The aim of this study was to compare the clinical efficacy of pemetrexed+cisplatin (PP) versus docetaxel+cisplatin (DP) for the treatment of stage IV lung adenocarcinoma. We retrospectively analyzed the clinical data of 147 patients with stage IV lung adenocarcinoma treated between January 2011 and December 2015, 100 of which were in the DP group whereas 47 were in the DP group. Main inclusion criteria were treatment-naive patients, first-line treatment with PP or DP with no molecular targeted therapy during treatment, 2–6 cycles of first-line chemotherapy with unknown status of epidermal growth factor receptor (EGFR) mutation, 18–75 years of age, and Karnofsky performance status score of at least 70. Prognostic factors for survival were identified by using univariate and multivariate analyses. Propensity score matching was performed to further adjust for confounding. A total of 47 pairs were successfully matched between the two groups. The median overall survival was 9.0 months in the DP group and 17.0 months in the PP group; the 1-year survival rate was 29.8 and 59.6%, respectively; the 2-year survival rate was 12.8 and 21.1%, respectively (χ2=4.128, P=0.042); and median progression-free survival was 6.0 and 8.0 months, respectively (χ2=4.839, P=0.028). Cox multivariate analysis showed that chemotherapy regimen and number of metastatic organs were independent factors for OS. The effect of the radiotherapy dose on the primary tumor on OS was close to statistically significant. The incidence of grade 3–4 neutropenia was more significantly reduced in the DP group than in the PP group after matching (61.7 vs. 27.7%, P=0.002), with no between-group difference for adverse effects on platelets or hemoglobin. For patients with stage IV lung adenocarcinoma and unknown EGFR mutation status, PP was more effective than DP in prolonging survival and had a less adverse effect on neutrophils. *ShengFa Su, LingFeng Liu, and YiChao Geng contributed equally to the writing of this article. Correspondence to Bing Lu, MD, Department of Thoracic Oncology, Guizhou Cancer Hospital, 1 Beijing Road West, Guiyang 550004, China Tel: +86 851 8651 3076; fax: +86 851 8650 3205; e-mail: lbgymaaaa@163.com Received August 22, 2018 Accepted November 12, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2ADUmvF
Πέμπτη 29 Νοεμβρίου 2018
Myeloablative chemotherapy and autologous stem cell transplantation can lead to successful postengraftment mobilization of hematopoietic progenitors to support planned subsequent cycle(s) of high-dose chemotherapy and autografting in a patient with relapsed germ-cell tumor
Salvage high-dose chemotherapy (HDC) together with autologous hematopoietic stem cell (HSC) transplantation (ASCT) represents a curative treatment option for patients with relapsed/refractory germ-cell tumor. Usually, 2–3 cycles of HDC are administered with encouraging results, and a sizeable percentage of patients experience long-term survival. However, an appreciable number of patients fail to mobilize adequate numbers of HSCs, adequate to support more than one HDC cycle. There have been no data so far on remobilization of HSCs after prior autografting. We report a unique case with relapsed germ-cell tumor that had undergone the first cycle of HDC with myeloablative doses of carboplatin–etoposide, and HSCs were mobilized successfully in the early posthematopoietic engraftment period to support further cycles of HDC. Four weeks after the first ASCT, an identical second cycle of myeloablative HDC was administered and rescued successfully with the HSCs collected after engraftment following the previous HDC cycle. The present case report illustrates that HSCs can be mobilized successfully in the early postengraftment period after myeloablative doses of carboplatin–etoposide, and these cells can be applied as the sole source of hematopoietic rescue in planned sequential cycles of myeloablative HDC, leading to successful multilineage engraftment. Provided that more extensive experience is gathered in future studies in large numbers of patients, this strategy could prove helpful in patients who cannot initially collect sufficient HSC numbers, before the first autografting cycle, and are in need of sequential HDC+ASCT cycles. A detailed literature review is provided to highlight the uniqueness of the presented case. Correspondence to Christos Kosmas, MD, Hematopoietic Cell Transplant Unit, Department of Medical Oncology, 'Metaxa' Memorial Cancer Hospital, 51 Botassi Street, 18537 Pireaus, Greece Tel/fax: +30 210 428 5009; e-mail: ckosmas1@hotmail.com Received September 4, 2018 Accepted October 22, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2TXpcse
https://ift.tt/2TXpcse
Caffeic acid phenethyl ester potentiates gastric cancer cell sensitivity to doxorubicin and cisplatin by decreasing proteasome function
Caffeic acid phenethyl ester (CAPE) is a major propolis component that possesses a variety of pharmacological properties such as antioxidant and anticancer effects. Herein, we investigated the effectiveness of CAPE on cytotoxicity of clinically used anticancer drugs, doxorubicin (DXR) and cisplatin (CDDP), in parental and the drug-resistant cells of stomach (MKN45) and colon (LoVo) cancers. Concomitant treatment with CAPE potentiated apoptotic effects of DXR and CDDP against the parental cells. The treatment significantly reduced the production of reactive oxygen species elicited by DXR but did not affect the DXR-mediated accumulation of 4-hydroxy-2-nonenal, a lipid peroxidation-derived aldehyde. Intriguingly, treatment of parental MKN45 cells with CAPE alone reduced 26S proteasome-based proteolytic activities, in which a chymotrypsin-like activity was most affected. This effect of CAPE was the most prominent among those of eight flavonoids and nine cinnamic acid derivatives and was also observed in parental LoVo cells. In the DXR-resistant or CDDP-resistant cells, the chymotrypsin-like activity was highly up-regulated and significantly decreased by CAPE treatment, which sensitized the resistant cells to DXR and CDDP. Reverse transcription-PCR analysis showed that CAPE treatment led to downregulation of five proteasome subunits (PSMB1–PSMB5) and three immunoproteasome subunits (PSMB8–PSMB10) in DXR-resistant MKN45 cells. The results suggest that CAPE enhances sensitivity of these cancer cells and their chemoresistant cells to DXR and CDDP, most notably through decreasing proteasome function. Thus, CAPE may be valuable as an adjuvant for DXR or CDDP chemotherapy in gastric cancer. Correspondence to Toshiyuki Matsunaga, PhD, Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196, Japan Tel: +81 582 308 100; fax: +81 582 308 105; e-mail: matsunagat@gifu-pu.ac.jp Received July 22, 2018 Accepted October 23, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2ACw9G2
https://ift.tt/2ACw9G2
Furoxans and tocopherol analogs–furoxan hybrids as anticancer agents
We determined the antiproliferative and nitric oxide (NO)-releasing activity of furoxans and tocopherol analogs–furoxan hybrids by tandem Griess/resazurin/sulforhodamin B assays in HeLa, 253J, T24, and HepG2 cancer cells. In addition, to investigate the NO implications in the inhibition of cell growth, cells were pretreated with the NO scavenger hemoglobin and the genotoxic damage was determined. The compounds 1 and 3 emerged as good anticancer agents for bladder cancer treatment. The NO-releasing activity of these compounds appears to be necessary to obtain the antiproliferative effect. Although compound 1 exerted a DNA damage mechanism of action, compound 3 seemed to act in a different way. The low toxicity levels against normal cell line HaCaT point them out as a very promising scaffold for the further design of new anticancer agents. *Florencia Pérez and María Varela contributed equally to the writing of this article. Correspondence to Paola Hernández, PhD, Epigenetics and Genomic Instability, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, 11600 Montevideo, Uruguay Tel: +598 2487 1616 x232; fax: +598 2487 5461; e-mails: phernandez@iibce.edu.uy, paohernz@gmail.com Received April 30, 2018 Accepted November 3, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2Ayp3CB
https://ift.tt/2Ayp3CB
Selenium attenuates docetaxel-induced apoptosis and mitochondrial oxidative stress in kidney cells
Docetaxel (DTX) is a chemotherapeutic agent, and it is used for the treatment of several cancers including prostate and glioblastoma, but it results in many adverse effects in normal tissues, including kidney. The cytoprotective properties of selenium (Se) against adverse effects of DTX were reported in several normal cells, except kidney cell lines. The purpose of this study was to investigate the effects of Se on DTX-induced nephrotoxicity in normal kidney cell lines. The human embryonic kidney 293 (HEK293) cells were divided into four groups as control, Se (200 nmol/l for 10 h), DTX (10 nmol/l for 48 h), and DTX+Se. Laser confocal microscope fluorescence intensity of apoptosis (annexin V and propidium iodide), mitochondrial membrane depolarization, reactive oxygen species production, and lipid peroxidation levels were increased in the cells by the DTX treatments, although cell number, cell viability, reduced glutathione and glutathione peroxidase values were decreased by the treatments. The fluorescence intensities and values were recovered in the DTX+Se group of the cells by Se treatment. In conclusion, DTX-induced adverse effects were recovered through inhibition of apoptosis and mitochondrial oxidative stress through upregulation of reduced glutathione and glutathione peroxidase in the normal kidney (HEK293) cells. Combination therapy of DTX and Se could be used as an effective strategy for protection of kidney cells against adverse effects of DTX. Correspondence to Mustafa Naziroğlu, PhD, Neuroscience Research Center, Suleyman Demirel University, Isparta TR-32260, Turkey Tel: +90 246 211 3641; fax: +90 246 237 1165; e-mail: mustafanaziroglu@sdu.edu.tr Received August 6, 2018 Accepted November 5, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2TSN9Rv
https://ift.tt/2TSN9Rv
The Value of Prognostic Nutritional Index in Follicular Lymphoma
Objectives: Previous studies reported that prognostic nutritional index (PNI), a marker of host inflammatory and nutritional status, is associated with prognoses in a number of cancer types. Thus, we investigated PNI at diagnosis as a prognostic factor in FL. Methods: We reviewed FL patients in Tuen Mun Hospital, Hong Kong from 2000 to 2014 (n=88). PNI was calculated by serum albumin (g/L)+5×absolute lymphocyte count (109/L). We determined the best PNI cut-off value using receiver-operating characteristic curves. The extent to which progression-free survival (PFS) and overall survival differed by PNI cut-off was assessed using Kaplan-Meier and log-rank tests. Cox proportional hazards model was utilized to adjust for covariates. Results: The best cut-off value for PNI was determined to be 45. Patients with high PNI (>45) had a higher complete response (CR) rate after primary treatment, 46 of 61 (75.4%) patients with high PNI had CR, compared with 10 of 23 (43.5%) for low PNI (2-sample test of proportions P-value=0.006). Further, higher PNI at relapse as a continuous variable was associated with superior postprogression survival with a hazard ratio (HR) 0.88 (95% confidence interval [CI], 0.81-0.96). In multivariate analysis, high PNI at diagnosis had superior PFS (adjusted HR of 0.37; 95% CI, 0.15-0.93). Conclusions: PNI was shown to be independent prognostic factor of PFS in FL. It is a cheap and widely available biomarker. Future study is needed to validate its prognostic value and clinical utility in a prospective cohort. The study protocol was approved by the New Territories West Cluster Clinical & Research Ethics Committee of Tuen Mun Hospital (Tuen Mun, Hong Kong). Informed consent from patients was not required because clinical data were retrieved from a computer database. S.F.L.: developed the concept and design of the study, also analyzed the data and wrote the manuscript. All authors interpreted the data, drafted and revised the manuscript critically and approved the final version of the manuscript. S.F.L.: is the guarantor of the paper. The authors declare no conflicts of interest. Reprints: Shing Fung Lee, MBBS, FRCR, Department of Clinical Oncology, Tuen Mun Hospital, 23 Tsing Chung Koon Road, Tuen Mun, Hong Kong. E-mail: leesfm@ha.org.hk. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2SlrVdc
https://ift.tt/2SlrVdc
Overall Survival of Men and Women With Breast Cancer According to Tumor Subtype: A Population-based Study
