As in many other countries, the ratio of caesarean section (c-section) delivery to total births in Japan is rising steadily, while the total number of deliveries is decreasing. Although c-sections can effectiv...
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Δευτέρα 3 Σεπτεμβρίου 2018
Public and social environment changes and caesarean section delivery choice in Japan
Elusive cranial lesions severely afflicting young endangered Patagonian huemul deer
Most subpopulations of endangered huemul deer (Hippocamelus bisulcus) fail to recover, frequently due to osteopathology. Equivalent pathology was detected only postmortem in an additional deer 365 km further nort...
https://ift.tt/2LU5b0x
Impact of exercise intensity on oxidative stress and selected metabolic markers in young adults in Ghana
This study aimed to evaluate the effect of different levels of exercise on markers of oxidative stress and selected metabolic parameters in Ghanaian young adults.
https://ift.tt/2LXgkh0
Research proposal: inflammation and oxidative stress in coronary artery bypass surgery graft: comparison between diabetic and non-diabetic patients
Diabetes mellitus patients (DM) have more severe progression of atherosclerotic disease than non-diabetic (NDM) individuals. In situ inflammation and oxidative stress are key points in the pathophysiology of a...
https://ift.tt/2oDj4Hf
Changes in hepatitis A virus (HAV) seroprevalence in medical students in Bangkok, Thailand, from 1981 to 2016
This study aimed to determine the seroprevalence of anti-HAV IgG in Thai medical students in 2016 compared with the previous data and to demonstrate the cross-effective strategy to screen HAV seropositivity.
https://ift.tt/2NNpYVk
Bone Mineral Density of Human Ear Ossicles: An Assessment of Structure in Relation to Function
Clinical Anatomy, EarlyView.
https://ift.tt/2PC9vnr
Anatomical analysis of gastric lymph nodes in cancer–free individuals
Clinical Anatomy, EarlyView.
https://ift.tt/2Q2HdTS
Keeping your eye on the target: eye–hand coordination in a repetitive Fitts’ task
Abstract
In a cyclical Fitts' task, hand movements transition from continuous to discrete movements when the Index of Difficulty (ID) increases. Moreover, at high ID (small target), the eyes saccade to and subsequently fixate the targets at every movement, while at low ID (large target) intermittent monitoring is used. By hypothesis, the (periodic) gaze shifts are abandoned for movement times shorter than about 0.350 s due to systemic constraints (i.e., a refractory period and intrinsic latency). If so, the transition in eye and hand movements is independent. To investigate these issues, the present study examined the effects of changing ID via the targets' width or distance as well as hysteresis in eye–hand coordination. To this aim, 14 participants performed a cyclical Fitts' task while their hand and eye movements were recorded simultaneously. The results show that the transition in eye–hand synchronization (at 2.87 bit; 0.25 s) and in hand dynamics (at 4.85 bit; 0.81 s) neither co-occurred nor correlated. Some small width vs. distance dissociations and hysteresis effects were found, but they disappeared when eye–hand synchronization was viewed as a function of movement time rather than ID. This confirms that a minimal between-saccade time is the limiting factor in eye–hand synchronization. Additionally, the timing between the start of the hand movement and the saccade appeared to be relatively constant (at 0.15 s) and independent of movement time, implying a constant delay that should be implemented in a dynamical model of eye–hand coordination.
https://ift.tt/2MNTmxY
Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study [Research]
BACKGROUND:
Dementia is a major cause of disability, and risk-factor reduction may have the potential to delay or prevent the disease. Our aim was to determine the absolute 10-year risk of dementia, by age, sex and apolipoprotein E (APOE) genotype.
METHODS:We obtained data from the Copenhagen General Population Study (from 2003 to 2014) and the Copenhagen City Heart Study (from 1991 to 1994 and 2001 to 2003). Participants underwent a questionnaire, physical examination and blood sampling at baseline. Diagnoses of dementia and cerebrovascular disease were obtained from the Danish National Patient Registry up to Nov. 10, 2014.
RESULTS:Among 104 537 individuals, the absolute 10-year risk of Alzheimer disease in 3017 women and men who were carriers of the APOE 44 genotype was, respectively, 7% and 6% at age 60–69 years, 16% and 12% at age 70–79 years, and 24% and 19% at age 80 years and older. Corresponding values for all dementia were 10% and 8%, 22% and 19%, and 38% and 33%, respectively. Adjusted hazard ratios (HRs) for all dementia increased by genotype, from genotype 22 to 32 to 33 to 42 to 43 to 44 (p for trend < 0.001). Compared with 33 carriers, 44 carriers were more likely to develop Alzheimer disease (adjusted HR 8.74, 95% confidence interval [CI] 7.08–10.79), vascular dementia (adjusted HR 2.87, 95% CI 1.54–5.33), unspecified dementia (adjusted HR 4.68, 95% CI 3.74–5.85) and all dementia (adjusted HR 5.77, 95% CI 4.89–6.81).
INTERPRETATION:Age, sex and APOE genotype robustly identify high-risk groups for Alzheimer disease and all dementia. These groups can potentially be targeted for preventive interventions.
https://ift.tt/2Q4931Y
Neurotoxicity after CTL019 in a Pediatric and Young Adult Cohort
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Q1uy3J
Antibody–drug conjugates in triple negative breast cancer
Future Oncology, Ahead of Print.
https://ift.tt/2LUDyV1
Cutting Healthcare Costs with Hematoma-Directed Ultrasound-Guided Breast Lumpectomy
Abstract
Background
Localization of nonpalpable breast lesions for breast-conserving surgery (BCS) remains highly variable and includes needle/wire localization (NL), radioactive seed localization, radar localization, and hematoma-directed ultrasound-guided (HUG) lumpectomy. The superiority of HUG lumpectomy over NL has been demonstrated repeatedly in terms of safety, accuracy, low positive margin rates, cosmesis, and patient satisfaction. In this study, we evaluate the cost effectiveness of HUG lumpectomy over NL for nonpalpable breast lesions.
Methods
We performed a retrospective review of 569 patients who underwent lumpectomy at the University of Arkansas for Medical Sciences from May 2014 through December 2017. Lumpectomies were stratified by localization technique, i.e. NL versus HUG. A cost-savings estimate was determined for the HUG localization technique, and a total amount of dollars saved over the study period was calculated.
Results
Overall, 569 lumpectomies were performed: 501 (88.0%) via HUG and 68 (12.0%) via NL. Intraoperative ultrasound was used in 566 operations (99.5%). Of the lumpectomies performed by HUG, 190 lesions (33.4%) were visible only on mammogram or breast magnetic resonance imaging prior to diagnostic core needle biopsy (CNB). Cost estimates comparing HUG with NL demonstrated a cost savings of $497.00 per procedure, the cost of preoperative needle localization by a radiologist, and a total of $94,430.00 for the study period.
Conclusion
In utilizing HUG lumpectomy, the initial CNB serves as the diagnostic and localization procedure, thus saving time and a painful second procedure on the day of operation. HUG lumpectomy is safe, accurate, reduces healthcare costs, and results in a better patient experience for the surgical removal of nonpalpable breast lesions.
https://ift.tt/2Nay3pW
The Value of a Second Opinion for Breast Cancer Patients Referred to a National Cancer Institute (NCI)-Designated Cancer Center with a Multidisciplinary Breast Tumor Board
Abstract
Background
This study aimed to investigate the changes in diagnosis after a second opinion for breast cancer patients from a multi-disciplinary tumor board (MTB) review at an National Cancer Institute (NCI)-designated cancer center.
Methods
A retrospective study analyzed patients with a breast cancer diagnosed at an outside institution who presented for a second opinion from August 2015 to March 2016 at the Medical University of South Carolina (MUSC). Radiology, pathology, and genetic testing reports from outside institutions were compared with reports generated after an MTB review and subsequent workup at MUSC. The second-opinion cases were categorized based on whether diagnostic variations were present or not.
Results
The review included 70 patients seeking second opinions, and 33 (47.1%) of these patients had additional radiologic images. A total of 30 additional biopsies were performed for 25 patients, with new cancers identified in 16 patients. Overall, 16 (22.8%) of the 70 of patients had additional cancers diagnosed. For 14 (20%) of the 70 patients, a second opinion led to a change in pathology interpretation. Genetic testing was performed for 11 patients (15.7%) who met the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing, but none showed a mutation other than a variant of unknown significance. After a complete workup, 30 (42.8%) of the 70 patients had a change in diagnosis as a result of the MTB review.
Conclusion
A review by an MTB at an NCI-designated cancer center changed the diagnosis for 43% of the patients who presented for a second opinion for breast cancer. The study findings support the conclusion that referral for a second opinion is beneficial and has a diagnostic impact for many patients.
https://ift.tt/2Nfqheu
Multidisciplinary Intraoperative Assessment of Breast Specimens Reduces Number of Positive Margins
Abstract
Background
Successful breast-conserving surgery requires achieving negative margins. At our institution, the whole surgical specimen is imaged and then serially sectioned with repeat imaging. A multidisciplinary discussion then determines need for excision of additional margins. The goal of this study was to determine the benefit of each component of this approach in reducing the number of positive margin.
Methods
This single-institution, prospective study included ten breast surgical oncologists who were surveyed to ascertain whether they would have taken additional margins based their review of whole specimen images (WSI) and review of serially sectioned images (SSI). These results were compared with the multidisciplinary decisions (MDD) and pathology results. Margin status was defined using consensus guidelines.
Results
One hundred surveys were completed. Margins on the original specimen were positive or close in 21%. After WSI, surgeons reported that they would have taken additional margins in 26 cases, reducing the number of positive/close margins from 21 to 13% (p < 0.001). After SSI, 52 would have taken additional margins; however, the number of positive/close margins remained 13%. MDD resulted in additional margins taken in 56 cases, reducing the number of positive/close margins to 7% (p < 0.001 compared with SSI).
Conclusions
While surgeon review of specimen radiographs can decrease the number of positive or close margins from 21 to 13%, more rigorous multidisciplinary, intraoperative margin assessment reduces the number of close or positive margins to 7%.
https://ift.tt/2CecuAz
Immunotherapy for Breast Cancer is Finally at the Doorstep: Immunotherapy in Breast Cancer
Abstract
Background
Although immunotherapy is making rapid inroads as a major treatment method for melanoma, lung, bladder, and hereditary colon cancer, breast cancer (BC) remains one of the tumors yet to experience the cellular immunology explosion despite the fact that heavy lymphocyte responses in breast tumors improve response to therapy and can predict for long-term survival.
Results
Immunotherapies in the form of monoclonal antibodies such as trastuzumab and pertuzumab have had an impact on HER2-positive breast cancer (HER2+BC) treatment through antibody-dependent cellular cytotoxicity. Current evidence suggests that checkpoint inhibitors and other cellular therapies are at the doorstep of improving outcomes in triple-negative BC (TNBC) and HER2+BC, especially when combined with standard therapies.
