Background. Recently, high-intensity intermittent training (HIIT) appears to have the same beneficial effects or even superior to those of continuous moderate-intensity training (CMIT) on body fat mass reduction. Exercise may induce myokine secretion such as irisin, which plays a role as a mediator of beiging process, and thus might contribute as treatment of obesity. However, the effects of those exercise formulas on irisin level changes as beiging agent are not known. In addition, metabolic states may affect the irisin responses to those exercise formulas. Therefore, this study was aimed to determine the different effects of exercises using HIIT and CMIT on circulating and tissue irisin levels in normal and abnormal metabolic conditions (obese). Methods. Sixteen male Sprague-Dawley rats (8 weeks of age) were randomized to 4 groups according to training regimens (HIIT and CMIT) and metabolic conditions (normal and abnormal/obese). The groups are (1) HIIT on normal metabolic (n=4), (2) CMIT on normal metabolic (n=4), (3) HIIT on abnormal metabolic (n=4), and (4) CMIT on abnormal metabolic (n=4). Abnormal metabolic condition was induced with high fat diet (19% fat) for 8 weeks in obese rats. Irisin levels in serum, skeletal muscle, and white adipose tissue were evaluated by ELISA. Results. Serum irisin levels were shown significantly higher in normal metabolic compared to abnormal metabolic condition (P0.05). Regarding exercise formula, no different effects were found between HIIT and CMIT on skeletal muscle irisin levels in both metabolic conditions (P>0.05). The similar findings were observed in serum irisin levels (P>0.05). Conclusions. The exercise effects in abnormal metabolic condition might be more adaptable in maintaining the irisin levels in skeletal muscle and induce the irisin uptake from circulation into adipose tissue. In addition, HIIT might be more involved to induce irisin uptake into adipose tissue; thus it might have the significant role in beiging process. However, further research about how the HIIT formula affects the regulation mechanisms of irisin uptake into adipose tissue is still warranted.
http://bit.ly/2TdjrW6
Τετάρτη 26 Δεκεμβρίου 2018
The Effects of Exercise Regimens on Irisin Levels in Obese Rats Model: Comparing High-Intensity Intermittent with Continuous Moderate-Intensity Training
Optimization of Subcritical Water Extraction (SWE) of Lipid and Eicosapentaenoic Acid (EPA) from Nannochloropsis gaditana
Microalgae are a promising source of omega-3. The purpose of this study was to extract lipid with a relatively high content of eicosapentaenoic acid (EPA) from Nannochloropsis gaditana using subcritical water extraction (SWE). The effects of different temperatures (156.1-273.9°C), extraction times (6.6-23.4 minutes), and biomass loadings (33-117 g algae/L) on the extraction yield were studied. From the optimization study using central composite design (CCD), quadratic models generated for lipid yield and EPA composition were considered to be significant models (p
http://bit.ly/2TaRpKT
Randomized-controlled phase II trial of salvage chemotherapy after immunization with a TP53 -transfected dendritic cell-based vaccine (Ad.p53-DC) in patients with recurrent small cell lung cancer
Abstract
Small cell lung cancer TP53 mutations lead to expression of tumor antigens that elicits specific cytotoxic T-cell immune responses. In this phase II study, dendritic cells transfected with wild-type TP53 (vaccine) were administered to patients with extensive-stage small cell lung cancer after chemotherapy. Patients were randomized 1:1:1 to arm A (observation), arm B (vaccine alone), or arm C (vaccine plus all-trans-retinoic acid). Vaccine was administered every 2 weeks (3 times), and all patients were to receive paclitaxel at progression. Our primary endpoint was overall response rate (ORR) to paclitaxel. The study was not designed to detect overall response rate differences between arms. Of 69 patients enrolled (performance status 0/1, median age 62 years), 55 were treated in stage 1 (18 in arm A, 20 in arm B, and 17 in arm C) and 14 in stage 2 (arm C only), per 2-stage Simon Minimax design. The vaccine was safe, with mostly grade 1/2 toxicities, although 1 arm-B patient experienced grade 3 fatigue and 8 arm-C patients experienced grade 3 toxicities. Positive immune responses were obtained in 20% of arm B (95% confidence interval [CI], 5.3–48.6) and 43.3% of arm C (95% CI 23.9–65.1). The ORRs to the second-line chemotherapy (including paclitaxel) were 15.4% (95% CI 2.7–46.3), 16.7% (95% CI 2.9–49.1), and 23.8% (95% CI 9.1–47.5) for arms A, B, and C, with no survival differences between arms. Although our vaccine failed to improve ORRs to the second-line chemotherapy, its safety profile and therapeutic immune potential remain. Combinations with the other immunotherapeutic agents are reasonable options.
http://bit.ly/2AiE4Jn
Hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts
Abstract
Background
Hepatocellular carcinoma (HCC) remains a global challenge due to its high morbidity and mortality rates as well as poor response to treatment. The communication between tumor-derived elements and stroma plays a critical role in facilitating cancer progression of HCC. Exosomes are small extracellular vesicles (EVs) that are released from the cells upon fusion of multivesicular bodies with the plasma membrane. There is emerging evidence indicating that exosomes play a central role in cell-to-cell communication. Much attention has been paid to exosomes since they are found to transport bioactive proteins, messenger RNA (mRNAs) and microRNA (miRNAs) that can be transferred in active form to adjacent cells or to distant organs. However, the mechanisms underlying such cancer progression remain largely unexplored.
Methods
Exosomes were isolated by differential ultracentrifugation from conditioned medium of HCC cells and identified by electron microscopy and Western blotting analysis. Hepatic stellate cells (HSCs) were treated with different concentrations of exosomes, and the activation of HSCs was analyzed by Western blotting analysis, wound healing, migration assay, Edu assay, CCK-8 assay and flow cytometry. Moreover, the different miRNA levels of exosomes were tested by real-time quantitative PCR (RT-PCR). The angiogenic ability of activated HSCs was analyzed by qRT-PCR, CCK-8 assay and tube formation assay. In addition, the abnormal lipid metabolism of activated HSCs was analyzed by Western blotting analysis and Oil Red staining. Finally, the relationship between serum exosomal miRNA-21 and prognosis of HCC patients was evaluated.
Results
We showed that HCC cells exhibited a great capacity to convert normal HSCs to cancer-associated fibroblasts (CAFs). Moreover, our data revealed that HCC cells secreted exosomal miRNA-21 that directly targeted PTEN, leading to activation of PDK1/AKT signaling in HSCs. Activated CAFs further promoted cancer progression by secreting angiogenic cytokines, including VEGF, MMP2, MMP9, bFGF and TGF-β. Clinical data indicated that high level of serum exosomal miRNA-21 was correlated with greater activation of CAFs and higher vessel density in HCC patients.
Conclusions
Intercellular crosstalk between tumor cells and HSCs was mediated by tumor-derived exosomes that controlled progression of HCC. Our findings provided potential targets for prevention and treatment of live cancer.
http://bit.ly/2AieAvP
RNA sequencing reveals the expression profiles of circRNA and indicates that circDDX17 acts as a tumor suppressor in colorectal cancer
Abstract
Background
Circular RNA (circRNA) is a novel class of noncoding RNAs with functions in various pathophysiological activities. However, the expression profiles and functions of circRNAs in colorectal cancer (CRC) remain largely unknown.
Methods
High-throughput RNA sequencing (RNA-seq) was performed to assess circRNA expression profiles in 4 paired CRC tissues, and significantly dysregulated circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of dysregulated circRNAs. Target miRNAs of circRNAs were predicted using miRanda software, and were further analyzed combining DIANA-miRPath v.3 platform (Reverse Search module) with KEGG pathways of COLORECTAL CANCER and MicroRNAs in cancer (Entry: map05210 and map05206). CircRNA-miRNA interaction networks were constructed using Cytoscape software. Expression levels of a significantly down-regulated circRNA, circDDX17 (hsa_circ_0002211), was detected by qRT-PCR in 60 paired CRC tissues. CircDDX17 was knockdown by siRNA, and the biological functions of circDDX17 were examined in CRC cell lines.
Results
Totally 448 differentially expressed circRNAs were identified, including 394 up-regulated and 54 down-regulated circRNAs. qRT-PCR validation confirmed the reliability of the RNA-Seq data. GO and KEGG analyses revealed that these dysregulated circRNAs were potentially implicated in CRC pathogenesis. Analyses by combining miRanda and miRPath softwares with KEGG pathways suggested that the miRNAs targeted by the top 10 dysregulated circRNAs were associated with the KEGG pathways of COLORECTAL CANCER and MicroRNAs in cancer, indicating that circRNA-miRNA interactions might play important functional roles in the initiation and progression of CRC. The results of qRT-PCR for circDDX17 in 60 paired CRC tissues showed that circDDX17 was significantly down-regulated in CRC tissues and associated with unfavorable clinicopathological parameters. In vitro experiments showed that silencing of circDDX17 promoted CRC cell proliferation, migration, invasion, and inhibited apoptosis.