Objectives: To analyze differences in overall survival (OS) between male breast cancer (MBC) and female breast cancer (FBC) according to tumor subtype compared with other factors. Materials and Methods: We evaluated men and women with breast cancer between 2010 and 2013 with known hormone receptor (HR) status and human epidermal growth factor receptor 2 (HER2) status reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Patient characteristics were compared between groups. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. Breast cancer–specific survival was a secondary endpoint. Results: We included 1187 MBC and 166,054 FBC. Median follow-up was 21 months (range, 1 to 48) for both groups. OS at 3 years for MBC and FBC was 85.6% and 90.4%, respectively (P=0.0002). MBC were more ductal, had higher grade, presented with more advanced stage and were often HR+/HER2− (each P
https://ift.tt/2E6Ssbk
https://ift.tt/2E6Ssbk
Outcomes and Characteristics of Patients Receiving Second-line Therapy for Advanced Pancreatic Cancer
Objectives: There is limited randomized data to guide second-line chemotherapy selection in advanced pancreatic cancer (APC). We aimed to characterize predictors and outcomes of second-line chemotherapy in patients with APC. Methods: We identified all patients with APC [locally advanced (LAPC) or metastatic (MPC)] who received ≥1 cycle of first-line chemotherapy between January 2012 and December 2015 across 6 cancer centers in British Columbia, Canada. Baseline characteristics and survival outcomes were summarized. Results: Of 676 patients with APC (31% LAPC, 69% MPC) who received ≥1 cycle of chemotherapy, 164 (24%) received second-line chemotherapy. These patients were younger, with lower ECOG and higher CA19-9 at presentation, compared with patients who did not receive second-line chemotherapy. There were no differences in rates of second-line chemotherapy between LAPC and MPC (28% vs. 23%; P=0.18). Only first-line FOLFIRINOX was associated with second-line chemotherapy. Median overall survival (OS) from second-line chemotherapy was longer with second-line gemcitabine/nab-paclitaxel than fluoropyrimidine or gemcitabine (7.9 vs. 5.1 vs. 4.3 mo; P=0.008). On multivariable analysis, longer OS from second-line chemotherapy was associated with gemcitabine/nab-paclitaxel, lower ECOG, and LAPC. Conclusions: In this population-based cohort, first-line FOLFIRINOX was the strongest predictor of second-line chemotherapy. Duration of therapy remains short and novel treatments are urgently needed. E.S.T. and H.-l.W. are joint first authors. The authors declare no conflicts of interest. Reprints: Hagen F. Kennecke, MD, MHA, FRCPC, Virginia Mason Hospital & Seattle Medical Center, 1100 Ninth Avenue, Seattle, WA 98101. E-mail: Hagen.Kennecke@virginiamason.org. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2SljgYm
https://ift.tt/2SljgYm
Management of Unresectable T4b Esophageal Cancer: Practice Patterns and Outcomes From the National Cancer Data Base
Purpose: Patients with unresectable cT4b esophageal cancer (EC) are rare and largely excluded from prospective trials. As a result, current treatment recommendations are based on limited evidence. This study sought to evaluate national practice patterns and outcomes for this population and evaluated 3 primary cohorts: patients receiving chemotherapy (CT) with or without subtherapeutic radiotherapy (RT), definitive chemoradiotherapy (CRT), or CT with or without RT followed by definitive surgery. Materials and Methods: The National Cancer Data Base was queried for cT4b Nany M0 EC. Exclusion criteria were patients with unspecified staging, palliative treatment, improper, or no histologic confirmation, or lack of CT. Multivariable logistic regression determined factors predictive of receiving surgical therapy. Kaplan-Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Results: Altogether, 519 patients met inclusion criteria; 195 (38%) underwent CT, 291 (56%) underwent definitive CRT, and 33 (6%) underwent surgical-based therapy. Surgery was more likely performed in patients residing in rural areas, living farther from the treating facility, and N1 status (P
https://ift.tt/2E6Sq3c
https://ift.tt/2E6Sq3c
CUSUM charts in the quality control of colon cancer lymph node analysis: a population-registry study
Abstract
Background
The most important determinant of survival in patients with colon cancer is the presence or absence of regional lymph node metastases. This factor is consistently associated with long-term and disease-specific survival. Cumulative summation of differences (CUSUM) charts can help to discriminate abnormalities that cannot be explained by the general variability of a process. We used CUSUM charts to analyse the quality of nodal analysis in colon cancer and to use a population-registry cancer database to estimate the optimal number of lymph nodes for adequate prognostic analysis.
Methods
This was a multicentre population-registry cancer study from January 2004 to December 2007. We used these data to produce the different CUSUM curves, focusing on the main variables. To calculate survival, we used the Kaplan–Meier method.
Results
In this study, we examined 548 patients. The CUSUM curves were calculated for overall mortality, specific mortality, and recurrence according to (1) the number of lymph nodes analysed and affected and (2) compared the ratio of the number of lymph nodes affected to the number analysed. Finally, the lymph node ratio was compared to the overall survival CUSUM curve.
Discussion
This CUSUM control chart analysis reinforces the unquestionable importance of analysing at least 12 lymph nodes in patients with colon cancer in order to accurately estimate their prognosis. However, our findings indicate that the analysis of at least 20 lymph nodes is a more appropriate cutoff point for accomplishing the demanding objective of diagnosing a high-quality prognosis in colon cancer patients.
https://ift.tt/2RoLlht
Mediating Effect of Family Caregivers' Hesitancy to Use Analgesics on Homecare Cancer Patients' Analgesic Adherence
Family caregivers play an increasingly critical role in cancer patients' symptom management as the number of cancer patients receiving home care grows. However, there is a lack of research measuring the impact of the family caregivers' hesitancy to use analgesics on analgesic adherence and the resulting influence on patient pain intensity.
https://ift.tt/2TYwLPe
Development and Implementation of a Wellbeing Program for Palliative Care (PC) Health Workers. Phase 1: Protection and Risk Factors Description
Context: The costs associated to the Quebec health care system, the desire to maintain high quality care, as well as being in perpetual contact with dying all have an impact on the equilibrium between the demands and resources available for PC workers. A social innovation is in progress in a PC hospice in Quebec and offers the co-construction, designed by and for PC workers, of a wellbeing program as a distinctive solution.
https://ift.tt/2TZaaC5
Planning a Phase III Study Using a Pilot Study with Mixed Method
A running pilot study using mixed methodology (quantitative and qualitative) on the effect of methylphenidate (MP) on cognitive deficits (CD) in women in remission of breast cancer in planning a Phase III study will be presented, specifically how this approach can be highly effective.
https://ift.tt/2AzKbZ3
Prevalence and Risk Factors of Suicidal Ideation in Head and Neck Cancer Patients: Longitudinal Study
Prospective longitudinal study with one-year follow-up.
https://ift.tt/2TYwxYo
Comparing Quebec Stakeholders’ Perspectives on Whether Medical Aid in Dying Should Be Made Accessible to Incompetent Patients, in Some Circumstances
Legislation was recently passed in the province of Quebec and Canada allowing medical aid in dying (MAiD) at the explicit request of a competent adult who meets strictly defined criteria. Both levels of government are currently considering extending MAiD to incompetent patients through written requests made in advance of loss of capacity.
https://ift.tt/2Aydj2T
Optimizing Communication with Parents During and After an Unsuccessful Neonatal Resuscitation
Providers are urged to communicate adequately when having difficult conversations with parents, generally without practical suggestions.
https://ift.tt/2TXtlfF
How Does the Bereavement Experiences of Seniors Living in Residence Affect Their Thinking About Their Own End-of-Life?
Seniors residences are living environments where death occurs on a regular basis (Hecquet, 2011). How do seniors living in these environments experience this reality? Research paying attention to this question is almost inexistent. The objective of this conference is to better understand how losses and bereavement experienced in this context affect the way in which the elderly think about the end of their own life.
https://ift.tt/2AyLcRo
Evaluation of an Intervention to Improve Supportive Care for Family Caregivers of Patients with Lung Cancer: Results of a Randomized Clinical Trial
Family caregivers (FC) of patients with cancer often report high distress. The trial is aimed to assess the effectiveness of an intervention to improve supportive care for FCs.
https://ift.tt/2TYwmfG
Analyse de l'impact des séances d’art-thérapie musicale "Pansement Schubert"
Les soins des patients en situation palliative sont parfois douloureux malgré une médication adéquate et cause de souffrance pour les soignants. Dans ce contexte, nous menons une étude visant à apprécier l'effet sur les soignants des séances d'art-thérapie musicale « Pansement Schubert » effectuées par une art-thérapeute lors de soins infirmiers.
https://ift.tt/2AF0T9s
Interprofessional Clinical Reasoning: Explaining How Interprofessional Teams Make Shared Decisions in Advanced Cancer and Cachexia Care
Interprofessional practice is important in palliative care, and involves sharing knowledge and responsibility between health care professionals (HCPs) to provide comprehensive patient care. When implemented, evidence has shown positive outcomes including improvements to patients' quality of life and HCP job satisfaction. Complex areas of care, such as treating advanced cancer and cachexia, require interprofessional practice and the use of multimodal interventions tailored to the needs of the patient.
https://ift.tt/2TYweNe
Use of the InterRAI Palliative Care (PC) Instrument: An Active Mediation Role for PC Nurses in their Professional Experience
To study the impact and contribution of using a comprehensive needs assessment tool (InterRAI PC) to the professional experience of PC nurses.
https://ift.tt/2AyL58q
Supportive Care Needs in Thai Women with Breast Cancer Undergoing Chemotherapy: A Qualitative Study
The diagnosis of breast cancer and the first chemotherapy treatment may result in long-term changes in life of women and may induce new supportive care needs. Despite ubiquitous use of the term supportive care needs for cancer population research, the concept still lack clarity for specific group. In particular in Thai context, it need to clarify a deeper understanding of the supportive care needs.
https://ift.tt/2TZ9lta
Innovative Education for the Development Competencies in the Care of People at the End of Life and Their Family Caregivers
The attention to people with advanced chronic disease requiring palliative care. It takes increasingly importance within the health system, the demands of patients and their families and the interest to avoid suffering of progressive sensitivity in their approach. The need of professional to management patient care situations in the end of life several times results difficult to extend that health professional are unprepared to lead effectivily the emerging feelings caused as a result of the care relationship.
https://ift.tt/2AyKZO6
Measuring Public Preferences for Health Outcomes and Expenditures in a Context of Healthcare Resource Re-Allocation
Abstract
Background
The final outcome of any resource allocation decision in healthcare cannot be determined in advance. Thus, decision makers, in deciding which new program to implement (or not), need to accommodate the uncertainty of different potential outcomes (i.e., change in both health and costs) that can occur, the size and nature (i.e., 'bad' or 'good') of these outcomes, and how they are being valued. Using the decision-making plane, which explicitly incorporates opportunity costs and relaxes the assumptions of perfect divisibility and constant returns to scale of the cost-effectiveness plane, all the potential outcomes of each resource allocation decision can be described.
