Hypermethylation of DMTN promotes the metastasis of colorectal cancer cells by regulating the actin cytoskeleton through Rac1 signaling activation

Abstract

Background

Colorectal cancer (CRC) is one of the most common digestive malignant tumors, and DMTN is a transcriptionally differentially expressed gene that was identified using CRC mRNA sequencing data from The Cancer Genome Atlas (TCGA). Our preliminary work suggested that the expression of DMTN was downregulated in CRC, and the Rac1 signaling pathway was significantly enriched in CRC tissues with low DMTN expression. However, the specific functions and underlying molecular mechanisms of DMTN in the progression of CRC and the upstream factors regulating the downregulation of the gene remain unclear.

Methods

DMTN expression was analyzed in CRC tissues, and the relationship between DMTN expression and the clinicopathological parameters was analyzed. In vitro and in vivo experimental models were used to detect the effects of DMTN dysregulation on invasion and metastasis of CRC cells. GSEA assay was performed to explore the mechanism of DMTN in invasion and metastasis of CRC. Westernblot, Co-IP and GST-Pull-Down assay were used to detect the interaction between DMTN and ARHGEF2, as well as the activation of the RAC1 signaling. Bisulfite genomic sequence (BSP) assay was used to test the degree of methylation of DMTN gene promoter in CRC tissues.

Results

We found that the expression of DMTN was significantly decreased in CRC tissues, and the downregulation of DMTN was associated with advanced progression and poor survival and was regarded as an independent predictive factor of CRC patient prognosis. The overexpression of DMTN inhibited, while the knockdown of DMTN promoted, invasion and metastasis in CRC cells. Moreover, hypermethylation and the deletion of DMTN relieved binding to the ARHGEF2 protein, activated the Rac1 signaling pathway, regulated actin cytoskeletal rearrangements, and promoted the invasion and metastasis of CRC cells.

Conclusion

Our study demonstrated that the downregulation of DMTN promoted the metastasis of colorectal cancer cells by regulating the actin cytoskeleton through RAC1 signaling activation, potentially providing a new therapeutic target to enable cancer precision medicine for CRC patients.

https://ift.tt/2UcAE3q

Mutated Von Hippel-Lindau-renal cell carcinoma (RCC) promotes patients specific natural killer (NK) cytotoxicity

Abstract

Background

Previous evidence demonstrated that restoration of wild type VHL in human renal cancer cells decreased in vitro NK susceptibility. To investigate on the role of tumoral VHL status versus NK capability in renal cancer patients, 51 RCC patients were characterized for VHL mutational status and NK function.

Methods

VHL mutational status was determined by direct DNA sequencing on tumor tissue. NK cytotoxicity was measured against specific target cells K562, VHL-wild type (CAKI-1) and VHL-mutated (A498) human renal cancer cells through externalization of CD107a and IFN-γ production. Activating NK receptors, NKp30, NKp44, NKp46, NKG2D, DNAM-1, NCAM-1 and FcγRIIIa were evaluated through quantitative RT-PCR. RCC tumoral Tregs were characterized as CD4⁺CD25⁺CD127^lowFoxp3⁺ and Treg function was evaluated as inhibition of T-effector proliferation.

Results

VHL mutations were detected in 26/55 (47%) RCC patients. IL-2 activated whole-blood samples (28 VHL-WT-RCC and 23 VHL-MUT-RCC) were evaluated for NK cytotoxicity toward human renal cancer cells A498, VHL-MUT and CAKI-1, VHL-WT. Efficient NK degranulation and increase in IFN-γ production was detected when IL-2 activated whole-blood from VHL-MUT-RCC patients were tested toward A498 as compared to CAKI-1 cells (CD107a⁺NK: 7 ± 2% vs 1 ± 0.41%, p = 0.015; IFN-γ⁺NK: 6.26 ± 3.4% vs 1.78 ± 0.9% respectively). In addition, IL-2 activated NKs induced higher CD107a exposure in the presence of RCC autologous tumor cells or A498 as compared to SN12C (average CD107a⁺NK: 4.7 and 2.7% vs 0.3% respectively at 10E:1 T ratio).

VHL-MUT-RCC tumors were NKp46⁺ cells infiltrated and expressed high NKp30 and NKp46 receptors as compared to VHL-WT-RCC tumors. A significant lower number of Tregs was detected in the tumor microenvironment of 13 VHL-MUT-RCC as compared to 13 VHL-WT-RCC tumors (1.84 ± 0.36% vs 3.79 ± 0.74% respectively, p = 0.04). Tregs isolated from VHL-MUT-RCC patients were less suppressive of patients T effector proliferation compared to Tregs from VHL-WT-RCC patients (Teff proliferation: 6.7 ± 3.9% vs 2.8 ± 1.1%).

Conclusions

VHL tumoral mutations improve NKs effectiveness in RCC patients and need to be considered in the evaluation of immune response. Moreover therapeutic strategies designed to target NK cells could be beneficial in VHL-mutated-RCCs alone or in association with immune checkpoints inhibitors.

https://ift.tt/2AT8KAm

RBMS2 inhibits the proliferation by stabilizing P21 mRNA in breast cancer

Abstract

Background

RNA binding proteins (RBPs) play an important role in regulating the metabolism of target RNAs. Aberrant expression of RBPs plays a vital role in the initiation and development of many cancers. The RBM family, which has the conserved RNA binding motif RNP1 and RNP2, shares the similar function in RNA processing and RBMS2 is a member of them. P21, also named CDKN1A, promotes cell cycle arrest and plays an important role in halting cell proliferation. In our study, we identified RBMS2 as a tumor suppressor in breast cancer. It inhibited the proliferation of breast cancer by positively regulating the stability of P21 mRNA in posttranscriptional way.

Methods

TCGA was used to identify differentially expressed RBPs in breast cancer.

The effect of RBMS2 on breast cancer proliferation was evaluated in vitro using CCK-8 assays, colony formation assays and cell-cycle assays and the in vivo effect was investigated using a mouse tumorigenicity model.

The main pathway and genes regulated by RBMS2 was detected by RNA sequencing. The RNA immunoprecipitation combined with dual-luciferase reporter assay were conducted to testify the direct binding between RBMS2 and P21. Rescue assay was used to detect P21 as the main target of RBMS2.

Results

The expression of RBMS2 was lower in breast cancer compared with normal tissues and was a favorable biomarker in breast cancer. RBMS2 inhibited the proliferation of breast cancer and P21 was the main target of RBMS2. RBMS2 stabilized the mRNA of P21 by directly binding to the AU-rich element of 3′-UTR region. Anti-proliferation activity induced by overexpression of RBMS2 was rescued by interfering with the expression of P21.

Conclusion

In conclusion, RBMS2 acted as a tumor suppressor in breast cancer and positively regulated the expression of P21 by stabilizing its mRNA.

https://ift.tt/2AP3HRG

Projected lifetime cancer risks from occupational radiation exposure among diagnostic medical radiation workers in South Korea

Abstract

Background

Timely assessment of cancer risk from current radiation exposure among medical radiation workers can contribute to the development of strategies to prevent excessive occupational radiation exposure. The purpose of the present study is to estimate the lifetime risk of cancers induced by occupational radiation exposure among medical radiation workers.

Methods

Using estimated organ doses and the RadRAT risk assessment tool, the lifetime cancer risk was estimated among medical radiation workers who were enrolled in the Korean National Dose Registry from 1996 to 2011. Median doses were used for estimating the risk because of the skewed distribution of radiation doses. Realistic representative exposure scenarios in the study population based on sex, job start year, and occupational group were created for calculating the lifetime attributable risk (LAR) and lifetime fractional risk (LFR).

Results

The mean estimated lifetime cancer risk from occupational radiation exposure varied significantly by sex and occupational group. The highest LAR was observed in male and female radiologic technologists who started work in 1991 (264.4/100,000 and 391.2/100,000, respectively). Female workers had a higher risk of radiation-related excess cancer, although they were exposed to lower radiation doses than male workers. The higher LAR among women was attributable primarily to excess breast and thyroid cancer risks. LARs among men were higher than women in most other cancer sites. With respect to organ sites, LAR of colon cancer (44.3/100,000) was the highest in male radiologic technologists, whereas LAR of thyroid cancer (222.0/100,000) was the highest in female radiologic technologists among workers who started radiologic practice in 1991. Thyroid and bladder cancers had the highest LFR among radiologic technologists.

Conclusions

Our findings provide an assessment of the potential cancer risk from occupational radiation exposure among medical radiation workers, based on current knowledge about radiation risk. Although the radiation-related risk was small in most cases, it varied widely by sex and occupational group, and the risk would be underestimated due to the use of median, rather than mean, doses. Therefore, careful monitoring is necessary to optimize radiation doses and protect medical radiation workers from potential health risks, particularly female radiologic technologists.

https://ift.tt/2FWJsqN

Exploring the efficacy of an electronic symptom assessment and self-care intervention to preserve physical function in individuals receiving neurotoxic chemotherapy

Abstract

Background

Impaired physical function due to chemotherapy-induced peripheral neuropathy (CIPN) symptoms may lead to diminished quality of life. However, even with the knowledge of the effects of CIPN on physical function, clinicians infrequently assess and manage CIPN. Interventions that prioritize the early identification of CIPN to provide prompt treatment may reduce the impact of CIPN on physical function. The purpose of this paper is to compare self-reported physical function in individuals receiving neurotoxic chemotherapy between Electronic Symptom Assessment-Cancer (ESRA-C) intervention group (e.g., opportunity for symptom screening, self-care recommendations, communication coaching, and symptom tracking) and control group participants (i.e., electronic assessment alone). Secondary outcomes include pain intensity, sensory/motor CIPN, depression, fatigue, and insomnia.

Methods

The data used in this paper are a subset of a randomized controlled trial that examined the impact of the ESRA-C intervention on symptom distress in individuals receiving cancer treatment. Since the interest in this analysis is on the effects of neurotoxic chemotherapy on physical function, subjects were included if they received platinum and/or taxane-based chemotherapy and completed the baseline and end-of-treatment measures. Participants completed standardized questionnaires of physical function, CIPN, fatigue, depression, pain intensity, and insomnia prior to treatment, 3–6 weeks after treatment initiation, and after the completion of treatment. Changes in mean scores are compared between groups using linear mixed models adjusting for age.

Results

Intervention group participants reported significantly less reduction in physical functioning (baseline: 87.4/100; end-of-treatment: 84.5/100) relative to the control (baseline: 90.2/100; end-of-treatment: 81.8/100) (p = 0.011). For secondary measures, significantly less depression (p = 0.005) was observed in the intervention group as compared to the control, but otherwise, there were no between-group differences. Among participants who received high cumulative doses of neurotoxic chemotherapy, the intervention group reported significantly less severe sensory (p = 0.007) and motor CIPN (p = 0.039) relative to the control.

Conclusion

Use of the ESRA-C intervention led to less reduction in physical function in comparison to the control in individuals receiving neurotoxic chemotherapy. Further research is needed to confirm our findings and to identify how electronic symptom assessment technology may mediate physical function preservation.

Trial registration

ClinicalTrials.Gov NCT00852852. Registered 27 February 2009.

https://ift.tt/2rf4tmC

Care coordination for complex cancer survivors in an integrated safety-net system: a study protocol

Abstract

Background

The growing numbers of cancer survivors challenge delivery of high-quality survivorship care by healthcare systems. Innovative ways to improve care coordination for patients with cancer and multiple chronic conditions ("complex cancer survivors") are needed to achieve better care outcomes, improve patient experience of care, and lower cost. Our study, Project CONNECT, will adapt and implement three evidence-based care coordination strategies, shown to be effective for primary care conditions, among complex cancer survivors. Specifically, the purpose of this study is to: 1) Implement a system-level EHR-driven intervention for 500 complex cancer survivors at Parkland; 2) Test effectiveness of the strategies on system- and patient-level outcomes measured before and after implementation; and 3) Elucidate system and patient factors that facilitate or hinder implementation and result in differences in experiences of care coordination between complex patients with and without cancer.

