A retrospective study of the CHOP, CHOPE, and CHOPE/G regimens as the first-line treatment of peripheral T-cell lymphomas

Abstract

Purpose

The standard treatment for peripheral T-cell lymphomas (PTCLs) is undetermined. We designed a CHOPE/G regimen (cyclophosphamide, pirarubicin, vincristine, prednisolone, and etoposide alternating with a gemcitabine-based regimen) as the first-line treatment of PTCLs and compared with CHOP (cyclophosphamide, pirarubicin, vincristine, and prednisolone) and CHOPE (CHOP plus etoposide) regimen to evaluate the optimal chemotherapy regimen.

Methods

116 previously untreated PTCL patients received CHOP (N = 46), CHOPE (N = 46), or CHOPE/G (N = 24) regimen at Peking University Cancer Hospital from 2009 to 2017 and were retrospectively analyzed.

Results

The overall response rates (ORRs) of the CHOP, CHOPE, and CHOPE/G groups were 82.6%, 76.1%, and 75.0% (p = 0.673), with complete response (CR) rates of 32.6%, 56.5%, and 45.7% (p = 0.063), respectively. Within a median follow-up time of 35.5 months, the 3-year overall survival (OS) rates of the CHOP, CHOPE, and CHOPE/G groups were 37.0%, 47.0%, and 56.3% (p = 0.107), and the 3-year progression-free survival (PFS) rates were 19.9%, 29.9%, and 5.3% (p = 0.093), respectively. Compared with the CHOP regimen alone, CHOPE had a significantly higher CR rate (p = 0.021) with more favorable OS (p = 0.046). The CHOPE/G regimen did not improve the ORR, CR rate, or OS compared with either the CHOP or CHOPE, with a significantly poorer PFS compared with the CHOPE regimen (p = 0.029). Anemia and thrombocytopenia occurred most frequently in the CHOPE/G group (anemia 83.3%, p = 0.035; thrombocytopenia 50%, p = 0.015).

Conclusions

Compared with CHOP alone, CHOPE regimen improved the efficacy and survival; while the addition of gemcitabine in the front-line therapy resulted in more adverse events without benefit of survival.

https://ift.tt/2rhYuNZ

Severe hypersensitivity reactions to platinum compounds post-pressurized intraperitoneal aerosol chemotherapy (PIPAC): first literature report

Abstract

Background

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) shows encouraging results for patients with unresectable peritoneal metastasis. Several reports demonstrated the safety of the procedure combined with systemic chemotherapy, with a low rate of complication. The aim of this study is to report severe hypersensitivity reactions to platinum compounds (SHRPC) during PIPAC procedures.

Methods

All patients who underwent PIPAC for non-resectable PC in Lyon Sud University hospital were included in a prospective institutional database. All patients who presented a SHRPC after PIPAC were included in our analysis.

Results

One hundred and thirty-two patients underwent 383 PIPAC procedures between December 2015 and December 2017. oxaliplatin's and cisplatin–doxorubicin's protocols were used in 71 and 312 PIPAC, respectively. Four patients (3%) developed SHRPC; two patients (2.8%) after oxaliplatin and two patients (0.6%) after cisplatin–doxorubicin protocols. SHRPC occurred during the 6th PIPAC with cisplatin–doxorubicin protocol and during 2nd and 3rd PIPAC of the oxaliplatin protocol. Three events appeared within 15 min and one event occurred 50 min following nebulization. All the SHRPC have been managed successfully without any complication.

Conclusions

This is the first report of SHRPC after PIPAC. The physician must constantly keep this rare but life-threatening complication in mind, especially after repeated PIPAC administration or previous platinum-based systemic chemotherapy.

https://ift.tt/2FTnm8A

Combined Treatment with Autologous CIK Cells, Radiotherapy and Chemotherapy in Advanced Cervical Cancer

Abstract

To investigate the clinical efficacy of autologous cytokine induced killer (CIK) cells transfusion combined with radiochemotherapy in the treatment of advanced cervical cancer. A total of 89 hospitalized patients with advanced cervical cancer were admitted and divided into the treatment group (44 cases, autologous CIK cells transfusion combined with radiochemotherapy) and the control group (45 cases, radiochemotherapy) by a randomized non-blind method. Comparisons of therapeutic efficacies, immune functions, life qualities and survival rates were analyzed between the two groups. The short-term therapeutic efficacy of the treatment group was significantly higher than that of the control group. There was no significant difference in 1, 2 and 3 year survival rates between the two groups. Compared with pre-treatment, levels of CD3⁺, CD4⁺/CD8⁺ in peripheral blood were increased in the CIK group, which were reduced in the control group. In the CIK group,only the feeling was depressed on the 25th day post-treatment (T25) compared with the day before treatment (B1). However in the control group, the function of body, role, social and holistic health was obvious disordered on day T25 compared with day B1. On day T25, there were significant differences in function of body, social and holistic health between two groups. Autologous CIK cells transfusion combined with radiochemotherapy shows better short-term efficacy than radiochemotherapy alone in the treatment of advanced cervical cancer, which obviously improves immune function and life quality of patients with low side effects.

https://ift.tt/2QvAtAV

To keep patients with COPD out of hospital, look beyond the lungs [Editorial]

https://ift.tt/2AMxBpL

Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial [Correction]

https://ift.tt/2UcBGwn

High-strength opioid formulations: the case for a ministerial recall [Commentary]

https://ift.tt/2AH3EqW

Tread carefully with #MeToo in the medical profession [Letters]

https://ift.tt/2U8jmnR

Clinical validation of a risk scale for serious outcomes among patients with chronic obstructive pulmonary disease managed in the emergency department [Research]

BACKGROUND:

The Ottawa chronic obstructive pulmonary disease (COPD) Risk Scale (OCRS), which consists of 10 criteria, was previously derived to identify patients in the emergency department with COPD who were at high risk for short-term serious outcomes. We sought to validate, prospectively and explicitly, the OCRS when applied by physicians in the emergency department.

METHODS:

We conducted this prospective cohort study involving patients in the emergency departments at 6 tertiary care hospitals and enrolled adults with acute exacerbation of COPD from May 2011 to December 2013. Physicians evaluated patients for the OCRS criteria, which were recorded on a data form along with the total risk score. We followed patients for 30 days and the primary outcome, short-term serious outcomes, was defined as any of death, admission to monitored unit, intubation, noninvasive ventilation, myocardial infarction (MI) or relapse with hospital admission.

RESULTS:

We enrolled 1415 patients with a mean age of 70.6 (SD 10.6) years and 50.2% were female. Short-term serious outcomes occurred in 135 (9.5%) cases. Incidence of short-term serious outcomes ranged from 4.6% for a total score of 0 to 100% for a score of 10. Compared with current practice, an OCRS score threshold of greater than 1 would increase sensitivity for short-term serious outcomes from 51.9% to 79.3% and increase admissions from 45.0% to 56.6%. A threshold of greater than 2 would improve sensitivity to 71.9% with 47.9% of patients being admitted.

INTERPRETATION:

In this clinical validation of a risk-stratification tool for COPD in the emergency department, we found that OCRS showed better sensitivity for short-term serious outcomes compared with current practice. This risk scale can now be used to help emergency department disposition decisions for patients with COPD, which should lead to a decrease in unnecessary admissions and in unsafe discharges.

https://ift.tt/2AO5ENZ

Overscheduled and glued to screens -- children are sleeping less than ever before [News]

https://ift.tt/2U9Z2Ct

Cardiac manifestations in Emery-Dreifuss muscular dystrophy [Practice]

https://ift.tt/2AJ76l1

Identity as a Reproducible Method [Humanities]

https://ift.tt/2U85wlw

Acute flaccid myelitis [Practice]

https://ift.tt/2AIF60J

The authors respond to "Tread carefully with #MeToo in the medical profession" [Letters]

https://ift.tt/2UfmEWC

Pituitary apoplexy [Practice]

https://ift.tt/2AKc8gV

Medical education needs reform to improve student well-being and reduce burnout, say experts [News]

https://ift.tt/2UfmEG6

Learning to touch [Humanities]

https://ift.tt/2AI5EiI

Primary care system outdated and inconvenient for many millennials [News]

https://ift.tt/2U9Yo8c

p53-mediated adaptation to serine starvation is retained by a common tumour-derived mutant

Abstract

Background

In response to oncogenic stress, the tumour suppressor protein p53 can induce the elimination of cells through induction of cell death or senescence, helping to restrain malignant progression. Conversely, under nutrient stress, p53 can protect cells by supporting metabolic adaptation. Many cancers express mutant p53 proteins that have lost the cell-elimination properties of wild-type p53. However, a previous report showed that a tumour-derived mutant can retain the ability to support cells under glutamine starvation.

Results

We show that a commonly occurring p53 mutant, R248W, retains wild-type ability to support survival under serine starvation. R248W, but not R175H, can engage p21 and MDM2, which both function to limit oxidative stress and facilitate the switch to de novo serine synthesis. In vivo, the growth of R248W-expressing tumours is resistant to dietary depletion of serine and glycine, correlating with an increased capacity to limit ROS compared to tumours expressing R175H. Human cancers expressing this p53 mutant show a worse outcome.