Objective
In this study, we describe the development and testing of an instrument, using a discrete choice experiment methodology, allowing the measurement of public preferences for potential outcomes falling in different quadrants of the decision-making plane.
Method
In a sample of 200 participants providing 4200 observations, we compared four versions of the preference-elicitation instrument using a range of indicators.
Results
We identified one version that was well accepted by the participants and with good measurement properties.
Conclusion
This validated instrument can now be used in a larger representative sample to study the preferences of the public for potential outcomes stemming from re-allocation of healthcare resources.
https://ift.tt/2reHXKq
Mixed Reviews for A2AR Inhibitor in NSCLC [News in Brief]
Trial suggests that a PD-1 inhibitor plus an adenosine 2A receptor blocker might benefit some patients.
https://ift.tt/2Q8m9PO
Climate Change Ups Heat Deaths, Especially Among Elderly
THURSDAY, Nov. 29, 2018 -- Risk for heat-related disease and death is rising worldwide due to climate change, according to a report published online Nov. 28 in The Lancet. Hotter temperatures threaten the elderly and other vulnerable people with...
https://ift.tt/2BGn3Kv
Ablation of cancer stem cells by therapeutic inhibition of the MDM2-p53 interaction in mucoepidermoid carcinoma
Purpose: Unique cells characterized by multipotency, self-renewal and high tumorigenic potential have been recently discovered in mucoepidermoid carcinomas (MEC). These cells are defined by high aldehyde dehydrogenase activity and high CD44 expression (ALDHhighCD44high) and function as cancer stem cells. It has been recently shown that p53 regulates cell differentiation, suggesting that induction of p53 by therapeutic blockade of the MDM2-p53 interaction may constitute a novel strategy to ablate cancer stem cells. Here, we evaluated the effect of a small molecule inhibitor of MDM2-p53 interaction (MI-773) on the fraction of cancer stem cells in mucoepidermoid carcinoma. Experimental design: Human mucoepidermoid carcinoma cells (UM-HMC-1,-3A,-3B) were used to assess the effect of MI-773 on cell survival, cell cycle, fraction of cancer stem cells and expression of p53, p21, MDM2, and Bmi-1 (key regulator of self-renewal). Mice bearing xenograft tumors generated with these MEC cells were treated with MI-773 to determine the effect of MDM2-p53 inhibition on cancer stem cells in vivo. Results: MDM2 is highly expressed in human MEC tissues. MI-773 induced expression of p53 and its downstream targets p21 and MDM2, caused G1 cell cycle arrest, and induced MEC tumor cell apoptosis in vitro. Importantly, a marked decrease in expression of Bmi-1 and in the fraction of ALDHhighCD44high (cancer stem cells) was caused by MI-773 in vitro and in mice harboring MEC xenografts. Conclusion: Collectively, these data demonstrate that MI-773 reduces the fraction of cancer stem cells, suggesting that patients with mucoepidermoid carcinoma might benefit from therapeutic inhibition of the MDM2-p53 interaction.
https://ift.tt/2E3VZHn
Expression of PD-1 by T cells in malignant glioma patients reflects exhaustion and activation
Purpose: Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Our recent pre-clinical work has suggested that PD-1/PD-L1 plays an important immunoregulatory role to limit effective anti-tumor T cell responses induced by active immunotherapy. However, little is known about the functional role that PD-1 plays on human T lymphocytes in malignant glioma patients. Experimental Design: In this study, we examined the immune landscape and function of PD-1 expression on T cells from the tumor and peripheral blood in malignant glioma patients. Results: We found several differences between PD-1+ tumor-infiltrating lymphocytes (TILs) and patient-matched PD-1+ peripheral blood T lymphocytes. Phenotypically, PD-1+ TILs exhibited higher expression of markers of activation and exhaustion than peripheral blood PD-1+ T cells, which instead had increased markers of memory. A comparison of the T cell receptor variable chain populations revealed decreased diversity in T cells that expressed PD-1, regardless of the location obtained. Functionally, peripheral blood PD-1+ T cells had a significantly increased proliferative capacity upon activation compared with PD-1- T cells. Conclusion: Our evidence suggests that PD-1 expression in glioma patients reflects chronically-activated effector T cells that display hallmarks of memory and exhaustion depending on its anatomical location. The decreased diversity in PD-1+ T cells suggests that the PD-1 expressing population has a narrower range of cognate antigen targets compared to the PD-1 non-expression population. This information can be used to inform how we interpret immune responses to PD-1 blocking therapies or other immunotherapies.
https://ift.tt/2SiEiH1
Clinical Development of Novel Drug-Radiotherapy Combinations
Radiotherapy is a fundamental component of treatment for the majority of patients with cancer. In recent decades, technological advances have enabled patients to receive more targeted doses of radiation to the tumour, with sparing of adjacent normal tissues. There had been hope that the era of precision medicine would enhance the combination of radiotherapy with targeted anticancer drugs, however this ambition remains to be realised. In view of this lack of progress, the FDA-AACR-ASTRO Clinical Development of Drug-Radiotherapy Combinations Workshop was held in February 2018 to bring together stakeholders and opinion leaders from academia, clinical radiation oncology, industry, patient advocacy groups and the FDA in order to discuss challenges to introducing new drug-radiotherapy combinations to the clinic. This "Perspectives in Regulatory Science and Policy" article summarises the themes and action points that were discussed. Intelligent trial design is required to increase the number of studies which efficiently meet their primary outcomes; endpoints to be considered include local control, organ preservation and patient-reported outcomes. Novel approaches including immune-oncology or DNA repair inhibitor agents combined with radiotherapy should be prioritised. In this article, we focus on how the regulatory challenges associated with defining a new drug-radiotherapy combination can be overcome in order to improve clinical outcomes for patients with cancer.
https://ift.tt/2E5r90S
FDA Approves Firdapse for Rare Autoimmune Disorder
THURSDAY, Nov. 29, 2018 -- Firdapse (amifampridine) tablets have been approved by the U.S. Food and Drug Administration for adults with Lambert-Eaton myasthenic syndrome (LEMS). The drug is the first agency-sanctioned treatment for the autoimmune...
https://ift.tt/2KKQwWc
FDA Approves Treatment for AML Patients With Gene Mutation
THURSDAY, Nov. 29, 2018 -- Xospata (gilteritinib) tablets were approved today by the U.S. Food and Drug Administration for treatment of relapsed or refractory acute myeloid leukemia (AML) in adults with an FLT3 mutation, the agency announced in a...
https://ift.tt/2KKQvS8
Genetic Analysis Shows Higher BMI May Up Risk for Depression
THURSDAY, Nov. 29, 2018 -- Being overweight likely plays a causal role in the development of depression, even in the absence of other health problems, according to a study published online Nov. 13 in the International Journal of...
https://ift.tt/2BI6AFs
Most Bills Enacted Into Law Limit Vaccine Exemptions
THURSDAY, Nov. 29, 2018 -- Most proposed bills in state legislatures from 2011 to 2017 sought to expand access to immunization exemptions, but the majority of bills enacted into law limited exemptions, according to a study published online Nov. 29...
https://ift.tt/2KKfN30
SNZ3 Encodes a PLP Synthase Involved in Thiamine Synthesis in Saccharomyces cerevisiae
Pyridoxal 5'-phosphate (the active form of vitamin B6) is a cofactor that is important for a broad number of biochemical reactions and is essential for all forms of life. Organisms that can synthesize pyridoxal 5'-phosphate use either the deoxyxylulose phosphate-dependent or -independent pathway, the latter is encoded by a two-component pyridoxal 5'-phosphate synthase. Saccharomyces cerevisiae contains three paralogs of the two-component SNZ/SNO pyridoxal 5'-phosphate synthase. Past work identified the biochemical activity of Snz1p, Sno1p and provided in vivo data that SNZ1 was involved in pyridoxal 5'-phosphate biosynthesis. Snz2p and Snz3p were considered redundant isozymes and no growth condition requiring their activity was reported. Genetic data herein showed that either SNZ2 or SNZ3 are required for efficient thiamine biosynthesis in Saccharomyces cerevisiae. Further, SNZ2 or SNZ3 alone could satisfy the cellular requirement for pyridoxal 5'-phosphate (and thiamine), while SNZ1 was sufficient for pyridoxal 5'-phosphate synthesis only if thiamine was provided. qRT-PCR analysis determined that SNZ2,3 are repressed ten-fold by the presence thiamine. In total, the data were consistent with a requirement for PLP in thiamine synthesis, perhaps in the Thi5p enzyme, that could only be satisfied by SNZ2 or SNZ3. Additional data showed that Snz3p is a pyridoxal 5'-phosphate synthase in vitro and is sufficient to satisfy the pyridoxal 5'-phosphate requirement in Salmonella enterica when the medium has excess ammonia.
https://ift.tt/2RnD4u1
Pre- and post-operative anti-PD-L1 plus anti-angiogenic therapies in mouse breast or renal cancer models of micro- or macro-metastatic disease
Pre- and post-operative anti-PD-L1 plus anti-angiogenic therapies in mouse breast or renal cancer models of micro- or macro-metastatic disease
Pre- and post-operative anti-PD-L1 plus anti-angiogenic therapies in mouse breast or renal cancer models of micro- or macro-metastatic disease, Published online: 30 November 2018; doi:10.1038/s41416-018-0297-1
Pre- and post-operative anti-PD-L1 plus anti-angiogenic therapies in mouse breast or renal cancer models of micro- or macro-metastatic diseasehttps://ift.tt/2P822vv
Causes of mouth sores in people with HIV
People living with HIV have a higher risk of developing mouth sores. Possible causes include viral, bacterial, and fungal infections, canker sores, and dry mouth. Learn more about the causes of HIV mouth sores and how to treat and prevent them here.
