Structure-Based Design: Synthesis, X-ray Crystallography, and Biological Evaluation of N-Substituted-4-Hydroxy-2-Quinolone-3-Carboxamides as Potential Cytotoxic Agents

Background: Oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has been highlighted as a therapeutic target for anticancer drug design.

Objective: Target compounds were designed to address the effect of different substitution patterns at the N atom of the carboxamide moiety on the bioactivity of this series.

Methods: Synthesis of the targeted compounds, crystallography, biological evaluation tests against human colon carcinoma (HCT-116), and Glide docking studies.

Results: A new series of N-substituted- 4-hydroxy-2-quinolone-3-carboxamides was prepared and characterized by means of FT-IR, 1H and 13C NMR, and elemental analysis. In addition, the identity of the core nucleus 5 was successfully characterized with the aid of X-ray crystallography. Biological activity of prepared compounds was investigated in vitro against human colon carcinoma (HCT-116) cell line. Results revealed that these compounds inhibit cell proliferation and induce apoptosis through an increase in caspase-3 activity and a decrease in DNA cellular content. Compounds 7, 14, and 17 which have H-bond acceptor moiety on p-position displayed promising PI3Kα inhibitory activity. On the other hand, derivatives tailored with bulky and hydrophobic motifs (16 and 18) on o- and m-positions exhibited moderate activity. Molecular docking studies against PI3Kα and caspase-3 showed an agreement between the predicted binding affinity (ΔGobsd) and IC50 values of the derivatives for the caspase-3 model. Furthermore, Glide docking studies against PI3Kα demonstrated that the newly synthesized compounds accommodate PI3Kα kinase catalytic domain and form H-bonding with key binding residues.

Conclusion: The series exhibited a potential PI3Kα inhibitory activity in HCT-116 cell line.

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Pyramidatine (Z88) Sensitizes Vincristine-Resistant Human Oral Cancer (KB/VCR) Cells to Chemotherapeutic Agents by Inhibition of P-glycoprotein

Background: Multi-drug resistance (MDR) remains a major impediment in cancer therapy. A major goal for scientists is to discover more effective compounds that are able to circumvent MDR and simultaneously have minimal adverse side effects.

Objective: In the present study, we aim to determine the anti-MDR effects of pyramidatine (Z88), a cinnamic acid-derived bisamide compound isolated from the leaves of Aglaia perviridis, on KB/VCR (vincristineresistant human oral cancer cells) and MCF-7/ADR (adriamycin-resistant human breast adenocarcinoma) cells.

Methods: Cell viability and average resistant fold (RF) of Z88 were examined by Cell Counting Kit-8 (CCK-8) assay. Flow cytometry, western blot, RT-PCR, Rhodamine 123 accumulation assay and P-glycoprotein (P-gp) ATPase assay were used to demonstrate the anti-MDR activity and mechanism of Z88.

Results: The average RF of Z88 is 0.09 and 0.51 in KB/VCR and MCF-7/ADR cells. A CCK-8 assay showed that Z88 could enhance the cytotoxicity of VCR toward KB/VCR cells. A FACS analysis revealed that Z88 could enhance the VCR-induced apoptosis as well as G2/M arrest in a dose-dependent manner in KB/VCR cells. Western blot results showed that the expression levels of PARP, Bax, and cyclin B1 all increased after treatment with 0.2 µmol/L (µM) of VCR combined with 10 µM of Z88 for 24 h in KB/VCR cells. Z88 also could enhance the accumulation of rhodamine 123. Further studies showed that Z88 could inhibit the verapamil stimulated Pgp ATPase activity. Additionally, qPCR detection and western blot assays revealed that Z88 could decrease the expression of P-gp at both RNA and protein level.

Conclusion: Z88 exerted potent anti-MDR activity in vitro and its mechanisms are associated with dualinhibition of the function and expression of P-gp. These findings encourage efforts to develop more effective reversal agents to circumvent MDR based on Z88.

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Stereocomplexation Assisted Assembly of Poly(γ-glutamic Acid)-graft-polylactide Nano-micelles and Their Efficacy as Anticancer Drug Carrier

Background: Micelles as drug carriers are characterized by their inherent instability due to the weak physical interactions that facilitate the self-assembly of amphiphilic block copolymers. As one of the strong physical interactions, the stereocomplexation between the equal molar of enantiomeric polylactides, i.e., the poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), may be harnessed to obtain micelles with enhanced stability and drug loading capacity and consequent sustained release.

Aims/Methods: In this paper, stereocomplexed micelles gama-PGA-g-PLA micelles) were fabricated from the stereocomplexation between poly(gama-glutamic acid)-graft-PLLA gama-PGA-g-PLA) and poly(gamaglutamic acid)-graft-PDLA gama-PGA-g-PLA). These stereocomplexed micelles exhibited a lower CMC than the corresponding enantiomeric micelles.

Result: Furthermore, they showed higher drug loading content and drug loading efficiency in addition to more sustained drug release profile in vitro. In vivo imaging confirmed that the DiR-encapsulated stereocomplexed gama-PGA-g-PLA micelles can deliver anti-cancer drug to tumors with enhanced tissue penetration. Overall, gama-PGA-g-PLA micelles exhibited greater anti-cancer effects as compared with the free drug and the stereocomplexation may be a promising strategy for fabrication of anti-cancer drug carriers with significantly enhanced efficacy.

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Global Research Highlights

Editor's note: Annals has partnered with a small group of selected journals of international emergency medicine societies to share from each a highlighted research study, as selected monthly by their editors. Our goals are to increase awareness of our readership to research developments in the international emergency medicine literature, promote collaboration among the selected international emergency medicine journals, and support the improvement of emergency medicine world-wide, as described in the WAME statement at https://ift.tt/2pnn4eO.

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Table of Contents

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Adolescent Female With Right Ear Redness

A 16-year-old female adolescent with no medical history presented to the emergency department with 2 days of right ear redness that began after a high-chondral ear piercing. Physical examination revealed tenderness and erythema over the pinna of the right ear, without appreciable fluctuance or abscess formation. Vital signs revealed no abnormalities. The ear piercing was expeditiously removed and a swab of the area was sent for wound culture (Figure).

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Editors

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Putting the Guidelines Ahead of the Evidence for the Use of Transesophageal Echocardiography by Emergency Physicians

Emergency physicians have demonstrated their ability to expeditiously perform and interpret myriad point-of-care ultrasonographic examinations. We have no doubt, therefore, that with proper physician training, transesophageal echocardiography should not be any different. Emergency physicians are often leaders in the adoption of new technologies, and thus we read with great interest the guidelines published by Fair et al1 on the use of transesophageal echocardiography in the emergency department (ED).

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Classified

FLORIDA, Port Charlotte: Stable, 22 year old, progressive independent group seeking residency trained, board certified EM physicians for expansion to second facility. 27k and 22k volume EDs. Full specialty backup. Excellent compensation based on productivity with full time income potential exceeding 350k. Flexible scheduling. Documentation by EMR. Malpractice, Health Insurance, Dental provided. Located on Charlotte Harbor with saltwater access to the Gulf. Short drive to Tampa, Sarasota, Fort Myers, Naples.

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Young Woman With Postpartum Chest and Abdominal Pain

A 16-year-old female adolescent presented to the emergency department with several days of pleuritic chest pain, abdominal pain, and fever. The patient was 2 weeks postpartum from an uncomplicated spontaneous vaginal delivery. She was afebrile, with a pulse rate of 122 beats/min and blood pressure of 95/56 mm Hg. Breath sounds were clear and diffuse abdominal tenderness was noted. Laboratory evaluation revealed a WBC count of 46.8×109/L. Bedside ultrasonography demonstrated fluid collections with prominent fibrinous stranding adjacent to the liver (Figure 1, and Video E1 and E2 [available online at http://www.annemergmed.com]) and uterus (Figure 2).

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Classified 2018 Advertising Rates & Information

Ads and complete payments must be received in writing by the issue's deadline date. These deadlines apply to insertions, cancellations, and changes.

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Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Suspected Acute Venous Thromboembolic Disease

Members of the American College of Emergency Physicians Clinical Policies Committee (Oversight Committee):Michael D. Brown, MD, MSc (Chair 2014-2017; Co-Chair 2017-2018)Stephen J. Wolf, MD (Co-Chair 2017-2018)Richard Byyny, MD, MSc (Methodologist)Deborah B. Diercks, MD, MScSeth R. Gemme, MDCharles J. Gerardo, MD, MHSSteven A. Godwin, MDSigrid A. Hahn, MD, MPHNicholas E. Harrison, MD (EMRA Representative 2017-2018)Benjamin W. Hatten, MD, MPHJason S. Haukoos, MD, MSc (Methodologist)Amy Kaji, MD, MPH, PhD (Methodologist)Heemun Kwok, MD, MS (Methodologist)Bruce M.

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Calendar

▮ Mock Oral Private Tutorial. May 2–4, 2018. Chicago, IL. Contact: Shannon Finucane. Email: shannonf@icep.org. Url: www.icep.org. (11.25)

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ACEP Accrediting Geriatric Emergency Departments

Kevin Biese, MD, said he trained for "helicopters and chest tubes" as he was wrapping up his residency about a dozen years ago. But his shifts as an emergency physician at the University of North Carolina at Chapel Hill are more likely to unfold far differently these days, with home health referrals, delirium assessments, fall-related concerns, and end-of-life treatment quandaries.

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American Board of Emergency Medicine Report on Residency and Fellowship Training Information (2017-2018)

The American Board of Emergency Medicine (ABEM) gathers extensive background information on emergency medicine–sponsored residency and fellowship programs, as well as the residents and fellows training in those programs. We present the 2018 annual report on the status of US emergency medicine training programs.

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Infant With Episodes of Bilious Vomiting

A 6-month-old female infant was brought to the pediatric emergency department (ED) for 2 episodes of bilious vomiting during the previous 3 hours. She had had 2 previous similar ED visits during the past 3 months, but the symptoms spontaneously resolved and no testing was conducted. Her physical examination result was unremarkable, and her abdomen was soft, nondistended and nontender. An abdominal radiograph showed nonspecific inferior displacement of the transverse colon (Figure 1). Point-of-care ultrasonography performed by the emergency physician (Figure 2) revealed the diagnosis.

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Information for Readers

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EMRA EKG Guide

The folks at EMRA are at it again! Jeremy Berberian and his team have put together another pocket guide (this time focusing on ECGs) to help fill the pockets and minds of emergency providers across the globe.

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What's Coming in Annals ● June 2018

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(Mis)understanding the Analysis of Apneic Oxygenation?

We read with great interest the recent systematic review and meta-analysis by Oliveira et al1 of apneic oxygenation (ApOx) during intubation. There remains controversy over the effect of ApOx during rapid sequence intubation of patients in the emergency department (ED) and how it relates to patient-centered outcomes.

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In reply:

We thank Drs. Caputo and West for their interest in our article.1

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In reply:

We appreciate the authors' comments in the letter to the editor about our article.