Conclusions
In conclusion, we have identified numerous circRNAs that are dysregulated in CRC tissues compared with adjacent normal mucosa tissues. Bioinformatic analyses suggested that these dysregulated circRNAs might play important functional roles in CRC tumorigenesis. CircDDX17 functions as a tumor suppressor and could serve as a potential biomarker and a therapeutic target for CRC.
http://bit.ly/2SmYI2a
Metaplastic carcinoma of breast
| : A series of nine cases from a regional cancer center in Northeast India | p. 69 |
| Srigopal Mohanty, Yumkhaibam Sobita Devi, Daffilyne Lyngdoh Nongrum, Laishram Jaichand Singh, Vimal Sekar, Deep Sikha Das DOI:10.4103/oji.oji_39_18 Background: Metaplastic carcinoma of the breast (MCB) is a rare histological subtype of breast carcinoma containing glandular and nonglandular components with mixed epithelial and mesenchymal differentiations. Aim of the Study: The study aimed to report clinical, radiological and pathological profiles, treatment and outcome of patients diagnosed with MCB from a tertiary care institute along with literature review. Materials and Methods:Diagnosed cases of MCB were obtained from the record over a period of January 2010 to December 2017, and data were recorded in a structured pro forma. Results: A total of 9 (0.9%) cases of MCB were identified out of 1031 breast cancer patients with the median age of presentation of 53 years. The palpable lump was the most common presentation (77.78%). The mean tumor size was 4.9 cm in greatest dimension. Sonographically, most of the lesions were solid (44.44%) followed by cystic (33.33%). Mammographically, microcalcifications were absent in eight cases. Histologically, 55.56% of cases were purely epithelial subtype (3: pure squamous and 2: adenosquamous) and 4 (44.44%) cases were mixed epithelial and mesenchymal subtypes (3: carcinosarcoma and 1: invasive lobular carcinoma with sarcomatous component and osseous metaplasia). All the cases were having triple-negative receptor status. Modified radical mastectomy (MRM) was performed in all cases and 33.33% of cases had axillary node positive. About 77.88% and 88.89% of cases received adjuvant chemotherapy and adjuvant radiotherapy, respectively. At median follow-up of 27 months, local recurrence and distant metastases were seen in 1 and 3 cases, respectively. At present, 33.33%, 22.22%, and 44.45% of patients were died, alive, and lost for follow-up, respectively. Conclusion: MCB is a rare histologic subtype of breast cancer with larger tumor size at presentation and MRM is the preferred surgical procedure over breast conservation surgery. Long-term and regular follow-up is necessary to know the outcome. |
Anti-cancer and anti-inflammatory activities of aronia (Aronia melanocarpa) leaves
Effects of phototherapy on outer hair cell function in infants with hyperbilirubinemia
Vikas Mysore Dwarakanath, Pavana Mohan, Sapthami Patel
DOI:10.4103/jisha.JISHA_8_17
Introduction: Hyperbilirubinemia in newborns has been hypothesized to cause damage to inner ear, thus leading to sensorineural hearing loss. Phototherapy is treatment protocol in most of the hospitals for newborns with high bilirubin levels. The present study aimed to determine the effects of phototherapy on outer hair cell (OHC) function of cochlea. Methods: Twenty-two neonates with hyperbilirubinemia undergoing phototherapy and 22 neonates without any high-risk registers were included in the study. Distortion product otoacoustic emission (DPOAE) was administered before and after phototherapy. Auditory brainstem response (ABR) evaluation was done during the postphototherapy recording. Results: Results showed that DP amplitude and signal-to-noise ratio improved significantly after phototherapy. ABR evaluation revealed; 19 neonates had significantly prolonged wave V latency compared to normal, whereas no peaks were identified among three neonates. Most of the infantile hyperbilirubinemia are found to be harmless until and unless treatment is not initiated at the earliest, but still it is found that short-term increase in bilirubin level can induce temporary changes in OAEs and ABR measures. ABR needs to be repeated over a period of time for these three neonates to rule out auditory dyssynchrony (AD). Conclusion: The results indicate that phototherapy has temporary effects on OHC function and can improve as the bilirubin levels reduce. Follow-up testing over a period of time helps in discriminating the sensory pathology and AD.
http://www.jisha.org/currentissue.asp?sabs=y
Long-term exposure to traffic noise
PG Vipin Ghosh, D Nagashreeya, V Hemavathi
DOI:10.4103/jisha.JISHA_24_18
Introduction: The acceptable noise level (ANL) measure is a subjective way of identifying how much of noise a person is able to put up with while listening to speech. Individuals with low ANL were observed to be satisfied hearing users than the individuals with high ANL. However, the reason for large individual variations of the measure is still not well understood. Exposure to noise may be one such factor that would affect the ANL which was never explored. Among the individuals who are exposed to noise, majority are exposed to occupational noise. Traffic police is such a working population who is exposed continuously to traffic noise during their duty hours. Hence, the present study was planned to investigate ANL measures in traffic police officers that might further provide insight toward the heterogeneity of the measure. Methods: A total of 38 participants were divided into two groups. Group 1 consisted of 19 traffic police officers with minimum of 5 years of job experience and Group 2 consisted of normal hearing individuals without any noise exposure. All the participants underwent routine audiological evaluations followed by ANL testing. Results: The mean ANL obtained in both the groups was statistically compared. The results revealed that the traffic police officers yielded better ANLs than participants in Group 2. Conclusion: This ability of traffic police officers to put up with more noise while listening to speech may be attributed to their long-standing experience in listening to wanted signals in noise.
http://www.jisha.org/currentissue.asp?sabs=y
Randomized-controlled phase II trial of salvage chemotherapy after immunization with a TP53 -transfected dendritic cell-based vaccine (Ad.p53-DC) in patients with recurrent small cell lung cancer
Abstract
Small cell lung cancer TP53 mutations lead to expression of tumor antigens that elicits specific cytotoxic T-cell immune responses. In this phase II study, dendritic cells transfected with wild-type TP53 (vaccine) were administered to patients with extensive-stage small cell lung cancer after chemotherapy. Patients were randomized 1:1:1 to arm A (observation), arm B (vaccine alone), or arm C (vaccine plus all-trans-retinoic acid). Vaccine was administered every 2 weeks (3 times), and all patients were to receive paclitaxel at progression. Our primary endpoint was overall response rate (ORR) to paclitaxel. The study was not designed to detect overall response rate differences between arms. Of 69 patients enrolled (performance status 0/1, median age 62 years), 55 were treated in stage 1 (18 in arm A, 20 in arm B, and 17 in arm C) and 14 in stage 2 (arm C only), per 2-stage Simon Minimax design. The vaccine was safe, with mostly grade 1/2 toxicities, although 1 arm-B patient experienced grade 3 fatigue and 8 arm-C patients experienced grade 3 toxicities. Positive immune responses were obtained in 20% of arm B (95% confidence interval [CI], 5.3–48.6) and 43.3% of arm C (95% CI 23.9–65.1). The ORRs to the second-line chemotherapy (including paclitaxel) were 15.4% (95% CI 2.7–46.3), 16.7% (95% CI 2.9–49.1), and 23.8% (95% CI 9.1–47.5) for arms A, B, and C, with no survival differences between arms. Although our vaccine failed to improve ORRs to the second-line chemotherapy, its safety profile and therapeutic immune potential remain. Combinations with the other immunotherapeutic agents are reasonable options.
http://bit.ly/2AiE4Jn
Randomized phase II study of the PDGFRα antibody olaratumab plus liposomal doxorubicin versus liposomal doxorubicin alone in patients with platinum-refractory or platinum-resistant advanced ovarian cancer
Abstract
Background
Olaratumab is a platelet-derived growth factor receptor-α (PDGFRα)-targeting monoclonal antibody blocking PDGFRα signaling. PDGFRα expression is associated with a more aggressive phenotype and poor ovarian cancer outcomes. This randomized, open label phase II study evaluated olaratumab plus liposomal doxorubicin compared with liposomal doxorubicin alone in advanced ovarian cancer patients.
Methods
Patients with platinum-refractory or platinum-resistant advanced ovarian cancer were randomized 1:1 to receive liposomal doxorubicin (40 mg/m2, intravenous infusion) administered every 4 weeks with or without olaratumab (20 mg/kg, IV infusion) every 2 weeks. Patients were stratified based on prior response to platinum therapy (refractory vs resistant). The primary efficacy endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, duration of response, and safety.
Results
A total of 123 patients were treated (62 olaratumab+liposomal doxorubicin; 61 liposomal doxorubicin). Median PFS was 4.2 months for olaratumab+liposomal doxorubicin and 4.0 months for liposomal doxorubicin (stratified hazard ratio [HR] = 1.043; 95% confidence interval [CI] 0.698–1.558; p = 0.837). Median OS was 16.6 months and 16.2 months in the olaratumab+liposomal doxorubicin and liposomal doxorubicin arms, respectively (HR = 1.098; 95% CI 0.71–1.71). In the platinum-refractory subgroup, median PFS was 5.5 months (95% CI 1.6–9.2) and 3.7 months (95% CI 1.9–9.2) in the olaratumab+liposomal doxorubicin (n = 15) and liposomal doxorubicin arms (n = 16), respectively (HR = 0.85; 95% CI 0.38–1.91). Overall, 59.7% (olaratumab+liposomal doxorubicin) and 65.6% (liposomal doxorubicin) of patients reported grade ≥ 3 adverse events regardless of causality. The most common treatment-emergent adverse events (all grades) regardless of causality were fatigue related (61%), nausea (57%), and constipation (52%) with olaratumab+liposomal doxorubicin and nausea (64%), fatigue related (62%), and mucositis (46%) with liposomal doxorubicin.
Conclusions
The addition of olaratumab to liposomal doxorubicin did not result in significant prolongation of PFS or OS in platinum-resistant or platinum-refractory ovarian cancer.
Trial registration
ClinicalTrials.gov identifier: NCT00913835; registered June 2, 2009.
http://bit.ly/2SnxpVg
“Slime” dermatitis, a fad‐associated chronic hand dermatitis - Kondratuk - - Pediatric Dermatology - Wiley Online Library
https://onlinelibrary.wiley.com/doi/10.1111/pde.13729
The impact of pediatric atopic dermatitis on families: A review - Yang - - Pediatric Dermatology - Wiley Online Library
Objective
This literature review outlines how atopic dermatitis impacts the quality of life of families of children affected by AD.
Methods
A total of 3436 articles were identified via an online search of the MEDLINE health literature database and were screened for relevance to quality of life impacts on families with children affected by AD.
Results
Caring for children affected by AD can be an extremely time‐consuming task that can impair personal relationships, decrease psychosocial functioning, and cause sleep loss among family members of affected patients. Additionally, AD may result in work absence or decreased work productivity for caregivers. Special diets, irritant and allergen avoidance strategies, and alternative therapies are commonly used by patients to manage their disease and require large amounts of family involvement.