https://ift.tt/2FQu9jH
Mutagenesis in Norovirus in Response to Favipiravir Treatment
https://ift.tt/2RjnnUx
Ramping Up the Response to Ebola
Before 2014, it seemed unimaginable to many experts that Ebola would rip through dense urban areas, ultimately sickening nearly 30,000 people and killing more than 13,000. Four years later, Ebola is again spreading in urban areas, this time in the Democratic Republic of Congo (DRC). Though there…
https://ift.tt/2P9kG6c
Pregnant Women and the Ebola Crisis
On August 1, 2018, the Ministry of Health of the Democratic Republic of Congo (DRC) reported the emergence of another Ebola virus outbreak, the 10th in the DRC since the virus was discovered in 1976. As of November 13, 2018, there were 341 cases and 215 deaths, making this the world's third-largest…
https://ift.tt/2zwqHoy
Reimagining Development Assistance for Health
Financing priorities in global health continue to lag behind the changing realities in lower- and lower-middle-income countries, where the burden of noncommunicable diseases (NCDs) is growing. In 2017, global health funding allocations remained essentially the same as they had for years: 5% and 7%…
https://ift.tt/2zwvpmr
Prednisone for the Prevention of Paradoxical Tuberculosis-Associated IRIS
https://ift.tt/2PZzM3z
Evidence of Artemisinin-Resistant Plasmodium falciparum Malaria in Eastern India
https://ift.tt/2RjTfZn
Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease
Many patients with chronic diseases remain without a diagnosis despite extensive medical evaluation. In 2008, the Undiagnosed Diseases Program (UDP) was established at the National Institutes of Health (NIH) Clinical Center to meet the needs of patients with undiagnosed diseases and to investigate…
https://ift.tt/2TWHzgW
Correction: Normocalcemic Primary Hyperparathyroidism: A Comparison with the Hypercalcemic Form in a Tertiary Referral Population
Horm Metab Res 2018; 50: e7-e7
DOI: 10.1055/a-0799-5387
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
https://ift.tt/2KGZKTp
Free IGF-1, Intact IGFBP-4, and PicoPAPP-A are Altered in Acute Myocardial Infarction Compared to Stable Coronary Artery Disease and Healthy Controls
Horm Metab Res
DOI: 10.1055/a-0794-6163
Insulin-like growth factor-1 (IGF-1) and its binding proteins have been implicated in the pathophysiology of coronary artery disease (CAD) and myocardial infarction (MI). We investigated components of the IGF-1 system in circulation at the time of acute MI and following reperfusion in relation to levels of stable CAD patients and controls. Patients with MI (MI Group, n=31) treated with percutaneous coronary intervention (PCI) were compared to patients with stable CAD subjected to scheduled PCI (CAD Group, n=40) and controls with symptoms mimicking CAD without stenosis in angiography (Control Group, n=43). The number and extent of stenosis were recorded. Total and free IGF-1, total and intact IGF binding protein (IGFBP)-3 and -4, pico-Pregnancy Associated Plasma Protein-A (PAPP-A), and the known markers ALT, AST, CK and CK-MB were measured at baseline and 6 or 24 h after the intervention. Patients with MI had higher free IGF-1 (p=0.003) and PAPP-A (p=0.011), but lower intact IGFBP-4 (p=0.006) compared with patients with stable CAD or healthy controls. None of the investigated molecules changed following reperfusion or correlated with the extent of stenosis. AST (p<0.001), CK (p<0.001) and CK-MB (p<0.001), were also higher. Free IGF-1, intact IGFBP-4 and PAPP-A could predict MI, but with lower accuracy than CK-MB. In conclusion, free IGF-1 levels are higher in MI compared to CAD patients and controls and this could result from increased cleavage of its binding protein IGFBP-4 by the higher PAPP-A levels. Free IGF-1, intact IGFBP-4, and/or PAPP-A are inferior to CK-MB as predictors or markers of myocardial damage.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2BGDQwY
Metabolic Syndrome is a Risk Factor for Post-Operative Adhesions: Need for Novel Treatment Strategies
Horm Metab Res
DOI: 10.1055/a-0798-3931
Metabolic syndrome is a group of disorders which include obesity, diabetes, dyslipidemias, and hypertension. This condition is rapidly increasing in an aging population. The rates of surgery in older patients is also growing and a wide range of operations including minimally invasive procedures is now available for this segment of the population. The number of patients suffering from postoperative adhesions is therefore correspondingly increasing. In addition to preventing and treating the metabolic disease itself, improved therapeutic strategies for the prevention of surgical adhesions have to be developed. Here we review the existing and novel treatment options.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2KI8rwV
Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer
Radical hysterectomy with pelvic lymphadenectomy remains the standard recommendation for patients with early-stage cervical cancer. Current guidelines from the National Comprehensive Cancer Network and European Society of Gynaecological Oncology indicate that either laparotomy (open surgery) or…
https://ift.tt/2QupmYY
Surgery in Cervical Cancer
Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer-related death in women worldwide. For early-stage disease, surgical removal of the uterus remains the primary treatment and has the greatest effect on long-term survival. However, abdominal…
https://ift.tt/2QqlpVf
Survival after Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer
https://ift.tt/2QmLzsb
Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer
Triple-negative breast cancer is the term used to describe breast cancers that lack estrogen- and progesterone-receptor expression and do not overexpress human epidermal growth factor receptor 2 (HER2). Patients with triple-negative breast cancer have poor clinical outcomes. Chemotherapy remains…
https://ift.tt/2DTttHH
The Role of Deferiprone in Iron Chelation
Treatment of chronic refractory anemias with regular blood transfusions results in iron accumulation, with potential damage to the liver, endocrine system, and heart. Each unit of blood adds 200 to 250 mg of iron to the body's iron burden. Initially, this excess iron is stored in the…
https://ift.tt/2ACgUgo
Surgery in Cervical Cancer
Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer-related death in women worldwide. For early-stage disease, surgical removal of the uterus remains the primary treatment and has the greatest effect on long-term survival. However, abdominal…
https://ift.tt/2QqlpVf
Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer
In 2018, approximately 266,000 new cases of breast cancer are estimated to occur in women in the United States, with 41,000 deaths. Of these, hormone-receptor–positive breast cancer is the most common disease subtype. The cyclin-dependent kinases 4 and 6 (CDK4/6) are key promoters of tumor growth…
https://ift.tt/2DSseZe
Case 35-2018: A 68-Year-Old Woman with Back Pain and a Remote History of Breast Cancer
Presentation of Case. Ms. Diane P. Doyle, M.S.N. (Medicine): A 68-year-old woman with a history of bilateral breast cancer was evaluated at the oncology clinic of this hospital for back and pelvic pain. Twenty-five years before the current evaluation, the patient was noted to have a small lump in…
https://ift.tt/2QqlnwB
Survival after Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer
https://ift.tt/2QmLzsb
Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer
Radical hysterectomy with pelvic lymphadenectomy remains the standard recommendation for patients with early-stage cervical cancer. Current guidelines from the National Comprehensive Cancer Network and European Society of Gynaecological Oncology indicate that either laparotomy (open surgery) or…
https://ift.tt/2QupmYY
Attention Deficit–Hyperactivity Disorder and Month of School Enrollment
Variable rates of diagnosis and treatment of attention deficit–hyperactivity disorder (ADHD) across the United States have aroused concern about overdiagnosis, underdiagnosis, and appropriate treatment. Over the past two decades, rates of diagnosis and treatment of ADHD have increased. Among…
https://ift.tt/2QszSAb
Case 37-2018: A 23-Year-Old Woman with Vision Loss
Presentation of Case. Dr. Seth N. Levin (Neurology): A 23-year-old right-handed woman with a history of migraines was evaluated at this hospital for vertigo and vision loss affecting the right eye. Six days before admission, a right frontal headache and right retro-orbital pain developed; these…
https://ift.tt/2DS7Ebe
Trauma-Informed Care — Reflections of a Primary Care Doctor in the Week of the Kavanaugh Hearing
https://ift.tt/2PaRNGL
The FDA Sentinel Initiative — An Evolving National Resource
The Food and Drug Administration (FDA) Sentinel Initiative, which was launched in 2008, has matured from a pilot program designed to assess potential drug-safety signals in insurance claims into a core component of the agency's evolving safety surveillance system. Sentinel is a flexible and robust…
https://ift.tt/2P9j903
Pregnant Women and the Ebola Crisis
On August 1, 2018, the Ministry of Health of the Democratic Republic of Congo (DRC) reported the emergence of another Ebola virus outbreak, the 10th in the DRC since the virus was discovered in 1976. As of November 13, 2018, there were 341 cases and 215 deaths, making this the world's third-largest…
https://ift.tt/2zwqHoy
Ramping Up the Response to Ebola
Before 2014, it seemed unimaginable to many experts that Ebola would rip through dense urban areas, ultimately sickening nearly 30,000 people and killing more than 13,000. Four years later, Ebola is again spreading in urban areas, this time in the Democratic Republic of Congo (DRC). Though there…
https://ift.tt/2P9kG6c
Case Studies in Social Medicine — Attending to Structural Forces in Clinical Practice
https://ift.tt/2zGL5nh
Looking beyond Mortality in Transplantation Outcomes
Consider three of our patients, nearly 1 year after lung transplantation. Mr. S. who is 67 years old, underwent transplantation for pulmonary fibrosis. He is alive, but weak, intermittently delirious, and unable to breathe without a ventilator. Ms. L. who is also in her 60s and has emphysema, was…
https://ift.tt/2Pb4Urp
Reimagining Development Assistance for Health
Financing priorities in global health continue to lag behind the changing realities in lower- and lower-middle-income countries, where the burden of noncommunicable diseases (NCDs) is growing. In 2017, global health funding allocations remained essentially the same as they had for years: 5% and 7%…
https://ift.tt/2zwvpmr
Medicalization and Demedicalization — A Gravely Disabled Homeless Man with Psychiatric Illness
https://ift.tt/2Pb4T6P
The SUPPORT for Patients and Communities Act — What Will It Mean for the Opioid-Overdose Crisis?