Conclusion

Our work shows that mutant p53s can selectively retain wild-type p53 functions that allow adaptation to serine starvation through the activation of antioxidant defence pathways. Tumours containing this p53 mutation are resistant to serine-limited conditions and less responsive to therapy.

https://ift.tt/2Q82HCp

The Prognostic Value of Nanog Overexpression in Lung Cancer: A Meta-Analysis

Background. Recent several studies have showed that the nanog overexpression leads to poor prognosis in some kinds of cancer including hepatocellular carcinoma and gastrointestinal luminal cancer. However, the correlations between prognosis and clinic-pathological features and nanog overexpression in lung cancer are still not well-known. Thus, we performed a meta-analysis to evaluate the role of nanog in lung cancer. Methods. An electronic retrieval for related studies was conducted in PubMed, Cochrane Library, Web of Science, EMBASE databases, Chinese CNKI, and the Chinese Wan Fang database up to May 2018. The relationships between nanog overexpression and overall survival (OS) and disease-free survival (DFS) as well as clinic-pathological features in lung cancer were investigated. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by STATA12. Results. 11 studies containing 1422 patients were identified in our meta-analysis. The overexpression of nanog showed decreased OS (HR = 1.83, 95% CI = 1.49-2.25, P ≤ 0.001) and DFS (HR = 1.86, 95% CI = 1.2-2.9, P = 0.006). Moreover, overexpression of nanog was significantly related to differentiation (OR = 4.17, 95% CI = 2.17-6.43, P ≤ 0.001), lymph node metastasis (OR = 1.76, 95% CI = 1.06-2.91, P = 0.028) and tumor size (OR = 1.93, 95% CI = 1.17-3.20, P = 0.010), and no correlation with T stage, TNM, stage, and gender. Conclusions. Our results suggested that nanog overexpression, a hazard factor of differentiation, lymph node metastasis, and tumor size, may predicate decreased OS and DFS for lung cancer.

https://ift.tt/2Skw9lw

Anti-Dengue, Cytotoxicity, Antifungal, and In Silico Study of the Newly Synthesized 3-O-Phospo--D-Glucopyranuronic Acid Compound

The aim of the current study was to synthesize new bioactive compounds and evaluate their therapeutic relevance. The chemical structure of compound 7 (methyl 3-O-phospo-α-D-glucopyranuronic acid was elucidated by physical and advance spectral technique. Also, this compound was assessed for various in vitro biological screening. The results showed that compound 7 has promising antifungal activity against selected fungal strains. Computational study was also carried out to find antimalarial efficacy of the synthesized compounds. Compounds (2-7) were tested for cytotoxicity by MTT assay, and no considerable cytotoxicity was observed. Molecular docking study was performed to predict the binding modes of new compound (7). The docking results revealed that the compound has strong attraction towards the target protein, as characterized by good bonding networks. On the basis of the acquired results, it can be predicted that compound (7) might show good inhibitory activity against dengue envelope protein.

https://ift.tt/2EauOea

Prospective Evaluation of a Rapid Functional Assay for Heparin-Induced Thrombocytopenia Diagnosis in Critically Ill Patients

Objectives: Overdiagnosis of heparin-induced thrombocytopenia remains an unresolved issue in the ICU leading to the unjustified switch from heparin to alternative anticoagulants or delays in anticoagulation. Platelet function assays significantly improve the specificity of heparin-induced thrombocytopenia diagnosis, but they are not readily available, involve technical difficulties and have a long turnaround time. We evaluated the performance of a rapid and easy to perform functional assay for heparin-induced thrombocytopenia diagnosis in ICU patients, known as "heparin-induced multiple electrode aggregometry." Design: In this observational prospective study patients were tested with the immunoglobulin G enzyme-linked immunosorbent assay, the serotonin release assay and heparin-induced multiple electrode aggregometry. Heparin-induced multiple electrode aggregometry was assessed against heparin-induced thrombocytopenia diagnosis (clinical picture in favor, serotonin release assay, and immunoglobulin G enzyme-linked immunosorbent assay positive) and serotonin release assay. Setting: Medical or surgical ICU of 35 medical centers. Patients: Patients suspected for heparin-induced thrombocytopenia hospitalized in medical or surgical ICU from January 2013 to May 2013. Interventions: None. Measurements and Main results: Heparin-induced thrombocytopenia diagnosis was retained in 12 patients (14%). Using heparin-induced thrombocytopenia diagnosis as reference, heparin-induced multiple electrode aggregometry showed an excellent negative predictive value and sensitivity, at 98% and 92% respectively. Its positive predictive value and specificity were 100%. Receiver operating characteristic analysis with the serotonin release assay as reference showed an optimal heparin-induced multiple electrode aggregometry cut-off at 1,300 AU × minutes (specificity, 100%; sensitivity, 90%; area under the curve, 0.98; 95% CI, 0.95–1.0). The Kappa coefficient between heparin-induced multiple electrode aggregometry and the serotonin release assay was at 0.90%. Conclusions: Heparin-induced multiple electrode aggregometry performed very well in heparin-induced thrombocytopenia diagnosis in ICU patients and agreed with the gold standard test for heparin-induced thrombocytopenia diagnosis, the serotonin release assay. Heparin-induced multiple electrode aggregometry is a reliable and rapid platelet functional assay that could decrease heparin-induced thrombocytopenia overdiagnosis in the ICU setting. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). The authors have disclosed that they do not have any potential conflicts of interest. All assays were performed at the Division of Hematology Laboratory of the Tenon University Hospital in Paris, France. Blood samples of patients were collected from surgical and medical ICUs of 35 hospitals located in Paris and its suburbs. For information regarding this article, E-mail: vasiliki.gkalea@aphp.fr Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2DVJUmF

Prediction of ICU Delirium: Validation of Current Delirium Predictive Models in Routine Clinical Practice

Objectives: To investigate the ability of available delirium risk assessment tools to identify patients at risk of delirium in an Australian tertiary ICU. Design: Prospective observational study. Setting: An Australian tertiary ICU. Patients: All patients admitted to the study ICU between May 8, 2017, and December 31, 2017, were assessed bid for delirium throughout their ICU stay using the Confusion Assessment Method for ICU. Patients were included in this study if they remained in ICU for over 24 hours and were excluded if they were delirious on ICU admission, or if they were unable to be assessed using the Confusion Assessment Method for ICU during their ICU stay. Delirium risk was calculated for each patient using the prediction of delirium in ICU patients, early prediction of delirium in ICU patients, and Lanzhou models. Data required for delirium predictor models were obtained retrospectively from patients medical records. Interventions: None. Measurements and Main Results: There were 803 ICU admissions during the study period, of which 455 met inclusion criteria. 35.2% (n = 160) were Confusion Assessment Method for ICU positive during their ICU admission. Delirious patients had significantly higher Acute Physiology and Chronic Health Evaluation III scores (median, 72 vs 54; p

https://ift.tt/2QDaIPz

Detecting Early Markers of Ventilator-Associated Pneumonia by Analysis of Exhaled Gas

Objectives: The detection of microbial volatile organic compounds or host response markers in the exhaled gas could give an earlier diagnosis of ventilator-associated pneumonia. Gas chromatography-ion mobility spectrometry enables noninvasive, rapid, and sensitive analysis of exhaled gas. Using a rabbit model of ventilator-associated pneumonia we determined if gas chromatography-ion mobility spectrometry is able to detect 1) ventilator-associated pneumonia specific changes and 2) bacterial species-specific changes in the exhaled gas. Design: Experimental in vivo study. Setting: University research laboratory. Subjects: Female New Zealand White rabbits. Interventions: Animals were anesthetized and mechanically ventilated. To induce changes in the composition of exhaled gas we induced ventilator-associated pneumonia via endobronchial instillation of either Escherichia coli group (n = 11) or Pseudomonas aeruginosa group (n = 11) after 2 hours of mechanical ventilation. In a control group (n = 11) we instilled sterile lysogeny broth endobronchially. Measurements and Main Results: Gas chromatography-ion mobility spectrometry gas analysis, CT scans of the lungs, and blood samples were obtained at four measurement points during the 10 hours of mechanical ventilation. The volatile organic compound patterns in the exhaled gas were compared and correlated with ventilator-associated pneumonia severity. Sixty-seven peak areas showed changes in signal intensity in the serial gas analyses. The signal intensity changes in 10 peak regions differed between the groups. Five peak areas (P_648_36, indole, P_714_278, P_700_549, and P_727_557) showed statistically significant changes of signal intensity. Conclusions: This is the first in vivo study that shows the potential of gas chromatography-ion mobility spectrometry for early detection of ventilator-associated pneumonia specific volatile organic compounds and species differentiation by noninvasive analyses of exhaled gas. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by a young investigators grant provided by the Medical Faculty of the Georg-August-University Göttingen. Dr. Kunze-Szikszay's institution received funding from Medical Faculty of the Georg-August-University Göttingen, and he received support for article research from Medical Faculty of the Georg-August-University Göttingen. Dr. Perl received funding from Humedics, The37°Company, and MSD Sharp and Dohme GmbH (Haar, Germany). The remaining authors have disclosed that they do not have any potential conflicts of interest. This work was performed at the University Medical Centre of Göttingen, Göttingen, Germany. For information regarding this article, E-mail: nkunze@gwdg.de Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2DVJTz7

MiR-23a-3p-regulated abnormal acetylation of FOXP3 induces regulatory T cell function defect in Graves’ disease

Journal Name: Biological Chemistry
Issue: Ahead of print


https://ift.tt/2Q9m6Dd

The comparative biochemistry of viruses and humans: an evolutionary path towards autoimmunity

Journal Name: Biological Chemistry
Issue: Ahead of print


https://ift.tt/2RzmQ1f

Ability to detect endodontic complications using three different CBCT units with and without artefact reduction modes: an ex vivo study

Abstract

Aim

To assess observer performance in detecting endodontic complications using three different CBCT units with and without the application of artefact reduction modes.

