bluuebunny/crossref_metadata_2025 huggingface dataset:
The eye and eyelids
Authors: Perry Mike
Published: February 2018

This chapter looks at diseases and conditions of the eye and eyelids that may present acutely to an emergency department, general practice, or ward. It aims to equip the reader with the necessary knowledge to enable them to quickly and accurately triage and diagnose common clinical problems. Referral pathways and management are also discussed. Generally speaking, patients do not present with a ready-made diagnosis, but rather with either a symptom located to an anatomical region (e.g. toothache, lump, or headache), or an obvious problem (e.g. nose bleed or injury). This is the starting point (‘Common presentations’ and ‘Common problems and their causes’). The next section (‘Useful questions and what to look for’) lists key diagnostic elements in relation to each symptom. The remainder of each chapter details how to examine each site, useful investigations (emergency department and outpatients), and some notes on the conditions themselves. This is a useful aid for the non-specialist and those preparing for clinical examinations.
The upper jaw and midface
Authors: Perry Mike
Published: February 2018

This chapter looks at diseases and conditions of the upper jaw and midface that may present acutely to an emergency department, general practice, or ward. It aims to equip the reader with the necessary knowledge to enable them to quickly and accurately triage and diagnose common clinical problems. Referral pathways and management are also discussed. Generally speaking, patients do not present with a ready-made diagnosis, but rather with either a symptom located to an anatomical region (e.g. toothache, lump, or headache), or an obvious problem (e.g. nose bleed or injury). This is the starting point (‘Common presentations’ and ‘Common problems and their causes’). The next section (‘Useful questions and what to look for’) lists key diagnostic elements in relation to each symptom. The remainder of each chapter details how to examine each site, useful investigations (emergency department and outpatients), and some notes on the conditions themselves. This is a useful aid for the non-specialist and those preparing for clinical examinations.
The mouth, lips, and teeth
Authors: Perry Mike
Published: February 2018

This chapter looks at diseases and conditions of the mouth, lips, and teeth that may present acutely to an emergency department, general practice, or ward. It aims to equip the reader with the necessary knowledge to enable them to quickly and accurately triage and diagnose common clinical problems. Referral pathways and management are also discussed. Generally speaking, patients do not present with a ready-made diagnosis, but rather with either a symptom located to an anatomical region (e.g. toothache, lump, or headache), or an obvious problem (e.g. nose bleed or injury). This is the starting point (‘Common presentations’ and ‘Common problems and their causes’). The next section (‘Useful questions and what to look for’) lists key diagnostic elements in relation to each symptom. The remainder of each chapter details how to examine each site, useful investigations (emergency department and outpatients), and some notes on the conditions themselves. This is a useful aid for the non-specialist and those preparing for clinical examinations.
Palliative Psychology
Authors: Strada E. Alessandra
Published: February 2018

Palliative Psychology: Clinical Perspectives on an Emerging Specialty is the first book that proposes palliative psychology as a new specialty defining the roles and competencies of psychologists working in the palliative care setting in the US context. As proposed and defined in this book, palliative psychology is a specialty for licensed psychologists interested in providing psychological assessment and interventions to patients with serious and advanced illness and their family caregivers. The psychologist’s involvement can begin after a diagnosis of serious illness and continue during treatment, transition of care, during the dying process, and in bereavement. This book follows the framework developed by the Clinical Practice Guidelines for Quality Palliative Care, which identifies eight domains of specialist palliative care. The chapters of the book explore each of the domains, describing some of the essential knowledge, skills, and attitudes that palliative psychologists should develop to become competent palliative care professionals. Tables and clinical case vignettes are used throughout the book to illustrate important clinical aspects related to the work of palliative psychologists.
Direct Lyman continuum and Ly α escape observed at redshift 4
Authors: Vanzella E , Nonino M , Cupani G , Castellano M , Sani E , Mignoli M , Calura F , Meneghetti M , Gilli R , Comastri A , Mercurio A , Caminha G B , Caputi K , Rosati P , Grillo C , Cristiani S , Balestra I , Fontana A , Giavalisco M
Published: February 2018