Opioid-overdose deaths have increased every year for the past two decades, driving a drug-overdose epidemic that killed more than 72,000 Americans in 2017. Thanks in large part to sustained efforts by health advocates, medical professionals, and affected people, Congress has acted on several…
https://ift.tt/2zrAFaT
Disclosing Prescription-Drug Prices in Advertisements — Legal and Public Health Issues
https://ift.tt/2PetoAo
Trauma-Informed Care — Reflections of a Primary Care Doctor in the Week of the Kavanaugh Hearing
https://ift.tt/2PaRNGL
Case 37-2018: A 23-Year-Old Woman with Vision Loss
Presentation of Case. Dr. Seth N. Levin (Neurology): A 23-year-old right-handed woman with a history of migraines was evaluated at this hospital for vertigo and vision loss affecting the right eye. Six days before admission, a right frontal headache and right retro-orbital pain developed; these…
https://ift.tt/2DS7Ebe
Sit Back and Listen — The Relevance of Patients’ Stories to Trauma-Informed Care
https://ift.tt/2zwvoPp
Simplified follow-up of patients with mild chronic hepatitis C in areas with limited access to antiviral therapy
In some areas of the world, antiviral therapy for chronic hepatitis C (CHC) is not available for all patients. The optimal interval for liver stiffness measures (LSM) and noninvasive scores to assess fibrosis progression has not been studied. We evaluated the usefulness of consecutive LSM, APRI, FIB-4 and Forns scores to predict disease progression.
https://ift.tt/2BFtmOi
Regulatory effect of hsa-miR-5590-3P on TGFβ signaling through targeting of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts
Journal Name: Biological Chemistry
Issue: Ahead of print
https://ift.tt/2E3i7Bz
Agency, Meaning, Perception and Mimicry: Perspectives from the Process of Life and Third Way of Evolution
Abstract
The concept of biological mimicry is viewed as a 'process of life' theory rather than a 'process of change' theory—regardless of the historical interest and heuristic value of the subject for the study of evolution. Mimicry is a dynamic ecological system reflecting the possibilities for mutualism and parasitism created by a pre-established bipartite signal-based relationship between two organisms – a potential model and its signal receiver (potential operator). In a mimicry system agency and perception play essential, interconnected roles. Mimicry thus describes emergent biologically meaningful relationships based on synergy, and is not an object-based theory. Biosemiotics offers a particularly valuable discipline for analysing the dynamics and nuances of mimicry systems, and can thus pave the way for a better and more complete understanding of how mimicry has evolved in the past, and how it might evolve in the future—presented here with special reference to the need for an integrated, 'third way of evolution' approach to biological relativity. A revised definition of mimicry is proposed.
https://ift.tt/2rdHkkh
Endoscopic intervention and cholecystectomy in pregnant women with acute biliary pancreatitis decreases early readmissions
Acute biliary pancreatitis (ABP) is associated with increased rates of morbidity in pregnancy. Because there is a paucity of population-based studies evaluating ABP in pregnancy, we sought to investigate clinical outcomes in hospitalized pregnant women on a national level.
https://ift.tt/2Q30sAA
A systematic description of the post-EMR defect to identify risk factors for clinically significant post-EMR bleeding in the colon
and Aims: Clinically significant bleeding (CSPEB) is the most frequent serious adverse event after endoscopic mucosal resection (EMR) of large laterally spreading colonic lesions (LSLs). There is no proven prophylactic therapy, and it remains a significant drawback of EMR. We aimed to systematically describe and evaluate the features of the post-EMR mucosal defect (PED) and their relationship to CSPEB.
https://ift.tt/2Q4y4xI
German National Case Collection for familial pancreatic Cancer (FaPaCa) - acceptance and psychological aspects of a pancreatic cancer screening program
Abstract
Background
Pancreatic cancer screening is recommended to individuals at risk (IAR) of familial pancreatic cancer (FPC) families, but little is known about the acceptance of such screening programs. Thus, the acceptance and psychological aspects of a controlled FPC screening program was evaluated.
Methods
IAR of FPC families underwent comprehensive counseling by a geneticist and pancreatologist prior to the proposed screening. Participating IAR, IAR who discontinued screening and IAR who never participated in the screening program were invited to complete questionnaires to assess the motivation for participating in surveillance, cancer worries, structural distress and experiences with participation. Questionnaires were completed anonymously to receive most accurate answers.
Results
Of 286 IAR to whom pancreatic ductal adenocarcinoma (PDAC) screening was recommended, 139 (48.6%) IAR regularly participated (group 1), 49 (17.1%) IAR (group 2) discontinued screening after median 1 (1–10) screening visits and 98 (34.2%) IAR (group 3) never underwent screening. The overall response rate of questionnaires was 67% (189/286) with rates of 100% (139 of 139 IAR), 49% (29 of 49 IAR) and 23.4% (23 of 98 IAR) for groups 1, 2 and 3, respectively. At least 93% of IAR felt adequately informed about the screening program after initial counseling. However, only 38.8% received knowledge of or the recommendation for PDAC screening by physicians. The reported cancer-related distress and the fear of investigations were highest in group 1, but acceptably low in all three groups. The main reasons to discontinue or not to participate in screening were the time efforts and travel costs (groups 2 and 3 48,7%).
Conclusion
Less than 50% of IAR regularly participate in a proposed PDAC screening program, although the associated psychological burden is quite low. Physicians should be educated about high risk PDAC groups and screening recommendations. Time and travel efforts must be reduced to encourage more IAR to participate in a recommended screening.
https://ift.tt/2RpBdor
EEG analysis in anti-NMDA receptor encephalitis: description of typical patterns
Anti-N-methyl D-aspartate receptor encephalitis (anti-NMDARE) is the most frequent human autoimmune encephalitis and is primarily directed against the NR1 subunit of the NMDAR (Dalmau et al., 2008). Clinical symptoms are initially marked by psychiatric manifestations, impaired cognition and seizures followed by movement disorders, loss of consciousness, and dysautonomia (Dalmau et al., 2011, 2008; Irani et al., 2010; Titulaer et al., 2013) The association of one of these symptoms and anti-NMDAR IgG antibodies detection made a definite diagnosis (Graus et al., 2016).
https://ift.tt/2FNh2j5
Reply
We agree with Drs Kumar and Yadav and with Dr Ziegler that the primary outcome, growth during the 28-day study, as noted in our article, was not significantly different between study groups.
https://ift.tt/2BHRDDn
Equivalence of fortifiers
Schanler et al have pulled off the admirable feat of studying a large cohort (n = 164) of premature infants in a multicenter study designed to compare the 2 available liquid human milk fortifiers, the acidified fortifier of Mead-Johnson and the nonacidified fortifier of Abbott.1 They found the 2 fortifiers to be equivalent with regard to growth, the main and all-important study outcome.
https://ift.tt/2KIw8Fw
Hepatocyte Transplantation: Quo Vadis?
Orthotopic liver transplantation (OLT) has been effective in managing end-stage liver disease since the advent of Cyclosporine immunosuppression therapy in 1980. The major limitations of OLT are organ supply, monetary cost and burden of lifelong immunosuppression. Hepatocyte transplantation (HT), as a substitute for OLT, has been an exciting topic of investigation for several decades. HT is potentially minimally invasive, and can also serve as a vehicle for delivery of personalized medicine through autologous cell transplant after modification ex vivo.
https://ift.tt/2zwZ0vK
Regeneration after radiation- and immune-mediated tissue injury is not enhanced by type III interferon signaling
Type III interferons (IFN-III) modulate the homeostasis of epithelial cells and help to clear mucosal viral infections. We analyzed the role of the IFN-III pathway in (1) radiation induced thymus injury and (2) graft-versus-host disease after total body irradiation (TBI) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), conditions which involve epithelial damage and cause patient morbidity. IFN-III did not significantly alter thymus regeneration after irradiation and did not affect GVHD after TBI and allo-HSCT.
https://ift.tt/2P7Kaks
Patients Prescribed Direct-acting Oral Anticoagulants Have Low Risk of Post-Polypectomy Complications
Use of direct-acting oral anticoagulants (DOACs) is increasing, but little is known about the associated risks in patients undergoing colonoscopy with polypectomy. We aimed to determine the risk of post-polypectomy complications in patients prescribed DOACs.
https://ift.tt/2zwdBYu
Low-literacy Level Instructions and Reminder Calls Improve Patient Handling of Fecal Immunochemical Test Samples
The fecal immunochemical test (FIT) is an alternative to colonoscopy and can increase overall screening for colorectal cancer (CRC). However, little is known about the frequency of and reasons for mishandled FIT samples.
https://ift.tt/2P9YusS
Efficacy of Endoscopic Dilation of gastroduodenal Crohn’s disease strictures: A Systematic Review and Meta-analysis of Individual Patient Data
Little is know about the effects of endoscopic balloon dilation (EBD) for strictures of the upper gastrointestinal (UGI) tract in patients with Crohn's disease (CD). We performed a pooled analysis of the efficacy and safety of EBD for UGI CD-associated strictures.
https://ift.tt/2P7K3p2
Sperm Collection of Differential Quality Using Density Gradient Centrifugation
In this paper, we aim to describe the performance of the density gradient centrifugation technique and its application in sperm physiology research.
https://ift.tt/2QpaU4M
Using High Content Imaging to Quantify Target Engagement in Adherent Cells
https://ift.tt/2DP9pGh
Establishment and Analysis of Tumor Slice Explants As a Prerequisite for Diagnostic Testing
We provide a method for the generation, cultivation and systematic analysis of organotypic slices derived from murine lung tumors. We also describe how to optimize for slice thickness, and how to select drug concentrations to treat tumor slices.
https://ift.tt/2Qu541K
The Dantastic Mr. Tox & Howard – S02E05 – Don’t Call Her Czarina
The Opioid Crisis with UMass Chief Opioid Officer, Dr. Kavita Babu Join Dan (@drusyniak) &Howard (@heshiegreshie) as they welcome the first Chief Opioid Officer at UMass Memorial Health Care, Dr. Kavita Babu (@kavitababu) and talk about tackling the opioid crisis as toxicologists from boots on the ground to the halls of government. Get involved and […]
EMCrit Project by Tox & Hound.
https://ift.tt/2TWdm1v
Photogeneration of N-Heterocyclic Carbenes: Application in Photoinduced Ring-Opening Metathesis Polymerization
https://ift.tt/2Sjxk4B
Effect of hip joint angle at seat-off on hip joint contact force during sit-to-stand movement: a computer simulation study
Sit-to-stand movements are a necessary part of daily life, and excessive mechanical stress on the articular cartilage has been reported to encourage the progression of osteoarthritis. Although a change in hip ...
https://ift.tt/2KHJAJH
A remotely sensed flooding indicator associated with cattle and buffalo leptospirosis cases in Thailand 2011–2013
Leptospirosis is an important zoonotic disease worldwide, caused by spirochetes bacteria of the genus Leptospira. In Thailand, cattle and buffalo used in agriculture are in close contact with human beings. During...
https://ift.tt/2Q00U2q
Prevalence and associated factors of diabetes mellitus among tuberculosis patients in Hanoi, Vietnam
Diabetes mellitus (DM) is recognized as an important comorbidity for the development of tuberculosis (TB). With the increase of DM burden globally, concerns have been raised about the emerging co-epidemics of ...
https://ift.tt/2RsHhgh
A Pulmonary Trunk Banding Model of Pressure Overload Induced Right Ventricular Hypertrophy and Failure
https://ift.tt/2PZ3ZzE
Generating a Murine Orthotopic Metastatic Breast Cancer Model and Performing Murine Radical Mastectomy
We introduce a murine orthotopic breast cancer model and radical mastectomy model with bioluminescence technology to quantify the tumor burden to mimic human breast cancer progression.
https://ift.tt/2Ro4sZ5
Cow manure as a lignocellulosic substrate for fungal cellulase expression and bioethanol production
Conversion of various lignocellulosic materials into bioethanol is growing in demand but greatly depends on feedstock availability. Dairy cow manure is an agricultural waste widely distributed worldwide. This ...