Conclusions
Although this approach has benefitted small numbers of patients to date, numerous clinical trials are underway to define the relative role immunotherapy may play in the treatment of BC.
https://ift.tt/2wES1j7
Underdiagnosis of Hereditary Breast and Ovarian Cancer in Medicare Patients: Genetic Testing Criteria Miss the Mark
Abstract
Background
An estimated 5–10% of breast and ovarian cancers are due to hereditary causes such as hereditary breast and ovarian cancer (HBOC) syndrome. Medicare, the third-party payer that covers 44 million patients in the United States, has implemented a set of clinical criteria to determine coverage for the testing of the BRCA1 and BRCA2 genes. These criteria, developed to identify carriers of BRCA1/2 variants, have not been evaluated in the panel testing era. This study investigated a series of Medicare patients undergoing genetic testing for HBOC to determine the efficacy of genetic testing criteria in identifying patients with hereditary risk.
Methods
This study retrospectively examined de-identified data from a consecutive series of Medicare patients undergoing genetic testing based on personal and family history of breast and gynecologic cancer. Ordering clinicians indicated whether patients did or did not meet established criteria for BRCA1/2 genetic testing. The genetic test results were compared between the group that met the criteria and the group that did not. Patients in families with known pathogenic (P) or likely pathogenic (LP) variants were excluded from the primary analysis.
Results
Among 4196 unique Medicare patients, the rate of P/LP variants for the patients who met the criteria for genetic testing was 10.5%, and for those who did not, the rate was 9% (p = 0.26).
Conclusions
The results of this study indicate that a substantial number of Medicare patients with clinically actionable genetic variants are being missed by current testing criteria and suggest the need for significant expansion and simplification of the testing criteria for HBOC.
https://ift.tt/2CaDD7r
Intraoperative Injection of 99m-Tc Sulfur Colloid for Sentinel Lymph Node Biopsy: Can the Preoperative Injection Procedure be Eliminated?
Abstract
Background
Sentinel lymph node biopsy (SLNB) historically involves a separate appointment in the Radiology Department to undergo injection of the radiocolloid tracer (RT) the day of, or prior to, surgery, which can lead to disruptions in scheduling. Furthermore, the patient must endure an additional procedure. In a pilot study, intraoperative injection of the RT was previously shown to be equally as effective as preoperative injection. This study evaluates the efficacy of this method in a large cohort and examines factors associated with failure of the RT to reach the axilla.
Methods
A retrospective review of patients who underwent SLNB between June 2010 and June 2017 was performed. All patients were injected immediately following intubation with sulfur colloid and blue dye, unless contraindicated. Operative records were reviewed to determine whether sentinel nodes were identified and if gamma counts were detected. Patient and tumor characteristics were examined to identify factors related to failed RT uptake in the axilla.
Results
In 7 years, 453 SLNBs were performed, with sentinel nodes being detected in 447 (98.7%) of these SLNBs. In the six cases where no nodes were detected, all had a prior ipsilateral axillary procedure. Sentinel nodes were undetectable with the gamma probe in 16 (3.5%) cases; a prior axillary procedure was the only statistically significant independent variable associated with this failure.
Conclusion
Intraoperative injection of the RT is highly effective in the detection of sentinel nodes in clinically node-negative breast cancer patients. Eliminating the need for a preoperative injection of RT can avoid scheduling conflicts and decrease patient morbidity.
https://ift.tt/2PwSsms
‘Driving’ Rates Down: A Population-Based Study of Opening New Radiation Therapy Centers on the Use of Mastectomy for Breast Cancer
Abstract
Background
Two new cancer centers providing radiation therapy opened in Alberta, Canada, in 2010 and 2013, respectively. We aimed to assess whether opening the new RT centers influenced mastectomy rates for breast cancer.
Method
Breast cancer patients who underwent surgery from 2004 through 2015 were identified from the Alberta Cancer Registry. Mastectomy rates for 64 predefined health status areas (HSAs) were calculated after adjusting for patient and system factors. Variations in mastectomy rates among the HSAs were quantified using weighted coefficient of variation (CV). Multivariable logistic regressions were performed to determine associations between driving time and mastectomy use in the entire cohort and in subgroups.
Results
Of the 21,872 patients, the proportion of patients who lived a ≤ 60 min drive from the nearest RT center significantly increased from 68.8% (95% CI 67.7–69.9%) to 80.7% (95% CI 79.5–81.9%) during the study period. Concurrently, the crude provincial mastectomy rate decreased from 56.2% (95% CI 55.3–57.1%) to 45.3% (95% CI 44.1–46.5%). However, variation in adjusted mastectomy rates (weighted CV) across the 64 HSAs increased from 9.5 to 14.6. Factors associated with mastectomy included age, larger tumor size, lymph node involvement, higher tumor grade, molecular subtype, lobular histology type, more comorbidities, academic institution, region, earlier period of diagnosis, and longer driving time to the nearest RT center.
Conclusions
Opening new RT centers in previously underserved regions reduced driving times to the nearest center, and was associated with a reduction in mastectomy rates; however, these reductions among regions across the province were not uniform.
https://ift.tt/2Pz9pN4
Patient-Reported Outcomes for Breast Cancer
Abstract
Patient-reported outcomes (PROs) provide insight into how patients perceive health and treatment effects, how treatments impact outcomes, and are helpful in determining how disease and surgical interventions impact many aspects of a patients' life. Commonly utilized metrics include survival and disease control, degree of recovery and functional status, access to treatment, treatment-related complications, health-related quality of life, and long-term consequences of therapy. The key to value-based, patient-centered health care is systematically incorporating patient input into the measures that they consider to be the most important outcomes for a particular medical condition while minimizing costs of care. This manuscript reviews the development and validation of multiple available PROs in breast surgical oncology and reconstruction, their impact in improving patient-physician communication and treatment outcome, and potential for impacting reimbursement. The implementation of PROs can be complex and challenging and care must be taken to minimize the potential for survey fatigue by patients and the potential financial burden for implementation, maintenance, and analyses of collected data. Because there is an increased emphasis in providing high-value care for cancer patients, the widespread incorporation of transparent breast-specific PROs stratified by treatments received and disease stage will be essential in delivering exceptional quality care.
https://ift.tt/2wGiTPT
Chronic Pain After Breast Surgery: A Prospective, Observational Study
Abstract
Background
Chronic pain is an important complication of breast surgery, estimated to affect 20–30% of patients. We prospectively examined surgical, demographic, and psychosocial factors associated with chronic pain 6 months after breast surgery.
Methods
Patients undergoing breast surgery for benign and malignant disease preoperatively completed validated questionnaires to assess baseline pain and psychosocial characteristics. Pain at 6 months was quantified as the Pain Burden Index (PBI), which encompasses pain locations, severity, and frequency. Surgical type was categorized as breast-conserving surgery (BCS), mastectomy, and mastectomy with reconstruction; axillary procedure was categorized as no axillary surgery, sentinel lymph node biopsy (SLNB), and axillary dissection. PBI was compared between groups using one-way analysis of variance (ANOVA) or Kruskal–Wallis ANOVA, and the relationship between baseline demographic and psychosocial factors and PBI was assessed using Spearman's Rank Correlation. p < 0.05 was considered significant.
Results
PBI was variable amongst patients reporting this endpoint (n = 216) at 6 months, but no difference was found between primary breast surgical types (BCS, mastectomy, and mastectomy with reconstruction) or with surgical duration. However, axillary dissection was associated with higher PBI than SLNB and no axillary procedure (p < 0.001). Younger age (< 0.001) and higher BMI (p = 0.010), as well as higher preoperative anxiety (p = 0.017), depression (p < 0.001), and catastrophizing scores (p = 0.005) correlated with higher 6-month PBI.
Conclusions
Amongst surgical variables, only axillary dissection was associated with greater pain at 6 months after surgery. Patient characteristics that were associated with higher PBI included lower age and higher BMI, as well as higher baseline anxiety, depression, and catastrophizing.
https://ift.tt/2wE2r2g
Improved False-Negative Rates with Intraoperative Identification of Clipped Nodes in Patients Undergoing Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy
Abstract
Background
Identification and resection of a clipped node was shown to decrease the false-negative rate (FNR) of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for patients presenting with initially node-positive breast cancer.
Methods
Between March 2014 and March 2016, a prospective trial analyzed 98 patients with axilla-positive locally advanced breast cancer (T1-4, N1-3) to assess the feasibility and efficacy of placing clips into most suspicious biopsy-proven node. The study considered blue, radioisotope active, and suspiciously palpable nodes as sentinel lymph nodes (SLNs).
Results
The SLN identification rate was 87.8%. The median age of the patients with an SLNB (n = 86) was 44 years (range 28–66 years). Of these patients, 77 (88.4%) had cT1-3 disease, and 10 (11.6%) had cT4 disease. The majority of the patients (n = 66, 76.7%) had cN1, whereas 21 patients (23.3%) had cN2 and cN3. A combined method was used for 37 patients (43%), whereas blue dye alone was used for the remaining patients (57%). The clipped node was the SLN in 70 patients (81.4%). For the patients with cN1 before NAC, the FNR was found to be 4.2% (1/24) when the clipped node was identified as an SLN. However, the FNR was estimated to be as high as 16.7% (1/6) for the patients with cN1 before NAC when the clipped node was found to be a non-SLN.
Conclusions
The study results also suggest that axillary dissection could be omitted for patients presenting initially with N1 disease and with a negative clipped node as the SLN after NAC due to the low FNR.
https://ift.tt/2PtDX2I
Select Choices in Benign Breast Disease: An Initiative of the American Society of Breast Surgeons for the American Board of Internal Medicine Choosing Wisely ® Campaign
Abstract
Background
Up to 50% of all women encounter benign breast problems. In contrast to breast cancer, high-level evidence is not available to guide treatment. Management is therefore largely based on individual physician experience/training. The American board of internal medicine (ABIM) initiated its Choosing Wisely® campaign to promote conversations between patients and physicians about challenging the use of tests or procedures which may not be necessary. The American society of breast surgeons (ASBrS) Patient safety and quality committee (PSQC) chose to participate in this campaign in regard to the management of benign breast disease.
Methods
The PSQC solicited initial candidate measures. PSQC surgeons represent a wide variety of practices. The resulting measures were ranked by modified Delphi appropriateness methodology in two rounds. The final list was approved by ASBrS and endorsed by the ABIM.
Results
The final five measures are as follows. (1) Don't routinely excise areas of pseuodoangiomatous stromal hyperplasia (PASH) of the breast in patients who are not having symptoms from it. (2) Don't routinely surgically excise biopsy-proven fibroadenomas that are < 2 cm. (3) Don't routinely operate for a breast abscess without an initial attempt to percutaneously aspirate. (4) Don't perform screening mammography in asymptomatic patients with normal exams who have less than a 5-years life expectancy. (5) Don't routinely drain nonpainful, fluid-filled cysts.
Conclusions
The ASBrS Choosing Wisely® measures that address benign breast disease management are easily accessible to patients via the internet. Consensus was reached by PSQC regarding these recommendations. These measures provide guidance for shared decision-making.
https://ift.tt/2wHbPCk
Intraoperative Radiation Therapy (IORT): A Series of 1000 Tumors
Abstract
Background
Two prospective, randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation therapy to be a safe alternative, with a low-risk of local recurrence, compared with whole breast radiation therapy, following breast-conserving surgery, for selected low-risk patients. We report the first 1000 tumors treated with this modality at our facility.
Methods
A total of 1000 distinct breast cancers in 984 patients (16 bilateral) were treated with breast conserving surgery and X-ray IORT from June 2010 to August 2017. Patients were enrolled in an IORT registry trial. Local recurrence was the primary endpoint.