We report on the serendipitous discovery of a z = 4.0, M1500 = −22.20 star-forming galaxy (Ion3) showing copious Lyman continuum (LyC) leakage (∼60 per cent escaping), a remarkable multiple peaked Ly α emission, and significant Ly α radiation directly emerging at the resonance frequency. This is the highest redshift confirmed LyC emitter in which the ionizing and Ly α radiation possibly share a common ionized channel (with NH I < 1017.2 cm−2). Ion3 is spatially resolved, it shows clear stellar winds signatures like the P-Cygni N vλ1240 profile, and has blue ultraviolet continuum (β = −2.5 ± 0.25, Fλ ∼ λβ) with weak low-ionization interstellar metal lines. Deep VLT/HAWKI Ks and Spitzer/IRAC 3.6 and 4.5μm imaging show a clear photometric signature of the H α line with equivalent width of 1000 Å rest-frame emerging over a flat continuum (Ks − 4.5μm ≃ 0). From the SED fitting, we derive a stellar mass of 1.5 × 109 M⊙, SFR of 140 M⊙ yr−1 and age of ∼10 Myr, with a low dust extinction, E(B − V) ≲ 0.1, placing the source in the starburst region of the SFR−M* plane. Ion3 shows similar properties of another LyC emitter previously discovered (z = 3.21, Ion2, Vanzella et al. 2016). Ion3 (and Ion2) represents ideal high-redshift reference cases to guide the search for reionizing sources at z > 6.5 with JWST.
Creation and Assessment of a Clinical Predictive Calculator and Mortality Associated With Candida krusei Bloodstream Infections
Authors: Kronen Ryan , Hsueh Kevin , Lin Charlotte , Powderly William G , Spec Andrej
Published: February 2018

Background

Candida krusei bloodstream infection (CK BSI) is associated with high mortality, but whether this is due to underlying comorbidities in affected patients or the organism itself is unknown. Identifying patient characteristics that are associated with CK BSI is crucial for clinical decision-making and prognosis.

Methods

We conducted a retrospective analysis of hospitalized patients with Candida BSI at our institution between 2002 and 2015. Data were collected on demographics, comorbidities, medications, procedures, central lines, vital signs, and laboratory values. Multivariable logistic and Cox regression were used to identify risk factors associated with CK and mortality, respectively.

Results

We identified 1873 individual patients who developed Candida BSI within the study period, 59 of whom had CK BSI. CK BSI was predicted by hematologic malignancy, gastric malignancy, neutropenia, and the use of prophylactic azole antifungals, monoclonal antibodies, and β-lactam/β-lactamase inhibitor combinations. The C-statistic was 0.86 (95% confidence interval, 0.81–0.91). The crude mortality rates were 64.4% for CK BSI and 41.4% for non-CK BSI. Although CK was associated with higher mortality in univariable Cox regression, this relationship was no longer significant with the addition of the following confounders: lymphoma, neutropenia, glucocorticoid use, chronic liver disease, and elevated creatinine.

Conclusions

Six patient comorbidities predicted the development of CK BSI with high accuracy. Although patients with CK BSI have higher crude mortality rates than patients with non-CK BSI, this difference is not significant when accounting for other patient characteristics.
Actinotignum schaalii Infection: A Clandestine Cause of Sterile Pyuria?
Authors: Horton Lucy E , Mehta Sanjay R , Aganovic Lejla , Fierer Joshua
Published: February 2018

Actinotignum schaalii is an underappreciated cause of urinary tract infections (UTIs) in older adults. The diagnosis may be missed due to difficulty isolating and identifying the organism. Complications can result because the organism is intrinsically resistant to 2 commonly used drugs to treat UTI, as illustrated by this case.
Reducing Opioid Use for Patients With Chronic Pain: An Evidence-Based Perspective
Authors: Wenger Sarah , Drott Jason , Fillipo Rebecca , Findlay Alyssa , Genung Amanda , Heiden Jessica , Bradt Joke
Published: February 2018