Methods

Project CONNECT is a quasi-experimental implementation study among 500 breast and colorectal cancer survivors with at least one of the following chronic conditions: diabetes, hypertension, chronic lung disease, chronic kidney disease, or heart disease. We will implement three evidence-based care coordination strategies in a large, county integrated safety-net health system: 1) an EHR-driven registry to facilitate patient transitions between primary and oncology care; 2) co-locating a nurse practitioner trained in care coordination within a complex care team; 3) and enhancing teamwork through coaching. Segmented regression analysis will evaluate change in system-level (i.e. composite care quality score) and patient-level outcomes (i.e. self-reported care coordination). To evaluate implementation, we will merge quantitative findings with structured observations and physician and patient interviews.

Discussion

This study will result in an evaluation toolkit identifying key model elements, barriers, and facilitators that can be used to guide care coordination interventions in other safety-net settings. Because Parkland is a vanguard of safety-net healthcare nationally, findings will be widely applicable as other safety-nets move toward increased integration, enhanced EHR capability, and experience with growing patient diversity. Our proposal recognizes the complexity of interventions and scaffolds evidence-based strategies together to meet the needs of complex patients, systems of care, and service integration.

Trial registration

ClinicalTrials.gov, NCT02943265. Registered 24 October 2016.

https://ift.tt/2FX2cGJ

The transverse and vertical distribution of prostate cancer in biopsy and radical prostatectomy specimens

Abstract

Background

Prostate biopsy is the most common method for the diagnosis of prostate cancer and the basis for further treatment. Confirmation using radical prostatectomy specimens is the most reliable method for verifying the accuracy of template-guided transperineal prostate biopsy. The study aimed to reveal the spatial distribution of prostate cancer in template-guided transperineal saturation biopsy and radical prostatectomy specimens.

Methods

Between December 2012 to December 2016, 171 patients were diagnosed with prostate cancer via template-guided transperineal prostate biopsy and subsequently underwent laparoscopic radical prostatectomy. The spatial distributions of prostate cancer were analyzed and the consistency of the tumor distribution between biopsy and radical prostatectomy specimens were compared.

Results

The positive rate of biopsy in the apex region was significantly higher than that of the other biopsy regions (43% vs 28%, P < 0.01). In radical prostatectomy specimens, the positive rate was highest at the region 0.9–1.3 cm above the apex, and it had a tendency to decrease towards the base. There was a significant difference in the positive rate between the cephalic and caudal half of the prostate (68% vs 99%, P < 0.01). There were no significant differences between the anterior and posterior zones for either biopsy or radical prostatectomy specimens.

Conclusion

The tumor spatial distribution generated by template-guided transperineal prostate biopsy was consistent with that of radical prostatectomy specimens in general. The positive rate was consistent between anterior and posterior zones. The caudal half of the prostate, especially the vicinity of the apex, was the frequently occurred site of the tumor.

https://ift.tt/2rj32U5

Omitting the lower neck and sparing the glottic larynx in node-negative nasopharyngeal carcinoma was safe and feasible, and improved patient-reported voice outcomes

Abstract

Background

Worsening voice and speech quality was frequently reported in head-and-neck patients after radiotherapy to the neck; omitting the lower neck and sparing the glottic larynx in node-negative nasopharyngeal carcinoma (NPC) patients might be safe and feasible, and improve voice and speech outcomes.

Methods

From January 2009 to January 2013, 71 patients were analyzed. All patients received bilateral neck irradiation. Upper group (UG) patients spared the glottic larynx while lower group (LG) patients did not. Voice and speech quality were evaluated at two time-points (T1 and T2) using the Communication Domain of the Head and Neck Quality of Life (HNQOL) instrument and the Speech question of the University of Washington Quality of Life instrument.

Results

At a median follow-up time of 32 months (T1),71.6% of patients reported worsened voice and speech quality. UG patients resulted in significant decreases in glottic larynx dose. With a median follow-up time of 71 months (T2), no patients experienced out-of-field nodal recurrence;there was no difference in the 5-year overall survival and nodal recurrence-free survival between two groups (P = 0.235 and 0.750, respectively). At T1, in patients who without concurrent chemotherapy (CCT), UG patients showed significantly better patient-reported voice quality, (P = 0.022). UG patients without CCT also showed higher scores in the HNQOL communication domain and pain domain (P = 0.012 and P = 0.019).

Conclusions

For node-negative NPC patients, omitting the lower neck and sparing the glottic larynx was safe and feasible, and better voice outcomes were achieved in patients without CCT. Further prospective longitudinal studies to investigate whether this approach would be beneficial to node-negative patients are warranted.

https://ift.tt/2UdXJ5Q

Cancers, Vol. 10, Pages 483: Sensitization of Drug Resistant Cancer Cells: A Matter of Combination Therapy

Cancers, Vol. 10, Pages 483: Sensitization of Drug Resistant Cancer Cells: A Matter of Combination Therapy

Cancers doi: 10.3390/cancers10120483

Authors: Meghan Leary Sarah Heerboth Karolina Lapinska Sibaji Sarkar

Cancer drug resistance is an enormous problem. It is responsible for most relapses in cancer patients following apparent remission after successful therapy. Understanding cancer relapse requires an understanding of the processes underlying cancer drug resistance. This article discusses the causes of cancer drug resistance, the current combination therapies, and the problems with the combination therapies. The rational design of combination therapy is warranted to improve the efficacy. These processes must be addressed by finding ways to sensitize the drug-resistant cancers cells to chemotherapy, and to prevent formation of drug resistant cancer cells. It is also necessary to prevent the formation of cancer progenitor cells by epigenetic mechanisms, as cancer progenitor cells are insensitive to standard therapies. In this article, we emphasize the role for the rational development of combination therapy, including epigenetic drugs, in achieving these goals.

https://ift.tt/2RxKtHp

Necitumumab for the treatment of advanced non-small-cell lung cancer

Future Oncology, Ahead of Print.


https://ift.tt/2RxUofQ

Differential expression profiles and functional analysis of plasma miRNAs associated with chronic myeloid leukemia phases

Future Oncology, Ahead of Print.


https://ift.tt/2QbKbcF

Synchronous follicular non-Hodgkin’s lymphoma and hairy cell leukaemia: a case report

https://ift.tt/2RwFKpf

Differential involvement of TAK1, RIPK1 and NF-κB signaling in Smac mimetic-induced cell death in breast cancer cells

Authors: Schmidt, Nadine / Kowald, Lisa / van Wijk, Sjoerd J.L. / Fulda, Simone


https://ift.tt/2zIaSLR

Regulatory effect of hsa-miR-5590-3P on TGFβ signaling through targeting of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts

Authors: Abedini Bakhshmand, Elham / Soltani, Bahram Mohammad


https://ift.tt/2E3i7Bz

Synthetic biology of B cell activation: understanding signal amplification at the B cell antigen receptor using a rebuilding approach

Authors: Kulathu, Yogesh / Zuern, Christa / Yang, Jianying / Reth, Michael


https://ift.tt/2zFgHcW

Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1

Authors: Fan, Linbing / Joseph, Jan Felix / Durairaj, Pradeepraj / Parr, Maria Kristina / Bureik, Matthias


https://ift.tt/2PjWL4a

Structural and mechanistic aspects of S-S bonds in the thioredoxin-like family of proteins

Authors: Sousa, Sérgio F. / Neves, Rui P.P. / Waheed, Sodiq O. / Fernandes, Pedro A. / Ramos, Maria João


https://ift.tt/2Aalfrb

An internally quenched peptide as a new model substrate for rhomboid intramembrane proteases

Authors: Arutyunova, Elena / Jiang, Zhenze / Yang, Jian / Kulepa, Ayodeji N. / Young, Howard S. / Verhelst, Steven / O'Donoghue, Anthony J. / Lemieux, M. Joanne


https://ift.tt/2PeHUrP

Frontmatter

https://ift.tt/2zFgwOO

The structural biology of the shelterin complex

Authors: Chen, Yong


https://ift.tt/2ATzhir

Is Maximal Heart Rate Decrease Similar Between Normobaric Versus Hypobaric Hypoxia in Trained and Untrained Subjects?

High Altitude Medicine &Biology, Ahead of Print.


https://ift.tt/2E5ev1Y

Abstract Author Index

High Altitude Medicine &Biology, Ahead of Print.


https://ift.tt/2Fw1dNy

Effects of Acute Exposure to Hypobaric Hypoxia on Mucosal Barrier Injury and the Gastrointestinal Immune Axis in Rats

High Altitude Medicine &Biology, Ahead of Print.


https://ift.tt/2DQtJH7

The Contribution of Genetic Variants of the Peroxisome Proliferator-Activated Receptor-Alpha Gene to High-Altitude Hypoxia Adaptation in Sherpa Highlanders

High Altitude Medicine &Biology, Ahead of Print.


https://ift.tt/2ByPtWq

Larotrectinib OK'd for Cancers with TRK Fusions [News in Brief]

Targeted agent is the first with an initial tumor-agnostic indication.

https://ift.tt/2FZSGTe

In vitro activity of Omadacycline against Chlamydia pneumoniae [Susceptibility]

The in vitro activity of omadacycline, azithromycin, doxycycline, moxifloxacin and levofloxacin, was tested against 15 isolates of Chlamydia pneumoniae. The minimum inhibitory concentrations at which 90% of the isolates of C. pneumoniae were inhibited (MIC₉₀) by omadacycline were 0.25 μg/ml (range 0.03-0.5 μg/ml).

https://ift.tt/2RxTLmK

Combination of aspirin plus macrolides in patients with severe community-acquired pneumonia: a hypothesis-generating study [Clinical Therapeutics]

Objectives. While the inflammatory response to severe pneumonia is paramount in reining in and resolving the infection, the excessive inflammation can lead to deleterious effects. We theorized that patients with severe community-acquired pneumonia (CAP), treated with macrolides and aspirin, would receive benefit beyond conventional antibiotic therapy.

Methods. An observational study was conducted on patients with severe CAP. All patients were admitted to 5 teaching hospitals (in Italy, USA, Japan, and China), and data were gathered from their electronic medical records. Severe pneumonia was defined according to ATS/IDSA criteria. Patients were divided in 4 groups: 1) Aspirin only (ASG), 2) Macrolides only (MG), 3) combination Aspirin + Macrolides (ASMG), or 4) neither (NASMG). Survival among the 4 groups was evaluated after adjustment for confounders, and after weighting by propensity score.

Results. A total of 1295 patients were included in the analysis. There were 237 (18.3%) patients in the ASG, 294 (22.7%) in the MG, 148 (11.4%) in the ASMG, and 616 (47.6%) in the NASMG. Mortality at 30 days was 15.5% in the ASMG, compared to 28.2% of the NASMG, 23.8% of the MG, and 21.1% of the ASG. After propensity score analysis, receipt of aspirin plus macrolide (Hazard Ratio 0.71, 95% Confidence Interval 0.58-0.88, p=0.002) was associated with higher 30-day survival.

Conclusions. This is a hypothesis generating a study in which data suggest that combination of aspirin plus a macrolide improves 30-day survival of patients with severe CAP. Further randomized studies will need to be undertaken to confirm this phenomenon.

https://ift.tt/2Q7xI9E

Real-Time PCR for the Evaluation of Treatment Response in Clinical Trials of Adult Chronic Chagas Disease: Usefulness of Serial Blood Sampling and qPCR Replicates. [Analytical Procedures]

This work evaluated a serial blood sampling procedure to enhance the sensitivity of duplex real-time PCR (qPCR) for baseline detection and quantification of parasitic loads and post-treatment identification of failure in the context of clinical trials for treatment of chronic Chagas disease, namely DNDi-CH-E1224-001 (NCT01489228) and MSF-DNDi PCR sampling optimization study (NCT01678599). Patients from Cochabamba (N= 294), Tarija (N= 257), and Aiquile (N= 220) were enrolled. Three serial blood samples were collected at each time-point and qPCR triplicates were tested per sample. The first two samples were collected during the same day and the third one seven days later.