Results
There have been 28 ipsilateral local recurrences, ten DCIS and 18 invasive. Four local recurrences were within the IORT field, 13 outside of the IORT field but within the same quadrant as the index cancer, and 11 were new cancers in different quadrants. There have been four regional nodal recurrences and one distant recurrence. There have been no breast cancer related deaths and 14 non-breast cancer deaths. With a median follow-up of 36 months, Kaplan–Meier analysis projects 3.9% of patients will recur locally at 4 years. This includes all ipsilateral events in all quadrants.
Conclusions
The local, regional, and distant recurrence rates observed in this trial were comparable to those of the prospective randomized TARGIT-A and ELIOT trials. The low complication rates previously reported by our group as well as the low recurrence rates reported in this study support the cautious use and continued study of X-ray IORT in women with low-risk breast cancer.
https://ift.tt/2CfT3r4
Basic Oncoplastic Surgery for Breast Conservation: Tips and Techniques
Abstract
Background
The demand for oncoplastic breast surgery has increased significantly in recent years. However, these procedures are often not taught in standard training for breast surgeons, and a simple guide for surgeons to start performing basic oncoplastic breast surgery techniques is not available.
Methods
The basic concepts of oncoplastic breast surgery and the tools needed prior to starting these types of procedures are discussed, and the procedure, in a stepwise pattern, for the building blocks of oncoplastic techniques is outlined.
Results
The importance of oncoplastics from a quality of life and oncologic standpoint are described. Key concepts are defined and the decision on when it is necessary to consult reconstructive plastic surgery is delineated. The basic necessities for oncoplastic breast surgery, including patient photographs, important intraoperative tools, anatomic knowledge, and patient selection, are discussed. The building block procedures include aesthetic scar placement, parenchymal closure, deepithelialization, and donut therapeutic mastopexy, which are described in detail.
Conclusions
Oncoplastic breast surgery techniques and clinical reasoning build on one another, allowing a surgeon to move from level I to level II oncoplastic procedures. Even the most basic level I breast conservation oncoplastic skills can improve a patient's cosmetic outcome and are easily learned by a general surgeon.
https://ift.tt/2NbhU3s
Epigenomic and Transcriptomic Characterization of Secondary Breast Cancers
Abstract
Background
Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast cancer (BC) tumors from patients with any prior malignancy.
Methods
RNA-sequencing and genome-wide DNA methylation profiles from BCs were generated in the Cancer Genome Atlas project. Patients with secondary breast cancer (SBC) were separated by histological subtype and matched to primary breast cancer controls to create two independent cohorts of invasive ductal (IDC, n = 36) and invasive lobular (ILC, n = 40) carcinoma. Differentially expressed genes, as well as differentially methylated genomic regions, were integrated to identify epigenetically regulated abnormal gene pathways in SBCs.
Results
Differentially expressed genes were identified in IDC SBCs (n = 727) and in ILC SBCs (n = 261; Wilcoxon's test; P < 0.05). In IDC SBCs, 105 genes were upregulated and hypomethylated, including an estrogen receptor gene, and 73 genes were downregulated and hypermethylated, including genes involved in antigen presentation and interferon response pathways (HLA-E, IRF8, and RELA). In ILC SBCs, however, only 17 genes were synchronously hypomethylated and upregulated, whereas 46 genes hypermethylated and downregulated. Interestingly, the SBC gene expression signatures closely corresponded with each histological subtype with only 1.51% of genes overlapping between the two histological subtypes.
Conclusions
Differential gene expression and DNA methylation signatures are seen in both IDC and ILC SBCs, including genes that are relevant to tumor growth and proliferation. Differences in gene expression signatures corresponding with each histological subtype emphasize the importance of disease subtype-specific evaluations of molecular alterations.
https://ift.tt/2CfSUUy
Phase 2 Open-Label Trial Investigating Percutaneous Laser Ablation for Treatment of Early-Stage Breast Cancer: MRI, Pathology, and Outcome Correlations
Abstract
Background
An institutional review board-approved, multicenter clinical trial was designed to determine the efficacy and outcome of percutaneous laser ablation (PLA) in the treatment of invasive ductal breast carcinoma (IDC). Post-ablation magnetic resonance imaging (MRI) was compared with surgical pathology in evaluation of residual post-ablation IDC and ductal carcinoma in situ.
Methods
Patients with a single focus of IDC 20 mm or smaller by pre-ablation MRI were treated with PLA. The patients underwent a 28-day post-ablation MRI, followed by surgical resection. Cell viability criteria were applied to pre- and post-ablation pathology specimens, which evaluated hematoxylin–eosin (H&E), cytokeratin (CK) 8/18, estrogen receptor, and Ki67 staining patterns.
Results
In this study, 61 patients were reported as the intention-to-treat cohort for determination of PLA efficacy. Of these 61 patients, 51 (84%) had complete tumor ablation confirmed by pathology analysis. One subject's MRI imaging was not performed per protocol, which left 60 subjects evaluable for MRI pathology correlation. Five patients (8.3%) had residual IDC shown by both MRI and pathology. Post-ablation discordance was noted between MRI and pathology, with four patients (6.7%) false-positive and four patients (6.7%) false-negative. The negative predictive value (NPV) of MRI for all the patients was 92.2% (95% confidence interval [CI], 71.9–91.9%). Of the 47 patients (97.9%) with tumors 15 mm or smaller, 46 were completely ablated, with an MRI NPV of 97.7% (95% CI, 86.2–99.9%).
Conclusions
Percutaneous laser ablation is a potential alternative to surgery for treatment of early-stage IDC. Strong correlations exist between post-ablation MRI and pathologic alterations in CK8/18, ER, and Ki67 staining.
https://ift.tt/2wEFjRv
Impact of Postmastectomy Radiation Therapy in Prepectoral Versus Subpectoral Implant-Based Breast Reconstruction
Abstract
Background
This study aimed to compare the impact of postmastectomy radiation therapy (PMRT) on outcomes after prepectoral versus subpectoral implant-based breast reconstruction with local deepithelialized dermal flap and acellular dermal matrix (ADM).
Methods
From 2010 to 2017, 274 patients (426 breasts) underwent prepectoral reconstruction. In this group, 241 patients (370 breasts) were not exposed to PMRT, whereas 45 patients (56 breasts) were exposed to PMRT. Of 100 patients (163 breasts) who underwent partial subpectoral reconstruction, 87 (140 breasts) were not exposed to PMRT, whereas 21 patients (23 breasts) were exposed. The outcomes were assessed by comparing complication rates between the pre- and subpectoral groups.
Results
A higher rate of capsular contracture was found for the prepectoral patients with PMRT than for those without PMRT (16.1 vs 3.5%; p = 0.0008) and for the subpectoral patients with PMRT than for those without PMRT (52.2 vs 2.9%; p = 0.0001). The contracture rate was three times higher for the subpectoral patients with PMRT than for the prepectoral patients with PMRT (52.2 vs 16.1%; p = 0.0018). In addition, 10 (83.3%) of 12 cases with capsular contracture in the subpectoral cohort that received PMRT were Baker grades 3 or 4 compared with only 2 (22.2%) of 9 cases of the prepectoral group with PMRT (p = 0.0092).
Conclusions
The patients undergoing subpectoral breast reconstruction who received PMRT had a capsular contracture rate three times greater with more severe contractures (Baker grade 3 or 4) than the patients receiving PMRT who underwent prepectoral breast reconstruction.
https://ift.tt/2Pyh4LD
Treatment Outcomes for Pleomorphic Lobular Carcinoma In Situ of the Breast
Abstract
Background
Pleomorphic lobular carcinoma in situ (PLCIS) is an uncommon high-grade in situ lesion that shares morphologic features of both classic lobular and ductal carcinoma in situ. Data on the natural history of pure PLCIS are limited, and no evidence-based consensus guidelines for management exist.
Methods
From our prospectively maintained institutional pathology and breast surgery databases, we identified all patients with a diagnosis of PLCIS on core needle biopsy (CNB) or excisional biopsy from 2004 to 2017. Patient, tumor, treatment, and outcome data were abstracted to analyze upstage rates and treatment outcomes.
Results
We identified 18 patients with pure PLCIS: 15 diagnosed on CNB, 2 diagnosed at operation for atypia on CNB, and 1 diagnosed after excisional biopsy without preceding CNB. Of the 15 patients with PLCIS on CNB, 3 (20%) were upgraded to invasive cancer on surgical excision. Overall, 7 patients were treated with mastectomy (all margin-negative) and 11 with lumpectomy (one with a focally positive margin). Eight patients received adjuvant therapy: six endocrine therapy, one radiation therapy, and one received both. Among patients with a final diagnosis of PLCIS, two ipsilateral recurrences were observed at follow-up: one invasive lobular carcinoma at 87 months and one PLCIS at 16 months postoperatively.
Conclusion
PLCIS on CNB mandates surgical resection as 20% of patients may be upgraded to invasive cancer, and outcomes following pathologic margin-negative surgical resection were excellent with only one invasive recurrence observed. Larger-scale investigation with longer follow-up is needed to define a role for adjuvant therapy and to develop evidence-based treatment guidelines.
https://ift.tt/2wGj8dr
Evaluating (and Improving) the Correspondence Between Deep Neural Networks and Human Representations
Cognitive Science, EarlyView.
https://ift.tt/2Q3APfd
Cross‐Cultural Differences in the Influence of Peers on Exploration During Play
Cognitive Science, EarlyView.
https://ift.tt/2NQoPvS
Unspoken Rules: Resolving Underdetermination With Closure Principles
Cognitive Science, EarlyView.
https://ift.tt/2Q2pyM0
The protective effect of Er-Xian decoction against myocardial injury in menopausal rat model
Er-Xian decoction (EXD), a formula of Chinese medicine, is often used to treat menopausal syndrome in China. The aim of the present study was to explore the potential cardioprotective mechanism of EXD against ...
https://ift.tt/2LUN76u
Efficacy of Andrographis paniculata against extended spectrum β-lactamase (ESBL) producing E. coli
A. paniculata is widely known for its medicinal values and is traditionally used to treat a wide range of diseases such as cancer, diabetes, skin infections, influenza, diarrhoea, etc. The phytochemical constitue...
https://ift.tt/2oCmutC
Efficacy and safety of minimal invasive surgery treatment in hypertensive intracerebral hemorrhage: a systematic review and meta-analysis
Recently, minimal invasive surgery (MIS) has been applied as a common therapeutic approach for treatment of hypertensive intracerebral hemorrhage (HICH). However, the efficacy and safety of MIS is still contro...
https://ift.tt/2PvRY03
Bilateral oculomotor ocular neuromyotonia: a case report
Ocular neuromyotonia (ONM) is characterized by episodic diplopia, which is usually triggered by prolonged eccentric gaze of the affected extraocular muscles. The spell is characterized by involuntary, occasion...
https://ift.tt/2ozPWjY
Epidemiology and microbiology of Gram-positive bloodstream infections in a tertiary-care hospital in Beijing, China: a 6-year retrospective study
Gram-positive bacterial bloodstream infections (BSIs) are serious diseases associated with high morbidity and mortality. The following study examines the incidence, clinical characteristics and microbiological...