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Anti‐epidermal growth factor receptor therapy concurrently with induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma

Cancer Science, EarlyView.


https://ift.tt/2JYoplE

Association of activities of daily living with the load during step ascent motion in nursing home-residing elderly individuals

Objective This study aimed to examine the association of independence in ADL with the loads during step ascent motion and other motor functions in 32 nursing home-residing elderly individuals. Design Independence in ADL was assessed by using the functional independence measure (FIM). The loads at the upper (i.e., pulling up) and lower (i.e., pushing up) levels during step ascent task was measured on a step ascent platform. Hip extensor, knee extensor, plantar flexor muscle, and quadriceps setting strengths; lower extremity agility using the stepping test; and hip and knee joint pain severities were measured. One-legged stance and functional reach distance for balance, and maximal walking speed, timed up-and-go (TUG) time, five-chair-stand time, and step ascent time were also measured to assess mobility. Results Stepwise regression analysis revealed that the load at pushing up during step ascent motion and TUG time were significant and independent determinants of FIM score. FIM score decreased with decreased the load at pushing up and increased TUG time. Conclusions The study results suggest that depending on task specificity, both one step up task's push up peak load during step ascent motion and TUG, can partially explain ADL's FIM score in the nursing home-residing elderly individuals. Lower extremity muscle strength, agility, pain or balance measures did not add to the prediction. Corressponding author Mitsuhiro Masaki, R.P.T., PhD., Department of Physical Therapy, Niigata University of Health and Welfare, Institute for Human Movement and Medical Sciences, Niigata University of Health and Welfare, 1398 Shimami-cho, Kita-ku, Niigata 950-3198, Japan. E-mail: masaki@nuhw.ac.jp. Office phone: +81-25-257-4312. Office fax: +81-25-257-4312 Author Disclosures No potential conflicts of interest were disclosed for the present study. Kyoritsu Denshi Kogyo Co. Ltd. financed this study. The financial providers did not contribute to the implementation of the study, analysis, interpretation of the data, or preparation of this article. The present study is an expansive analysis of our cross-sectional study that has been published previously as an article titled "Association between physical function and the load pattern during stepping-up motion in community-dwelling elderly women" (2016). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Radio-pharmaceuticals for cancer treatment – are they ready for prime time yet?

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Functional immune characterization of HIV-associated non-small cell lung cancer

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It’s time to rethink weight loss in cancer

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Letter to the editor on “Body mass index and 20-specific cancers - re-analyses of dose-response meta-analyses of observational studies”

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Representation of Obese Participants in Obesity-Related Cancer Randomized Trials

Abstract

Background

Obesity is a risk factor for numerous cancer types, and may influence cancer treatment outcomes. Underrepresentation of obese patients in obesity-related cancer randomized controlled trials (RCTs) may affect generalizability of results. We aimed to assess the reporting of information about eligibility and enrollment of obese participants in obesity-related cancer RCTs.

Methods

We conducted a systematic review of RCTs of 10 obesity-related cancer types (esophagus, colon/rectum, liver, gallbladder, pancreas, postmenopausal breast, endometrium, ovary, kidney, and thyroid cancer). We selected RCTs published between 2013 and 2016 in 5 major journals. For each trial, we examined the article, the protocol, and the registration record. We assessed if eligibility criteria limiting the enrollment of obese participants were reported, the proportion of obese participants that were enrolled, and if a subgroup analysis according to obesity status was reported. We systematically contacted corresponding authors and asked for information about eligibility of obese participants and the proportion of obese participants.

Results

We included 76 RCTs. Colon/rectum (n = 20), postmenopausal breast (n = 11), and kidney (n = 11) cancers were the most frequent types. Based on publicly available sources, information on the eligibility of obese participants was available in 5 (7%) trials. The proportion of obese participants could be estimated in 9 (12%) trials only. We found a subgroup analysis in only one RCT. When considering unpublished information, the eligibility of obese participants was explicitly stated in 31 (41%) trials but it was unclear if the remaining 59% trials considered obese participants as eligible and what proportion of obese participants was included. Across 22 trials, the median proportion of obese participants included was 18% [Q1-Q3 11-23].

Conclusion

Information on the eligibility and enrollment of obese participants in cancer RCTs is dramatically underreported. More transparency is needed to understand the applicability of obesity-related cancer RCT results to obese patients with cancer.

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“ARTE and Craft of Bevacizumab in Elderly Patients with Glioblastoma”

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Tailoring treatment of salivary duct carcinoma (SDC) by liquid biopsy:ARv7 expression in circulating tumor cells

https://ift.tt/2JYHEvH

Primary Tumor Sidedness and Benefit from FOLFOXIRI plus Bevacizumab as Initial Therapy for Metastatic Colorectal Cancer

Abstract

Background

Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status.

Patients and methods

Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined as right- or left-sided if they originated from the caecum to the transverse colon or within the splenic flexure and beyond, respectively. Patients with available information about both primary sidedness and RAS and BRAF status were included in the present analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumor location and RAS and BRAF mutational status.

Results

Information about primary sidedness and RAS and BRAF status was available for 358 (70.5%) out of 508 randomized patients. Patients with right-sided tumors (N = 173) presented shorter OS (23.7 vs 31.0 months, HR = 1.42 [95%CI, 1.09-1.84], P=0.010) and a trend toward shorter PFS (10.2 vs 11.5 months, HR = 1.24 [95%CI:0.98-1.56], P=0.083) than those with left-sided tumors (N = 185), but these associations were no longer evident when adjusting for RAS and BRAF status. Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS (HR = 0.59 vs. 0.89, P-for-interaction=0.099) and OS (HR = 0.56 vs. 0.99, P-for-interaction=0.030) and this advantage was independent of their RAS and BRAF status.

Conclusions

FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status. Trial registration: clinicaltrials.gov identifier NCT00719797.

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Effects of Ascorbic Acid on Tax, NF-κB and MMP-9 in Human T-cell Lymphotropic Virus Type 1 Positive Malignant T-Lymphocytes

Background: HTLV1 is a retrovirus that infects CD4-positive cells and leads to Adult T-cell leukemia by constitutive activation of nuclear factor kappa B. Ascorbic acid (AA) is an essential nutrient that possess anti-proliferative and pro-apoptotic activity against a number of malignant cell lines. This study delineates the effect of AA on Tax protein expression as well as NF-κB and MMP9 activity in two HTLV1-positive leukemia cells (HuT-102 and C91-PL).

Methods: The cytotoxic and antiproliferative effect of AA were studied by LDH release and MTT tests, respectively. The proteins expression level was assessed by western blotting. RT-PCR was used to study mRNAs level. Finally, ELISA/EMSA and Zymography were used to evaluate NF-κB and MMP-9 activities, respectively.

Results: Cell lines were treated with non-cytotoxic concentrations of AA for 48h and 96h, which resulted in a significant inhibition of proliferation at a concentration of 50µg/ml at 96h in both cell lines. The same concentration inhibited Tax protein expression as well as the NF-κB nuclearization and DNA binding activity. The inhibitory effect of AA on MMP9 protein expression and activity started at 100µg/ml and 50µg/ml in HuT-102 and C91-PL cells respectively, with no effect at the transcriptional levels of MMP-9 in either one of the two cell lines.

Conclusion: These results indicated that while AA exerted its anti-proliferative effect on the NF- κB activation pathway by suppressing Tax expression, its effects on MMP9 seemed to be independent of this mechanism and follow a different approach.

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Targeting Cell Necroptosis and Apoptosis Induced by Shikonin via Receptor Interacting Protein Kinases in Estrogen Receptor Positive Breast Cancer Cell Line, MCF-7

Background: Recognition of a new therapeutic agent may activate an alternative programmed cell death for the treatment of breast cancer.

Objective: Here, it has been tried to evaluate the effects of Shikonin, a naphthoquinone derivative of Lithospermum erythrorhizon, on the induction of necroptosis and apoptosis mediated by RIPK1-RIPK3 in the ER+ breast cancer cell line, MCF-7.

Methods: In the current study, cell death modalities, cell cycle patterns, RIPK1 and RIPK3 expressions, caspase-3 and caspase-8 activities, reactive oxygen species and mitochondrial membrane potential have been evaluated in the Shikonin-treated MCF-7 cells.

Results: Necroptosis and apoptosis have been occurred by Shikonin, with a significant increase in RIPK1 and RIPK3 expressions, although necroptosis was the major rout in MCF-7 cells. Shikonin significantly increased the percentage of the cells in sub-G1 and also those in the later stages of cell cycle, which represents an increase in necroptosis and apoptosis. Under caspase inhibition by Z-VAD-FMK, Shikonin has stimulated necroptosis, which could be arrested by Nec-1. An increase in ROS levels and a decrease in the mitochondrial membrane potential have also been observed.

Conclusion: On the basis of present findings, Shikonin has been suggested as a good candidate for the induction of cell death in ER+ breast cancer, although further investigations, experimental and clinical, are required.

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Mohs Micrographic Surgery Volume and Payment Patterns Among Dermatologists in the Medicare Population, 2013

Objectives: Mohs micrographic surgery (MMS) has expanded markedly in recent years but there is limited information on volume, practice patterns or reimbursement. This study characterizes MMS utilization in the Medicare population. Materials and Methods: We analyzed the Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File Calendar Year 2013 data set for provider service volume and reimbursement for dermatologists who did and did not perform MMS procedures. Results: Total Medicare-funded MMS procedures increased 25% from 2009 (558,447) to 2013 (700,262). Dermatologists who performed MMS had significantly more average services per provider (5419.4 vs. 3627.1, r=0.16, P

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Characterization of PD-L1 and PD-1 Expression and CD8+ Tumor-infiltrating Lymphocyte in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma

Objectives: Immunotherapies that target the programmed death-1/ programmed death-1 ligand (PD-1/PD-L1) immune checkpoint pathway have shown promise in nasopharyngeal carcinoma (NPC) in early phases clinical studies. Here, we evaluated PD-1 and PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) in NPC patients. Materials and Methods: Newly diagnosed NPC patients were identified through the institutional database between January 2007 and December 2012. PD-L1 and PD-1 expression, Epstein-Barr virus (EBV) status, and CD8+ TIL numbers were measured in archival tumor samples at diagnosis and their correlations with clinicopathologic features, including survival, were evaluated. Results: A total of 114 NPC patients were analyzed. Most patients (96%) were EBV positive. PD-L1 was expressed in ≥1% of tumor cells (TCs) in 69% of patients, in ≥50% of TCs in 12% of patients, and in ≥5% of either TCs or infiltrating immune cells in 71% of patients. CD8+ TILs were present in tumors from all patients, whereas only 11% of tumors expressed PD-1. There were no correlations between PD-L1 expression and CD8+ TIL abundance, PD-1 expression, or survival. Conclusions: Approximately 70% of EBV-positive NPC expressed PD-L1, but this did not correlate with patient survival or clinicopathologic features. The findings of this study represent the immune biomarker profile of confirmed EBV-associated NPC in an endemic region. Since the current clinical development of immune checkpoint inhibitor for NPC is mostly focusing on an EBV-associated tumor, differences in immune biomarker profiles and EBV status of endemic and nonendemic regions should be further explored. N.L. and K.M. contributed equally. Supported by the Ramathibodi Cancer Center grant. N.N. received funding from the Research University Network (RUN) and Talent Management Program of Mahidol University, and the Ramathibodi Grant for Research Development from Ramathibodi Hospital. An abstract of this work was presented at the 2015 ASCO Annual Meeting, May 29 to June 2, 2015, Chicago, IL. The authors declare no conflicts of interest. Reprints: Nuttapong Ngamphaiboon, MD, Department of Medicine, Division of Medical Oncology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. E-mail: nuttapong.nga@mahidol.ac.th. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The Impact of Epidemiological Factors and Treatment Interventions on Survival in Patients With Signet Ring Cell Carcinoma of the Pancreas

Objectives: Primary pancreatic signet ring cell carcinoma (SRCC) is a rare histologic variant of pancreatic carcinoma. A population-based analysis of pancreatic SRCC was performed to determine the predictive effects of epidemiological factors and treatment interventions on overall survival (OS) and disease-specific survival (DSS). Materials and Methods: The Surveillance, Epidemiology, and End Results registry was searched for pancreatic SRCC cases diagnosed between January 1, 1973 and December 31, 2013. Statistical analysis was performed using the Fisher exact test, χ2 analysis, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. Results: The mean age among 497 patients was 66.6 years (SD, 11.9). Most patients were white (82.7%) and male (54.5%). The 1-, 2-, and 5-year OS rates were 17%, 9%, and 4%, respectively, while the corresponding 1-, 2-, and 5-year rates for DSS were 18%, 10%, and 5%, respectively. On univariable analysis; age, site, grade, stage, and treatment were predictive of OS and DSS (P

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Optical trocar access for initial trocar placement in laparoscopic gastrointestinal surgery: A propensity score‐matching analysis

Asian Journal of Endoscopic Surgery, EarlyView.