A patient was considered PCR positive if at least one qPCR replicate was detectable. Cumulative results of multiple samples and qPCR replicates enhanced the proportion of pre-treatment sample positivity from 54.8 to 76.2%, 59.5 to 77.8%, and 73.5 to 90.2% in Cochabamba, Tarija, and Aiquile cohorts, respectively. This strategy increased the detection of treatment failure from 72.9 to 91.7%, 77.8 to 88.9%, and 42.9 to 69.1% for E1224 low, short, and high dosage regimens, respectively; and from 4.6 to 15.9% and 9.5 to 32.1% for the benznidazole arm in the DNDi-CH-E1224-001 and MSF-DNDi studies, respectively. The addition of the third blood sample and third qPCR replicate in patients with non-detectable PCR results in the first two samples, gave a small, non-statistically significant improvement in qPCR positivity. No change in clinical sensitivity was seen with a blood volume increase from 5 to 10 ml. The monitoring of patients treated with placebo in the DNDi-CH-E1224-001 trial revealed fluctuations in parasitic loads and occasional non-detectable results. In conclusion, serial sampling strategy enhanced PCR sensitivity to detecting treatment failure during follow-up and has the potential for improving recruitment capacity in Chagas disease trials, which require an initial positive qPCR result for patient admission.

https://ift.tt/2RxTUqi

Carbapenem versus Cefepime or Piperacillin-Tazobactam for the Empiric Treatment of Extended Spectrum {beta}-lactamase Producing Escherichia coli Bacteremia in Patients with Hematologic Malignancy [Clinical Therapeutics]

Infections with extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are common in patients with hematologic malignancy. The utility of cefepime and piperacillin-tazobactam as empiric therapy for ESBL E. coli bacteremia in patients with hematologic malignancy is largely unknown. We conducted a single center, retrospective cohort review of 103 adult inpatients with leukemia and/or hematopoietic stem cell transplant (HCT) recipients with monomicrobial ESBL E. coli bacteremia. No association between increased fourteen-day mortality and empiric treatment with cefepime (8%) or piperacillin-tazobactam (0%) relative to carbapenems (19%) was observed (p = 0.19 and p = 0.04, respectively). This observation was consistent in multivariate Cox proportional hazards models adjusted for confounding and an inverse probability of treatment weighted (IPTW) Cox proportional hazards model. Fever and persistent bacteremia were both more common in patients treated empirically with cefepime or piperacillin-tazobactam. Empiric treatment with cefepime or piperacillin-tazobactam does not result in increased mortality relative to treatment with carbapenems in patients with hematologic malignancy and ESBL E. coli bacteremia, although most patients were changed to carbapenems early in treatment. However, due to prolonged fever and persistent bacteremia, their role may be limited in this patient population.

https://ift.tt/2Qa7Z0o

Comparative activity of ceftriaxone, ciprofloxacin and gentamicin as a function of bacterial growth rate probed by Escherichia coli chromosome replication in the mouse peritonitis model [Clinical Therapeutics]

Commonly used antibiotics exert their effect predominantly on rapidly growing bacterial cells, yet growth dynamics taking place during infection in a complex host environment remain largely unknown. Hence, means to measure in situ bacterial growth rate is essential to predict the outcome of antibacterial treatment. We have recently validated chromosome replication as readout for in situ bacterial growth rate during Escherichia coli infection in the mouse peritonitis model. By the use of two complementary methods (qPCR and fluorescence microscopy) for differential genome origin and terminus copy number quantification, we demonstrated the ability to track bacterial growth rate, both on a population average and on a single-cell level; from one single biological specimen. Here, we asked whether the in situ growth rate could predict antibiotic treatment effect during infection in the same model. Parallel in vitro growth experiments were conducted as proof-of-concept. Our data demonstrate that the activity of commonly used antibiotics ceftriaxone and gentamicin correlated with pre-treatment bacterial growth rate; both drugs performing better during rapid growth than during slow growth. Conversely, ciprofloxacin was less sensitive to bacterial growth rate, both in a homogenous in vitro bacterial population and in a more heterogeneous in vivo bacterial population. The method serves as a platform to test any antibiotic's dependency upon active in situ bacterial growth. Improved insight into this relationship in vivo could ultimately prove helpful in evaluating future antibacterial strategies.

https://ift.tt/2RxTQH4

Genetic and transcriptomic analyses of ciprofloxacin-tolerant Staphylococcus aureus isolated by the Replica Plating Tolerance Isolation System (REPTIS) [Mechanisms of Resistance]

We developed a simple, efficient, and cost-effective method, named the Replica Plating Tolerance Isolation System (REPTIS), to detect the antibiotic-tolerance potential of a bacterial strain. This method can also be used to quantify the antibiotic-tolerant subpopulation in a susceptible population. Using REPTIS, we isolated ciprofloxacin (CPFX)-tolerant mutants (R2, R3, R5 and R6) carrying a total of 12 mutations in 12 different genes from a methicillin-sensitive Staphylococcus aureus (MSSA) FDA209P strain. Each mutant carried multiple mutations, while few strains shared the same mutation. The R2 strain carried a nonsense mutation in the stress-mediating gene, relA. Additionally, two strains carried the same point mutation in the leuS gene encoding leucyl-tRNA synthetase. Furthermore, RNA-sequencing of R strains showed a common up-regulation of relA. Overall, transcriptome analysis showed down-regulation of genes related to translation; carbohydrate, fat, and energy metabolism; and nucleotide synthesis, and up-regulation of amino acid biosynthesis and transportation genes in R2, R3, and R6, similar to that observed in the FDA209P strain treated with mupirocin (MUP0.03). However, R5 showed a unique transcription pattern that differed from that of MUP0.03. REPTIS is a unique and convenient method for quantifying the level of tolerance of a clinical isolate. Genomic and transcriptomic analyses of R strains demonstrated that CPFX tolerance in these S. aureus mutants occurs via at least two distinct mechanisms, one of which is similar to mupirocin treatment.

https://ift.tt/2Qa7V0E

Is One Sample Enough? {beta}-lactam Target Attainment and Penetration into Epithelial Lining Fluid based on Multiple Bronchoalveolar Lavage Sampling Time Points in a Swine Pneumonia Model [Pharmacology]

Describing the disposition of antimicrobials agents at the site of infection is crucial to guide optimal dosing for investigational agents. For antibiotics in development for nosocomial pneumonia, concentrations are frequently determined in the epithelial lining fluid (ELF) of the lung from a bronchoscopy at a single time point. The influence of profiles constructed from a single ELF concentration point for each subject has never been reported. This study compares the pharmacokinetics of two β-lactams, ceftolozane and piperacillin, among different ELF sampling approaches using simulated human regimens in a swine pneumonia model. Plasma and ELF concentration-time profiles were characterized in two-compartment models by robustly sampled ELF concentrations and by random selection of one or two ELF concentrations from each swine. A 5,000 subject Monte Carlo simulation was performed for each model to define the ELF penetration, as described by the ratio area under the concentration curve (AUC) in ELF to free AUC in plasma (AUC_ELF/fAUC_plasma) and probability of target attainment (PTA). Given the intersubject variability of ELF penetrations observed, differences between models developed using robust versus one or two ELFs per swine were minimal for both drugs (maximum dispersion < 20%). Using a threshold exposure of 60% free time above the MIC, ceftolozane and piperacillin regimens achieved PTAs of ≥90% at MICs up to 4 and 1 µg/mL, respectively, among different ELF sampling strategies. These models suggest that ELF models constructed from sparse ELF time points result in similar exposure estimates to robustly sampled ELF profiles.

https://ift.tt/2QeIkE1

Mutagen Synergy: The Antibiotic Trimethoprim Displays Strong Mutagenic Synergy with 2-aminopurine [Mechanisms of Action]

We show that trimethoprim (TMP), an antibiotic in current use, displays a strong synergistic effect on mutagenesis in Escherichia coli when paired with the base analog 2-aminopurine (2AP), resulting in a 35-fold increase in mutation frequencies in the rpoB/Rif^r system. Combination therapies are often employed both as antibiotic treatments and in cancer chemotherapy. However, mutagenic effects of these combinations are rarely examined. An analysis of the mutational spectra of TMP, 2AP, and the combination indicates that together they trigger a response via an alteration in deoxynucleoside triphosphate (dNTP) ratios that neither compound alone can trigger. A similar, although less strong, response is seen with the frameshift mutagen ICR191 and 2AP. These results underscore the need for testing the effects on mutagenesis of combinations of antibiotics and chemotherapeutics.

https://ift.tt/2RxTGPY

In Vitro Susceptibility Testing of Bedaquiline Against Mycobacterium abscessus Complex [Susceptibility]

We performed bedaquiline broth microdilution susceptibility using Clinical and Laboratory Standards Institute (CLSI) guidelines on 104 non-duplicate isolates of Mycobacterium abscessus complex [M. abscessus subsp. abscessus (76), M. abscessus subsp. massiliense (10), M. abscessus subsp. bolletii, (2) and M. abscessus subsp. abscessus/subsp. massiliense hybrid, i.e., M. abscessus subsp. abscessus by rpoB gene and subsp. massiliense by erm(41) gene (16)]. All isolates from patients not known to have been on prior bedaquiline had MIC values ≤0.25 µg/mL. The bedaquiline MIC₅₀ values for 76 isolates of M. abscessus subsp. abscessus and 16 isolates of M. abscessus subsp. abscessus/subsp. massiliense hybrid were 0.06 µg/mL. The MIC₅₀ and MIC₉₀ values for 10 isolates of M. abscessus subsp. massiliense were 0.12 µg/mL. Only two isolates of M. abscessus subsp. bolletii were tested with bedaquiline MICs of 0.06 µg/mL.

Our study suggests that oral bedaquiline may have potential use in treatment of disease caused by the M. abscessus complex. Combination therapy with other agents (imipenem, cefoxitin, amikacin, and/or tigecycline) is recommended.

https://ift.tt/2Qa7O5e

Mutations in cdsA and pgsA Correlate With Daptomycin Resistance in S. mitis/oralis [Mechanisms of Resistance]

We investigated the ability of several recent clinical viridans group streptococci (VGS) bloodstream isolates (S. mitis/oralis sub-group) from daptomycin (DAP)-naïve patients to develop DAP resistance in vitro. All strains rapidly developed high-level and stable DAP-resistance. Substitutions in two enzymes involved in the cardiolipin biosynthesis pathway were identified: CdsA (phosphatidate cytidylyltransferase) and/or PgsA (CDP-diacylglycerol-glycerol-3-phosphate-3-phosphatidyltransferase). These mutations were associated with complete disappearance of phosphatidylglycerol and cardiolipin from cell membranes. DAP interactions with the cell membrane differed between isolates with PgsA vs CdsA substitutions.

https://ift.tt/2RxTCjc

Antibiotics stimulate vesicles formation in Staphylococcus aureus in a phage-dependent and independent fashion and via different routes [Clinical Therapeutics]

Bacterial membrane vesicles research has so far mainly focussed on Gram-negative bacteria. Only recently Gram-positive bacteria have been demonstrated to produce and release extracellular membrane vesicles (MVs) that contribute to bacterial virulence. Although treatment of bacteria with antibiotics is a well-established trigger of bacterial MVs formation, the underlying mechanisms are poorly understood. In this study we show that antibiotics can induce MVs through different routes in the important human pathogen Staphylococcus aureus. DNA damaging agents and antibiotics inducing the SOS response triggered vesicle formation in lysogenic strains of S. aureus but not in their phage-devoid counterparts. β-lactam antibiotics flucloxacillin and ceftaroline increased vesicle formation in a prophage-independent manner by weakening the peptidoglycan layer. We present evidence that the amount of DNA associated with MVs formed by phage lysis is higher than that of MVs formed by β-lactam antibiotics-induced blebbing. The purified MVs derived from S. aureus protected the bacteria from challenge with daptomycin, a membrane-targeting antibiotic, both in vitro and ex vivo in whole blood. In addition, the MVs protected S. aureus from killing in whole blood, indicating that antibiotic-induced MVs function as a decoy and thereby contribute to the survival of the bacterium.

https://ift.tt/2Qa7P9i

Population Pharmacokinetics and Dosing Optimization of Amoxicillin in Neonates and Young Infants [Pharmacology]

Backgrounds: Amoxicillin is widely used to treat bacterial infections in neonates. However, considerable inter-center variability in dosage regimens of antibiotic exist in clinical practice. Pharmacokinetics of amoxicillin has been described in only a few preterm neonates. Thus, we aimed to evaluate population pharmacokinetics of amoxicillin through a large samples covered entire age range of neonates and young infants, and establish evidence-based dosage regimens based on developmental pharmacokinetics–pharmacodynamics.

