely disrupted at the first cleavage division, accompanied by irregular behavior of mitotic centrosomes. The Nup160 introgression from D. simulans shows close resemblance to that of the Elys mutations, suggesting a common role for those proteins in the first cleavage division. Our genetic experiments indicated critical interactions between ELYS and three Nup107-160 subcomplex components; hemizygotes of either Nup37, Nup96 or Nup160 were lethal in the genetic background of the Elys mutation. Not only Nup96 and Nup160 but also Nup37 of D. simulans behave as recessive hybrid incompatibility genes with D. melanogaster. An evolutionary analysis indicated positive natural selection in the ELYS-like domain of ELYS. Here we propose that genetic incompatibility between Elys and Nups may lead to reproductive isolation between D. melanogaster and D. simulans, although direct evidence is necessary.
https://ift.tt/2L88QIO
STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS-Mutant Lung Adenocarcinoma [Research Articles]
KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) co-mutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine the efficacy of PD-1 inhibitors in these subgroups. Objective response rates to PD-1 blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) subgroups (P<0.001) in the SU2C cohort (174 patients) with KRAS-mutant LUAC and in patients treated with nivolumab in the CheckMate-057 phase 3 trial (0% vs 57.1% vs 18.2%, P=0.047). In the SU2C cohort, KL LUAC exhibited shorter progression-free (P<0.001) and overall survival (P=0.0015) compared to KRASMUT;STK11/LKB1WT LUAC. Among 924 LUAC, STK11/LKB1 alterations were the only marker significantly associated with PD-L1 negativity in TMBIntermediate/High LUAC. The impact of STK11/LKB1 alterations on clinical outcomes with PD-1/PD-L1 inhibitors extended to PD-L1-positive NSCLC. In Kras-mutant murine LUAC models, Stk11/Lkb1 loss promoted PD-1/PD-L1 inhibitor resistance, suggesting a causal role. Our results identify STK11/LKB1 alterations as a major driver of primary resistance to PD-1 blockade in KRAS-mutant LUAC.
https://ift.tt/2wQOW1S
Impact of timing of trastuzumab initiation on long-term outcome of patients with early-stage HER2-positive breast cancer: the “one thousand HER2 patients” project
Impact of timing of trastuzumab initiation on long-term outcome of patients with early-stage HER2-positive breast cancer: the "one thousand HER2 patients" project
Impact of timing of trastuzumab initiation on long-term outcome of patients with early-stage HER2-positive breast cancer: the "one thousand HER2 patients" project, Published online: 18 May 2018; doi:10.1038/s41416-018-0114-x
Impact of timing of trastuzumab initiation on long-term outcome of patients with early-stage HER2-positive breast cancer: the "one thousand HER2 patients" projecthttps://ift.tt/2rPxENL
Microbial networking in cancer: when two toxins collide
Microbial networking in cancer: when two toxins collide
Microbial networking in cancer: when two toxins collide, Published online: 18 May 2018; doi:10.1038/s41416-018-0101-2
Microbial networking in cancer: when two toxins collidehttps://ift.tt/2rNT392
Delayed diagnosis of spontaneous rupture of a congenital bladder diverticulum as a rare cause of an acute abdomen
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2KyBTnG
Trauma and fear in Australian midwives
Publication date: Available online 16 May 2018
Source:Women and Birth
Author(s): J. Toohill, J. Fenwick, M. Sidebotham, J. Gamble, D.K. Creedy
BackgroundRelatively little is known about the extent of trauma and birth-related fear in midwives and how this might affect practice.Aim(1) Determine prevalence of birth related trauma and fear in midwives and associations with midwives' confidence to advise women during pregnancy of their birth options and to provide care in labour. (2) Describe midwives' experiences of birth related trauma and/or fear.MethodA mixed methods design. A convenience sample of midwives (n=249) completed an anonymous online survey. Descriptive and inferential statistics were used to analyse the quantitative data. Latent content analysis was used to extrapolate meaning from the 170 midwives who wrote about their experiences of personal and/or professional trauma.ResultsThe majority of midwives (93.6%) reported professional (n=199, 85.4%) and/or personal (n=97, 41.6%) traumatic birth experiences. Eight percent (n=20) reported being highly fearful of birth. Trauma was not associated with practice concerns but fear was. Midwives categorised as having 'high fear' reported more practice concerns (Med 23.5, n=20) than midwives with 'low fear' (Med 8, n=212) (U=1396, z=−3.79, p<0.001, r=0.24). Reasons for personal trauma included experiencing assault, intervention and stillbirth. Professional trauma related to both witnessing and experiencing disrespectful care and subsequently feeling complicit in the provision of poor care. Feeling unsupported in the workplace and fearing litigation intensified trauma.ConclusionHigh fear was associated with lower confidence to support childbearing women. Fear and trauma in midwives warrants further investigation to better understand the impact on professional practice.
https://ift.tt/2Isgxf4
On edge correction of conditional and intrinsic autoregressions
SUMMARY
This paper discusses edge correction for a large class of conditional and intrinsic autoregressions on two-dimensional finite regular arrays. The proposed method includes a novel reparameterization, retains the simple neighbourhood structure, ensures the nonnegative definiteness of the precision matrix, and enables scalable matrix-free statistical computation. The edge correction provides new insight into how higher-order differencing enters into the precision matrix of a conditional autoregression.https://ift.tt/2rRhGBN
European cancer mortality predictions for the year 2018 with focus on colorectal cancer
Abstract
Background
We projected cancer mortality statistics for 2018 for the European Union (EU) and its six more populous countries, using the most recent available data. We focused on colorectal cancer. Materials and methods
We obtained cancer death certification data from stomach, colorectum, pancreas, lung, breast, uterus, ovary, prostate, bladder, leukaemia, and total cancers from the World Health Organisation database and projected population data from Eurostat. We derived figures for France, Germany, Italy, Poland, Spain, the UK, and the EU in 1970–2012. We predicted death numbers by age group and age-standardized (world population) rates for 2018 through joinpoint regression models. Results
EU total cancer mortality rates are predicted to decline by 10.3% in men between 2012 and 2018, reaching a predicted rate of 128.9/100 000, and by 5.0% in women with a rate of 83.6. The predicted total number of cancer deaths is 1 382 000 when compared with 1 333 362 in 2012 (+3.6%). We confirmed a further fall in male lung cancer, but an unfavourable trend in females, with a rate of 14.7/100 000 for 2018 (13.9 in 2012, +5.8%) and 94 500 expected deaths, higher than the rate of 13.7 and 92 700 deaths from breast cancer. Colorectal cancer predicted rates are 15.8/100 000 men (−6.7%) and 9.2 in women (−7.5%); declines are expected in all age groups. Pancreatic cancer is stable in men, but in women it rose +2.8% since 2012. Ovarian, uterine and bladder cancer rates are predicted to decline further. In 2018 alone, about 392 300 cancer deaths were avoided compared with peak rates in the late 1980s. Conclusion
We predicted continuing falls in mortality rates from major cancer sites in the EU and its major countries to 2018. Exceptions are pancreatic cancer and lung cancer in women. Improved treatment and—above age 50 years—organized screening may account for recent favourable colorectal cancer trends.https://ift.tt/2wRUt8j
Targeting cell cycle dependencies represent a novel therapeutic approach for selected sarcoma subgroups
Adult soft tissue sarcoma (STS) represents a group of rare malignant tumours associated with a very poor prognosis in the metastatic setting, with <20% of patients surviving 5 years after diagnosis [1]. Beyond their biological aggressiveness, under-recognition misdiagnosis of STS also contributes to this increased mortality. Management by specialized multidisciplinary boards is recommended and improves patients' survival [2].
https://ift.tt/2wZPeDV
https://ift.tt/2wZPeDV
ESR1 and endocrine therapy resistance: more than just mutations
Estrogen receptor (ER)-positive breast cancer accounts for 70%–80% of all diagnosed breast cancers [1]. The adoption of endocrine therapies, including ER modulators/degraders (SERMs/SERDs), which antagonize ER, and aromatase inhibitors (AIs), which suppress estrogen synthesis, as the mainstay of treatment of ER-positive breast cancer patients has resulted in substantial survival benefit for patients with early stage disease [2]. Treating ER-positive metastatic breast cancer (MBC), however, remains a significant clinical challenge, due to the development of secondary resistance to all modalities of endocrine therapy [3]. Recently, studies have identified recurrent somatic mutations within the ligand-binding domain (LBD) of ESR1 (encoding ER) in >30% of ER-positive MBC [4–8]. These mutations alter the conformation of ER and produce a constitutively active form of the protein. Mutations at residues 536–538, in particular, promote ER activity in the absence of ligand, resulting in resistance to AIs and reduced sensitivity to SERMs/SERDs [4, 5]. ESR1 fusion genes have also been reported in ER-positive MBCs; however, a detailed description of their manifestations and clinical prevalence is lacking [9]. In this issue of Annals of Oncology, Hartmaier et al. reported the identification of recurrent hyperactive ESR1 fusion genes in breast cancers resistant to endocrine therapy [10], adding to the diversity of reported ESR1 alterations.
https://ift.tt/2IMJ4vo
https://ift.tt/2IMJ4vo
Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer
Abstract
Background
There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC. Patients and methods
In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m2 intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS). Results
A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P = 0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P = 0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P = 0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%). Conclusions
Vinflunine 280 mg/m2 q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m2 merits evaluation. ClinicalTrials.gov
NCT01091168.https://ift.tt/2rRoC1L
Computational prediction of neoantigens: do we need more data or new approaches?
