The Evolving Dilemma of Factor XI in Pregnancy: Suggestions for Management

A case of a patient with severe factor XI (FXI) deficiency who presented for her seventh labor and delivery is presented. The nature of FXI deficiency, its prevalence, and issues related to genetic screening are discussed. Published literature on the topic is reviewed, including criteria that were developed to assess bleeding, laboratory tools used to estimate bleeding risk, and available treatments. Within the context of this challenging clinical dilemma, specific recommendations are provided for the antepartum, intrapartum, and postpartum stages of pregnancy. These include recommendations that take into account both FXI levels and history of any abnormal bleeding. While there are effective treatments available, it is important to consider that institutional multidisciplinary protocols are needed to manage this complex disorder. More work is needed to define the best management protocols. Accepted for publication December 19, 2017. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Aryeh Shander, MD, Department of Anesthesiology, Englewood Hospital and Medical Center, 350 Engle St, Englewood, NJ 07631. Address e-mail to aryeh.shander@ehmchealth.org. © 2018 International Anesthesia Research Society

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Sex Difference of Angiotensin IV–, LVV-Hemorphin 7–, and Oxytocin-Induced Antiallodynia at the Spinal Level in Mice With Neuropathic Pain

Background: We demonstrated previously that angiotensin IV (Ang IV) and LVV-hemorphin 7 (LVV-H7) act through the blockade of insulin-regulated aminopeptidase to decrease oxytocin degradation, thereby causing antihyperalgesia at the spinal level in rats. We determined that intrathecal oxytocin can induce significant antihyperalgesia in male rats with inflammation but not in female rats. Thus, we speculate that Ang IV, LVV-H7, and oxytocin can induce antiallodynia, which could be of great therapeutic potential. Because the antihyperalgesia by using these peptides was with sex difference, their possible antiallodynia was examined in male and female mice for comparison. We investigated whether Ang IV, LVV-H7, and oxytocin produce antiallodynia at the spinal level in mice and whether this antiallodynia differs between the sexes. METHODS: Partial sciatic nerve ligation surgery was performed on adult male and female C57BL/6 mice from the same litter (25–30 g). The effects of intrathecal injections of Ang IV (25.8 nmol), LVV-H7 (27.2 nmol), and oxytocin (0.125 or 1.25 nmol) were assessed through the von Frey test 3 days after partial sciatic nerve ligation. RESULTS: Intrathecal injection of Ang IV, LVV-H7, and oxytocin all produced a potent antiallodynia in male mice. However, these antiallodynia effects were either extremely weak or absent in female mice at the same dose. CONCLUSIONS: Intrathecal Ang IV, LVV-H7, and oxytocin can all cause significant antiallodynia in male mice. The Ang IV-, LVV-H7-, and oxytocin-induced antiallodynia effects differed between the sexes at the spinal level in mice. Accepted for publication November 28, 2017. Funding: The study was supported by National Defense Medical Center, Taipei, Taiwan, and was funded by the Tri-Service General Hospital Songshan Branch, Taipei, Taiwan (TSGH-SSB-10407), and the Ministry of Science and Technology, Taiwan (103-2320-B-016-016-MY3). This manuscript was edited by Wallace Academic Editing The authors E. Y.-K. Huang and J.-H. Kao have contributed equal to this study. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Eagle Yi-Kung Huang, PhD and Jen-Hsin Kao, PhD, Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. Address e-mail to eyh58@mail.ndmctsgh.edu.tw and cindykao1128@gmail.com. © 2018 International Anesthesia Research Society

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A Systematic Review of Outcomes Associated With Withholding or Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Before Noncardiac Surgery

BACKGROUND: The global rate of major noncardiac surgical procedures is increasing annually, and of those patients presenting for surgery, increasing numbers are taking either an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin receptor blocker (ARB). The current recommendations of whether to continue or withhold ACE-I and ARB in the perioperative period are conflicting. Previous meta-analyses have linked preoperative ACE-I/ARB therapy to the increased incidence of postinduction hypotension; however, they have failed to correlate this with adverse patient outcomes. The aim of this meta-analysis was to determine whether continuation or withholding ACE-I or ARB therapy in the perioperative period is associated with mortality and major morbidity. METHODS: This meta-analysis was prospectively registered on PROSPERO (CRD42017055291). A comprehensive search of MEDLINE (PubMed), CINAHL (EBSCO host), ProQuest, Cochrane database, Scopus, and Web of Science was conducted on December 6, 2016. We included adult patients >18 years of age on chronic ACE-I or ARB therapy who underwent noncardiac surgery in which ACE-I or ARB was either withheld or continued on the morning of surgery. Primary outcomes included all-cause mortality and major cardiac events (MACE). Secondary outcomes included the risk of congestive heart failure, acute kidney injury, stroke, intraoperative/postoperative hypotension, and the length of hospital stay. RESULTS: After abstract review, the full text of 25 studies was retrieved, of which 9 fulfilled the inclusion criteria: 5 were randomized control trials, and 4 were cohort studies. These studies included a total of 6022 patients on chronic ACE-I/ARB therapy before noncardiac surgery. A total of 1816 patients withheld treatment the morning of surgery and 4206 continued their ACE-I/ARB. Preoperative demographics were similar between the 2 groups. Withholding ACE-I/ARB therapy was not associated with a difference in mortality (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.62–1.52; I2 = 0%) or MACE (OR, 1.12; 95% CI, 0.82–1.52; I2 = 0%). However, withholding therapy was associated with significantly less intraoperative hypotension (OR, 0.63; 95% CI, 0.47–0.85; I2 = 71%). No effect estimate could be pooled concerning length of hospital stay and congestive heart failure. CONCLUSIONS: This meta-analysis did not demonstrate an association between perioperative administration of ACE-I/ARB and mortality or MACE. It did, however, confirm the current observation that perioperative continuation of ACE-I/ARBs is associated with an increased incidence of intraoperative hypotension. A large randomized control trial is necessary to determine the appropriate perioperative management of ACE-I and ARBs. Accepted for publication December 19, 2017. Funding: No outside funding was utilized in the search and retrieval of all articles. All funding was from departmental resources. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). PROSPERO registry: CRD42017055291. Reprints will not be available from the authors. Address correspondence to Caryl Hollmann, MBChB, DA (SA), Department of Anaesthesia and Perioperative Medicine, D23, Groote Schuur Hospital, University of Cape Town, Observatory, Cape Town 7925, South Africa. Address e-mail to carylhollmann@gmail.com. © 2018 International Anesthesia Research Society

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Activation of Melatonin Receptors by Ramelteon Induces Cardioprotection by Postconditioning in the Rat Heart

Activation of melatonin receptors protects the heart against ischemia-reperfusion injury. Ramelteon, a clinically used drug for insomnia, acts via activation of melatonin receptors. We investigated whether ramelteon induces acute infarct size reduction by postconditioning. Male Wistar rats were randomized to 6 groups. Hearts were treated with melatonin and ramelteon at the beginning of reperfusion. The melatonin receptor inhibitor luzindole was administered with and without melatonin and ramelteon, respectively. Ramelteon reduced infarct size to the same extent as melatonin. Both effects were completely abolished by luzindole. The results show for the first time that ramelteon induces cardioprotection by postconditioning. Accepted for publication September 27, 2017. Funding: This work was supported by departmental funding only. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Ragnar Huhn, MD, PhD, Department of Anesthesiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany. Address e-mail to Ragnar.Huhn@med.uni-duesseldorf.de. © 2018 International Anesthesia Research Society

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In Response

No abstract available

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Flupirtine: A Less-Explored, Neglected Nonopioid Analgesic

No abstract available

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Misguided by INR in Liver Disease Patients? Implications for Clinicians Including Pain Proceduralists

No abstract available

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ABC of Clinical Leadership, 2nd ed

No abstract available

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Summative Objective Structured Clinical Examination Assessment at the End of Anesthesia Residency for Perioperative Ultrasound

While standardized examinations and data from simulators and phantom models can assess knowledge and manual skills for ultrasound, an Objective Structured Clinical Examination (OSCE) could assess workflow understanding. We recruited 8 experts to develop an OSCE to assess workflow understanding in perioperative ultrasound. The experts used a binary grading system to score 19 graduating anesthesia residents at 6 stations. Overall average performance was 86.2%, and 3 stations had an acceptable internal reliability (Kuder–Richardson formula 20 coefficient >0.5). After refinement, this OSCE can be combined with standardized examinations and data from simulators and phantom models to assess proficiency in ultrasound. Accepted for publication December 11, 2017. Funding: This study was funded by the Foundation for Anesthesia Research and Education (FAER) as part of a grant awarded to Robina Matyal. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). J. D. Mitchell and R. Amir contributed equally to this work. Reprints will not be available from the authors. Address correspondence to John D. Mitchell, MD, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Rd, RB-470, Boston, MA 02215. Address e-mail to jdmitche@bidmc.harvard.edu. © 2018 International Anesthesia Research Society

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Novel TOF-MS means of quantifying apoAI amyloid protein load following combined liver kidney transplantation

No abstract available

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Gender, Race and Disease Etiology Predict De Novo Malignancy Risk following Liver Transplantation: Insights for Future Individualized Cancer Screening Guidance

AbstractBackgroundMalignancy after liver transplant (LT) is a leading cause of mortality, but data is limited. The aim of this study was to identify patients at higher risk for de novo malignancies after LT in a large multicenter database.MethodsThe Scientific Registry of Transplant Recipients database comprising all 108,412 liver transplant recipients across the U.S. between 1987 and March 2015 was analyzed with a median follow-up of 6.95 years. Potential risk factors for malignancies after LT were assessed using Cox regression analysis for the outcome of time to first malignancy.ResultsMean age 51.9 ± 10.8 years, 64.6% male, 74.5% Caucasian, and 15.8% with previous malignancy. Malignancies during follow-up were 4,483 (41.3%) skin, 1,519 (14.0%) hematologic, and 4,842 (44.7%) solid organ. The 10-year probability of de novo malignancy was 11.5% (11.3-11.8%). On multivariable analysis, age by decade (HR 1.52; p

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Incidence of Cytomegalovirus DNAemia in Pediatric Kidney Transplant Recipients after Cessation of Antiviral Prophylaxis

AbstractBackgroundLate cytomegalovirus (CMV) infection can occur after cessation of viral prophylaxis in kidney transplant recipients, yet, timing of infection is unclear and longer duration of prophylaxis may be warranted.MethodsWe conducted a retrospective cohort study of 86 children (35 CMV donor seropositive, recipient seronegative [D+R-] and 51 CMV recipient seropositive [R+])

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Successful sequential liver and haematopoietic stem cell transplantation in a child with CD40 ligand deficiency and Cryptosporidium-induced liver cirrhosis

ABSTRACTBACKGROUNDHematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiencies. However, pre-HSCT conditioning entails unacceptably high risks if the liver is compromised. The presence of a recurrent opportunistic infection affecting the biliary tree and determining liver cirrhosis with portal hypertension posed particular decisional difficulties in a seven-year-old child with X-linked CD40-ligand deficiency. We aim at adding to the scanty experience available on such rare cases, as successful management with sequential liver transplantation (LT) and HSCT has been reported in detail only in one young adult to date.METHODSa closely sequential strategy, with a surgical complication-free LT, followed by reduced-intensity conditioning, allowed HSCT to be performed only one month after LT, preventing Cryptosporidium parvum recolonization of the liver graft.RESULTScombined sequential LT and HSCT resolved the cirrhotic evolution and corrected the immunodeficiency so that the infection responsible for the progressive sclerosing cholangitis did not recur.CONCLUSIONShopefully this report of the successful resolution of a potentially fatal combination of immunodeficiency and chronic opportunistic infection with end-stage organ damage in a child, will encourage others to adopt a sequential transplant approach to this highly complex pathology. However, caution is to be exercised to carefully balance the risks intrinsic to transplant surgery and immunosuppression in primary immunodeficiencies. BACKGROUND Hematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiencies. However, pre-HSCT conditioning entails unacceptably high risks if the liver is compromised. The presence of a recurrent opportunistic infection affecting the biliary tree and determining liver cirrhosis with portal hypertension posed particular decisional difficulties in a seven-year-old child with X-linked CD40-ligand deficiency. We aim at adding to the scanty experience available on such rare cases, as successful management with sequential liver transplantation (LT) and HSCT has been reported in detail only in one young adult to date. METHODS a closely sequential strategy, with a surgical complication-free LT, followed by reduced-intensity conditioning, allowed HSCT to be performed only one month after LT, preventing Cryptosporidium parvum recolonization of the liver graft. RESULTS combined sequential LT and HSCT resolved the cirrhotic evolution and corrected the immunodeficiency so that the infection responsible for the progressive sclerosing cholangitis did not recur. CONCLUSIONS hopefully this report of the successful resolution of a potentially fatal combination of immunodeficiency and chronic opportunistic infection with end-stage organ damage in a child, will encourage others to adopt a sequential transplant approach to this highly complex pathology. However, caution is to be exercised to carefully balance the risks intrinsic to transplant surgery and immunosuppression in primary immunodeficiencies. Corresponding Author: Pier Luigi Calvo, MD, Paediatrician, Gastroenterologist & Hepatologist, Regina Margherita Children's Hospital, AOU Città della Salute e della Scienza, Piazza Polonia, 94, 10126 Turin, ITALY. pcalvo@cittadellasalute.to.it AUTHORSHIP PAGE QP, DOD and CPL had the patient under their care and conceived, designed and wrote the article. TF, RR, SM planned and performed liver transplant and critically reviewed the paper. DE performed liver histological analysis. CF, VE, FF performed haematopoietic stem cell transplantation and critically reviewed the paper. PM followed the patient after liver transplant and critically reviewed the paper. All authors listed contributed to writing the manuscript and are responsible for the content of the paper. The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Simultaneous detection of barrier- and immune-related gene variations in patients with atopic dermatitis by reverse blot hybridization assay

Summary

Background

Hereditary factors are involved in the pathogenesis of atopic dermatitis (AD). However, AD-related gene variations are significantly different across ethnicities.

Aim

To identify mutations and single-nucleotide polymorphisms (SNPs) in barrier- or immune-related genes from Korean patients with AD and compare the variations with those observed in nonatopic healthy controls (HCs), and to use novel reverse blot hybridization assay (REBA) for AD-related gene variants.

Methods

We carried out REBA to simultaneously detect variations in genes related to barrier or immune function, namely, FLG, SPINK5, KLK7, DEFB1, TNFα, KDR, FCER1A, IL4, IL5,IL5RA, IL9, IL10, IL12, IL12R, IL13 and IL18, from Korean patients with AD, and compared the variation to that in nonatopic healthy controls.

Results

The homozygous mutants of KLK7 and SPINK5-2475, and the heterozygous mutants of FLG 3321delA, SPINK5-1156, DEFB1, KDR, IL5RA, IL9 and IL12RB1 were significantly more frequent in AD. It has been predicted that the larger the number of gene variants, the higher the odds ratio of AD prevalence; however, we did not find any significant correlation between the number of gene variants and AD severity.

Conclusion

Using REBA, we identified more genetic variants that can predict AD occurrence. We also verified that REBA can be used to easily and accurately detect multiple AD-related gene variants simultaneously. In addition, we identified a correlation between KLK7 mutation and AD in Koreans, which is the first such report, to our knowledge.

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The Lateral Femoral Cutaneous Nerve: Description of the Sensory Territory and a Novel Ultrasound-Guided Nerve Block Technique

Background and Objectives Nerve blockade of the lateral femoral cutaneous (LFC) nerve provides some analgesia after hip surgery. However, knowledge is lacking about the extent of the cutaneous area anesthetized by established LFC nerve block techniques, as well as the success rate of anesthetic coverage of various surgical incisions. Nerve block techniques that rely on ultrasonographic identification of the LFC nerve distal to the inguinal ligament can be technically challenging. Furthermore, the branching of the LFC nerve is variable, and it is unknown if proximal LFC nerve branches are anesthetized using the current techniques. The primary aim of this study was to investigate a novel ultrasound-guided LFC nerve block technique based on injection into the fat-filled flat tunnel (FFFT), which is a duplicature of the fascia lata between the sartorius and the tensor fasciae latae muscle, in order to assess the success rate of anesthetizing the proximal LFC nerve branches and covering of the different surgical incisions used for hip surgery. Methods First, a cadaveric study was conducted in order to identify an FFFT injection technique that would provide adequate injectate spread to the proximal LFC nerve branches. Second, a clinical study was conducted in a group of 20 healthy volunteers over 2 consecutive days. On trial day 1, successful complete anesthesia of the LFC nerve was defined by performing a suprainguinal fascia iliaca block bilaterally in each subject. On trial day 2, a triple-blind randomized controlled trial compared the effect of the novel ultrasound-guided LFC nerve block technique for bupivacaine versus placebo. The primary end point was the success rate of anesthesia of the proximal cutaneous area innervated by the LFC nerve for the FFFT injection with bupivacaine versus placebo. Results Adequate spread of injectate to the proximal LFC nerve branches in cadavers was obtained by injecting 10 mL with dynamic needle-tip tracking in the FFFT. Application of this technique in the randomized controlled trial provided anesthesia of the lateral thigh with a success rate of 95% (95% confidence interval, 73.9%–99.8%) for the active side and 0% for placebo (P

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Efficacy and Safety of Lidocaine Infusion Treatment for Neuropathic Pain: A Randomized, Double-Blind, and Placebo-Controlled Study

Background and Objectives Lidocaine infusion therapy (LIT) is an effective treatment for relieving neuropathic pain (NeP). However, it remains unclear whether pain relief can be sustained through repeated lidocaine infusions. This study aimed to determine whether repeated intravenous administration of low-dose lidocaine could provide prolonged pain relief in patients with specific NeP conditions. Methods This is a prospective, randomized, double-blind, placebo-controlled, parallel study. We compared the efficacy and safety of lidocaine infusions (3 mg/kg) in the LIT group and normal saline infusions in the control group once a week for 4 consecutive weeks in patients with postherpetic neuralgia or complex regional pain syndrome type II. The primary outcome was the difference in the percentage change in the 11-point numerical rating scale (NRS) pain score from baseline to after the final infusion. Secondary outcomes included pain scores during 4 weeks of follow-up and any complications. Results Forty-two patients completed this study protocol. The percentage reduction in NRS pain scores after the final infusion was significantly greater in the LIT group compared with the control group (P = 0.011). However, this pain reduction was not detectable at the 4-week follow-up. The difference in the percentage change in NRS pain scores was especially prominent in the LIT group after the third and fourth infusions. None of the study participants experienced serious complications from the treatment. Conclusions Lidocaine infusion therapy (3 mg/kg of lidocaine administered over 1 hour) provided effective short-term pain relief, which was substantially prominent after repeated infusions were administered to patients with refractory NeP. Clinical Trial Registration This study was registered at ClinicalTrials.gov, identifier NCT02597257. Accepted for publication September 2, 2017. Address correspondence to: Jee Youn Moon, MD, PhD, FIPP, CIPS, Department of Anesthesiology and Pain Medicine, Seoul National University Hospital College of Medicine, 110 Daehang-ro, Jongno-gu, Seoul 110-744, Korea (e-mail: jymoon0901@gmail.com). This research was supported by a grant (14172MFDS178) from Korean Ministry of Food and Drug Safety in 2014. The agency was not involved in conduct of this study or its submission. The authors declare no conflict of interest. Y.-C.K., A.M.C., and C.-S.L. contributed equally to this study. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Dexamethasone as an Adjuvant to Femoral Nerve Block in Children and Adolescents Undergoing Knee Arthroscopy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

Background and Objectives Perineural dexamethasone has been demonstrated to extend postsurgical analgesia after peripheral nerve blockade in adults. The mechanism of action of dexamethasone as a regional anesthetic adjuvant is unclear as intravenous dexamethasone has been shown to have similar analgesic efficacy as perineural dexamethasone. The efficacy of perineural dexamethasone has not been previously explored in the pediatric population. Methods After obtaining informed consent, children (aged 10–18 years) presenting for arthroscopic knee surgery with a femoral nerve block were randomized to 1 of 3 groups: ropivacaine 0.5% and intramuscular saline (group R), ropivacaine 0.5% plus perineural dexamethasone 0.1 mg/kg (maximum 4 mg) and intramuscular saline (group D), and ropivacaine 0.5% and intramuscular dexamethasone 0.1 mg/kg (maximum 4 mg) (group M). The primary outcome was the number of doses of analgesic agents in the first 48 hours after hospital discharge. The number of doses was compared across study groups using Wilcoxon rank sum tests. Results Seventy-seven patients were enrolled in the study, of whom 4 were withdrawn because of additional surgical repair being performed, emergence delirium requiring unblinding, or loss to follow-up. The remaining 36 boys and 37 girls (aged 15 ± 2 years) included 23 patients randomized to group D, 23 patients randomized to group M, and 27 patients randomized to group R. The median number of pain medication doses within 48 hours of discharge was 2, 3, and 2 in groups D, M, and R, respectively. There were no significant differences in this outcome between groups D and M (difference in medians, 1; 95% confidence interval [CI] of difference in medians, −1 to 2; P = 0.475), groups D and R (difference in medians, 0; 95% CI of difference, −2 to 1; P = 0.821), or groups M and R (difference in medians, −1; 95% CI of difference, −2 to 1; P = 0.594). Other secondary outcomes, including time to first analgesic consumption after discharge, visual analog scale pain score, and subjective intensity of motor block, did not evince statistically significant differences among the study groups. Conclusions In the pediatric population, perineural or intramuscular dexamethasone did not improve analgesia after femoral nerve blockade for knee arthroscopy. Whether the observed lack of benefit reflects a true adult-pediatric difference or a limitation of the study could not be determined. Future pediatric studies are needed to evaluate dexamethasone for other block types and other types of surgery. Clinical Trial Registration This study was registered at ClinicalTrials.gov, identifier NCT01971645. Accepted for publication October 4, 2017. Address correspondence to: Giorgio Veneziano, MD, Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, 700 Children's Dr, Columbus, OH 43205 (e-mail: Giorgio.Veneziano@Nationwidechildrens.org). This project was supported by The Clinical and Translational Intramural Funding Program (award grant number UL1TR001070), through the Research Institute at Nationwide Children's Hospital (Columbus, OH). The content is solely the responsibility of the authors and does not necessarily represent the official views of Nationwide Children's Hospital. This work was presented in part at moderated abstract presentations at the Society of Pediatric Pain Medicine's CCAS 2017 Annual Meeting on March 2 and the SPA-AAP Pediatric Anesthesiology 2017, on March 3, 2017, both in Austin, TX. The authors declare no conflict of interest. This study was registered with the Food and Drug Administration as an investigational new drug (IND 120188). Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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A topical treatment containing heat-treated Lactobacillus johnsonii NCC 533 reduces Staphylococcus aureus adhesion and induces antimicrobial peptide expression in an in vitro reconstructed human epidermis model

Abstract

Staphylococcus aureus colonization is thought to contribute to the pathophysiology of atopic dermatitis (AD). AD patients exhibit reduced levels of cutaneous antimicrobial peptides (AMPs), which may explain their increased susceptibility to infections. Using an in vitro reconstructed human epidermis (RHE) model, we sought to determine whether topical application of a non-replicating probiotic, heat-treated Lactobacillus johnsonii NCC 533 (HT La1), could inhibit S. aureus adhesion to skin and boost cutaneous innate immunity. We found that application of HT La1 suspension to RHE samples reduced the binding of radiolabeled S. aureus by up to 74%. To investigate a potential effect of HT La1 on innate immunity, we analyzed the expression of nine AMP genes, including those encoding beta defensins and S100 proteins, following topical application of HT La1 in suspension or in a daily moisturizer lotion. Analyzed genes were induced by up to four-fold in a dose-dependent manner by HT La1 in suspension, and by up to 2.4-fold by HT La1 in the moisturizer lotion. Finally, using ELISA and immunohistochemical detection, we evaluated the expression and secretion of the AMPs hBD-2 and psoriasin, and determined that both proteins were induced by topical HT La1, particularly in the stratum corneum of the RHE. These findings demonstrate that a topically applied, non-replicating probiotic can modulate endogenous AMP expression and inhibit binding of S. aureus to an RHE model in vitro. Moreover, they suggest that a topical formulation containing HT La1 could benefit atopic skin by enhancing cutaneous innate immunity and reducing S. aureus colonization.