The implementation of recent Centers for Disease Control and Prevention recommendations to move away from opioids and toward nonpharmacological therapies for the treatment of chronic pain could involve a difficult transition period for patients and practitioners. The focus of treatment should shift from eliminating pain completely to minimizing the impact of pain on quality of life. Many patients with chronic pain take opioids either because opioids were previously prescribed as a first-line treatment for chronic pain, on the basis of old standards of care, or because opioids were initially prescribed for acute pain. Patients currently taking opioids will need a tapering period during which they transition their pain management to interdisciplinary care and nonpharmacological treatments. To provide useful treatment options, physical therapists need to have a good understanding of the neuroscientific mechanisms of chronic pain, biopsychosocial components of chronic pain management, issues related to opioid use, and pain management strategies used by other health care professionals. Armed with knowledge and good communication skills, physical therapists can work within an interdisciplinary team to adapt care to each patient's needs and abilities. This perspective article provides guidance for physical therapists to effectively treat patients with chronic pain during the opioid tapering process. A framework has been created to help health care providers structure their reasoning as they collaborate to develop a unique approach for each patient.
A Large-Scale Mutational Analysis of Two-Component Signaling Systems of Lonsdalea quercina Revealed that KdpD-KdpE Regulates Bacterial Virulence Against Host Poplar Trees
Authors: Yang Ruo-Lan , Deng Chao-Ying , Wei Jin-Wei , He Wei , Li Ai-Ning , Qian Wei
Published: February 2018

Poplar, which is a dominant species in plant communities distributed in the northern hemisphere, is commonly used as a model plant in forestry studies. Poplar production can be inhibited by infections caused by bacteria, including Lonsdalea quercina subsp. populi, which is a gram-negative bacterium responsible for bark canker disease. However, the molecular basis of the pathogenesis remains uncharacterized. In this study, we annotated the two-component signal transduction systems (TCSs) encoded by the L. quercina subsp. populi N-5-1 genome and identified 18 putative histidine kinases and 24 response regulators. A large-scale mutational analysis revealed that 19 TCS genes regulated bacterial virulence against poplar trees. Additionally, the deletion of kdpE or overexpression of kdpD resulted in almost complete loss of bacterial virulence. We observed that kdpE and kdpD formed a bi-cistronic operon. KdpD exhibited autokinase activity and could bind to KdpE (Kd = 5.73 ± 0.64 μM). Furthermore, KdpE is an OmpR family response regulator. A chromatin immunoprecipitation sequencing analysis revealed that KdpE binds to an imperfect palindromic sequence within the promoters of 44 genes, including stress response genes Lqp0434, Lqp3037, and Lqp3270. A comprehensive analysis of TCS functions may help to characterize the regulation of poplar bark canker disease.
A Chemotaxis-Like Pathway of Azorhizobium caulinodans Controls Flagella-Driven Motility, Which Regulates Biofilm Formation, Exopolysaccharide Biosynthesis, and Competitive Nodulation
Authors: Liu Wei , Sun Yu , Shen Rimin , Dang Xiaoxiao , Liu Xiaolin , Sui Fu , Li Yan , Zhang Zhenpeng , Alexandre Gladys , Elmerich Claudine , Xie Zhihong
Published: February 2018

The genome of the Azorhizobium caulinodans ORS571 contains a unique chemotaxis gene cluster (che) including five chemotaxis genes: cheA, cheW, cheY1, cheB, and cheR. Analysis of the role of the chemotaxis cluster of A. caulinodans using deletion mutant strains revealed that CheA or the Che signaling pathway controls chemotaxis behavior and flagella-driven motility and plays important roles in formation of biofilms and production of extracellular polysaccharides (EPS). Furthermore, the deletion mutants (ΔcheA and ΔcheA-R) were defective in competitive adsorption and colonization on the root surface of host plants. In addition, a functional CheA or Che pathway promoted competitive nodulation on roots and stems. Interestingly, a nonflagellated mutant, ΔfliM, displayed a phenotype highly similar to that of the ΔcheA or ΔcheA-R mutant strains. These findings suggest that through controlling flagella-driven motility behavior, the chemotaxis signaling pathway in A. caulinodans coordinates biofilm formation, EPS, and competitive colonization and nodulation.
Assessing Potato Cultivar Sensitivity to Tuber Necrosis Caused by Tobacco rattle virus
Authors: Yellareddygari S. K. R. , Brown Charles R. , Whitworth Jonathan L. , Quick Richard A. , Hamlin Launa L. , Gudmestad Neil C.
Published: February 2018