The capability of the immune system for self-recognition has recently become the focus of interest for a broadening research community due to the impressive clinical results achieved with immune checkpoint inhibitors and other immunotherapies in the treatment of advanced metastatic carcinoma [1]. A significant portion of this clinical efficacy is attributed to the fact that the genomic instability of cancer generates mutation-derived peptides (neopeptides) that are not present in normal cells. A subset of these neopeptides may be neoantigens (also called neoepitopes) which are recognized as alien by cytotoxic T cells. Ideally, a cell producing neoantigens should be eliminated by the immune system. However, tumors are able to inhibit this immune response by activating various checkpoint mechanisms; these can be overcome by the now widely used therapeutic agents of checkpoint inhibitors such as anti PD-L1 or anti-CTLA-4 antibodies. There is increasing evidence that such neoantigen-driven immune responses are responsible for the significant clinical response shown to immune checkpoint inhibitors in at least one specific type of tumors, microsatellite instable cancer [2, 3].
https://ift.tt/2k845Tt
https://ift.tt/2k845Tt
Toward optimizing outcomes in Her2-positive gastric cancer: timing and genomic context matter
In 2010, the ToGA trial demonstrated a 2.7-month improvement in overall survival (OS) with the addition of the anti-HER2 monoclonal antibody trastuzumab to platinum-5-FU in first-line treatment of advanced HER2-positive gastric cancer [1]. Subsequent attempts to address HER2-directed therapies in first and second lines have been met with largely disappointing results [2–5]. In the phase III LOGiC trial, the addition of the small molecule HER2-inhibitor lapatinib to first-line CapeOx failed to improve OS in the primary efficacy population (12.2 versus 10.5, Hazard Ratio (HR) 0.91, P = 0.35), though preplanned subset analysis suggested a benefit with the addition of lapatinib in Asian patients (HR 0.68) and patients < 60 years old (HR 0.69) [2]. There was no correlation between Immunohistochemistry (IHC)-status and OS benefit in the study population, which were all amplified by FISH. Contemporary with the LOGiC trial was several publications associating magnitude of HER2 amplification with degree of benefit from trastuzumab, as well as the recognition that HER2-positive gastric cancer is a highly heterogeneous disease complicated by chronologic HER2 changes, and inter- and intratumoral variations in molecular features [6–9]. The incorporation of cell-free DNA (cfDNA) has allowed for perhaps more representative sampling of global tumor makeup, potentially facilitating identification of patient subsets with better or worse outcomes though limited prospective data exist in esophagogastric cancers [10].
https://ift.tt/2rPXvEw
https://ift.tt/2rPXvEw
Introducing whole-genome sequencing into routine cancer care: the Genomics England 100 000 Genomes Project
Large-scale sequencing studies such as the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) have begun to catalogue the spectra of somatic mutations present in different solid tumour types [1, 2]. However, to date there has been minimal traction for solid tumours in alignment of large-scale sequencing data to longitudinal data on therapy and outcome. Such data are essential if we are to better target conventional cytotoxics, as well as emerging drugs such as immunotherapeutics. Stratification using molecular markers could improve benefit against cost and side-effects, especially critical in the adjuvant setting. Molecular heterogeneity of tumours and confounding patient factors mean datasets of daunting size and depth will be required. Arguably these will only be achieved through molecular analyses as standard for cancer patients entering clinical trials and, by adopting a population level approach to molecular analysis of patients undergoing routine cancer treatments.
https://ift.tt/2k6qUXl
https://ift.tt/2k6qUXl
Overexpression of BLM promotes DNA damage and increased sensitivity to platinum salts in triple-negative breast and serous ovarian cancers
Abstract
Background
Platinum-based therapy is an effective treatment for a subset of triple-negative breast cancer and ovarian cancer patients. In order to increase response rate and decrease unnecessary use, robust biomarkers that predict response to therapy are needed. Patients and methods
We performed an integrated genomic approach combining differential analysis of gene expression and DNA copy number in sensitive compared with resistant triple-negative breast cancers in two independent neoadjuvant cisplatin-treated cohorts. Functional relevance of significant hits was investigated in vitro by overexpression, knockdown and targeted inhibitor treatment. Results
We identified two genes, the Bloom helicase (BLM) and Fanconi anemia complementation group I (FANCI), that have both increased DNA copy number and gene expression in the platinum-sensitive cases. Increased level of expression of these two genes was also associated with platinum but not with taxane response in ovarian cancer. As a functional validation, we found that overexpression of BLM promotes DNA damage and induces sensitivity to cisplatin but has no effect on paclitaxel sensitivity. Conclusions
A biomarker based on the expression levels of the BLM and FANCI genes is a potential predictor of platinum sensitivity in triple-negative breast cancer and ovarian cancer.https://ift.tt/2rR6WUa
Beyond second-line therapy in patients with metastatic colorectal cancer: a systematic review
Abstract
Background
The optimal chemotherapeutic regimen for use beyond the second line for patients with metastatic colorectal cancer (mCRC) remains unclear. Materials and methods
We systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the efficacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC. Studies were assessed for design and quality, and a qualitative data synthesis was conducted to understand the impact of treatment on overall survival and other relevant cancer-related outcomes. Results
The search yielded 938 references of which 68 were included for qualitative synthesis. There was limited evidence to support rechallenge with chemotherapy, targeted therapy or both. Compared with placebo, an overall survival benefit for trifluridine/tipiracil (also known as TAS-102) or regorafenib has been shown for patients previously treated with conventional chemotherapy and targeted therapy. There was no evidence to suggest a difference in efficacy between these treatments. Patient choice and quality of life at this stage of treatment should also be considered when choosing an appropriate therapy. Conclusions
These findings support the introduction of an approved agent such as trifluridine/tipiracil or regorafenib beyond the second line before any rechallenge in patients with mCRC who have failed second-line treatment.https://ift.tt/2k5IPxn
Predictive biomarkers and EGFR inhibitors in squamous cell carcinoma of head and neck (SCCHN)
Squamous cell carcinoma of the head and neck (SCCHN) represents the sixth most common cancer globally and accounts for ∼5% of all cancers [1, 2]. The management of these cancers is complex and requires a multidisciplinary approach with multi-modality treatments but the survival outcome of these patients remain poor [2].
https://ift.tt/2Ipnm17
https://ift.tt/2Ipnm17
Lifestyle factors and risk of sporadic colorectal cancer by microsatellite instability status: a systematic review and meta-analyses
Abstract
Introduction
The association of lifestyle factors with molecular pathological subtypes of colorectal cancer (CRC), such as microsatellite instability (MSI), could provide further knowledge about the colorectal carcinogenic process. The aim of this review was to evaluate possible associations between lifestyle factors and risk of sporadic CRC by MSI status. Methods
PubMed and Web of Science were searched for studies investigating the association between alcohol, body mass index, dietary fiber, hormone replacement therapy (HRT), non-steroidal anti-inflammatory drugs, physical activity, red meat, smoking, or statin use, with MSI-high (MSI-H) and microsatellite stable (MSS) CRC. Meta-analyses were carried out to calculate summary relative risks (sRR). Results
Overall, 31 studies reporting on the association between lifestyle factors and CRC according to MSI status were included in this review. Ever smoking was associated with MSI-H (sRR = 1.62; 95% CI: 1.40–1.88) and MSS/MSI-low CRC (sRR = 1.10; 95% CI: 1.01–1.20), but the association was significantly stronger for MSI-H CRC. The use of HRT was associated with a 20% decrease (sRR = 0.80; 95% CI: 0.73–0.89) in the risk of MSS CRC, but was not associated with MSI-H CRC. An increase in body mass index per 5 kg/m2 was equally associated with MSS and MSI-H CRC (sRR = 1.22, in both cases), but was statistically significant for MSS CRC only (95% CI: 1.11–1.34 and 0.94–1.58, respectively). Limited evidence for associations between other lifestyle factors and CRC by MSI status exists. Conclusions
Lifestyle factors, such as HRT and smoking are differentially associated with the risk of MSI-H and MSS CRC. Further research on associations of lifestyle factors and CRC subtypes is necessary to provide a better understanding of the CRC disease pathway.https://ift.tt/2k6YHQw
Management of metastatic retroperitoneal sarcoma: a consensus approach from the Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG)†
Abstract
Introduction
Retroperitoneal sarcoma (RPS) is a rare disease accounting for 0.1%–0.2% of all malignancies. Management of RPS is complex and requires multidisciplinary, tailored treatment strategies at all stages, but especially in the context of metastatic or multifocal recurrent disease. Due to the rarity and heterogeneity of this family of diseases, the literature to guide management is limited. Methods
The Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaboration of sarcoma experts from all disciplines convened in an effort to overcome these limitations. The TARPSWG has compiled the available evidence surrounding metastatic and multifocally recurrent RPS along with expert opinion in an iterative process to generate a consensus document regarding the complex management of this disease. The objective of this document is to guide sarcoma specialists from all disciplines in the diagnosis and treatment of multifocal recurrent or metastatic RPS. Results
All aspects of patient assessment, diagnostic processes, local and systemic treatments, and palliation are reviewed in this document, and consensus recommendations provided accordingly. Recommendations were guided by available evidence, in conjunction with expert opinion where evidence was lacking. Conclusions
This consensus document combines the available literature regarding the management of multifocally recurrent or metastastic RPS with the practical expertise of high-volume sarcoma centers from multiple countries. It is designed as a tool for decision making in the complex multidisciplinary management of this condition and is expected to standardize management across centers, thereby ensuring that patients receive the highest quality care.https://ift.tt/2rSK5HJ
Epigenetic modifiers as new immunomodulatory therapies in solid tumours
Abstract
Background
Immune therapies have revolutionized cancer treatment over the last few years by allowing improvements in overall survival. However, the majority of patients is still primary or secondary resistant to such therapies, and enhancing sensitivity to immune therapies is therefore crucial to improve patient outcome. Several recent lines of evidence suggest that epigenetic modifiers have intrinsic immunomodulatory properties, which could be of therapeutic interest. Material and methods
We reviewed preclinical evidence and clinical studies which describe or exploit immunomodulatory properties of epigenetic agents. Experimental approaches, clinical applicability and corresponding ongoing clinical trials are described. Results
Several epigenetic modifiers, such as histone deacetylase inhibitors, DNA methyl transferase inhibitors, bromodomain inhibitors, lysine-specific histone demethylase 1 inhibitors and enhancer of zeste homolog 2 inhibitors, display intrinsic immunomodulatory properties. The latter can be achieved through the action of these drugs either on cancer cells (e.g. presentation and generation of neoantigens, induction of immunogenic cell death, modulation of cytokine secretion), on immune cells (e.g. linage, differentiation, activation status and antitumor capability), or on components of the microenvironment (e.g. regulatory T cells and macrophages). Several promising combinations, notably with immune checkpoint blockers or adoptive T-cell therapy, can be envisioned. Dedicated clinically relevant approaches for patient selection and trial design will be required to optimally develop such combinations. Conclusion
In an era where immune therapies are becoming a treatment backbone in many tumour types, epigenetic modifiers could play a crucial role in modulating tumours' immunogenicity and sensitivity to immune agents. Optimal trial design, including window of opportunity trials, will be key in the success of this approach, and clinical evaluation is ongoing.https://ift.tt/2k6aqPd
Genetic profiling of cell-free DNA from cerebrospinal fluid: opening the barrier to leptomeningeal metastasis in EGFR-mutant NSCLC
Over the past decade, remarkable progress has been made in the management of advanced non-small-cell lung cancer (NSCLC), when tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors have been added to the therapeutic armamentarium. Indeed, dramatic responses to epidermal growth factor receptor (EGFR)-TKIs are observed in patients with NSCLC harbouring activating EGFR driver mutations [1, 2]. Unfortunately, all tumours ultimately develop secondary resistance, half of these due to the acquirement of the gatekeeper EGFR T790M mutation [3]. Fortunately, T790M-induced resistance can now be successfully addressed by use of third-generation EGFR-TKIs that show impressive activity in these patients [4].