Methods: This is a prospective, multi-center, pharmacokinetic study using an opportunistic sampling design. Amoxicillin plasma concentrations were determined using high performance liquid chromatography. Population pharmacokinetic analysis was performed using NONMEM.

Results: A total of 224 pharmacokinetic samples from 187 newborns (postmenstrual age range: 28.4 – 46.3 weeks) were available for analysis. A 2-compartment model with first-order elimination was used to describe population pharmacokinetics. Covariate analysis showed that current weight, postnatal age and gestational age were significant covariates. The final model was further validated for predictive performance in an independent cohort of patients. Monte Carlo simulation demonstrated that for early-onset sepsis, the currently used dosage regimen (25mg/kg BID) resulted in 99.0% of premature neonates and 87.3% of term neonates achieving the pharmacodynamic target (% time above MIC), using MIC breakpoint of 1 mg/L. For late-onset sepsis, 86.1% of premature neonates treated with 25mg/kg TID and 79.0% of term neonates receiving 25mg/kg QID reached the pharmacodynamic target, using MIC breakpoint of 2 mg/L.

Conclusion: The population pharmacokinetics of amoxicillin was assessed in neonates and young infants. A dosage regimen was established based on developmental pharmacokinetics-pharmacodynamics.

https://ift.tt/2RxTwYS

Response to immune checkpoint antibodies: Not all responses are created equal

Early reports from immunotherapy trials conclude durable responses. Long-term data may indicate otherwise. Better delineation of clinical courses of long-term survivors will accelerate the discovery and application of biomarkers. Two pressing issues amongst those treated with anti-PD-1/PD-L1 are understanding whether responders can have therapy abbreviated and overcoming resistance in non-responders.

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CDC: Acute Flaccid Myelitis Cases Appear to Have Peaked for 2018

MONDAY, Dec. 3, 2018 -- The number of cases of acute flaccid myelitis (AFM) in the United States this year appears to have peaked and is expected to decline for the remainder of 2018, according to the U.S. Centers for Disease Control and...

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Cost-Related Insulin Underuse May Affect One in Four Patients

MONDAY, Dec. 3, 2018 -- About one in four patients report cost-related insulin underuse, which is associated with poor glycemic control, according to a research letter published online Dec. 3 in JAMA Internal Medicine. Darby Herkert, from Yale...

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ASH: Ibrutinib Tops Bendamustine + Rituximab for CLL

MONDAY, Dec. 3, 2018 -- For older patients with untreated chronic lymphocytic leukemia (CLL), treatment with ibrutinib alone or in combination with rituximab is associated with improved progression-free survival versus bendamustine plus rituximab,...

https://ift.tt/2rkXJmY

Prevalence of Ever-Diagnosed ASD 2.79 Percent in U.S. Children

MONDAY, Dec. 3, 2018 -- The prevalence of ever-diagnosed autism spectrum disorder (ASD) is 2.79 percent in the United States, with state-level variations in prevalence, according to a study published online Dec. 3 in JAMA Pediatrics. Guifeng Xu,...

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Rare Variants Associated With Interval Breast Cancers

MONDAY, Dec. 3, 2018 -- Though common breast cancer variants indicate increased breast cancer risk, certain rare variants are associated with an increased risk for interval breast cancers and death, according to a study published in the Nov. 1 issue...

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Barriers and Advances in Kidney Preservation

Despite the fact that a significant fraction of kidney graft dysfunctions observed after transplantation is due to ischemia-reperfusion injuries, there is still no clear consensus regarding optimal kidney preservation strategy. This stems directly from the fact that as of yet, the mechanisms underlying ischemia reperfusion injury are poorly defined, and the role of each preservation parameter is not clearly outlined. In the meantime, as donor demography changes, organ quality is decreasing which directly increases the rate of poor outcome. This situation has an impact on clinical guidelines and impedes their possible harmonization in the transplant community, which has to move towards changing organ preservation paradigms: new concepts must emerge and the definition of a new range of adapted preservation method is of paramount importance. This review presents existing barriers in transplantation (e.g., temperature adjustment and adequate protocol, interest for oxygen addition during preservation, and clear procedure for organ perfusion during machine preservation), discusses the development of novel strategies to overcome them, and exposes the importance of identifying reliable biomarkers to monitor graft quality and predict short and long-term outcomes. Finally, perspectives in therapeutic strategies will also be presented, such as those based on stem cells and their derivatives and innovative models on which they would need to be properly tested.

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Approaches in Physical Activity: From Basic to Applied Research 2017

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A Preliminary Study on Discriminant Analysis of Syndrome Types in the Recovery Period of Stroke in Traditional Chinese Medicine

Objective. The purpose of this study is to understand the distribution of syndrome types, the data of four diagnostic information variables, and the correlative degree and diagnostic value of four diagnosis indexes and syndromes in patients with the recovery period of ischemic stroke through clinical case data. Methods. This study developed a unified clinical case collection table, following the clinical research design, measurement, and evaluation methods, using Chi-Square test, logistic regression analysis, and diagnostic test evaluation methods for data screening, analysis, and testing. Results. According to the comprehensive comparison, analysis, and evaluation, the study concluded that the specificity, sensitivity, positive likelihood ratio, positive predictive value, negative predictive value, accuracy, and Youden index of "thick fur, slippery pulse" was the highest. Conclusion. "thick fur, slippery pulse" is the best combination to diagnose the phlegm-stasis in channels during the recovery period of ischemic stroke.

https://ift.tt/2DYmxZG

Bronchopulmonary Sequestration with Fetal Hydrops in a Monochorionic Twin Successfully Treated with Multiple Courses of Betamethasone

AJP Rep 2018; 08: e359-e361
DOI: 10.1055/s-0038-1676339

Aim We present a case of severe bronchopulmonary sequestration (BPS) and fetal hydrops in one of the monochorionic twin successfully treated with multiple courses of betamethasone. Case Report A 21-year-old gravida 2 para 1 was referred to our hospital for suspected twin-to-twin transfusion syndrome (TTTS) at 280/7 weeks of gestational age. However, prenatal ultrasound of the larger twin revealed a chest lesion that was associated with significant ascites, massive hydrothorax, scant hepatomegaly, subcutaneous edema, and severe polyhydramnios. Magnetic resonance imaging confirmed the diagnosis of BPS and fetal hydrops. The estimated fetal weight discrepancy between the fetuses was 39% but the criteria for TTTS were not met. Repeated courses of betamethasone (3 courses, each with 2 × 14 mg of betamethasone intramuscularly/week) were administered with subsequent recovery from hydrops and reduction in BPS parameters. Amniodrainage was performed twice to reduce the amniotic fluid amount in affected twin. Postnatally, surgery of BPS was not required and follow-up at 6 months of corrected age revealed no side effects of antenatal steroids in either twin. Conclusion Antenatal steroids might be considered for noninvasive therapy in high-risk fetal patients with BPS especially when fetal intervention is unsuitable or not available.
[...]

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Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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Rare Case of Severe Lower Gastrointestinal Bleeding: Primary Colonic Choriocarcinoma

https://ift.tt/2SuIK5L

Harmonization of quality of care in an IBD center impacts disease outcomes: importance of structure, process indicators and rapid access clinic

We aimed to evaluate the quality of care at a tertiary inflammatory bowel disease (IBD) center using quality of care indicators (QIs) including patient assessment strategy, monitoring, treatment decisions and outcomes.

https://ift.tt/2Ecbr46

Gut mucosal-associated microbiota better discloses Inflammatory Bowel Disease differential patterns than fecal microbiota

growing evidence supports the potential role of intestinal microbiota in the pathophysiology of Inflammatory Bowel Diseases (IBD) even if the literature does not reveal uniform alterations. The aim of the study was to evaluate the mucosal (MM) and fecal microbiota (FM) composition in a cohort of IBD patients compared to healthy controls (CTRLs).

https://ift.tt/2Stufix

A risk-scoring model for the prediction of delayed bleeding after colorectal endoscopic submucosal dissection

Delayed bleeding is an important adverse event after colorectal endoscopic submucosal dissection (ESD). We aimed to investigate the incidence and risk factors of delayed bleeding after colorectal ESD, and to develop a risk scoring model for predicting delayed bleeding.

https://ift.tt/2Smix9a

Trends in Drug Use–Associated Infective Endocarditis and Heart Valve Surgery, 2007 to 2017 A Study of Statewide Discharge Data

Background:

Drug use–associated infective endocarditis (DUA-IE) is increasing as a result of the opioid epidemic. Infective endocarditis may require valve surgery, but surgical treatment of DUA-IE has invoked controversy, and the extent of its use is unknown.

Objective:

To examine hospitalization trends for DUA-IE, the proportion of hospitalizations with surgery, patient characteristics, length of stay, and charges.

Design:

10-year analysis of a statewide hospital discharge database.

Setting:

North Carolina hospitals, 2007 to 2017.

Patients:

All patients aged 18 years or older hospitalized for IE.

Measurements:

Annual trends in all IE admissions and in IE hospitalizations with valve surgery, stratified by patients' drug use status. Characteristics of DUA-IE surgical hospitalizations, including patient demographic characteristics, length of stay, disposition, and charges.

Results:

Of 22 825 IE hospitalizations, 2602 (11%) were for DUA-IE. Valve surgery was performed in 1655 IE hospitalizations (7%), including 285 (17%) for DUA-IE. Annual DUA-IE hospitalizations increased from 0.92 to 10.95 and DUA-IE hospitalizations with surgery from 0.10 to 1.38 per 100 000 persons. In the final year, 42% of IE valve surgeries were performed in patients with DUA-IE. Compared with other surgical patients with IE, those with DUA-IE were younger (median age, 33 vs. 56 years), were more commonly female (47% vs. 33%) and white (89% vs. 63%), and were primarily insured by Medicaid (38%) or uninsured (35%). Hospital stays for DUA-IE were longer (median, 27 vs. 17 days), with higher median charges ($250 994 vs. $198 764). Charges for 282 DUA-IE hospitalizations exceeded $78 million.

Limitation:

Reliance on administrative data and billing codes.

Conclusion:

DUA-IE hospitalizations and valve surgeries increased more than 12-fold, and nearly half of all IE valve surgeries were performed in patients with DUA-IE. The swell of patients with DUA-IE is reshaping the scope, type, and financing of health care resources needed to effectively treat IE.

Primary Funding Source:

National Institutes of Health.

https://ift.tt/2KSFr5w

Prevalence of Atopic Eczema Among Patients Seen in Primary Care: Data From The Health Improvement Network

https://ift.tt/2BP1dEs

Notice of Retraction: The Joy of Cooking Too Much: 70 Years of Calorie Increases in Classic Recipes

https://ift.tt/2BQzsLX

Drug-Associated Infective Endocarditis Trends: What's All the Buzz About?