https://ift.tt/2CdRpGb
Pain Management in Athletes With Impairment: A Narrative Review of Management Strategies
Objective: To review the literature related to different treatment strategies for the general population of individuals with amputation, spinal cord injury, and cerebral palsy, as well as how this may impact pain management in a correlated athlete population. Data Sources: A comprehensive literature search was performed linking pain with terms related to different impairment types. Main Results: There is a paucity in the literature relating to treatment of pain in athletes with impairment; however, it is possible that the treatment strategies used in the general population of individuals with impairment may be translated to the athlete population. There are a wide variety of treatment options including both pharmacological and nonpharmacological treatments which may be applicable in the athlete. Conclusions: It is the role of the physician to determine which strategy of the possible treatment options will best facilitate the management of pain in the individual athlete in a sport-specific setting.https://ift.tt/2PBJTaf
Nonpharmacological Management of Persistent Pain in Elite Athletes: Rationale and Recommendations
Abstract: Persistent pain is common in elite athletes. The current review arose from a consensus initiative by the International Olympic Committee to advance the development of a standardized, scientific, and evidence-informed approach to management. We suggest that optimal management of persistent pain in elite athletes requires an understanding of contemporary pain science, including the rationale behind and implementation of a biopsychosocial approach to care. We argue that athletes and clinicians need to understand the biopsychosocial model because it applies to both pain and the impact of pain with special reference to the sport setting. Management relies on thorough and precise assessment that considers contributing factors across nociceptive, inflammatory, neuropathic, and centrally acting domains; these can include contextual and psychosocial factors. Pain management seeks to remove contributing factors wherever possible through targeted education; adjustment of mechanical loading, training, and performance schedules; psychological therapies; and management of inflammation.https://ift.tt/2oDmucY
Analgesic Management of Pain in Elite Athletes: A Systematic Review
Objective: To identify the prevalence, frequency of use, and effects of analgesic pain management strategies used in elite athletes. Design: Systematic literature review. Data Sources: Six databases: Ovid/Medline, SPORTDiscus, CINAHL, Embase, Cochrane Library, and Scopus. Eligibility Criteria for Selecting Studies: Empirical studies involving elite athletes and focused on the use or effects of medications used for pain or painful injury. Studies involving recreational sportspeople or those that undertake general exercise were excluded. Main Results: Of 70 articles found, the majority examined the frequency with which elite athletes use pain medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, anesthetics, and opioids. A smaller set of studies assessed the effect of medications on outcomes such as pain, function, and adverse effects. Oral NSAIDs are reported to be the most common medication, being used in some international sporting events by over 50% of athletes. Studies examining the effects of pain medications on elite athletes typically involved small samples and lacked control groups against which treated athletes were compared. Conclusions: Existing empirical research does not provide a sufficient body of evidence to guide athletes and healthcare professionals in making analgesic medication treatment decisions. Based on the relatively robust evidence regarding the widespread use of NSAIDs, clinicians and policymakers should carefully assess their current recommendations for NSAID use and adhere to a more unified consensus-based strategy for multidisciplinary pain management in elite athletes. In the future, we hope to see more rigorous, prospective studies of various pain management strategies in elite athletes, thus enabling a shift from consensus-based recommendations to evidence-based recommendations.https://ift.tt/2PvNvdN
Cannabis and the Health and Performance of the Elite Athlete
Objective: Cannabis (marijuana) is undergoing extensive regulatory review in many global jurisdictions for medical and nonmedical access. Cannabis has potential impact on the health of athletes as well as on performance in both training and in competition. The aim of this general review is to identify and highlight the challenges in interpreting information with respect to elite athletic performance, and to point to important research areas that need to be addressed. Data Sources: A nonsystematic literature review was conducted using Medline and PubMed for articles related to cannabis/marijuana use and sports/athletic performance; abstracts were reviewed by lead author and key themes identified and explored. Main Results: Cannabis may be primarily inhaled or ingested orally for a range of medical and nonmedical reasons; evidence for efficacy is limited but promising for chronic pain management. Although evidence for serious harms from cannabis use on health of athletes is limited, one should be cognizant of the potential for abuse and mental health issues. Although the prevalence of cannabis use among elite athletes is not well-known, use is associated with certain high-risk sports. There is no evidence for cannabis use as a performance-enhancing drug. Conclusions: Medical and nonmedical cannabis use among athletes reflects changing societal and cultural norms and experiences. Although cannabis use is more prevalent in some athletes engaged in high-risk sports, there is no direct evidence of performance-enhancing effects in athletes. The potential beneficial effects of cannabis as part of a pain management protocol, including reducing concussion-related symptoms, deserve further attention.https://ift.tt/2oB4qjJ
Novel Factors Associated With Analgesic and Anti-inflammatory Medication Use in Distance Runners: Pre-race Screening Among 76 654 Race Entrants—SAFER Study VI
Objective: Analgesic/anti-inflammatory medication (AAIM) increases the risk of medical complications during endurance races. We determined how many runners use AAIM before or during races, AAIM types, and factors associated with AAIM use. Design: Cross-sectional study. Setting: 21.1-km and 56-km races. Participants: Seventy-six thousand six hundred fifty-four race entrants. Methods: Participants completed pre-race medical screening questions on AAIM use, running injury or exercise-associated muscle cramping (EAMC) history, and general medical history. Main Outcome Measures: Analgesic/anti-inflammatory medication use, types of AAIM (% runners; 95% confidence interval), and factors associated with AAIM use (sex, age, race distance, history of running injury or EAMC, and history of chronic diseases) [prevalence ratio (PR)]. Results: Overall, 12.2% (12.0-12.5) runners used AAIM 1 week before and/or during races (56 km = 18.6%; 18.0-19.1, 21.1 km = 8.3%; 8.1-8.6) (Phttps://ift.tt/2CboeUc
Injectable Corticosteroids in Sport
Objective: To review the literature guiding all aspects of the use of injectable corticosteroids for painful musculoskeletal conditions, with a focus on the treatment of athletes. Data Sources: An extensive search of the literature was completed including search terms of corticosteroid, steroid, athlete, and injection, among others. Additional articles were used after being identified from previously reviewed articles. Main Results: Injections of corticosteroids for a variety of painful conditions of the extremities and the axial spine have been described. Numerous minor and major complications have been reported, including those with a high degree of morbidity. There is a dearth of published research on the use of corticosteroid injections in athletes, with most of the research on this topic focused on older, nonathlete populations. Generally, these injections are well tolerated and can provide short-term pain improvement with little or no long-term benefits. Conclusions: Corticosteroid injections should be used cautiously in athletes and only after a full consideration of the pharmacology, pathogenesis of disease, potential benefits, complications, factors specific to the athlete, and rules of athletic governing bodies. Corticosteroid injections are just one component of a comprehensive rehabilitation plan available to the physician providing care to athletes.https://ift.tt/2oDmA4k
Long-Term Safety of Using Local Anesthetic Injections in Professional Rugby League for Modified Indications
Objective: To assess and evaluate the long-term safety of local anesthetic injections before or during games in professional rugby league players. Design: Retrospective case series. Setting: Professional rugby league team. Participants: Sydney Roosters players over a 6-year period (2008-2013), who had been administered a local anesthetic injection for an injury before or during a match to aid return to play. Interventions: Follow-up survey (no active intervention). Main Outcome Measures: Player self-reported satisfaction. Survey results were compared with a previous cohort who had received local anesthetic injection from 1998 to 2007. Results: Thirty-two players who had been injected with local anesthetic on 249 occasions for 81 injuries completed the current survey at an average of 5.64 years postinjection. In the cohort of 2008 to 2013, fewer injections were performed to areas deemed higher risk compared with the 1998 to 2007 cohort (Phttps://ift.tt/2Cbo536
Injectable Nonsteroidal Anti-Inflammatory Drugs in Sport
Objective: The primary objective of this article is to review the basic science of nonsteroidal anti-inflammatory drugs (NSAIDs), their clinical effects, indications, potential complications, and ethical issues associated with the use of injectable NSAIDs in the treatment of athletes. These objectives are presented taking into consideration the contemporaneous issues associated with the treatment of amateur and professional athletes. Data Sources: A nonformal review of the published medical literature and lay media focusing on the use of injectable NSAIDs in athletes was used for this article. Main Results: All NSAIDs work through the inhibition of the cyclooxygenase (COX) pathway (either one or both subtypes) to reduce inflammation and inhibit pain by reducing prostaglandin and thromboxane synthesis. Complications related to NSAID use involve primarily the gastrointestinal, renal, and cardiovascular systems through this COX pathway inhibition. Ketorolac is the only NSAID currently available in an injectable form. Despite its analgesic efficacy comparable with opioid medication, injectable ketorolac has the potential to cause bleeding in collision athletes resulting from impaired hemostasis. Conclusions: Nonsteroidal anti-inflammatory drug medications are currently used at every level of competition. Injectable ketorolac is an effective analgesic and anti-inflammatory drug. However, its potential effectiveness must be weighed against the risk of potential complications in all athletes, especially those who participate in contact/collision sports. The team physician must balance the goal of treating pain and inflammation with the ethical implications and medical considerations inherent in the administration of injectable medications solely to prevent pain and/or return the athlete to competition.https://ift.tt/2Cbo0fO
Management of Pain in Elite Athletes: Identified Gaps in Knowledge and Future Research Directions
Objective: For elite athletes to train and compete at peak performance levels, it is necessary to manage their pain efficiently and effectively. A recent consensus meeting on the management of pain in elite athletes concluded that there are many gaps in the current knowledge and that further information and research is required. This article presents the crystallization of these acknowledged gaps in knowledge. Data sources: Information was gathered from a wide variety of published scientific sources that were reviewed at the consensus meeting and the gaps in knowledge identified. Main Results: Gaps have been identified in the epidemiology of analgesic use, the management of pain associated with minor injuries, and the field of play management of pain for athletes with major injuries. From a pharmacological perspective, there is a lack of information on the prescribing of opioid medications in elite athletes and more data are required on the use of local anesthetics injections, corticosteroids, and nonsteroidal anti-inflammatory drugs during training and in competition. Pain management strategies for the general population are widely available, but there are few for the elite sporting population and virtually none for elite athletes with a disability. More research is also needed in assessing cognitive-behavior therapies in improving specific outcomes and also into the new process of psychologically informed physiotherapy. A key issue is the paucity of data relating to incidence or prevalence of persistent pain and how this relates to persistent dysfunction, exercise performance, and physiological function in later life. Conclusions: The identification of the gaps in knowledge in the management of pain in elite athletes will provide a unified direction for the retrieval of information and further research that will provide reassurance, speed return to active sport, and benefit performance.