https://ift.tt/2rRof7n
https://ift.tt/2rRof7n
Gastrointestinal Endoscopy Editorial Board top 10 topics: advances in GI endoscopy in 2017
GI endoscopy is a rapidly changing, continually evolving discipline. To identify major new advances in 2017, the Editorial Board of Gastrointestinal Endoscopy (GIE) and VideoGIE, publications of the American Society for Gastrointestinal Endoscopy (ASGE) reviewed endoscopy-related original articles published in 10 major journals in addition to GIE. These journals, selected on the basis of impact factor, included medical journals (Annals of Internal Medicine, Journal of the American Medical Association, Lancet, New England Journal of Medicine), gastroenterology journals (American Journal of Gastroenterology, Clinical Gastroenterology and Hepatology, Gastroenterology, Gut, Hepatology), and specific endoscopy journals (Endoscopy, GIE).
https://ift.tt/2wQm9uk
Immunoassay helps limit overdiagnosis of Clostridium difficile infection
The recently published study by Brumbaugh et al1 summarized their retrospective experience with intragastric fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection (CDI) in 42 children (47 FMTs). The authors noted a much lower response rate of FMT in children with inflammatory bowel disease (IBD), 54% (7/13), compared with 94% (16//17) success in otherwise-healthy children.
https://ift.tt/2rKKmxh
Genomic and probiotic characterization of SJP-SNU strain of Pichia kudriavzevii
The yeast strain SJP-SNU was investigated as a probiotic and was characterized with respect to growth temperature, bile salt resistance, hydrogen sulfide reducing activity, intestinal survival ability and chic...
https://ift.tt/2ItsUYF
Using Graphene Liquid Cell Transmission Electron Microscopy to Study in Situ Nanocrystal Etching
Graphene liquid cell electron microscopy can be used to observe nanocrystal dynamics in a liquid environment with greater spatial resolution than other liquid cell electron microscopy techniques. Etching premade nanocrystals and following their shape using graphene liquid cell Transmission Electron Microscopy can yield important mechanistic information about nanoparticle transformations.
https://ift.tt/2wZrXC3
Protocol for the Evaluation of MRI Artifacts Caused by Metal Implants to Assess the Suitability of Implants and the Vulnerability of Pulse Sequences
We describe a standardized method to evaluate magnetic resonance imaging artifacts caused by implants to estimate the suitability of the implants for magnetic resonance imaging and/or the vulnerability of different pulse sequences to metallic artifacts simultaneously.
https://ift.tt/2LbfX3e
Health Research Participation, Opportunity, and Willingness Among Minority and Rural Communities of Arkansas
Clinical and Translational Science, EarlyView.
https://ift.tt/2GsWAPu
The Dantastic Mr Tox & Howard Podcast 5 – Conflicts of Approval
Join Dan (@drusyniak) &howard (@heshiegreshie) as we talk with Dr. Jeanmarie Perrone (@JMPerroneMD) about the FDA and taking on "Big Pain" during her time on the FDA Drug Safety and Risk Management committee. Don't drink the raspberries . . . Brought to you by BrownApron. Stay healthy true believers! Delicious Links: John Oliver and Supplements […]
EMCrit Project by Tox & Hound.
https://ift.tt/2rLyZ7o
Magnet Assisted Composite Manufacturing: A Flexible New Technique for Achieving High Consolidation Pressure in Vacuum Bag/Lay-Up Processes
https://ift.tt/2rOXpxH
5 ways to empower your EMS employees
Create a culture of recognition and invest in the proper equipment to support your EMS personnel
https://ift.tt/2KABHEn
Giving Employees ‘Decoy’ Sanitizer Options Could Improve Hand Hygiene
Introducing a less convenient option for hand sanitizing may actually boost workers' use of hand sanitizer and increase sanitary conditions in the workplace, according to findings in Psychological Science, a journal of the Association for Psychological Science. The findings revealed that employees in a food factory used more of their regular sanitizer and had cleaner hands and workspaces after a "decoy" sanitizer option was offered to them.
"Our research suggests that the decoy effect can be used as a powerful intervention to guide behavior, and that we should add it to the 'nudge' tool kit and test it in other field settings," says psychological scientist Meng Li of the University of Colorado Denver, first author on the study. "This is important, as it opens a door to a whole new set of solutions to real-world problems."
Previous research has provided evidence that the "decoy effect" – when the introduction of an inferior option makes a preexisting option more favorable – can influence individuals' decision making, at least with regard to hypothetical choices. Li and coauthors Yan Sun and Hui Chen of the Chinese Academy of Sciences wanted to know whether the effect would emerge in a meaningful, real-world setting.
"The work started because of an opportunity to conduct field experiments to improve hand hygiene practice in a food factory in China," says Li. "We wanted to test the decoy effect in this setting because it seemed like a very clever and low-cost intervention to implement."
The researchers conducted experiments with a combined total of 163 participants in three different Chinese food factories. Li and colleagues observed participants' hand hygiene behaviors for 20 days without any intervention. Then, they provided employees in the experimental groups — but not the comparison groups — with an inferior hand-sanitizing option and observed participants' hand hygiene behavior for another 20 days.
The employees were routinely supplied with a sanitizer spray bottle as part of their everyday work before the study; although they were supposed to be using it to sanitize their hands and workstations every hour while working with food, factory management reported that compliance with these guidelines was less than optimal.
In one factory, the researchers placed a harder-to-use (decoy) squeeze bottle with hand sanitizer right beside the regular spray bottle on each participant's work table. The squeeze bottle was just as effective as the spray bottle but less convenient to use.
In another factory, participants were notified that they could use a wash basin with a soaking solution as another means of sanitizing their hands; the soaking method was very effective but considerably less convenient than the usual spray bottle.
In the third factory, the researchers gave employees in the experimental group a harder-to-use squeeze bottle next to the regular spray bottle, just as in the first factory; in this case, the comparison group received a second spray bottle identical to the spray bottle they typically used but in a different color, as a way of controlling for the potential influence of an additional, novel item.
Every day, quality control employees measured how much sanitizer the participants used; they also swabbed employees' hands and work tables, a routine procedure in the factories.
The results were clear: The experimental groups in each factory used more hand sanitizer after the decoy method was introduced relative to the comparison groups. In two of the factories, the experimental group kept increasing their use of the original spray sanitizer throughout the 20-day intervention period, whereas the comparison groups did not.
Importantly, the appearance of the decoy sanitizer improved cleanliness. During the baseline period, the "pass" rates on the hand swabs were 70-74% among the experimental groups in the three factories; after the decoy sanitizing method was introduced, the pass rates rose to 92-98% in the experimental group, but did not change in the control group. And the data revealed a similar increase in pass rates for the work table swab tests.
"It was surprising how long the effect of our decoy intervention lasted," says Li. "Incidentally, when we went back to talk to one of the factories, the management team had decided to implement the intervention among all of the workers since they thought it had worked so well."
Li, Sun, and Chen acknowledge that the sample size in each factory was limited, ranging from 40 to 83 participants, but they note that the longitudinal data from each participant provide robust support for a decoy effect.
Drawing from these real-world findings, Li plans to conduct similar field experiments in hospital settings.
"There are many settings where hand hygiene is a critical issue and the stakes of poor hand hygiene practice are very high, and this research is very relevant in these settings. But more importantly, we should start thinking about the decoy effect as a viable tool to nudge other real-world behaviors" she concludes.
This project was partially supported by the National Natural Science Foundation of China (71001098) and the Beijing National Science Foundation (9162017).
All data and materials have been made publicly available via the Open Science Framework. The complete Open Practices Disclosure for this article is available online. This article has received badges for Open Data and Open Materials.
https://ift.tt/2k7pdt1
Automated CT Perfusion Prediction of Large Vessel Acute Stroke from Intracranial Atherosclerotic Disease
Background and Purpose: We have observed that large vessel occlusion acute strokes (LVOS) due to intracranial atherosclerotic disease (ICAD) present with more benign CT perfusion (CTP) profiles, which we presume to potentially represent enhanced collateralization compared to embolic LVOS. We aim to determine if CTP profiles can predict ICAD in LVOS. Methods: Retrospective review of a prospectively collected interventional stroke database from September 2010 to March 2015. Patients with intracranial ICA/MCA-M1/M2 occlusions and CTP were dichotomized into ICAD versus non-ICAD etiologies. Ischemic core (relative cerebral blood flow #x3c; 30%) and hypoperfusion volumes were estimated by automated CTP. Results: A total of 250 patients met the inclusion criteria, comprised of 21 (8%) ICAD and 229 non-ICAD etiologies. Baseline characteristics were similar between groups, except for higher HbA1c levels (p #x3c; 0.01), LDL cholesterol (p #x3c; 0.01), systolic blood pressure (p #x3c; 0.01), and lower rate of atrial fibrillation (p #x3c; 0.01) in ICAD patients. There were no significant differences in volumes of baseline ischemic core (p = 0.54) among groups. ICAD patients had smaller Tmax #x3e; 4 s, Tmax #x3e; 6 s, and Tmax #x3e; 10 s absolute lesions, and a higher ratio of Tmax #x3e; 4 s/Tmax #x3e; 6 s volumes (median 2 [1.6–2.3] vs. 1.6 [1.4–2.0]; p = 0.02). A Tmax #x3e; 4 s/Tmax #x3e; 6 s ratio ≥2 showed specificity = 73%/sensitivity = 52% for ICAD and was observed in 47.6% of ICAD versus 26.1% of non-ICAD patients (p = 0.07). Clinical outcomes were comparable amongst groups. Multivariate logistic regression revealed that Tmax #x3e; 4 s/Tmax #x3e; 6 s ratio ≥2 (OR 3.75, 95% CI 1.05–13.14, p = 0.04), higher LDL cholesterol (OR 1.1, 95% CI 1.01–1.03, p = 0.01), and higher systolic pressure (OR 1.03, 95% CI 1.01–1.04, p = 0.01) were independently associated with ICAD. Conclusion: An automated CTP Tmax #x3e; 4 s/Tmax #x3e; 6 s ratio ≥2 profile was found independently associated with underlying ICAD LVOS.
Intervent Neurol 2018;7:334–340
https://ift.tt/2L7M1F6
Intervent Neurol 2018;7:334–340
https://ift.tt/2L7M1F6
Evaluating the Role of Mitochondrial Function in Cancer-related Fatigue
https://ift.tt/2wQ83ZV
Serum serotonin levels in patients with epileptic seizures
Epilepsia, EarlyView.
https://ift.tt/2k6PZlb
EMCrit Guest Post – The good, the bad, and the ugly of the Joint Statement on REBOA by Zaffer Qasim
@emeddoc on the current state of REBOA and that bad, bad joint agreement:
EMCrit Project by Guest Author.
https://ift.tt/2k3KJ1D
Long-Term Omalizumab Treatment: A Multicenter, Real-Life, 5-Year Trial
Background: Omalizumab has demonstrated therapeutic benefits both in controlled clinical trials and real-life studies. However, research concerning the long-term effects and tolerability of omalizumab is needed. The main objective of this study was to evaluate the effectiveness and tolerability of treatment with omalizumab for up to 5 years. Methods: A multicenter, retrospective, chart-based study was carried out to compare documented exacerbations, hospitalizations, systemic steroid requirement, FEV1, and asthma control test (ACT) results during 1 year prior to omalizumab treatment versus at 1, 3, and 5 years of treatment. Adverse events and reasons for discontinuation were also recorded at each time point. Results: Four hundred and sixty-five patients were enrolled in the study. Outcome variables had improved after the 1st year and were sustained after the 3rd and 5th years of treatment with omalizumab. Omalizumab treatment reduced the asthma exacerbation rate by 71.3% (p #x3c; 0.001) at 1 year, 64.3% (p #x3c; 0.001) at 3 years, and 54.8% (p = 0.002) at 5 years. The hospitalization rate also decreased; by the 5th year of the treatment no patients were hospitalized. ACT results had also improved significantly: 12 (p #x3c; 0.001) at 1 year, 12 (p #x3c; 0.001) at 3 years, and 12 (p = 0.002) at 5 years. Overall, 12.7% of patients reported adverse events (most of these were mild-to-moderate) and the overall dropout rate was 9.0%. Conclusion: Omalizumab had a significant effect on asthma outcomes and this effect was maintained over 5 years. The drug was found to be generally safe and treatment compliance was good.