Conclusions
Atopic dermatitis can greatly decrease quality of life of families of affected children in various domains, including sleep, finances, and relationships. Early intervention and psychotherapy may be needed in some patients to address these quality of life impairments.
https://onlinelibrary.wiley.com/doi/10.1111/pde.13727
Successful treatment of hemorrhagic bullous Henoch‐Schonlein purpura with intravenous immunoglobulins - Mauro - - Pediatric Dermatology - Wiley Online Library
https://onlinelibrary.wiley.com/doi/10.1111/pde.13715
Biology of human melanocyte development, Piebaldism, and Waardenburg syndrome - Saleem - - Pediatric Dermatology - Wiley Online Library
https://onlinelibrary.wiley.com/doi/10.1111/pde.13713
Focal facial dermal dysplasia type 4.Bilateral preauricular scarlike defects surrounded by a hair collar, resembling membranous aplasia cutis congenita.
https://onlinelibrary.wiley.com/doi/10.1111/pde.13730
Bullous pemphigoid in adolescence - Patsatsi - - Pediatric Dermatology - Wiley Online Library
https://onlinelibrary.wiley.com/doi/10.1111/pde.13717
Functional near‐infrared spectroscopy as a tool for assessing speech and spoken language processing in pediatric and adult cochlear implant users
Abstract
Much of what is known about the course of auditory learning in following cochlear implantation is based on behavioral indicators that users are able to perceive sound. Both prelingually deafened children and postlingually deafened adults who receive cochlear implants display highly variable speech and language processing outcomes, although the basis for this is poorly understood. To date, measuring neural activity within the auditory cortex of implant recipients of all ages has been challenging, primarily because the use of traditional neuroimaging techniques is limited by the implant itself. Functional near‐infrared spectroscopy (fNIRS) is an imaging technology that works with implant users of all ages because it is non‐invasive, compatible with implant devices, and not subject to electrical artifacts. Thus, fNIRS can provide insight into processing factors that contribute to variations in spoken language outcomes in implant users, both children and adults. There are important considerations to be made when using fNIRS, particularly with children, to maximize the signal‐to‐noise ratio and to best identify and interpret cortical responses. This review considers these issues, recent data, and future directions for using fNIRS as a tool to understand spoken language processing in children and adults who hear through a cochlear implant.
http://bit.ly/2ArWGHd
DPM as a radiation transport engine for PRIMO
Abstract
Background
PRIMO is a dose verification system based on the general-purpose Monte Carlo radiation transport code penelope, which implements an accurate physics model of the interaction cross sections and the radiation transport process but with low computational efficiency as compared with fast Monte Carlo codes. One of these fast Monte Carlo codes is the Dose Planning Method (DPM). The purpose of this work is to describe the adaptation of DPM as an alternative PRIMO computation engine, to validate its performance against penelope and to validate it for some specific cases.
Methods
DPM was parallelized and modified to perform radiation transport in quadric geometries, which are used to describe linacs, thus allowing the simulation of dynamic treatments. To benchmark the new code versus penelope, both in terms of accuracy of results and simulation time, several tests were performed, namely, irradiation of a multi-layer phantom, irradiation of a water phantom using a collimating pattern defined by the multileaf collimator (MLC), and four clinical cases. The gamma index, with passing criteria of 1 mm/1%, was used to compare the absorbed dose distributions. Clinical cases were compared using a 3-D gamma analysis.
Results
The percentage of voxels passing the gamma criteria always exceeded 99% for the phantom cases, with the exception of the transport through air, for which dose differences between DPM and penelope were as large as 24%. The corresponding percentage for the clinical cases was larger than 99%. The speedup factor between DPM and penelope ranged from 2.5 ×, for the simulation of the radiation transport through a MLC and the subsequent dose estimation in a water phantom, up to 11.8 × for a lung treatment. A further increase of the computational speed, up to 25 ×, can be obtained in the clinical cases when a voxel size of (2.5 mm)3 is used.
Conclusions
DPM has been incorporated as an efficient and accurate Monte Carlo engine for dose estimation in PRIMO. It allows the concatenated simulation of the patient-dependent part of the linac and the patient geometry in static and dynamic treatments. The discrepancy observed between DPM and penelope, which is due to an artifact of the cross section interpolation algorithm for low energy electrons in air, does not affect the results in other materials.
http://bit.ly/2LBz0En
Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple negative breast cancer patients after neo-adjuvant chemotherapy
http://bit.ly/2RkNg9V
A Deeply Hypothermic Patient Presenting with Vital Signs
High Altitude Medicine &Biology, Ahead of Print.
http://bit.ly/2Q4E9W3
The development of a GPR44 targeting radioligand [ 11 C]AZ12204657 for in vivo assessment of beta cell mass
Abstract
Background
The G-protein-coupled receptor 44 (GPR44) is a beta cell-restricted target that may serve as a marker for beta cell mass (BCM) given the development of a suitable PET ligand.
Methods
The binding characteristics of the selected candidate, AZ12204657, at human GPR44 were determined using in vitro ligand binding assays. AZ12204657 was radiolabeled using 11C- or 3H-labeled methyl iodide ([11C/3H]CH3I) in one step, and the conversion of [11C/3H]CH3I to the radiolabeled product [11C/3H]AZ12204657 was quantitative. The specificity of radioligand binding to GPR44 and the selectivity for beta cells were evaluated by in vitro binding studies on pancreatic sections from human and non-human primates as well as on homogenates from endocrine and exocrine pancreatic compartments.
Results
The radiochemical purity of the resulting radioligand [11C]AZ12204657 was > 98%, with high molar activity (MA), 1351 ± 575 GBq/μmol (n = 18). The radiochemical purity of [3H]AZ12204657 was > 99% with MA of 2 GBq/μmol. Pancreatic binding of [11C/3H]AZ12204657 was co-localized with insulin-positive islets of Langerhans in non-diabetic individuals and individuals with type 2 diabetes (T2D). The binding of [11C]AZ12204657 to GPR44 was > 10 times higher in islet homogenates compared to exocrine homogenates. In human islets of Langerhans GPR44 was co-expressed with insulin, but not glucagon as assessed by co-staining and confocal microscopy.
Conclusion
We radiolabeled [11C]AZ12204657, a potential PET radioligand for the beta cell-restricted protein GPR44. In vitro evaluation demonstrated that [3H]AZ12204657 and [11C]AZ12204657 selectively target pancreatic beta cells. [11C]AZ12204657 has promising properties as a marker for human BCM.
http://bit.ly/2LBwL3V
Recommendation for the definition of postoperative radiotherapy target volume based on a pooled analysis of patterns of failure after radical surgery among patients with thoracic esophageal squamous cell carcinoma
Abstract
Background
Elective use of radiation therapy to treat regionally involved lymph nodes (LNs) after radical surgery for esophageal squamous cell carcinoma (ESCC) is controversial. We studied metastasis patterns through a pooled analysis of published results to guide post-operative radiotherapy (PORT) target designation.
Methods
We searched the MEDLINE database for literature published from May 1977 to March 2018, and found 14 relevant original studies that included 2738 patients with thoracic ESCC. We calculated probabilities of recurrence and metastasis in local (including anastomoses and tumor bed), LNs and distal areas.
Results
Recurrence rates were 1.88% for local, 13.18% for distal, and 22.16% for LNs. Within LNs, recurrence rates were cervical/supraclavicular: 37.69%, upper mediastinal: 44.30%, middle mediastinal: 21.81%, lower mediastinal: 2.57%, abdominal paraaortic: 25% and upper abdominal: 9.56%. Whereas cervical/supraclavicular and upper mediastinal LNs had the highest recurrence rates, abdominal LNs also had high recurrence rates in patients with lower thoracic ESCC.
Conclusions
PORT volume should include the cervical/supraclavicular and upper mediastinal LNs for all thoracic ESCC, and abdominal paraaortic LNs for lower thoracic ESCC. Anastomoses and tumor beds should not be included in the PORT volume if they are not adjacent to the PORT-LN regions. Upper abdominal LNs might not necessarily be included in the PORT volume for thoracic ESCC.
http://bit.ly/2AevvPF
Image-guided study of inter-fraction and intra-fraction set-up variability and margins in reverse semi-decubitus breast radiotherapy
Abstract
Background
This study aimed to evaluate the inter-fraction set-up error and intra-fraction motion during reverse semi-decubitus (RSD) breast radiotherapy, and to determine a planning target volume (PTV) margin.
Material and methods
Pre- and post-treatment cone-beam computed tomography (CBCT) scans were prospectively acquired at fractions 1, 4, 7, 8, 11, and 14 for 30 patients who underwent RSD breast radiotherapy. Online correction for initial set-up error greater than 5 mm or 2° was performed and post-correction CBCT was acquired. An off-line analysis was performed to quantify initial and residual inter-fraction set-up errors and intra-fraction motion in three-dimensions. Patient inter-fraction errors were analysed for time trends during the course of radiotherapy. PTV margins were calculated from the systematic and random errors.
Results
The initial inter-fraction population systematic errors were 1.8–3.3 mm (translation) and 0.5° (rotation); random errors were 1.8–2.1 mm (translation) and 0.3–0.5° (rotation). After online correction, the residual inter-fraction population systematic errors were 1.2–1.8 mm (translation) and 0.3–0.4° (rotation); random errors were 1.4–1.6 mm (translation) and 0.3–0.4° (rotation). Intra-fraction population systematic and random errors were ≤ 1.3 mm (translation) and ≤ 0.2° (rotation). The magnitude of inter-fraction set-up errors in the anterior-posterior direction, roll, and yaw were significantly correlated with higher body weight and body mass index (BMI). The inter-fraction set-up error did not change significantly as a function of time during the course of radiotherapy. The magnitude of intra-fraction motion was not correlated with patient characteristics and treatment time. The total PTV margins accounting for pre-correction and intra-fraction errors were 6.5–10.2 mm; those accounting for post-correction and intra-fraction errors were 4.7–6.3 mm.
Conclusions
CBCT is an effective modality to evaluate and improve the inter-fraction set-up reproducibility in RSD breast radiotherapy, particularly for patients with higher BMI. Intra-fraction motion was minimal during RSD breast radiotherapy.
http://bit.ly/2Sk4ykI
Volume-of-interest-based supervised cluster analysis for pseudo-reference region selection in [ 18 F]DPA-714 PET imaging of the rat brain
Abstract
Method
Aim of this study was to automatically select a suitable pseudo-reference brain region for the accurate, non-invasive quantification of neuroinflammation in a rat brain using dynamic [18F]DPA-714 PET imaging.
Procedures
A supervised clustering analysis approach considering three kinetic classes (SVCA3) was used to select an appropriate pseudo-reference brain region. This pseudo-reference region was determined by selecting only brain regions with low specific tracer uptake (SVCA3low) or by taking into account all brain regions and weighting each brain region with the corresponding fraction of low specific binding (SVCA3wlow). Both SVCA3 approaches were evaluated in an animal model of neuro-inflammation induced by lipopolysaccharide injection in the right striatum of female Wistar rats. For this study setup, a population of 25 female Wistar rats received a dynamic PET scan after injection of ~ 60 MBq [18F]DPA-714. Animals were scanned at baseline (n = 3) and at different time points after inducing neuroinflammation: 1 day (n = 3), 3 days (n = 12), 7 days (n = 4), and 30 days (n = 3). Binding potential (BP) values using a simplified reference tissue model (SRTM) and the contralateral striatum as pseudo-reference region were considered as a reference method (BPL STR) and compared with SRTM BP values using a pseudo-reference region obtained by either the SVCA3low or SVCA3wlow approach for both a 90- and 120-min acquisition time interval.