https://ift.tt/2oyHnpI
https://ift.tt/2oyHnpI
The Impact of Noncavity-Distorting Intramural Fibroids on the Efficacy of In Vitro Fertilization-Embryo Transfer: An Updated Meta-Analysis
Aim. To address the impact of noncavity-distorting intramural fibroids on the efficacy of in vitro fertilization-embryo transfer (IVF-ET) outcomes. Methods. The PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure were searched systematically. A meta-analysis was performed based on comparative or cohort studies that explored the impact of noncavity-distorting intramural fibroids on the efficacy of IVF-ET treatment. The IVE-ET outcomes of study group (women with noncavity-distorting intramural fibroids) and control group (women without fibroids) were compared, including live birth rate (LBR), clinical pregnancy rate (cPR), implantation rate (IR) , miscarriage rate (MR), and ectopic pregnancy rate (ePR). Results. A total of 28 studies involving 9189 IVF cycles were included. Our meta-analysis showed a significant reduction of LBR in the study group compared to control group (RR = 0.82, 95% CI: 0.73-0.92, and P = 0.005). In addition, it indicated that study group had a significant reduction in cPR (RR = 0.86, 95% CI: 0.80-0.93, P = 0.0001) and IR (RR = 0.90, 95% CI: 0813-1.00, P = 0.04) and have a significantly increase in MR (RR = 1.27, 95% CI: 1.08-1.50, and P = 0.004) compared with control group. Conclusions. The present evidence suggests that noncavity-distorting intramural fibroids would significantly reduce the IR, cRP, and LBR and significantly increase the MR after IVF treatment, but it would not significantly increase the ePR.
https://ift.tt/2Q0ayOS
The Standardized Pediatric Expedited Encounters for ART Drugs Initiative (SPEEDI): description and evaluation of an innovative pediatric, adolescent, and young adult antiretroviral service delivery model in Tanzania
As countries scale up antiretroviral therapy (ART) for children, innovative strategies to deliver quality services to children are needed. Differentiated ART delivery models have been successful in adults, but...
https://ift.tt/2wFvxh8
Pipeline for specific subtype amplification and drug resistance detection in hepatitis C virus
Despite the high sustained virological response rates achieved with current directly-acting antiviral agents (DAAs) against hepatitis C virus (HCV), around 5–10% of treated patients do not respond to current a...
https://ift.tt/2oCoUsb
Role of MIRU-VNTR and spoligotyping in assessing the genetic diversity of Mycobacterium tuberculosis in Henan Province, China
Tuberculosis remains a serious threat to human health as an infectious disease in China. Henan, a most populated province in China, has a high incidence of tuberculosis (TB). Though the genetic diversity of Mycob...
https://ift.tt/2LWDHYd
Epidemiology of influenza in Ethiopia: findings from influenza sentinel surveillance and respiratory infection outbreak investigations, 2009–2015
Influenza is an acute viral disease of the respiratory tract which is characterized by fever, headache, myalgia, prostration, coryza, sore throat and cough. Globally, an estimated 3 to 5 million cases of sever...
https://ift.tt/2oBUZjS
Adenovirus associated with acute diarrhea: a case-control study
Diarrhea is a major source of morbidity and mortality among young children in low-income and middle-income countries. Human adenoviruses (HAdV), particular HAdV species F (40, 41) has been recognized as import...
https://ift.tt/2wDYvhs
Right Lobe Split Liver Graft Versus Whole Liver Transplantation: A Systematic Review by updated traditional and Cumulative Meta-analysis
Advancements in surgical techniques and experience of donor–recipient pairing has led to a wider use of right split liver grafts in adults. An update meta-analysis was conducted to compare right split liver graft (RSLG) and whole liver transplantation (WLT) using traditional and cumulative approaches.
https://ift.tt/2NGhijb
Analysis of endoscopic features for histologic discrepancies between biopsy and endoscopic submucosal dissection in gastric neoplasms: 10-year results
The histologic discrepancies between preoperative endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) specimens sometimes confuse the endoscope operator. This study aimed to analyze the limitation of the biopsy-based diagnosis before ESD and to evaluate which factors affect the discordant pathologic results between EFB and ESD.
https://ift.tt/2oDVBpg
Medicines for Treatment Intensification in Type 2 Diabetes and Type of Insulin in Type 1 and Type 2 Diabetes in Low-Resource Settings: Synopsis of the World Health Organization Guidelines on Second- and Third-Line Medicines and Type of Insulin for the Control of Blood Glucose Levels in Nonpregnant Adults With Diabetes Mellitus
Description:
The World Health Organization developed these guidelines to provide guidance on selection of medicines for treatment intensification in type 2 diabetes and on use of insulin (human or analogue) in type 1 and 2 diabetes. The target audience includes clinicians, policymakers, national diabetes program managers, and medicine procurement officers. The target population is adults with type 1 or 2 diabetes in low-resource settings in low- or high-income countries. The guidelines also apply to disadvantaged populations in high-income countries. Methods:
The recommendations were formulated by a 12-member guideline development group and are based on high-quality systematic reviews identified via a search of several bibliographic databases from 1 January 2007 to 1 March 2017. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to assess the quality of the evidence and the strength of the recommendations. The guideline was peer-reviewed by 6 external reviewers. Recommendation 1:
Give a sulfonylurea to patients with type 2 diabetes who do not achieve glycemic control with metformin alone or who have contraindications to metformin (strong recommendation, moderate-quality evidence). Recommendation 2:
Introduce human insulin treatment to patients with type 2 diabetes who do not achieve glycemic control with metformin and/or a sulfonylurea (strong recommendation, very-low-quality evidence). Recommendation 3:
If insulin is unsuitable, a dipeptidyl peptidase-4 (DPP-4) inhibitor, a sodium–glucose cotransporter-2 (SGLT-2) inhibitor, or a thiazolidinedione (TZD) may be added (weak recommendation, very-low-quality evidence). Recommendation 4:
Use human insulin to manage blood glucose in adults with type 1 diabetes and in adults with type 2 diabetes for whom insulin is indicated (strong recommendation, low-quality evidence). Recommendation 5:
Consider long-acting insulin analogues to manage blood glucose in adults with type 1 or type 2 diabetes who have frequent severe hypoglycemia with human insulin (weak recommendation, moderate-quality evidence for severe hypoglycemia).https://ift.tt/2wFLrc1
Scoping Reviews and Systematic Reviews: Is It an Either/Or Question?
Tricco and colleagues engaged 26 experts across the globe and used a structured Delphi approach to examine and adapt the 27 PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) items for application to scoping reviews. The editorialist discusses the definition of scoping reviews in relation to systematic reviews and highlights examples of scoping reviews.
https://ift.tt/2LUOodx
https://ift.tt/2LUOodx
PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation
Scoping reviews, a type of knowledge synthesis, follow a systematic approach to map evidence on a topic and identify main concepts, theories, sources, and knowledge gaps. Although more scoping reviews are being done, their methodological and reporting quality need improvement. This document presents the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist and explanation. The checklist was developed by a 24-member expert panel and 2 research leads following published guidance from the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network. The final checklist contains 20 essential reporting items and 2 optional items. The authors provide a rationale and an example of good reporting for each item. The intent of the PRISMA-ScR is to help readers (including researchers, publishers, commissioners, policymakers, health care providers, guideline developers, and patients or consumers) develop a greater understanding of relevant terminology, core concepts, and key items to report for scoping reviews.
https://ift.tt/2PWtUo9
World Health Organization Guidelines on Medicines for Diabetes Treatment Intensification: Commentary From the American College of Physicians High Value Care Committee
The World Health Organization (WHO) guideline on managing diabetes mellitus contains important considerations, including evidence about benefits and harms of medications, intervention costs, and application to resource-poor settings. This commentary from the American College of Physicians High Value Care Committee considers the nuances of clinical decision making in the face of limited evidence and resources, and discusses the implications of the WHO guideline for clinicians in the United States.
https://ift.tt/2LX0yTc
https://ift.tt/2LX0yTc
Parallel algorithm for myeloproliferative neoplasms testing: the frequency of double mutations is found in the JAK2/MPL genes more often than the JAK2/CALR genes, but is there a clinical benefit?
Authors: Gorbenko, Aleksey S. / Stolyar, Marina A. / Olkhovskiy, Igor A. / Vasiliev, Evgeniy V. / Mikhalev, Mikhail A.
https://ift.tt/2wpvh6G
Procalcitonin as guide to therapy in endovascular infections: caveat emptor!
Authors: Spaziante, Martina / Ceccarelli, Giancarlo / Venditti, Mario
https://ift.tt/2NxgNIx
A very rare interference with the valproate method on the Beckman DxC 800 general chemistry analyser
Authors: Dimeski, Goce / Treacy, Oliver / Marshall, George
https://ift.tt/2MG2mFG
Mid-regional pro-adrenomedullin predicts poor outcome in non-selected patients admitted to an intensive care unit
Authors: Bellia, Chiara / Agnello, Luisa / Lo Sasso, Bruna / Bivona, Giulia / Raineri, Maurizio Santi / Giarratano, Antonino / Ciaccio, Marcello
https://ift.tt/2wpv838
Standardization and harmonization of autoimmune diagnostics
Authors: Jacobs, Joannes F.M. / Bossuyt, Xavier
https://ift.tt/2vW3bzv
Observing an analyzer’s operational life cycle: a useful management tool for clinical laboratories
Authors: Hoffmann, Johannes J.M.L.
https://ift.tt/2MaZobL
Eslicarbazepine acetate as monotherapy in clinical practice: outcomes from Euro‐Esli
Acta Neurologica Scandinavica, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Q2TJms
Zika in 2018: Advising Travelers Amid Changing Incidence
Many gaps in our knowledge about key features of Zika virus infection make it difficult to counsel patients who are contemplating travel to Zika-affected countries and to determine appropriate testing strategies on their return. The authors suggest an approach to shared decision making between travel medicine providers and patients.