Int Arch Allergy Immunol
https://ift.tt/2rVUSBd
Int Arch Allergy Immunol
https://ift.tt/2rVUSBd
High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping
Organoids derived from human iPSCs have great potential for drug screening, but their complexity poses a challenge for miniaturization and automation. Freedman and colleagues establish a robotic pipeline to manufacture and analyze kidney organoids in microwell arrays. They apply this system to improve differentiation, measure toxicity, and comprehend disease.
https://ift.tt/2Iq9bce
Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium
Winton and colleagues describe stem cell dynamics in normal human colon to identify the efficiency of clone fixation within the epithelium and the rate of subsequent lateral expansion. Against these benchmarks biased stem cell behaviors advantaged in both fixation and expansion can be quantified to predict the age-related burden of pro-oncogenic mutation.
https://ift.tt/2GorHvH
Epithelial Sodium Channel Regulates Adult Neural Stem Cell Proliferation in a Flow-Dependent Manner
Stem cells need to adapt to signals from the environment to regulate their output. Here, we show the key role of a flow-sensitive ion channel in regulating the activation of adult neural stem cells and their output.
https://ift.tt/2Iq8UpI
Sporulation environment influences spore properties in Bacillus: evidence and insights on underlying molecular and physiological mechanisms
Abstract
Bacterial spores are resistant to physical and chemical insults, which make them a major concern for public health and for industry. Spores help bacteria to survive extreme environmental conditions that vegetative cells cannot tolerate. Spore resistance and dormancy are important properties for applications in medicine, veterinary health, food safety, crop protection, and other domains. The resistance of bacterial spores results from a protective multilayered structure and from the unique composition of the spore core. The mechanisms of sporulation and germination, the first stage after breaking of dormancy, and organization of spore structure have been extensively studied in Bacillus species. This review aims to illustrate how far the structure, composition and properties of spores are shaped by the environmental conditions in which spores form. We look at the physiological and molecular mechanisms underpinning how sporulation media and environment deeply affect spore yield, spore properties like resistance to wet heat and physical and chemical agents, germination, and further growth. For example, spore core water content decreases as sporulation temperature increases, and resistance to wet heat increases. Controlling the fate of Bacillus spores is pivotal to controlling bacterial risks and process efficiencies in, for example, the food industry, and better control hinges on better understanding how sporulation conditions influence spore properties.https://ift.tt/2Io1mng
Phase I study of oncolytic vaccinia virus GL-ONC1 in patients with peritoneal carcinomatosis
Objective: Peritoneal carcinomatosis (PC) is common in advanced tumor stages or disease recurrence arising from gastrointestinal cancers, gynecologic malignancies, or primary peritoneal carcinoma. Since current therapies are mostly ineffective, new therapeutic approaches are needed. Here, we report on a phase I study designed to assess safety, MTD, and anti-tumor activity of intraperitoneal (i.p.) administration of oncolytic vaccinia virus GL-ONC1 in advanced stage PC patients. Design: GL-ONC1 was administered i.p. every four weeks for up to four cycles at three different dose levels (107-109 pfu) following a standard 3 + 3 dose escalation design. GL-ONC1 was infused via an indwelling catheter which enabled repetitive analyses of peritoneal fluid biopsies. The primary study objective was safety of GL-ONC1 according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4.0). Results: Patients with advanced stage PC (n=7) or advanced peritoneal mesothelioma (n=2) received 24 doses of GL-ONC1. Adverse events were limited to grades 1-3, including transient flu-like symptoms and increased abdominal pain, resulting from treatment-induced peritonitis. No DLT was reported and the MTD was not reached. Furthermore, no signs of viral shedding were observed. Importantly, in eight out of nine study patients effective i.p. infections, in-patient replication of GL-ONC1, as well as subsequent oncolysis were demonstrated in cycle 1. All patients developed neutralizing activities against GL-ONC1. Conclusions: GL-ONC1 was well tolerated when administered into the peritoneal cavity of patients with advanced stage PC. Efficient tumor cell infection, in-patient virus replication as well as oncolysis were limited to treatment cycle 1. (ClinicalTrials.gov number, NCT01443260)
https://ift.tt/2IsWM7d
Project-based learning methodology in the area of microbiology applied to undergraduate medical research
Abstract
In the recent years, there has been a decrease in the number of medical professionals dedicated to a research career. There is evidence that students with a research experience during their training acquire knowledge and skills that increase the probability of getting involved in research more successfully. In the Degree of Medicine (University of the Basque Country) the annual core subject 'Research Project' introduces students to research. The aim of this work was to implement a project-based learning methodology, with the students working on microbiology, and to analyse its result along time. Given an initial scenario, the students had to come up with a research idea related to medical microbiology and to carry out a research project, including writing a funding proposal, developing the experimental assays, and analyzing and presenting their results to a congress organized by the University. Summative assessment was performed by both students and teachers. A satisfaction survey was carried out to gather the students' opinion. The overall results regarding to the classroom dynamics, learning results and motivation after the implementation were favourable. Students referred a greater interest about research than they had before. They would choose the project based methodology versus the traditional one.https://ift.tt/2k9vJQ1
Conformational plasticity of molecular chaperones involved in periplasmic and outer membrane protein folding
Abstract
How proteins reach their native conformation and location has been a major question of biology during the last 50 years. To counterbalance protein misfolding and the accumulation of aggregation products, a complex network of chaperones and proteases takes care of protein quality control in the cell. Such a chaperone network is in place in the periplasm of Gram-negative bacteria, where it is necessary for the survival of the bacteria as well as for outer membrane biogenesis. First mechanistic insights into the periplasmic chaperones that comprise this system came from crystal structures of their apo-states. While these crystal structures represent stable conformations of the proteins, they typically lack the information to understand the conformational changes that regulate the functional cycle as well as the mechanisms coordinating the dynamic adaptation of the chaperones to client proteins. During the past few years, the main actors of periplasmic and outer membrane protein folding have been extensively studied by a combination of experimental techniques. This review aims to give an overview of how recent structural biology developments have helped to achieve a better understanding of the functional cycles of the molecular chaperones Skp, SurA and BamA and how these cycles are regulated by dynamic conformational rearrangements.https://ift.tt/2rO6OVx
Deletion of PBP1a/LpoA complex compromises cell envelope integrity in Shewanella oneidensis
Abstract
High molecular weight penicillin binding proteins (PBPs) are responsible for the biosynthesis of peptidoglycan. In Escherichia coli, PBP1a and PBP1b form multienzyme peptidoglycan-synthesizing complexes with outer-membrane lipoproteins LpoA and LpoB, respectively. The two complexes appear to be largely redundant, although their distinct physiological roles remain unclear. PBP1a/LpoA and PBP1b/LpoB also exist in Shewanella oneidensis strain MR-1, but effects of the two complexes on aerobic growth and β-lactam resistance are quite different. In this study, the phenotypes of strains lacking a certain complex in S. oneidensis were compared. Deletion of PBP1a/LpoA caused aberrant cell morphology (including branches and bulges), enhanced sensitivity to various envelope stresses and outer membrane permeability. On the contrary, strains lacking PBP1b/LpoB displayed phenotypes similar to the wild type.https://ift.tt/2k6lgo4
Sucrose challenges to Streptococcus mutans biofilms and the curve fitting for the biofilm changes
Abstract
The relationship between sugar level and development of dental caries has long been a main topic in dentistry. However, as a ubiquitous component of the modern diet, sucrose is mainly derived from three meals a day, rather than a long time exposure. In this study, various concentrations of sucrose were provided to Streptococcus mutans biofilms for 1h per exposure (3 times per day) to imitate a human meal pattern. And then the relationship between sucrose concentration and changes in the treated biofilms was determined. The results indicated that the components and acid production of the treated biofilms changed in a second-order polynomial curve pattern with sucrose concentration increase, which were confirmed by CLSM and SEM analyses. However, gene expression related to EPS formation, acid production and tolerance was up-regulated with sucrose concentration increase, which might have been due to compensation for the decrease in EPS formation and acid production by the biofilms at higher concentrations of sucrose. These findings suggest that sucrose in the range of 1–5% can support the highest acid production and accumulation of S. mutans biofilms, which may further increase its cariogenic potential. However, additional studies are required to confirm the relationships in human cariogenic biofilms.https://ift.tt/2rOTqBi
Bacterial biofilm formation on the hyphae of ectomycorrhizal fungi: a widespread ability under controls?