This article is protected by copyright. All rights reserved.

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Staphylococcal scalded skin syndrome in a 4-year-old child: a case report

Staphylococcal scalded skin syndrome is an exfoliating skin disease which primarily affects children. Differential diagnosis includes toxic epidermal necrolysis, staphylococcal scalded skin syndrome, epidermol...

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Post-transplant lymphoproliferative disease with features of cutaneous natural killer/T-cell lymphoma

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Homeobox transcription factor DLX4 is not necessary for skin development and homeostasis

Abstract

Dlx4 is a member of a family of homeobox genes with homology to Drosophila distal-less (dll) gene. We show that Dlx4 expression pattern partially overlaps with its cis-linked gene Dlx3 during mouse development as well as in neonatal and adult skin. In mice, Dlx4 is expressed in the branchial arches, embryonic limbs, digits, nose, hair follicle and in the basal and suprabasal layers of mouse interfollicular epidermis in neonatal and adult skin. We show that inactivation of Dlx4 in mice did not result in any overtly gross pathology. Skin development, homeostasis and response to TPA treatment was similar in mice with loss of Dlx4 compared to wild type counterparts.

This article is protected by copyright. All rights reserved.

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The prevalence of human papillomavirus in pediatric tonsils: a systematic review of the literature

Abstract

Background

HPV-related head and neck cancer rates have been increasing in recent years, with the tonsils being the most commonly affected site. However, the current rate of HPV infection in the pediatric population remains poorly defined. The objective of this study was to systematically review and evaluate the prevalence and distribution of HPV in the tonsils of pediatric patients undergoing routine tonsillectomy.

Methods and Results

The literature was searched using PubMed, EMBASE, Scopus, CINAHL, Cochrane Library, and ProQuest Dissertations & Theses Global databases (inception to December 2017) by two independent review authors. Inclusion criteria included articles which evaluated the prevalence of HPV in a pediatric cohort without known warts or recurrent respiratory papillomatosis, those which used tonsil biopsy specimens for analysis, and those with six or more subjects and clear outcomes reported. Eleven studies met the inclusion criteria. Using the Oxford Clinical Evidence-based Medicine (OCEBM) guidelines, two reviewers appraised the level of evidence of each study, extracted data, and resolved discrepancies by consensus. The systematic review identified 11 articles (n = 2520). Seven studies detected HPV in the subject population, with prevalence values ranging from 0 to 21%. The level of evidence for all included studies was OCEBM Level 3.

Conclusions

HPV may be present in pediatric tonsillectomy specimens; however, the largest included study demonstrated a prevalence of 0%. Future testing should be performed using methods with high sensitivities and specificities, such as reverse transcript real-time PCR or digital droplet PCR.

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Nickel hypersensitivity following closure of atrial septal defect: A case report and review of the literature

Abstract

We present an unusual case where symptoms of headache and chest pain persisted for 3 years following the implantation of a septal occluder device for an atrial septal defect despite endothelialisation of the device. The patient was found to have nickel hypersensitivity on patch testing. Following the removal of the device the patient had complete resolution of headaches and chest pain up to 10 months post-explantation.

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Rapid exacerbation of malignant melanoma during short-term discontinuation of vemurafenib

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Increasing Prevalence of Rifampicin-Resistant Mycobacterium tuberculosis is Associated with the Transmission of Strains Harboring Compensatory Mutations in China: A 10-year Comparative Analysis [PublishAheadOfPrint]

In this report, we conducted bacterial population profile studies to assess trends of rifampicin (RIF) resistance from 2005 to 2015 of Mycobacterium tuberculosis (MTB) isolates collected across China. A total of randomly selected 273 and 269 MTB isolates from 2005 and 2015, respectively, were analyzed. The rates of RIF resistance (36.4%), isoniazid resistance (39.0%), and levofloxacin resistance (25.7%) in 2015 were significantly higher than in 2005 (28.2%, 30.0%, and 15.4%, respectively; P < 0.05). Genotypic data revealed 256 (95.2%) Beijing-type isolates in 2015, a rate significantly higher than that of 2005 (86.4%) (P < 0.01). A higher proportion of mutations were identified within the rifampin resistance determining region (RRDR) of rpoB in isolates from 2015 (99.0%) than in 2005 isolates (85.7%, P < 0.01). In addition, a significantly higher proportion of RIF-resistant isolates carrying compensatory mutations were observed in 2015 (31.6%) than in 2005 (7.8%). Notably, the great majority of these compensatory mutations (91.9%) were observed in isolates that harbored a mutation of codon 531 of the rpoB gene. In conclusion, our data demonstrate that resistance to RIF, isoniazid, and levofloxacin has become significantly more prevalent during the past decade. In addition, the prevalence of the Beijing genotype significantly increased from 2005 to 2015. Notably, a significantly increased frequency of strains with mutations in rpoC or rpoA is observed in those that have codon 531 mutations suggests that they may be compensatory, and may play a role in facilitating transmission.

http://ift.tt/2EqhRKx

Norepinephrine in Combination with Antimicrobial Therapy Increases both the Bacterial Replication Rate and Bactericidal Activity [PublishAheadOfPrint]

We previously demonstrated that the rate and extent of an antimicrobial agent's bactericidal effects was coupled to bacterial replication rate, the latter of which was modulated with sodium chloride concentration. Herein, we describe the results from a 24-h one-compartment in vitro infection model study that was designed to demonstrate that an antimicrobial agent's bactericidal effects could be amplified when administered with a pharmaceutical agent that increases bacterial replication rate. The antimicrobial and growth-promoting agents selected were levofloxacin and norepinephrine, respectively. The challenge isolate was Escherichia coli JMI 21711R (levofloxacin MIC, 8 mg/liter). Within the in vitro infection model, human levofloxacin concentration-time profile (half-life, 7 h) was simulated and the challenge isolate was subjected to an ineffective monotherapy exposure (free-drug area under the concentration-time curve over 24 h divided by the MIC [AUC/MIC ratio] of 6) with and without norepinephrine as a continuous infusion (275 mg/L). Samples were collected from the model during the course of the study for bacterial density determinations and drug concentration assay using liquid chromatography-tandem mass spectrometry (LC-MS/MS). As expected, the norepinephrine and no-treatment control arms failed immediately, followed by levofloxacin monotherapy arm, which failed slowly over time. The levofloxacin-epinephrine regimen resulted in a 2-log₁₀ CFU reduction in bacterial density over the first 6-8 hours of the study, which was followed by regrowth of a highly levofloxacin-resistant subpopulation (MIC, 64 mg/L). These data demonstrate that increasing the rate of bacterial replication with a pharmaceutical product in combination with antimicrobial therapy represents an opportunity to increase the rate and magnitude of bactericidal effect.

http://ift.tt/2DKmo9m

Enhanced ex vivo Plasmodium vivax intraerythrocytic enrichment and maturation for rapid and sensitive parasite growth assays [PublishAheadOfPrint]

Plasmodium vivax chloroquine resistance has been documented in nearly every region endemic for this malaria-causing parasite. Unfortunately, P. vivax resistance surveillance and drug discovery is challenging due to low parasitemias of patient isolates, and poor parasite survival through ex vivo maturation, that reduce the sensitivity and scalability of current P. vivax antimalarial assays. Using cryopreserved patient isolates from Brazil and fresh patient isolates from India, we established a robust enrichment method for P. vivax parasites. We next performed a media screen for formulations that enhance ex vivo survival. Finally, we optimized an isotopic metabolic labelling assay for measuring P. vivax maturation and sensitivity to antimalarials. A KCl Percoll density gradient enrichment method increased parasitemias from small-volume ex vivo isolates by an average of >40-fold. Using Iscove's Modified Dulbecco's Medium for P. vivax ex vivo culture approximately doubled parasite survival through maturation. Coupling these with ³H-hypoxanthine metabolic labeling permitted sensitive and robust measurement of parasite maturation, which was used to measure the sensitivities of Brazilian P. vivax isolates to chloroquine and several novel antimalarials. These techniques can be applied to rapidly and robustly assess the P. vivax isolate sensitivities to antimalarials for resistance surveillance and drug discovery.

http://ift.tt/2EllOji

Identification of the In Vivo Pharmacokinetics and Pharmacodynamic Drivers of Iclaprim [PublishAheadOfPrint]

The neutropenic, murine thigh infection model was used to define the PK/PD index linked to efficacy of iclaprim against S. aureus ATCC 29213 and S. pneumoniae ATCC 10813. The 24h AUC/MIC index was most closely linked to efficacy for S. aureus (R²=0.65), while both the 24h AUC/MIC and the %T>MIC were both strongly associated with effect (R²=0.86 for both parameters) for S. pneumoniae.

http://ift.tt/2DLS4v9

Pharmacokinetics of tedizolid in obese patient after bariatric surgery: a case report [PublishAheadOfPrint]

An obese woman was treated orally by tedizolid 200 mg once daily for a pseudoarthrosis, 10 years after a Roux-en-Y bypass surgery.

Total plasma peak concentration was 2.12 mg/L, 3h after intake and AUC_0-24h was 28.3 mg/L*h. The AUC_0-24h/MIC ratio for unbound concentrations and for sensible Staphylococcus and Streptococcus strains was at least 10.8, higher than a targeted ratio of 3.

These results support the use of tedizolid without adjustment after a bariatric surgery.

http://ift.tt/2EoNqnC

Population pharmacokinetics and dosing optimisation of ceftazidime in infants [PublishAheadOfPrint]

Objective: Ceftazidime, a third-generation cephalosporin, can be used for thetreatment of adults and children with infections due to susceptible bacteria. To date, the pediatric pharmacokinetic data is limited in infants, and therefore we aimed to evaluate the population pharmacokinetics of ceftazidime in infants and define the appropriate dose to optimize ceftazidime treatment.

Methods: Blood samples were collected from children treated with ceftazidime, and concentrations of drug were quantified by HPLC-UV. A population pharmacokinetic analysis was performed using NONMEM software (version 7.2.0).

Results: Fifty-one infants (age range: 0.1-2.0 years) were included. Sparse pharmacokinetic samples (n = 90) were available for analysis. A one-compartment model with first-order elimination showed the best fit with the data. A covariate analysis identified that body weight, and CL_CR were significant covariates influencing ceftazidime clearance. Monte Carlo simulation demonstrated that the currently used dosing regimen of 50 mg/kg twice daily was associated with a high risk of underdosing in infants. In order to reach the target 70% the time of free antimicrobial drug concentration above the minimum inhibitory concentration (fT>MIC), 25 mg/kg q8h and 50 mg/kg q8h were required for a MIC 4 mg/liter and for a MIC 8 mg/liter, respectively.