Methodology

The study involved 40 freshly extracted human mandibular teeth (n=10 per group) and divided randomly into four endodontic complication groups. Group 1) Instrument fracture; Group 2) Strip perforation; Group 3) Canal underfilling; Group 4) Canal overfilling. Images of each tooth were obtained using three different CBCT units offering artefact reduction algorithms: the ProMax 3D Max, the Pax Flex 3D, and the Dentri S. Four observers evaluated the images for the presence/absence of the four simulated endodontic complications. Weighted kappa coefficients and intra‐class correlation coefficients (ICCs) were calculated to reveal the intra‐ and inter‐observer agreement for each imaging mode, respectively. Receiver operating characteristic (ROC) analysis was used to evaluate the observers'performance. DeLong tests were used to compare the results for each image mode and observer using a significance level of α=0.05.

Results

In each of the four simulated endodontic complication groups, no significant differences were observed with and without application of artefact reduction for any of the three CBCT units tested. Only two significant differences were detected, and both were between the ProMax 3D Max at low mode AR and ProMax 3D Max without AR: observer 2 in group 1 (p=0.0001) and observer 4 in group 4 (p=0.0256).

Conclusion

For each of the three CBCT units tested, application of artefact reduction for detecting endodontic complications is not recommended as a routine tool.

This article is protected by copyright. All rights reserved.

https://ift.tt/2rgq6CQ

An In Vivo Method to Study Mouse Blood-Testis Barrier Integrity

Here, we present a protocol to assess the blood-testis barrier integrity by injecting inulin-FITC into testes. This is an efficient in vivo method to study blood-testis barrier integrity that can be compromised by genetic and environmental elements.

https://ift.tt/2PbVADH

Enhancement of lipid content and inflammatory cytokine secretion in SZ95 sebocytes by palmitic acid suggests a potential link between free fatty acids and acne aggravation

Abstract

A relationship between acne and free fatty acids (FFAs) has been suggested recently. However, the effects of FFAs on sebaceous glands are still largely unknown. At the same time, the role of FFAs during chronic inflammation is well established. Considering that FFAs are also a major component of sebum, it is likely that changes in FFA affect both the synthesis of sebum and the inflammatory response in sebaceous glands.

In this study, we examined a hypothesis that FFAs increase the production of sebum and induce inflammation in the sebaceous glands. We found that treatment of SZ95 sebocytes with exogenously applied palmitic acid (PA), a major saturated FFA, induced a significant increase in intracellular lipid levels. Moreover, PA treatment also increased the expression and secretion of the proinflammatory cytokines in SZ95 sebocytes. We also found that Toll‐like receptors were required for the inflammatory response triggered by PA.

The results of our study strengthen the notion about the link between acne and FFAs and suggest the mechanism underlying this relationship. Our results serve as a foundation for future work that will explore the association between FFA and acne and pave way to the development of novel treatment options for acne.

This article is protected by copyright. All rights reserved.

https://ift.tt/2Ea9sxl

Ultraviolet radiation, both UVA and UVB, influences the composition of the skin microbiome

Abstract

Background

Studies have begun to investigate the complex relationship between host and microorganisms in non‐infectious pathologies such as acne, atopic dermatitis, and psoriasis. Though the skin is exposed to environmental stressors such as ultraviolet radiation (UVR), no studies exist examining the effects of both UVA and UVB on the skin microbiome.

Objective

To test the effect of UVA and UVB on human skin microbiome.

Methods

To test whether UV will alter the cutaneous microbiome, participants were exposed to doses of UVA (22‐47 J/cm²) or UVB (100‐350 mJ/cm²) and samples were collected. DNA was isolated and sequenced to identify the microbial composition of each sample.

Results

There was vast intra‐ and inter‐subject variation at all time points and phylum and species‐level differences were identified. These included an increase in the phylum Cyanobacteria and a decrease in the family Lactobacillaceae and Pseudomonadaceae. The sensitivity of microbes to UVR and their re‐colonization potential following exposure differed in UVA vs UVB samples.

Limitations

The sample size was small, and the study was limited to males.

Conclusion

The results demonstrate that UVR has profound qualitative and quantitative influences on the composition of the skin microbiome, possibly effecting skin pathology in which UVR is a factor.

This article is protected by copyright. All rights reserved.

https://ift.tt/2SqJrx0

Pigmented skin lesions displaying regression features: dermoscopy and reflectance confocal microscopy criteria for diagnosis

Abstract

Melanomas and nevi displaying regression features can be difficult to differentiate.

To describe reflectance confocal microscopy features in benign and malignant pigmented skin lesions characterized by regression features in dermoscopy.

Methods: Observational retrospective study. Inclusion criteria were presence of dermoscopic features of regression; availability of clinical, dermoscopic and RCM imaging; definite histopathologic diagnosis.

The study sample comprised 217 lesions; 108 (49.8%) melanomas and 109 were benign lesions, of which 102 (47.0%) nevi and 7 (3.2%) lichen planus like keratosis (lplk). Patients with melanoma were significantly older than those with benign lesions (61.9±15.4 vs. 46.1±14.8; p<0.001) and a higher proportion of melanomas displayed dermoscopic regression structures in more than 50% of lesion surface (n=83/108; 76.9%; p<0.001). On RCM examination, pagetoid cells were significantly more reported in melanoma group, than in benign lesions (86.1% vs. 59.6%; p<0.001) and were more frequently widespread distributed (65.6% vs. 20.0%; p<0.001) and both dendritic and roundish (36.6% vs. 15.4%; p<0.001) in shape. Aspecific architecture at the dermo‐epidermal junction (DEJ) was more commonly seen among melanomas than benign lesions (23.1% vs. 11.9%; p=0.002) with higher presence of dendritic and both dendritic and roundish atypical cells at the DEJ (28.7% vs. 18.3% and 19.4% vs. 3.7%; p<0.001, respectively). Focal pagetoid infiltration and ringed or clod patterns were more commonly seen in benign lesion.

In conclusion, the correct interpretation of regressing lesions remains a challenge, assessing carefully the extent and characteristics of architectural and cytologic atypia on RCM is an additional piece of the complex puzzle of melanoma diagnosis.

This article is protected by copyright. All rights reserved.

https://ift.tt/2Ea3jRD

Periodic patterns in Rodentia: development and evolution

Abstract

Mammalian periodic pigment patterns, such as spots and stripes, have long interested mathematicians and biologists because they arise from nonrandom developmental processes that are programmed to be spatially constrained, and can therefore be used as a model to understand how organized morphological structures develop. Despite such interest, the developmental and molecular processes underlying their formation remain poorly understood. Here, we argue that Arvicanthines, a clade of African rodents that naturally evolved a remarkable array of coat patterns, represent a tractable model system in which to dissect the mechanistic basis of pigment pattern formation. Indeed, we review recent insights into the process of stripe formation that were obtained using an Arvicanthine species, the African striped mouse (Rhabdomys pumilio), and discuss how these rodents can be used to probe deeply into our understanding of the factors that specify and implement positional information in the skin. By combining naturally evolved pigment pattern variation in rodents with classic and novel experimental approaches, we can substantially advance our understanding of the processes by which spatial patterns of cell differentiation are established during embryogenesis, a fundamental question in developmental biology.

This article is protected by copyright. All rights reserved.

https://ift.tt/2SpPlOC

Dismantling, personalising and optimising internet cognitive-behavioural therapy for depression: a study protocol for individual participant data component network meta-analysis

Introduction

Psychotherapy is a complex intervention, consisting of various components and being implemented flexibly in consideration of individual patient's characteristics. It is then of utmost importance to know which of the various components or combinations thereof are more efficacious, what their specific effect sizes are and which types of patients may benefit more from different components or their combinations.

Methods and analysis

Internet-delivered cognitive–behavioural therapy (iCBT) offers a unique opportunity to systematically review and quantitatively disentangle the efficacy of various components because, unlike face-to-face cognitive–behavioural therapy, it allows identification of constituent components that are actually delivered to patients. We will systematically identify all randomised controlled trials that compared any form of iCBT against another form or a control intervention in the acute phase treatment of adult depression. We will apply component network meta-analysis (cNMA) to dismantle efficacy of individual components. We will use individual participant data in the cNMA to identify participant-level prognostic factors and effect modifiers for different components.

Ethics and dissemination

The investigators of the primary trials will have obtained ethical approval for the data used in the present study and for sharing the data, if this was necessary, according to local requirements and was not covered from the initial ethic assessment. Results from this study will be published in peer-reviewed journals and presented at relevant conferences.

PROSPERO registration number

CRD42018104683.

https://ift.tt/2PfPMsP

Can mid-regional pro-adrenomedullin (MR-proADM) increase the prognostic accuracy of NEWS in predicting deterioration in patients admitted to hospital with mild to moderately severe illness? A prospective single-centre observational study

Objective

To assess the value added to the National Early Warning Score (NEWS) by mid-regional pro-adrenomedullin (MR-proADM) blood level in predicting deterioration in mild to moderately ill people.

Design

Prospective observational study.

Setting

The Medical Admissions Suite of the Royal Victoria Infirmary, Newcastle.

Participants

300 adults with NEWS between 2 and 5 on admission. Exclusion criteria included receiving palliative care, or admitted for social reasons or self-harming. Patients were enrolled between September and December 2015, and followed up for 30 days after discharge.

Outcome measure

The primary outcome measure was the proportion of patients who, within 72 hours, had an acuity increase, defined as any combination of an increase of at least 2 in the NEWS; transfer to a higher-dependency bed or monitored area; death; or for those discharged from hospital, readmission for medical reasons.

Results

NEWS and MR-proADM together predicted acuity increase more accurately than NEWS alone, increasing the area under the curve (AUC) to 0.61 (95% CI 0.54 to 0.69) from 0.55 (95% CI 0.48 to 0.62). When the confounding effects of presence of chronic obstructive pulmonary disease or heart failure and interaction with MR-proADM were included, the prognostic accuracy further increased the AUC to 0.69 (95% CI 0.63 to 0.76).