Results
For the right striatum, SRTM BP values using a SVCA3low- or SVCA3wlow-based pseudo-reference region demonstrated a strong and highly significant correlation with SRTM BPL STR values (Spearman r ≥ 0.89, p < 0.001). For the SVCA3low approach, Friedman tests revealed no significant difference with SRTM BPL STR values for a 120-min acquisition time while small but signification differences were found for a 90-min acquisition time (p < 0.05). For the SVCA3wlow approach, highly signification differences (p < 0.001) were found with SRTM BPL STR values for both a 90- and 120-min acquisition time interval.
Conclusions
A SVCA3 approach using three kinetic classes allowed the automatic selection of pseudo-reference brain regions with low specific tracer binding for accurate and non-invasive quantification of rat brain PET imaging using [18F]DPA-714. A shorter acquisition time interval of 90 min can be considered with only limited impact on the SVCA3-based selection of the pseudo-reference brain regions.
http://bit.ly/2EPgQ1v
Updated Guidelines Developed for Diagnosing, Treating Influenza
WEDNESDAY, Dec. 26, 2018 -- The Infectious Diseases Society of America has updated their recommendations for the care of patients with suspected or diagnosed influenza; the clinical practice guidelines were published online Dec. 19 in Clinical...
http://bit.ly/2LAOM2t
Initiative Can Cut Gender Gap in Medical School Faculty Salaries
WEDNESDAY, Dec. 26, 2018 -- An institutional gender equity initiative (GEI) can reduce gender-based salary gaps among medical school faculty, according to a study published online Dec. 21 in JAMA Network Open. Avani D. Rao, M.D., from the Johns...
http://bit.ly/2rXKSYy
Complications, Costs Up With Cardiac Sx in Opioid Use Disorder
WEDNESDAY, Dec. 26, 2018 -- Patients with opioid use disorder (OUD) undergoing cardiac surgery have increased complications and costs, according to a study published online Dec. 5 in JAMA Surgery. Krish C. Dewan, from the Cleveland Clinic...
http://bit.ly/2LD0Gsz
Study IDs Risk Factors for Violent Sleep Disorder
WEDNESDAY, Dec. 26, 2018 -- Rapid eye movement (REM) sleep behavior disorder (RBD) is more common among men, as well as those with psychological distress, mental illness, or posttraumatic stress disorder, according to a study published online Dec....
http://bit.ly/2rU5noR
Exome Sequencing Provides Genetic Diagnosis for Some With CKD
WEDNESDAY, Dec. 26, 2018 -- Genes are responsible for approximately one in 10 cases of chronic kidney disease in adults, according to a study published online Dec. 26 in the New England Journal of Medicine. Emily E. Groopman, from Columbia...
http://bit.ly/2LAOKYp
An Epithelial-to-Mesenchymal transcriptional switch triggers evolution of Pulmonary Sarcomatoid Carcinoma (PSC) and identifies dasatinib as new therapeutic option
Purpose: Pulmonary Sarcomatoid Carcinoma (PSC) is an aggressive form of NSCLC. Rarity and poor characterization have limited development of PSC-tailored treatment protocols, leaving patients with inadequate therapeutic options. In this study, we investigated the gene expression profile of PSCs, with the aim to characterize the molecular mechanisms responsible for their evolution and to identify new drugs for their treatment. Experimental Design: A training set of 17 biphasic PSCs was tested for the expression of a large panel of 770 genes related to cancer progression using Nanostring technology. Computational analyses were used to characterize a PSCs-gene specific signature from which pathways and drivers of PSC evolution were identified and validated using functional assays in vitro. This signature was validated in a separate set of 15 PSCs and 8 differentiated NSCLC and used to interrogate the cMAP database searching for FDA-approved small molecules able to counteract PSC phenotype. Results: We demonstrated that transcriptional activation of an Epithelial Mesenchymal Transition (EMT) program drives PSC phylogeny in vivo. We showed, that loss of the epithelial-associated transcription factor (TF) OVOL2 characterizes the transition to sarcomatoid phenotype triggering the expression of EMT promoting TFs, including TWIST,ZEB and the expression of the membrane kinase DDR2. Finally, using a drug repurposing approach, we identified dasatinib as potential inhibitor of the PSC-gene expression signature and we confirmed in vitro that this drug efficiently restrains proliferation and reverts the sarcomatoid-associated phenotype. Conclusions: Our data provide new insights into PSC evolution and provide the rationale for further clinical studies with dasatinib.
http://bit.ly/2Czrl6K
Epigenetic silencing of miRNA-338-5p and miRNA-421 drives SPINK1-positive prostate cancer
Purpose: Serine Peptidase Inhibitor, Kazal type-1 (SPINK1) overexpression defines the second most recurrent and aggressive prostate cancer (PCa) subtype. However, the underlying molecular mechanism and pathobiology of SPINK1 in PCa remains largely unknown. Experimental Design: MicroRNA-prediction tools were employed to examine the SPINK1-3'UTR for miRNAs binding. Luciferase reporter assays were performed to confirm the SPINK1-3'UTR binding of shortlisted miR-338-5p/miR-421. Further, miR-338-5p/-421 overexpressing cancer cells (SPINK1-positive) were evaluated for oncogenic properties using cell-based functional assays and mice xenograft model. Global gene expression profiling was performed to unravel the biological pathways altered by miR-338-5p/-421. Immunohistochemistry and RNA in-situ hybridization was carried-out on PCa patients' tissue microarray for SPINK1 and EZH2 expression respectively. Chromatin immunoprecipitation assay was performed to examine EZH2 occupancy on the miR-338-5p/-421 regulatory regions. Bisulfite sequencing and methylated DNA-immunoprecipitation was performed on PCa cell lines and patients' specimens. Results: We established a critical role of miRNA-338-5p/-421 in post-transcriptional regulation of SPINK1. Ectopic expression of miRNA-338-5p/-421 in SPINK1-positive cells abrogate oncogenic properties including cell-cycle progression, stemness and drug resistance, and show reduced tumor burden and distant metastases in mice model. Importantly, we show SPINK1-positive PCa patients exhibit increased EZH2 expression, suggesting its role in epigenetic silencing of miRNA-338-5p/-421. Furthermore, presence of CpG dinucleotide DNA methylation marks on the regulatory regions of miR-338-5p/-421 in SPINK1-positive PCa cells and patients' specimens confirms epigenetic silencing. Conclusion: Our findings revealed that miRNA-338-5p/-421 are epigenetically silenced in SPINK1-positive PCa, while restoring the expression of these miRNAs using epigenetic drugs or synthetic mimics could abrogate SPINK1-mediated oncogenesis.
http://bit.ly/2TaQkTf
Dynamic contrast-enhanced MRI detects responses to stroma-directed therapy in mouse models of pancreatic ductal adenocarcinoma
Purpose: The dense stroma underlies the drug resistance of pancreatic ductal adenocarcinoma (PDA) and has motivated the development of stroma-directed drugs. Our objective is to test the concept that dynamic contrast-enhanced (DCE) MRI using FDA-approved contrast media, an imaging method sensitive to the tumor microenvironment, can detect early responses to stroma-directed drug. Experimental Design: Imaging studies were performed in three mouse models exhibiting high desmoplastic reactions: the autochthonous PDA in genetically engineered mice (KPC), an orthotopic model in syngeneic mice and a xenograft model of human PDA in athymic mice. An investigational drug, PEGPH20 (pegvorhyaluronidase alfa), which degrades hyaluronan in the stroma of PDA, was injected alone or in combination with gemcitabine. Results: At 24 hours after a single injection of PEGPH20, Ktrans, a DCE MRI derived marker that measures how fast a unit volume of contrast media is transferred from capillaries to interstitial space, increased 56% and 50% from baseline in the orthotopic and xenograft tumors respectively, compared to a 4% and 6% decrease in vehicle groups (both P<0.05). Similarly, after three combined treatments, Ktrans in KPC mice increased 54% while it decreased 4% in controls treated with gemcitabine alone (P<0.05). Consistently, after a single injection of PEGPH20, tumor hyaluronan content assessed by immunohistochemistry, was reduced substantially in all three models while drug delivery (measured by paclitaxel accumulation in tumor) was increased by 2.6-fold. Conclusions: These data demonstrated a DCE-MRI marker, Ktrans, can detect early responses to stroma-directed drug and reveal the sustained effect of combination treatment (PEGPH20+ gemcitabine).
http://bit.ly/2Czrk2G
SMAD4 loss in colorectal cancer patients correlates with recurrence, loss of immune infiltrate, and chemoresistance
Purpose: SMAD4 has shown promise in identifying patients with colorectal cancer (CRC) at high risk of recurrence or death. Experimental Design: A discovery cohort and independent validation cohort were classified by SMAD4 status. SMAD4 status and immune infiltrate measurements were tested for association with recurrence-free survival (RFS). Patient-derived xenografts from SMAD4-deficient and SMAD4-retained tumors were used to examine chemoresistance. Results: The discovery cohort consisted of 364 patients with stage I-IV CRC. Median age at diagnosis was 53 years. The cohort consisted of 61% left-sided tumors and 62% stage II/III patients. Median follow-up was 5.4 years (interquartile range, 2.3 - 8.2). SMAD4 loss, noted in 13% of tumors, was associated with higher tumor and nodal stage, adjuvant therapy use, fewer tumor-infiltrating lymphocytes (TIL) and lower peritumoral lymphocyte aggregates (PLA) scores (all p<0.04). SMAD4 loss was associated with worse RFS (p=0.02). When stratified by SMAD4 and immune infiltrate status, patients with SMAD4 loss and low TIL or PLA had worse RFS (p=0.002 and p=0.006, respectively). Among patients receiving 5-fluorouracil-based systemic chemotherapy, those with SMAD4 loss had a median RFS of 3.8 years compared with 13 years for those patients with SMAD4 retained. In xenografted mice, the SMAD4-lost tumors displayed resistance to 5- fluorouracil. An independent cohort replicated our findings, in particular the association of SMAD4 loss with decreased immune infiltrate, as well as worse disease-specific survival. Conclusions: Our data show SMAD4 loss correlates with worse clinical outcome, resistance to chemotherapy, and decreased immune infiltrate-supporting its use as a prognostic marker in CRC patients.
http://bit.ly/2TeWySi
Biomarkers for immunotherapy toxicity: are cytokines the answer?