Schranz and colleagues studied the epidemiology of infective endocarditis (IE) in North Carolina between 2007 and 2017 and found a remarkable increase in drug use–associated IE. The editorialist discusses the findings and the need for innovative research on how to prevent endocarditis and to provide equitable, evidence-based treatment focusing not only on the microbe, but also on the underlying substance use disorder.

https://ift.tt/2KQI6wB

Notice of Retraction: Meal Size Explains Errors in Estimating How Many Calories Are in a Meal [Summary for Patients]

https://ift.tt/2BPY9rX

Weighing the Harms and Benefits of Using Statins for Primary Prevention: Raising the Risk Threshold

In this issue, Yebyo and colleagues challenge the risk thresholds in current guidelines for use of statins for primary prevention of cardiovascular disease. The editorialists discuss how the findings can support patient-centered decision making, particularly for older adults or those who are more concerned about harms of treatment.

https://ift.tt/2KPdiMN

Ensuring Fairness in Machine Learning to Advance Health Equity

Machine learning is used increasingly in clinical care to improve diagnosis, treatment selection, and health system efficiency. Because machine-learning models learn from historically collected data, populations that have experienced human and structural biases in the past—called protected groups—are vulnerable to harm by incorrect predictions or withholding of resources. This article describes how model design, biases in data, and the interactions of model predictions with clinicians and patients may exacerbate health care disparities. Rather than simply guarding against these harms passively, machine-learning systems should be used proactively to advance health equity. For that goal to be achieved, principles of distributive justice must be incorporated into model design, deployment, and evaluation. The article describes several technical implementations of distributive justice—specifically those that ensure equality in patient outcomes, performance, and resource allocation—and guides clinicians as to when they should prioritize each principle. Machine learning is providing increasingly sophisticated decision support and population-level monitoring, and it should encode principles of justice to ensure that models benefit all patients.

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Benefits and Harms of Using Statins to Prevent Cardiovascular Disease

https://ift.tt/2KOJEqW

Effect of Liraglutide on Cardiovascular Outcomes in Elderly Patients: A Post Hoc Analysis of a Randomized Controlled Trial

https://ift.tt/2BPucI8

Machine Learning, Health Disparities, and Causal Reasoning

Rajkomar and colleagues warn us that the introduction of machine-learned predictive algorithms into medicine might inadvertently reinforce or create inequitable treatment of protected groups, for which the computer science community has adopted the terminology of "fairness." They present a taxonomy of pitfalls and an oversight structure to minimize ethical harms. The editorialists discuss the taxonomy and oversight structure Rajkomar and colleagues propose and conclude that no formulaic solution will be sufficient to achieve fairness.

https://ift.tt/2KTry7h

Notice of Retraction: Meal Size, Not Body Size, Explains Errors in Estimating the Calorie Content of Meals

https://ift.tt/2BPu5MI

Finding the Balance Between Benefits and Harms When Using Statins for Primary Prevention of Cardiovascular Disease A Modeling Study

Background:

Many guidelines use expected risk for cardiovascular disease (CVD) during the next 10 years as a basis for recommendations on use of statins for primary prevention of CVD. However, how harms were considered and weighed against benefits is often unclear.

Objective:

To identify the expected risk above which statins provide net benefit.

Design:

Quantitative benefit–harm balance modeling study.

Data Sources:

Network meta-analysis of primary prevention trials, a preference survey, and selected observational studies.

Target Population:

Persons aged 40 to 75 years with no history of CVD.

Time Horizon:

10 years.

Perspective:

Clinicians and guideline developers.

Intervention:

Low- or moderate-dose statin versus no statin.

Outcome Measures:

The 10-year risk for CVD at which statins provide at least a 60% probability of net benefit, with baseline risk, frequencies of and preferences for statin benefits and harms, and competing risk for non-CVD death taken into account.

Results of Base-Case Analysis:

Younger men had net benefit at a lower 10-year risk for CVD than older men (14% for ages 40 to 44 years vs. 21% for ages 70 to 75 years). In women, the risk required for net benefit was higher (17% for ages 40 to 44 years vs. 22% for ages 70 to 75 years). Atorvastatin and rosuvastatin provided net benefit at lower 10-year risks than simvastatin and pravastatin.

Results of Sensitivity Analysis:

Most alternative assumptions led to similar findings.

Limitation:

Age-specific data for some harms were not available.

Conclusion:

Statins provide net benefits at higher 10-year risks for CVD than are reflected in most current guidelines. In addition, the level of risk at which net benefit occurs varies considerably by age, sex, and statin type.

Primary Funding Source:

Swiss Government Excellence Scholarship Office, Béatrice Ederer-Weber Foundation, and North-South Cooperation at the University of Zurich.

https://ift.tt/2KRKuDB

Annals Story Slam - Chocolate Mousse

https://ift.tt/2EbFiK3

Annals for Educators - 4 December 2018

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Use of High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia A Cohort Study

Background:

Many patients with coronary artery disease (CAD) are routinely referred for surveillance stress testing despite recommendations against it.

Objective:

To determine whether low levels of resting high-sensitivity cardiac troponin I (hs-cTnI) can identify persons without inducible myocardial ischemia.

Design:

Observational study.

Setting:

A university-affiliated hospital network.

Patients:

Persons with stable CAD: 589 in the derivation group and 118 in the validation cohort.

Measurements:

Presence of inducible myocardial ischemia was determined by myocardial perfusion imaging with technetium-99m single-photon emission computed tomography during either treadmill or pharmacologic stress testing. Resting plasma hs-cTnI was measured within 1 week of the stress test, and the negative predictive value (NPV) for inducible ischemia was calculated. The derivation cohort was followed for 3 years for incident cardiovascular death and myocardial infarction.

Results:

In the derivation cohort, 10 of 101 patients with an hs-cTnI level below 2.5 pg/mL had inducible myocardial ischemia (NPV, 90% [95% CI, 83% to 95%]) and 3 of 101 had inducible ischemia involving at least 10% of the myocardium (NPV, 97% [CI, 92% to 99%]). In the validation cohort, 4 of 32 patients with an hs-cTnI level below 2.5 pg/mL had inducible ischemia (NPV, 88% [CI, 71% to 96%]) and 2 of 32 had ischemia of 10% or greater (NPV, 94% [CI, 79% to 99%]). After a median follow-up of 3 years in the derivation cohort, no adverse events occurred in patients with an hs-cTnI level below 2.5 pg/mL, compared with 33 (7%) cardiovascular deaths or incident myocardial infarctions among those with an hs-cTnI level of 2.5 pg/mL or greater.

Limitation:

The data may not be applicable to a population without known CAD or to persons with unstable angina, and the modest sample sizes warrant further validation in a larger cohort.

Conclusion:

Very low hs-cTnI levels may be useful in excluding inducible myocardial ischemia in patients with stable CAD.

Primary Funding Source:

National Institutes of Health.

https://ift.tt/2qt6zih

Effectiveness and Safety of Bariatric Procedures for Weight Loss

https://ift.tt/2DaBacQ

Long-Term Protection After Fractional-Dose Yellow Fever Vaccination Follow-up Study of a Randomized, Controlled, Noninferiority Trial

Background:

Outbreaks of yellow fever and a frequently depleted vaccine stock increase demand for a dose-sparing strategy. A fractional dose of 17D yellow fever virus (17D-YFV) vaccine has been shown to be noninferior to the standard dose in inducing seroprotection.

Objective:

To evaluate whether fractional-dose vaccination can confer long-term immunity.

Design:

10-year follow-up of a subgroup of a randomized, controlled, noninferiority trial. (Dutch Trial Register: NTR7094 [current study] and ISRCTN46326316 [original study])

Setting:

The Netherlands.

Participants:

Seventy-five of 155 participants in the original trial provided a blood sample for this study. These 75 participants had received primary vaccination with 17D-YFV vaccine 10 years before. Forty received a 0.1-mL fractional dose intradermally, and 35 received the standard 0.5-mL dose subcutaneously.

Measurements:

Virus-neutralizing antibody responses were measured by a plaque reduction neutralization test.

Results:

Thirty-nine of 40 (98% [95% CI, 89% to 100%]) participants had protective levels of yellow fever–neutralizing antibodies more than 10 years after receiving a fractional dose of 17D-YFV vaccine compared with 34 of 35 (97% [CI, 87% to 100%]) in the standard-dose group.

Limitation:

Only 48% of participants from the original trial participated in this study.

Conclusion:

Intradermal administration of a one-fifth dose of yellow fever vaccine induced a protective immune response that lasted for 10 years after vaccination. Persons receiving a fractional dose of yellow fever vaccine do not require a booster vaccination for long-term protection against yellow fever.

Primary Funding Source:

Leiden University Medical Center and the International Society of Travel Medicine.

https://ift.tt/2RgU9po

Annals Story Slam - A Beautiful Death

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Diagnosis of Pulmonary Embolism During Pregnancy A Multicenter Prospective Management Outcome Study

Background:

Data on the optimal diagnostic management of pregnant women with suspected pulmonary embolism (PE) are limited, and guidelines provide inconsistent recommendations on use of diagnostic tests.

Objective:

To prospectively validate a diagnostic strategy in pregnant women with suspected PE.

Design:

Multicenter, multinational, prospective diagnostic management outcome study involving pretest clinical probability assessment, high-sensitivity D-dimer testing, bilateral lower limb compression ultrasonography (CUS), and computed tomography pulmonary angiography (CTPA). (ClinicalTrials.gov: NCT00740454)

Setting:

11 centers in France and Switzerland between August 2008 and July 2016.

Patients:

Pregnant women with clinically suspected PE in emergency departments.

Intervention:

Pulmonary embolism was excluded in patients with a low or intermediate pretest clinical probability and a negative D-dimer result. All others underwent lower limb CUS and, if results were negative, CTPA. A ventilation–perfusion (V/Q) scan was done if CTPA results were inconclusive. Pulmonary embolism was excluded if results of the diagnostic work-up were negative, and untreated pregnant women had clinical follow-up at 3 months.

Measurements:

The primary outcome was the rate of adjudicated venous thromboembolic events during the 3-month follow-up.

Results:

441 women were assessed for eligibility, and 395 were included in the study. Among these, PE was diagnosed in 28 (7.1%) (proximal deep venous thrombosis found on ultrasonography [n = 7], positive CTPA result [n = 19], and high-probability V/Q scan [n = 2]) and excluded in 367 (clinical probability and negative D-dimer result [n = 46], negative CTPA result [n = 290], normal or low-probability V/Q scan [n = 17], and other reason [n = 14]). Twenty-two women received extended anticoagulation during follow-up, mainly for previous venous thromboembolic disease. The rate of symptomatic venous thromboembolic events was 0.0% (95% CI, 0.0% to 1.0%) among untreated women after exclusion of PE on the basis of negative results on the diagnostic work-up.

Limitation:

There were several protocol deviations, reflecting the difficulty of performing studies in pregnant women with suspected PE.

Conclusion:

A diagnostic strategy based on assessment of clinical probability, D-dimer measurement, CUS, and CTPA can safely rule out PE in pregnant women.

Primary Funding Source:

Swiss National Foundation for Scientific Research, Groupe d'Etude de la Thrombose de Bretagne Occidentale, and International Society on Thrombosis and Haemostasis.

https://ift.tt/2An8OJK

Annals Story Slam - White Lies

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Interventions for Preventing Thromboembolic Events in Patients With Atrial Fibrillation A Systematic Review

Background:

The comparative safety and effectiveness of treatments to prevent thromboembolic complications in atrial fibrillation (AF) remain uncertain.

Purpose:

To compare the effectiveness of medical and procedural therapies in preventing thromboembolic events and bleeding complications in adults with nonvalvular AF.

Data Sources:

English-language studies in several databases from 1 January 2000 to 14 February 2018.

Study Selection:

Two reviewers independently screened citations to identify comparative studies of treatments to prevent stroke in adults with nonvalvular AF who reported thromboembolic or bleeding complications.

Data Extraction:

Two reviewers independently abstracted data, assessed study quality and applicability, and rated strength of evidence.

Data Synthesis:

Data from 220 articles were included. Dabigatran and apixaban were superior and rivaroxaban and edoxaban were similar to warfarin in preventing stroke or systemic embolism. Apixaban and edoxaban were superior and rivaroxaban and dabigatran were similar to warfarin in reducing the risk for major bleeding. Treatment effects with dabigatran were similar in patients with renal dysfunction (interaction P > 0.05), and patients younger than 75 years had lower bleeding rates with dabigatran (interaction P < 0.001). The benefit of treatment with apixaban was consistent in many subgroups, including those with renal impairment, diabetes, and prior stroke (interaction P > 0.05 for all). The greatest bleeding risk reduction was observed in patients with a glomerular filtration rate less than 50 mL/min/1.73 m² (P = 0.003). Similar treatment effects were observed for rivaroxaban and edoxaban in patients with prior stroke, diabetes, or heart failure (interaction P > 0.05 for all).