Conclusions

MR-proADM is potentially a clinically useful biomarker for deterioration in patients admitted to hospital with a mild to moderately severe acute illness, that is, with NEWS between 2 and 5. As a growing number of National Health Service hospitals are routinely recording the NEWS on their clinical information systems, further research should assess the practicality and use of developing a decision aid based on admission NEWS, MR-proADM level, and possibly other clinical data and other biomarkers that could further improve prognostic accuracy.

https://ift.tt/2zE8Vjs

Development and validation of a clinical rule for recognition of early inflammatory arthritis

Objectives

National and international guidelines recommend prompt referral of patients presenting with inflammatory arthritis (IA), but general practitioners (GPs) feel uncertain in their proficiency to detect synovitis through joint examination, the method of choice to identify IA. Our objective was to develop and validate a rule composed of clinical characteristics to assist GPs and other physicians in identifying IA when in doubt.

Design

Split-sample derivation and validation study.

Setting

The Leiden Early Arthritis Recognition Clinic (EARC), a screening clinic for patients in whom GPs suspected but were unsure of the presence of IA.

Participants

1288 consecutive patients visiting the EARC.

Primary and secondary outcome measures

Associations of clinical characteristics with presence of IA were determined using logistic regression in 644 patients, while validating the results in the other 644 patients (split-sample validation). To facilitate application in clinical practice, a simplified rule (with scores ranging from 0 to 7.5) was derived and validated.

Results

IA was identified by a rheumatologist in 41% of patients. In univariable analysis, male gender, age ≥60 years, symptom duration <6 weeks, morning stiffness >60 min, a low number of painful joints (1–3 joints), presence of patient-reported joint swelling and difficulty with making a fist were associated with IA in the derivation data set. Using multivariable analysis, a simplified rule consisting of these seven items was derived and validated, yielding an area under the receiver operator characteristic curve (AUC) of 0.74 (95% CI 0.70 to 0.78) in the derivation data set. Validation yielded an AUC of 0.71 (95% CI 0.67 to 0.75). Finally, the model was repeated to study predicted probabilities with a lower prevalence of inflammatory arthritis to simulate performance in primary care settings.

Conclusions

Our rule, composed of clinical parameters, had reasonable discriminative ability for IA and could assist physicians in decision-making in patients with suspected IA, increasing appropriateness of healthcare utilisation.

https://ift.tt/2Pf2d8y

Using competing risk and multistate model to estimate the impact of nosocomial infection on length of stay and mortality in burn patients in Southeast China

Objective

Due to the defects in skin barrier function and immune response, burn patients who survive the acute phase of a burn injury are at a high risk of nosocomial infection (NI). The aim of this study is to evaluate the impacts of NI on length of stay (LOS) and hospital mortality in burn patients using a multistate model.

Design and setting

A retrospective observational study was conducted in burn unit and intensive care unit in the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Participants

Data were obtained from 1143 records of patients admitted with burn between 1 January 2013 and 31 December 2016.

Methods

Risk factors for NIs were determined by binary logistic regression. The extended Cox model with time-varying covariates was used to determine the impact of NIs on hospital mortality, and cumulative incidence functions were calculated. Multiple linear regression analysis was applied to detect the variables associated with LOS. Using a multistate model, the extra LOS due to NI were determined.

Results

15.8% of total burn patients suffered from NIs and incidence density of NIs was 9.6 per 1000 patient-days. NIs significantly increased the rate of death (HR 4.266, 95% CI 2.218 to 8.208, p=0.000). The cumulative probability of death for patients with NI was greater that for those without NI. The extra LOS due to NIs was 17.68 days (95% CI 11.31 to 24.05).

Conclusions

Using appropriate statistical methods, the present study further illustrated that NIs were associated with the increased cumulative incidence of burn death and increased LOS in burn patients.

https://ift.tt/2zEJrSQ

High-risk basal cell carcinoma excision in primary care: a retrospective observational study of compliance with NICE guidance

Objectives

To assess compliance with 2010 National Institute for Health and Care Excellence (NICE) guidance on cancer services relating to the management of basal cell carcinomas (BCC) in the community, where except in specific circumstances it is recommended that only low-risk BCCs should be excised routinely.

Design and setting

A retrospective observational study of the histopathology reports of BCC excisions received from primary care in two district general hospitals in the South of England. One hundred consecutive BCC excisions were analysed from each hospital.

Outcome measures

The numbers of high-risk BCCs excised in primary care according to histological subtype, anatomical site and age and if these excisions were compliant with NICE 2010 guidance. Completeness of excision and mention of BCC on histology request were secondary outcomes.

Results

Histologically high-risk subtypes were present in 32% (64/200) of BCCs excised in the community. Only 17/64 were excised by general practitioners (GPs) who were accredited to do so. Non-compliance regarding anatomical site occurred in 16% of samples; only one was non-compliant regarding patient age. There was a high overall rate of complete excision (94.5%) with variation in presence of the term BCC on histology request forms.

Conclusions

NICE 2010 guidance relating to BCC excision in primary care was not followed in a considerable number of cases. Compliance with NICE 2010 guidance depends on the ability to recognise high-risk BCCs clinically and manage appropriately. It also shows that despite close supervision by secondary care, there are still failures of compliance.

GP training in identification of subtypes of BCC might be improved, as well as an increase in numbers of GPs accredited to carry out high-risk BCC excisions. Difficulty in diagnosing high-risk histological subtypes of BCC preoperatively should be considered in any future revision of NICE guidance.

https://ift.tt/2Ph0IXv

Effect of fenofibrate on plasma apolipoprotein C-III levels: a systematic review and meta-analysis of randomised placebo-controlled trials

Objectives

This meta-analysis of randomised placebo-controlled clinical trials aimed to assess the effect of fenofibrate on apolipoprotein C-III (apo C-III), a key regulator of triglyceride metabolism.

Materials and methods

Randomised placebo-controlled trials investigating the impact of fenofibrate treatment on apo C-III levels were searched in PubMed-Medline, Scopus, Web of Science and Google Scholar databases from inception to 18 August 2017. Quantitative data synthesis was determined by a random-effects model and generic inverse variance method. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate glycaemic parameter confounders.

Results

Meta-analysis of 10 clinical trials involving 477 subjects showed fenofibrate therapy decreased apo C-III levels (weighted mean difference (WMD) –4.78 mg/dL, 95% CI –6.95 to –2.61, p<0.001; I²66.87%). Subgroup analysis showed that fenofibrate reduced plasma apo C-III concentrations in subgroups of trials with treatment durations of either <12 weeks (WMD –4.50 mg/dL, p=0.001) or ≥12 weeks (WMD: –4.73 mg/dL, p=0.009) and doses of fenofibrate <200 mg/day (WMD –6.33 mg/dL, p<0.001) and >200 mg/day (p=0.006), with no significant difference between the subgroups.

Conclusion

This meta-analysis found that fenofibrate therapy significantly decreases apo C-III levels, an effect evident with both short-term treatment and doses less than 200 mg/day.

https://ift.tt/2zFwFDF

Comparison of the periodontal condition in Korean and Japanese adults: a cross-sectional study

Objectives

Reports from national surveys in South Korea and Japan have indicated that the prevalence of periodontal disease is lower in Korea than in Japan. However, these national surveys have not evaluated factors related to periodontal health condition, including diabetes and metabolic syndrome. This study compared periodontal conditions between Korean and Japanese adults, in the context of general health status.

Design

Cross-sectional study.

Setting

National survey in South Korea (Korean National Health and Nutrition Examination Survey, 'KNHANES') and a population-based study in Japan (Hisayama study); both were conducted in 2012.

Participants

This study included 3574 Korean and 2205 Japanese adults aged 40–79 years.

Outcome measures

Periodontal condition was assessed by using the Community Periodontal Index (CPI). Examiners in Japan underwent clinical calibration training for periodontal examination with a gold-standard examiner from KNHANES, prior to the Hisayama study.

Results

The age-adjusted prevalences of periodontal disease, defined as CPI score ≥3, were 31.4% and 42.1% in South Korea and Japan, respectively (p<0.001). The age-adjusted prevalences of diabetes (p=0.018) and metabolic syndrome (p=0.001) were higher in Korea than in Japan. The numbers of present and filled teeth and percentages of participants who visited a dental clinic in the last 12 months were higher in Japan than in Korea (all p<0.001). Logistic regression analysis showed that the Japanese participants were more likely to have periodontal disease than were the Korean participants, after adjusting for age, sex, occupation, oral health status, oral health behaviour, diabetes and metabolic syndrome.

Conclusions

A higher prevalence of periodontal disease was found in Japanese participants than in Korean participants. Further studies are needed to more clearly elucidate factors underlying the difference in periodontal conditions between the two populations, including those related to the dental healthcare system and dietary intake.

https://ift.tt/2PfE2GM

Timing of household food insecurity exposures and asthma in a cohort of US school-aged children

Objective

Food insecurity is positively associated with asthma, the most common chronic childhood disease, yet directionality is unclear. The objective was to determine the association between exposure to food insecurity in early childhood and the odds of asthma later in childhood.

Design

Data from four waves of the Early Childhood Longitudinal Study-Kindergarten (ECLS-K) cohort, a prospective, dual-frame, multistage probability cluster sampling study of school-aged US children were entered in multivariate logistic regression models, adjusted for covariates. Exposures to food insecurity were based on parental responses to the validated USDA 18-item module at each wave.

Setting

Public and private primary and secondary schools between 1998 and 2007.