Immune checkpoint inhibitors induce durable responses in some advanced cancer patients, but may simultaneously trigger auto-inflammatory immune-related adverse events (irAEs). The pathogenesis of irAEs may relate to genetic predisposition, environmental insults, or tumor-host interactions. Elevated expression of certain cytokines may signal subclinical inflammation that evolves into severe irAEs with treatment.
http://bit.ly/2Cz7R1V
Risk of biochemical recurrence based on extent and location of positive surgical margins after robot-assisted laparoscopic radical prostatectomy
Abstract
Background
There are no published studies on the simultaneous effect of extent and location of positive surgical margins (PSMs) on biochemical recurrence (BCR) after robot-assisted laparoscopic prostatectomy (RALP). The aim was to report the incidence, extent, and location of PSMs over the inclusion period as well as the rates of BCR and cancer-related mortality, and determine if BCR is associated with PSM extent and/or location.
Methods
Retrospective review of 530 consecutive patients who underwent RALP between 2003 and 2012. Kaplan-Meier (KM) survival analyses and Cox regressions were performed to determine variables associated with BCR.
Results
For the 530 operated patients, evaluated at a median of 92 months (IQR, 87–99), PSMs were observed in 156 (29%), of which 24% were focal. Out of 172 PSMs, 126 (73%) were focal and 46 (27%) were extensive. The KM survival using BCR as endpoint was 0.81 (CI, 0.78–0.85) at 5 years and was 0.67 (CI, 0.61–0.72) at 10 years; and using cancer-related mortality as endpoint was 0.99 (CI, 0.99–1.00) at 5 years and 0.95 (CI, 0.92–0.98) at 10 years. Multi-variable analysis revealed the strongest predictors of BCR to be Gleason score ≥ 8 (HR = 7.97; CI, 4.38–14.51) and 4 + 3 (HR = 3.88; CI, 2.12–7.07), lymph nodes invasion (HR = 3.42; CI, 1.70–6.91), pT stage 3b or 4 (HR = 3.07; CI, 1.93–4.90), and extensive apical PSMs (HR = 2.62; CI, 1.40–4.90) but not focal apical PSMs (HR = 0.86; CI, 0.49–1.50; p = 0.586).
Conclusion
Extensive apical PSMs significantly increased the risk of BCR, independently from pT stage, Gleason score and lymph nodes invasion, while focal apical PSMs had no significant effect on BCR.
http://bit.ly/2TaQmKR
Breast cancer primary tumor ER expression pattern predicts its expression concordance in matched synchronous lymph node metastases
Abstract
Background
Estrogen receptor (ER) expression is important for treatment selection and prognostication of breast cancer patients. Although the metastases are the main targets of endocrine therapy, ER status is often based on the primary tumor. However, ER expression in breast cancer primary lesion may not match with its synchronous metastatic lesions in some cases. In this study, we analyzed ER expression concordance between breast cancer primary tumor and metastatic lesions.
Methods
Paraffin blocks of 100 primary breast invasive ductal carcinoma cases with axillary lymph node metastases were collected. Five tissue cores were punched out from individual primary breast cancer, and one tissue core from each lymph node metastases to assemble tissue microarrays for ER staining. Samples were then scored as 0, 1+, 2+, and 3+ according to the number and intensity of ER stained tumor cells.
Results
For cases with ER 3+ (strong expression) in all cores of primary lesions (n = 38), ER expression in metastatic lymph node was found in 94.7% of the patients. 91.0% of the metastatic lymph nodes were ER positive, and 84.3% of them to be 3+. Among the 46 cases of ER negative expression in all cores of primary lesions, 39 of them had all the metastatic nodes being ER negative, and ER negative nodes were seen in 95.7% of the metastases. As for 16 cases of ER inconsistent expression in primary lesions, 4 cases showed negative ER expression in all metastatic nodes, 2 cases displayed diffuse consistent ER 3+ expression, and 10 cases displayed variant ER expression.
Conclusions
The findings suggest that ER expression concordance between breast cancer primary lesion and its matched metastatic lesions could be estimated by primary tumor ER expression pattern.
http://bit.ly/2Cz7OTN
Effects of a combined physical and psychosocial training for children with cancer: a randomized controlled trial
Abstract
Background
Physical fitness and psychosocial function is often reduced in children during or shortly after cancer treatment. This study evaluates the effect of a combined physical exercise and psychosocial intervention on cardiorespiratory fitness, muscle strength, body composition, psychosocial function and health-related quality of life (HrQoL). In addition, intervention mediators, applicability and adherence were examined.
Methods
This multicenter randomized controlled trial included 68 children with cancer [mean age 13.2 (SD: 3.1) years; 54% male] during treatment or within 12-months post-treatment. The 12-week intervention consisted of 24 individual physical exercise sessions supervised by a physiotherapist, and 6 psychosocial training sessions for children and 2 for parents. Physical fitness and psychosocial function were assessed at baseline, directly post-intervention and at 12 months' post-baseline. Generalized estimating equations were used to simultaneously assess intervention effects at short and long-term. Additionally, we evaluated within-group differences over time. Potential physical and psychosocial mediators in the intervention effect on HrQoL were examined using the product-of-coefficient test. Applicability and adherence were assessed by trainer-report.
Results
This study was able to compare 26 children who received the study intervention, with 33 children who received usual care. No significant differences in the effects of the intervention were found on physical fitness and psychosocial function at short-term. At 12-months follow-up, significantly larger improvements in lower body muscle strength (β = 56.5 Newton; 95% CI: 8.5; 104.5) were found in the intervention group when compared to the control group. Within-group changes showed significant improvements over time in HrQoL and bone density in both groups. Intervention effects on HrQoL were not significantly mediated by physical fitness and psychological function. Intervention applicability was satisfactory with an average session attendance of 67% and 22% dropout (mainly due to disease recurrence).
Conclusions
This 12-week physical exercise and psychosocial training intervention for children with cancer was applicable and showed satisfactory adherence. We found no significant between-group differences in effect, except for a significant improvement in lower body muscle strength at long-term in the intervention group compared to the control group. Yet, both the intervention and the control group showed improvements in bone mineral density and HrQoL over time.
Trial registration
The trial was registered at the Dutch Trial Registry (NTR1531). Registered 12 November 2008.
http://bit.ly/2TeWAto
Dynamic metrics-based biomarkers to predict responders to anti-PD-1 immunotherapy
Dynamic metrics-based biomarkers to predict responders to anti-PD-1 immunotherapy
Dynamic metrics-based biomarkers to predict responders to anti-PD-1 immunotherapy, Published online: 27 December 2018; doi:10.1038/s41416-018-0363-8
Dynamic metrics-based biomarkers to predict responders to anti-PD-1 immunotherapy
https://go.nature.com/2EQYJYS
Tumor Resection Guided by Intraoperative Indocyanine Green Dye Fluorescence Angiography Results in Negative Surgical Margins and Decreased Local Recurrence in an Orthotopic Mouse Model of Osteosarcoma
Abstract
Background
Surgical resection with negative margins is the foundation of extremity sarcoma management. Failure to achieve negative surgical margins can result in local recurrence (LR), a potentially devastating complication. Indocyanine green (ICG) is a US FDA-approved fluorophore previously used to guide carcinoma resections. We investigated the potential of ICG as an intraoperative guide during experimental sarcoma resection.
Methods
Fifty 6-week-old immunocompetent Balb/c female mice received left proximal tibia paraphyseal injections of 5 × 105 K7M2 murine osteosarcoma cells. Animals were separated into two groups (n = 25 each): (1) ICG-assisted surgical resection; and (2) no ICG-assisted resection. Resections were performed 4 weeks after primary tumor engraftment. All animals received 7.5 ug ICG via retro-orbital injection 12 h prior to surgery. ICG fluorescence measurements and clinical evaluations were performed 4 weeks after resection to detect LR.
Results
Eleven of 25 animals from each group developed gross tumors. Four weeks after resection, group 1 had 0/11 tumor recurrences, while group 2 had recurrences in 9/11 (81.8%) experimental mice (p < 0.0002) (Fig. 2). There was a 100% NPV in group 1, and no tumor recurrence with fluorescence-free margins after the primary surgery. Group 2 had a 100% positive predictive value for the development of an LR if any fluorescent signal was present at the surgical margin after resection.
Conclusion
Intraoperative ICG guidance led to reliably negative surgical margins and a diminished LR rate. Given the benign safety profile of ICG and its prior clinical success, these results could be immediately translatable to the clinical realm.