Abstract
Ectomycorrhizal (ECM) fungi establish symbiosis with roots of most trees of boreal and temperate ecosystems and are major drivers of nutrient fluxes between trees and the soil. ECM fungi constantly interact with bacteria all along their life cycle and the extended networks of hyphae provide a habitat for complex bacterial communities. Despite the important effects these bacteria can have on the growth and activities of ECM fungi, little is known about the mechanisms by which these microorganisms interact. Here we investigated the ability of bacteria to form biofilm on the hyphae of the ECM fungus Laccaria bicolor. We showed that the ability to form biofilms on the hyphae of the ECM fungus is widely shared among soil bacteria. Conversely, some fungi, belonging to the Ascomycete class, did not allow for the formation of bacterial biofilms on their surfaces. The formation of biofilms was also modulated by the presence of tree roots and ectomycorrhizae, suggesting that biofilm formation does not occur randomly in soil but that it is regulated by several biotic factors. In addition, our study demonstrated that the formation of bacterial biofilm on fungal hyphae relies on the production of networks of filaments made of extracellular DNA.https://ift.tt/2rQ59yt
Erratum Regarding “Bidirectional Association of Retinal Vessel Diameters and Estimated GFR Decline: The Beaver Dam CKD Study” (Am J Kidney Dis. 2011;57[5]:682-691)
Regarding the Original Investigation entitled "Bidirectional Association of Retinal Vessel Diameters and Estimated GFR Decline: The Beaver Dam CKD Study" that appeared in the May 2011 issue of AJKD (Sabanayagam et al, volume 57, issue 5, pages 682-691), based on information received by the AJKD editorial office, there is ambiguity about the credentials for the corresponding author, Anoop Shankar. In the absence of requested updated information from this author regarding his correct credentials, his name as corresponding author should be changed to "Anoop Shankar" (no degrees).
https://ift.tt/2wPnvFQ
Complete Response for More than 4 Years following Neoadjuvant FOLFOX and Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for a Patient with Advanced Gastric Cancer with Extensive Peritoneal Carcinomatosis
Background: Peritoneal carcinomatosis is usually a terminal disease with short median survival in patients with gastric cancer. Systemic FOLFOX is one of the most used regimens in the first-line treatment of metastatic gastric cancer. However, there is scarce evidence that cytoreductive surgery (CRS) and intraperitoneal heated chemotherapy (HIPEC) improves oncological outcomes of patients with advanced gastric cancer. Methods: Herein we present a case of a young woman with advanced gastric cancer with omental and peritoneal metastases who achieved an excellent response after 6 months of FOLFOX followed by CRS and HIPEC. Results: A 53-year-old woman was diagnosed with advanced gastric carcinoma, with extensive omental caking and several peritoneal implants measuring 2 cm at the largest diameter. The patient received mFOLFOX6 for 6 months with excellent clinical and radiographic response. She was then submitted to a D2 total gastrectomy followed by CRS and HIPEC with mitomycin. The final pathology report showed a focal adenocarcinoma in the stomach measuring 0.4 mm with no residual tumor in the peritoneum (ypT1ypN0). The patient has been well and disease free for more than 4 years. Conclusion: While still controversial, CRS followed by HIPEC may be a curative therapeutic option for highly selected patients.
Case Rep Oncol 2018;11:305–310
https://ift.tt/2L6hh7s
Case Rep Oncol 2018;11:305–310
https://ift.tt/2L6hh7s
Malignant Transformation of Nodular Hidradenoma in the Lower Leg
Nodular hidradenoma (NH) is a benign adnexal tumor that arises from either eccrine or apocrine sweat glands. NH can originate from any cutaneous site, but the most common sites are the head and anterior surface of the trunk, with very rare cases in the extremities. Long-standing NH has been reported to undergo malignant transformation to malignant NH (MNH); however, its occurrence in the lower leg is extremely rare with only one other case reported to date. In this report, we present a rare case of MNH occurring in the lower leg which was resected with the intent to make a diagnosis. At the final follow-up after 11 months, no local recurrence or metastasis has been observed.
Case Rep Oncol 2018;11:298–304
https://ift.tt/2KzmaVv
Integrated Diagnostic Model That Incorporates Epstein-Barr Virus DNA, Imaging, and Nasal Endoscopy to Stratify Primary Tumor and Lymph Nodes in a Patient with N1 Nasopharyngeal Carcinoma: Multidisciplinary Management
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, with a high metastatic potential. Epstein-Barr virus (EBV) infection plays a fundamental role, even if it is not well understood. The diagnosis of the disease in its early stage is infrequent. Imaging studies, positron emission tomography scans in addition to clinical examination, endoscopic examination, and biopsy provide information on the extent of the disease. The application of neoadjuvant chemotherapy followed by concomitant chemoradiation can improve the control of NPC. In March 2016, a 54-year-old male with NPC cT1 cN2 cM0, stage III (8th edition of American Joint Committee on Cancer (AJCC) staging system) underwent to a two-step treatment: induction chemotherapy by TPF regimen (docetaxel, cisplatin, 5-fluorouracil), followed by concomitant chemoradiotherapy (weekly cisplatin). The quantity of free plasma EBV-DNA can be related to the disease stage, and the detection of EBV-DNA during follow-up can be predictive of distant metastases. Especially, either plasma or serum EBV-DNA titer is estimated to reflect tumor volume. Biologically, such EBV-DNA reflects reproduced or released DNA from dead or dying tumor cells. On the other hand, EBV-specific DNA released as exosome may reflect the biological feature of the alive NPC tumor cell. The follow-up is ongoing after 21 months from a complete response.
Case Rep Oncol 2018;11:289–297
https://ift.tt/2L6gWlc
What are the boundaries of unconscious semantic cognition?
European Journal of Neuroscience, EarlyView.
https://ift.tt/2wO2pYa
Imagery ability: the individual difference gradient and novel training methods (Commentary on Kraeutner et al. (2018))
European Journal of Neuroscience, EarlyView.
https://ift.tt/2IN6xfW
Cholinergic mechanisms in adaptive behaviour
European Journal of Neuroscience, EarlyView.
https://ift.tt/2wOlrxJ
Effectiveness and Safety of Peritoneal Dialysis Treatment in Patients with Refractory Congestive Heart Failure due to Chronic Cardiorenal Syndrome
Aims. To evaluate the effectiveness and safety of peritoneal dialysis (PD) in treating refractory congestive heart failure (RCHF) with cardiorenal syndrome (CRS). Methods. A total of 36 patients with RCHF were divided into type 2 CRS group (group A) and non-type 2 CRS group (group B) according to the patients' clinical presentations and the ratio of serum urea to creatinine and urinary analyses in this prospective study. All patients were followed up till death or discontinuation of PD. Data were collected for analysis, including patient survival time on PD, technique failure, changes of heart function, and complications associated with PD treatment and hospitalization. Results. There were 27 deaths and 9 patients quitting PD program after a follow-up for 73 months with an average PD time of months. A significant longer PD time was found in group B as compared with that in group A ( versus months, ). Kaplan–Meier curves showed a higher survival probability in group B than that in group A (). Multivariate regression demonstrated that type 2 CRS was an independent risk factor for short survival time on PD. The benefit of PD on the improvement of survival and LVEF was limited to group B patients, but absent from group A patients. The impairment of exercise tolerance indicated by NYHA classification was markedly improved by PD for both groups. The technique survival was high, and the hospital readmission was evidently decreased for both group A and group B patients. Conclusions. Our data suggest that PD is a safe and feasible palliative treatment for RCHF with type 2 CRS, though the long-term survival could not be expected for patients with the type 2 CRS. Registration ID Number is ChiCTR1800015910.
https://ift.tt/2rVld2j
Wiedemann‐Steiner syndrome as a major cause of syndromic intellectual disability: A study of 33 French cases
Clinical Genetics, EarlyView.
https://ift.tt/2k4Zgdh
Supplementation with Alpha-Tocopherol and Ascorbic Acid to Nonalcoholic Fatty Liver Disease’s Statin Therapy in Men
Oxidative stress and inflammation contribute to the pathogenesis and progression of nonalcoholic fatty liver disease (NAFLD), and the control of lipid status by statins may help to stop the progression of NAFLD. We hypothesized that the addition of antioxidant vitamins C and E to atorvastatin therapy is associated with improved serum enzyme antioxidant status. NAFLD-related serum parameters and the activity of antioxidant enzymes, before and after 3 months of treatment, were determined in patients receiving atorvastatin alone or atorvastatin plus antioxidants. Compared to healthy controls, the patients, before receiving therapy, had increased catalase and glutathione reductase, with no significant difference in glutathione peroxidase activity. After the treatment, the levels of all three antioxidant markers were reduced to the same degree in both groups of patients, indicating therapy-induced lower level of reactive oxygen species production and/or improved nonenzymatic antioxidant mechanisms. Both therapies led to the normalization of the serum lipid profile and aminotransferase levels in the patients, but the reduction in CRP, although significant, did not reduce levels to those of the controls. The obtained results favor the notion that therapy with atorvastatin alone is equally efficient during the early stages of NAFLD, regardless of the addition of antioxidant vitamins. This trial is registered with TCTR20180425001.
https://ift.tt/2Ir5I93
Evaluation of dental implant stability in bone phantoms: Comparison between a quantitative ultrasound technique and resonance frequency analysis
Clinical Implant Dentistry and Related Research, EarlyView.
https://ift.tt/2L3Eyad
Ten years of the Surgical Safety Checklist
British Journal of Surgery, EarlyView.
https://ift.tt/2Gqhn6t
Clinical Drug–Drug Interaction Potential of BFE1224, Prodrug of Antifungal Ravuconazole, Using Two Types of Cocktails in Healthy Subjects
Clinical and Translational Science, EarlyView.
https://ift.tt/2rN5e6Y
Innovation at the Intersection of Clinical Trials and Real‐World Data Science to Advance Patient Care
Clinical and Translational Science, EarlyView.
https://ift.tt/2rOkpMw
Editorial: grey zone, a new area of interest in chronic hepatitis B
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1547-1548, June 2018.
https://ift.tt/2IvXkW8
Editorial: let's take a break from studying the PPI‐fracture association
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1543-1544, June 2018.
https://ift.tt/2IuWw3H
Editorial: retreatment of DAA‐failures—no problem at all?
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1552-1553, June 2018.
https://ift.tt/2rOamHY
Editorial: let's take a break from studying the PPI‐fracture association—Authors’ reply
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1544-1545, June 2018.
https://ift.tt/2IsKkR0
Editorial: platelet transfusions in cirrhosis—do the risks outweigh the unclear benefits?
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1553-1554, June 2018.
https://ift.tt/2rQHezV
Editorial: the durability of seroconversion of hepatitis B e antigen in the treatment of chronic hepatitis B with PEG‐interferon alfa‐2a
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1556-1557, June 2018.
https://ift.tt/2Iq5Q8S
Issue Information
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1425-1427, June 2018.
https://ift.tt/2rQH2AH
Editorial: de novo inflammatory bowel disease following bariatric surgery—potential implications for research and clinical practice. Authors’ reply
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1540-1540, June 2018.
https://ift.tt/2IqeeVL
Letter: tacrolimus may be hazardous in decompensated autoimmune liver disease with hyperbilirubinemia—authors’ reply
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1568-1569, June 2018.
https://ift.tt/2IPf7uy
Letter: adoption of uniform nomenclature is crucial for estimating the true risk of HBV reactivation in patients treated with direct‐acting antivirals for hepatitis C
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1573-1574, June 2018.
https://ift.tt/2rO31YX
Editorial: measuring hypervigilance and anxiety in oesophageal disorders
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1559-1560, June 2018.
https://ift.tt/2ItyBBC
Letter: improvements in mental health after faecal microbiota transplantation—an underexplored treatment‐related benefit?