Tobacco rattle virus (TRV) causes the economically important corky ring spot disease in potato. Chemical control is difficult due to the soilborne nature of the TRV-transmitting nematode vector, and identifying natural host resistance against TRV is considered to be the optimal control measure. The present study investigated the sensitivity of 63 cultivars representing all market types (evaluated at North Dakota and Washington over 2 years) for the incidence of TRV-induced tuber necrosis and severity. This article also investigates the cultivar–location interaction (using a mixed-effects model) for TRV-induced necrosis. TRV-induced tuber necrosis (P < 0.0001) and severity (P < 0.0001) were significantly different among cultivars evaluated separately in North Dakota and Washington trials. Mixed-effects model results of pooled data (North Dakota and Washington) demonstrated that the interaction of cultivar and location had a significant effect (P = 0.03) on TRV-induced necrosis. Based on the virus-induced tuber necrosis data from both years and locations, cultivars were categorized into sensitive, moderately sensitive, insensitive, and moderately insensitive groups. Based on data from North Dakota, 10 cultivars, including Bintje, Centennial Russet, Ciklamen, Gala, Lelah, Oneida Gold, POR06V12-3, Rio Colorado, Russian Banana, and Superior, were rated as insensitive to TRV-induced tuber necrosis. Similar trials assessing TRV sensitivity among cultivars conducted in Washington resulted in a number of differences in sensitivity rankings compared with North Dakota trials. A substantial shift in sensitivity of some potato cultivars to TRV-induced tuber necrosis was observed between the two locations. Four cultivars (Centennial Russet, Oneida Gold, Russian Banana, and Superior) ranked as insensitive for North Dakota trials were ranked as sensitive for Washington trials. These results can assist the potato industry in making cultivar choices to reduce the economic impact of TRV-induced tuber necrosis.
CE: Original Research: An Investigation into the Safety of Oral Intake During Labor
Authors: Shea-Lewis Anne , Eckardt Patricia , Stapleton Donna
Published: February 2018

Purpose: The purpose of this study was to compare the maternal and neonatal outcomes among laboring women permitted ad lib oral intake with those permitted nothing by mouth except for ice chips.

Design: This was a quantitative retrospective observational cross-sectional study.

Sample: The initial data set consisted of all closed medical records for 2,817 women who were admitted to a suburban community hospital in the northeastern United States between January 2008 and December 2012. Some subjects’ records were missing either covariate data or outcomes data, resulting in final sample sizes of 2,797 women (for comparison across covariates) and 2,784 women (for comparison across outcomes).

Methods: A deidentified limited data set was extracted from the electronic health record for descriptive and inferential comparisons between groups. Demographics and maternal comorbidities present on admission were compared between groups before data analysis. Outcome comparisons were obtained with traditional between-groups analysis and propensity score matching.

Results: The groups were found to be sufficiently equivalent for comparison. The group permitted nothing by mouth was significantly more likely to have unplanned cesarean section births than the group permitted ad lib oral intake. There were no significant differences in unplanned maternal ICU admissions postpartum, in neonate condition as determined by Apgar scores, or in the need for a higher level of care. Allowing women ad lib oral intake during labor caused no increase in morbidity, and there were no mortalities in either group.

Conclusion: Allowing women ad lib oral intake during labor does not increase adverse maternal or neonatal outcomes. It stands to reason that allowing such intake could increase patient satisfaction. Further study is needed to determine what types of food and drink are most beneficial as well as what types are preferred.
Lymph node ratio as a prognostic factor in melanoma: results from European Organization for Research and Treatment of Cancer 18871, 18952, and 18991 studies
Authors: Testori Alessandro A. , Suciu Stefan , van Akkooi Alexander C.J. , Suppa Mariano , Eggermont Alexander M.M. , de Vries Esther , Joosse Arjen
Published: February 2018