Conclusion: The population pharmacokinetics characteristics of ceftazidime were evaluated in infants. An evidence-based dosing regimen was established based on simulation.

http://ift.tt/2DLfJMd

CTX-M-55, MCR-1 and fosA producing multi-resistant E. coli in a pediatric infection in France [PublishAheadOfPrint]

Horizontally transferable plasmid-mediated mcr-1 gene encoding a phosphoethanolamine transferase conferring resistance to colistin in multiresistant pathogen may lead to therapeutic impasse....

http://ift.tt/2EnCO8y

Evaluation of a System-specific Function to Describe the Pharmacokinetics of Benzylpenicillin in Term Neonates Undergoing Moderate Hypothermia [PublishAheadOfPrint]

The pharmacokinetic (PK) properties of i.v. benzylpenicillin in term neonates undergoing moderate hypothermia after perinatal asphyxia were evaluated, as to date these are unknown. To do so, a system-specific modeling approach was applied, in which our recently developed covariate model describing developmental and temperature induced changes in amoxicillin clearance (CL) in the same patient study population, was incorporated into a population PK model of benzylpenicillin with a priori birthweight (BW) based allometric scaling. Pediatric population covariate models describing the developmental changes in drug elimination may constitute system-specific information and may therefore be incorporated into PK models of drugs cleared through the same pathway. The performance of this system-specific model was compared to a reference-model. Furthermore, Monte-Carlo simulations were performed to evaluate the optimal dose.

The system-specific model performed as well as the reference-model. Significant correlations were found between CL and postnatal age (PNA), gestational age (GA), body temperature (TEMP), urine output (UO; system-specific model) and multi-organ-failure (reference-model). For a typical patient GA 40 weeks, BW3000 g, 2 days PNA (TEMP 33.5°C), and normal UO (2 ml/kg/h)) benzylpenicillin CL was 0.48 L/h (inter-individual variability (IIV) 49%) and volume of distribution of the central compartment was 0.62 L/kg (IIV of 53%) in the system-specific model.

Based on simulations, we advise a benzylpenicillin i.v. dose regimen of 75,000 IU/kg/day q8h, 150,000 IU/kg/day q8h, and 200,000 IU/kg/day q6h for patients with GA36-37 weeks, 38-41 weeks, and ≥42 weeks, respectively. The system-specific model may be used for other drugs cleared through the same pathway accelerating model development.

http://ift.tt/2DKirBs

Efficacy and Safety of Plazomicin Compared with Levofloxacin in the Treatment of Complicated Urinary Tract Infection and Acute Pyelonephritis: A Multicenter, Randomized, Double-Blind, Phase 2 Study [PublishAheadOfPrint]

Increasing antimicrobial resistance among uropathogens limits treatment options for patients with complicated urinary tract infection (cUTI). Plazomicin, a next-generation aminoglycoside, has in vitro activity against multidrug-resistant Enterobacteriaceae, including isolates resistant to currently available aminoglycosides as well as extended-spectrum β-lactamase-producing and carbapenem-resistant Enterobacteriaceae. We evaluated the efficacy and safety of plazomicin in a double-blind, comparator-controlled, phase 2 study in adults with cUTI or acute pyelonephritis. Patients were randomized 1:1:1 to intravenous plazomicin (10 or 15 mg/kg) or intravenous levofloxacin (750 mg) once daily for 5 days. Co-primary efficacy endpoints were microbiological eradication at test-of-cure (TOC; 5-12 days after last dose) in the modified intent-to-treat (MITT) and microbiologically evaluable (ME) populations. Overall, 145 patients were randomized to treatment. In the plazomicin 10 mg/kg, 15 mg/kg, and levofloxacin groups, respectively, microbiological eradication rates (n/N [95% CI]) were 50.0% (6/12 [21.1-78.9]), 60.8% (31/51 [46.1-74.2]), and 58.6% (17/29 [38.9-76.5]) in the MITT population and 85.7% (6/7 [42.1-99.6]), 88.6% (31/35 [73.3-96.8]), and 81.0% (17/21 [58.1-94.6]) in the ME population. In the MITT population, 66.7% (34.9-90.1), 70.6% (56.2-82.5), and 65.5% (45.7-82.1) of patients were assessed as clinically cured by the investigator at TOC. Adverse events were reported in 31.8%, 35.1%, and 47.7% of patients. Serum creatinine values were generally stable over the course of the study. No plazomicin-treated patients with evaluable audiometry data had postbaseline sensorineural, conductive, or mixed hearing loss. In summary, plazomicin demonstrated microbiological and clinical success rates and an overall safety profile supportive of further clinical development. (ClinicalTrials.gov registration: NCT01096849.)

http://ift.tt/2ElW7PL

Surveillance of omadacycline activity tested against clinical isolates from the United States and Europe: Report from the SENTRY Antimicrobial Surveillance Program, 2016 [PublishAheadOfPrint]

Omadacycline was tested against 21,000 bacterial isolates collected prospectively from medical centers in Europe and the United States during 2016. Omadacycline was active against Staphylococcus aureus (MIC_50/90, 0.12/0.25 mg/L) including MRSA; streptococci (MIC_50/90, 0.06/0.12 mg/L) including Streptococcus pneumoniae, viridans group streptococci, and β-hemolytic streptococci; Enterobacteriaceae including Escherichia coli (MIC_50/90, 0.5/2 mg/L); Haemophilus influenzae (MIC_50/90, 1/1 mg/L); and Moraxella catarrhalis (MIC_50/90, 0.25/0.25 mg/L). Omadacycline merits further study in serious infections where resistant pathogens may be encountered.

http://ift.tt/2DNRrAU

Azithromycin resistance in Shigella spp. in Southeast Asia [PublishAheadOfPrint]

Infection by Shigella spp. is a common cause of dysentery in Southeast Asia. Antimicrobials are thought to be beneficial for treatment, however antimicrobial resistance in Shigella spp. is becoming widespread. We aimed to assess the frequency and mechanisms associated with decreased susceptibility to azithromycin in Southeast Asian Shigella isolates and use these data to assess appropriate susceptibility breakpoints. Shigella isolated in Vietnam and Laos were screened for susceptibility against azithromycin (15μg) by disc diffusion and minimum inhibitory concentration (MIC). Phenotypic resistance was confirmed by PCR amplification of macrolide resistance loci. We compared the genetic relationships and plasmid contents of azithromycin resistant S. sonnei using whole genome sequences. From 475 available Shigella spp. isolated in Vietnam and Laos between 1994 and 2012, 6/181 S. flexneri (3.3%, MIC≥16g/L) and 16/294 S. sonnei (5.4%, MIC≥32g/L) were phenotypically resistant to azithromycin. PCR amplification confirmed a resistance mechanism in 22/475 (4.6%) isolates (19 mphA and 3 ermB). Susceptibility data demonstrated the acceptability of S. flexneri (MIC≥16g/L, zone≤15mm) and S. sonnei (MIC≥32g/L, zone≤11mm) breakpoints with <3% discrepancy. Phylogenetic analysis demonstrated that decreased susceptibility has arisen sporadically in Vietnamese S. sonnei on at least seven occasions between 2000 and 2009, but failed to become established. While the proposed susceptibility breakpoints may allow better recognition of resistant isolates, additional studies are required to assess the impact on clinical outcome. The potential emergence of azithromycin resistance highlights the need for alternative management options for Shigella infections in endemic countries.

http://ift.tt/2EqhQ9r

Population pharmacokinetics of cefotaxime and dosage recommendations in children with sickle cell disease. [PublishAheadOfPrint]

The pharmacokinetic profile of most drugs is dependent on patient's covariates and may be influenced by the disease. Cefotaxime is frequently prescribed in pediatric patients with sickle-cell disease (SCD), characterized by vaso-occlusive complications, chronic haemolytic anaemia and defective immunological function predisposing to severe infection. Data on the impact of the disease on cefotaxime disposition are missing. In the present study, our aims were to determine cefotaxime pharmacokinetics when prescribed in SCD children for suspected or proven bacterial infection, identify significant covariates and perform Monte-Carlo simulations to optimize drug dosage. Cefotaxime serum concentrations were measured in 78 pediatric SCD patients receiving cefotaxime intravenously at the daily dose of 200 mg/kg in three or four divided doses over 30 min. A total of 107 concentrations were available for pharmacokinetic analysis. A population pharmacokinetic model was developed with NONMEM and used for Monte-Carlo simulations. Cefotaxime concentrations ranged from 0.05 to 103.7 mg/l. Cefotaxime pharmacokinetics was best described by a one compartment model: The median (range) of estimated weight-normalized V and CL were 0.42 (0.2 to 1.1) l/kg and 0.38 (0.1 to 1.2) l/h/kg. Cefotaxime clearance increased by 22% in patients with acute chest syndrome. Dosing optimization, performed using EUCAST Minimum Inhibitory Concentration (MIC) susceptibility breakpoints, showed that the dose of 100 mg/kg/6h should be used, depending on patients' characteristics and clinical presentation, in order to reach a Time/MIC of 80% in 80% of patients when targeting sensitive Gram positive cocci and Gram negative bacilli with MICs of 1 mg/L or below.

http://ift.tt/2DIIx7X

Clofazimine for Treatment of Pulmonary Extensively Drug-Resistant Tuberculosis in China [PublishAheadOfPrint]

We performed a multicenter, prospective and randomized study to investigate the efficacy and safety of clofazimine (CLO) for treatment of extensively drug-resistant tuberculosis (XDR-TB) in China. Forty-nine patients infected with XDR-TB were randomly assigned to either the control group or the CLO group, both of which received 36 months of individually customized treatment. The primary end-point was the time to sputum-culture conversion on solid medium. Clinical outcomes of patients were evaluated at the time of treatment completion. Of the 22 patients in the experimental group, 7 (31.8%) met the treatment criterion of "cure" and 1 (4.5%) "complete treatment," for a total of 8 (36.4%) exhibiting successful treatment outcomes without relapse. In the control group, 6 patients (22.2%) were "cure" and 6 (22.2%) "complete treatment" by the end of the study. Statistical analysis revealed no significant difference in successful outcome rates between CLO and control groups. The average sputum-culture conversion time was 19.7 months for the experimental group, which was statistically no different than that of the control group (20.3 months, P=0.57). Of the 22 patients in the CLO group, 12 (54.5%) had adverse events after starting CLO treatment. The most frequently observed adverse event was liver damage, with 31.8% (7/22) of patients exhibiting this adverse effect in the CLO group versus 11.1% (3/27) for the control group. Our study demonstrates that inclusion of CLO in background treatment regimens for XDR-TB is of limited benefit, especially since hepatic disorders arise as major adverse events with CLO treatment.

http://ift.tt/2DKmldG

Antibiotic susceptibility and genotyping of Mycobacterium avium strains that cause pulmonary and disseminated infection [PublishAheadOfPrint]

Mycobacterium avium subsp. hominissuis (MAH) causes mainly disseminated infection in immunocompromised hosts, such as individuals with human immunodeficiency virus (HIV) infection, and pulmonary infection in immunocompetent hosts. However, many aspects of the different types of MAH infection remain unclear. We examined antibiotic susceptibility and genotype in MAH isolates from different hosts by performing drug susceptibility testing using eight antibiotics (clarithromycin, rifampicin, ethambutol, streptomycin, kanamycin, amikacin, ethionamide, and levofloxacin) and variable number tandem repeats (VNTR) typing analysis for 46 isolates from the sputa of HIV-negative patients with pulmonary MAH disease without previous antibiotic treatment and 30 isolates from blood of HIV-positive patients with disseminated MAH disease. Interestingly, isolates from pulmonary MAH disease patients were more resistant to seven drugs except for rifampicin compared with isolates from HIV-positive patients. Moreover, VNTR typing analysis showed that the strains examined in this study were roughly classified into three clusters, and the genetic distance from a reference strain 104 in isolates from pulmonary MAH disease patients was statistically different from that in isolates from HIV-positive patients (p = 0.0018), suggesting that MAH strains that cause pulmonary and disseminated disease have genetically distinct features. Significant differences were noted in susceptibility for seven drugs except for ethambutol among the three clusters. Collectively, these results suggest that an association between types of MAH infection, drug susceptibility, and VNTR genotypes and the properties of MAH strains associated with the development of pulmonary disease are involved in higher antibiotic resistance.