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Belatacept and auto-immune adverse events

No abstract available

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More Than Just Wait Time? Regional Differences in Liver Transplant Outcomes for Hepatocellular Carcinoma

Background Regional allocation of deceased donor livers has led to variable wait times for HCC patients on the liver transplant list. The purpose of our study was to evaluate how regional differences in wait time affect outcomes for HCC patients. Methods A retrospective, observational study was performed using the OPTN database from 2/27/2002 to 9/25/2015. The cumulative incidences of transplant and waitlist death as well as intention-to-treat and posttransplant survival were evaluated for patients ≥ 18 years of age listed for DDLT with stage II HCC exception points in each UNOS region. A multivariable analysis of predictive factors for posttransplant survival was performed. Results Cumulative incidence of transplant decreased and cumulative incidence of waitlist death increased as regional wait time increased. Intention-to-treat survival decreased with increased regional wait time with long wait time regions 1, 5, and 9 having significantly lower intention-to-treat survival compared to many of the shorter wait time regions (p

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Antigen Presentation Keeps Trending in Immunotherapy Resistance

Through a gain-of-function kinome screen, MEX3B was identified as a mediator of resistance to T cell immunotherapy not previously identified using CRISPR based screens. MEX3B is a post-transcriptional regulator of HLA-A, validating the critical role of tumor-intrinsic antigen presentation in T cell immunotherapy and indicating a new putative molecular target.

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Combined BRAF and HSP90 inhibition in patients with unresectable BRAF V600E mutant melanoma

Purpose: BRAF inhibitors are clinically active in patients with advanced BRAF^V600-mutant melanoma, although acquired resistance remains common. Preclinical studies demonstrated that resistance could be overcome using concurrent treatment with the HSP90 inhibitor XL888. Methods: Vemurafenib (960 mg PO BID) combined with escalating doses of XL888 (30, 45, 90 or 135 mg PO twice weekly) was investigated in 21 patients with advanced BRAF^V600-mutant melanoma. Primary endpoints were safety and determination of a maximum tolerated dose. Correlative proteomic studies were performed to confirm HSP inhibitor activity. Results: Objective responses were observed in 15/20 evaluable patients (75%; 95% CI: 51-91%), with 3 complete and 12 partial responses. Median progression-free and overall survival were 9.2 months (95% CI: 3.8-not reached) and 34.6 months (6.2-not reached), respectively. The most common grade 3/4 toxicities were skin toxicities such as rash (n=4, 19%) and cutaneous squamous cell carcinomas (n=3, 14%), along with diarrhea (n=3, 14%). Pharmacodynamic analysis of patients' PBMCs showed increased day 8 HSP70 expression compared to baseline in the three cohorts with XL888 doses ≥45 mg. Diverse effects of vemurafenib-XL888 upon intratumoral HSP-client protein expression were noted, with the expression of multiple proteins (including ERBB3 and BAD) modulated on therapy. Conclusion. XL888 in combination with vemurafenib has clinical activity in patients with advanced BRAF^V600-mutant melanoma, with a tolerable side-effect profile. HSP90 inhibitors warrant further evaluation in combination with current standard-of-care BRAF plus MEK inhibitors in BRAF^V600-mutant melanoma.

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Tamoxifen Resistance Trumped and Oral Selective Estrogen Receptor Degraders Arrive

Predictive tests, to refine the estrogen receptor assay, for the adjuvant treatment of breast cancer with tamoxifen and oral Selective Estrogen Receptor Degraders (SERDs) are required.  A splice variant of the corepressor NCOR2, BQ2313636.1 predicts tamoxifen resistence to adjuvant tamoxifen and AZ9496, the first oral SERD, completes phase one studies

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Blockade of myeloid-derived suppressor cell expansion with all-trans retinoic acid increases the efficacy of anti-angiogenic therapy

Intrinsic and adaptive resistance hamper the success of anti-angiogenic therapies (AAT), especially in breast cancer where this treatment modality has proven largely ineffective. Therefore, novel strategies to improve the efficacy of AAT are warranted. Solid tumors such as breast cancer are characterized by a high infiltration of myeloid-derived suppressor cells (MDSC) which are key drivers of resistance to AAT. Therefore, we hypothesized that all-trans retinoic acid (ATRA), which induces differentiation of MDSC into mature cells, could improve the therapeutic effect of AAT. ATRA increased the efficacy of anti-VEGFR-2 antibodies alone and in combination with chemotherapy in preclinical breast cancer models. ATRA reverted the anti-VEGFR-2-induced accumulation of intratumoral MDSC, alleviated hypoxia, and counteracted the disorganization of tumor microvessels. Mechanistic studies indicate that ATRA treatment blocked the AAT-induced expansion of MDSC secreting high levels of vessel-destabilizing S100A8. Thus, concomitant treatment with ATRA holds the potential to improve AAT in breast cancer and possibly other tumor types.

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Universal influenza virus vaccines and therapeutics: where do we stand with influenza B virus?

Jessica Tan | Guha Asthagiri Arunkumar | Florian Krammer

https://ift.tt/2HObaDI

Mapping of Leaf Rust Resistance Genes and Molecular Characterization of the 2NS/2AS Translocation in the Wheat Cultivar Jagger

Winter wheat cultivar 'Jagger' was recently found to have an alien chromosomal segment 2NS that has Lr37, a gene conferring resistance against leaf rust caused by Puccinia triticina. The objective of this study was to map and characterize the gene(s) for seedling leaf rust resistance in Jagger. The recombinant inbred line (RIL) population of Jagger x '2174' was inoculated with leaf rust pathogen THBJG and BBBDB, and evaluated for infection type (IT) response. A major quantitative trait locus (QTL) for THBJG and BBBDB was coincidently mapped to chromosome arm 2AS, and the QTL accounted for 56.6% - 66.2% of total phenotypic variation in infection type (IT) response to THBJG, and 72.1% - 86.9% to BBBDB. The causal gene for resistance to these rust races was mapped to the 2NS segment in Jagger. The 2NS segment was located in a region of approximately 27.8 Mb starting from the telomere of chromosome arm 2AS, based on the sequences of the A genome in tetraploid wheat. The Lr17a gene on chromosome arm 2AS was delimited to 3.1 Mb in the genomic region, which was orthologous to the 2NS segment. Therefore, the Lr37 gene in the 2NS segment can be pyramided with other effective resistance genes, rather than Lr17a in wheat, to improve resistance to rust diseases.

https://ift.tt/2Jb68k1

Phylogenetic and Phylogenomic Definition of Rhizopus Species

Phylogenomic approaches have the potential to improve confidence about the inter-relationships of species in the order Mucorales within the fungal tree of life. Rhizopus species are especially important as plant and animal pathogens and bioindustrial fermenters for food and metabolite production. A dataset of 192 orthologous genes was used to construct a phylogenetic tree of 21 Rhizopus strains, classified into four species isolated from habitats of industrial, medical and environmental importance. The phylogeny indicates that the genus Rhizopus consists of three major clades, with R. microsporus as the basal species and the sister lineage to R. stolonifer and two closely related species R. arrhizus and R. delemar. A comparative analysis of the mating type locus across Rhizopus reveals that its structure is flexible even between different species in the same genus, but shows similarities between Rhizopus and other mucoralean fungi. The topology of single-gene phylogenies built for two genes involved in mating is similar to the phylogenomic tree. Comparison of the total length of the genome assemblies showed that genome size varies by as much as three-fold within a species and is driven by changes in transposable element copy numbers and genome duplications.

https://ift.tt/2HDbebw

Prescribing of Gluten-Free Foods Declining in England

THURSDAY, April 19, 2018 -- Recent policy changes have led to a decline in the prescribing of gluten-free foods in England, according to research published online April 16 in BMJ Open. Alex J. Walker, Ph.D., from the University of Oxford in the...

https://ift.tt/2Hi009f

Opioids Tied to Adverse Outcomes in Hemodialysis Patients

THURSDAY, April 19, 2018 -- For patients on hemodialysis, opioids are associated with adverse outcomes, according to a study published online April 19 in the Clinical Journal of the American Society of Nephrology. Julie H. Ishida, M.D., from the...

https://ift.tt/2K1YWYz

First Opioid Lawsuit Targeting Pharmacy Benefit Managers

THURSDAY, April 19, 2018 -- A first opioid lawsuit is targeting pharmacy benefit managers (PBMs), according to a report published in Managed Healthcare Executive. Noting that until now, PBMs have not been sued for the opioid crisis, in February, a...

https://ift.tt/2HhD7lZ

Most Smokers With Head and Neck Cancer Have Tried to Quit

THURSDAY, April 19, 2018 -- Most active smokers with head and neck squamous cell carcinoma (HNSCC) have made one or more quit attempts, according to a study published online April 12 in JAMA Otolaryngology-Head & Neck Surgery. Samir S....

https://ift.tt/2K1lTuY

Adults Using Benzodiazepines More Likely to Receive Opioid Rx

THURSDAY, April 19, 2018 -- New opioid prescriptions for U.S. adults using benzodiazepines stopped increasing in 2010, although the likelihood of receiving a prescription is still elevated versus the general population, according to a study...

https://ift.tt/2HhD6yr

NxtGen Botanicals Maeng Da Kratom by NGB Corp.: Recall - Possible Salmonella Contamination

[Posted 04/19/2018] AUDIENCE: Consumer ISSUE: NGB Corp. of West Jordan, Utah is voluntarily recalling NxtGen Botanicals Maeng Da Kratom labeled bottles of encapsulated product because it has the potential to be contaminated with Salmonella, an...

https://ift.tt/2Hg2WTu

NxtGen Botanicals Maeng Da Kratom by NGB Corp.: Recall - Possible Salmonella Contamination

[Posted 04/19/2018] AUDIENCE: Consumer ISSUE: NGB Corp. of West Jordan, Utah is voluntarily recalling NxtGen Botanicals Maeng Da Kratom labeled bottles of encapsulated product because it has the potential to be contaminated with Salmonella, an...

https://ift.tt/2Hg2WTu

Metastatic hepatocellular carcinoma masquerading as soft tissue sarcoma: A diagnostic challenge

Diagnostic Cytopathology, EarlyView.