Limitation:

Heterogeneous study populations, interventions, and outcomes.

Conclusion:

The available direct-acting oral anticoagulants (DOACs) are at least as effective and safe as warfarin for patients with nonvalvular AF. The DOACs had similar benefits across several patient subgroups and seemed safe and efficacious for a wide range of patients with nonvalvular AF.

Primary Funding Source:

Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42017069999)

https://ift.tt/2JsuDus

Comparative Effectiveness and Safety of Bariatric Procedures for Weight Loss A PCORnet Cohort Study

Background:

There has been a dramatic shift in use of bariatric procedures, but little is known about their long-term comparative effectiveness.

Objective:

To compare weight loss and safety among bariatric procedures.

Design:

Retrospective observational cohort study, January 2005 to September 2015. (ClinicalTrials.gov: NCT02741674)

Setting:

41 health systems in the National Patient-Centered Clinical Research Network.

Participants:

65 093 patients aged 20 to 79 years with body mass index (BMI) of 35 kg/m² or greater who had bariatric procedures.

Intervention:

32 208 Roux-en-Y gastric bypass (RYGB), 29 693 sleeve gastrectomy (SG), and 3192 adjustable gastric banding (AGB) procedures.

Measurements:

Estimated percent total weight loss (TWL) at 1, 3, and 5 years; 30-day rates of major adverse events.

Results:

Total numbers of eligible patients with weight measures at 1, 3, and 5 years were 44 978 (84%), 20 783 (68%), and 7159 (69%), respectively. Thirty-day rates of major adverse events were 5.0% for RYGB, 2.6% for SG, and 2.9% for AGB. One-year mean TWLs were 31.2% (95% CI, 31.1% to 31.3%) for RYGB, 25.2% (CI, 25.1% to 25.4%) for SG, and 13.7% (CI, 13.3% to 14.0%) for AGB. At 1 year, RYGB patients lost 5.9 (CI, 5.8 to 6.1) percentage points more weight than SG patients and 17.7 (CI, 17.3 to 18.1) percentage points more than AGB patients, and SG patients lost 12.0 (CI, 11.6 to 12.5) percentage points more than AGB patients. Five-year mean TWLs were 25.5% (CI, 25.1% to 25.9%) for RYGB, 18.8% (CI, 18.0% to 19.6%) for SG, and 11.7% (CI, 10.2% to 13.1%) for AGB. Patients with diabetes, those with BMI less than 50 kg/m², those aged 65 years or older, African American patients, and Hispanic patients lost less weight than patients without those characteristics.

Limitation:

Potential unobserved confounding due to nonrandomized design; electronic health record databases had missing outcome data.

Conclusion:

Adults lost more weight with RYGB than with SG or AGB at 1, 3, and 5 years; however, RYGB had the highest 30-day rate of major adverse events. Small subgroup differences in weight loss outcomes were observed.

Primary Funding Source:

Patient-Centered Outcomes Research Institute.

https://ift.tt/2Da0dg1

How Would You Manage This Patient With Gout? Grand Rounds Discussion From Beth Israel Deaconess Medical Center

Gout is the most common form of inflammatory arthritis. In 2012, the American College of Rheumatology (ACR) issued a guideline, which was followed in 2017 by one from the American College of Physicians (ACP). The guidelines agree on treating acute gout with a corticosteroid, nonsteroidal anti-inflammatory drug, or colchicine and on not initiating long-term urate-lowering therapy (ULT) for most patients after a first gout attack and in those whose attacks are infrequent (<2 per year). However, they differ on treatment of both recurrent gout and problematic gout. The ACR advocates a "treat-to-target" approach, and the ACP did not find enough evidence to support this approach and offered an alternative strategy that bases intensity of ULT on the goal of avoiding recurrent gout attacks ("treat-to-avoid-symptoms") with no monitoring of urate levels. They also disagree on the role of a gout-specific diet. Here, a general internist and a rheumatologist discuss these guidelines; they debate how they would manage an acute attack of gout, if and when to initiate ULT, and the goals for ULT. Lastly, they offer specific advice for a patient who is uncertain about whether to begin this therapy.

https://ift.tt/2EbNKsM

Annals On Call - Hidden Curriculum

https://ift.tt/2St9lAe

Principles for Patient and Family Partnership in Care: An American College of Physicians Position Paper

In this position paper, the American College of Physicians (ACP) examines the rationale for patient and family partnership in care and reviews outcomes associated with this concept, including greater adherence to care plans, improved satisfaction, and lower costs. The paper also explores and acknowledges challenges associated with implementing patient- and family-centered models of care. On the basis of a comprehensive literature review and a multistakeholder vetting process, the ACP's Patient Partnership in Healthcare Committee developed a set of principles that form the foundation for authentic patient and family partnership in care. The principles position patients in their rightful place at the center of care while acknowledging the importance of partnership between the care team and patient in improving health care and reducing harm. The principles state that patients and families should be treated with dignity and respect, be active partners in all aspects of their care, contribute to the development and improvement of health care systems, and be partners in the education of health care professionals. This paper also recommends ways to implement these principles in daily practice.

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Annals Story Slam - About Believing in Santa

https://ift.tt/2St9io2

Losing Embryos, Finding Justice: Life, Liberty, and the Pursuit of Personhood

In March 2018, a liquid nitrogen storage tank broke down at a fertility center in Ohio, causing the loss of over 4000 eggs and embryos from more than 950 persons. This incident has precipitated lawsuits and raised thorny legal and ethical issues. The authors of this commentary present the legal theories tried in similar cases and some of the difficulties encountered.

https://ift.tt/2qWsJto

Annals Story Slam - Red All Over

https://ift.tt/2SvdzHz

Pitfalls and Potential in Medicare's Move Toward Outpatient Care Episodes

The authors evaluate the potential benefits and challenges in developing programs for Medicare's episode-based bundled payments for the management of chronic conditions among outpatients.

https://ift.tt/2FFSKro

Annals Story Slam - Words We Learn

https://ift.tt/2SvdyDv

More Evidence to Help Guide Decision Making About Aspirin for Primary Prevention

This commentary reviews the results of 2 large trials, 1 in healthy older adults and 1 in middle-aged and older adults with diabetes, that provide information to assist in decision making on aspirin use in patients without a history of cardiovascular disease.

https://ift.tt/2RejekP

Treatment of Dilated Cardiomyopathy With Interleukin-1 Inhibition

https://ift.tt/2ApNc1p

Randomized trial of two types of gastrojejunostomy after pancreatoduodenectomy and risk of delayed gastric emptying (PAUDA trial)

Background

Delayed gastric emptying (DGE) is the most important cause of an extended hospital stay after pancreatoduodenectomy. Reports suggest that a Roux‐en‐Y gastroenteric anastomosis may have lower incidence of DGE than a Billroth II reconstruction. The primary aim of this RCT was to compare Billroth II (single loop) and Roux‐en‐Y (double loop) after pancreatoduodenectomy to determine whether Roux‐en‐Y reconstruction is associated with a lower incidence of DGE. Secondary endpoints were postoperative complications.

Methods

This was a randomized unblinded single‐centre trial without masked evaluation of the main outcome. Patients undergoing pancreatoduodenectomy between 2013 and 2015 were randomized to undergo one of two types of gastroenteric anastomosis for reconstruction.

Results

A total of 80 patients were randomized, 40 in each group. The incidence of DGE was the same in patients undergoing Billroth II or Roux‐en‐Y gastroenteric anastomosis (both 18 of 40 patients; P = 1·000). The grade of DGE was also similar in the Billroth II and Roux‐en‐Y groups (grade A, both 10 of 40; grade B, 5 of 40 versus 6 of 40; grade C, 3 of 40 versus 2 of 40; P = 0·962). The mortality rate was 3 per cent, with no significant difference between the two groups. There were no differences in the overall rate of postoperative morbidity, relaparotomy rate or duration of hospital stay.

Conclusion

The incidence and severity of DGE does not differ between single‐ or double‐loop gastroenteric anastomosis performed after pancreatoduodenectomy. Registration number: NCT00915863 (http://www.clinicaltrials.gov).

https://ift.tt/2SpMNA7

Impairment of brain functions in Parkinson’s disease reflected by alterations in neural connectivity in EEG studies: a viewpoint

Parkinson's disease (PD) is characterized mainly by motor symptoms of tremor, rigidity, bradykinesia, and postural instability (Aarsland et al. 2011) and is accompanied by several non-motor symptoms. The phenotype of the disease varies among patients. The speed progression is very individual, as is the representation of motor and non-motor symptoms (Eggers et al. 2012). Cognitive impairment and dementia are common in advanced PD. Severe cognitive impairment increases disability and mortality in advanced PD.

https://ift.tt/2PhJ8Cu

Mosaic Y loss is moderately associated with solid tumor risk

Mosaic loss of the Y chromosome (mLOY) in peripheral leukocytes is a somatic event in which a fraction of leukocytes have lost the entire Y chromosome. The frequency of mLOY increases with age and may reflect poor genomic maintenance as well as clonal imbalances in normal immune function, making mLOY an attractive candidate marker for cancer risk. Here we investigated the relationship between mLOY and incident cancer in a large sample of 207,603 cancer-free men from the UK Biobank in which 13,895 men developed an incident solid tumor during follow-up. We identified mLOY by scanning for deviations in genotyping array log R intensity ratios (LRR) across the male-specific chromosome Y region. Overall, we detected low proportions of cells with mLOY in 3,358 (1.6%) men and high proportions of mLOY in 524 (0.3%) men. We found an association of mLOY with overall solid tumor incidence using both low and high mLOY thresholds (HRlow=1.18, 95% CIlow=1.07-1.30, P-valuelow=0.001; HRhigh=1.36, 95% CIhigh=1.09-1.71, P-valuehigh=0.007) and more specifically we observed an association with lung cancer (HRhigh=2.25, 95% CIhigh=1.36-3.71, P-valuehigh=0.002). Stronger associations were observed without adjustment for smoking, suggesting that smoking is an important confounder of tumor incidence. It is unlikely that mLOY is a major mediator of the effect of cigarette smoking on cancer risk, as mLOY was observed in only a small fraction of smokers who developed cancer. In summary, mLOY was modestly associated with incidence of solid tumors in the UK Biobank, although for some cancer subtypes these findings may reflect residual confounding by smoking.

https://ift.tt/2Smd4iE

Lactic acid accumulation in the tumor microenvironment suppresses 18F-FDG uptake

The process by which tumor cells take up 18F-fluorodeoxyglucose (FDG) is heterogeneous and influenced by a multitude of factors. In mouse tumor grafts, the core of the tumor often presents lower FDG uptake than the periphery. Whether this pattern is caused by the intrinsic avidity of individual cells for FDG, the density of viable cells in the tumor, or the perfusion of the radiotracer remains unknown. In this study, we used radioluminescence microscopy to measure FDG uptake in single cells isolated from the core and periphery of the tumor and found that differences in FDG uptake persist on the level of single cells. Single cells from the core of 4T1 and MDA-MB-231 tumors grafts took up 26−84% less FDG than those from the periphery. These differences were observed in mice with large tumors (> 8 mm diameter) but not in those with smaller tumors. To explain the origin of these differences, we examined the influence of three microenvironmental factors on FDG uptake. Hypoxia was ruled out as a possible explanation because its presence in the core would increase and not decrease FDG uptake. Higher cell proliferation in the periphery was consistent with higher FDG uptake but there was no evidence of a causal relationship. Finally, lactate was higher in the core of the tumor and it suppressed FDG uptake in a dose-dependent fashion. We therefore conclude that lactic acidosis-the combination of lactate ion buildup and acidic pH-can increase the heterogeneity of FDG uptake in MDA-MB-231 and 4T1 tumor grafts.

https://ift.tt/2EcphUq

Tolerance to Sodium in Patients With CKD-Induced Metabolic Acidosis: Does the Accompanying Anion Matter?