The aim of this study was to assess the prognostic importance of lymph node ratio (LNR) in stage III melanoma after complete lymph nodal dissections. From European Organization for Research and Treatment of Cancer randomized trials 18871, 18952, and 18991, 2358 patients had full information on positive and examined lymph nodes (LNs) and were included. Cox proportional hazards models stratified by trial were used to assess the prognostic impact of LNR adjusted for confounders on melanoma-specific survival. Optimal cutoff values for LNR were calculated for each LN dissection site (axillary, inguinal, and neck). LNR (≥ vs. <35%: hazard ratio=1.44, 95% confidence interval: 1.23–1.69) and number of positive LNs appeared to be of independent strong prognostic importance. Dissection sites impacted the optimal LNR cutoff: 35% for axillary, 40% for inguinal, and 50% for neck dissections. Combining these into one ‘high versus low LNR’ resulted in a highly significant multivariately adjusted hazard ratio of 1.48 (95% confidence interval: 1.26–1.74). In subgroup analyses, LNR was only significant in advanced disease (American Joint Committee on Cancer stage N2b, N3; IIIC). LNR was most significant for inguinal dissections, followed by axillary dissections, but seemed less useful in neck dissections. LNR is an independent significant prognostic factor in stage III melanoma patients. Our study showed higher than previously reported cutoffs that differed per dissection site. However, because of conflicting results compared with other studies and apparent limited prognostic impact confined to subgroups, the practical use of LNR seems limited.
A Systematic Review and Meta-analysis of Free-style Flaps: Risk Analysis of Complications
Authors: Qian Youlei , Li Guangxue , Zang Huiran , Cao Saisai , Liu Yan , Yang Kai , Mu Lan
Published: February 2018

Background:

Free-style flaps allow surgeons to overcome anatomical variations and raise perforator flaps wherever a pulsatile signal can be detected. We performed a systematic review and meta-analysis to identify the risk factors for complications and indications for free-style flaps in soft-tissue defect reconstructions.

Methods:

This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The databases of MEDLINE, PubMed, ScienceDirect, and Cochrane Library were searched from January 1991 to January 2017 for original articles describing free-style flaps in soft-tissue defect reconstruction.

Results:

A total of 17 articles met the inclusion criteria, representing 453 free-style flaps. The percentage of free-style flaps conducted after primary oncologic resection was 54.4% (246/453). Free-style flaps were mostly used in the head and neck region (35.5%), and most of them were designed as pedicled perforator flaps (96.7%). Complete flap survival was accomplished in 91.8% of the free-style flaps. Complications were found in 13.5% of cases, and 2 risk factors were identified: extremity defects (risk ratio, 2.39; P = 0.006) and single perforator flaps (risk ratio, 4.93; P = 0.002). No significant differences were found among the criteria including patients aged greater than 60 years, female gender, chronic etiology, flap size over 100 cm2, flap rotation, or perforator skeletonization.

Conclusions:

Free-style flaps are both reliable and advanced forms of perforator flaps for use in soft-tissue defect reconstructions. Defects located on the extremities and flaps with single perforators are risk factors for flap failure and complications.
Personalized 3D Printed Surgical Tool for Guiding the Chisel during Hump Reduction in Rhinoplasty
Authors: Herrero Antón de Vez Hugo , Herrero Jover Javier , Silva-Vergara Claudio
Published: February 2018

The authors aimed to present an introduction of patient-specific model in rhinoplasty by introducing a 3D printed surgical guide designed and adapted in an individualized manner for guiding dorsal hump reduction. To introduce the tool, we have designed a six step workflow. First, we obtain a digital 3D model of patient anatomy using computed tomography (CT) images. Second, we conduct a surgical preoperative planning of the rhinoplasty on the mentioned model. Third step consists of designing the guide, while taking into account nasal anthropometries and resection objectives. Fourth step is printing the guide and sterilizing it. Fifth step is performing the surgery. The last step is analyzing the main outcomes of the surgery. Our surgical guide allowed us to perform only 1 step osteotomy instead of the usual multistep osteotomy and remove exactly the amount of dorsum that we decided to remove during the preoperative planning. The duration of intervention was considerably shorter than conventional osteotomy. Using the guide was technically easier than the conventional method and reduced the learning curve from years to minutes (once the guide is printed). Moreover, the patient understanding of the procedure was significantly better after showing the 3D model of the surgery. The surgical guide allows a surgeon to transfer with extreme simplicity the presurgical planning to the surgical field. We have to point out that the design of the study does not allow us to quantify predictability, so future studies are needed to demonstrate an accuracy benefit over the former techniques.
Successful Treatment of Disseminated Cutaneous Leishmaniasis With Liposomal Amphotericin B and Miltefosine in an Eight-year-old Girl
Authors: Hamzavi Seyedeh Sedigheh , Sanaei Dashti Anahita , Kadivar Mohammad Rahim , Pouladfar Gholamreza , Pourabbas Bahman
Published: February 2018