https://ift.tt/2HMBJc5

Liquid‐based cytology in the diagnosis of Langerhans cell sarcoma: A case report

Diagnostic Cytopathology, EarlyView.


https://ift.tt/2F0vcry

Cytodiagnosis of inflammatory myofibroblastic tumor: A report of three cases in infants

Diagnostic Cytopathology, EarlyView.


https://ift.tt/2HMloEv

Evaluation of photoshop based image analysis in cytologic diagnosis of pleural fluid in comparison with conventional modalities

Diagnostic Cytopathology, EarlyView.


https://ift.tt/2F4JqaY

Certain Kratom-Containing Powder Products by Viable Solutions: Recall -Possible Salmonella Contamination

[Posted 04/19/2018] AUDIENCE: Consumer ISSUE: Viable Solutions of Nampa, ID has initiated a recall of certain Kratom-containing powder products, because it has the potential to be contaminated with Salmonella, an organism which can cause serious...

https://ift.tt/2K1bW0T

Certain Kratom-Containing Powder Products by Viable Solutions: Recall -Possible Salmonella Contamination

[Posted 04/19/2018] AUDIENCE: Consumer ISSUE: Viable Solutions of Nampa, ID has initiated a recall of certain Kratom-containing powder products, because it has the potential to be contaminated with Salmonella, an organism which can cause serious...

https://ift.tt/2K1bW0T

Coming to the rescue of first responders

Addressing behavioral health needs must be a priority

https://ift.tt/2qQyxo7

An Ultra-clean Multilayer Apparatus for Collecting Size Fractionated Marine Plankton and Suspended Particles

Plankton and suspended particles play a major role in the biogeochemical cycles in the ocean. Here, we provide an ultra-clean, low stress method for the collection of various sizes of particles and plankton at sea with the capability of handling large volumes of seawater.

https://ift.tt/2HdowvV

Combining Microfluidics and Microrheology to Determine Rheological Properties of Soft Matter during Repeated Phase Transitions

We demonstrate the fabrication and use of a microfluidic device that enables multiple particle tracking microrheology measurements to study the rheological effects of repeated phase transitions on soft matter.

https://ift.tt/2qKtchX

Small Link for Cannabis Use, Reduced Cognitive Functioning

THURSDAY, April 19, 2018 -- For adolescents and young adults, frequent or heavy cannabis use has a small association with reduced cognitive functioning, according to research published online April 18 in JAMA Psychiatry. J. Cobb Scott, Ph.D., from...

https://ift.tt/2qKTJeZ

Artificial Pancreas Treatment Efficacious for Type 1 Diabetes

THURSDAY, April 19, 2018 -- For patients with type 1 diabetes, artificial pancreas treatment is efficacious, increasing the proportion of time spent in the near normoglycemic range, according to a study published online April 18 in The BMJ. Eleni...

https://ift.tt/2HeM0RH

Less Pain Post TKA With Addition of Peripheral Nerve Blocks

THURSDAY, April 19, 2018 -- Addition of an interspace between the popliteal artery and capsule of the posterior knee (IPACK) block and adductor canal block (ACB) to periarticular injection (PAI) is associated with less pain after total knee...

https://ift.tt/2qNl2VQ

Gene Therapy Found to Be Promising for β-Thalassemia

THURSDAY, April 19, 2018 -- For patients with severe β-thalassemia, the need for red-cell transfusions can be reduced or eliminated by transducing cells with the LentiGlobin BB305 vector, according to a study published in the April 18 issue of the...

https://ift.tt/2Hdv4uH

Number of Cigarettes Smoked Daily Tied to Stroke Risk

THURSDAY, April 19, 2018 -- There is a strong dose-response relationship between the number of cigarettes smoked daily and ischemic stroke risk among men younger than 50 years of age, according to a study published online April 19 in Stroke. Janina...

https://ift.tt/2qLF0R1

Hearing Aids May Mitigate Cognitive Decline, Memory Loss

THURSDAY, April 19, 2018 -- Using hearing aids may slow cognitive decline in later life, according to a study published online April 10 in the Journal of the American Geriatrics Society. Asri Maharani, Ph.D., from the University of Manchester in the...

https://ift.tt/2Hcx3PR

AAN: Erenumab Shows Promise for Hard-to-Treat Migraine

THURSDAY, April 19, 2018 -- For patients with episodic migraine who have failed prior preventive migraine treatments (PMTs), erenumab is associated with an increase in the proportion of patients achieving a ≥50 percent reduction in mean monthly...

https://ift.tt/2qMhd3d

Delayed Coronary Obstruction Rare After TAVR

THURSDAY, April 19, 2018 -- Delayed coronary obstruction (DCO) after transcatheter aortic valve replacement (TAVR) is a rare phenomenon but is associated with a high in-hospital mortality rate, according to a study published in the April 10 issue...

https://ift.tt/2HbXVj3

AAN: New Drug May Help Infants With Spinal Muscular Atrophy

THURSDAY, April 19, 2018 -- For infants with type 1 spinal muscular atrophy who have two copies of the survival motor neuron (SMN) 2 gene, RG7916 can increase SMN protein levels in the blood, according to a study presented at the annual meeting of...

https://ift.tt/2qKnLj3

Time-Related Deployment Factors Predict Suicide Attempt Risk

THURSDAY, April 19, 2018 -- For soldiers who have been deployed twice, suicide attempt (SA) risk is associated with timing of first deployment and dwell time (DT; i.e., length between deployments), according to a study published online April 18 in...

https://ift.tt/2HhdF4s

Systematic review of the mesopancreas: concept and clinical implications

Abstract

Background

In 2007, Gockel et al. coined the term mesopancreas (MP). In the next 10 years, a limited number of publications about MP have been published, but little is known about the oncological benefit of MP resection. We performed a systematic review of the literature on MP.

Methods

An electronic search was performed in PubMed, EMBASE, Cochrane, Latindex, Scielo, and Koreamed databases until 15 June 2017 to identify all published articles dealing with the subject of MP. Some language restriction was done (Chinese and Rumanian).

Results

The search yielded 51 articles; 28 articles were selected as relevant. All were retrospective studies focused more on describing technical variants, feasibility and safety than on the cancer results. The R0 rate in patients with MP resection ranged between 57 and 96.7%. In all the articles with a control group, the R0 rate was higher in the MP excision group. Survival data were explicitly stated only in five series.

Conclusion

MP is a difficult-to-excise retropancreatic area. In theory, it is agreed that MP excision raises the rate of R0 resections, which in turn reflected in an improvement in the oncological results; however, at present there are no randomized studies to prove this. Achieving a worldwide consensus on its concept, landmarks, excision technique and oncological results is essential.

https://ift.tt/2qKoXnv

Licorice-induced apparent mineralocorticoid excess compounded by excessive use of terbutaline and high water intake

This case highlights the clinical course of a 54-year-old male patient presenting with hypertension and long-term refractory hypokalaemia. He reported long-term malaise, fatigue and physical discomfort. Diarrhoea, vomiting, over-the-counter drugs, dietary supplements and any kind of medical abuse were all denied. Physical examination was normal. Suppressed plasma renin activity along with a low aldosterone level and elevated urinary cortisone/cortisol metabolite excretion ratio raised the suspicion of apparent mineralocorticoid excess (AME). The patient started treatment with spironolactone, but serum potassium levels were persistently fluctuating and the patient was hospitalised for further evaluation. During hospitalisation, repeated medical history and diagnostic examinations revealed licorice-induced AME complicated by excessive use of terbutaline and massive water intake. Licorice discontinuation, reduction of terbutaline and normalisation of water intake led to fully normalised potassium levels. Despite careful clinical history and diagnostic work-up, hospitalisation may be necessary in selected patients with long-term hypokalaemia.

https://ift.tt/2JXqHl8

Localised perforation of locally advanced transverse colon cancer with spontaneous colocutaneous fistula formation: a clinical challenge

Colon cancer can present with complications such as obstruction, perforation and bleeding. The clinical presentation has been recognised as an independent prognostic factor for morbidity and mortality.¹ We present a rare case of localised perforation of a locally advanced colon cancer arising from mid-transverse colon in an elderly woman in the absence of widely metastatic disease with eventual cutaneous involvement of the overlying skin by direct extension, resulting in formation of colocutaneous fistula. The management of such cases is complex as usually tailored to the situation encountered.² This case was a clinical challenge to choose between initial palliative resection and curative R0 resection following neoadjuvant chemotherapy.

https://ift.tt/2Hi7YyM

Laparoscopic management of an internal hernia in a pregnant woman with Roux-en-Y gastric bypass

Management of abdominal pain in a pregnant patient with a history of Roux-en-Y gastric bypass presents unique challenges. A misdiagnosis or delay in management can result in lethal maternal–fetal outcomes. We present a 30-year-old woman at 21 weeks of pregnancy presented with abdominal pain. She had a history of laparoscopic Roux-en-Y gastric bypass performed 3 years earlier. The clinical examination was remarkable for epigastric pain and tenderness. The vital signs and laboratory examinations were unremarkable. The CT scan was suggestive of an internal hernia. On an exploratory laparoscopy, the distal common small bowel was found to be herniating through the jejunojejunostomy mesenteric defect, causing intestinal obstruction with dilatation of the Roux limb and the biliopancreatic limb. The internal hernia was reduced, and no bowel resection was required. The mesenteric defect was closed with 3-0 silk sutures in a continuous fashion. The patient was discharged after 3 days and delivered a healthy baby at 40 weeks of gestation.

https://ift.tt/2JZwPJv

Unexpected case of pneumomediastinum and subcutaneous emphysema: primary or secondary aetiology?

A 77-year-old man was admitted with a relapse of antineutrophil cytoplasmic antibody-positive vasculitis with pulmonary involvement and acute kidney injury. There was a background of pulmonary fibrosis (non-specific interstitial pneumonia type pattern) and superadded pulmonary haemorrhage, acute pulmonary oedema and sepsis. The patient was intubated for 4 days and remained dependent on high flow oxygen and continuous positive airway pressure after extubation. A chest radiograph performed 2 weeks after extubation demonstrated unexpected, extensive pneumomediastinum and subcutaneous emphysema. This was confirmed on CT which raised the possibility of a tracheal defect at the level of the prior endotracheal tube cuff position. Tracheal injury was considered clinically unlikely due to the considerable interval since extubation and a short, uneventful intubation period. The cardiothoracic team recommended a diagnostic bronchoscopy but this was felt too high risk by the clinical team. The cause of pneumomediastinum and subcutaneous emphysema remained indeterminate.

https://ift.tt/2HdWLzm

Massive haemoptysis secondary to mycotic pulmonary artery aneurysm in subacute invasive aspergillosis

A 68-year-old man, presented with 3 week history of infective symptoms and mild haemoptysis. Past medical history included severe emphysema and a chronic right upper lobe (RUL) cavity. He was discharged from follow-up a year ago in view of clinical and radiological stability; previous bronchoscopic examinations yielded no specific diagnosis. CT scan on admission confirmed complex cavitary consolidation of RUL. He developed massive haemoptysis requiring intubation and ventilation. CT pulmonary angiogram (CTPA) revealed 16 mm RUL pulmonary artery (PA) aneurysm which was successfully embolized. Sputum cultures, aspergillus antigen and rapidity of clinical progression suggested a diagnosis of subacute invasive aspergillosis (SAIA), prompting treatment with Voriconazole. Bronchoscopy showed blood ooze from RUL even after embolization. Unfortunately, patient continued to deteriorate and succumbed to profound septicaemia.

https://ift.tt/2JYji52

Recognition of supraduodenal artery from hepatic artery is essential to avoid untoward complications at HAIC: two cases

Description 

Supraduodenal artery (SDA) supplies the proximal duodenum, which originates most commonly from gastroduodenal artery (GDA), followed by common and proper hepatic artery.1 2 Origination from left hepatic artery (LHA) is relatively rare and only few articles have addressed this anatomic variation.3 Recognition of such an aberrant artery and proper coiling before liver-directed therapy are essential to prevent non-target organ injury. Herein, we report two rare cases of SDA that originated from the LHA.