http://bit.ly/2EQ1pFB
Prognostic Value of Lactate Dehydrogenase in Patients with Hepatocellular Carcinoma: A Meta-Analysis
Background. Previous studies have shown the prognostic value of lactate dehydrogenase (LDH) in hepatocellular carcinoma (HCC), but the results are not persuasive. Therefore, the purpose of our study was to quantitatively explore the prognostic value of LDH in hepatocellular carcinoma. Methods. We searched the Web of Science, Embase, PubMed, and the Cochrane Library for literature published before October 2018 on the prognostic value of LDH in patients with hepatocellular carcinoma. The combined hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized to assess the prognostic value of LDH in overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) of HCC. Subgroup analysis, sensitivity analysis, and metaregression were used to explore the source of heterogeneity. Funnel plots with Begg's test and Egger's test were used to detect potential publication biases. Furthermore, combined odds ratios (ORs) were utilized to assess the correlation between LDH and clinicopathological features. Results. A total of 10 nonrandomized controlled studies were included in this meta-analysis. The combined effects of LDH on HCC patients' OS, RFS/DFS, and PFS were HR = 2.07, 95% CI: 1.63-2.62, P
http://bit.ly/2CCgmJJ
Physical Fitness and Body Composition in 10–12-Year-Old Danish Children in Relation to Leisure-Time Club-Based Sporting Activities
This study investigated whether the physical fitness and body composition of 10–12-year-old Danish children are related to participation in leisure-time club-based sporting activities. The study involved 544 Danish 10–12-year-old 5th-grade municipal schoolchildren (269 boys and 275 girls, 11.1 ± 0.4 years). After answering a questionnaire about leisure-time sporting activities, the children were divided into four groups: football club participation (FC; n=141), other ball games (OBG; n=42), other sports (OS; n=194), and no sports-club participation (NSC; n=167). The children completed a battery of health and fitness tests, including a 20 m sprint test, a standing long-jump test, the Yo-Yo IR1 children's test (YYIR1C), and body composition, blood pressure, resting heart rate (), and the flamingo balance test. The children engaged in club-based ball games (FC and OBG) had higher (p
http://bit.ly/2CzDzMP
Challenges and Limitations of Clinical Trials on Labor Induction: A Review of the Literature
AJP Rep 2018; 08: e365-e378
DOI: 10.1055/s-0038-1676577
Induction of labor is a common obstetric procedure performed in nearly a quarter of all deliveries in the United States. Pharmacological (prostaglandins, oxytocin) and/or mechanical methods (balloon catheters) are commonly used for labor induction; however, there is ongoing debate as to which method is the safest and most effective. This narrative review discusses key limitations of published trials on labor induction, including the lack of well-designed randomized controlled trials directly comparing specific methods of induction, heterogeneous trial populations, and wide variation in the protocols used and outcomes reported. Furthermore, the majority of published trials were underpowered to detect significant differences in the most clinically relevant efficacy and safety outcomes (e.g., cesarean delivery, neonatal mortality). By identifying the limitations of labor induction trials, we hope to highlight the importance of quality published data to better inform guidelines and drive evidence-based treatment decisions.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
http://bit.ly/2TfuOwT
Diagnostic Errors in the Neonatal Intensive Care Unit: A Case Series
AJP Rep 2018; 08: e379-e383
DOI: 10.1055/s-0038-1676619
Diagnostic errors remain understudied in neonatal intensive care units (NICUs). The few available studies are primarily autopsy-based, and do not evaluate diagnostic errors that did not result in the patient's death. This case series presents 10 examples of nonlethal diagnostic errors in the NICU—classified according to the component of the diagnostic process which led to the error. These cases demonstrate the presence of diagnostic error in the NICU and highlight the need for further research on this important topic.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
http://bit.ly/2CAY1wQ
Pregnancies Complicated by Familial Hypertriglyceridemia: A Case Report
AJP Rep 2018; 08: e362-e364
DOI: 10.1055/s-0038-1676832
Background Although rare, familial hypertriglyceridemia can cause acute and life-threatening complications in pregnancy. Cases The first patient's pregnancy was complicated by multiple admissions for pancreatitis due to hypertriglyceridemia and noncompliance with gemfibrozil. In her second pregnancy, she was compliant with gemfibrozil and only experienced pancreatitis episodes toward the end of pregnancy. The second patient had diabetes mellitus and familial hypertriglyceridemia. She required multiple hospitalizations for diabetic ketoacidosis secondary to insulin noncompliance. In both pregnancies, she was compliant with gemfibrozil and had no complications related to hypertriglyceridemia. Conclusion Treatment with gemfibrozil in pregnancies complicated by hypertriglyceridemia may prevent complications without adverse maternal or fetal effects and could be considered in treating pregnant patients with severe hypertriglyceridemia. These cases also demonstrate the importance of medication compliance in the prevention of poor outcomes.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
http://bit.ly/2TfuNJl
Metagenomic next-generation sequencing as a diagnostic tool for toxoplasmic encephalitis
More than 100 different pathogens can cause encephalitis. Testing of all the neurological pathogens by conventional methods can be difficult. Metagenomic next-generation sequencing (NGS) could identify the inf...
http://bit.ly/2VcN63l
“No one wants to die alone”: Incarcerated patients’ knowledge and attitudes about early medical release
Deaths among incarcerated individuals have steadily increased in the United States, exceeding 5,000 in 2014. Nearly every state has a policy to allow patients with serious life-limiting illness to apply for release from prison or jail to die in the community ("early medical release"). Although studies show these policies are rarely used, patient-level barriers to their use are unknown.
http://bit.ly/2GFj2uf
Factors that Hinder and Facilitate Cancer Patients’ Knowledge About Pain Management- a qualitative study
Pain management education may improve pain control for some patients, while individual differences exist.
http://bit.ly/2RjP5Ux
Behaviors indicative of pain in brain-injured adult patients with different levels of consciousness in the intensive care unit
Many brain-injured patients are unable to self-report their pain during their hospitalization in the intensive care unit (ICU), and existing behavioral pain scales may not be well suited.
http://bit.ly/2GHfszA
Attitudes of the General Public, Cancer Patients, Family Caregivers, and Physicians toward Advance Care Planning: A Nationwide Survey Prior to the Enforcement of the Life-Sustaining Treatment Decision-Making Act
To respect a patient's wish for end-of-life care, "the Act on Decisions on Life-Sustaining Treatment for Patients at the End-of-Life" was enacted in South Korea in 2016. Current understanding of people who would be involved in advance care planning (ACP) is crucial to disseminate it systematically.
http://bit.ly/2RlRw8Y
Spirituality in Aotearoa New Zealand: personal reflections from a spirituality in healthcare researcher
Spirituality is about what is of utmost value, it is a values lens that asks 'what really matters most to me, my family, our community, our country and our world'. This personal reflection comes from a New Zealand academic who works in the spirituality and healthcare research field. While largely biographical, this reflection offers some insight into the New Zealand context and this emergent field.
http://bit.ly/2GH3QwL
Dynamic metrics-based biomarkers to predict responders to anti-PD-1 immunotherapy
https://go.nature.com/2EOuhOw
Timing of Local Therapy Impacts Survival in Ewing Sarcoma
The optimal timing of local therapy in Ewing sarcoma patients is unclear. We queried the National Cancer Database for localized Ewing sarcoma patients treated with chemotherapy and local therapy and analyzed overall survival by time to local therapy following chemotherapy initiation. Delayed time to local therapy > 16 weeks after chemotherapy initiation was independently associated with worse survival in patients receiving radiotherapy with localized Ewing sarcoma.
http://bit.ly/2Ag5oIe
Immunosuppressive TNI -based reconditioning regimens after graft rejection or graft failure in pediatric patients treated with myeloablative allogeneic hematopoietic cell transplantation
This retrospective analysis aims to address the efficacy of total nodal irradiation- based reconditioning regimens on pediatric patients with graft failure or graft rejection after allogeneic haematopoietic cell transplantation. Results of 33 pediatric patients with malignant (n=25) and non-malignant diseases (n=8) were analysed. The TNI-based reconditioning regimen provides sustained engraftment combined with a favourable acute and late toxicity profile leading to long-term event-free and overall survival.
http://bit.ly/2Sl08Kw
Risk factors associated with 31-day unplanned readmission in 50,912 discharged patients after stroke in China
Unplanned readmission within 31 days of discharge after stroke is a useful indicator for monitoring quality of hospital care. We evaluated the risk factors associated with 31-day unplanned readmission of strok...
http://bit.ly/2GEUKR5
Acute-onset multiple acyl-CoA dehydrogenase deficiency mimicking Guillain-Barré syndrome: two cases report
Multiple acyl-CoA dehydrogenase deficiency (MADD) showed great clinical heterogeneity and poses a challenge to diagnosis. Guillain-Barré syndrome (GBS) is an acute-onset autoimmune-mediated peripheral neuropat...
http://bit.ly/2RefVxv
IBCC chapter & cast: Community-acquired urosepsis
Urosepsis is one of my favorite ICU diagnoses. In almost all cases, patients will improve dramatically within 12-24 hours and leave the ICU with minimal sequelae. But that shouldn't lull us into a false sense of security: careful antibiotic selection, aggressive resuscitation, and (in some cases) emergent drainage may be required for a good outcome.
EMCrit Project by Josh Farkas.
http://bit.ly/2Ai1Ntb
Home Oxygen Users Experience Problems Related to Equipment
WEDNESDAY, Dec. 26, 2018 -- Home oxygen users often experience problems related to their oxygen equipment that may impact their quality of life, according to a report published in the December issue of the Annals of the American Thoracic...
http://bit.ly/2LF1cq8
Appalachia, Western States Have Highest Hep C Prevalence
WEDNESDAY, Dec. 26, 2018 -- States in the West and in Appalachia have a higher prevalence of hepatitis C virus (HCV) infection than other states, according to a study published online Dec. 21 in JAMA Network Open. Eli S. Rosenberg, Ph.D., from the...
http://bit.ly/2rTsZdl
ACOG: Interpregnancy Period Should Maximize Women's Health
WEDNESDAY, Dec. 26, 2018 -- Providers should maximize women's health during the interpregnancy period, continuing care beyond the immediate postpartum period, according to a consensus report published online Dec. 20 in the American Journal of...
http://bit.ly/2LyiGnQ
Malnutrition Ups Risk of Postop Issues in Pediatric Crohn Disease
WEDNESDAY, Dec. 26, 2018 -- For children with Crohn disease (CD), malnutrition is associated with increased risk of complications after bowel surgery, according to a study published in the November issue of the Journal of Pediatric Surgery. Mitchell...
http://bit.ly/2rV5iBf
Drug Use-Associated Infective Endocarditis Up 2007 to 2017
WEDNESDAY, Dec. 26, 2018 -- From 2007 to 2017 there was an increase in drug-use associated infective endocarditis (DUA-IE) hospitalizations and valve surgeries, according to a study published online Dec. 4 in the Annals of Internal Medicine. Asher...
http://bit.ly/2Lz07Qw
Fecal Occult Blood Test May Improve CRC Outcomes in Some
WEDNESDAY, Dec. 26, 2018 -- Fecal occult blood test (FOBT) screening for colorectal cancer (CRC) is associated with several improved outcomes in men but not women, according to a study recently published in the British Journal of Surgery. Laura...
http://bit.ly/2rV5ekZ
Risk of Arterial Thromboembolic Events Up Prior to Cancer Diagnosis
WEDNESDAY, Dec. 26, 2018 -- In older adults, the risk of arterial thromboembolic events begins to increase 150 days before the date of cancer diagnosis and peaks 30 days before, according to a study published online Dec. 21 in Blood. Babak B. Navi,...
http://bit.ly/2LBpOjB
New AAP Guideline Available for Infantile Hemangioma Treatment
WEDNESDAY, Dec. 26, 2018 -- The American Academy of Pediatrics has developed its first guideline for the management of infantile hemangiomas (IHs); the clinical practice guideline was published online Dec. 24 in Pediatrics. Noting that IHs may occur...