Participants

At its inception (1999), the ECLS-K had 20 578 kindergarteners; by the spring of eighth grade (2007), the cohort dropped to 9725 due to attrition. Children missing an exposure, outcome or confounding variable were excluded, final n=6731.

Primary outcome measure

Child's diagnosis of asthma by a healthcare professional as reported by the parent.

Results

Household food insecurity (vs food security) in the year before kindergarten and in second grade had a higher odds of asthma by 18% (95% CI 1.17 to 1.20) and 55% (95% CI 1.51 to 1.55). After removing asthmatics before third grade from the model, food insecurity in second grade was associated with higher odds of asthma at fifth or eighth grades (OR 1.55; 95% CI 1.53 to 1.58), whereas food insecurity in the year before kindergarten had a lower odds at fifth or eighth grades.

Conclusions

Food insecurity in the year before kindergarten and in second grade were associated with a higher odds of asthma in third grade. Food insecurity in second grade retained the signal for increased odds of asthma after third and through eighth grades. Additional research is needed to explore childhood windows of vulnerability to asthma.

https://ift.tt/2zE8V2W

To what extent do education and physical work load factors explain occupational differences in disability retirement due to knee OA? A nationwide register-based study in Finland

Objectives

To examine the association of education and physical work load factors on the occupational differences in disability retirement due to knee osteoarthritis (OA).

Design

Longitudinal study.

Setting

Linkage of several nationwide registers and a job exposure matrix in Finland.

Participants

A total of 1 135 654 Finns aged 30–60 years in gainful employment were followed from 2005 to 2013 for full disability retirement due to knee OA.

Primary and secondary outcome measures

We calculated age-adjusted incidence rates and examined the association of occupation, education and physical work load factors with disability retirement using competing risk regression model. Disability retirement due to other causes than knee OA, old-age retirement and death were treated as competing risk.

Results

A total of 6117 persons had disability retirement due to knee OA. Women had a higher age-adjusted incidence rate than men (72 vs 60 per 100 000 person-years, respectively). In men, a very high risk of disability retirement was found among construction workers, electricians and plumbers (HR 16.6, 95% CI 12.5 to 22.2), service workers (HR 12.7, 95% CI 9.2 to 17.4) and in women among building caretakers, cleaners, assistant nurses and kitchen workers (HR 15.5, 95% CI 11.7 to 20.6), as compared with professionals. The observed occupational differences were largely explained by educational level and noticeably mediated by physical work load factors in both genders.

Conclusion

Our observational study suggests that the risk of disability retirement among manual workers is strongly attributed to the physically heavy work.

https://ift.tt/2Pdb6iL

Assessment of surgical outcomes of femtosecond laser-assisted in situ keratomileusis in patients with low compliance to postoperative follow-up: a retrospective observational study in a tertiary hospital in China

Objectives

Poor follow-up after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) is common in general clinical practice. We aimed to assess the surgical outcomes of patients with poor compliance to FS-LASIK follow-up but who returned to the clinic with additional prompting at a 1-year visit. We also compared their surgical outcomes with those of patients who returned unprompted.

Design

Retrospective and observational study.

Setting

An urban tertiary hospital in China.

Participants

We reviewed the medical records of myopic patients who underwent binocular FS-LASIK. These patients were all recommended, but not compulsively required, to return for termly postoperative examinations including measurement of uncorrected distance visual acuity (UDVA), refraction and assessment of complications. According to records of follow-up visits, 1009 eligible patients were categorised as follows: (1) 124 who returned unprompted at the 1-year visit (group 1) and (2) 885 lost to follow-up at the 1-year visit. We randomly selected and called back 105 (group 2) out of the 885 patients for an extra postoperative examination.

Results

At the 1-year visit, the visual outcomes of the two groups of patients were comparable. No differences in postoperative UDVA were found between the two groups (–0.02±0.06 logarithm of the minimum angle of resolution (logMAR) and –0.02±0.05 logMAR for groups 1 and 2, respectively, p=0.175). Patients in group 2 showed greater hyperopic dioptres than patients in group 1 (0.37±0.59 D vs –0.29±0.69, p<0.0001). No vision-threatening complications were observed in either group of patients.

Conclusions

The visual and refractive outcomes of patients who were lost to follow-up after FS-LASIK surgery were good and comparable to those who returned unprompted. The results indicated that rigorous postoperative follow-up may be unnecessary in general clinical practice, except for patients who are at a high risk for postoperative complications.

https://ift.tt/2zDba6n

Clinical indicators for reporting the effectiveness of patient quality and safety-related interventions: a protocol of a systematic review and Delphi consensus process as part of the international Standardised Endpoints for Perioperative Medicine initiative (StEP)

Introduction

Clinical indicators are used to measure and quantify the safety and quality of patient care. They are also often used as endpoints in clinical trials. Definitions of clinical indicators in common use are extremely heterogeneous, limiting their applicability. As part of the international Standardised Endpoints in Perioperative Medicine initiative, this study will identify clinical indicators by systematically reviewing the anaesthesia and perioperative medicine literature, and will provide consensus, clinically useful definitions for those indicators using a Delphi process.

Methods and analysis

An electronic database search will be conducted of Medline (PubMed/OVID), EMBASE and the Cochrane Library in order to meet this review's objectives that are: (1) To identify clinical indicators and their definitions used in randomised controlled trials that assess patient-related quality and safety interventions in perioperative medicine; (2) To select a shortlist of recommended indicators and definitions that are the most suitable for evaluation of quality and safety interventions following an expert-based consensus-gaining process (Delphi method) and (3) To provide a classification scale for each indicator related to its clarity of definition, validity (strength), reliability, feasibility (ease of use) and frequency of use. This systematic review protocol is reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidance.

Ethics and dissemination

Ethical approval is not required for this systematic review and Delphi process. The results of this study will be disseminated to the anaesthesia and perioperative medicine clinical and academic community through national and international presentations and through publication in a peer reviewed journal.

PROSPERO registration number

CRD42016042102.

https://ift.tt/2PfGPzN

Being there: protocol for a scoping review of the medical education literature on grief support training for medical professionals

Introduction

Medical trainees and professionals do not perceive that they are adequately taught the skills to address issues of grief with their patients. Atypical grief responses can prolong suffering, interrupt normal activities and lead to increased morbidity and mortality. Grief training can help physicians cope with feelings about and responses to suffering, loss and death in a way that improves both physician and patient/family wellness. This scoping review will describe the current landscape of grief training worldwide in medical school and residency and in continuing professional development in the disciplines of paediatrics, family medicine and psychiatry. The ultimate goal is to help physicians support patients experiencing grief.

Methods and analysis

The study design has been adapted from Arksey and O'Malley's review methodology. We will work with an information specialist who will run searches in six multidisciplinary databases. To supplement the search, we will scan the reference lists of included studies. Two levels of screening will take place: a title and abstract review for articles that fit predefined criteria and a full-text review of articles that meet those criteria. To be included in the review, articles must report on grief training for medical residents and professionals in the fields of paediatrics, family medicine and psychiatry. Two investigators will review each article and extract data.

Ethics and dissemination

Research ethics approval is not required for this review. We plan to share the findings through national and international medical education conferences and to publish the results in a peer-reviewed academic journal. We have the support of several directors of medical education at our institution who are interested in the growing focus on humanism in medical education as a way of decreasing burnout among medical students, residents and faculty.

https://ift.tt/2zByFwQ

PARENTS 2 Study: a qualitative study of the views of healthcare professionals and stakeholders on parental engagement in the perinatal mortality review--from 'bottom of the pile to joint learning

Objective

Engaging bereaved parents in the review process that examines their care before and after a perinatal death might help parents deal with their grief more effectively and drive improvements in patient safety. The objective of this study is to explore whether healthcare professionals would accept or support parent engagement in the perinatal mortality review process.

Design

Qualitative focus group interviews. Transcripts were analysed with an inductive thematic approach.

Setting

Two geographically distinct tertiary maternity hospitals in the UK.

Participants

Five focus groups were conducted with clinical staff including midwives, obstetricians, neonatologists, nursing staff and chaplaincy services.

Results

Twenty-seven healthcare professionals unanimously agreed that parents' involvement in the perinatal mortality review process is useful and necessary. Six key themes emerged including: parental engagement; need for formal follow-up; critical structure of perinatal mortality review meeting; coordination and streamlining of care; advocacy for parents including role of the bereavement care lead; and requirement for training and support for staff to enable parental engagement.

Conclusions

Healthcare professionals strongly advocated engaging bereaved parents in the perinatal mortality review: empowering parents to ask questions, providing feedback on care, helping generate lessons and providing them with the opportunity to discuss a summary of the review conclusions with their primary healthcare professional contact. The participants agreed it is time to move on from 'a group of doctors reviewing notes' to active learning and improvement together with parents, to enable better care and prevention of perinatal death.

https://ift.tt/2PfPx0T

Acupuncture for migraine: a protocol for a meta-analysis and meta-regression of randomised controlled trials

Introduction

Although the effectiveness of acupuncture for episodic migraine has been confirmed by multiple clinical trials and Cochrane systematic reviews, the mechanisms underlying the specific effect of acupuncture for migraine remain controversial. We aim to evaluate the effectiveness and safety of acupuncture for both episodic migraine and chronic migraine by meta-analysis and explore the possible factors influencing the specific effect of acupuncture for migraine by meta-regression.

Methods and analysis

We will search for randomised control trials of acupuncture for migraine in the following eight databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED (via OVID) and four Chinese databases (Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database and Wanfang Database) from inception to 31 December 2017. We will also search OpenSIGLE (opensigle.inist.fr) for conference abstracts. No language restriction will be applied. The selection of studies, data extraction and coding and assessment of risk of bias of the included studies will be conducted independently by two reviewers. Standard meta-analysis and, if appropriate, meta-regression will be performed using the R packages Meta and Metafor.