http://ift.tt/2EmzJFL

Importance of Site of Infection and Antibiotic Selection in the Treatment of Carbapenem-Resistant Pseudomonas aeruginosa Sepsis [PublishAheadOfPrint]

In a retrospective analysis of 215 patients with carbapenem-resistant Pseudomonas aeruginosa sepsis, we observed significantly higher risk of mortality associated with respiratory tract infection (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.04-1.39 P=0.010) and lower risk with urinary tract infection (RR, 0.80; 95% CI, 0.71-0.90; P=0.004). Aminoglycoside monotherapy was associated with increased mortality, even after adjusting for confounders (adjusted RR [aRR], 1.72; 95% CI, 1.03-2.85; P=0.037), consistent across multiple sites of infection.

http://ift.tt/2DMorto

The emergence and spread of kelch 13 mutations associated with artemisinin resistance in Plasmodium falciparum parasites in twelve Thai provinces from 2007 - 2016 [PublishAheadOfPrint]

Artemisinin-based combination therapy (ACT) is the most effective and widely used treatment for uncomplicated Plasmodium falciparum (Pf) malaria and is a cornerstone for malaria control and prevention globally. Resistance to artemisinin derivatives has been confirmed in the Greater Mekong Subregion (GMS), which manifest as slow parasite clearance in patients and reduced ring-stage susceptibility to artemisinins in survival assays. The Pf kelch 13 gene mutations associated with artemisinin resistant parasites are now wide-spread in the GMS. We genotyped 277 samples collected during an observational study from 2012-2016 from eight provinces in Thailand to identify Pf kelch 13 mutations. The results were combined with previously reported genotyping results from Thailand to construct a map illustrating the evolution of Pf kelch 13 mutations from 2007 – 2016 in the country. Different mutant alleles were found in strains with different geographical origins. The artemisinin resistant Y493H and R539T mutations were detected mainly in eastern Thailand (bordering Cambodia), while P574L was only found in western Thailand and R561H in northwestern Thailand. The C580Y mutation was found across the entire country and was nearing fixation along the Thai-Cambodia border. Overall the prevalence of artemisinin resistant mutations increased over the last ten years across Thailand, especially along the Thai-Cambodia border. Molecular surveillance and therapeutic efficacy monitoring should be intensified in the region to further assess the extent and spread of artemisinin resistance.

http://ift.tt/2EnCIhc

Risk factors and outcomes of endocarditis due to non-HACEK Gram-negative bacilli: data from the prospective multicenter SEI cohort [PublishAheadOfPrint]

Objective: To investigate predisposing factors and outcomes of non-HACEK Gram-negative bacilli (GNB) infective endocarditis (IE) in a multicenter, contemporary cohort.

Patients and Methods: Patients with IE due to GNB prospectively observed in 26 Italian centers from 2004 to 2011 were analyzed. Using a case-control design, each case was compared to three controls with IE by other etiologies matched for age and sex. Logistic regression was performed to identify risk factors for GNB IE. Factors associated with early and late mortality were assessed by Cox regression analysis.

Results: The study group comprised 58 patients with GNB IE. Escherichia coli was the most common pathogen followed by Pseudomonas aeruginosa and Klebsiella pneumoniae. Genitourinary tract as source of infection (OR 13.59, 95% CI 4.63-39.93, p<.001), immunosuppression (OR 5.16, 95% CI 1.60-16.24, p=.006) and presence of a cardiac implantable electronic device (CIED) (OR 3.57, 95% CI 1.55-8.20, p=.003) were factors independently associated with GNB IE. The in-hospital mortality was 13.8%, and rose up to 30.6% at 1 year. A multidrug-resistant etiology was associated with in-hospital (HR 21.849, 95% CI 2.672-178.683, p=0.004) and 1-year mortality (HR 4.408, 95% CI 1.581-12.287, p=0.005).

Conclusions: The presence of a genitourinary focus, immunosuppressive therapy and an indwelling CIED are factors associated with GNB IE. MDR etiology is the major determinant of in-hospital and long-term mortality.

http://ift.tt/2DLAvLA

Role of three Cryptococcus neoformans and C. gattii efflux pump coding genes in response to drug treatment [PublishAheadOfPrint]

Cryptococcus neoformans and C. gattii species complexes are the etiologic agents of cryptococcosis. We have deciphered the roles of three ABC transporters, Afr1, Afr2 and Mdr1 in the representative strains of the two species, C. neoformans H99 and C. gattii R265. Deletion of AFR1 in H99 and R265 drastically reduced the resistance levels to three xenobiotics and three triazoles suggesting that Afr1 is the major drug efflux pump in both strains. Fluconazole susceptibility was not affected when AFR2 or MDR1 was deleted in both strains. However, when these genes were deleted in combination with AFR1, a minor additive effect in susceptibility toward several drugs was observed. Deletion of all three genes in both strains displayed further increases in susceptibility toward fluconazole and itraconazole suggesting that Afr2 and Mdr1 augment Afr1 function in pumping these triazoles. Intracellular accumulation of Nile Red significantly increased in afr1 of both strains but Rhodamine 6G accumulation increased only in mdr1 of H99. Thus, the three efflux pumps play different roles in the two strains when exposed to different azoles and xenobiotics. AFR1 and AFR2 expression were upregulated in H99 and R265 when treated with fluconazole. However, MDR1 expression was only upregulated in R265 under the same conditions. We screened a library of transcriptional factor mutants and identified several mutants that manifested either altered fluconazole sensitivity or an increase in the frequency of fluconazole heteroresistance. Gene expression analysis suggests that the three efflux pumps are regulated independently by different transcription factors in response to fluconazole exposure.

http://ift.tt/2EnCxT4

Clinical Outcomes of Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia Treated with Vancomycin at an Institution with Suppressed MIC Reporting: Impact of Vancomycin MIC [PublishAheadOfPrint]

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of bacteremia and is associated with significant morbidity and mortality. Prior studies evaluating the association of vancomycin MIC and clinical outcomes in patients with MRSA bacteremia have been inconsistent. This study evaluated the association between vancomycin MIC and 30-day in-hospital mortality in patients with MRSA bacteremia. This was a retrospective cohort study of patients with MRSA bacteremia treated with vancomycin for ≥72 hours from January 2013 to August 2016. Vancomycin MICs were determined by broth microdilution via automated susceptibility testing methods. Study groups consisted of patients with MRSA isolates that had vancomycin MIC<2 μg/ml and MIC=2 μg/ml. Covariates included demographics, severity of illness, comorbidities, ICU admission, infectious diseases consultation, infectious sources, and hospital onset of bacteremia. The primary outcome was 30-day in-hospital mortality. Secondary outcomes included duration of bacteremia, persistent bacteremia ≥7 days, recurrence within 30 days, change to alternative antibiotic therapy, and hospital length of stay. Multivariate logistic regression models were analyzed to control for potential confounding variables. There were a total of 166 patients included for analysis, 91patients with vancomycin MIC<2 μg/ml and 75 patients with MIC=2 μg/ml. In the multivariate logistic regression model, a vancomycin MIC=2 μg/ml, compared to MIC<2 μg/ml, was not significantly associated with 30-day in-hospital mortality after adjusting for confounders. Additionally, all secondary outcomes were not statistically significantly different between study groups. In patients with MRSA bacteremia treated with vancomycin, the vancomycin MIC was not associated with differences in clinical outcomes.

http://ift.tt/2DJJgWA

In Vitro Susceptibility of Clinical Staphylococcus aureus Small Colony Variants to {beta}-Lactam and Non-ss-Lactam Antibiotics [PublishAheadOfPrint]

Staphylococcus aureus small colony-variant (SCV) phenotype has been associated with relapsing and antibiotic-refractory infections. However, little is known about the activity of antibiotics on clinical SCVs. Here, we demonstrated that SCVs without detectable auxotrophies were at least as susceptible to most β-lactam and non-β-lactam antibiotics in vitro as their corresponding clonally identical strains with normal phenotype. After prolonged incubation, a regrowth phenomenon has been observed in gradient diffusion inhibition zones irrespective of the strains' phenotype.

http://ift.tt/2EnCiYa

Intra-Arterial Thrombolytic Therapy Is Not a Therapeutic Option for Filler-Related Central Retinal Artery Occlusion

Facial plast Surg
DOI: 10.1055/s-0037-1621730

Cosmetic facial filler-related central retinal artery occlusion (CRAO) is a devastating complication of facial hyaluronic acid (HA) injection and can be managed by intra-arterial thrombolytic therapy (IATT). The authors report on a 20-year-old woman who developed unilateral CRAO due to facial HA injection and who, despite prompt IATT, lost vision. A review of the related literature found 14 other female patients who developed cosmetic facial filler-related CRAO and accepted IATT management. In no case was vision loss clinically improved. IATT is not an effective preventive treatment of dermal filler-associated CRAO. The authors suggest careful preprocedural patient selection to prevent this complication.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

http://ift.tt/2BBKdyj

Unerwartete Folgen einer HNO-Standardtherapie

Laryngo-Rhino-Otol
DOI: 10.1055/s-0044-100257

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2rSrfUq

Immunohistochemical Analysis of Inflammatory Rheumatoid Synovial Tissues Using Anti-Human Podoplanin Monoclonal Antibody Panel

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.


http://ift.tt/2Furvel

Polypoidal Choroidal Vasculopathy Associated with Optic Disc Coloboma

Purpose: To report a case of polypoidal choroidal vasculopathy associated with optic disc coloboma. Methods: Case report. Results: A 50-year-old woman presented with optic disc coloboma and retinochoroidal coloboma associated with subretinal hemorrhage and serous retinal detachment (SRD) in her left eye. Optical coherence tomography (OCT) confirmed SRD at the macula and showed a sharply elevated retinal epithelial detachment at the choroidal excavation. OCT also revealed choroidal cavitation along the temporal side of the optic coloboma. Fluorescein angiography showed hyperfluorescent dye leakage and indocyanine green angiography revealed polypoidal lesions. We diagnosed polypoidal choroidal vasculopathy (PCV). PCV was located at the end of the choroidal cavitation. Her left eye was treated with an intraocular injection of the anti-vascular endothelial growth factor aflibercept (2 mg). Photodynamic therapy was performed using the standard protocol 1 week after the intravitreal application of aflibercept. One month after the combined treatment, OCT showed completely resolved SRD and her symptoms disappeared. Her best-corrected visual acuity remained stable and no recurrence was found during a 12-month follow-up period. Conclusion: PCV associated with optic disc coloboma has not been previously reported. The morphological abnormality of choroidal cavitation and choroidal excavation connecting with optic disc coloboma may contribute to the development of PCV in this case.
Case Rep Ophthalmol 2018;9:92–95

http://ift.tt/2BBQ4U4

Optical Coherence Tomography Angiography of Foveal Neovascularization in Diabetic Retinopathy

Purpose: To report a case of foveal neovascularization in a patient with proliferative diabetic retinopathy as seen on optical coherence tomography angiography (OCT-A). Methods: Multimodal imaging was used for diagnostic investigation. Patient: A 61-year-old male with a 16-year history of insulin-dependent diabetes mellitus was referred to our medical retina department for examination and management. Meticulous fundus examination and multimodal imaging revealed proliferative diabetic retinopathy lesions, including neovascularization located in the foveal area. Results: OCT-A allowed us to detect the neovascular lesion, confirm that it originated from perifoveal capillaries, estimate its retinal depth, and evaluate the vessel blood flow in multiple layers. Conclusion: To the best of our knowledge this is the first report of OCT-A imaging of foveal neovascularization in diabetic retinopathy. OCT-A is a very useful examination for the diagnostic investigation of patients with diabetic retinopathy.
Case Rep Ophthalmol 2018;9:87–91

http://ift.tt/2nluWgz

Anaemia in Pregnancy: Factors Associated with Maternal Anaemia in the Dadaab Refugee Camps, Kenya (2001-2002)