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1562-1563, June 2018.
https://ift.tt/2rN4NJI
Editorial: platelet transfusions in cirrhosis—do the risks outweigh the unclear benefits? Authors’ reply
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1555-1556, June 2018.
https://ift.tt/2Iw3rcE
Letter: concordance of SVR4 and SVR12 following direct‐acting anti‐viral treatment in Egypt
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1564-1566, June 2018.
https://ift.tt/2INSbf6
Editorial: gastrointestinal safety of COX‐2 selective and nonselective NSAIDs—the impact of the PRECISION trial
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 11, Page 1545-1546, June 2018.
https://ift.tt/2Iq5K10
Testing a longitudinal compensation model in premanifest Huntington’s disease
Abstract
The initial stages of neurodegeneration are commonly marked by normal levels of cognitive and motor performance despite the presence of structural brain pathology. Compensation is widely assumed to account for this preserved behaviour, but despite the apparent simplicity of such a concept, it has proven incredibly difficult to demonstrate such a phenomenon and distinguish it from disease-related pathology. Recently, we developed a model of compensation whereby brain activation, behaviour and pathology, components key to understanding compensation, have specific longitudinal trajectories over three phases of progression. Here, we empirically validate our explicit mathematical model by testing for the presence of compensation over time in neurodegeneration. Huntington's disease is an ideal model for examining longitudinal compensation in neurodegeneration as it is both monogenic and fully penetrant, so disease progression and potential compensation can be monitored many years prior to diagnosis. We defined our conditions for compensation as non-linear longitudinal trajectories of brain activity and performance in the presence of linear neuronal degeneration and applied our model of compensation to a large longitudinal cohort of premanifest and early-stage Huntington's disease patients from the multisite Track-On HD study. Focusing on cognitive and motor networks, we integrated progressive volume loss, task and resting state functional MRI and cognitive and motor behaviour across three sequential phases of neurodegenerative disease progression, adjusted for genetic disease load. Multivariate linear mixed models were fitted and trajectories for each variable tested. Our conceptualization of compensation was partially realized across certain motor and cognitive networks at differing levels. We found several significant network trends that were more complex than that hypothesized in our model. These trends suggest changes to our theoretical model where the network effects are delayed relative to performance effects. There was evidence of compensation primarily in the prefrontal component of the cognitive network, with increased effective connectivity between the left and right dorsolateral prefrontal cortex. Having developed an operational model for the explicit testing of longitudinal compensation in neurodegeneration, it appears that general patterns of our framework are consistent with the empirical data. With the proposed modifications, our operational model of compensation can be used to test for both cross-sectional and longitudinal compensation in neurodegenerative disease with similar patterns to Huntington's disease.https://ift.tt/2rR0BIf
Topology optimization of fusiform muscles with a maximum contraction
International Journal for Numerical Methods in Biomedical Engineering, EarlyView.
https://ift.tt/2KwVVPH
Emotional Availability, Neuropsychological Functioning, and Psychopathology: The Context of Parental Substance Use Disorder
Parental Substance Use Disorder (SUD) constitutes a high-risk condition for parent-child interactions and child development. Empirical evidence indicates high rates of psychopathology and neuropsychological impairments in individuals with SUD. Despite research indicating that parenting skills are related to psychological well-being and cognitive/neuropsychological functioning, prior studies have not examined the associations between these areas of parental functioning and the quality of parent-child interactions in the context of SUD. Aim(s). The present study adopts an integrated perspective to investigate the way in which maternal neuropsychological functioning and psychopathology are associated with mother-child emotional availability (EA), in the context of parental Substance Use Disorder. Methods. Twenty-nine mothers with SUD were assessed in interaction with their children, as well as with respect to their neuropsychological functioning and psychopathology. Results. In this group, high rates of maternal neuropsychological impairments and psychopathology, as well as generally low levels of EA, were uncovered. Regression analyses showed that maternal neuropsychological functioning was significantly associated with mother-child EA, specifically sensitivity; the role of maternal psychopathology, however, was only marginally significant. Conclusion. In the context of SUD, maternal neuropsychological impairments are significantly associated with mother-child EA. Clinical implications of the findings are discussed.
https://ift.tt/2IMplvP
Prospective analysis of different combined regimens of stereotactic body radiation therapy and chemotherapy for locally advanced pancreatic cancer
Cancer Medicine, EarlyView.
https://ift.tt/2rNywlb
Regenerative surgical therapy for peri‐implantitis using deproteinized bovine bone mineral with 10% collagen, enamel matrix derivative and Doxycycline—A prospective 3‐year cohort study
Clinical Oral Implants Research, EarlyView.
https://ift.tt/2IpXRIW
Food preservation by Larrea divaricata extract: participation of polyphenols
Food Science &Nutrition, EarlyView.
https://ift.tt/2Ilz0tM
The battle over indoor tanning heats up
Cancer Cytopathology, Volume 126, Issue 5, Page 297-298, May 2018.
https://ift.tt/2k3h3BH
Issue Information
Cancer Cytopathology, Volume 126, Issue 5, Page 291-296, May 2018.
https://ift.tt/2rQPDCJ
How does dementia with Lewy bodies start? prodromal cognitive changes in REM sleep behavior disorder
Annals of Neurology, EarlyView.
https://ift.tt/2L84txt
Somatic SLC35A2 variants in the brain are associated with intractable neocortical epilepsy
Annals of Neurology, EarlyView.
https://ift.tt/2Kxiio1
Continuous electroencephalography predicts delayed cerebral ischemia after subarachnoid hemorrhage: A prospective study of diagnostic accuracy
Annals of Neurology, EarlyView.
https://ift.tt/2L9KG0n
T cell‐derived IFN‐γ downregulates protective group 2 innate lymphoid cells in murine lupus erythematosus
European Journal of Immunology, EarlyView.
https://ift.tt/2L82Lfm
Engulfment of Hb‐activated platelets differentiates monocytes into pro‐inflammatory macrophages in PNH patients
European Journal of Immunology, EarlyView.
https://ift.tt/2KtQnp6
Front cover story: Eur. J. Immunol. 5'18
European Journal of Immunology, Volume 48, Issue 5, May 2018.
https://ift.tt/2Kz9FcL
In this issue
European Journal of Immunology, Volume 48, Issue 5, Page 729-731, May 2018.
https://ift.tt/2wOYTNh
Journal roundup
European Journal of Immunology, Volume 48, Issue 5, Page 731-731, May 2018.
https://ift.tt/2L7axpK
Impressum
European Journal of Immunology, Volume 48, Issue 5, Page 888-888, May 2018.
https://ift.tt/2Kz9j5V
Editorial Board: Eur. J. Immunol. 5'18
European Journal of Immunology, Volume 48, Issue 5, May 2018.
https://ift.tt/2L9M6YY
EFIS is welcoming Immunologists to build even more bridges in Amsterdam
European Journal of Immunology, Volume 48, Issue 5, Page 732-735, May 2018.
https://ift.tt/2KvujtZ
Bruno Kyewski (1950‐2018)
European Journal of Immunology, Volume 48, Issue 5, Page 736-737, May 2018.
https://ift.tt/2L9LVgg
Inside cover story: Eur. J. Immunol. 5'18
European Journal of Immunology, Volume 48, Issue 5, May 2018.
https://ift.tt/2wPPKUD
Contents: Eur. J. Immunol. 5'18
European Journal of Immunology, Volume 48, Issue 5, Page 725-728, May 2018.
https://ift.tt/2L9BOIs
An optimized method to measure human FOXP3+ regulatory T cells from multiple tissue types using mass cytometry
European Journal of Immunology, EarlyView.
https://ift.tt/2KyX9Ki
Value of additional endoscopic ultrasonography for surveillance after surgical removal of intraductal papillary mucinous neoplasms
Digestive Endoscopy, EarlyView.
https://ift.tt/2L78EcZ
Umbilical resection during laparoscopic surgery for urachal remnants
Asian Journal of Endoscopic Surgery, EarlyView.
https://ift.tt/2IlwpQy
Primary lumbar hernia: A rare case report and a review of the literature
Asian Journal of Endoscopic Surgery, EarlyView.
https://ift.tt/2rRdlOW
Primary tumor sidedness is an independent prognostic marker for survival in metastatic colorectal cancer: Results from a large retrospective cohort with mutational analysis
Cancer Medicine, EarlyView.
https://ift.tt/2Iryvuc
Serum SP70 is a sensitive predictor of chemotherapy response in patients with advanced nonsmall cell lung cancer
Cancer Medicine, EarlyView.
https://ift.tt/2rNIjZc
Prognosis of patients with hepatocellular carcinoma treated with sorafenib: a comparison of five models in a large Canadian database
Cancer Medicine, EarlyView.
https://ift.tt/2It3rKP
Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco‐induced lung cancer
Cancer Medicine, EarlyView.
https://ift.tt/2rMD7F8
Rituximab maintenance therapy of follicular lymphoma in clinical practice
Cancer Medicine, EarlyView.
https://ift.tt/2IsLJHh
The combination of a sphingosine kinase 2 inhibitor (ABC294640) and a Bcl‐2 inhibitor (ABT‐199) displays synergistic anti‐myeloma effects in myeloma cells without a t(11;14) translocation
Cancer Medicine, EarlyView.
https://ift.tt/2IMJSQU
FM19G11 inhibits O6‐methylguanine DNA‐methyltransferase expression under both hypoxic and normoxic conditions
Cancer Medicine, EarlyView.
https://ift.tt/2IriaWl
Arsenic Trioxide–Coated Stent Is an Endothelium‐Friendly Drug Eluting Stent
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2ImTAKt
Ampli: A Construction Set for Paperfluidic Systems
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2wORaif
Poly(β‐amino ester)‐co‐poly(caprolactone) Terpolymers as Nonviral Vectors for mRNA Delivery In Vitro and In Vivo
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2IhsX9F
Endometrial cancer—how many patients could benefit from sentinel lymph node dissection?
Abstract
Background
Sentinel lymph node dissection (SLND) may reduce morbidity in patients with endometrial cancer. The objective of this study is to estimate how many systematic lymph node dissections (LND) can be spared with an implementation of a SLN-procedure.
Methods
Retrospective, single-center study, SLND according to NCCN-Guidelines.
Results
In 109 patients of 154 consecutive patients, SLND was performed. The detection rate was 61% on both sides and 86% on at least one side. Classification of uterine risk factors is as follows: low risk 53, intermediate risk 25, high-intermediate risk 13, and high-risk 18. Stage IIIC: 0, 3, 7, 11, respectively. Under the assumption that 56 patients with "higher than low risk" factors would be treated by systematic LND, we spared 26 pelvic and paraaortic LND. After failures of SLN detection, unilateral pelvic LND was performed in 15 patients. Patients with "higher than low risk" factors and node-negative SLN are candidates for a randomized study to prove safety and efficacy. Only every third patient in our study met these criteria.