Ethics and dissemination

The results of this meta-analysis and meta-regression will be disseminated through publication in a peer-reviewed journal and presented at a relevant conference. The data used in this meta-analysis will not contain individual patient data; therefore, ethical approval is not required.

PROSPERO registration number

CRD42018087270.

https://ift.tt/2zzP6th

Impact of selective reporting of antibiotic susceptibility test results in urinary tract infections in the outpatient setting: a protocol for a pragmatic, prospective quasi-experimental trial

Introduction

Antibiotic resistance is a serious and increasing worldwide threat to global public health. One of antibiotic stewardship programmes' objectives are to reduce inappropriate broad-spectrum antibiotics' prescription. Selective reporting of antibiotic susceptibility test (AST) results, which consists of reporting to prescribers only few (n=5-6) antibiotics, preferring first-line and narrow-spectrum agents, is one possible strategy advised in recommendations. However, selective reporting of AST has never been evaluated using an experimental design.

Methods and analysis

This study is a pragmatic, prospective, multicentre, controlled (selective reporting vs usual complete reporting of AST), before-after (year 2019 vs 2017) study. Selective reporting of AST is scheduled to be implemented from September 2018 in the ATOUTBIO group of 21 laboratories for all Escherichia coli identified in urine cultures in adult outpatients, and to be compared with the usual complete AST performed in the EVOLAB group of 20 laboratories. The main objective is to assess the impact of selective reporting of AST for E. coli-positive urine cultures in the outpatient setting on the prescription of broad-spectrum antibiotics frequently used for urinary tract infections (amoxicillin-clavulanate, third-generation cephalosporins and fluoroquinolones). The primary end point is the after (2019)–before (2017) difference in prescription rates for the previously mentioned antibiotics/classes that will be compared between the two laboratory groups, using linear regression models. Secondary objectives are to evaluate the feasibility of selective reporting of AST implementation by French laboratories and their acceptability by organising focus groups and individual semi-structured interviews with general practitioners and laboratory professionals.

Ethics and dissemination

This protocol was approved by French national ethics committees (Comité d'expertise pour les recherches, les études et les évaluations dans le domaine de la santé (TPS 29064) and Commission Nationale de l'Informatique et des Libertés (Décision DR-2018–141)). Findings of this study will be widely disseminated through conference presentations, reports, factsheets and academic publications and generalisation will be further discussed.

Trial registration number

NTC03612297.

https://ift.tt/2Pf2c4u

Correction: Community-deliverable exercise and anxiety in adults with arthritis and other rheumatic diseases: a systematic review with meta-analysis of randomised controlled trials

Kelley GA, Kelley KS, Callahan LF. Community-deliverable exercise and anxiety in adults with arthritis and other rheumatic diseases: a systematic review with meta-analysis of randomised controlled trials. BMJ Open 2018;8:e019138. doi: 10.1136/bmjopen-2017-019138

The original version of this manuscript contained an error in table 4.

Negative signs were missing from confidence intervals that have been replaced in the updated version provided below:

VariableES (n)Participants
(n) X(95% CI) Q (P) I²(95% CI)²Primary outcome Anxiety16883–0.40
(–0.65 to –0.15)*40.3
(<0.001)**62.8
(36.2 to 78.3)0.14Secondary outcomes

https://ift.tt/2zEDCF5

Corrections: Body mass index, waist-to-hip ratio and cognitive function among Chinese elderly: a cross-sectional study

Zhang T, Yan R, Chen Q, et al. Body mass index, waist-to-hip ratio and cognitive function among Chinese elderly: a cross-sectional study. BMJ Open 2018;8:e022055. doi: 10.1136/bmjopen-2018-022055.

This article was previously published with missing equal contributor statement.

Tao Zhang, Rui Yan, and Qifeng Chen, contributed equally to this work.

https://ift.tt/2PcvEba

Protocol for a participatory study for developing qualitative instruments measuring the quality of long-term care relationships

Introduction

In long-term care (LTC), it is unclear which qualitative instruments are most effective and useful for monitoring the quality of the care relationship from the client's perspective. In this paper, we describe the research design for a study aimed at finding and optimising the most suitable and useful qualitative instruments for monitoring the care relationship in LTC.

Methods and analysis

The study will be performed in three organisations providing care to the following client groups: physically or mentally frail elderly, people with mental health problems and people with intellectual disabilities. Using a participatory research method, we will determine which determinants influence the quality of a care relationship and we will evaluate up to six instruments in cooperation with client-researchers. We will also determine whether the instruments (or parts thereof) can be applied across different LTC settings.

Ethics and dissemination

This study protocol describes a participatory research design for evaluating the quality of the care relationship in LTC. The Medical Ethics Committee of the Radboud University Nijmegen Medical Centre decided that formal approval was not needed under the Dutch Medical Research Involving Human Subjects Act. This research project will result in a toolbox and implementation plan, which can be used by clients and care professionals to measure and improve the care relationship from the client's perspective. The results will also be published in international peer-reviewed journals.

https://ift.tt/2zFUKKB

Efficacy and Safety of Hou Gu Mi Xi on Spleen Qi Deficiency in Patients with Nonorganic Gastrointestinal Disorders: Protocol for a Multicenter, Randomized, Placebo-Controlled Trial

Background. There is a worldwide epidemic of nonorganic gastrointestinal disorders (NOGDs), which are a class of disorders that cause various discomforts and ultimately progress into organic gastrointestinal diseases. Because of the unsatisfactory efficacy of Western medical treatments, traditional Chinese medicine (TCM) is becoming a promising complementary and alternative treatment to manage NOGDs. Objectives. To investigate the efficacy and safety of Hou Gu Mi Xi (HGMX), a newly developed dietary TCM formula, on the syndrome of spleen qi deficiency (SQD) in patients with NOGDs. Methods/Design. This study is a multicenter, randomized, double-blinded, parallel, and placebo-controlled trial that will last for 2 years. All qualified subjects with NOGDs and SQD will be included. The study population will be divided into the HGMX and placebo groups. To assess the efficacy of HGMX, we will mainly focus on changes in SQD symptoms scored by a Spleen Qi Deficiency Symptoms Grading and Quantifying Scale and evaluate changes in gastrin-17, the negative Helicobacter pylori conversion rate, body weight, body mass index, and gastroscopy findings. The safety of HGMX will be assessed by recording adverse events (AEs), severe AEs, treatment-related AEs and withdrawal due to AEs. Discussion. This trial is part of our study series that intends to validate the potential of HGMX in the management of chronic gastrointestinal diseases. This series of RCTs is the first committed to the evaluation of a dietary TCM formula and will hopefully establish an evidence-based clinical research model for dietary TCM formulas. Ethics. The protocol was approved by Ethics Committee of five research hospitals and was registered in Clinicaltrials.gov (NCT03019042).

https://ift.tt/2SqVXwl

Zuo Jin Wan Reverses DDP Resistance in Gastric Cancer through ROCK/PTEN/PI3K Signaling Pathway

Gastric cancer (GC) is the third leading cause of cancer-related death. Chemotherapy resistance remains the major reason for GC treatment failure and poor overall survival of patients. Our previous studies have proved that Zuo Jin Wan (ZJW), a traditional Chinese medicine (TCM) formula, could significantly enhance the sensitivity of cisplatin (DDP)-resistant gastric cancer cells to DDP by inducing apoptosis via mitochondrial translocation of cofilin-1. However, the underlying mechanism remains poorly understood. This study aimed to evaluate the effects of ROCK/PTEN/PI3K on ZJW-induced apoptosis in vitro and in vivo. We found that ZJW could significantly activate the ROCK/PTEN pathway, inhibit PI3K/Akt, and promote the apoptosis of SGC-7901/DDP cells. Inhibition of ROCK obviously attenuated ZJW-induced apoptosis as well as cofilin-1 mitochondrial translocation, while inhibition of PI3K had the opposite effects. In vivo, combination treatment of DDP and ZJW (2000 mg/kg) significantly reduced tumor growth compared with DDP alone. Moreover, the combined administration of ZJW and DDP increased the expression of cleaved ROCK and p-PTEN while it decreased p-PI3K and p-cofilin-1, which was consistent with our in vitro results. These findings indicated that ZJW could effectively inhibit DDP resistance in GC by regulating ROCK/PTEN/PI3K signaling and provide a promising treatment strategy for gastric cancer.

https://ift.tt/2U58ffn

Clinical Pharmacology of Citrus aurantium and Citrus sinensis for the Treatment of Anxiety

Objective. The aim of this review is to analyze preclinical and clinical studies investigating the anxiety effects of Citrus aurantium or Citrus sinensis essential oils (EOs). Design. The bibliographic research was made on the major scientific databases. Analysis included only articles written in English and published on peer-reviewed scientific journals describing preclinical experiments and clinical trials carried out to investigate the antianxiety effects of Citrus aurantium or Citrus sinensis EOs on anxiety disorders. Clinical studies reporting the antianxiety effects of products containing Citrus aurantium or Citrus sinensis EOs in combination with other active substances, including medicinal plants, were excluded. Nine clinical studies fulfilled the criteria adopted for analysis. Results. Data show that Citrus aurantium or Citrus sinensis EOs produce anxiolytic effects both in preclinical experiments and in different clinical conditions. Citrus aurantium EO aromatherapy reduced anxiety level in the great part of stress conditions studied (subjects affected by chronic myeloid leukemia and preoperative patients) except for a sample of patients subjected to colonoscopy. Exposition to Citrus sinensis EO in clinical studies shows to be positive in reducing anxiety level in patients waiting for dental treatment as well as in healthy volunteers submitted to an anxiogenic situation. Conclusions. Overview of clinical trials conducted with Citrus aurantium or Citrus sinensis on people with anxiety showed that inhalation or oral administration of Citrus aurantium and inhalation of Citrus sinensis can exert beneficial effects on anxiety; however, because of incomplete accuracy in the reporting of methodology, further more complete clinical studies are warranted.

https://ift.tt/2AGBPix

Effect of Implant‐Supported Mandibular Overdentures versus Reline on Masticatory Performance and Salivary Flow Rates in Very Old Adults ‐ a randomized clinical trial

Abstract

Purpose

To compare the masticatory efficiency (ME), maximum voluntary bite force (MBF), masseter muscle thickness (MMT) and salivary flow rates (SFR) in completely edentulous dependent elders treated either with a conversion of their existing mandibular complete removable dental prostheses (CRDP) into a 2‐implant overdenture (IOD) or a conventional reline of the CRDP.