Smith, J; Ruth, L; Kassim, I; Oman, A; Wilkinson, C; Seal, AJ; (2015) Anaemia in Pregnancy: Factors Associated with Maternal Anaemia in the Dadaab Refugee Camps, Kenya (2001-2002). Presented at: The Micronutrient Forum Global Conference – Bridging Discovery and Delivery, Addis Ababa. Green open access

http://ift.tt/2DHKAcn

The Global Urban: Difference and Complexity in Urban Studies and the Science of Cities

Parnell, S; Robinson, JD; (2017) The Global Urban: Difference and Complexity in Urban Studies and the Science of Cities. In: Hall, S and Burdett, R, (eds.) The SAGE Handbook of the 21st Century City. (pp. 13-31). SAGE Publications Ltd: London, UK.

http://ift.tt/2EmdfFd

Exploring a Mechanistic Approach to Experimentation in Computing

Hatleback, E; Spring, JM; (2014) Exploring a Mechanistic Approach to Experimentation in Computing. Philosophy & Technology , 27 (3) pp. 441-459. 10.1007/s13347-014-0164-9 . Green open access

http://ift.tt/2DLimgL

Explaining Cross-National Variation in Workplace Employee Representation

Forth, J; Bryson, AJ; George, A; (2016) Explaining Cross-National Variation in Workplace Employee Representation. (IZA Discussion Papers 9963). Forschungsinstitut zur Zukunft der Arbeit/Institute for the Study of Labor: Bonn, Germany. Green open access

http://ift.tt/2ElpLES

III-V Quantum Dot Lasers Epitaxially Grown on Si

Chen, S; Tang, M; Wu, J; Liao, M; Seeds, A; Liu, H; (2017) III-V Quantum Dot Lasers Epitaxially Grown on Si. In: Proceedings of 2017 Conference on Lasers and Electro-Optics Pacific Rim (CLEO-PR). IEEE: Singapore. Green open access

http://ift.tt/2DLifBR

Explaining cross-national variation in workplace employee representation

Forth, J; Bryson, A; George, A; (2017) Explaining cross-national variation in workplace employee representation. European Journal of Industrial Relations , 23 (4) pp. 415-433. 10.1177/0959680117697861 . Green open access

http://ift.tt/2ElRsx9

Interactional regions in cities: making sense of flows across networked systems

Kempinska, K; Longley, P; Shawe-Taylor, J; (2017) Interactional regions in cities: making sense of flows across networked systems. International Journal of Geographical Information Science 10.1080/13658816.2017.1418878 . (In press).

http://ift.tt/2DLMDMD

Mixed-methods evaluation of a novel online STI results service

Gibbs, J; Aicken, CRH; Sutcliffe, LJ; Gkatzidou, V; Tickle, LJ; Hone, K; Sadiq, ST; ... Estcourt, CS; + view all Gibbs, J; Aicken, CRH; Sutcliffe, LJ; Gkatzidou, V; Tickle, LJ; Hone, K; Sadiq, ST; Sonnenberg, P; Estcourt, CS; - view fewer (2018) Mixed-methods evaluation of a novel online STI results service. Sexually Transmitted Infections 10.1136/sextrans-2017-053318 . (In press). Green open access

http://ift.tt/2EkLaOd

Chaînes Opératoire, Transect et Théories. Quelques réflexions sur le parcours d’une méthode classique

Coupaye, Ludovic; (2015) Chaînes Opératoire, Transect et Théories. Quelques réflexions sur le parcours d'une méthode classique. In: André Leroi-Gourhan « l'homme, tout simplement ». (pp. 69-84). Éditions de Boccard: Paris, France.

http://ift.tt/2DLhTLx

Risk and Self-Respect

Barnes, L; Baderin, A; (2018) Risk and Self-Respect. British Journal of Political Science (In press). Green open access

http://ift.tt/2EkKQPv

Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition

Danquah, CA; Kakagianni, E; Khondkar, P; Maitra, A; Rahman, M; Evangelopoulos, D; McHugh, TD; ... Gibbons, S; + view all Danquah, CA; Kakagianni, E; Khondkar, P; Maitra, A; Rahman, M; Evangelopoulos, D; McHugh, TD; Stapleton, P; Malkinson, J; Bhakta, S; Gibbons, S; - view fewer (2018) Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition. Scientific Reports , 8 , Article 1150. 10.1038/s41598-017-18948-w . Green open access

http://ift.tt/2DIGWz2

Bat Detective - Deep learning tools for bat acoustic signal detection

Mac Aodha, O; Gibb, R; Barlow, KE; Browning, E; Firman, M; Freeman, R; Harder, B; ... Jones, KE; + view all Mac Aodha, O; Gibb, R; Barlow, KE; Browning, E; Firman, M; Freeman, R; Harder, B; Kinsey, L; Mead, GR; Newson, SE; Pandourski, I; Parsons, S; Russ, J; Szodoray-Paradi, A; Szodoray-Paradi, F; Tilova, E; Girolami, M; Brostow, G; Jones, KE; - view fewer (2018) Bat Detective - Deep learning tools for bat acoustic signal detection. PLoS Computational Biology (In press).

http://ift.tt/2EjAzDe

Non-freezing cold injury: a multi-faceted syndrome

Eglin, CM; Montgomery, H; Tipton, MJ; (2018) Non-freezing cold injury: a multi-faceted syndrome. Brain 10.1093/brain/awx321 . (In press).

http://ift.tt/2DJGUHf

The Strategic Management of Government Affairs in Brussels

Coen, DJ; Vannoni, M; (2018) The Strategic Management of Government Affairs in Brussels. Business and Society (In press). Green open access

http://ift.tt/2ElpGB4

Lifetime and Aging of Chromatography Resins during Biopharmaceutical Manufacture

Nweke, MC; Rathore, AS; Bracewell, DG; (2018) Lifetime and Aging of Chromatography Resins during Biopharmaceutical Manufacture. Trends in Biotechnology 10.1016/j.tibtech.2018.01.001 . (In press).

http://ift.tt/2DKN9ut

Imperial reflections: China, Rome and the spatial logics of history in the Ásia of João de Barros

Biedermann, Zoltan; (2017) Imperial reflections: China, Rome and the spatial logics of history in the Ásia of João de Barros. In: Couto, D and Lachaud, F, (eds.) Empires en marche. Rencontres entre la Chine et l'Occident à l'âge modern (XVIe-XIXe siècles). (pp. 23-47). École française d'Extrême-Orient: Paris, France.

http://ift.tt/2EjEm3y

Stephen Graham 2016: Vertical: The City from Satellites to Bunkers. London: Verso

Harker, CG; (2017) Stephen Graham 2016: Vertical: The City from Satellites to Bunkers. London: Verso. International Journal of Urban and Regional Research , 41 (6) pp. 1029-1030. 10.1111/1468-2427.12572 .

http://ift.tt/2DJA3xt

Quantitative chemical near-infrared hyperspectral imaging of Islamic paper

Mahgoub, H; Chen, H; Gilchrist, J; Fearn, T; Strlic, M; (2017) Quantitative chemical near-infrared hyperspectral imaging of Islamic paper. In: Bridgland, J, (ed.) (Proceedings) ICOM-CC 18th Triennial Conference. International Council of Museums: Paris. (In press).

http://ift.tt/2EjFZ11

2016 United Kingdom national guideline on the sexual health care of men who have sex with men

Clutterbuck, D; Asboe, D; Barber, T; Emerson, C; Field, N; Gibson, S; Hughes, G; ... Sullivan, A; + view all Clutterbuck, D; Asboe, D; Barber, T; Emerson, C; Field, N; Gibson, S; Hughes, G; Jones, R; Murchie, M; Nori, AV; Rayment, M; Sullivan, A; - view fewer (2018) 2016 United Kingdom national guideline on the sexual health care of men who have sex with men. International Journal of STD & AIDS 10.1177/0956462417746897 . (In press).

http://ift.tt/2DJA18P

A Case of Anterior Spinal Artery Syndrome Caused by Streptococcus mitis Endocarditis

Background. Infectious endocarditis (IE) typically occurs in the setting of intravenous drug use, prosthetic heart valves, or rheumatic heart disease. However, there are a few reports of IE occurring in the setting of immunosuppression secondary to cancer and/or chemotherapy. Here, we present a case of a cancer patient who developed anterior spinal artery (ASA) syndrome secondary to a septic embolus from IE. Case Presentation. A 78-year-old male with a history of gastroesophageal cancer treated with chemotherapy and radiation presented to the hospital after a fall at home. He reported experiencing dyspnea and orthopnea for two weeks prior to presentation. In the ED, his vital signs were stable, and his examination was significant for a flaccid paralysis of the right lower extremity. Diagnosis of septic emboli secondary to IE was made after the echocardiogram showed the presence of vegetations on the aortic valve, blood cultures were positive for Streptococcus mitis, and thoracic spine MRI was indicative of an infarction at T10. Discussion. This case highlights the presence of IE in the setting of cancer and chemotherapy. Although cancer is a rare cause of IE, clinicians must maintain a high index of suspicion in order to minimize the sequelae of IE.

http://ift.tt/2BBlcTQ

Dosage adjustments in patients with psoriasis on adalimumab: a retrospective chart review

Abstract

Adalimumab is a well-established treatment for chronic plaque psoriasis. While many clinical trials have shown its efficacy, few studies have looked at deviations from labeled dosing in the real-world setting.¹ The aim of this study was to determine the frequency of off-label dosing in patients with psoriasis on adalimumab and the reasons for these deviations.

This article is protected by copyright. All rights reserved.

http://ift.tt/2DHvkw1

Patch testing in facial dermatitis using Chinese Baseline Series (60 allergens) and Cosmetic Series (58 allergens)

Abstract

Facial dermatitis (FD) is a common problem encountered in clinical practice. It effects patients' self-esteem and quality of life. Mild reactions such as itching, pricking, dryness can occur in more than 10% of patients[1]. Recurrence is common in FD. The cause of FD is often difficult to determine. Metals, cosmetics, air pollution and physical factors such as wind or changes in temperature and humidity in the environment may all contribute to the development of FD[2]. Patch test is useful in establishing the identification of FD[1,2]. The present study was carried out to determine the incidence and role of contact allergy in FD, using the Chinese Baseline Series and Cosmetic Series.

This article is protected by copyright. All rights reserved.

http://ift.tt/2EkG5p7

The influence of exposome on acne

Abstract

Background

Acne vulgaris is one of the main reasons for dermatological consultations. Severity and response to treatment may be impacted by various external factors or exposome.

Aim

to assess the impact of environmental factors on acne and to provide a comprehensive overview of the acne exposome.

Methods

two consensus meetings of five European dermatologists and a comprehensive literature search on exposome factors triggering acne served as a basis for this review.

Results

acne exposome was defined as the sum of all environmental factors influencing the occurrence, duration and severity of acne. Exposome factors impact on the response and the frequency of relapse to treatments by interacting with the skin barrier, sebaceous gland, innate immunity and cutaneous microbiota. They may be classified in the following six main categories: nutrition, psychological and lifestyle factors, occupational factors including cosmetics, as well as pollutants, medication and climatic factors. Moreover, practical considerations for the dermatologist's clinical practice are proposed.

Conclusion

Exposome factors including nutrition, medication, occupational factors, pollutants, climatic factors, and psychosocial and lifestyle factors may impact on the course and severity of acne and on treatment efficacy. Identifying and reducing the impact of exposome is important for an adequate acne disease management.