Case 1

A 56-year-old man had a massive type hepatocellular carcinoma (HCC) in right hepatic lobe with right portal vein tumour thrombosis (figure 1). He had one episode of massive upper gastrointestinal bleeding at 2nd hepatic arterial infusion chemotherapy (HAIC) and panendoscope revealed haemorrhagic duodenitis with duodenal bulb ulcer. In our hospital, a SDA that originated from the LHA was found at angiography, which was successfully embolised with a minicoil (

https://ift.tt/2J7z8cq

Intestinal granulomatous disease: what is the first call

A 15-year-old girl presented with erythema nodosum and mild abdominal complaints. Her intestinal granulomatous disease was erroneously diagnosed as Crohn's disease despite the fact that the possibility of tuberculosis was considered. The final diagnosis of tuberculosis was made only when an anti-tumour necrosis factor therapy resulted in further deterioration. The patient was treated with isoniazid, rifampin, pyrazinamide and ethambutol, with slow and steady clinical improvement until complete recovery was achieved.

https://ift.tt/2K0TaXk

Cutaneous lymphangitis carcinomatosa made cervicofacial oedema intractable in a patient with superior vena cava syndrome

Cutaneous lymphangitis carcinomatosa (CLC) is a rare form of cutaneous metastasis that causes lymphoedema and various eruptions. We report a case of lung cancer with CLC that caused both superior vena cava (SVC) stenosis and cervicofacial oedema, suggestive of SVC syndrome. A 64-year-old woman with lung adenocarcinoma presented with cervicofacial oedema and erythema, followed by severe dyspnoea 2 months after four cycles of carboplatin, pemetrexed and bevacizumab triplet therapy. Although chest CT indicated SVC stenosis, cervicofacial oedema remained despite treating the SVC stenosis via balloon dilation. A skin biopsy of the erythematic sample confirmed CLC as the cause of the patient's symptoms. CLC should be considered as a differential diagnosis of cervicofacial oedema in addition to SVC syndrome, especially when it is observed in combination with skin erythema and induration. Moreover, a skin biopsy should be performed promptly for accurate diagnosis of CLC and to decide on appropriate treatment.

https://ift.tt/2HgsWhA

Liver chemistry abnormalities and leg oedema in rheumatoid arthritis

A 66-year-old man with seronegative, erosive rheumatoid arthritis for 12 years presented with malaise, elevated alkaline phosphatase and gamma-glutamyl transferase, and leg oedema. He subsequently developed ascites. No liver pathology was found, but cardiac analysis including right heart catheterisation revealed constrictive pericarditis. Rheumatoid constrictive pericarditis is a rare condition, but, despite current effective treatment for rheumatoid arthritis, still occurs. Diagnostic delay is frequent. Although mortality of the intervention is high, pericardiectomy is needed for most patients.

https://ift.tt/2JZ8BPy

Gas in the right hemiscrotum? Amyands hernia in a neonate

Description 

A 10-day-old boy, born at 36 weeks' gestation, was brought to our emergency department (ED) with irritability. He was able to suck as usual, but his temperature was 37.9°C and his right inguinal region was slightly erythematous. Laboratory data showed leucocytosis with a total leucocyte count of 23x10⁹/L (neutrophils 72.5%), but a low C reactive protein (<0.10 mg/dL). Urinalysis showed no pyuria and no organisms. Abdominal X-ray was unremarkable. Initial inguinal ultrasonography by a paediatric surgeon revealed no suggestion of testicular torsion or incarcerated hernia. The neonate was discharged home with a tentative diagnosis of acute epididymitis.

Six hours after discharge, he returned to ED with high fever of 38.7°C and extreme redness of the scrotum (figure 1). Repeat abdominal X-ray demonstrated gas in the right hemiscrotum (figure 2) and abdominal sonography revealed what appeared to be a bright cord in the right hemiscrotum (figure 3),...

https://ift.tt/2J9wq62

Spontaneous rupture of seminoma in undescended testis with hemoperitoneum: a rare presentation

Cryptorchidism is associated with increased risk of malignancy and infertility. We present a case of a 30-year-old man who presented to the Emergency Department of our tertiary care hospital with spontaneous intra-abdominal rupture of the seminoma in undescended testis with hemoperitoneum. This is a rare presentation of seminoma and emphasises the importance of scrotal examination in young men presenting with acute abdomen. Surgical management is the definitive treatment and should be instituted as soon as possible, after appropriate resuscitation.

https://ift.tt/2K0nKQI

Bilateral tension pneumothorax after acupuncture

Acupuncture is an ancient complementary medicine which is currently used worldwide. Many serious adverse events have been reported which include a spectrum of mild-to-fatal complications. However, the level of awareness with regard to complications is still low both to physicians and patients. We report a 63-year-old who presented with acute shortness of breath 2 hours after having had acupuncture. On examination, there was absent breath sound heard on the left lung and slightly reduced breath sound on the right lung. She had type 1 respiratory failure. Urgent chest radiograph confirmed bilateral pneumothorax which was more severe on the left with tension pneumothorax and mediastinal shift. Chest tubes were inserted bilaterally after failed needle aspiration attempts. Subsequently, the pneumothoraces resolved, and she was discharged well. The bilateral pneumothoraces caused by acupuncture were curable but could have been potentially fatal if diagnosis was delayed. This case report adds to the limited current literature on the complications of acupuncture leading to bilateral pneumothoraces.

https://ift.tt/2Jal2qJ

Retreatment with pembrolizumab in advanced non-small cell lung cancer patients previously treated with nivolumab: emerging reports of 12 cases

Abstract

Purpose

After approval of anti-programmed cell death (PD)-1 antibodies, treatment for non-small cell lung cancer (NSCLC) has drastically changed. However, even in patients with favorable effects, therapeutic efficacy does not last long. Recently, retreatment with anti-PD-1 antibody has received attention. The aim of this study was to evaluate the efficacy and safety of retreatment with pembrolizumab in NSCLC patients previously treated with nivolumab.

Patients and methods

We retrospectively reviewed NSCLC patients retreated with pembrolizumab who were previously treated with nivolumab. We collected the following data: patient characteristics, number of cycles of nivolumab and pembrolizumab, treatment interval between nivolumab and pembrolizumab, best response, and immune-related adverse events.

Results

Twelve patients were reviewed. The median number of cycles of nivolumab was 12.5 (range 2–32 cycles). Seven patients (58.3%) achieved a partial response (PR) and two patients (16.7%) achieved stable disease (SD). Eight patients (66.7%) received cytotoxic chemotherapy between nivolumab and pembrolizumab. The median number of cycles of chemotherapy treatment was 4 (range 1–9 cycles). The median number of cycles of pembrolizumab was 3.5 (range 1–17 cycles). One patient (8.3%) achieved PR and four patients (33.3%) achieved SD as their best response to pembrolizumab. All patients showing response to pembrolizumab had very high (≥ 80%) tumor PD-Ligand 1 expression.

Conclusions

This study suggested that retreatment with anti-PD-1 antibody is a reasonable option for selected NSCLC patients.

https://ift.tt/2qHlQvA

Incidence, pattern and prognosis of brain metastases in patients with metastatic triple negative breast cancer

Abstract

Background

To identify the incidence, recurrence pattern and prognosis of brain metastases (BM) among women with metastatic triple negative breast cancer (mTNBC) treated consecutively at a single institution during a 7-year period.

Methods

Patients with histologically confirmed mTNBC were retrospectively identified. The incidence of BM as first site of recurrence and the cumulative BM incidence were computed. We used the Cox proportional hazards model to identify the univariate and multivariate factors associated with survival.

Results

Four hundred thirty three patients were included with a median overall survival (OS) of 21.6 months after median follow-up for 48.1 months. BM was found in 29% (127/433) of the patients and about a quarter (32/127) of BM was first recurrence. The cumulative incidence of BM at 1 and 2 years was 17 and 25%, respectively. The median time from the diagnosis of extracranial metastases to BM was 10 months. Median OS following a diagnosis of BM was 7.3 months. The longer median OS from time of first recurrent BM was noted compared with those of subsequent recurrent (17.3 vs 6.3 months, p = 0.008). However, patients with first recurrent BM were associated with shorter OS compared with those without BM (17.3 vs 22.1 months, p = 0.006). The independent factors that increased BM death risk were > 3 brain lesions, no BM-directed treatment, subsequent recurrent BM, symptomatic BM and uncontrolled extracranial metastasis.

Conclusions

Patients with mTNBC have a high incidence of early BM with subsequent poor survival. The findings lend support to consideration of screening imaging of the brain for mTNBC patients.

https://ift.tt/2HcfefI

Dietary patterns, BCMO1 polymorphisms, and primary lung cancer risk in a Han Chinese population: a case-control study in Southeast China

Abstract

Background

We investigated whether BCMO1 variants and dietary patterns are associated with lung cancer risk.

Methods

Case-control study including 1166 lung cancer cases and 1179 frequency matched controls was conducted for three BCMO1 variants (rs6564851, rs12934922, and rs7501331) and four dietary patterns were investigated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results

The rs6564851, rs12934922, and rs7501331 were not found to be associated with lung cancer risk (P > 0.05). In multivariable-adjusted models, compared to the lowest quartile of the score on the "fruits and vegetables" pattern, the highest quintile was associated with a 78.4% decreased risk (OR _{Q4 vs. Q1} = 0.216; 95% CI, 0.164–0.284; P for trend < 0.001). Other patterns were not found the association. The "fruits and vegetables" pattern was associated with a reduced risk of lung cancer with all 3 SNPs irrespective of genotypes (all P for trend< 0.001). The association for the "Frugal" pattern was associated with increased risk of lung cancer among smokers (P for interaction = 0.005). The protective effects of the "cereals/wheat and meat" pattern was more evident for squamous cell carcinoma and other histological type.

Conclusions

We did not observe associations of BCMO1 variants and lung cancer. Diets rich in fruits and vegetables may be protective against lung cancer.

https://ift.tt/2K0LGDI

AB0 blood groups and rhesus factor expression as prognostic parameters in patients with epithelial ovarian cancer – a retrospective multi-centre study

Abstract

Background

AB0 blood groups and Rhesus factor expression have been associated with carcinogenesis, response to treatment and tumor progression in several malignancies. The aim of the present study was to test the hypothesis that AB0 blood groups and Rhesus factor expression are associated with clinical outcome in patients with epithelial ovarian cancer (EOC).

Methods

AB0 blood groups and Rhesus factor expression were evaluated in a retrospective multicenter study including 518 patients with EOC. Their association with patients' survival was assessed using univariate and multivariable analyses.