http://bit.ly/2s4xjGR
Most Nurses Unsatisfied With Hospitals' End-of-Life Care
WEDNESDAY, Dec. 26, 2018 -- The majority of nurses have an unfavorable opinion of their hospital's end-of-life care, according to a study published online Dec. 2 in the Journal of the American Geriatrics Society. Karen B. Lasater, Ph.D., R.N., from...
http://bit.ly/2LyNK79
Massage Offers Short-Term Relief of Knee Pain in Arthritis Patients
WEDNESDAY, Dec. 26, 2018 -- Weekly massage sessions may provide short-term symptom relief for knee osteoarthritis patients, but the benefit is not maintained over one year of follow-up, according to a study published online Dec. 12 in the Journal of...
http://bit.ly/2rXZtms
A Customizable Protocol for String Assembly gRNA Cloning (STAgR)
Here, we present string assembly gRNA cloning (STAgR), a method to easily multiplex gRNA vectors for CRISPR/Cas9 approaches. STAgR makes gRNA multiplexing simple, efficient and customizable.
http://bit.ly/2Tcc1Cm
Cancers, Vol. 11, Pages 22: Honokiol Eliminates Glioma/Glioblastoma Stem Cell-Like Cells Via JAK-STAT3 Signaling and Inhibits Tumor Progression by Targeting Epidermal Growth Factor Receptor
Cancers, Vol. 11, Pages 22: Honokiol Eliminates Glioma/Glioblastoma Stem Cell-Like Cells Via JAK-STAT3 Signaling and Inhibits Tumor Progression by Targeting Epidermal Growth Factor Receptor
Cancers doi: 10.3390/cancers11010022
Authors: Yipu Fan Weikang Xue Melitta Schachner Weijiang Zhao
Malignant gliomas are the most aggressive forms of brain tumors; whose metastasis and recurrence contribute to high rates of morbidity and mortality. Glioma stem cell-like cells are a subpopulation of tumor-initiating cells responsible for glioma tumorigenesis, metastasis, recurrence and resistance to therapy. Epidermal growth factor receptor (EGFR) has been reported to be dysregulated in most cancers, including gliomas and its functions are closely linked to initiating tumor metastasis and a very poor prognosis. In search for compounds that may reduce the tumorigenic potential of gliomas/glioblastomas honokiol attracted our attention. Honokiol, purified from the bark of traditional Chinese herbal medicine Magnolia species, is beneficial in vitro and in animal models via a variety of pharmacological effects, including anti-inflammatory, anti-angiogenetic, anti-arrhythmic and antioxidant activities, as well as anti-proliferative and proapoptotic effects in a wide range of human cancer cells. However, its effects on glioma cells are unknown. Here, we used different concentrations of honokiol in treating U251 and U-87 MG human glioma/glioblastoma cells in cell culture. Results showed that honokiol inhibited glioma cell viability and colony formation and promoted apoptosis. It also inhibited glioma cell migration/proliferation and invasion. In addition, honokiol promoted apoptosis and reduced Bcl-2 expression, accompanied by increase in Bax expression. Honokiol reduced expression of EGFR, CD133 and Nestin. Moreover, honokiol inhibited the activation of both AKT and ERK signaling pathways, increased active caspase-3 level and reduced phosphorylation of STAT3. U-87 MG xenografts in nude mice and in immunotolerant zebrafish yolk sac showed that honokiol inhibits tumor growth and metastasis. Altogether, results indicate that honokiol reduces tumorigenic potentials, suggesting hopes for honokiol to be useful in the clinical management of glioma/glioblastoma.
http://bit.ly/2QS1IqF
Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta
Dermal immature adipocytes fight against Staphylococcus aureus infection by secreting antimicrobial peptides during adipogenesis. Zhang et al. demonstrate that activation of the TGF-β pathway suppresses the adipogenic potential of dermal fibroblasts and therefore leads to an age-dependent loss of antimicrobial protection from dermal fat.
http://bit.ly/2EOpe0j
Correlation Between HER-2 Gene Amplification or Protein Expression and Clinical Pathological Features of Breast Cancer
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
http://bit.ly/2Czv585
Clinical Value of Positron Emission Tomography-Computed Tomography Combined with Ultrasound in Detection of Primary Tumors in Patients with Malignant Ascites
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
http://bit.ly/2T9XR4I
Adenovirus-Mediated CRM197 Sensitizes Human Glioma Cells to Gemcitabine by the Mitochondrial Pathway
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
http://bit.ly/2CzuYJH
A Predictive Scoring Model for Short-term Local Recurrent Nasopharyngeal Carcinoma Based on Magnetic Resonance Imaging
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
http://bit.ly/2T9Rz5d
Combined Detection of HER2, Ki67, and GSTP1 Genes on the Diagnosis and Prognosis of Breast Cancer
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
http://bit.ly/2CzuTWp
What is the added value of digital image analysis of HER2 immunohistochemistry in breast cancer in clinical practice? A study with multiple platforms
Abstract
Aims
We aimed to compare digital image analysis (DIA) of HER2 immunohistochemistry (IHC) in breast cancer by two platforms; to validate DIA against standard diagnostics; and to evaluate the added value of DIA in clinical practice.
Methods and results
HER2 IHC and in‐situ hybridisation (ISH) were performed on 152 consecutive invasive breast carcinomas. IHC scores were determined with DIA using two independent platforms. Manual scoring was performed by two independent observers. HER2 status was considered positive in 3+ and ISH‐positive 2+ cases. HER2 status using DIA was compared to HER2 status with standard diagnostics (manual scoring with ISH in 2+ cases). Inter‐platform agreement of IHC scores was 'moderate' (linear weighted κ=0.58), agreement between manual scoring and platform A was 'moderate' (κ=0.60) and between manual scoring and platform B 'almost perfect' (κ=0.85). Compared to manual scoring, DIA resulted in a reduction of 2+ cases from 17.1% to 1.3% with platform A and from 17.1% to 15.8% with platform B. However, compared to standard diagnostics, there were three false‐negative cases with DIA using platform A (81.3% sensitivity, 100% specificity, 100% positive predictive value [PPV], 97.8% negative predictive value [NPV]). Sensitivity, specificity, PPV and NPV were 100% with DIA using platform B.
Conclusions
DIA of HER2 IHC is a valid tool in determining HER2 status in breast carcinoma. Algorithms in different platforms can behave differently and optimal calibration is essential. In clinical practice, DIA offers an objective alternative to manual scoring, but a reduction in 2+ cases could result in loss of sensitivity.
This article is protected by copyright. All rights reserved.
http://bit.ly/2EJVDFc
Cancers, Vol. 11, Pages 20: The Response of Prostate Cancer to Androgen Deprivation and Irradiation Due to Immune Modulation
Cancers, Vol. 11, Pages 20: The Response of Prostate Cancer to Androgen Deprivation and Irradiation Due to Immune Modulation
Cancers doi: 10.3390/cancers11010020
Authors: Chun-Te Wu Wen-Cheng Chen Miao-Fen Chen
This study investigated changes in the immune system and the biological consequences of androgen deprivation therapy (ADT) and radiotherapy (RT) for augmenting the treatment response in prostate cancer, particularly for castration-resistant prostate cancer (CRPC). Human and murine prostate cancer cell lines were used to examine the response to ADT and RT in vitro and in vivo. Biological changes following treatment and related immune modulation in the tumor microenvironment were examined. Our results showed that CRPC cells were demonstrated to be more resistant to the RT and ADT treatments. ADT increased tumor inhibition following irradiation. The underlying changes included increased cell death, attenuated myeloid-derived suppressor cell recruitment, and an increase in the number of tumor-infiltrating T cells (TILs). Furthermore, when high-dose fractionated RT was given to the primary CRPC tumor, a smaller size of secondary non-irradiated tumor associated with increased TILs was noted in ADT-treated mice. In conclusion, treatment resistance in CRPC was associated with a more immunosuppressive microenvironment. Enhanced antitumor immunity was responsible for the augmented RT-induced tumoricidal effect induced by ADT. Immune modulation could be a promising strategy for prostate cancer, especially for metastatic CRPC.
http://bit.ly/2QNCbid
Cancers, Vol. 11, Pages 21: The Tumor Microenvironment of High Grade Serous Ovarian Cancer
Cancers, Vol. 11, Pages 21: The Tumor Microenvironment of High Grade Serous Ovarian Cancer
Cancers doi: 10.3390/cancers11010021
Authors: M. Sharon Stack Kenneth P. Nephew Joanna E. Burdette Anirban K. Mitra
The Special Issue on high grade serous ovarian cancer (HGSOC) and the contribution of the tumor micro-environment (TME) consisted of reviews contributed by leaders in the ovarian cancer (OC) field. [...]
http://bit.ly/2BGVQG6
Rudimentary Meningocele of the Scalp: A Pitfall in the Diagnosis of Vascular Neoplasms
We present a case of sequestrated meningocele in a 1-year-old girl, who presented with a 1x1cm occipital swelling since birth. CT brain revealed the soft tissue swelling to be extracranial. She underwent surgical excision of the specimen and the excised mass was sent for histopathological examination. The specimen consisted of skin and subcutaneous tissue measuring 2 x 1 x 1 cm. The entire tissue was paraffin processed. Multiple sections studied from the lesion showed an ill circumscribed locally infiltrative dermal lesion. The lesion was composed of whorled proliferations of meningothelial cells enclosing pseudovascular spaces. Immunohistochemically the lesion was positive for EMA, Desmin, and negative for endothelial markers. The present case was documented as a rare case of a rudimentary meningocele.
http://bit.ly/2Q6NPQc
Optimization of Cultural Conditions for Bacillus megaterium Cultured in Agaricus bisporus Industrial Wastewater
The aim of this study was to optimize the cultural conditions for Bacillus megaterium using Agaricus bisporus industrial wastewater as nature culture through response surface methodology. In our present study, we analyzed the total number of living B. megaterium in the fermentation broth using multispectral imaging flow cytometry. Plackett-Burman design was applied to evaluate the effects of six variables, namely, initial pH, industrial wastewater solubility, rotating speed, culture temperature, inoculum size, and loading volume. Loading volume, initial pH, and culture temperature were found to influence the biomass of B. megaterium significantly and were further optimized by Box-Behnken design. After verification test, the optimum fermentation conditions of B. megaterium using the A. bisporus processing wastewater as nature culture media were obtained as follows: initial pH of 7.4, culture temperature of 25°C, loading volume of 40 mL/250 mL, culture time of 24 h, industrial wastewater solubility of 1%, rotating speed of 200 rpm, and inoculum size of 8%. The predicted optimum model's value was 8.88 × 108 Obj/mL and the average experimental value was 9.03 ± 0.02 × 108 Obj/mL, which met the national microbial fertilizers' standard. Furthermore, the field experiment results showed that the fermentation broth of B. megaterium could significantly improve the yield of Spinacia oleracea L.