https://ift.tt/2PZ3UvQ
Deep Learning Algorithm Detects Thoracic Pathologies on CXRs
THURSDAY, Nov. 29, 2018 -- A deep learning algorithm, CheXNeXt, performs comparably to radiologists in detecting multiple thoracic pathologies in frontal-view chest radiographs, according to a study published online Nov. 20 in PLOS Medicine. Pranav...
https://ift.tt/2QwsnbC
Dementia Often Misclassified With Brief Cognitive Assessments
THURSDAY, Nov. 29, 2018 -- When using brief cognitive assessments, dementia is often misclassified, according to a study published online Nov. 28 in Neurology Clinical Practice. Janice M. Ranson, from the University of Edinburgh in Scotland, and...
https://ift.tt/2DQXlEl
Monitoring Movement Reflects Efficacy of Mandibular Splint
THURSDAY, Nov. 29, 2018 -- For individuals with obstructive sleep apnea (OSA) treated with an optimally titrated mandibular advancement splint, normalization of the respiratory effort index derived from vertical mandibular movements (MM-REI)...
https://ift.tt/2Qwskws
Liquid Biopsy Can Assess Tx Response of Peds Brain Tumors
THURSDAY, Nov. 29, 2018 -- A liquid biopsy using blood or cerebrospinal fluid (CSF) can effectively quantify changes in mutation levels among pediatric patients being treated for diffuse midline gliomas (DMGs), according to a study recently...
https://ift.tt/2DRVmQb
Higher-Volume Hospitals Have Better Laryngectomy Outcomes
THURSDAY, Nov. 29, 2018 -- Laryngectomy outcomes appear to be associated with hospital volume for such cases, according to a study published online Nov. 21 in JAMA Otolaryngology-Head & Neck Surgery. Christine G. Gourin, M.D., from Johns Hopkins...
https://ift.tt/2QqRY5w
CDC: U.S. Life Expectancy Decreased From 2016 to 2017
THURSDAY, Nov. 29, 2018 -- From 2016 to 2017, there was a decrease in life expectancy in the United States, with recent increases noted in drug overdose deaths and suicide mortality, according to three reports published by the U.S. Centers for...
https://ift.tt/2DOtMDk
Persistent Back Pain Linked to Earlier Mortality in Older Women
THURSDAY, Nov. 29, 2018 -- Frequent persistent back pain is associated with increased mortality in older women, according to a study recently published in the Journal of General Internal Medicine. Eric J. Roseen, D.C., from Boston Medical Center,...
https://ift.tt/2QtUiss
Age-Related Vaginal Symptoms Tied to Worse Quality of Life
THURSDAY, Nov. 29, 2018 -- Severe vulvovaginal atrophy (VVA) symptoms are associated with worse quality of life in postmenopausal women, according to a study published online Nov. 12 in Menopause. Rossella E. Nappi, M.D., Ph.D., from the University...
https://ift.tt/2DOtKvc
Dry Eye Found to Have Negative Impact on Prolonged Reading
THURSDAY, Nov. 29, 2018 -- Dry eye seems to have a significant negative impact on prolonged reading, according to a study published online Nov. 15 in Optometry and Vision Science. Sezen Karakus, M.D., from Johns Hopkins University in Baltimore, and...
https://ift.tt/2QpWktz
Certain SGLT2 Inhibitors, GLP-1 RAs for T2DM Also Cut CV Risk
THURSDAY, Nov. 29, 2018 -- Certain sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) demonstrate significant cardiovascular (CV) benefit and should be used for reducing CV risk in patients...
https://ift.tt/2DOtHj0
Implementation of patient dosimetry in the clinical practice after targeted radiotherapy using [ 177 Lu-[DOTA0, Tyr3]-octreotate
Abstract
Background
This study's aim was to develop our dosimetric methodology using a commercial workstation for the routine evaluation of the organs at risk during peptide receptor radionuclide therapy (PRRT) with 177Lu.
Methods
First, planar and SPECT sensitivity factors were determined on phantoms. The reconstruction parameters were optimized by SPECT/CT image acquisition using a NEMA IEC phantom containing a 500 ml bottle of 177Lu, to simulate a kidney. The recovery coefficients were determined on various phantoms. For the red marrow, this was calculated using a NEMA IEC phantom that contained a centrally placed bottle of 80 ml of 177Lu (to model the L2-L4 red marrow) flanked by two 200 ml bottles with 177Lu to simulate the kidneys.
Then, SPECT/CT images were acquired at 4, 24, 72, and 192 h after injection in 12 patients with neuroendocrine tumors who underwent PRRT with 177Lu-DOTATATE. SPECT data were reconstructed using the iterative ordered subset expectation maximization (OSEM) method, with six iterations and ten subsets, attenuation, scatter, recovery resolution corrections, and a Gaussian post-filter of 0.11 cm. The liver, spleen, kidneys, and red marrow dose per administered activity (AD/A admin) values were calculated with the Medical Internal Radiation Dose (MIRD) formalism and the residence times (Dosimetry toolkit® application) using standard and CT imaging-based organ masses (OLINDA/EXM® V1.0 software).
Results
Sensitivity factors of 6.11 ± 0.01 and 5.67 ± 0.08 counts/s/MBq were obtained with planar and SPECT/CT acquisitions, respectively. A recovery coefficient of 0.78 was obtained for the modeled L2–L4 red marrow. The mean AD/A admin values were 0.43 ± 0.13 mGy/MBq [0.27–0.91] for kidneys, 0.54 ± 0.58 mGy/MBq [0.12–2.26] for liver, 0.61 ± 0.13 mGy/MBq [0.42–0.89] for spleen, and 0.04 ± 0.02 mGy/MBq [0.01–0.09] for red marrow. The AD/A admin values varied when calculated using the personalized and standard organ mass, particularly for kidneys (p = 1 × 10−7), spleen (p = 0.0069), and red marrow (p = 0.0027). Intra-patient differences were observed especially in organs close to or including tumor cells or metastases.
Conclusions
The obtained AD/A admin values were in agreement with the literature data. This study shows the technical feasibility of patient dosimetry in clinical practice and the need to obtain patient-specific information.
https://ift.tt/2Q3DQ2P
Identification of novel compound heterozygous SPG7 mutations-related hereditary spastic paraplegia in a Chinese family: a case report
Autosomal recessive hereditary spastic paraplegias (ARHSPs) are a group of clinically and genetically heterogeneous neurodegenerative diseases with progressive spasticity and weakness in the lower limbs. Mutat...
https://ift.tt/2AxV4e0
Therapeutic evaluation of a patient with ruptured intracranial aneurysm without subarachnoid hemorrhage by CT imaging: a case report
The majority of ruptured intracranial aneurysms are combined with subarachnoid hemorrhage, but patients with only intracerebral hematoma without any subarachnoid hemorrhage are extremely rare.
https://ift.tt/2TU1cq1
Pre-stroke warfarin enhancement of collateralization in acute ischemic stroke: a retrospective study
Warfarin therapies not only are used to prevent stroke in patients with high risk of cardioembolism such as patients with atrial fibrillation (AF) and rheumatic heart disease (RHD), but also was associated wit...
https://ift.tt/2Az2ZYF
A novel nonsense mutation in WNK1/HSN2 associated with sensory neuropathy and limb destruction in four siblings of a large Iranian pedigree
Hereditary sensory and autonomic neuropathy type 2 (HSAN2) is an autosomal recessive disorder with predominant sensory dysfunction and severe complications such as limb destruction. There are different subtype...
https://ift.tt/2TW9VrE
Large variations in the practice patterns of surgical antiseptic preparation solutions in patients with open and closed extremity fractures: a cross-sectional survey
Surgically-managed fractures, particularly open fractures, are associated with high rates of surgical site infections (SSIs). To reduce the risk of an SSI, orthopaedic surgeons routinely clean open fracture wo...
https://ift.tt/2AxIz2e
Costs of outpatient and inpatient MRSA screening and treatment strategies for patients at elective hospital admission - a decision tree analysis
Nosocomial infections are among the most common complications in hospitals. A major part is caused by multidrug-resistant organisms (MDRO). MRSA is still the most prominent and frequent MDRO. The early detecti...
https://ift.tt/2TZGcxM
Travel to Asia is a strong predictor for carriage of cephalosporin resistant E. coli and Klebsiella spp. but does not explain everything; prevalence study at a Norwegian hospital 2014–2016
We aimed to estimate the prevalence of faecal carriage of extended-spectrum cephalosporin (ESC) resistant E. coli and K. pneumoniae (ESCr-EK) and vancomycin resistant enterococci (VRE) in patients upon hospital a...
https://ift.tt/2TTTfBb
2D and 3D Echocardiography in the Axolotl (Ambystoma Mexicanum)
https://ift.tt/2PZL7R2
Biofilm model systems for root canal disinfection: a literature review
Abstract
The aim of this review is to present an overview of laboratory root canal biofilm model systems described in the endodontic literature, and to critically appraise the various factors that constitute these models.
The electronic databases MEDLINE, Web of Science and EMBASE were searched up to and including December 2016 to identify laboratory studies using endodontic biofilm models. The following search terms were used in various combinations: biofilm, root canal, in vitro, endodontic, bacteria, root canal infection model, colony‐forming unit. Only English papers from journals with an impact factor were selected. The records were screened by two reviewers and full‐text articles were assessed according to predefined criteria. The following data were extracted from the included studies: the microbial composition of the biofilm, the substrate, growth conditions, validation and quantification.
Seventy‐seven articles met the inclusion criteria. In the majority (86%) of the studies, a mono‐species biofilm was cultured. In two studies a dual‐species biofilm was grown; others cultivated a multispecies biofilm, containing at least three species. Enterococcus faecalis was the most frequently used test species (in 79% of all studies, 92% of the mono‐species studies). Four studies used an inoculum derived directly from the oral cavity. Human dentine was the most frequently used substratum (88% of the studies). Incubation times differed considerably, ranging from one to seventy days. The most common quantification method (in 87% of the studies) was bacterial culturing, followed by microscopy techniques.
The variation in laboratory root canal biofilm model systems is notable. Because of substantial variation in experimental parameters it is difficult to compare results between studies. This demonstrates the need for a more standardized approach and a validated endodontic biofilm model.
This article is protected by copyright. All rights reserved.
https://ift.tt/2G0Uw6D
Presence of osteocalcin, osteopontin, and reactive oxygen species‐positive cells in pulp tissue after dental bleaching
Abstract
Aim
To analyse the influence of H2O2 on pulp repair through osteocalcin and osteopontin immunolabelling, and in cellular defence by using the anti‐reactive oxygen species (ROS) antibody.
Methodology
The maxillary molars of 50 rats were treated with 35% H2O2 (Ble groups) or placebo gel (control groups). At 0 h and 2, 7, 15, and 30 days (n=10 hemimaxillae), the rats were killed and pulp tissue was evaluated using inflammation and immunolabelling scores (osteocalcin/osteopontin); ROS‐positive cells were counted. Paired t‐test and Wilcoxon signed‐rank test were used (P<0.05).