Results

Neither AB0 blood groups nor Rhesus factor expression were associated with clinico-pathological parameters, recurrence-free, cancer-specific, or overall survival. In a subgroup of patients with high-grade serous adenocarcinoma, however, blood groups B and AB were associated with a better 5-year cancer-specific survival rate compared to blood groups A and 0 (60.3 ± 8.6% vs. 43.8 ± 3.6%, p = 0.04). Yet, this was not significant in multivariable analysis.

Conclusions

AB0 blood groups and Rhesus factor expression are both neither associated with features of biologically aggressive disease nor clinical outcome in patients with EOC. Further investigation of the role of the blood group B antigen on cancer-specific survival in the subgroup of high-grade serous should be considered.

https://ift.tt/2HgNhTV

Optimization of training periods for the estimation model of three-dimensional target positions using an external respiratory surrogate

Abstract

Background

During therapeutic beam irradiation, an unvisualized three-dimensional (3D) target position should be estimated using an external surrogate with an estimation model. Training periods for the developed model with no additional imaging during beam irradiation were optimized using clinical data.

Methods

Dual-source 4D-CBCT projection data for 20 lung cancer patients were used for validation. Each patient underwent one to three scans. The actual target positions of each scan were equally divided into two equal parts: one for the modeling and the other for the validating session. A quadratic target position estimation equation was constructed during the modeling session. Various training periods for the session—i.e., modeling periods (T_M)—were employed: T_M ∈ {5,10,15,25,35} [s]. First, the equation was used to estimate target positions in the validating session of the same scan (intra-scan estimations). Second, the equation was then used to estimate target positions in the validating session of another temporally different scan (inter-scan estimations). The baseline drift of the surrogate and target between scans was corrected. Various training periods for the baseline drift correction—i.e., correction periods (T_Cs)—were employed: T_C ∈ {5,10,15; T_C ≤ T_M} [s]. Evaluations were conducted with and without the correction. The difference between the actual and estimated target positions was evaluated by the root-mean-square error (RMSE).

Results

The range of mean respiratory period and 3D motion amplitude of the target was 2.4–13.0 s and 2.8–34.2 mm, respectively. On intra-scan estimation, the median 3D RMSE was within 1.5–2.1 mm, supported by previous studies. On inter-scan estimation, median elapsed time between scans was 10.1 min. All T_Ms exhibited 75th percentile 3D RMSEs of 5.0–6.4 mm due to baseline drift of the surrogate and the target. After the correction, those for each T_Ms fell by 1.4–2.3 mm. The median 3D RMSE for both the 10-s T_M and the T_C period was 2.4 mm, which plateaued when the two training periods exceeded 10 s.

Conclusions

A widely-applicable estimation model for the 3D target positions during beam irradiation was developed. The optimal T_M and T_C for the model were both 10 s, to allow for more than one respiratory cycle.

Trial registration

UMIN000014825. Registered: 11 August 2014.

https://ift.tt/2qF95T9

Prognostic factors of radiation dermatitis following passive-scattering proton therapy for breast cancer

Abstract

Background

To identify prognostic factors for grade 3 radiation dermatitis following passive-scattering proton therapy for breast cancer.

Methods

This retrospective study included data on 23 (11 post-mastectomy and 12 post-lumpectomy) breast cancer patients who underwent proton therapy with the passive scattering technique in our institute from 2012 to 2016. Each patient received 50–50.4 cobalt Gy equivalent (CGE) at 1.8 or 2 CGE per daily fraction. Logistic regression analysis was performed to identify prognostic factors for grade 3 skin toxicity. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the performance of the models.

Results

43% of the studied patients developed grade 3 radiation dermatitis. The dose-volume histogram (DVH) parameters of V52.5CGE and D10cm³ to skin5mm were correlated with grade 3 radiation dermatitis in both univariate and multivariate logistic regression analyses. Univariate logistic regression analysis suggested that D10cm³ to skin5mm (AUC = 0.69) and V52.5CGE to skin5mm (AUC = 0.70) were prognostic for grade 3 skin toxicity. The models using the combination of D10cm³ to skin5mm or V52.5CGE to skin5mm with breast volume marginally increased the AUC to 0.72 and 0.73, respectively. Models using the combination of D10cm³ to skin5mm or V52.5CGE to skin5mm with history of smoking increased the AUC to 0.75 and 0.83, respectively.

Conclusion

In the current study, we identified prognostic factors for grade 3 radiation dermatitis in patients treated with passive-scattering proton therapy for breast cancer. This study provides promising tool for identifying high risk patients for whom treatment plan adjustment could be done to reduce the risk of radiation-induced grade 3 skin toxicity.

https://ift.tt/2vsv44F

Identification of Skeletal Muscle Satellite Cells by Immunofluorescence with Pax7 and Laminin Antibodies

The precise identification of satellite cells is essential for studying their functions under various physiological and pathological conditions. This article presents a protocol to identify satellite cells on adult skeletal muscle sections by immunofluorescence-based staining.

https://ift.tt/2JXq5w1

Computational Analysis of the Caenorhabditis elegans Germline to Study the Distribution of Nuclei, Proteins, and the Cytoskeleton

We present an automated method for three-dimensional reconstruction of the Caenorhabditis elegans germline. Our method determines the number and position of each nucleus within the germline and analyses germline protein distribution and cytoskeletal structure.

https://ift.tt/2J9nk9t

Colorectal dysplasia and adenocarcinoma in patients with ulcerative colitis: an experience from a tertiary care hospital

Abstract

Background

The rationale behind this study was to find out the frequency of dysplasia and colorectal cancer (CRC) in young patients with ulcerative colitis (UC) using histopathological examination. This facilitated early detection of dysplasia and CRC by regular endoscopic biopsies and also guided physicians on appropriate surveillance and management, thus improved outcome.

Methods

It was a prospective cross-sectional study conducted at the Department of Pathology, PIMS, Islamabad. Seventy-six biopsies of already diagnosed cases of UC of young patients aged between 15 and 40 years of either gender were included. Specimens were fixed in 10% buffer formalin, paraffin embedded followed by cutting, slide preparation, and staining with hematoxylin and eosin (H&E) stain, and examined under light microscope. Statistical package for social sciences (SPSS 21) was used for data compilation and analysis. Mean and standard deviation were calculated for quantitative variables. Frequency and percentage were calculated for qualitative variables.

Results

There were 13 (17.2%) patients who were diagnosed with colorectal dysplasia, 3 (4.0%) with indefinite for dysplasia, 8 (10.5%) with low-grade dysplasia, and 2 (2.6%) with high-grade dysplasia. There were three (3.9%) patients who were diagnosed for colorectal carcinoma, one (1.3%) with grade 1, one (1.3%) with grade 2, and one (1.3%) with grade 3 CRC.

Conclusion

Routine biopsies can identify dysplastic epithelium, which is an established sign for synchronized carcinoma with ulcerative colitis, and give the rationale for surveillance of the patients.

https://ift.tt/2qJAGBO

Clinical outcomes of ultrashort sloping shoulder implant design: A survival analysis

Clinical Implant Dentistry and Related Research, EarlyView.


https://ift.tt/2qK8Bei

A long‐term prospective cohort study on immediately restored single tooth implants inserted in extraction sockets and healed ridges: CBCT analyses, soft tissue alterations, aesthetic ratings, and patient‐reported outcomes

Clinical Implant Dentistry and Related Research, EarlyView.


https://ift.tt/2vy2zm4

Human Adult Neurogenesis: Evidence and Remaining Questions

Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan.

https://ift.tt/2HfRzPG

The Dystrophin Glycoprotein Complex Regulates the Epigenetic Activation of Muscle Stem Cell Commitment

Establishment of cell polarity by the dystrophin complex is required for muscle stem cell asymmetric divisions. Chang et al. identify p38γ MAPK as a critical downstream regulator of satellite stem cell commitment, providing a link between dystrophin and epigenetic gene regulation to mediate asymmetric fates of daughter satellite cells.

https://ift.tt/2qL5gLe

Super-Obese Patient-Derived iPSC Hypothalamic Neurons Exhibit Obesogenic Signatures and Hormone Responses

Human hypothalamic neurons (HTNs) implicated in obesity have a limited availability. This study describes a reliable method for generating functional hormone-responsive HTNs from multiple normal and obese patient reprogrammed hiPSCs. Obese-patient-induced HTNs retained transcriptome profiles and functional phenotypes of high BMI, exhibiting aberrant obesity-related metabolic and respiratory pathways.

https://ift.tt/2HcxZDP

SNAI1, an endothelial–mesenchymal transition transcription factor, promotes the early phase of ocular neovascularization

Abstract

Ocular neovascularization is a comprehensive process involved in retinal vascular development and several blinding diseases such as age-related macular degeneration and retinopathy of prematurity, with vascular endothelial growth factor (VEGF) regarded as the master regulator. However, the qualified effect of anti-VEGF therapy reveals that the underlying mechanisms are still not clearly identified. To initialize angiogenesis, endothelial cells undergo a phenotype switching to generate highly migratory and invasive cells. This process shares certain similar characters observed in endothelial–mesenchymal transition (EndMT). Here, we found that SNAI1, an EndMT transcription factor, was expressed by endothelial cells in both physiological and pathological ocular neovascularization. SNAI1 overexpression triggered cell morphological change and enhanced cell motility, while loss of SNAI1 attenuated migration, invasion and sprouting. RNA sequence analysis further revealed that SNAI1 knockdown decreased the expression of genes related to cytoskeleton rearrangement and ECM remodeling. Moreover, intravitreal injection of small interfering RNA of SNAI1 suppressed new vessel formation in developing retina as well as mice model of choroidal neovascularization and oxygen-induced retinopathy. Therefore, we propose that the EndMT transcription factor SNAI1 promotes the early phase of ocular neovascularization and may provide a potential therapeutic target.

https://ift.tt/2K0tiLl

Efficacy of Aloe vera, Ananas comosus, and Sansevieria masoniana Cream on the Skin Wound Infected with MRSA

The tropical area has a lot of herbal medicines such as Aloe vera (AV), Ananas comosus (AC), and Sansevieria masoniana (SM). All the three have a unique potential effect as an antibacterial and wound-healing promoter. The aim of this study is to explore the role of AV, AC, and SM on the skin wound infected with methicillin-resistant Staphylococcus aureus (MRSA). Forty-five adult female Sprague Dawley rats weighing 250–300 grams were divided into 5 groups. All the groups were exposed to two round full-thickness punch biopsy and infected with MRSA. The group C was the control group/untreated; group BC was treated with base cream/without extract; group AV was treated with 75% AV cream; group AC was treated with 75% AC cream, and group SM was treated with 75% SM cream. The wounds were observed on days 5, 10, and 15. The healing of skin wounds was measured by a percentage of closure, skin tensile strength, and histopathology. The result showed that AV, AC, and SM have a similar potential effect on healing in the wound that was infected with MRSA compared to the groups C and BC (). It shows that all the three herbal formulations can be used as the alternative therapy to the wound infected with MRSA.

https://ift.tt/2Hd5cyY

Identification of Risk Factors in High-Dose Methotrexate-Induced Acute Kidney Injury in Childhood Acute Lymphoblastic Leukemia