https://ift.tt/2NgvfDS
https://ift.tt/2NgvfDS
Risks and Benefits of Marijuana Use A National Survey of U.S. Adults
Background:
Despite insufficient evidence regarding its risks and benefits, marijuana is increasingly available and is aggressively marketed to the public. Objective:
To understand the public's views on the risks and benefits of marijuana use. Design:
Probability-based online survey. Setting:
United States, 2017. Participants:
16 280 U.S. adults. Measurements:
Proportion of U.S. adults who agreed with a statement. Results:
The response rate was 55.3% (n = 9003). Approximately 14.6% of U.S. adults reported using marijuana in the past year. About 81% of U.S. adults believe marijuana has at least 1 benefit, whereas 17% believe it has no benefit. The most common benefit cited was pain management (66%), followed by treatment of diseases, such as epilepsy and multiple sclerosis (48%), and relief from anxiety, stress, and depression (47%). About 91% of U.S. adults believe marijuana has at least 1 risk, whereas 9% believe it has no risks. The most common risk identified by the public was legal problems (51.8%), followed by addiction (50%) and impaired memory (42%). Among U.S. adults, 29.2% agree that smoking marijuana prevents health problems. About 18% believe exposure to secondhand marijuana smoke is somewhat or completely safe for adults, whereas 7.6% indicated that it is somewhat or completely safe for children. Of the respondents, 7.3% agree that marijuana use is somewhat or completely safe during pregnancy. About 22.4% of U.S. adults believe that marijuana is not at all addictive. Limitation:
Wording of the questions may have affected interpretation. Conclusion:
Americans' view of marijuana use is more favorable than existing evidence supports. Primary Funding Source:
National Heart, Lung, and Blood Institute.https://ift.tt/2uZUgf0
Tumor Necrosis Factor Inhibitors and Cancer Recurrence in Swedish Patients With Rheumatoid Arthritis A Nationwide Population-Based Cohort Study
Background:
Use of tumor necrosis factor inhibitors (TNFi) in patients with a history of cancer remains a clinical dilemma. Objective:
To investigate whether TNFi treatment in rheumatoid arthritis (RA) is associated with increased risk for cancer recurrence. Design:
Population-based cohort study based on linkage of nationwide registers. Setting:
Sweden. Participants:
Patients with RA who started TNFi treatment between 2001 and 2015, after being diagnosed with cancer, and matched patients with RA and a history of the same cancer who had never received biologics. Measurements:
The primary outcome was the first recurrence of cancer. Adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs), taking into account time, cancer type, and whether the cancer was invasive or in situ (or tumor, node, metastasis [TNM] classification system stage in a subset of patients). Results:
Among 467 patients who started TNFi treatment (mean time after cancer diagnosis, 7.9 years), 42 had cancer recurrences (9.0%; mean follow-up, 5.3 years); among 2164 matched patients with the same cancer history, 155 had recurrences (7.2%; mean follow-up, 4.3 years) (HR, 1.06 [95% CI, 0.73 to 1.54). Hazard ratios were close to 1 in analyses of patient subsets matched on cancer stage or with similar time from index cancer diagnosis to the start of TNFi treatment, as well as in unmatched analyses. Several CIs had upper limits close to 2. Limitation:
The outcome algorithm was partly nonvalidated, and channeling bias was possible if patients with a better index cancer prognosis were more likely to receive TNFi. Conclusion:
The findings suggest that TNFi treatment is not associated with increased risk for cancer recurrence in patients with RA, although meaningful risk increases could not be ruled out completely. Primary Funding Source:
ALF (an agreement in Stockholm County Council concerning medical education and research in health and medical care), the Swedish Cancer Society, the Swedish Foundation for Strategic Research, and the Swedish Research Council.https://ift.tt/2MqdHZl
Microvascular Outcomes in Patients With Diabetes After Bariatric Surgery Versus Usual Care A Matched Cohort Study
Background:
Bariatric surgery improves glycemic control in patients with type 2 diabetes mellitus (T2DM), but less is known about microvascular outcomes. Objective:
To investigate the relationship between bariatric surgery and incident microvascular complications of T2DM. Design:
Retrospective matched cohort study from 2005 to 2011 with follow-up through September 2015. Setting:
4 integrated health systems in the United States. Participants:
Patients aged 19 to 79 years with T2DM who had bariatric surgery (n = 4024) were matched on age, sex, body mass index, hemoglobin A1c level, insulin use, diabetes duration, and intensity of health care use up to 3 nonsurgical participants (n = 11 059). Intervention:
Bariatric procedures (76% gastric bypass, 17% sleeve gastrectomy, and 7% adjustable gastric banding) compared with usual care. Measurements:
Adjusted Cox regression analysis investigated time to incident microvascular disease, defined as first occurrence of diabetic retinopathy, neuropathy, or nephropathy. Results:
Median follow-up was 4.3 years for both surgical and nonsurgical patients. Bariatric surgery was associated with significantly lower risk for incident microvascular disease at 5 years (16.9% for surgical vs. 34.7% for nonsurgical patients; adjusted hazard ratio [HR], 0.41 [95% CI, 0.34 to 0.48]). Bariatric surgery was associated with lower cumulative incidence at 5 years of diabetic neuropathy (7.2% for surgical vs. 21.4% for nonsurgical patients; HR, 0.37 [CI, 0.30 to 0.47]), nephropathy (4.9% for surgical vs. 10.0% for nonsurgical patients; HR, 0.41 [CI, 0.29 to 0.58]), and retinopathy (7.2% for surgical vs. 11.2% for nonsurgical patients; HR, 0.55 [CI, 0.42 to 0.73]). Limitation:
Electronic health record databases could misclassify microvascular disease status for some patients. Conclusion:
In this large, multicenter study of adults with T2DM, bariatric surgery was associated with lower overall incidence of microvascular disease (including lower risk for neuropathy, nephropathy, and retinopathy) than usual care. Primary Funding Source:
National Institute of Diabetes and Digestive and Kidney Diseases.https://ift.tt/2ANbAu1
Screening for Urinary Incontinence in Women: A Systematic Review for the Women's Preventive Services Initiative
Background:
Urinary incontinence is infrequently addressed during routine health care despite its high prevalence and adverse effects on health. Purpose:
To evaluate whether screening for urinary incontinence in women not previously diagnosed improves outcomes (symptoms, quality of life, and function) and to evaluate the accuracy of screening methods and potential harms of screening. Data Sources:
English-language searches of Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (1 January 1996 to 30 March 2018); ClinicalTrials.gov (April 2018); and reference lists of studies and reviews. Study Selection:
Randomized trials, cohort studies, systematic reviews of studies that enrolled nonpregnant women without previously diagnosed urinary incontinence and compared clinical outcomes and adverse effects between women who were and were not screened, and diagnostic accuracy studies that reported performance measures of screening tests. Data Extraction:
Dual extraction and quality assessment of individual studies. Data Synthesis:
No studies evaluated the overall effectiveness or harms of screening. Seventeen studies evaluated the diagnostic accuracy of 18 screening questionnaires against a clinical diagnosis or results of diagnostic tests. Of these, 14 poor-quality studies were based in referral clinics, enrolled only symptomatic women, or had other limitations. One good-quality and 2 fair-quality studies (evaluating 4 methods) enrolled women not recruited on the basis of symptoms. Areas under the receiver-operating characteristic curve for stress, urge, and any type of incontinence in these studies were 0.79, 0.88, and 0.88 for the Michigan Incontinence Symptom Index; 0.85, 0.83, and 0.87 for the Bladder Control Self-Assessment Questionnaire; and 0.68, 0.82, and 0.75 for the Overactive Bladder Awareness Tool. The Incontinence Screening Questionnaire had a sensitivity of 66% and specificity of 80% for any type of incontinence. Limitation:
Studies enrolled few participants, often from symptomatic referral populations; used various reference standards; and infrequently reported CIs. Conclusion:
Evidence is insufficient on the overall effectiveness and harms of screening for urinary incontinence in women. Limited evidence in general populations suggests fairly high accuracy for some screening methods. Primary Funding Source:
Health Resources and Services Administration.https://ift.tt/2MEqMeq
Screening for Urinary Incontinence in Women: A Recommendation From the Women's Preventive Services Initiative
Description:
Recommendation on screening for urinary incontinence in women by the Women's Preventive Services Initiative (WPSI), a national coalition of women's health professional organizations and patient representatives. The WPSI's recommendations are intended to guide clinical practice and coverage of services for the Health Resources and Services Administration and other stakeholders. The target audience for this recommendation includes all clinicians providing preventive health care for women, particularly in primary care settings. This recommendation applies to women of all ages, as well as adolescents. Methods:
The WPSI developed this recommendation after evaluating evidence regarding the benefits and harms of screening for urinary incontinence in women. The evaluation included a systematic review of the accuracy of screening instruments and the benefits and harms of treatments. Indirect evidence was used to link screening and health outcomes in the chain of evidence that might support screening in the absence of direct evidence. The WPSI also considered the effect of screening on symptom progression and avoidance of costly and complex treatments, as well as implementation factors. Recommendation:
The WPSI recommends screening women for urinary incontinence annually. Screening ideally should assess whether women experience urinary incontinence and whether it affects their activities and quality of life. The WPSI recommends referring women for further evaluation and treatment if indicated.https://ift.tt/2MLIKvt
Is It Ethical to Use Genealogy Data to Solve Crimes?
Information from online genealogy services might be used in manners not anticipated by consumers, including as forensic evidence in crime solving. The authors discuss the informed consent, privacy, and justice issues of such use.
https://ift.tt/2Jf7gXm
https://ift.tt/2Jf7gXm
Integrating Treatment at the Intersection of Opioid Use Disorder and Infectious Disease Epidemics in Medical Settings: A Call for Action After a National Academies of Sciences, Engineering, and Medicine Workshop
In this article, the authors discuss 5 action steps from a recent workshop on the integration of infectious disease considerations and responses to the opioid use disorder epidemic.
https://ift.tt/2zDylA8
https://ift.tt/2zDylA8
Twelve-Month Outcomes After Transplant of Hepatitis C–Infected Kidneys Into Uninfected Recipients A Single-Group Trial
Background:
Organs from hepatitis C virus (HCV)–infected deceased donors are often discarded. Preliminary data from 2 small trials, including THINKER-1 (Transplanting Hepatitis C kidneys Into Negative KidnEy Recipients), suggested that HCV-infected kidneys could be safely transplanted into HCV-negative patients. However, intermediate-term data on quality of life and renal function are needed to counsel patients about risk. Objective:
To describe 12-month HCV treatment outcomes, estimated glomerular filtration rate (eGFR), and quality of life for the 10 kidney recipients in THINKER-1 and 6-month data on 10 additional recipients. Design:
Open-label, nonrandomized trial. (ClinicalTrials.gov: NCT02743897) Setting:
Single center. Participants:
20 HCV-negative transplant candidates. Intervention:
Participants underwent transplant with kidneys infected with genotype 1 HCV and received elbasvir–grazoprevir on posttransplant day 3. Measurements:
The primary outcome was HCV cure. Exploratory outcomes included 1) RAND-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) quality-of-life scores at enrollment and after transplant, and 2) posttransplant renal function, which was compared in a 1:5 matched sample with recipients of HCV-negative kidneys. Results:
The mean age of THINKER participants was 56.3 years (SD, 6.7), 70% were male, and 40% were black. All 20 participants achieved HCV cure. Hepatic and renal complications were transient or were successfully managed. Mean PCS and MCS quality-of-life scores decreased at 4 weeks; PCS scores then increased above pretransplant values, whereas MCS scores returned to baseline values. Estimated GFRs were similar between THINKER participants and matched recipients of HCV-negative kidneys at 6 months (median, 67.5 vs. 66.2 mL/min/1.73 m2; 95% CI for between-group difference, −4.2 to 7.5 mL/min/1.73 m2) and 12 months (median, 72.8 vs. 67.2 mL/min/1.73 m2; CI for between-group difference, −7.2 to 9.8 mL/min/1.73 m2). Limitation:
Small trial. Conclusion:
Twenty HCV-negative recipients of HCV-infected kidneys experienced HCV cure, good quality of life, and excellent renal function. Kidneys from HCV-infected donors may be a valuable transplant resource. Primary Funding Source:
Merck.https://ift.tt/2AIgTuG
Making the Voices of Female Trainees Heard
Female physicians are less likely to become full professors and are paid lower salaries than their male colleagues. This article describes the discovery of a gender disparity in "shout-outs" in a residency program and actions that rectified the disparity.
https://ift.tt/2NmrGwe
https://ift.tt/2NmrGwe
Blue laser imaging-bright improves real-time detection rate of early gastric cancer: a randomized controlled study
Blue laser imaging (BLI)-bright (BLI-bright) has shown promise as a more useful tool for detection of early gastric cancer (EGC) than white-light imaging (WLI). However, the diagnostic performance of BLI-bright in the detection of EGC has not been investigated. We aimed to compare real-time detection rates of WLI with that of BLI-bright for EGC.