This article is protected by copyright. All rights reserved.

http://ift.tt/2DMAs29

Retrospective study on the correlation between 18-fluorodeoxyglucose uptake in positron emission tomography-computer tomography and tumor volume, cytological activity as assessed with Ki-67 and GLUT-1 staining in 10 cases of Merkel cell carcinoma

Abstract

Merkel cell carcinoma (MCC) is a rare malignant neuro-endocrine tumor of the skin that shows aggressive behavior and has a high tendency for local recurrence and lymph node or distant metastasis.¹ Recently, some reports have stated that 18-fluorodeoxyglucose positron emission tomography-computer tomography (FDG PET-CT) is more useful than conventional CT.^{2, 3} However, the utility of FDG PET-CT for determining the proliferative or metabolic activity of MCC is unclear. In this study, we investigated the correlation between FDG uptake and proliferative of metabolic activity as revealed by PET-CT imaging with Ki-67 immunological staining or GLUT-1 immunological staining in 10 cases of MCC. In addition, we tested the correlation between FDG uptake and tumor volume.

This article is protected by copyright. All rights reserved.

http://ift.tt/2EkFS5j

Frailty in Thoracic Surgery

Conditions:   Thoracic;   Thoracic Neoplasm;   Lung Cancer;   Esophageal Cancer;   Surgery--Complications;   Surgery;   Sarcopenia;   Malnutrition;   Frail Elderly Syndrome
Intervention:   Diagnostic Test: Frailty model
Sponsor:   The Cleveland Clinic
Recruiting

http://ift.tt/2EjqOFa

Lenvatinib Mesylate and Pembrolizumab in Treating Patients With Metastatic or Recurrent Gastric or Gastroesophageal Cancer

Conditions:   Gastric Adenocarcinoma;   Gastroesophageal Junction Adenocarcinoma;   Recurrent Gastric Carcinoma;   Stage IV Gastric Cancer AJCC v7
Interventions:   Other: Laboratory Biomarker Analysis;   Drug: Lenvatinib Mesylate;   Biological: Pembrolizumab
Sponsors:   New York University School of Medicine;   National Cancer Institute (NCI)
Recruiting

http://ift.tt/2DIClgm

Investigation of Neurocognitive Measures of Sport-Related Injury

Condition:   Concussion, Brain
Intervention:   Other: Cervical spine musculature
Sponsor:   Mayo Clinic
Not yet recruiting

http://ift.tt/2EjRQMJ

Lobaplation or Cisplatin in Adjuvant Chemotherapy for Esophageal Carcinoma

Condition:   Esophageal Cancer
Interventions:   Drug: Lobaplatin;   Drug: Cisplatin
Sponsor:   Henan Cancer Hospital
Not yet recruiting

http://ift.tt/2DMremx

Evaluation of Plaque Removal Efficacy & Patient Acceptability of Knotted Floss Technique in Type II Gingival Embrasures

Conditions:   Oral Hygiene;   Dental Devices, Home Care
Interventions:   Device: Knotted floss technique;   Device: Conventional flossing technique;   Device: Conventional Interdental Brushing
Sponsor:   Uttaranchal Dental & Medical Research Institute
Not yet recruiting

http://ift.tt/2EjRKER

Frontal fibrosing alopecia after antiandrogen hormonal therapy in a male patient

Abstract

An 82-year-old man with a prostate adenocarcinoma, started eight years before a treatment with oral bicalutamide 50 mg daily and subcutaneous goserelin 10,8 mg each three months, an antiandrogen and a LHRH analogue, respectively. The rest of his past medical history was unremarkable. A few months after starting with the treatment, he began with recession of the frontotemporal hairline also with hypopigmentation and atrophy of the areas of alopecia and loss of axillary and pubic hair (Figure 1). He did not present any clinical signs or patterns of male androgenetic alopecia. He denied having any siblings or kindreds with a scarring alopecia and therefore a familial FFA was excluded. Laboratory test showed low levels of prostate specific antigen (0,024ɥg/L) and undetectable free serum testosterone levels (<0,1 nmol/L). A biopsy on the scalp revealed a lichenoid lymphocitic inflammatory infiltrate, important fibrosis with loss of elastic fibers and hair follicle destruction (Figure 2,3). The clinical and histopathological features were consistent with frontal fibrosing alopecia. He is still having this treatment in order to prevent the progression of the prostate adenocarcinoma.

This article is protected by copyright. All rights reserved.

http://ift.tt/2BBBdcr

A study of androgenic signs and disorders in Greek female patients with acne

Abstract

Acne represents an established cutaneous manifestation of hyperandrogenism (1). There are scarce studies of androgenic signs or disorders including polycystic ovary syndrome (PCOS), hirsutism, menstrual irregularities or androgenic alopecia, in patients with acne.

This article is protected by copyright. All rights reserved.

http://ift.tt/2ngN23y

Oncologic outcomes of extended neck dissections in human papillomavirus-related oropharyngeal squamous cell carcinoma

Abstract

Background

Oncologic outcomes of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) requiring resection of major muscular or neurovascular tissue during neck dissection for invasive nodal disease remain uncertain.

Methods

Patients with HPV-related oropharyngeal SCC requiring resection of major muscular or neurovascular tissue during their neck dissections were retrospectively identified.

Results

Seventy-two patients were included. Regional and distant recurrences occurred in 6% and 17% of patients. Advanced T classification, pathological node number of 5 or more, and omission of adjuvant therapy were associated with decreased disease-free survival (DFS). The addition of adjuvant chemotherapy was not associated with improved survival.

Conclusion

Patients with invasive nodal disease from HPV-related oropharyngeal SCC can be managed with up-front surgery and adjuvant therapy, as indicated with good regional control. Although distant recurrence was the primary site of failure, adjuvant chemotherapy was not associated with improved outcomes. The T classification, node number, and adjuvant radiotherapy are independent prognostic factors in this patient population.

http://ift.tt/2EjjE3K

Risk analysis of malignant potential of oral verrucous hyperplasia: A follow-up study of 269 patients and copy number variation analysis

Abstract

Background

Oral verrucous hyperplasia is commonly observed in the oral cavity of betel quid chewers and is a potential malignant disorder. However, the prognostic factors and genetic alterations of oral verrucous hyperplasia are unclear.

Methods

We calculate the survival rate and prognostic factors using a Kaplan-Meier analysis and Cox proportional hazards regression model. Copy number variations were analyzed using a single-nucleotide polymorphism (SNP) array.

Results

The 5-year disease-free and cancer-free survival rates of patients with oral verrucous hyperplasia were approximately 40% and 70%, respectively. Heavy betel quid chewing, advanced oral submucous fibrosis, and nonbuccal and nontongue lesions were risk factors for malignant transformation, whereas dysplasia did not affect outcomes. The gene amplification of CTTN, FOLR3, ORAOV1, PPFIA1, and RNF121 were associated with the poor prognosis of oral verrucous hyperplasia.

Conclusion

Heavy betel quid chewing, advanced oral submucous fibrosis, and nonbuccal and nontongue lesions are high-risk factors of patients with oral verrucous hyperplasia. The 5-copy number variation-associated genes could be used for early diagnosis and predicting the prognosis.

http://ift.tt/2DHLHJe

Potts disease associated with large and multiple abscesses in a 30-year-old migrant from Chad

Description 

After a 1-year history of increasing mechanical back pain, a 30-year-old Chadian man with no medical record progressively developed a voluminous paravertebral mass (figure 1A). He described night sweats without fever for several months associated with a 20 kg weight loss (admission weight at 68 kg). Physical examination revealed no neurological defect. Laboratory tests showed a biological inflammatory syndrome with C reactive protein (CRP) plasmatic level at 80 mg/L and fibrinogen at 5.1 g/L. A vertebral MRI showed a T11–T12 vertebral osteomyelitis with a discal and corporeal abscess surrounded by important adjacent bone oedema, epiduritis causing mild spinal cord compression, as well as voluminous, prevertebral (12x8x5 cm), left psoas (9x8x8 cm) and retrovertebral (16x5x4 cm) liquid collections with peripheral contrast enhancement, suggestive of abscesses (figure 1B–D). Culture of the punctured collection of the retrovertebral abscess yielded multisusceptible Mycobacterium tuberculosis. Body scan revealed no other disease localisation. HIV serological test was negative and...

http://ift.tt/2nkmvCu

Intravascular lymphoma presenting with postural hypotension

An 84-year-old woman presented with severe postural hypotension. Further assessment revealed weight loss, fatigue and fever at night. On examination, she had bilateral skin lesions on the inner thighs and skin biopsy revealed intravascular high grade B cell lymphoma. This was successfully treated with curative chemotherapy. The cause of the postural hypotension in this case was felt likely to be autonomic neuropathy caused by neurovascular infiltration by intravascular lymphoma. Treatment of the lymphoma has resolved the postural hypotension, although some symptoms of postural instability persist.

http://ift.tt/2BBIatU

Fuchs syndrome: a case of fever, mucositis and conjunctivitis

Description

A 5-year-old boy presented with fever and cough of 2 weeks' duration, conjunctivitis and lip swelling with blistering for 6 days, and 1 day of skin rash. His past medical history was significant for incomplete Kawasaki disease (KD) at 3 years of age with no cardiac sequelae. Significant findings on physical examination included bilateral conjunctival injection with perilimbic sparing, red and cracked lips with crusting, oral mucositis and ulcerations of the buccal mucosae and tongue (figure 1), and a mild generalised maculopapular rash. He was systemically well otherwise, and there were no target lesions evident on his skin.

Figure 1

Oral mucositis with blistering of lips in a patient with Fuchs syndrome.

Differential diagnoses at that point included recurrent incomplete KD, Stevens-Johnson syndrome (SJS) and gingivostomatitis. However, oral mucositis was not consistent with KD. Furthermore, the absence of any skin...

http://ift.tt/2nkmjTM

Cryptosporidium diagnosed on endoscopic biopsy in a paediatric patient with inflammatory bowel disease

Cryptosporidium, a parasitic infection commonly associated with diarrhoea, may be difficult to differentiate from a flare in patients with inflammatory bowel disease and can lead to unnecessary therapy and increase in morbidity and mortality. We report the case of a paediatric patient who had substantial stool output requiring significant fluid resuscitation and who was later diagnosed with cryptosporidium on endoscopic biopsy. Diagnostic work up for cryptosporidium should be strongly considered when a patient presents with a flare involving massive stool output.

http://ift.tt/2BBI9WS

Segmental dilatation of small bowel presenting with severe anaemia: a diagnostic puzzle

A 7-year-old boy presented to Paediatric outpatient with worsening lethargy and tiredness. On examination he had extreme pallor. Blood investigations confirmed severe iron deficiency anaemia. He was started on iron supplements and received blood transfusion. However, the response to iron treatment was suboptimal, he therefore underwent extensive workup for the cause of iron deficiency anaemia. The barium meal showed dilated segments of ileum with two distal stenoses. The surgical resection of the involved segment was performed with end to end anastamosis. Histology of the resected segment was inconclusive of inflammatory bowel disease, malignancy or vascular malformation. The child has remained well since surgery with no further blood transfusion or iron therapy.

http://ift.tt/2njw7NL

Chronic incomplete non-puerperal uterine inversion due to huge submucous fibroid: diagnosis and management

Description

Incomplete non-puerperal uterine inversion is a rare complication that can arise secondary to the presence of submucous fibroid.1 In the majority of cases reported in the literature, the definitive diagnosis is usually made at the time of hysterectomy.2 In reported cases where hysterectomy was not done, Haultain procedure was done to correct the inversion.3 In the following case, the diagnosis was made preoperatively and the fibroid was resected vaginally by LigaSure.