Results
The Ble group had necrosis in the coronal pulp at 0 h, and in the occlusal third of the coronal pulp at 2 days; at 7, 15, and 30 days, no inflammation was noted similar to the controls (P>0.05). Osteocalcin was absent in the Ble at 0 h, moderate at 2 days, and increased thereafter, differing from the controls at all two periods (P<0.05). Osteopontin was higher principally at 7 and 15 days in Ble groups, but differing with control groups from 2 days after bleaching (P<0.05). The Ble group had more ROS‐positive cells in the pulp at 7 and 15 days (P<0.05). Tertiary dentine was observed at 7 days, increasing thereafter (P<0.05).
Conclusions
Post‐bleaching pulp repair was associated with increased osteocalcin over time. Osteopontin also participate in this process, and anti‐ROS was involved in cellular defence against H2O2.
This article is protected by copyright. All rights reserved.
https://ift.tt/2rcc0CD
Collaborating filtering using unsupervised learning for image reconstruction from missing data
In the image acquisition process, important information in an image can be lost due to noise, occlusion, or even faulty image sensors. Therefore, we often have images with missing and/or corrupted pixels. In t...
https://ift.tt/2PbNlrz
Validation of a new WIND classification compared to ICC classification for weaning outcome
Although the WIND (Weaning according to a New Definition) classification based on duration of ventilation after the first separation attempt has been proposed, this new classification has not been tested in cl...
https://ift.tt/2zxeqQH
Mammographic density and breast tissue expression of inflammatory markers, growth factors, and vimentin
Abstract
Background
Mammographic density is a known risk factor for breast cancer, but the underlying pathologic characteristics are not well understood. The current analysis investigated the expression of several markers of interest, e.g., inflammation and growth, with mammographic density (MD) in normal and malignant breast tissue specimens from 279 women of the Multiethnic Cohort (MEC).
Methods
Breast cancer cases, recruited from a nested case-control study within the MEC, provided mammograms for density evaluation. Protein expression (COX-2, TNF-α, TGF-β, IGF-1R, IGFBP-2, and vimentin) was assessed by immunohistochemical detection. Linear regression was applied to evaluate the relation between marker expression and percent density and to compute adjusted means with 95% confidence intervals (CI) by marker status while adjusting for confounders.
Results
Due to missing cores and tissue, normal tissue could only be evaluated for COX-2 and vimentin. No significant associations with mammographic density were detected for all markers analyzed. For inflammatory markers (TNF-α, COX-2, and TGF-β) in tumor tissue, MD were non-significantly higher with stronger expression but the differences were very small. For example, the mean MD values for no, weak, and strong TNF-α expression were 35% (95% CI 24–47%), 39% (95% CI 29–48%), and 38% (95% CI 27–50%). In a posthoc analysis among postmenopausal women only, the difference across categories of TNF-α expression increased to 25% (95% CI 12–39%), 35% (95% CI 23–48%), and 35% (95% CI 20–49%).
Conclusions
The current analysis offers little support for an involvement of immunohistochemical markers representing inflammatory and growth factor pathways as predictors of breast density.
https://ift.tt/2TWtgZJ
The presumed MTH1-inhibitor TH588 sensitizes colorectal carcinoma cells to ionizing radiation in hypoxia
Abstract
Background
The nudix family member enzyme MutT homologue-1 (MTH1) hydrolyses the oxidized nucleotides 8-oxo-dGTP and 2-hydroxy-dATP and thus prevents the incorporation of damaged nucleotides into nuclear and mitochondrial DNA. Therefore MTH1 was proposed to protect cancer cells from oxidative DNA lesions and subsequent cell death. We investigated whether the bona fide MTH1 inhibitor TH588 affects responses of cultured colorectal tumor cells to ionizing radiation (IR) in normoxia and in moderate or severe hypoxia.
Methods
TH588 was tested in cell viability and survival assays (tetrazolium dye (MTT), propidium iodide staining, caspase-3 activity, and colony formation assays (CFA)) in colorectal carcinoma cells (HCT116 and SW480) in combination with IR in normoxia and in hypoxia. Additionally, MTH1 was targeted by lentiviral shRNA expression. Human umbilical vein endothelial cells (HUVEC) were assessed in MTT assays.
Results
In all cell lines tested, TH588 dose-dependently impaired cell survival. In CFAs, TH588 and IR effects on carcinoma cells were additive in normoxia and in hypoxia. Using 3 different shRNAs, the lentiviral approach was detrimental to SW480, but not to HCT116.
Conclusions
TH588 has cytotoxic effects on transformed and untransformed cells and synergizes with IR in normoxia and in hypoxia. TH588 toxicity is not fully explained by MTH1 inhibition as HCT116 were unaffected by lentiviral suppression of MTH1 expression. TH588 should be explored further because it has radiosensitizing effects in hypoxia.
https://ift.tt/2AxFNda
Is it sufficient to evaluate bone marrow involvement in newly diagnosed lymphomas using 18 F-FDG PET/CT and/or routine iliac crest biopsy? A new approach of PET/CT-guided targeted bone marrow biopsy
Abstract
Background
To investigate whether PET/CT-guided bone marrow biopsy adds complementary information for evaluation of bone marrow involvement (BMI) in newly diagnosed lymphomas.
Methods
Patients with newly diagnosed lymphomas that received both 18F-FDG PET/CT and bone marrow biopsy (BMB) were included in this retrospective study. PET/CT classification of bone lesions was classified as isolated, multifocal (2 lesions or more), diffuse (homogeneous uptake of the entire axial skeleton), or negative. BMBs included PET/CT-guided targeted BMB and/or the routine unilateral iliac crest biopsy. Of 34 patients with focal lesions on PET/CT scan, 30 received both PET/CT-guided targeted BMB and iliac crest biopsy, and 4 patients received targeted biopsy without iliac crest biopsy. The final diagnosis of BMI depends on BMB results.
Results
A total of 299 patients with lymphomas were included. PET/CT classification of bone lesions was isolated (16/5.4%), multifocal (67/22.4%), diffuse (52/17.4%), and negative (164/54.8%). If only positive iliac crest biopsy was considered as the reference standard, the sensitivity of 18F-FDG PET/CT for identifying focal and diffuse BMI was 48 and 56%, respectively, and the respective specificities were 70 and 83%. Three of 30 patients (10.0%) with focal lesions on PET/CT were confirmed to be false-positive by targeted BMB, and 25 of 30 patients (83.3%) with focal lesions on PET/CT were confirmed as false-negative by iliac crest biopsy.
Conclusion
It is insufficient to evaluate BMI in newly diagnosed lymphomas using both 18F-FDG PET/CT and routine iliac crest biopsy. 18F-FDG PET/CT imaging should be performed before BMB. In focal bone lesions, PET/CT-guided targeted BMB may complement the results of possible false-positive PET/CT and false-negative iliac crest biopsy findings. However, in diffuse and negative lesions, iliac crest biopsy cannot be safely omitted.
https://ift.tt/2TY639p
Comparison of clinical features, management and outcomes of osteosarcoma located in proximal fibula and proximal tibia: a propensity score matching analysis
Abstract
Background
The aim of this study was to compare proximal fibular and proximal tibial sites regarding osteosarcoma in the proximal crus. Furthermore, we proposed a hypothesis explaining the differences.
Methods
From Jaunary 2000 to February 2015, 28 patients with non-metastatic proximal fibular osteosarcoma and 214 patients with non-metastatic proximal tibial osteosarcoma underwent surgery were identified in our center. All clinical data were analyzed retrospectively. Propensity score matching of patients in a 1:2 ratio was conducted based on age, gender and Enneking stage. To analyze possible factors resulting in amputation, we investigated extraosseous tumor volumes (ETVS), the nearest of the blood vessel to reactive zone (NBR) and the nearest of the blood vessel to tumor (NBT).
Results
Amputation rates were higher in the proximal fibula cohort (35.7%) than in the proximal tibia cohort (14.3%; p = 0.046). Comparing possible clinical characteristics related with amputation between two cohorts, the proximal fibula cohort had larger ETVS (p = 0.000). Moreover, the proximal fibula cohort had a smaller NBT for anterior tibial vessels (p = 0.025), a smaller NBR for posterior tibial vessels (p = 0.013) and a smaller NBT for posterior tibial vessels (p = 0.007) than the proximal tibia cohort. Univarite and multivariable analyses showed that NBT for posterior tibial vessels was the only independent factor associated with amputation. The 3-year event-free survival (EFS) and overall survival (OS) rates for the proximal fibula cohort vs. the proximal tibia cohort were 52.6% vs. 78.0% (p = 0.045) and 63.7% vs. 81.2% (p = 0.177), respectively. The MSTS scores for the functional evaluation of limb-salvaging surgery were similar in both groups (p = 0.212).
Conclusions
Amputation rates among patients were higher when osteosarcoma was located in proximal fibula than in proximal tibia. A smaller NBT for posterior tibial vessels was associated with higher amputation rates. Prognosis of the proximal fibula cohort was poorer than that of the proximal tibia cohort of osteosarcoma patients.
https://ift.tt/2AxCHGg
MiR-20a, a novel promising biomarker to predict prognosis in human cancer: a meta-analysis
Abstract
Background
Recently, microRNA-20a (miR-20a) has been reported to influence the clinical features and may have prognostic value in human cancers. The present meta-analysis assessed the prognostic role of miR-20a in various carcinomas.
Methods
Literature searches of seven electronic databases were performed for eligible articles of the prognostic role of miR-20a in human cancers. Hazard ratios (HR) for overall survival (OS), disease free survival (DFS), progression-free survival (PFS) as well as their 95% confidence intervals (95%CIs) were used to assess the influence of miR-20a expression on patient prognosis. Odds ratio (OR) and 95%CIs were applied to evaluate the correlation between miR-20a expression and clinicopathological characteristics.
Results
Based on the OS analyzed by log rank tests, there was a significant association between miR-20a levels and OS by fixed effects model. By subgroup analyses, the significance was also observed in the studies of specimen derived from blood and gastrointestinal cancer group. The independent prognostic role of miR-20a expression for the OS was observed significantly by fixed effects model. In addition, we observed significant association between miR-20a expression levels and DFS of log rank tests, DFS of cox regression. Significant relation of gender/differentiation and the expression level of miR-20a was identified.
Conclusions
Base on the findings, the elevated miR-20a expression level is related to poor prognosis of gastrointestinal cancer patients. As for other types of carcinomas, the results are still not stable and more studies are required to further identify miR-20a prognostic values. In addition, miR-20a expression level is relatively higher in women than that in men, and increased miR-20a expression level is linked to poor tumor differentiation.
https://ift.tt/2TVEyxj
Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [ 18 F]FDG and sodium [ 18 F]fluoride PET
Abstract
Background
Osteosarcoma is the most common malignant bone tumor in children and young adults that produces aberrant osteoid. The aim of this study was to assess the utility of 2-deoxy-2-[18F-] fluoro-D-glucose ([18F] FDG) and sodium [18F] Fluoride (Na [18F] F) PET scans in orthotopic murine models of osteosarcoma to describe the metabolic pattern of the tumors, to detect and diagnose tumors and to evaluate the efficacy of a new treatment based in oncolytic adenoviruses.