Aims: Although high-dose methotrexate (HDMTX) is an effective means for the treatment of acute lymphoblastic leukemia (ALL), the development of renal dysfunction remains a significant management challenge. This study aimed to identify the key factors in HDMTX-induced acute kidney injury (AKI) in childhood ALL. Methods: We retrospectively analyzed the clinical data in 1,329 courses of HDMTX treatment in 336 Chinese ALL children at the First Affiliated Hospital of Guangxi Medical University from September 2012 to November 2016. The clinical data were compared between the groups of children with development of AKI and those without. Risk factors were identified by multiple logistic regression analysis, and the diagnostic performance of plasma MTX concentration was evaluated by receiver operating characteristic (ROC) curve analysis. Results: AKI was observed in 88 patients (26.2%) and 104 courses (7.8%). Binary logistic regression revealed that age (OR 1.349; p = 0.005), first HDMTX course (OR 1.767; p = 0.013), MTX dose per body surface area (BSA; OR 1.944; p = 0.015), and baseline serum total protein (OR 0.929; p = 0.021) significantly correlated with AKI. The area under the ROC for 48-h plasma MTX concentration was 0.890 (95% CI 0.850–0.930), and sensitivity and specificity values of the cut-off value were 78.8 and 90.4%, respectively. Conclusion: Increasing age, higher MTX dose per BSA, lower baseline serum protein, and first HDMTX course were significant risk factors for developing HDMTX-induced AKI in childhood ALL. The threshold of 48-h MTX plasma concentration is valuable for the prediction of HDMTX-induced AKI.
Chemotherapy 2018;63:101–107

https://ift.tt/2F004Z9

Complement receptor 1 gene ( CR1 ) intragenic duplication and risk of Alzheimer’s disease

Abstract

Single nucleotide variants (SNVs) within and surrounding the complement receptor 1 (CR1) gene show some of the strongest genome-wide association signals with late-onset Alzheimer's disease. Some studies have suggested that this association signal is due to a duplication allele (CR1-B) of a low copy repeat (LCR) within the CR1 gene, which increases the number of complement C3b/C4b-binding sites in the mature receptor. In this study, we develop a triplex paralogue ratio test assay for CR1 LCR copy number allowing large numbers of samples to be typed with a limited amount of DNA. We also develop a CR1-B allele-specific PCR based on the junction generated by an historical non-allelic homologous recombination event between CR1 LCRs. We use these methods to genotype CR1 and measure CR1-B allele frequency in both late-onset and early-onset cases and unaffected controls from the United Kingdom. Our data support an association of late-onset Alzheimer's disease with the CR1-B allele, and confirm that this allele occurs most frequently on the risk haplotype defined by SNV alleles. Furthermore, regression models incorporating CR1-B genotype provide a better fit to our data compared to incorporating the SNV-defined risk haplotype, supporting the CR1-B allele as the variant underlying the increased risk of late-onset Alzheimer's disease.

https://ift.tt/2HN6TQO

Secondary prevention and lifestyle indices after stroke in a long‐term perspective

Acta Neurologica Scandinavica, EarlyView.


https://ift.tt/2Hf1CQX

Toxic effects of arsenic trioxide on Echinococcus granulosus protoscoleces through ROS production, and Ca2+-ER stress-dependent apoptosis

Abstract

Cystic echinococcosis is a severe parasitic disease that commonly affects the liver and causes abscesses or rupture into the surrounding tissues, leading to multiple complications, such as shock, severe abdominal pain, and post-treatment abscess recurrence. Currently, there are no efficient measures to prevent these complications. We previously confirmed that arsenic trioxide (As₂O₃) exhibited in vitro cytotoxicity against Echinococcus granulosus protoscoleces. In the present study, we aimed to explore the mechanism of As₂O₃-induced E. granulosus protoscoleces apoptosis. After exposing E. granulosus protoscoleces to 0, 4, 6, and 8 μM of As₂O₃, reactive oxygen species (ROS) level was detected by fluorescence microscopy; superoxide dismutase (SOD), and caspase-3 activities were measured; intracellular Ca²⁺ was detected by flow cytometry; GRP-78 and caspase-12 protein levels were measured by western blot analysis. Our results showed that the expression of caspase-3 was gradually increased and the expression of SOD was gradually decreased in As₂O₃-treated groups of protoscoleces. Simultaneously, fluorescence microscopy and flow cytometry showed that the ROS level and the intracellular Ca²⁺ level were increased in a time- and dose-dependent manner. Western blot analysis showed that the expressions of GRP-78 and caspase-12 were higher in As₂O₃-treated groups than in the control group. These results suggest that As₂O₃-induced apoptosis in E. granulosus protoscoleces is related to elevation of ROS levels, disruption of intracellular Ca²⁺ homeostasis, and endoplasmic reticulum stress. These mechanisms can be targeted in the future by safer and more effective drugs to prevent recurrence of cystic echinococcosis.

https://ift.tt/2JYviDH

Mitochondria-associated endoplasmic reticulum membranes (MAMs) involve in the regulation of mitochondrial dysfunction and heart failure

https://ift.tt/2JaS8qD

BET 2: Blood biomarkers as an alternative to imaging in diagnosing acute ischaemic stroke

A short-cut review was carried out to establish the diagnostic accuracy of blood biomarkers as an alternative to imaging for the diagnosis of ischaemic stroke. Nine studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that that blood biomarkers are currently not suitable for the diagnosis of acute ischaemic stroke.

https://ift.tt/2qL7REV

Towards evidence-based emergency medicine: Best BETs from the Manchester Royal Infirmary

Best Evidence Topic reports (BETs) summarise the evidence pertaining to particular clinical questions. They are not systematic reviews, but rather contain the best (highest level) evidence that can be practically obtained by busy practising clinicians. The search strategies used to find the best evidence are reported in detail in order to allow clinicians to update searches whenever necessary. Each BET is based on a clinical scenario and ends with a clinical bottom line which indicates, in the light of the evidence found, what the reporting clinician would do if faced with the same scenario again.

The BETs published below were first reported at the Critical Appraisal Journal Club at the Manchester Royal Infirmary1 or placed on the BestBETs website. Each BET has been constructed in the four stages that have been described elsewhere.2 The BETs shown here, together with those published previously and those currently...

https://ift.tt/2HcmvjM

Abstracts from international Emergency Medicine journals

Editor's note: EMJ has partnered with the journals of multiple international emergency medicinesocieties to share from each a highlighted research study, as selected by their editors. This editionwill feature an abstract from each publication.

https://ift.tt/2HcH8w3

Authors response to 'Impact of physician navigators: looking beyond productivity metrics and silver bullets by Leung et al

We would like to thank Dr Leung et al1 and the editors for the opportunity to engage in further discussion on the issues presented in our commentary entitled 'Tackling the demand for emergency department services: there are no silver bullets'.2 We believe that the intervention proposed by Leung et al3 demonstrated improved timeliness to definitive patient care and was an important contribution to the medical literature around emergency department (ED) flow optimisation. Furthermore, we applaud the authors on a broader adoption of the programme to their local clinical environment and their ability to change culture in the clinical setting.

Our initial commentary centred around quality improvement (QI) science methodology and appropriate application of its tenets. In the paper by Leung et al,3 a novel application was proposed in face of a common ED problem. While the study contributes to our understanding...

https://ift.tt/2HcmD2K

Impact of Physician Navigators: Looking beyond productivity metrics and silver bullets

We thank Mercuri and Mondoux for their commentary1 on our study which introduced Physician Navigators as a novel intervention to improve ED productivity and efficiency.2 The authors expressed concern about the potential trade-off between improved productivity and compromised patient outcomes, and described Physician Navigators as limited to improving timely care with potential negative consequences on the other dimensions of quality. This is a limited approach to understanding the utility of Physician Navigators.

The Province of Ontario started to systematically tracked ED return rates to any hospital within 72 hours of discharge and rates of sentinel diagnoses (ie, missed acute myocardial infarction, subarachnoid hemorrhage, paediatric sepsis) within 7 days of discharge from an ED. Although collection of this data started after our study's conclusion, our current rates of ED return and sentinel diagnoses have remained on par with the provincial averages.3 To our knowledge, there...

https://ift.tt/2qK8i2m

BET 1: Can Salter-Harris type I fractures be diagnosed by ultrasound?

A short-cut review was carried out to establish the diagnostic accuracy of ultrasound for Salter-Harris type 1 fractures. Three studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that ultrasound may allow visualisation of Salter-Harris type 1 fractures. However, little is known as to its sensitivity and specificity, and therefore it cannot be used to eliminate the diagnosis.

https://ift.tt/2qKXstb

What is positionality and should it be expressed in quantitative studies?

Although we are increasingly reaping the benefits of qualitative studies, their approach and that of quantitative studies remain rather separate. Emergency medicine practitioners thrive off research in context as we deal with such an undifferentiated population however quantitative 'hard-science' work is conspicuous for its absence of positionality. This contrasts strongly with the way in which qualitative research, within the domain of so-called soft-science literature, uses positionality as an integral element of the research process. Without contextualising the researcher and research environment in qualitative studies, often the meaning of any research output is lost. What follows is that positionality does not undermine the truth of such research, instead it defines the boundaries within which the research was produced. The absence of positionality when considered alongside the notion of bias, may challenge the quantitative idea of validity.

https://ift.tt/2HbxppO

Effects of prophylactic anticholinergic medications to decrease extrapyramidal side effects in patients taking acute antiemetic drugs: a systematic review and meta-analysis

Objectives

To determine the effectiveness of prophylactic anticholinergic medications in reducing extrapyramidal symptoms in patients taking acute antiemetics with a dopamine D2 receptor antagonist effect.

Methods

Systematic searches of all published studies through March 2017 were identified from PubMed, Cochrane library, Embase, Web of Science and Scopus. Only randomised controlled trials of patients receiving dopamine D2 antagonist antiemetic therapy for acute migraine in which an anticholinergic or placebo was compared were included. Pooled ORs were calculated for incidence of extrapyramidal symptoms and sedation.

Results

Four placebo-controlled randomised controlled trials consisting of 737 patients met the inclusion criteria for our meta-analysis. The effect of diphenhydramine differed depending on the method of administration of the antiemetic. When the antiemetic was delivered as a 2 min antiemetic bolus, the odds of extrapyramidal symptoms were significantly reduced in the diphenhydramine group compared with placebo (OR 0.42; 95% CI 0.22 to 0.81; P=0.01). However, when the antiemetic was given as a 15 min infusion, there was no significant difference in extrapyramidal symptoms with or without diphenhydramine (OR 1.06; 95% CI 0.58 to 1.91; P=0.85). The lowest incidence of extrapyramidal symptoms was observed in patients receiving a 15 min antiemetic infusion without diphenhydramine prophylaxis (9.8%). In two trials including 351 patients that dichotomously reported sedation scales, diphenhydramine had significantly higher rates of sedation (31.6%vs19.2%, OR 2.01, 95% CI 1.21 to 3.33; P=0.007).

Conclusion

Prophylactic diphenhydramine reduces extrapyramidal symptoms in patients receiving bolus antiemetic therapy with a dopamine D2 antagonist effect, but not when it is given as an infusion. Because of significantly greater sedation with diphenhydramine, the most effective strategy is to administer the D2 antagonist antiemetic as a 15 min infusion without prophylaxis.

https://ift.tt/2qL8233

Image challenge: acute chest pain after tooth extraction

Clinical introduction

A previously healthy 55-year-old woman presented to the ED with chest discomfort. She underwent wisdom tooth extraction the same morning, during which she experienced discomfort over the right side of neck, which gradually spread to the right and central chest region, and was associated with discomfort while breathing. On examination, there was tenderness over the neck and chest. Range of motion of the neck was limited due to pain. Her vitals were stable, and the rest of the physical examination was unremarkable.