Patients with chronic kidney disease (CKD) continue to produce endogenous acids but have a reduction in net acid excretion, resulting in a primary decrease in serum bicarbonate concentration, which is termed chronic metabolic acidosis. Recent prospective studies, along with retrospective cohort analyses, demonstrate a higher risk for CKD progression with untreated metabolic acidosis. To normalize serum bicarbonate levels, acidemic patients are often treated with sodium bicarbonate (NaHCO3) or sodium citrate, which have been shown to slow the progression of CKD.

https://ift.tt/2zHI2uM

Promoter DNA Methylation and mRNA Expression Level of p16 Gene in Oral Squamous Cell Carcinoma: Correlation with Clinicopathological Characteristics

Abstract

The aim of this study was to investigate the relationship between p16 methylation and its expression in oral squamous cell carcinoma (OSCC). Also the contribution of clinicopathological factors, HPV infection and smoking in p16 expression and promoter methylation has been investigated. In this study 67 consecutive OSCC patients and 59 normal individuals were enrolled. All patients were candidates for surgery of oral cavity and fresh tumor biopsies were collected and processed for DNA and RNA extraction. Normal gingival tissues were collected from individuals referred to dentistry clinic and considered as controls. All the cases and controls were checked for HPV infection and then promoter methylation and expression of p16 gene were determined using Methylation-specific PCR (MSP) and real-time PCR (QPCR), respectively. Methylation of p16 in tumors and normal tissues were 59.7 and 38.9%, respectively. Most of hypermethylated samples (>82%) were in high grades. P16 methylation was comparable in HPV+ and HPV- patients or smokers. P16 was overexpressed (~3 fold; p = 0.044) in HPV+ tumors, but it was significantly down-regulated in smoker patients (40% of all tumors). Comparison of P16 expression in OSCC tumors with different degrees of promoter methylation further suggest the relationship of methylation rate and down-regulation of P16 expression. The p16 methylation and expression was differentially affected in patients with HPV infection and the smoker cases. Regardless of the influence of environmental factors, it appears that P16 status is useful for classifying patients with OSCC and for influencing treatment strategies in accordance with this classification. Moreover, targeting the upregulation of p16 could be a promising therapeutic option.

https://ift.tt/2rerYw6

The Role and Prognostic Significance of Aortopulmonary, Anterior Mediastinal, and Tracheobronchial Lymph Nodes in Esophageal Cancer: Update of the Eighth-Edition TNM Staging System (2018)

Abstract

Background

The eighth edition of TNM staging for esophageal cancer will be implemented at 2018. The stations 5, 6, and 10 lymph nodes (LNs) have been omitted from the regional lymph node map for the new TNM staging. However, the role and prognostic significance of these LN stations were not clear. The purpose of this study was to investigate whether the revised nodal staging is appropriate and to verify the role, prognostic significance, and therapeutic value of these LNs in esophageal cancer.

Methods

The records of patients who underwent esophagectomy for cancer in our department between 2007 and 2013 were retrospectively analyzed. The rate of metastases was calculated for stations 5, 6, and 10 LNs. LN metastasis and patient survival were analyzed.

Results

A total of 1637 patients were included. The calculated rate of metastasis to stations 5, 6, and 10 was 3.2%, 2.3%, and 4.9%, respectively. No difference was found in the N stage determined by the seventh and eighth edition N staging systems. The status of station 5, 6, or 10 was not associated with long-term survival according to Cox proportional hazards model analysis.

Conclusions

Metastasis to stations 5, 6, or 10 LNs was infrequent. Omitting of stations 5, 6, and 10 LNs in the eighth edition TNM staging did not influence the accuracy and survival-predicting efficacy. The therapeutic value of lymphadenectomy of stations 5, 6, and 10 was limited. The status of stations 5, 6, and 10 LNs was not associated with long-term survival.

https://ift.tt/2DYXoOD

ASO Author Reflections: Colorectal Liver Metastases Early Progression After Chemotherapy: A Possible Contraindication to Surgery?

https://ift.tt/2QupXu1

Hydrolytic denitrification and decynidation of acrylonitrile in wastewater with Arthrobacter nitroguajacolicus ZJUTB06-99

Acrylonitrile (C3H3N) widely used in chemical raw materials has biological toxicity with –CN bond, so it is the key to removal of cyanide from acrylonitrile wastewater. In our previous research and investigation,...

https://ift.tt/2KPAiLx

Primary cutaneous infection due to Microascus cirrosus: a case report

Microascus cirrosus, the teleomorph of Scopulariopsis spp., is a saprobic species with a worldwide distribution and rarely causes human infection. In the present paper, we present the first case of primary cutane...

https://ift.tt/2St0rCr

Differences in Chlamydia trachomatis seroprevalence between ethnic groups cannot be fully explained by socioeconomic status, sexual healthcare seeking behavior or sexual risk behavior: a cross-sectional analysis in the HEalthy LIfe in an Urban Setting (HELIUS) study

In the Netherlands, there are strong disparities in Chlamydia trachomatis (CT) prevalence between ethnic groups. The current study aims to identify whether socioeconomic status, sexual risk behavior and sexual he...

https://ift.tt/2Ecg8Lp

Environmental disinfection with photocatalyst as an adjunctive measure to control transmission of methicillin-resistant Staphylococcus aureus: a prospective cohort study in a high-incidence setting

Environmental disinfection with continuously antimicrobial surfaces could offer superior control of surface bioburden. We sought to decide the efficacy of photocatalyst antimicrobial coating in reducing methic...

https://ift.tt/2St0luz

Seroprevalence and risk factors of brucellosis among slaughtered indigenous cattle, abattoir personnel and pregnant women in Ngaoundéré, Cameroon

Brucellosis is a neglected debilitating zoonosis with a high prevalence in many developing countries. Bovine brucellosis is widespread in Cameroon but the epidemiological situation of human brucellosis is not ...

https://ift.tt/2Ecga5Z

Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016

The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the Europea...

https://ift.tt/2St0ePF

Meso-Scale Particle Image Velocimetry Studies of Neurovascular Flows In Vitro

Here we present simplified methods for fabricating transparent neurovascular phantoms and characterizing the flow therein. We highlight several important parameters and demonstrate their relationship to field accuracy.

https://ift.tt/2FWOW59

November 2018 Briefing - Pain Management

Here are what the editors at HealthDay consider to be the most important developments in Pain Management for November 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes...

https://ift.tt/2AJ9gku

More People Worldwide Now Know Their HIV Status

MONDAY, Dec. 3, 2018 -- Three-quarters of patients living with HIV worldwide know their infection status, according to Knowledge Is Power, a new report released Nov. 22 by UNAIDS. In 2017, three-quarters of people living with HIV (75 percent) knew...

https://ift.tt/2UcdrOx

November 2018 Briefing - Ophthalmology

Here are what the editors at HealthDay consider to be the most important developments in Ophthalmology for November 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that...

https://ift.tt/2ALiNYq

Core Language Skill Stable From Infancy to Adolescence

MONDAY, Dec. 3, 2018 -- A core language skill, extracted from multiple measures, is stable from infancy to adolescence in children, including atypically developing children, according to a study published online Nov. 21 in Science Advances. Marc H....

https://ift.tt/2Ucdvhf

Risk of Sudden Death in Epilepsy Can Decline Over Time

MONDAY, Dec. 3, 2018 -- The risk for sudden unexpected death in epilepsy (SUDEP) may decrease over time, according to a study presented at the annual meeting of the American Epilepsy Society, held from Nov. 30 to Dec. 4 in New Orleans. Neishay Ayub,...

https://ift.tt/2AMtWIi

ASH: High Response to Tx After Checkpoint Blockade in NHL, HL

MONDAY, Dec. 3, 2018 -- For heavily pretreated patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL), response rates are high for treatment subsequent to checkpoint blockade therapy (CBT), according to two...

https://ift.tt/2UcfWk4

Shifting Pattern Seen for Primary Care Office Visits

MONDAY, Dec. 3, 2018 -- Among patients with employer-sponsored insurance, there was a decline in visits to primary care physicians (PCPs) from 2012 to 2016, according to a brief released Nov. 15 by the Health Care Cost Institute (HCCI). Amanda...

https://ift.tt/2ALiPzw

Joint Mobilization Plus Exercise Beneficial for Knee Osteoarthritis

MONDAY, Dec. 3, 2018 -- Patellar mobilization therapy (PMT) plus exercise has the potential to reduce pain and improve function and quality of life for patients with knee osteoarthritis, according to a phase 2 study published Nov. 12 in the Annals...

https://ift.tt/2AKwV3V

Targeted Hep C Testing Misses High Number of Cases in Prisons

MONDAY, Dec. 3, 2018 -- Targeted hepatitis C virus (HCV) testing misses a substantial number of cases among individuals in correctional facilities, according to a study published online Nov. 19 in the American Journal of Preventive Medicine. Sabrina...

https://ift.tt/2UcfT7S

New BP Goals Could Prevent 3 Million CVD Events Over 10 Years

MONDAY, Dec. 3, 2018 -- Achieving and maintaining 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) goals could prevent a greater number of cardiovascular disease (CVD) events than achieving prior U.S....

https://ift.tt/2AMepZ5

Higher Staffing Linked to Lower C-Section Rates

MONDAY, Dec. 3, 2018 -- Higher staffing levels in maternity units reduce the rate of cesarean deliveries, according to a study published online Nov. 28 in PLOS ONE. Saad Zbiri, from Versailles Saint Quentin University in France, and colleagues...

https://ift.tt/2UcfSAQ

Impact of Fructose Varies With Energy Control, Food Source

MONDAY, Dec. 3, 2018 -- Energy control and food source appear to mediate the effect of fructose-containing sugars on glycemic control, according to a review published online Nov. 21 in The BMJ. Vivian L. Choo, from St. Michael's Hospital in Toronto,...

https://ift.tt/2AONOuv

November 2018 Briefing - Diabetes & Endocrinology

Here are what the editors at HealthDay consider to be the most important developments in Diabetes & Endocrinology for November 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and...

https://ift.tt/2UcfRgg

November 2018 Briefing - Nursing

Here are what the editors at HealthDay consider to be the most important developments in Nursing for November 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are...

https://ift.tt/2UcfPVG

November 2018 Briefing - Nephrology

Here are what the editors at HealthDay consider to be the most important developments in Nephrology for November 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are...

https://ift.tt/2APh2cw

November 2018 Briefing - Anesthesiology

Here are what the editors at HealthDay consider to be the most important developments in Anesthesiology for November 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that...

https://ift.tt/2UcfNNy

November 2018 Briefing - Orthopedics

Here are what the editors at HealthDay consider to be the most important developments in Orthopedics for November 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that...

https://ift.tt/2Ucdk5z

November 2018 Briefing - HIV & AIDS

Here are what the editors at HealthDay consider to be the most important developments in HIV & AIDS for November 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that...

https://ift.tt/2AQeCu7

November 2018 Briefing - Pharmacy

Here are what the editors at HealthDay consider to be the most important developments in Pharmacy for November 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are...

https://ift.tt/2UcdhGV

November 2018 Briefing - Neurology

Here are what the editors at HealthDay consider to be the most important developments in Neurology for November 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are...

https://ift.tt/2AQeAlZ

Quality evaluation of smartphone applications for laboratory medicine

Authors: Jovičić, Snežana / Siodmiak, Joanna / Watson, Ian D. /


https://ift.tt/2Axy3rD

Response to Letter to the Editor about immunochemical measurement of urine free light chains

Authors: Tate, Jillian R. / Mollee, Peter


https://ift.tt/2Q7Jwcb

Reference intervals for thyroid-stimulating hormone, free thyroxine, and free triiodothyronine in elderly Chinese persons

Authors: Wang, Danchen / Yu, Songlin / Ma, Chaochao / Li, Honglei / Qiu, Ling / Cheng, Xinqi / Guo, Xiuzhi / Yin, Yicong / Li, Dandan / Wang, Zhenjie / Hu, Yingying / Lu, Shuangyu / Yang, Guohua / Liu, Huaicheng


https://ift.tt/2TVIhea

Digital networks for laboratory data: potentials, barriers and current initiatives