Material and Methods

Participants were randomly allocated into intervention (IG), and control (CG) group. The IG received two implants in the mandibular canine regions and their CRDPs were transformed into IODs. The CG received a conventional reline of their mandibular CRDPs. Outcomes were recorded at each recall visit (baseline, immediately‐, 3 months‐, 12 months‐ after intervention and, subsequently on an annual basis). Statistical analyses used mixed linear regression models (level of significance: p<0.05).

Results

The IG comprised 16 participants (age=85.0±6.2 years), while the CG comprised 16 (age=84.8±5.4 years), with a mean follow‐up of 2.7± 2.2 years (range 3m to 7y). A significant increase of MBF in the IG (p<0.001) was observed with an overall gain of 80 N (p<0.001) compared with the reline group. There were no significant long‐term changes in SFR, MMT, or ME within/between groups.

Conclusion

Since dependent elders with mandibular IODs present a significant gain in MBF, but no relative increase in SFR, MMT, and ME, it seems that this increased capacity of MBF is not exploited by the elders during their habitual chewing.

This article is protected by copyright. All rights reserved.

https://ift.tt/2RqHdNO

Altered Functional Network Affects Amyloid and Structural Covariance in Alzheimer’s Disease

Background. We aimed to investigate how altered intrinsic connectivity networks (ICNs) affect pathologic changes of Alzheimer's disease (AD) at a network-based level. Methods. Thirty normal controls (NCs), 23 patients with AD-mild cognitive impairment (MCI), and 20 patients with AD-dementia were enrolled. We compared the organization of grey matter structural covariance and functional connectivity in ICNs between NCs and all AD patients who were amyloid β (Aβ)-positive. We further used seed-based interregional covariance analysis to compare structural and Aβ plaque covariance in default mode network (DMN) between AD-MCI and AD-dementia groups. Results. The patients with AD had increased functional interregional covariance among the regions of the ICN anchored to dorsal caudate (DC) seeds compared to the NCs. The increased connectivity was associated with extended patterns of reduced Aβ plaque covariance in the AD-dementia group compared to the AD-MCI group within the striatal network anchored to DC seeds. Patterns of lower Aβ plaque covariance in the AD-dementia group compared to the AD-MCI group were more extended within the network anchored to DC seeds than within the DMN, which was undergoing functional failure in the patients with AD. Significant decreased structural covariance in the AD-dementia group compared to the AD-MCI group was more extended in the DMN during functional failure. Conclusions. Functional connectivity in ICNs affects the topographic spread of molecular pathologies. The temporal trajectory of pathologic alterations can be well demonstrated by pathologic covariance comparisons between different clinical stages. Pathologic covariance can provide critical support to pathologic interactions at network and molecular levels.

https://ift.tt/2FXdzOX

Streptococcus thoraltensis Bacteremia: First Described Case as a Fever of Unknown Origin in Human

Streptococcus thoraltensis has mainly been reported to cause infections in animals. Its clinical significance as a human pathogen has not yet been fully elucidated and needs further investigation. We describe here a case of bacteremia attributed to S. thoraltensis in a 55-year-old female patient admitted to our department due to fever of unknown origin. To the best of our knowledge, this is the first reported case of S. thoraltensis bacteremia in a human and the first reported case of S. thoraltensis as a cause of fever of unknown origin in human.

https://ift.tt/2EaAhS6

Noncontrast Computed Tomography Parameters for Predicting Shock Wave Lithotripsy Outcome in Upper Urinary Tract Stone Cases

Kidney stones are a major public health concern with continuously increasing worldwide prevalence. Shock wave lithotripsy (SWL) is the first line treatment choice for upper urinary tract calculi with ureteroscopy and has advantages of safety and noninvasiveness, but the treatment success rate of SWL is lower than that of other therapies. It is therefore important to identify predictive factors for SWL outcome and select a suitable treatment choice for patients with upper urinary tract calculi. In recent years, computed tomography (CT) has become the gold standard for diagnosis of upper urinary tract calculi. Several factors based on CT images, including skin-to-stone distance, mean stone density, stone heterogeneity index, and variation coefficient of stone density, have been reported to be useful for predicting SWL outcome. In addition, a new method of analysis, CT texture analysis, is reportedly useful for predicting SWL outcomes. This review aims to summarize CT parameters for predicting the outcome of shock wave lithotripsy in stone cases in the upper urinary tract.

https://ift.tt/2RtY0Qe

Neuroprotection by Paeoniflorin against Nuclear Factor Kappa B-Induced Neuroinflammation on Spinal Cord Injury

Background. Acute spinal cord injury (SCI) is one of the most common and devastating causes of sensory or motor dysfunction. Nuclear factor-kappa B(NF-κB)-mediated neuroinflammatory responses, in addition to nitric oxide (NO), are key regulatory pathways in SCI. Paeoniflorin (PF), a major active component extracted from Paeonia roots, has been suggested to exert neuroprotective effects in the central nervous system. However, whether PF could improve the motor function after SCI in vivo is still unclear. Method. Immunohistochemical analysis, western blot, real-time quantitative PCR, immunofluorescence staining, and histopathological and behavioral evaluation were used to explore the effects of paeoniflorin after SCI for 14 days. Results. In this study, PF treatment significantly inhibited NF-κB activation and downregulated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2(COX-2), and Nogo-A. Comparing behavioral and histological changes in SCI and PF treatment groups, we found that PF treatment improved motor function recovery, attenuated the histopathological damage, and increased neuronal survival in the SCI model. PF treatment also reduced expression levels of Bax and c-caspase-3 and increased the expression level of Bcl-2 and cell viabilities. Upregulation of TNF-α, IL-6, and IL-1β after injury was also prevented by PF. Conclusion. These results suggest that the neuroprotective effects of PF are related to the inhibition of the NF-κB signaling pathway. And PF may be a therapeutic strategy in spinal cord injury.

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Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

New England Journal of Medicine, Ahead of Print.


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Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2PcA5CP

Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2Pex8lo

A Matrix Metalloproteinase-1 Polymorphism, MMP1–1607 (1G>2G), Is Associated with Increased Cancer Risk: A Meta-Analysis Including 21,327 Patients

Although the matrix metalloproteinase-1 (MMP1) polymorphism MMP1–1607 (1G>2G) has been associated with susceptibility to various cancers, these findings are controversial. Therefore, we conducted this meta-analysis to explore the association between MMP1–1607 (1G>2G) and cancer risk. A systematic search of literature through PubMed, Embase, ISI Web of Knowledge, and Google Scholar yielded 77 articles with 21,327 cancer patients and 23,245 controls. The association between the MMP1–1607 (1G>2G) polymorphism and cancer risks was detected in an allele model (2G vs. 1G, overall risk [OR]: 1.174, 95% confidence interval [CI]: 1.107–1.244), a dominant model (2G2G/1G2G vs. 1G1G OR, OR: 1.192, 95% CI: 1.090–1.303), and a recessive model (2G2G vs. 1G2G/1G1G, OR: 1.231, 95% CI: 1.141–1.329). In subgroup analysis, these associations were detected in both Asians and Caucasians. After stratification by cancer types, associations were found in lung, colorectal, nervous system, renal, bladder, and nasopharyngeal cancers. This meta-analysis revealed that MMP1–1607 (1G>2G) polymorphism was significantly associated with elevated risk of cancers.

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Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2PcA5CP

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2zCzcyp

Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2Pex8lo

Effects of Chicory on Serum Uric Acid, Renal Function, and GLUT9 Expression in Hyperuricaemic Rats with Renal Injury and In Vitro Verification with Cells

Hyperuricaemia (HUA) is an independent risk factor for chronic kidney disease. Urate crystals are deposited in the kidney and can cause renal tubular interstitial fibrosis, leading to renal dysfunction. Chicory extract (hereafter referred to as chicory) clearly reduced serum uric acid levels in rats with HUA induced by 10% fructose. This is the first study to observe the effect of chicory on serum uric acid levels and renal function in rats with HUA and renal injury. In vivo studies using hyperuricaemic rats with renal injury induced by yeast and adenine demonstrated that chicory decreased serum uric acid level, and its effect of delaying the progression of kidney injury was better than that of benzbromarone. In vitro cell experiments showed that this effect is related to the inhibition of GLUT9 protein expression in renal tubules and that lowering blood uric acid concentrations is one of the factors that alleviates renal damage. The results of this study indicate that chicory can be used as an alternative for alleviating renal dysfunction in hyperuricaemia.

https://ift.tt/2G30tQu

Gallic Acid Attenuates Dimethylnitrosamine-Induced Liver Fibrosis by Alteration of Smad Phosphoisoform Signaling in Rats

Dimethylnitrosamine (DMN) is a potent hepatotoxin, carcinogen, and mutagen. In our previous study, a candidate gallic acid (GA) that widely exists in food and fruit was selected for its capability to alleviate DMN toxicity in vivo. We aimed to investigate the therapeutic potential of GA against DMN-induced liver fibrosis. During the first four weeks, DMN was administered to rats via intraperitoneal injection every other day, except the control group. GA or silymarin was given to rats by gavage once daily from the second to the sixth week. GA significantly reduced liver damage in serum parameters and improved the antioxidant capacity in liver and kidney tissues. Cytokines involved in liver fibrosis were measured at transcriptional and translational levels. These results indicate that GA exhibits robust antioxidant and antifibrosis effects and may be an effective candidate natural medicine for liver fibrosis treatment.