A 31-year-old nulliparous woman presented to the emergency room with history of excessive bleeding for a few months. She also had urine retention for 1 day. On examination, she was pale. Vaginal examination showed a large mass distending the vagina with foul smell and moderate bleeding. Her haemoglobin was 6.2 g/L. Pelvic ultrasound scan was not conclusive in ascertaining the origin of the mass. MRI revealed the presence of a pedunculated,...

http://ift.tt/2BCWPVU

New onset diabetes after nivolumab treatment

The authors describe a case of a life-threatening diabetic emergency 25 days after initiation of nivolumab (3 mg/kg) for stage 4 lung adenocarcinoma. She was admitted to the emergency department, with hyperglycaemia-related signs and symptoms, such as polyuria, polydipsia, weight loss, confusion, asthenia, dehydration, hypotension and Kussmaul respiratory pattern. Her body mass index was 21.9 kg/m² and she did not show acanthosis nigricans. Arterial blood gas determination revealed high anion gap metabolic acidaemia and blood tests showed hyperglycaemia (1060 mg/dL), hyperketonaemia (beta-hydroxybutyrate: 6.6 mmol/dL), elevated total serum osmolality (389 mOsm/kg), low serum and urinary C-peptide and positive antiglutamic acid decarboxylase antibodies. Since nivolumab was initiated a few days before, and due to its known immune-mediated endocrine adverse events, we assumed the diagnosis of new onset immune-mediated type 1 diabetes mellitus. After prompt and adequate treatment of diabetic ketoacidosis/hyperosmolar hyperglycaemic state, she was discharged improved on multiple daily injections of insulin.

http://ift.tt/2nljJwy

Single vs multiallergen sublingual immunotherapy in the polysensitized patient: a pilot study

Background

Sublingual immunotherapy (SLIT) has emerged as an effective and exceptionally safe method of treatment of the atopic patient. However, the optimal number of allergens that should be included in the SLIT treatment regimen for the polysensitized patient is not known and practices vary widely. This study aims to compare the efficacy of single-allergen SLIT with pauci-allergen vs multiallergen aqueous SLIT in polysensitized patients.

Methods

Sixteen subjects sensitized to 6+ allergens were enrolled in the study. Subjects were blinded and randomized to SLIT treatment groups that included 1 (single), 3 (pauci), or all sensitized allergens (multi). Allergens selected were those to which the patient was most sensitized and correlated with history. Primary outcomes included daily allergy medication use, weekly Rhinoconjunctivitis Symptom Score (RCSS), and the mini–Rhinoconjuncitivitis Quality of Life Questionnaire (m-RQLQ). All metrics were measured at baseline, 6 weeks, 3 months, 6 months, and 9 months.

Results

There were significant decreases from baseline in RCSS and m-RQLQ scores in all study groups at each interval after beginning SLIT (p < 0.05). There was no significant decrease in number of daily allergy medications used regardless of number of allergens in patient's treatment vial (p = 0.50). No significant differences emerged based on number of allergens used.

Conclusion

Single-antigen, pauci-antigen, and multiantigen aqueous SLIT significantly improved allergy symptoms. There was no significant difference observed in efficacy of single-allergen SLIT vs pauci-allergen or multi-allergen SLIT in polysensitized patients.

http://ift.tt/2EkPSvE

‘Spalatro on Thames’: How Diocletian’s Palace inspired Robert Adam’s most audacious development – the Adelphi

Thom, Andrew; (2017) 'Spalatro on Thames': How Diocletian's Palace inspired Robert Adam's most audacious development – the Adelphi. In: Belamarić, J and Šverko, A, (eds.) Robert Adam and Diocletian's Palace in Split. Školska knjiga: Zagreb, Croatia.

http://ift.tt/2DTFLAe

Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population Women

Manchanda, R; Patel, S; Gordeev, VS; Antoniou, AC; Smith, S; Lee, A; Hopper, JL; ... Legood, R; + view all Manchanda, R; Patel, S; Gordeev, VS; Antoniou, AC; Smith, S; Lee, A; Hopper, JL; MacInnis, RJ; Turnbull, C; Ramus, SJ; Gayther, SA; Pharoah, PDP; Menon, U; Jacobs, I; Legood, R; - view fewer (2018) Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population Women. Journal of the National Cancer Institute (JNCI) 10.1093/jnci/djx265 . (In press).

http://ift.tt/2FsDRnf

Detecting differential gene expression in blastocysts following pronuclear transfer

Morrow, EH; Ingleby, FC; (2017) Detecting differential gene expression in blastocysts following pronuclear transfer. BMC Research Notes , 10 , Article 97. 10.1186/s13104-017-2421-3 . Green open access

http://ift.tt/2DYMJnt

Debt space: Topologies, ecologies and Ramallah, Palestine

Harker, C; (2017) Debt space: Topologies, ecologies and Ramallah, Palestine. Environment and Planning D: Society and Space , 35 (4) pp. 600-619. 10.1177/0263775816686973 . Green open access

http://ift.tt/2FrQwqt

Inflation Targets and the Zero Lower Bound in a Behavioural Macroeconomic Model

Ji, Y; De Grauwe, P; (2018) Inflation Targets and the Zero Lower Bound in a Behavioural Macroeconomic Model. Economica (In press).

http://ift.tt/2DTGlO9

High Frequency Guided Waves for Disbond Detection in Multi-Layered Structures

Fromme, P; Reymondin, J-P; Masserey, B; (2017) High Frequency Guided Waves for Disbond Detection in Multi-Layered Structures. Acta Acustica united with Acustica , 103 (6) pp. 932-940. 10.3813/AAA.919122 .

http://ift.tt/2FofjeQ

Impact of 3 Tesla MRI on interobserver agreement in clinically isolated syndrome: A MAGNIMS multicentre study

Hagens, MH; Burggraaff, J; Kilsdonk, ID; Ruggieri, S; Collorone, S; Cortese, R; Cawley, N; ... MAGNIMS Study Group, .; + view all Hagens, MH; Burggraaff, J; Kilsdonk, ID; Ruggieri, S; Collorone, S; Cortese, R; Cawley, N; Sbardella, E; Andelova, M; Amann, M; Lieb, JM; Pantano, P; Lissenberg-Witte, BI; Killestein, J; Oreja-Guevara, C; Wuerfel, J; Ciccarelli, O; Gasperini, C; Lukas, C; Rovira, A; Barkhof, F; Wattjes, MP; MAGNIMS Study Group, .; - view fewer (2018) Impact of 3 Tesla MRI on interobserver agreement in clinically isolated syndrome: A MAGNIMS multicentre study. Multiple Sclerosis Journal 10.1177/1352458517751647 . (In press). Green open access

http://ift.tt/2DTG8KR

Killing zoo animals surplus to requirements: response

Reiss, Michael J; McCulloch, Steven P; (2017) Killing zoo animals surplus to requirements: response. In: Mullan, S and Fawcett, A, (eds.) Veterinary ethics: navigating tough classes. (pp. 461-465). 5M: Sheffield, United Kingdom.

http://ift.tt/2Fqujcc

A novel adaptive algorithm for 3D finite element analysis to model extracortical bone growth

Cheong, VS; Blunn, GW; Coathup, MJ; Fromme, P; (2018) A novel adaptive algorithm for 3D finite element analysis to model extracortical bone growth. Computer Methods in Biomechanics and Biomedical Engineering 10.1080/10255842.2018.1425997 . (In press).

http://ift.tt/2DYwyq4

Chronic kidney disease and arrhythmias: conclusions from a kidney disease: Improving Global Outcomes (KDIGO) Controversies Conference

Wheeler, DC; Turakhia, MP; Blankestijn, PJ; Carrero, JJ; Clase, C; Deo, R; Herzog, CA; ... Wanner, C; + view all Wheeler, DC; Turakhia, MP; Blankestijn, PJ; Carrero, JJ; Clase, C; Deo, R; Herzog, CA; Kasner, SE; Passman, RS; Pecoits-Filho, R; Reinecke, H; Zareba, W; Cheung, M; Winkelmayer, W; Wanner, C; - view fewer (2018) Chronic kidney disease and arrhythmias: conclusions from a kidney disease: Improving Global Outcomes (KDIGO) Controversies Conference. In: Proceedings of the Improving Global Outcomes (KDIGO) Controversies Conference. Kidney International (In press).

http://ift.tt/2Fns2yD

Effects of the sodium–glucose co-transporter 2 inhibitor dapagliflozin in patients with type 2 diabetes and Stages 3b–4 chronic kidney disease

Wheeler, DC; Dekkers, CCJ; Sjostrom, CD; Stefansson, BV; Cain, V; Heerspink, HJL; (2018) Effects of the sodium–glucose co-transporter 2 inhibitor dapagliflozin in patients with type 2 diabetes and Stages 3b–4 chronic kidney disease. Nephrology Dialysis Transplantation 10.1093/ndt/gfx350 . (In press). Green open access

http://ift.tt/2DWJEUI

Las tierras antrópicas amazónicas: algo más que un puñado de tierra

Arroyo-Kalin, Manuel; (2017) Las tierras antrópicas amazónicas: algo más que un puñado de tierra. In: Rostain, S and Jaimes Betancourt, C, (eds.) Las Siete Maravillas de la Amazonia precolombina. (pp. 99-117). 4- EIAA/BAS/Plural Publicaciones: La Paz.

http://ift.tt/2FpuCEi

Inspecting School Social Quality: Assessing and Improving School Effectiveness in the Social Domain

Dijkstra, A; Daas, R; De la Motte, P; Ehren, M; (2017) Inspecting School Social Quality: Assessing and Improving School Effectiveness in the Social Domain. Journal of Social Science Education , 16 (4) pp. 75-84. 10.4119/UNIBI/jsse-v16-i4-1640 . Green open access

http://ift.tt/2DTMfim

Gray matter networks and cognitive impairment in multiple sclerosis

Rimkus, CM; Schoonheim, MM; Steenwijk, MD; Vrenken, H; Eijlers, AJ; Killestein, J; Wattjes, MP; ... Tijms, BM; + view all Rimkus, CM; Schoonheim, MM; Steenwijk, MD; Vrenken, H; Eijlers, AJ; Killestein, J; Wattjes, MP; Leite, CC; Barkhof, F; Tijms, BM; - view fewer (2018) Gray matter networks and cognitive impairment in multiple sclerosis. Multiple Sclerosis Journal 10.1177/1352458517751650 . (In press). Green open access

http://ift.tt/2Fo7yWA

Obstacles facing an effective national tuberculosis treatment program: a case study of India

Pan, D; Neihaus, L; Abubakar, I; Batra, S; Lipman, M; (2018) Obstacles facing an effective national tuberculosis treatment program: a case study of India. Tuberculosis and Pulmonology (In press).

http://ift.tt/2DYw2bC

From voting to engaging: promoting democratic values in an international school network

Higham, RJE; Djohari, N; (2018) From voting to engaging: promoting democratic values in an international school network. Oxford Review of Education 10.1080/03054985.2018.1433649 . (In press).

http://ift.tt/2Fqz71q

Assessment of the general quality of sunscreen products available in Palestine and method verification of the sun protection factor using Food and Drug Administration guidelines

Summary

Background

Sunlight exposure affects all skin types causing skin tanning, burns or even skin cancer. Sunscreens were invented to prevent these outcomes by scattering or absorbing the UV light.

Aims

This study aimed to verify the effectiveness of Mansur method in SPF measurement and to find out how much reliable the labeled sun protection factor (SPF) value for the products that are imported to Palestine knowing that they are considered as cosmetics and they don't undergo tests by the Ministry Of Health (MOH).

Materials

In this research, sun protection factor (SPF) was determined for 16 commercially available sunscreen products using Mansur equation which was also validated; moreover sunscreen classification, product phase determination and pH measurement were also done.

Results

Sun protection factor values were mostly 50, 43.75% of the analyzed samples were close to the labeled SPF, 31.25% were under the labeled value, and 25% SPF value above the labeled value. All samples exhibited a pH close to skin pH. 62% of them were found to be O/W. Cosmetic companies and importers should focus on pediatric sunscreens, since only 12.5% are pediatric sunscreens.

Conclusions

Ministry Of Health should ask prove about the quality of an SPF value of sunscreens for final registration of these products. More instructions should be available on the label regarding the proper use especially, if they are not water proof.

http://ift.tt/2noejQK