Methods
Orthotopic osteosarcoma murine models were created by the injection of 143B and 531MII cell lines. [18F]FDG and Na [18F] F PET scans were performed 30 days (143B) and 90 days (531MII) post-injection. The antitumor effect of two doses (107 and 108 pfu) of the oncolytic adenovirus VCN-01 was evaluated in 531 MII model by [18F] FDG PET studies. [18F] FDG uptake was quantified by SUVmax and Total Lesion Glycolysis (TLG) indexes. For Na [18F] F, the ratio tumor SUVmax/hip SUVmax was calculated. PET findings were confirmed by histopathological techniques.
Results
The metabolic pattern of tumors was different between both orthotopic models. All tumors showed [18F] FDG uptake, with a sensitivity and specificity of 100%. The [18F] FDG uptake was significantly higher for the 143B model (p < 0.001). Sensitivity for Na [18F] F was around 70% in both models, with a specificity of 100%. 531MII tumors showed a heterogeneous Na [18F] F uptake, significantly higher than 143B tumors (p < 0.01). Importantly, [18F] FDG and Na [18F] F uptake corresponded to highly cellular or osteoid-rich tumors in the histopathological analysis, respectively. [18F] FDG data confirmed that the oncolytic treatment of 531MII tumors produced a significant reduction in growth even with the 107 pfu dose.
Conclusions
PET studies demonstrated that the different osteosarcoma xenograft models developed tumors with diverse metabolic patterns that can be described by multitracer PET studies. Since not all tumors produced abundant osteoid, [18F] FDG demonstrated a better sensitivity for tumor detection and was able to quantitatively monitor in vivo response to the oncolytic adenovirus VCN-01.
https://ift.tt/2Av6zmk
Protective role of all-trans retinoic acid (ATRA) against hypoxia-induced malignant potential of non-invasive breast tumor derived cells
Abstract
Background
The presence of hypoxic areas is common in all breast lesions but no data clearly correlate low oxygenation with the acquisition of malignant features by non-invasive cells, particularly by cells from ductal carcinoma in situ (DCIS), the most frequently diagnosed tumor in women.
Methods
By using a DCIS-derived cell line, we evaluated the effects of low oxygen availability on malignant features of non-invasive breast tumor cells and the possible role of all-trans retinoic acid (ATRA), a well-known anti-leukemic drug, in counteracting the effects of hypoxia. The involvement of the β2 isoform of PI-PLC (PLC-β2), an ATRA target in myeloid leukemia cells, was also investigated by specific modulation of the protein expression.
Results
We demonstrated that moderate hypoxia is sufficient to induce, in DCIS-derived cells, motility, epithelial-to-mesenchymal transition (EMT) and expression of the stem cell marker CD133, indicative of their increased malignant potential.
Administration of ATRA supports the epithelial-like phenotype of DCIS-derived cells cultured under hypoxia and keeps down the number of CD133 positive cells, abrogating almost completely the effects of poor oxygenation. We also found that the mechanisms triggered by ATRA in non-invasive breast tumor cells cultured under hypoxia is in part mediated by PLC-β2, responsible to counteract the effects of low oxygen availability on CD133 levels.
Conclusions
Overall, we assigned to hypoxia a role in increasing the malignant potential of DCIS-derived cells and we identified in ATRA, currently used in treatment of acute promyelocytic leukemia (APL), an agonist potentially useful in preventing malignant progression of non-invasive breast lesions showing hypoxic areas.
https://ift.tt/2TVEopH
Recognising Lung Cancer in Primary Care
Abstract
Significant advances in the management of both early and advanced stage lung cancer have not yet led to the scale of improved outcomes which have been achieved in other cancers over the last 40 years. Diagnosis of lung cancer at the earliest stage of disease is strongly associated with improved survival. Therefore, although recent advances in oncology may herald breakthroughs in effective treatment, achieving early diagnosis will remain crucial to obtaining optimal outcomes. This is challenging, as most lung cancer symptoms are non-specific or are common respiratory symptoms which usually represent benign disease. Identification of patients at risk of lung cancer who require further investigation is an important responsibility for general practitioners (GPs). Diagnosis has historically relied upon plain chest X-ray (CXR), organised in response to symptoms. The sensitivity of this modality, however, compares unfavourably with that of computed tomography (CT). In some jurisdictions screening high-risk individuals with low dose CT (LDCT) is now recommended. However uptake remains low and the eligibility for screening programmes is restricted. Therefore, even if screening is widely adopted, most patients will continue to be diagnosed after presenting with symptoms. Achieving early diagnosis requires GPs to maintain an appropriate level of suspicion and readiness to investigate in high-risk patients or those with non-resolving symptoms. This article discusses the early detection of lung cancer from a primary care perspective. We outline risk factors and epidemiology, the role of screening and offer guidance on the recognition of symptomatic presentation and the investigation and referral of suspected lung cancer.
https://ift.tt/2TWp7VF
Development of an improved parameter fitting method for planar biaxial testing using rakes
Summary
A correct estimation of the material parameters from a planar biaxial test is crucial since they will affect the outcome of the finite element model in which they are used. In a virtual planar biaxial experiment, a difference can be noticed in the stress calculated from the force measured experimentally at the rakes and the actual stress at the center of the sample. As a consequence, a classic parameter fitting does not result in a correct estimation of the material parameters. This difference is caused by the boundary conditions of the set‐up and is among others dependent on the sample material. To overcome this problem, a new parameter fitting procedure is proposed that takes this difference into account by calculating a finite element‐based correction vector.
This paper describes the methodology to apply this new parameter fitting procedure on real experimental data from a planar biaxial test using rakes. To this end, image processing is used to extract the experiment characteristics. This information is used to construct a finite element model. Two variations of the new parameter fitting procedure are investigated using two human aortic samples: a basic and an image‐based approach. The performance of the method is assessed by the difference between the force measured at the rakes during the experiment and the force at the rakes obtained from the finite element simulation.
Both approaches of the new parameter fitting procedure lead to an improved estimation of the sample behavior compared to the classic approach.
https://ift.tt/2P6lF7n
Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool
Fu et al. demonstrate the presence and multilineage differentiation potential of hematopoietic stem and progenitor cells (HSPCs) carried in human intestinal allografts. These contribute to peripheral blood mixed chimerism in the recipient. Kinetic turnover studies revealed the gradual replacement of intestinal mucosal HSPCs by a circulating pool in humans.
https://ift.tt/2E4heZp
Mesenchymal Precursor Cells in Adult Nerves Contribute to Mammalian Tissue Repair and Regeneration
Carr et al. demonstrate that peripheral nerves contain mesenchymal precursor-like cells that participate in repair of damaged mesenchymal tissues. Utilizing scRNA-seq, lineage tracing, and transplantation approaches, the authors show that neural crest-derived endoneurial mesenchymal precursor cells generate bone and dermal cells during digit tip regeneration and skin wound healing.
https://ift.tt/2SlMBSA
Single-Cell Sequencing of iPSC-Dopamine Neurons Reconstructs Disease Progression and Identifies HDAC4 as a Regulator of Parkinson Cell Phenotypes
Bulk and single-cell RNA-seq of iPSC-derived dopamine neurons from control and PD GBA-N370S patients stratified a clinically distinct patient and revealed HDAC4 as a potential therapeutic PD target. Pharmacological modulation of HDAC4 rescued PD-related phenotypes in GBA-N370S neurons. HDAC4 perturbation was also observed in a subset of sporadic PD patients.
https://ift.tt/2E4oiWb
Cancers, Vol. 10, Pages 475: Identification and Characterization of MicroRNAs Associated with Somatic Copy Number Alterations in Cancer
Cancers, Vol. 10, Pages 475: Identification and Characterization of MicroRNAs Associated with Somatic Copy Number Alterations in Cancer
Cancers doi: 10.3390/cancers10120475
Authors: Jihee Soh Hyejin Cho Chan-Hun Choi Hyunju Lee
MicroRNAs (miRNAs) are key molecules that regulate biological processes such as cell proliferation, differentiation, and apoptosis in cancer. Somatic copy number alterations (SCNAs) are common genetic mutations that play essential roles in cancer development. Here, we investigated the association between miRNAs and SCNAs in cancer. We collected 2538 tumor samples for seven cancer types from The Cancer Genome Atlas. We found that 32−84% of miRNAs are in SCNA regions, with the rate depending on the cancer type. In these regions, we identified 80 SCNA-miRNAs whose expression was mainly associated with SCNAs in at least one cancer type and showed that these SCNA-miRNAs are related to cancer by survival analysis and literature searching. We also identified 58 SCNA-miRNAs common in the seven cancer types (CC-SCNA-miRNAs) and showed that these CC-SCNA-miRNAs are more likely to be related with protein and gene expression than other miRNAs. Furthermore, we experimentally validated the oncogenic role of miR-589. In conclusion, our results suggest that SCNA-miRNAs significantly alter biological processes related to cancer development, confirming the importance of SCNAs in non-coding regions in cancer.
https://ift.tt/2SmD4e1
Survival, local control, and health‐related quality of life in patients with oligometastatic and polymetastatic spinal tumors: A multicenter, international study
Abstract
Background
The treatment of oligometastatic (≤5 metastases) spinal disease has trended toward ablative therapies, yet to the authors' knowledge little is known regarding the prognosis of patients presenting with oligometastatic spinal disease and the value of this approach. The objective of the current study was to compare the survival and clinical outcomes of patients with cancer with oligometastatic spinal disease with those of patients with polymetastatic (>5 metastases) disease.
Methods
The current study was an international, multicenter, prospective study. Patients who were admitted to a participating spine center with a diagnosis of spinal metastases and who underwent surgical intervention and/or radiotherapy between August 2013 and May 2017 were included. Data collected included demographics, overall survival, local control, and treatment information including surgical, radiotherapy, and systemic therapy details. Health‐related quality of life (HRQOL) measures included the EuroQOL 5 dimensions 3‐level questionnaire (EQ‐5D‐3L), the 36‐Item Short Form Health Survey (SF‐36v2), and the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ).
Results
Of the 393 patients included in the current study, 215 presented with oligometastatic disease and 178 presented with polymetastatic disease. A significant survival advantage of 90.1% versus 77.3% at 3 months and 77.0% versus 65.1% at 6 months from the time of treatment was found for patients presenting with oligometastatic disease compared with those with polymetastatic disease. It is important to note that both groups experienced significant improvements in multiple HRQOL measures at 6 months after treatment, with no differences in these outcome measures noted between the 2 groups.
Conclusions
The treatment of oligometastatic disease appears to offer a significant survival advantage compared with polymetastatic disease, regardless of treatment choice. HRQOL measures were found to improve in both groups, demonstrating a palliative benefit for all treated patients.
https://ift.tt/2raA9tl
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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...