Conclusions
In a cohort of patients with "higher than low risk" endometrial cancer, the implementation of SLND nearly divided the number of radical lymph node dissections in half. Further studies are required to define the best modalities for SLND.
https://ift.tt/2k3nqoH
Spectroscopic Studies on the Metal–Insulator Transition Mechanism in Correlated Materials
Advanced Materials, EarlyView.
https://ift.tt/2InWBtW
Cost‐effectiveness of antiviral treatment after resection in hepatitis B virus–related hepatocellular carcinoma patients with compensated cirrhosis
Hepatology, EarlyView.
https://ift.tt/2KyDCtf
Flatlands in the Holy Land: The Evolution of Layered Materials Research in Israel
Advanced Materials, EarlyView.
https://ift.tt/2wNglBI
A 2D Conductive Organic–Inorganic Hybrid with Extraordinary Volumetric Capacitance at Minimal Swelling
Advanced Materials, EarlyView.
https://ift.tt/2IngKAd
Design of a New Fused‐Ring Electron Acceptor with Excellent Compatibility to Wide‐Bandgap Polymer Donors for High‐Performance Organic Photovoltaics
Advanced Materials, EarlyView.
https://ift.tt/2Gt2Zds
Corannulene‐Incorporated AIE Nanodots with Highly Suppressed Nonradiative Decay for Boosted Cancer Phototheranostics In Vivo
Advanced Materials, EarlyView.
https://ift.tt/2GpyvJB
All‐Solution‐Processed Metal‐Oxide‐Free Flexible Organic Solar Cells with Over 10% Efficiency
Advanced Materials, EarlyView.
https://ift.tt/2IMjpTz
From UV to Near‐Infrared Light‐Responsive Metal–Organic Framework Composites: Plasmon and Upconversion Enhanced Photocatalysis
Advanced Materials, EarlyView.
https://ift.tt/2wMsze7
Asymmetrical Ladder‐Type Donor‐Induced Polar Small Molecule Acceptor to Promote Fill Factors Approaching 77% for High‐Performance Nonfullerene Polymer Solar Cells
Advanced Materials, EarlyView.
https://ift.tt/2IPuK5o
Metallic Graphene‐Like VSe2 Ultrathin Nanosheets: Superior Potassium‐Ion Storage and Their Working Mechanism
Advanced Materials, EarlyView.
https://ift.tt/2GqvSHf
Laser‐Induced Molybdenum Carbide–Graphene Composites for 3D Foldable Paper Electronics
Advanced Materials, EarlyView.
https://ift.tt/2wUi88q
Ultrafast Zn2+ Intercalation and Deintercalation in Vanadium Dioxide
Advanced Materials, EarlyView.
https://ift.tt/2IqLqAM
Nanomaterial‐Based Organelles Protect Normal Cells against Chemotherapy‐Induced Cytotoxicity
Advanced Materials, EarlyView.
https://ift.tt/2wOsMNB
Analysis of the Bipolar Resistive Switching Behavior of a Biocompatible Glucose Film for Resistive Random Access Memory
Advanced Materials, EarlyView.
https://ift.tt/2IJ2WQ9
Generalized Access to Mesoporous Inorganic Particles and Hollow Spheres from Multicomponent Polymer Blends
Advanced Materials, EarlyView.
https://ift.tt/2Gqyh4E
Caging Nb2O5 Nanowires in PECVD‐Derived Graphene Capsules toward Bendable Sodium‐Ion Hybrid Supercapacitors
Advanced Materials, EarlyView.
https://ift.tt/2rPQtj1
A “Sticky” Mucin‐Inspired DNA‐Polysaccharide Binder for Silicon and Silicon–Graphite Blended Anodes in Lithium‐Ion Batteries
Advanced Materials, EarlyView.
https://ift.tt/2IHaHGj
Ultrastretchable Conductor Fabricated on Skin‐Like Hydrogel–Elastomer Hybrid Substrates for Skin Electronics
Advanced Materials, EarlyView.
https://ift.tt/2wOn5zz
Increased centrosome number in BRCA‐related breast cancer specimens determined by immunofluorescence analysis
Cancer Science, EarlyView.
https://ift.tt/2ImR9HP
Quantitative T2-Mapping and T2-Mapping Evaluation of Changes in Cartilage Matrix after Acute Anterior Cruciate Ligament Rupture and the Correlation between the Results of Both Methods
Objectives. To quantitatively assess changes in cartilage matrix after acute anterior cruciate ligament (ACL) rupture using T2- and T2⁎-mapping and analyze the correlation between the results of both methods. Methods. Twenty-three patients and 23 healthy controls were enrolled and underwent quantitative MRI examination. The knee cartilage was segmented into six compartments, including lateral femur (LF), lateral tibia (LT), medial femur (MF), medial tibia (MT), trochlea (Tr), and patella (Pa). T2 and T2⁎ values were measured in full-thickness as well as superficial and deep layers of each cartilage compartment. Differences of T2 and T2⁎ values between patients and controls were compared using unpaired Student's -test, and the correlation between their reciprocals was analyzed using Pearson's correlation coefficient. Results. ACL-ruptured patients showed higher T2 and T2⁎ values in full-thickness and superficial layers of medial and lateral tibiofemoral joint. Meanwhile, patients exhibited higher T2⁎ values in deep layers of lateral tibiofemoral joint. The elevated percentages of T2 and T2⁎ value in superficial LT were most significant (20.738%, 17.525%). The reciprocal of T2⁎ value was correlated with that of T2 value (, ). Conclusion. The early degeneration could occur in various knee cartilage compartments after acute ACL rupture, especially in the superficial layer of LT. T2⁎-mapping might be more sensitive in detecting deep layer of cartilage than T2-mapping.
https://ift.tt/2wPs9U3
Hydrogen-Rich Saline Activated Autophagy via HIF-1α Pathways in Neuropathic Pain Model
Background. Neuropathic pain is a chronic and intractable pain, with very few effective analgesics. It involves an impaired cell autophagy process. Hydrogen-rich saline (HRS) reportedly reduces allodynia and hyperalgesia in a neuropathic pain model; however, it is unknown whether these effects involve autophagy induction. Methods. We investigated the relationship between HRS and cell autophagy in a neuropathic pain model generated by chronic constriction injury (CCI) in Sprague–Dawley rats. Rats received an intraperitoneal injection of HRS (10 mL/kg daily, from 1 day before until 14 days after CCI), 3MA (autophagy inhibitor), 2ME2 (HIF-1α inhibitor), or EDHB (HIF-1α agonist). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were tested 1 day before and 1, 3, 7, 10, and 14 days after the operation. HIF-1α and cell autophagy markers in the spinal cord were evaluated by western blotting and real-time PCR assays at 14 days after CCI. Autophagosomes with double membranes were identified by transmission electron microscopy. Results. CCI caused behavioral hypersensitivity to mechanical and thermal stimulation in the hind-paw of the injured side. HRS improved MWT and TWL, activated autophagy, and increased autophagosomes and autolysosomes in CCI rats. 3-MA aggravated hyperalgesia and allodynia and suppressed autophagy, while EDHB attenuated hyperalgesia and activated the autophagy procedure and the HIF-1α downstream target gene BNIP3. HIF-1α inhibitors reversed the regulatory effects of HRS on autophagy in CCI rats at 14 days after spinal cord injury. Conclusion. HRS reduced mechanical hyperalgesia and activation of cell autophagy in neuropathic pain through a HIF1-dependent pathway.
https://ift.tt/2wKY4VW
Pandemic Avian Influenza and Intra/Interhaemagglutinin Subtype Electrostatic Variation among Viruses Isolated from Avian, Mammalian, and Human Hosts
Host jump can result in deadly pandemic events when avian influenza A viruses broaden their host specificity and become able to infect mammals, including humans. Haemagglutinin—the major capsid protein in influenza A viruses—is subjected to high rate mutations, of which several occur at its "head": the receptor-binding domain that mediates specific binding to host cell receptors. Such surface-changing mutations may lead to antigenically novel influenza A viruses hence in pandemics by host jump and in vaccine escape by antigenic drift. Changes in haemagglutinin surface electrostatics have been recently associated with antigenic drift and with clades evolution and spreading in H5N1 and H9N2 viruses. We performed a comparative analysis of haemagglutinin surface electrostatics to investigate clustering and eventual fingerprints among representative pandemic (H5 and H7) and nonpandemic (H4 and H6) avian influenza viral subtypes. We observed preferential sorting of viruses isolated from mammalian/human hosts among these electrostatic clusters of a subtype; however, sorting was not "100% specific" to the different clusters. Therefore, electrostatic fingerprints can help in understanding, but they cannot explain alone the host jumping mechanism.
https://ift.tt/2Ipewwo
Treatment of Leptomeningeal Carcinomatosis in a Patient with Metastatic Pancreatic Cancer: A Case Report and Review of the Literature
Pancreatic cancer is the fourth leading cause of cancer-related death with a median survival of 3–11 months when metastatic. We present a patient with metastatic pancreatic cancer and an exceptional response to initial systemic chemotherapy with FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin). Despite evidence of disease control on body imaging, he developed symptomatic leptomeningeal disease and brain metastases 29 months into treatment. He received aggressive treatment with capecitabine and irinotecan, intrathecal topotecan, and eventually bevacizumab. He did well for 36 weeks on this regimen until developing sepsis. This patient significantly outlived his expected survival and, moreover, did so with very good quality of life. This case demonstrates the natural history of pancreatic cancer progressing to involve the central nervous system when systemic disease is otherwise responsive to chemotherapy. It is the first case to demonstrate the potential effectiveness of intrathecal topotecan in combination with systemic chemotherapy for the treatment of leptomeningeal metastases of pancreatic cancer.
Case Rep Oncol 2018;11:281–288
https://ift.tt/2L8nz6p
Concomitant Radioembolization and Immune Checkpoint Inhibition in Metastatic Renal Cell Carcinoma
This case represents the challenge and creativity necessary when treating patients with metastatic renal cell carcinoma who have been exposed to multiple lines of therapy. At present, treatment with immune checkpoint inhibition has stabilized and improved the metastatic disease of this patient with the exception of hepatic lesions. This isolated progression within the liver led the employment of radioembolization, which successfully treated those metastases. This is the first documented case of metastatic renal cell carcinoma controlled with concurrent use of immune checkpoint inhibition and radioembolization for both extrahepatic and hepatic metastases, respectively. This case can be construed as a potential example of the abscopal effect and may provide the basis for understanding this type of response in select patients.