Authors: Ganslandt, Thomas / Neumaier, Michael


https://ift.tt/2AJv4wz

Provisional standardization of hepcidin assays: creating a traceability chain with a primary reference material, candidate reference method and a commutable secondary reference material

Authors: Diepeveen, Laura E. / Laarakkers, Coby M.M. / Martos, Gustavo / Pawlak, Marta E. / Uğuz, Fatih F. / Verberne, Kim E.S.A. / van Swelm, Rachel P.L. / Klaver, Siem / de Haan, Anton F.J. / Pitts, Kelly R. / Bansal, Sukhvinder S. / Abbas, Ioana M. / Fillet, Marianne / Lefebvre, Thibaud / Geurts-Moespot, Anneke J. / Girelli, Domenico / Castagna, Annalisa / Herkert, Matthias / Itkonen, Outi / Olbina, Gordana / Tomosugi, Naohisa / Westerman, Mark E. / Delatour, Vincent / Weykamp, Cas W. / Swinkels, Dorine W.


https://ift.tt/2rbxM9A

Preoperative proteinuria and clinical outcomes in type B aortic dissection after thoracic endovascular aortic repair

Authors: Yang, Hongwei / Zhou, Jianwei / Huang, Keli / Yu, Tao / Wang, Zuhui / Chen, Heng / Yu, Wenshui / Lin, Xiaodong / Zhang, Yan / Zhu, Guoxian


https://ift.tt/2TY0d8c

Danger of false negative (exclusion) or false positive (diagnosis) for ‘congenital thrombophilia’ in the age of anticoagulants

Authors: Favaloro, Emmanuel J.


https://ift.tt/2r87AN9

Liquid biopsy: novel technologies and clinical applications

Authors: Reimers, Natalie / Pantel, Klaus


https://ift.tt/2KpoPlT

The long way to standardization of practices: HbA1c as archetypal example

Authors: Gillery, Philippe


https://ift.tt/2BqiaVx

Communicating laboratory results to patients and families

Authors: Witteman, Holly O. / Zikmund-Fisher, Brian J.


https://ift.tt/2Qu47Do

Time Course of Neoangiogenesis After Indirect Bypass Surgery for Moyamoya Disease

Abstract

Objective

Indirect bypass surgery, which induces spontaneous neoangiogenesis in ischemic brain tissue and improves cerebral blood flow, is an effective treatment for moyamoya disease (MMD). The time course of neoangiogenesis development has not yet been investigated. This study aimed to determine the critical period of neovascularization after indirect bypass in MMD patients.

Methods

Patients with MMD who underwent indirect bypass surgery at Peking University International Hospital between January 2015 and October 2017 were retrospectively reviewed. Surgically treated hemispheres with short-term (3–6 months) and long-term (1 year) follow-up digital subtraction angiography (DSA) were included. The effects of revascularization were evaluated on lateral and anteroposterior views using angiography and compared between two follow-ups of the same hemisphere.

Results

This study included 25 hemispheres from 24 MMD patients (mean age: 22.48 ± 14.83 years), among whom 13 were pediatric patients and 12 were adults. Qualitative measurements including the Matsushima scale and coverage of neoangiogenesis on anteroposterior views were not significantly different between the short term and long term (P = 0.083 and P = 0.157, respectively). Quantitative measurements including the greatest width and height of the area covered by neovascularization on lateral views of DSA and the greatest depth of neovascularization penetration on anteroposterior views (P = 0.488, 0.298 and 0.527, respectively) were also not significantly different. The mean count of newly formed veins was more at long-term than short-term follow-up (5.5 ± 2.5 vs. 5.1 ± 2.4, P = 0.005). Subgroup analysis of pediatric patients and adults yielded the same results as in the whole series.

Conclusion

After indirect bypass surgery, the major time window of arterial neoangiogenesis development was within 6 months after surgery. The general effect of revascularization was very similar in the short and long term; therefore, a follow-up angiography scheduled at 6 months after surgery is recommended. Growth of veins might continue after 6 months.

https://ift.tt/2BODWm8

Computer-aided diagnosis using deep learning in the evaluation of early oesophageal adenocarcinoma

Message

Computer-aided diagnosis using deep learning (CAD-DL) may be an instrument to improve endoscopic assessment of Barrett's oesophagus (BE) and early oesophageal adenocarcinoma (EAC). Based on still images from two databases, the diagnosis of EAC by CAD-DL reached sensitivities/specificities of 97%/88% (Augsburg data) and 92%/100% (Medical Image Computing and Computer-Assisted Intervention [MICCAI] data) for white light (WL) images and 94%/80% for narrow band images (NBI) (Augsburg data), respectively. Tumour margins delineated by experts into images were detected satisfactorily with a Dice coefficient (D) of 0.72. This could be a first step towards CAD-DL for BE assessment. If developed further, it could become a useful adjunctive tool for patient management.

In more detail

The incidence of BE and EAC in the West is rising significantly, and because of its close association with the metabolic syndrome this trend is expected to continue.1–3 Reports of CAD in BE...

https://ift.tt/2zB6oq4

Role of endoscopy in chronic diarrhoea when functional bowel disease is suspected

We thank Ong and colleagues1 for their comment on the indication for lower GI endoscopy when functional bowel disease such as IBS diarrhoea predominant (IBS-D) is suspected.

In most patients with chronic diarrhoea, some form of endoscopic investigation will be necessary. However, it has been recommended that in young patients (less than 40 years) reporting 'diarrhoea' but who have other typical symptoms of a functional bowel disorder and negative initial investigations including faecal calprotectin, a positive diagnosis of IBS-D may be made in the primary care setting without recourse to further investigations.2

We are concerned that many patients with severe, persistent or atypical symptoms fail to have other specific treatable diagnoses made. Hence, the guidelines subsequently clarify this further within section 4.2, to state 'patients under 40 years without typical symptoms of functional bowel disorder and/or severe symptoms and documented diarrhoea (as previously defined) should have further evaluation'.

https://ift.tt/2PgiJF6

Defending a mean arterial pressure in the intensive care unit: Are we there yet?

https://ift.tt/2Edv1gH

Patterns of Use of Docetaxel-Containing Adjuvant Chemotherapy Among Chinese Patients with Operable Breast Cancer: A Multicenter Observational Study

Abstract

Introduction

Adjuvant docetaxel-based chemotherapy is frequently used in the treatment of operable early breast cancer (EBC). This study investigated patterns of docetaxel use in patients with EBC in real-world clinical practice in China.

Methods

This was a multicenter, prospective, observational study of Chinese women with operable breast cancer in tier 1 non-oncology-specific hospitals and other city hospitals in China. Adult Chinese female patients (≥ 18 years) with newly diagnosed breast cancer who underwent surgery and received docetaxel-containing adjuvant chemotherapy were eligible for inclusion. The primary end point of the study was to assess patterns of docetaxel use for adjuvant therapy in Chinese clinical practice. Secondary end points included factors associated with treatment selection, patterns of G-CSF use and safety.

Results

In total, 502 patients were enrolled, 475 of whom were included in the analysis. The results showed that 31.6% of patients received docetaxel and anthracyclines in combination, 47.2% received docetaxel and anthracyclines sequentially, 18.5% received docetaxel and other medication either in combination or sequentially and 2.7% received 'other' chemotherapy regimens. Factors influencing selection of docetaxel/anthracycline in combination versus sequentially included age, breast cancer subgroup, PR status, and preoperative neoadjuvant chemotherapy. A total of 258 (54.3%), 35 (7.4%), and 108 (22.7%) patients received G-CSF as primary prevention, secondary prevention and treatment, respectively. Treatment-emergent adverse events (TEAEs) occurred in 54.5% (259) of patients, and the most frequently reported TEAEs (≥ 5% of patients) included bone marrow failure (10.1%), granulocytopenia (9.9%), nausea (8.8%) and vomiting (6.9%). Neutropenia and febrile neutropenia were reported by 10 and 12 patients, respectively.

Conclusion

Docetaxel for adjuvant chemotherapy of operable EBC in China was most commonly given in combination or sequentially with anthracyclines. The study also showed that in China G-CSF is most frequently used as primary prophylactic, and no unexpected safety events were observed during docetaxel treatment.

Funding

Sanofi (China).

https://ift.tt/2KR4S7E

Evaluation of MCQs from MOOCs for common item writing flaws

There is a dearth of research into the quality of assessments based on Multiple Choice Question (MCQ) items in Massive Open Online Courses (MOOCs). This dataset was generated to determine whether MCQ item writ...

https://ift.tt/2Ph2kAa

Promising efficacy of SHR‐1210, a novel anti–programmed cell death 1 antibody, in patients with advanced gastric and gastroesophageal junction cancer in China

Background

The clinical response to anti–programmed cell death 1 (PD‐1) antibodies in patients with advanced gastric and gastroesophageal junction (GEJ) cancer in China has not been reported.

Methods

This study evaluated the efficacy and safety of SHR‐1210, an anti–PD‐1 antibody, in patients with advanced gastric/GEJ cancer in a phase 1 trial. The associations between candidate biomarkers (programmed death ligand 1 [PD‐L1] expression, mismatch repair status, tumor mutation load, and lactate dehydrogenase [LDH] levels) and the efficacy of SHR‐1210 were also explored.

Results

Thirty patients with recurrent or metastatic gastric/GEJ adenocarcinoma who were refractory or intolerant to previous chemotherapy were enrolled between June 2, 2016, and June 8, 2017. Seven patients (23.3%) demonstrated objective responses, including 1 complete response. The objective response rates for patients with PD‐L1–positive and PD‐L1–negative tumors were 23.1% (3 of 13) and 26.7% (4 of 15), respectively (P = 1.000). Two treatment‐related grade 3 or higher adverse events were reported: one was grade 3 pruritus, and the other (3.3%) was grade 5 interstitial lung disease. All 20 patients tested for the mismatch repair status had mismatch repair–proficient tumors, and the response rate was 30.0% (95% confidence interval, 11.9%‐54.3%). Patients with a higher mutation load (4 of 10) tended to have better responses than those with fewer mutations (2 of 10), but the difference was not significant (P = .628). Patients with a >10% relative increase from the baseline LDH level were more likely to experience disease progression (90% [9 of 10]) than patients with a ≤10% change (40% [8 of 20]; P = .017).

Conclusions

Anti–PD‐1 antibody SHR‐1210 shows encouraging efficacy in patients with advanced gastric/GEJ cancer in China, including mismatch repair–proficient subgroups.

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Unmet social support needs among older adults with cancer

Abstract

Background

Adequate social support for older adults is necessary to maintain quality of life and reduce mortality and morbidity. However, little is known regarding the social support needs of older adults with cancer. The objective of the current study was to examine social support needs, specifically the unmet needs, among older adults with cancer.

Methods

Medicare beneficiaries (those aged ≥65 years) with cancer were identified from the University of Alabama at Birmingham Health System Cancer Community Network. Social support needs were assessed using a modified version of the Medical Outcomes Study Social Support Survey. The authors defined an "unmet need" if participants reported having some/a little/never availability of support and requiring support for that need.

Results

Of the 1460 participants in the current study, the average age was 74 years (standard deviation, 5.8 years). Approximately two‐thirds of participants (986 participants; 67.5%) reported having at least 1 social support need, with the highest needs noted in the emotional (49.5%) and physical (47.4%) support subdomains. Of those individuals with a support need, approximately 45% had at least 1 unmet need, with the greatest percentages noted in the medical (39%) and informational (36%) subdomains. Multivariable analyses demonstrated that participants who were nonwhite, were divorced or never married, or had a high symptom burden were at greatest risk of having unmet social support needs across subdomains.

Conclusions

In this population of older adults with cancer, the authors found high levels of unmet social support needs, particularly in the medical and informational support subdomains. Participants who were nonwhite, were divorced or never married, or had a high symptom burden were found to be at greatest risk of having unmet needs.

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