https://ift.tt/2LR4Onb
Single-stage EUS-guided choledochoduodenostomy using a lumen-apposing metal stent for malignant distal biliary obstruction
EUS-guided choledochoduodenostomy(EUS-CD) using a lumen-apposing metal stent (LAMS) has been recently reported as an alternative treatment approach for patients with malignant obstructive jaundice and failed endoscopic retrograde cholangiopancreatography (ERCP). We analyzed the safety, technical and clinical efficacy of EUS-CD using LAMS in patients with malignant obstructive jaundice.
https://ift.tt/2Q4UvQ3
Retraction: Guiding Cell Migration Using One‐Way Micropattern Arrays
Advanced Materials, Volume 30, Issue 36, September 6, 2018.
https://ift.tt/2wCrJxW
Transparent Conductors: A Deformable and Highly Robust Ethyl Cellulose Transparent Conductor with a Scalable Silver Nanowires Bundle Micromesh (Adv. Mater. 36/2018)
Advanced Materials, Volume 30, Issue 36, September 6, 2018.
https://ift.tt/2oAsMtR
Graphene Sheets: Strong, Conductive, Foldable Graphene Sheets by Sequential Ionic and π Bridging (Adv. Mater. 36/2018)
Advanced Materials, Volume 30, Issue 36, September 6, 2018.
https://ift.tt/2PyUWB0
Seedcoat Suture Tessellation: Amplifying Strength, Toughness, and Auxeticity via Wavy Sutural Tessellation in Plant Seedcoats (Adv. Mater. 36/2018)
Advanced Materials, Volume 30, Issue 36, September 6, 2018.
https://ift.tt/2oyh0QK
Cancer Theranostics: A Novel Top‐Down Synthesis of Ultrathin 2D Boron Nanosheets for Multimodal Imaging‐Guided Cancer Therapy (Adv. Mater. 36/2018)
Advanced Materials, Volume 30, Issue 36, September 6, 2018.
https://ift.tt/2Cc2Ka3
Versatility of Carbon Enables All Carbon Based Perovskite Solar Cells to Achieve High Efficiency and High Stability
Advanced Materials, Volume 30, Issue 36, September 6, 2018.
https://ift.tt/2PBsmip
Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding
Advanced Materials, Volume 30, Issue 36, September 6, 2018.
https://ift.tt/2wCrDGA
Contents: (Adv. Mater. 36/2018)
Advanced Materials, Volume 30, Issue 36, September 6, 2018.
https://ift.tt/2Cq49tN
Masthead: (Adv. Mater. 36/2018)
Advanced Materials, Volume 30, Issue 36, September 6, 2018.
https://ift.tt/2oAO5LO
Artificial Synapses: Low‐Power, Electrochemically Tunable Graphene Synapses for Neuromorphic Computing (Adv. Mater. 36/2018)
Advanced Materials, Volume 30, Issue 36, September 6, 2018.
https://ift.tt/2PB6nIt
Feroxyhyte Nanosheets: Iron Vacancies Induced Bifunctionality in Ultrathin Feroxyhyte Nanosheets for Overall Water Splitting (Adv. Mater. 36/2018)
Advanced Materials, Volume 30, Issue 36, September 6, 2018.
https://ift.tt/2oAstzd
Flexible Photodetectors: Low‐Temperature Heteroepitaxy of 2D PbI2/Graphene for Large‐Area Flexible Photodetectors (Adv. Mater. 36/2018)
Advanced Materials, Volume 30, Issue 36, September 6, 2018.
https://ift.tt/2PsToIs
Scaling beta‐lactam antimicrobial pharmacokinetics from early life to old age
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2wDevRl
herapeutic drug monitoring of tacrolimus and mycophenolic acid in outpatient renal transplant recipients using a volumetric dried blood spot sampling device
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2PwQt1y
Contourlet-based hippocampal magnetic resonance imaging texture features for multivariant classification and prediction of Alzheimer’s disease
Abstract
The study is aimed to assess whether the addition of contourlet-based hippocampal magnetic resonance imaging (MRI) texture features to multivariant models improves the classification of Alzheimer's disease (AD) and the prediction of mild cognitive impairment (MCI) conversion, and to evaluate whether Gaussian process (GP) and partial least squares (PLS) are feasible in developing multivariant models in this context. Clinical and MRI data of 58 patients with probable AD, 147 with MCI, and 94 normal controls (NCs) were collected. Baseline contourlet-based hippocampal MRI texture features, medical histories, symptoms, neuropsychological tests, volume-based morphometric (VBM) parameters based on MRI, and regional CMgl measurement based on fluorine-18 fluorodeoxyglucose-positron emission tomography were included to develop GP and PLS models to classify different groups of subjects. GPR1 model, which incorporated MRI texture features and was based on GPG, performed better in classifying different groups of subjects than GPR2 model, which used the same algorithm and had the same data as GPR1 except that MRI texture features were excluded. PLS model, which included the same variables as GPR1 but was based on the PLS algorithm, performed best among the three models. GPR1 accurately predicted 82.2% (51/62) of MCI convertors confirmed during the 2-year follow-up period, while this figure was 53 (85.5%) for PLS model. GPR1 and PLS models accurately predicted 58 (79.5%) vs. 61 (83.6%) of 73 patients with stable MCI, respectively. For seven patients with MCI who converted to NCs, PLS model accurately predicted all cases (100%), while GPR1 predicted six (85.7%) cases. The addition of contourlet-based MRI texture features to multivariant models can effectively improve the classification of AD and the prediction of MCI conversion to AD. Both GPR and LPS models performed well in the classification and predictive process, with the latter having significantly higher classification and predictive accuracies. Advances in knowledge: We combined contourlet-based hippocampal MRI texture features, medical histories, symptoms, neuropsychological tests, volume-based morphometric (VBM) parameters, and regional CMgl measurement to develop models using GP and PLS algorithms to classify AD patients.
https://ift.tt/2oANslp
Prevalence and Impact of Human Papillomavirus on Head and Neck Cancers: Review of Indian Studies
Abstract
Human papillomavirus (HPV) is an important emerging etiology for head and neck cancers (HNCs) worldwide. Considering its impact on prognosis, it is important to understand the true prevalence of HPV-associated HNCs in India. This article reviews the prevalence of HPV-related HNCs across various studies in India where the population is predominantly tobacco users, and studies its outcomes with respect to HPV.
https://ift.tt/2Pu3lWi
Tandem DNAzyme for double digestion: a new tool for circRNA suppression
Authors: Ding, Junyao / Zhou, Wenhu / Li, Xiaojing / Sun, Meng / Ding, Jingsong / Zhu, Qubo
https://ift.tt/2LSfNNt
An alternative processing pathway of APP reveals two distinct cleavage modes for rhomboid protease RHBDL4
Authors: Recinto, Sherilyn Junelle / Paschkowsky, Sandra / Munter, Lisa Marie
https://ift.tt/2wLmtIz
A single domain antibody against the Cys- and His-rich domain of PCSK9 and evolocumab exhibit different inhibition mechanisms in humanized PCSK9 mice
Authors: Essalmani, Rachid / Weider, Elodie / Marcinkiewicz, Jadwiga / Chamberland, Ann / Susan-Resiga, Delia / Roubtsova, Anna / Seidah, Nabil G. / Prat, Annik
https://ift.tt/2wwyQal
Highlight: sphingolipids in infectious biology and immunology
Authors: Carpinteiro, Alexander / Becker, Katrin Anne / Gulbins, Erich
https://ift.tt/2owNcEd
Resveratrol alleviates early brain injury following subarachnoid hemorrhage: possible involvement of the AMPK/SIRT1/autophagy signaling pathway
Authors: Li, Zhiguo / Han, Xinwei
https://ift.tt/2P63aA8
Aberrant expression of hsa_circ_0025036 in lung adenocarcinoma and its potential roles in regulating cell proliferation and apoptosis
Authors: Wu, Shujun / Li, Hui / Lu, Chunya / Zhang, Furui / Wang, Huaqi / Lu, Xinhua / Zhang, Guojun
https://ift.tt/2wLmlc3
MicroRNA-1225-5p acts as a tumor-suppressor in laryngeal cancer via targeting CDC14B
Authors: Sun, Peng / Zhang, Dan / Huang, Haiping / Yu, Yafeng / Yang, Zhendong / Niu, Yuyu / Liu, Jisheng
https://ift.tt/2LSfxht
Advanced glycation endproducts and polysialylation affect the turnover of the neural cell adhesion molecule (NCAM) and the receptor for advanced glycation endproducts (RAGE)
Authors: Frank, Franziska / Bezold, Veronika / Bork, Kaya / Rosenstock, Philip / Scheffler, Jonas / Horstkorte, Rüdiger
https://ift.tt/2wDbCQz
Modulation of dynamin function by small molecules
Authors: Eschenburg, Susanne / Reubold, Thomas F.
https://ift.tt/2o2qcwh
Chemotherapeutic resistance: a nano-mechanical point of view
Authors: Nyongesa, Collins Otieno / Park, Soyeun
https://ift.tt/2BEDxoh
Safety implications of plasma-induced effects in living cells – a review of in vitro and in vivo findings
Authors: Boehm, Daniela / Bourke, Paula
https://ift.tt/2BDvic1
Cold atmospheric plasma is a viable solution for treating orthopaedic infection: a review
Authors: Nguyen, Ly / Lu, Peng / Boehm, Daniela / Bourke, Paula / Gilmore, Brendan F. / Hickok, Noreen J. / Freeman, Theresa A.
https://ift.tt/2wAXTdi
Transcriptional regulation of human defense peptides: a new direction in infection control
Authors: Mandal, Santi M. / Manna, Sounik / Mondal, Sneha / Ghosh, Ananta K. / Chakraborty, Ranadhir
https://ift.tt/2nurgZw
p21Waf1 deficiency does not decrease DNA repair in E1A+cHa-Ras transformed cells by HDI sodium butyrate
Authors: Igotti, Maria / Gnedina, Olga / Morshneva, Alisa / Svetlikova, Svetlana / Pospelov, Valery
https://ift.tt/2OtWBXP
Inhibition of JAK2/STAT3 signaling suppresses bone marrow stromal cells proliferation and osteogenic differentiation, and impairs bone defect healing
Authors: Yu, Xin / Li, Zhi / Wan, Qilong / Cheng, Xin / Zhang, Jing / Pathak, Janak L. / Li, Zubing
https://ift.tt/2nqwNAr
Tumor necrosis as a prognostic variable for the clinical outcome in patients with renal cell carcinoma: a systematic review and meta-analysis
Abstract
Background
Tumor necrosis (TN) correlates with adverse outcomes in numerous solid tumors. However, its prognostic value in renal cell carcinoma (RCC) remains unclear. In this study, we performed a meta-analysis to evaluate associations between TN and cancer-specific survival (CSS), overall survival (OS), recurrence-free survival (RFS) and progression-free-survival (PFS) in RCC.
Methods
Electronic searches in PubMed, EMBASE and Web of Science were conducted according to the PRISMA statement. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate relationships between TN and RCC. A fixed- or random-effects model was used to calculate pooled HRs and 95%CIs according to heterogeneity.