Case Rep Oncol 2018;11:276–280
https://ift.tt/2wQowxi
HIV Population Surveys — Bringing Precision to the Global Response
https://ift.tt/2Ivg9s8
Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA
New England Journal of Medicine, Ahead of Print.
https://ift.tt/2Gq9VrP
Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source
New England Journal of Medicine, Ahead of Print.
https://ift.tt/2IQ1nju
Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke
New England Journal of Medicine, Ahead of Print.
https://ift.tt/2GsbHbQ
MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset
New England Journal of Medicine, Ahead of Print.
https://ift.tt/2ILSqrm
MRI-Guided Intravenous Alteplase for Stroke — Still Stuck in Time
New England Journal of Medicine, Ahead of Print.
https://ift.tt/2IpJEzE
Antiplatelet Therapy after Ischemic Stroke or TIA
New England Journal of Medicine, Ahead of Print.
https://ift.tt/2wNSB0f
Improving the Supply and Quality of Deceased-Donor Organs for Transplantation
New England Journal of Medicine, Volume 378, Issue 20, Page 1920-1929, May 2018.
https://ift.tt/2ILSc3u
Inhaled Combined Budesonide–Formoterol as Needed in Mild Asthma
New England Journal of Medicine, Volume 378, Issue 20, Page 1865-1876, May 2018.
https://ift.tt/2wNe3mi
As-Needed Budesonide–Formoterol versus Maintenance Budesonide in Mild Asthma
New England Journal of Medicine, Volume 378, Issue 20, Page 1877-1887, May 2018.
https://ift.tt/2ILS440
Raindrop Skull
New England Journal of Medicine, Volume 378, Issue 20, Page 1930-1930, May 2018.
https://ift.tt/2GpC8zb
Initial Treatment of Hypertension
New England Journal of Medicine, Volume 378, Issue 20, Page 1952-1954, May 2018.
https://ift.tt/2wP8WSr
On-Demand versus Maintenance Inhaled Treatment in Mild Asthma
New England Journal of Medicine, Volume 378, Issue 20, Page 1940-1942, May 2018.
https://ift.tt/2ISwmLs
HIV Population Surveys — Bringing Precision to the Global Response
New England Journal of Medicine, Volume 378, Issue 20, Page 1859-1861, May 2018.
https://ift.tt/2wTEzu2
Trametinib in Histiocytic Sarcoma with an Activating MAP2K1 (MEK1) Mutation
New England Journal of Medicine, Volume 378, Issue 20, Page 1945-1947, May 2018.
https://ift.tt/2IqpYvK
Addressing Generic-Drug Market Failures — The Case for Establishing a Nonprofit Manufacturer
New England Journal of Medicine, Volume 378, Issue 20, Page 1857-1859, May 2018.
https://ift.tt/2IQDB6Z
Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes
New England Journal of Medicine, Volume 378, Issue 20, Page 1908-1919, May 2018.
https://ift.tt/2GpNC5M
Leadership Development in Medicine
New England Journal of Medicine, Volume 378, Issue 20, Page 1862-1863, May 2018.
https://ift.tt/2IpE9Bh
Tuberculous Pericarditis
New England Journal of Medicine, Volume 378, Issue 20, May 2018.
https://ift.tt/2wQRL36
Rapid Progression of Adult T-Cell Leukemia–Lymphoma after PD-1 Inhibitor Therapy
New England Journal of Medicine, Volume 378, Issue 20, Page 1947-1948, May 2018.
https://ift.tt/2IsJgRi
Balanced Crystalloids versus Saline in Critically Ill Adults
New England Journal of Medicine, Volume 378, Issue 20, Page 1949-1951, May 2018.
https://ift.tt/2wKHntq
Impact of out-of-hours admission on patient mortality: longitudinal analysis in a tertiary acute hospital
Background
Emergency hospital admission on weekends is associated with an increased risk of mortality. Previous studies have been limited to examining single years and assessing day—not time—of admission. We used an enhanced longitudinal data set to estimate the 'weekend effect' over time and the effect of night-time admission on all-cause mortality rates.
MethodsWe examined 246 350 emergency spells from a large teaching hospital in England between April 2004 and March 2014. Outcomes included 7-day, 30-day and in-hospital mortality rates. We conducted probit regressions to estimate the impact on the absolute difference in the risk of mortality of two key predictors: (1) admission on weekends (19:00 Friday to 06:59 Monday); and (2) night-time admission (19:00 to 06:59). Logistic regressions were used to estimate ORs for relative mortality risk differences.
ResultsCrude 30-day mortality rate decreased from 6.6% in 2004/2005 to 5.2% in 2013/2014. Adjusted mortality risk was elevated for all out-of-hours periods. The highest risk was associated with admission on weekend night-times: 30-day mortality increased by 0.6 percentage points (adjusted OR: 1.17, 95% CI 1.10 to 1.25), 7-day mortality by 0.5 percentage points (adjusted OR: 1.23, 95% CI 1.12 to 1.34) and in-hospital mortality by 0.5 percentage points (adjusted OR: 1.14, 95% CI 1.08 to 1.21) compared with admission on weekday daytimes. Weekend night-time admission was associated with increased mortality risk in 9 out of 10 years, but this was only statistically significant (p<0.05) in 5 out of 10 years.
ConclusionsThere is an increased risk of mortality for patients admitted as emergencies both on weekends and during the night-time. These effects are additive, so that the greatest risk of mortality occurs in patients admitted during the night on weekends. This increased risk appears to be consistent over time, but the effects are small and are not statistically significant in individual hospitals in every year.
https://ift.tt/2k1FIGL
Evaluation of the association between Nursing Home Survey on Patient Safety culture (NHSOPS) measures and catheter-associated urinary tract infections: results of a national collaborative
Background
Recent efforts to reduce patient infection rates emphasise the importance of safety culture. However, little evidence exists linking measures of safety culture and infection rates, in part because of the difficulty of collecting both safety culture and infection data from a large number of nursing homes.
ObjectiveTo examine the association between nursing home safety culture, measured with the Nursing Home Survey on Patient Safety Culture (NHSOPS), and catheter-associated urinary tract infection rates (CAUTI) using data from a recent national collaborative for preventing healthcare-associated infections in nursing homes.
MethodsIn this prospective cohort study of nursing homes, facility staff completed the NHSOPS at intervention start and 11 months later. National Healthcare Safety Network-defined CAUTI rates were collected monthly for 1 year. Negative binomial models examined CAUTI rates as a function of both initial and time-varying facility-aggregated NHSOPS components, adjusted for facility characteristics.
ResultsStaff from 196 participating nursing homes completed the NHSOPS and reported CAUTI rates monthly. Nursing homes saw a 52% reduction in CAUTI rates over the intervention period. Seven of 13 NHSOPS measures saw improvements, with the largest improvements for 'Management Support for Resident Safety' (3.7 percentage point increase in facility-level per cent positive response, on average) and 'Communication Openness' (2.5 percentage points). However, these increases were statistically insignificant, and multivariate models did not find significant association between CAUTI rates and initial or over-time NHSOPS domains.
ConclusionsThis large national collaborative of nursing homes saw declining CAUTI rates as well as improvements in several NHSOPS domains. However, no association was found between initial or over-time NHSOPS scores and CAUTI rates.
https://ift.tt/2k22cYg
Implementation of diagnostic pauses in the ambulatory setting
Background
Diagnostic errors result in preventable morbidity and mortality. The outpatient setting may be at increased risk, where time constraints, the indolent nature of outpatient complaints and single decision-maker practice models predominate.
MethodsWe developed a self-administered diagnostic pause to address diagnostic error. Clinicians (physicians and nurse practitioners) in an academic primary care setting received the tool if they were seeing urgent care patients who had previously been seen in the past two weeks in urgent care. We used pre–post-intervention surveys, focus groups and chart audits 6 months after the urgent care visit to assess the impact of the intervention on participant perceptions and actions.
ResultsWe piloted diagnostic pauses in two phases (3 months and 6 months, respectively); 9 physicians participated in the first phase, and 16 physicians and 2 nurse practitioners in the second phase. Subjects received 135 alerts for diagnostic pauses and responded to 82 (61% response). Thirteen per cent of alerts resulted in clinicians reporting new actions as a result of the diagnostic pauses. Thirteen per cent of cases at a 6-month chart audit resulted in diagnostic discrepancies, defined as differences in diagnosis from the initial working diagnosis. Focus groups reported that the diagnostic pauses were brief and fairly well integrated into the overall workflow for evaluation but would have benefited as a real-time application for patients at higher risk for diagnostic error.
ConclusionThis pilot represents the first known examination of diagnostic pauses in the outpatient setting, and this work potentially paves the way for more broad-based systems and/or electronic interventions to address diagnostic error.
https://ift.tt/2rOTsrP
Pathology of poverty: the need for quality improvement efforts to address social determinants of health
A massive body of literature characterises the impact of poverty on health outcomes. In 1817, Rene Villermé, a young French surgeon (and later economist-cum-social commentator), demonstrated stark differences in life expectancy across Parisian neighbourhoods or arondissements.1 This demonstration of disparities in basic health outcomes across income levels helped configure our early understanding of the 'social determinants of health'. These determinants refer to the conditions in which people are born, grow, live, work and age, including income, housing and education, among others. Even 200 years after Villermé, with so many technological advances both within and outside of healthcare, the unequal distribution of resources across society continues to exert tremendous influence on the health outcomes of individuals and their communities.2–5
Underappreciated impacts of poverty as a cognitive impedimentIn this issue of BMJ Quality and Safety, two papers draw attention...
https://ift.tt/2k3anDz
Simplifying care: when is the treatment burden too much for patients living in poverty?
It is usually a grand affair when 'Ms Noelle' makes it to clinic. The 52-year-old mother with a history of hepatitis C cirrhosis, hypertension, uterine fibroids and migraines has been in our care for over a year. Even so, each visit still brings a new crisis. Today, we found out that Ms Noelle, the caretaker of a daughter with bipolar disorder and nine grandchildren, had just been evicted from her home. She had been without any income for months, and her applications for temporary cash assistance and disability were denied. Ms Noelle maintained a remarkable ability to keep her family protected and fed despite all this, but we have watched as she became the ultimate victim: she struggled to remember her medications, their doses and indications, and her cirrhosis was frequently on the verge of decompensation during appointments she was barely able to keep. She was overwhelmed by even...
https://ift.tt/2Ku9Aa6
Effect of a population-level performance dashboard intervention on maternal-newborn outcomes: an interrupted time series study
Objectives
To assess the effect of the Maternal Newborn Dashboard on six key clinical performance indicators in the province of Ontario, Canada.
DesignInterrupted time series using population-based data from the provincial birth registry covering a 3-year period before implementation of the Dashboard and 2.5 years after implementation (November 2009 through March 2015).
SettingAll hospitals in the province of Ontario providing maternal-newborn care (n=94).
InterventionA hospital-based online audit and feedback programme.
Main outcome measuresRates of the six performance indicators included in the Dashboard.
Results2.5 years after implementation, the audit and feedback programme was associated with statistically significant absolute decreases in the rates of episiotomy (decrease of 1.5 per 100 women, 95% CI 0.64 to 2.39), induction for postdates in women who were less than 41 weeks at delivery (decrease of 11.7 per 100 women, 95% CI 7.4 to 16.0), repeat caesarean delivery in low-risk women performed before 39 weeks (decrease of 10.4 per 100 women, 95% CI 9.3 to 11.5) and an absolute increase in the rate of appropriately timed group B streptococcus screening (increase of 2.8 per 100, 95% CI 2.2 to 3.5). The audit and feedback programme did not significantly affect the rates of unsatisfactory newborn screening blood samples or formula supplementation at discharge. No statistically significant effects were observed for the two internal control outcomes or the four external control indicators—in fact, two external control indicators (episiotomy and postdates induction) worsened relative to before implementation.
ConclusionAn electronic audit and feedback programme implemented in maternal-newborn hospitals was associated with clinically relevant practice improvements at the provincial level in the majority of targeted indicators.
https://ift.tt/2k1o5Hg
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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...