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The Role of Berberine in the Prevention of HIF-1α Activation to Alleviate Adipose Tissue Fibrosis in High-Fat-Diet-Induced Obese Mice

Berberine (BBR) is the main active ingredient of a traditional Chinese herb Coptis chinensis. It has been reported to exhibit beneficial effects in treating diabetes and obesity. However, the underlying mechanism has not been fully elucidated. Adipose tissue fibrosis is a hallmark of obesity-associated adipose tissue dysfunction. HIF-1α plays a key role in adipose tissue fibrosis, which closely linked to metabolic dysfunction in obese state. We hypothesized that BBR may alleviate obesity-induced adipose tissue fibrosis and associated metabolic dysfunction through inhibition of HIF-1α. To test this hypothesis, we treated high fat diet (HFD) feeding mice with different dose of BBR (100 mg/kg, 200 mg/kg, and 300 mg/kg) for 8 weeks. We found that BBR treatment greatly decreased the body weight gain and reduced insulin resistance induced by HFD. Data also revealed that BBR improved histologic fibrous of epididymal white adipose tissue (eWAT) and was accompanied with inhibition of the abnormal synthesis and deposition of extracellular matrix (ECM) proteins, such as collagen and fibronectin. We also found that BBR treatment suppressed the expression of HIF-1α and decreased the mRNA expression of LOX in epididymal adipose tissue, which plays a key role in fibrosis development. Taken together, these results suggest that BBR can regulate metabolic homeostasis and suppress adipose tissue fibrosis through inhibiting the expression of HIF-1α.

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Ethanol Extract of Cudrania tricuspidata Leaf Ameliorates Hyperuricemia in Mice via Inhibition of Hepatic and Serum Xanthine Oxidase Activity

Cudrania tricuspidata Bureau (Moraceae) (CT) is a dietary and medicinal plant distributed widely in Northeast Asia. There have been no studies on the effect of CT and/or its active constituents on in vivo xanthine oxidase (XO) activity, hyperuricemia, and gout. The aim of this study was to investigate XO inhibitory and antihyperuricemic effects of the ethanol extract of CT leaf (CTLE) and its active constituents in vitro and in vivo. Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) analyses were used to determine a chemical profile of CTLE. XO inhibitory and antihyperuricemic effects of CTLE given orally (30 and 100 mg/kg per day for 1 week) were examined in potassium oxonate-induced hyperuricemic ICR mice. CTLE exhibited XO inhibitory activity in vitro with an IC50 of 368.2 μg/mL, significantly reduced serum uric acid levels by approximately 2-fold (7.9 nM in normal mice; 3.8 nM in 30 mg/kg CTLE; 3.9 nM in 100 mg/kg CTLE), and significantly alleviated hyperuricemia by reducing hepatic (by 39.1 and 41.8% in 30 and 100 mg/kg, respectively) and serum XO activity (by 30.7 and 50.1% in 30 and 100 mg/kg, respectively) in hyperuricemic mice. Moreover, several XO inhibitory and/or antihyperuricemic phytochemicals, such as stigmasterol, β-sitosterol, vitamin E, rutin, and kaempferol, were identified from CTLE. Compared with rutin, kaempferol showed markedly higher XO inhibitory activity in vitro. Our present results demonstrate that CTLE may offer a promising alternative to allopurinol for the treatment of hyperuricemia and gout.

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Enhanced Recovery After Surgery (ERAS) Eliminates Racial Disparities in Postoperative Length of Stay After Colorectal Surgery

Objective: To investigate the effects of enhanced recovery after surgery (ERAS) on racial disparities in postoperative length of stay (pLOS) after colorectal surgery. Background: Racial disparities in surgical outcomes exist. We hypothesized that ERAS would reduce disparities in pLOS between black and white patients. Methods: Patients undergoing ERAS in 2015 were 1:1 matched by race/ethnicity, age, sex, and procedure to a pre-ERAS group from 2010 to 2014. After stratification by race/ethnicity, expected pLOS was calculated using the American College of Surgeons National Surgical Quality Improvement Project Risk Calculator. Primary outcome was the observed pLOS and observed-to-expected difference in pLOS. Secondary outcomes were National Surgical Quality Improvement Project postoperative complications including 30-day readmissions and mortality. Adjusted sensitivity analyses on pLOS were also performed. Results: Of 420 patients (210 ERAS and 210 pre-ERAS) examined, 28.3% were black. Black and white patients were similar in age, body mass index, sex, American Anesthesia Association class, and minimally invasive approaches. Within the pre-ERAS group, black patients stayed a mean of 2.7 days longer than expected compared with white patients (P

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Grading of Neuroendocrine Carcinomas: Correlation of 68Ga-PET/CT Scan with Tissue Biomarkers

There is a growing need for more accurate biomarkers to facilitate the diagnosis and prognosis of patients with grade (G) 3 neuroendocrine carcinomas (NECs). In particular, the discrimination between well-differentiated neuroendocrine carcinomas (WD-NECs) and poorly differentiated neuroendocrine carcinomas (PD-NECs) is still an unmet need. We previously showed that 68Gallium-(68Ga-) PET/CT positivity is a prognostic factor in patients with gastroenteropancreatic (GEP) G3 NECs, correlating with a better outcome in terms of overall survival. Here, we hypothesize that 68Ga-PET/CT could help to discriminate between WD-NECs and PD-NECs, adding complementary information to that obtained from morphologic and biologic factors. A retrospective, single-institution study was performed on 11 patients with histologically confirmed, measurable G3 large- or small-cell GEP-NECs according to the 2017 WHO classification. The staging procedures included a 68Ga-PET/CT scan. Results of 68Ga-PET/CT were correlated in univariate analysis with loss of tissue immunohistochemical expression of DAXX/ATRX or RB1 frequently associated with WD-NECs or PD-NECs, respectively. None of the patients with positive 68Ga-PET/CT showed loss of RB1 expression, whereas among those () with negative 68Ga-PET/CT, 4 showed loss of expression. A trend towards a correlation between loss of RB1 expression and negative 68Ga-PET/CT was observed. Our preliminary data support the hypothesis that PD-NECs carrying RB1 mutation and loss of its expression may be associated with negative 68Ga-PET/CT. If confirmed in a larger clinical trial, 68Ga-PET/CT would help in the stratification of G3 NECs.

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Rab27b Is a Potential Indicator for Lymph Node Metastasis and Unfavorable Prognosis in Lung Adenocarcinoma

Rab27b is reported to associate with the development and progression of several types of human cancers. However, the relationship between Rab27b expression and the clinical characteristics of lung adenocarcinoma (LUAD) is rarely explored. In this present study, the TCGA database was consulted, followed by one-step quantitative reverse transcription polymerase chain reaction (qPCR), Western blot, and immunohistochemistry (IHC) analyses in LUAD cell lines and tissue samples. Rab27b expression levels were statistically higher in LUAD cell lines and tissue samples compared with a noncancerous cell line and tissue samples (). Rab27b expression was statistically correlated with lymph node metastasis () and TNM stage (). Survival analysis and Kaplan-Meier curve revealed that Rab27b expression () and TNM stage () were independently associated with the unfavorable overall survival of patients with LUAD. These results indicate that high expression of Rab27b correlates with malignant attributes of LUAD and Rab27b may be identified as a potential indicator of metastasis and prognosis for LUAD.

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Drug-Target Interaction Prediction via Dual Laplacian Graph Regularized Matrix Completion

Drug-target interactions play an important role for biomedical drug discovery and development. However, it is expensive and time-consuming to accomplish this task by experimental determination. Therefore, developing computational techniques for drug-target interaction prediction is urgent and has practical significance. In this work, we propose an effective computational model of dual Laplacian graph regularized matrix completion, referred to as DLGRMC briefly, to infer the unknown drug-target interactions. Specifically, DLGRMC transforms the task of drug-target interaction prediction into a matrix completion problem, in which the potential interactions between drugs and targets can be obtained based on the prediction scores after the matrix completion procedure. In DLGRMC, the drug pairwise chemical structure similarities and the target pairwise genomic sequence similarities are fully exploited to serve the matrix completion by using a dual Laplacian graph regularization term; i.e., drugs with similar chemical structure are more likely to have interactions with similar targets and targets with similar genomic sequence similarity are more likely to have interactions with similar drugs. In addition, during the matrix completion process, an indicator matrix with binary values which indicates the indices of the observed drug-target interactions is deployed to preserve the experimental confirmed interactions. Furthermore, we develop an alternative iterative strategy to solve the constrained matrix completion problem based on Augmented Lagrange Multiplier algorithm. We evaluate DLGRMC on five benchmark datasets and the results show that DLGRMC outperforms several state-of-the-art approaches in terms of 10-fold cross validation based AUPR values and PR curves. In addition, case studies also demonstrate that DLGRMC can successfully predict most of the experimental validated drug-target interactions.

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