http://bit.ly/2VdWbcz
Systematic Exposition of Mesenchymal Stem Cell for Inflammatory Bowel Disease and Its Associated Colorectal Cancer
Mesenchymal stem cells (MSCs) therapy has been applied to a wide range of diseases with excessive immune response, including inflammatory bowel disease (IBD), owing to its powerful immunosuppression and its ability to repair tissue lesions. Different sources of MSCs show different therapeutic properties. Engineering managements are able to enhance the immunomodulation function and the survival of MSCs involved in IBD. The therapeutic mechanism of MSCs in IBD mainly focuses on cell-to-cell contact and paracrine actions. One of the promising therapeutic options for IBD can focus on exosomes of MSCs. MSCs hold promise for the treatment of IBD-associated colorectal cancer because of their tumor-homing function and chronic inflammation inhibition. Encouraging results have been obtained from clinical trials in IBD and potential challenges caused by MSCs therapy are getting solved. This review can assist investigators better to understand the research progress for enhancing the efficacy of MSCs therapy involved in IBD and CAC.
http://bit.ly/2Q2FiOb
Randomised clinical trial: Bifidobacterium lactis NCC2818 probiotic vs placebo, and impact on gut transit time, symptoms, and gut microbiology in chronic constipation
Summary
Background
Constipation is a prevalent gastrointestinal disorder. Patient dissatisfaction with prescribed medications is common, and there is need for alternative management strategies. Evidence shows that Bifidobacterium species may be beneficial in constipation.
Aim
To investigate changes in physiological and clinical measures of gut function in patients with chronic constipation following the consumption of Bifidobacterium lactis NCC2818, compared to placebo.
Methods
Participants were randomised to a 4‐week supplementation with B. lactis NCC2818 (1.5 x 1010 CFU/d) or placebo. Gut transit time was measured using a radio‐opaque marker, while symptoms and quality of life were assessed using validated questionnaires. Gut microbiota composition was assessed using quantitative polymerase chain reaction. Analysis of covariance was used for normally distributed variables, and Mann‐Whitney test for non‐normally distributed variables.
Results
Seventy‐five participants were randomised. There was no significant difference between the probiotic and placebo groups in gut transit time change from baseline to week 2 (−11.7 hours, SD 33.0 hours vs −12.9 hours, SD 33.6 hours; P = 0.863) or to week 4 (−20.4 hours, SD 32.5 h vs −8.7 hours, SD 33.8 hours; P = 0.103). There were also no improvements in stool output, symptoms, or quality of life. No differences were found in Bifidobacterium concentrations between the probiotic and placebo groups at week 4 (9.5 log10/g dry faeces, SD 0.3 vs 9.4 log10/g, SD 1.0; P = 0.509).
Conclusions
Bifidobacterium lactis NCC2818 was not effective in the management of mild chronic constipation. This study highlights the importance of further studies and their publication to better understand the strain‐specific effects of probiotics.
http://bit.ly/2EOyiSL
Illness severity scoring in status epilepticus—When STESS meets APACHE II, SAPS II, and SOFA
Summary
Objective
To characterize a critically ill cohort with status epilepticus (SE) by the illness severity scoring systems SAPS II (Simplified Acute Physiology Score II), APACHE II (Acute Physiology and Chronic Health Evaluation II), and SOFA (Sequential Organ Failure Assessment), and to compare their performance with the STESS (Status Epilepticus Severity Score) for outcome prediction.
Methods
The prospective cohort study was carried out at the University Hospital Basel, a Swiss tertiary academic medical care center. Consecutive adult SE patients hospitalized in the intensive care units from 2011 to 2016 were included. Illness severity scores and additional clinical data were recorded. Logistic regression models using automated variable selection were applied to identify scores associated with no return to functional and neurological baseline and death. Measures of discrimination and calibration were assessed.
Results
Among 184 patients, 33% returned to baseline. Median scores of the illness severity scores were within the lowest third of the possible scoring ranges, and all differed significantly between patients with and without return to baseline. The areas under the receiver operating curves for the prediction of no return to baseline and death ranged from 0.64 to 0.73, with the highest value for the STESS predicting no return to baseline. Measures of calibration revealed adequate model fit for all analyses. Among integral components of the scoring systems, only the Glasgow Coma Scale (GCS) differed significantly between patients with and without return to baseline. In multivariable analyses, decreasing GCS and increasing STESS had the strongest associations (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.77‐0.93 and OR = 1.34, 95% CI = 1.05‐1.68, respectively) with no return to baseline independent of all other scoring systems, whereas the APACHE II revealed the strongest association with death (OR = 1.15, 95% CI = 1.06‐1.25).
Significance
Although complex illness severity scoring systems in SE patients facilitate benchmarking and comparisons with other severely ill patient cohorts, they offer no advantages over the STESS and GCS regarding prediction of no return to baseline.
http://bit.ly/2EMUjSb
Do neurologists agree in diagnosing drug resistance in adults with focal epilepsy?
Summary
Objective
To evaluate interrater agreement in categorizing treatment outcomes and drug responsiveness status according to the International League Against Epilepsy (ILAE) definition of drug‐resistant epilepsy.
Methods
A total of 1053 adults with focal epilepsy considered by the investigators to meet ILAE criteria for drug resistance were enrolled consecutively at 43 centers and followed up prospectively for 18‐34 months. Treatment outcomes for all antiepileptic drugs (AEDs) used up to enrollment (retrospective assessment), and on an AED newly introduced at enrollment, were categorized by individual investigators and by 2 rotating members of a 16‐member expert panel (EP) that reviewed the patient records independently. Interrater agreement was tested by Cohen's kappa (k) statistics and rated according to Landis and Koch's criteria.
Results
Agreement between EP members in categorizing outcomes on the newly introduced AED was almost perfect (90.1%, k = 0.84, 95% confidence interval [CI] 0.80‐0.87), whereas agreement between the EP and individual investigators was moderate (70.4%, k = 0.57, 95% CI 0.53‐0.61). Similarly, categorization of outcomes on previously used AEDs was almost perfect between EP members (91.7%, k = 0.83, 95% CI 0.81‐0.84) and moderate between the EP and investigators (68.2%, k = 0.50, 95% CI 0.48‐0.52). Disagreement was related predominantly to outcomes considered to be treatment failures by the investigators but categorized as undetermined by the EP. Overall, 19% of patients classified as having drug‐resistant epilepsy by the investigators were considered by the EP to have "undefined responsiveness."
Significance
Interrater agreement in categorizing treatment outcomes according to ILAE criteria ranges from moderate to almost perfect. Nearly 1 in 5 patients considered by enrolling neurologists to be "drug‐resistant" were classified by the EP as having "undefined responsiveness."
http://bit.ly/2EPV8KQ
Arid1a loss drives non‐alcoholic steatohepatitis in mice via epigenetic dysregulation of hepatic lipogenesis and fatty acid oxidation
Abstract
Nonalcoholic steatohepatitis (NASH) is a rapidly growing cause of chronic liver damage, cirrhosis, and hepatocellular carcinoma (HCC). How fatty liver pathogenesis is subject to epigenetic regulation is unknown. We hypothesized that chromatin remodeling is important for the pathogenesis of fatty liver disease. ARID1A, a DNA‐binding component of the SWI/SNF ATP‐dependent chromatin‐remodeling complex, contributes to nucleosome repositioning and access by transcriptional regulators. Liver‐specific deletion of Arid1a (Arid1a LKO) caused the development of age‐dependent fatty liver disease in mice. Transcriptome analysis revealed upregulation of lipogenesis and down‐regulation of fatty acid oxidation genes. As evidence of direct regulation, ARID1A demonstrated direct binding to the promoters of many of these differentially regulated genes. Additionally, Arid1a LKO mice were more susceptible to high‐fat diet‐induced liver steatosis and fibrosis. We deleted Pten in combination with Arid1a to synergistically drive fatty liver progression. Inhibition of lipogenesis using CAT‐2003, a potent SREBP inhibitor, mediated improvements in markers of fatty liver disease progression in this Arid1a/Pten double knockout model.
Conclusion
ARID1A plays a role in the epigenetic regulation of hepatic lipid homeostasis, and its suppression contributes to fatty liver pathogenesis. Combined Arid1a and Pten deletion shows accelerated fatty liver disease progression and is a useful mouse model for studying new therapeutic strategies for NASH.
This article is protected by copyright. All rights reserved.
http://bit.ly/2VbBPjP
Prospective comparison of cytological specimen adequacy assessment by different rapid staining techniques for rapid on‐site evaluation in fine needle aspiration cytology and their cost‐effectiveness
Objective
Rapid on‐site evaluation (ROSE) is a technique beneficial in determining the adequacy of the samples, thereby increasing the diagnostic yield, useful in triage of specimens for ancillary studies and can also help determine a preliminary diagnosis in emergency cases. The different rapid stains for on‐site evaluation described in the literature are diff quik, toluidine blue (TB), brilliant cresyl blue (BCB), ultra‐fast Pap stains, and rapid hematoxylin and eosin (H&E). This study was undertaken as there is sparse literature regarding the best and the most cost‐effective rapid stain.
Method
Fine needle aspiration samples from 200 patients with palpable swellings in easily accessible regions were taken. Smears stained by rapid and routine stains were assessed based on four parameters, with provisional diagnosis on the rapid stained smears. A comparative analysis of the advantages and disadvantages of the rapid stains was carried out with appropriate statistical tests with the routinely stained smears as gold standard.
Results
There was adequate material in 100% of ROSE smears. rapid pap stained smears showed well preserved cytoplasmic details, nuclear details, and background details. The time taken was least with TB and BCB being 5 s each. The most cost‐effective was found to be TB.
Conclusions
We conclude that TB is the most cost‐effective, quick, least labor‐intensive, and reliable rapid stain for ROSE especially in resource‐poor settings.
http://bit.ly/2LEphxi
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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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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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