Results
A total of 34 cohort studies met the eligibility criteria of this meta-analysis. The results showed that TN was significantly predictive of poorer CSS (HR = 1.37, 95% CI: 1.23–1.53, p < 0.001), OS (HR = 1.29, 95% CI: 1.20–1.40, p < 0.001), RFS (HR = 1.55, 95% CI: 1.39–1.72, p < 0.001) and PFS (HR = 1.31, 95% CI: 1.17–1.46, p < 0.001) in patients with RCC. All the findings were robust when stratified by geographical region, pathological type, staging system, number of patients, and median follow-up.
Conclusions
The present study suggests that TN is associated with CSS, OS, RFS and PFS clinical outcomes of RCC patients and may serve as a predictor of poor prognosis in these patients.
https://ift.tt/2wDwjen
Postoperative resveratrol administration improves prognosis of rat orthotopic glioblastomas
Abstract
Background
Although our previous study revealed lumbar punctured resveratrol could remarkably prolong the survival of rats bearing orthotopic glioblastomas, it also suggested the administration did not completely suppress rapid tumour growth. These evidences led us to consider that the prognosis of tumour-bearing rats may be further improved if this treatment is used in combination with neurosurgery. Therefore, we investigated the effectiveness of the combined treatment on rat orthotopic glioblastomas.
Methods
Rat RG2 glioblastoma cells were inoculated into the brains of 36 rats. The rats were subjected to partial tumour removal after they showed symptoms of intracranial hypertension. There were 28 rats that survived the surgery, and these animals were randomly and equally divided into the control group without postoperative treatment and the LP group treated with 100 μl of 300 μM resveratrol via the LP route. Resveratrol was administered 24 h after tumour resection in 3-day intervals, and the animals received 7 treatments. The intracranial tumour sizes, average life span, cell apoptosis and STAT3 signalling were evaluated by multiple experimental approaches in the tumour tissues harvested from both groups.
Results
The results showed that 5 of the 14 (35.7%) rats in the LP group remained alive over 60 days without any sign of recurrence. The remaining nine animals had a longer mean postoperative survival time (11.0 ± 2.9 days) than that of the (7.3 + 1.3 days; p < 0.05) control group. The resveratrol-treated tumour tissues showed less Ki67 labelling, widely distributed apoptotic regions, upregulated PIAS3 expression and reduced p-STAT3 nuclear translocation.
Conclusions
This study demonstrates that postoperative resveratrol administration efficiently improves the prognosis of rat advanced orthotopic glioblastoma via inhibition of growth, induction of apoptosis and inactivation of STAT3 signalling. Therefore, this therapeutic approach could be of potential practical value in the management of glioblastomas.
https://ift.tt/2MNoEoM
The plasma glutamate concentration as a complementary tool to differentiate benign PET-positive lung lesions from lung cancer
Abstract
Background
Pulmonary imaging often identifies suspicious abnormalities resulting in supplementary diagnostic procedures. This study aims to investigate whether the metabolic fingerprint of plasma allows to discriminate between patients with lung inflammation and patients with lung cancer.
Methods
Metabolic profiles of plasma from 347 controls, 269 cancer patients and 108 patients with inflammation were obtained by 1H-NMR spectroscopy. Models to discriminate between groups were trained by PLS-LDA. A test set was used for independent validation. A ROC curve was built to evaluate the diagnostic performance of potential biomarkers.
Results
Sensitivity, specificity, PPV and NPV of PET-CT to diagnose cancer are 96, 23, 76 and 71%. Metabolic profiles differentiate between cancer and inflammation with a sensitivity of 89%, a specificity of 87% and a MCE of 12%. Removal of the glutamate metabolite results in an increase of MCE (38%) and a decrease of both sensitivity and specificity (62%), demonstrating the importance of glutamate for discrimination. At the cut-off point 0.31 on the ROC curve, the relative glutamate concentration discriminates between cancer and inflammation with a sensitivity of 85%, a specificity of 81%, and an AUC of 0.88. PPV and NPV are 92 and 69%. In PET-positive patients with a relative glutamate level ≤ 0.31 the sensitivity to diagnose cancer reaches 100% with a PPV of 94%. In PET-negative patients, a relative glutamate level > 0.31 increases the specificity of PET from 23% to 58% and results in a high NPV of 100%. In case of discrepancy between SUVmax and the glutamate concentration, lung cancer is missed in 19% of the cases.
Conclusion
This study indicates that the 1H-NMR-derived relative plasma concentration of glutamate allows discrimination between lung cancer and lung inflammation. A glutamate level ≤ 0.31 in PET-positive patients corresponds to the diagnosis of lung cancer with a higher specificity and PPV than PET-CT. Glutamate levels > 0.31 in patients with PET negative lung lesions is likely to correspond with inflammation. Caution is needed for patients with conflicting SUVmax values and glutamate concentrations. Confirmation is needed in a prospective study with external validation and by another analytical technique such as HPLC-MS.
https://ift.tt/2wDCQGa
Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis
Abstract
Background
The MRE11/RAD50/NBS1 (MRN) complex plays an essential role in detecting and repairing double-stranded breaks, and thus the potential roles of MRE11, RAD50 and NBS1 proteins in the pathogenesis of various cancers is the subject of investigation. This study was aimed at assessing the three-protein panel of MRN complex subunits as a potential radiosensitivity marker and evaluating the prognostic and clinicopathological implications of MRN expression in rectal cancer.
Methods
Samples from 265 rectal cancer patients treated with surgery and adjuvant chemoradiotherapy, including samples from 55 patients who were treated with neoadjuvant radiotherapy between 2000 and 2011, were analyzed. Expression of MRN complex proteins in tissue samples was determined by immunohistochemistry. Univariate and multivariate analyses were carried out to identify clinicopathological characteristics that are associated with the MRN three-protein panel expression in rectal cancer samples.
Results
In Kaplan–Meier survival analyses, we found that high level expression of MRN complex proteins in postoperative samples was associated with poor disease-free (p = 0.021) and overall (P = 0.002) survival. Interestingly, high MRN expression also correlated with poor disease-free (P = 0.047) and overall (P = 0.024) survival in the neoadjuvant radiotherapy subgroup. In multivariate analysis, combined MRN expression (hazard ratio = 2.114, 95% confidence interval 1.096–4.078, P = 0.026) and perineural invasion (hazard ratio = 2.160, 95% confidence interval 1.209–3.859, P = 0.009) were significantly associated with a worse disease-free survival.
Conclusions
Expression levels of MRN complex proteins significantly predict disease-free survival in rectal cancer patients, including those treated with neoadjuvant radiotherapy, and may have value in the management of these patients.
https://ift.tt/2NaI5Hr
Liquid biopsy for liver diseases
With the growing number of novel therapeutic approaches for liver diseases, significant research efforts have been devoted to the development of liquid biopsy tools for precision medicine. This can be defined as non-invasive reliable biomarkers that can supplement and eventually replace the invasive liver biopsy for diagnosis, disease stratification and monitoring of response to therapeutic interventions. Similarly, detection of liver cancer at an earlier stage of the disease, potentially susceptible to curative resection, can be critical to improve patient survival. Circulating extracellular vesicles, nucleic acids (DNA and RNA) and tumour cells have emerged as attractive liquid biopsy candidates because they fulfil many of the key characteristics of an ideal biomarker. In this review, we summarise the currently available information regarding these promising and potential transformative tools, as well as the issues still needed to be addressed for adopting various liquid biopsy approaches into clinical practice. These studies may pave the way to the development of a new generation of reliable, mechanism-based disease biomarkers.
https://ift.tt/2NJInlC
Stromal biology and therapy in pancreatic cancer: ready for clinical translation?
Pancreatic ductal adenocarcinoma (PDA) is notoriously aggressive and hard to treat. The tumour microenvironment (TME) in PDA is highly dynamic and has been found to promote tumour progression, metastasis niche formation and therapeutic resistance. Intensive research of recent years has revealed an incredible heterogeneity and complexity of the different components of the TME, including cancer-associated fibroblasts, immune cells, extracellular matrix components, tumour vessels and nerves. It has been hypothesised that paracrine interactions between neoplastic epithelial cells and TME compartments may result in either tumour-promoting or tumour-restraining consequences. A better preclinical understanding of such complex and dynamic network systems is required to develop more powerful treatment strategies for patients. Scientific activity and the number of compelling findings has virtually exploded during recent years. Here, we provide an update of the most recent findings in this area and discuss their translational and clinical implications for basic scientists and clinicians alike.
https://ift.tt/2NaNVc6
Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA
Abstract
Hepatocellular carcinoma (HCC) is a highly malignant disease with a poor prognosis and high mortality due to a low early diagnosis rate, resistance to systemic treatments and progression to late-stage liver disease. Owing to limitations in the detection of HCC and the lack of awareness of healthcare systems, fewer than 40% of HCC patients are eligible for surgery due to advanced stages of the disease at the time of diagnosis and the occurrence of multiple lesions in the cirrhotic or fibrotic liver. At present, the updated American Association for the Study of Liver Disease (AASLD) guidelines no longer recommend alpha-fetoprotein (AFP) testing as a part of diagnostic evaluation. Thus, it is imperative to establish a novel diagnostic strategy with high sensitivity and reliability to monitor risk factors to detect HCC at an early stage. In recent years, "liquid biopsy," (including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)), has emerged as a technique for the characterization of circulating cells, providing a strong basis for the individualized treatment of patients. As a noninvasive detection method, liquid biopsy is expected to play an important role in the early diagnosis, dynamic monitoring of cancer patients and drug screening. In this review, we will focus on the clinical applications, recent studies and future prospects of liquid biopsy, particularly focusing on HCC.
https://ift.tt/2wH3u0y
Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression
Abstract
Background
Emerging evidences have indicated that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of cancers. Dysregulation of lncRNA MIR31HG has recently been reported in several types of cancers, and researches on the function of MIR31HG in cancers suggested that MIR31HG could act as either oncogene or tumor suppressor. But the functional involvement of MIR31HG has not been studied in hepatocellular carcinoma (HCC).
Methods
In this study, MTS assays, colony formation assay, Wound-healing assay, Transwell assy, and tumor xenografts experiments were used to identify biological effects of MIR31HG on HCC cells HCC proliferation and metastasis in vitro and in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to show the interactions of MIR31HG and miR-575. The bioinformatics methods were completed to find the target genes of miR-575. And Dual-luciferase reporter assay and Western blot analysis were further used to confirm the target gene of miR-575.
Results
We found that overexpression of MIR31HG obviously suppressed HCC proliferation and metastasis in vitro and in vivo, whereas knockdown of MIR31HG had the opposite effects. Besides, overexpression of MIR31HG significantly decreased the expression of microRNA-575 (miR-575), which plays an oncogenic role in HCC. Moreover, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay revealed that MIR31HG exerted tumor-suppressive functions by binding directly to miR-575, and there was a reciprocal inhibition between MIR31HG and miR-575 in the same RNA-induced silencing complex (RISC). Furthermore, overexpression of MIR31HG enhanced the expression of suppression of tumorigenicity 7 like (ST7L), which was identified as a downstream target gene of miR-575. Thus, MIR31HG positively regulated ST7L expression through sponging miR-575, and acted as tumor suppressor in HCC.
Conclusions
Overall, our study illuminates the role of MIR31HG as a miRNA sponge in HCC, and sheds new light on lncRNA-directed diagnostics and therapeutics in HCC.
https://ift.tt/2Neb90T
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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...