A frontal chest radiograph was obtained (figure 1).

Question

What is the most likely diagnosis for this patient?

Spontaneous pneumothorax

Spontaneous pneumomediastinum

Spontaneous pneumopericardium

Foreign body in respiratory tract

Answer: B

The chest radiograph of this patient shows pneumomediastinum and soft tissue emphysema in the neck (figure 2). Pneumomediastinum is the presence of air within...

https://ift.tt/2HcmGeW

Ultrasound evaluation of the respiratory changes of the inferior vena cava and axillary vein diameter at rest and during positive pressure ventilation in spontaneously breathing healthy volunteers

Introduction

Ultrasound assessment of the inferior vena cava (IVC) has gained favour in aiding fluid management decisions for controlled, mechanically ventilated patients as well as in non-mechanically ventilated, spontaneously breathing patients. Its utility in spontaneously breathing patients during positive pressure non-invasive ventilation has not yet been determined. The use of the axillary vein, as an alternative option to the IVC due to its ease of accessibility and independence from intra-abdominal pressure, has also not been evaluated. The aim of this study was to assess respiratory variation in IVC and axillary vein diameters in spontaneously breathing participants (Collapsibility Index) and with the application of increasing positive end-expiratory pressure (PEEP) via positive pressure non-invasive ventilation (Distensibility Index).

Methods

The IVC and axillary vein diameters of 28 healthy adult volunteers were measured, using ultrasound, at baseline and with increasing PEEP via non-invasive ventilation. The Collapsibility Index and Distensibility Index of these vessels were calculated and compared for each vessel. The association between increasing PEEP levels and the indices was evaluated.

Results

Positive pressure delivered via non-invasive ventilation produced a similar degree of diameter change in the IVC and the axillary vein, that is, the Distensibility Index was similar whether measured in the IVC or the axillary vein (P=0.21, 0.47 and 0.17 at baseline, 5 and 10 cmH₂O PEEP, respectively). Individual study participants' IVC and axillary veins, however, had variable responses to PEEP; that is, there appeared to be no consistent relationship between PEEP and the diameter changes.

Conclusion

While the axillary vein could potentially be used as an alternative vessel to the IVC to assess for volume responsiveness in controlled, mechanically ventilated patients as well as in non-mechanically ventilated, spontaneously breathing patients, neither vein should be used to guide fluid management decisions in spontaneously breathing patients during positive pressure non-invasive ventilation.

https://ift.tt/2qLZA3P

Impact of emergency department surge and end of shift on patient workup and treatment prior to referral to internal medicine: a health records review

Background

The goal of this study was to determine if ED surge and end-of-shift assessment of patients affect the extent of diagnostic tests, therapeutic interventions and accuracy of diagnosis prior to referral to internal medicine.

Methods

This study was a health records review of consecutive patients referred to the internal medicine service with an ED diagnosis of heart failure, chronic obstructive pulmonary disease (COPD) or sepsis starting 1 December 2013 until 100 cases for each condition had been obtained. We developed a scoring system in consultation with emergency and internal medicine physicians to uniformly assess the completeness of treatments and investigations performed. These scores, expressed as percentage of possible points, were compared at high and low surge levels and at middle and end of shift at time of patient referral. End of shift was defined as 7:30–8:30, 15:30–16:30 and 23:30–00:30 as our shift changes occur at 8:00, 16:00 and 24:00. Rate of admission, diversion to other services and diagnosis disagreements were also assessed.

Results

We included 308 patients (101 heart failure, 101 COPD, 106 sepsis) with a mean age of 74.7. Comparing middle of shift to end of shift, the mean scores were 91.9% versus 91.8% (difference 0.1% (95% CI –2.4 to 3.0)) for investigations and 73.0% versus 70.4% (difference 2.6% (95% CI –1.8 to 7.4)) for treatments. Comparing low to high surge times, the mean scores were 92.1% versus 91.7% (difference 0.4% (95% CI –1.2 to 2.4)) for investigations and 71.4% versus 73.6% (difference –2.2% (95% CI –5.6 to 1.3)) for treatments. We found low rates of diversion to alternate services (8.9% heart failure, 0% COPD, 6.6% sepsis) and low rates of diagnosis disagreement (4.0% heart failure, 10.9% COPD, 8.5% sepsis).

Conclusions

We found no evidence that surge levels and end of shift impact the extent of investigations and treatments provided to patients diagnosed in the ED with heart failure, COPD or sepsis and referred to internal medicine.

https://ift.tt/2qJPgt3

New decision formulas for predicting endotracheal tube depth in children: analysis of neck CT images

Introduction

The purpose of this study was to construct a prediction model for endotracheal tube depth using neck CT images.

Methods

A retrospective image review was conducted that included patients who had undergone neck CT. Using sagittal neck CT images, we calculated the length between upper incisor and mid-trachea and then derived the model via regression analysis. The model was validated externally using chest radiographs of patients who had undergone endotracheal intubation. We compared performance of our model with that of other methods (Broselow tape and APLS formula) via Bland-Altman analysis and the percentage of estimations within 10% of the measured values.

Results

A total of 1111 children were included in this study. The tube depth obtained from CT images was linearly related to body weight (tube depth (cm)=5.5+0.5xbody wt (kg)) in children younger than 1 year and to height (tube depth (cm)=3+0.1xheight (cm)) in children older than 1 year. External validation demonstrated that our new model showed better agreement with the desired tube depth than Broselow tape and APLS formula. The mean differences in children younger than 1 year were 0.61 cm and –1.24 cm for our formula and Broselow tape, respectively. The mean differences in children older than 1 year were –0.43 cm, –1.98 and –1.64 cm for our formula, Broselow tape and APLS formula, respectively. The percentages of estimates within 10% of the measured values were 52.7% and 35.8% for our formula and Broselow tape in children younger than 1 year, respectively, and 54.3%, 33.8% and 37.2% for our formula, Broselow tape and APLS formula in children older than 1 year, respectively (P<0.01).

Conclusion

Our new formula is useful and more accurate than the currently available methods.

https://ift.tt/2HcmU5M

Absence of a quick fix does not mean 'do nothing: time to address drug use in the ED

It is unsurprising that a brief counselling intervention for drug use has no effect on drug use or linkage to drug treatment. Although psychological interventions sometimes have delayed effects, the brief intervention studied by Merchant et al1 had none at 3 months and still had none at 12 months. The study had some limitations as described by the authors, but it was null, just like prior studies in the ED and in primary care.2 3 Screening, brief intervention and referral to treatment (SBIRT in the USA), simply does not improve outcomes for unhealthy drug use.

Unhealthy substance use is not just one risk factor (eg, weekly cannabis use) or disease (eg, opioid use disorder) just as heart disease comprises many diseases all of which have specific treatments. A one-size-fits-all approach like SBIRT will not be effective; tailoring will be necessary.

No experienced clinician (or researcher...

https://ift.tt/2HckCDH

Comparison of epidemiology, treatments and outcomes of ST segment elevation myocardial infarction between young and elderly patients

Background

With an ageing population, there is a need to understand the relative risk/benefit of interventions for elderly ST segment elevation myocardial infarction (STEMI) patients. The primary aim of this study was to compare epidemiology, treatments and outcomes between young and elderly STEMI patients. Our secondary aim was to determine the cut-off age when the benefits of primary percutaneous coronary intervention (PCI) were less pronounced.

Methods

Data were collected by the Singapore Myocardial Infarction Registry. Patients were categorised into young (age <65 years) and elderly STEMI (age ≥65 years) patients.

Results

We analysed 14 006 STEMI cases collected between January 2007 and December 2014; 33.9% were elderly STEMI patients. Elderly STEMI patients had longer median door to balloon (73 vs 64 min, P<0.001) time and were less likely to receive PCI (proportion difference=–23.6%, 95% CI –25.3 to –22.0). In the absence of PCI, elderly STEMI patients had a higher mortality within 30 days (elderly: HR 1.65, 95% CI 1.36 to 1.99, P<0.001; young: HR 1.10, 95% CI 0.79 to 1.54, P=0.573) and 1 year (elderly: HR 1.83, 95% CI 1.57 to 2.14, P<0.001; young: HR 1.41, 95% CI 1.09 to 1.83, P=0.009) of admission. The 1 year survival benefit of PCI started to decline after the age of 65 years.

Conclusion

Elderly STEMI patients were less likely to receive PCI and had longer door to balloon times. Survival benefit of PCI decreased after the age of 65 years, with the decline most evident from age 85 years onwards. The risks of PCI need to be weighed carefully against its benefits, especially in very elderly patients.

https://ift.tt/2HckiEV

Lack of efficacy in a randomised trial of a brief intervention to reduce drug use and increase drug treatment services utilisation among adult emergency department patients over a 12-month period

Objectives

Assess the 12-month efficacy of a brief intervention (BI) on reducing drug use and increasing drug treatment services utilisation among adult emergency department (ED) patients.

Methods

This randomised, controlled trial enrolled 18–64-year-old ED patients needing a drug use intervention. Treatment arm participants received a tailored BI while control arm participants only completed the study questionnaires. Self-reported past 3-month drug use and engagement in drug treatment services were compared by study arm at 3-month intervals over 1 year. Multiple imputations were performed to overcome loss-to-follow-up.

Results

Of the 1030 participants, follow-up completion ranged 55%–64% over the four follow-ups. At 12 months, the two study arms were similar in regards to mean: (1) proportion reporting any drug use (treatment: 67.1% (61.6 to 72.6), control: 74.4% (69.4 to 79.4)); (2) drug use frequency on a five-point scale (treatment: 3.7 (3.3 to 4.2), control: 4.6 (4.0 to 5.2)); (3) total days of drug use (treatment: 28.3 (23.2 to 33.4), control: 33.4 (28.5 to 38.2)); (4) most number of times drugs used/day (treatment: 4.6 (3.6 to 5.5), control: 6.1 (4.8 to 7.3)) and (5) typical number of times drugs used/day (treatment: 3.3 (2.5 to 4.1), control: 5.1 (3.9 to 6.2)). Utilisation of drug treatment services also was similar by study arm. In multivariable regression analyses, patients who were homeless or had higher drug use at baseline continued to have greater drug use in follow-up.

Conclusions

Among adult ED patients requiring a drug use intervention, this BI did not decrease drug use or increase drug treatment services utilisation over a 12-month period more than the control condition.

Trial registration number

NCT01124591; Pre-trial.

https://ift.tt/2qMFt5g

Sudden onset paraplegia

Clinical introduction

A 75-year-old man presented with acute onset thoracic back pain, progressive leg weakness with numbness and urinary retention. His symptoms started suddenly and progressed overnight. He denied a recent history of trauma. On neurological examination he had complete loss of all sensations below Th10 level and leg paraplegia (American Spinal Injury Association grade A myelitis). Admission lateral spine X-ray and non-contrast CT were performed (figures 1 and 2).

Question

What is the most likely cause of the clinical presentation?

Fracture of Th12 vertebral body

Acute cerebrovascular accident

Intramedullary tumour

Acute spontaneous spinal haematoma

Answer:D

Acute spontaneous spinal epidural haematoma (ASSEDH). The patient's X-rays and CT showed a compression fracture at Th12, but the neurological examination was consistent with a lesion at the Th10 neurological level. Moreover, the fracture was likely old due to the finding of endplate and cortical osteosclerosis and remodelling...

https://ift.tt/2HcmNXU