This case report presents an 8-year-old girl, from Fars province in Iran, diagnosed with cutaneous leishmaniasis in the form of multiple nodular, ulcerative and crusted lesions disseminated on the face, trunk and extremities. The result of direct smear of ulcers was positive for Leishmania parasite. The patient had no immunodeficiency or relevant family history making her susceptible for disseminated cutaneous leishmaniasis. The skin lesions failed to respond to multiple treatment courses of meglumine antimoniate or amphotericin B but were successfully treated with simultaneous miltefosine and liposomal amphotericin B.
Safety and Immunogenicity of the HPV-16/18 AS04-adjuvanted Vaccine in 4–6-year-old Girls
Authors: Lin Lan , Parra Mercedes Macias , Sierra Victor Y. , Cespedes Albino Salas , Granados Maria Angelica , Luque Adriana , Damaso Silvia , Castrejon Alba Maria Mercedes , Romano-Mazzotti Luis , Struyf Frank
Published: February 2018

Background:

The burden of cervical cancer caused by human papillomavirus (HPV) is high in Latin America. The suboptimal HPV vaccination coverage in adolescents could be improved by pediatric immunization. HPV vaccination has not yet been reported in girls <9 years of age.

Methods:

This ongoing phase III, controlled, randomized, single-blind, multicenter study conducted in Colombia, Mexico and Panama (NCT01627561) evaluated the safety and immunogenicity of AS04-HPV-16/18 vaccine in 4–6-year-old girls. Healthy girls (randomized 1:1) received either 2 doses of AS04-HPV-16/18 vaccine (HPV group, N=74) or 1 dose of each measles-mumps-rubella and diphtheria-tetanus-acellular-pertussis vaccines (control group, N=74) 6 months apart. We report the safety and serum anti–HPV-16 and anti–HPV-18 antibodies (measured by enzyme-linked immunosorbent assay) up to 6 months postvaccination, that is, month (M) 12.

Results:

Injection site pain was the most frequently reported solicited local symptom in HPV vaccinees. The incidence of other solicited and unsolicited symptoms after each vaccination was similar between the HPV and control group. Until M12, 1 girl in the HPV group and 2 in the control group reported serious adverse events; all serious adverse events were assessed as unrelated to study vaccines. No potential immune-mediated diseases were identified. All girls seroconverted for both antigens after 2 doses of AS04-HPV-16/18. In initially seronegative girls, anti–HPV-16 geometric mean concentrations were 20080.0 enzyme-linked immunosorbent assay units (EU)/mL at M7 and 3246.5 EU/mL at M12; anti–HPV-18 geometric mean concentrations were 10621.8 EU/mL at M7 and 1216.6 EU/mL at M12.

Conclusions:

Two-dose vaccination with AS04-HPV-16/18 was well tolerated and induced adequate antibody responses in 4–6-year-old girls.
No Effect of Adjunctive Minocycline Treatment on Body Metabolism in Patients With Schizophrenia
Authors: Liu Fang , Xie Liqin , Zhang Bingkui , Ruan Ye , Zeng Yong , Xu XiuFeng , Zhao Jingping , Fan Xiaoduo
Published: February 2018

Purpose/Background

This study examined the effect of adjunctive minocycline on body metabolism in risperidone-treated patients with schizophrenia.

Methods/Procedures

Each subject had a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia and had been on stable dose of risperidone for at least 4 weeks. In a 16-week randomized, double-blind, placebo-controlled study, subjects received either minocycline (200 mg/d) or placebo. Various metabolic parameters, including weight, waist circumference, fasting insulin, glucose, and lipids, were measured at baseline and week 16.

Findings/Results

A total of 63 subjects with schizophrenia were enrolled in the study. Fifty-five patients completed week-16 assessments (27 in the minocycline group, 28 in the placebo group). There were no significant differences between the 2 groups in week 16 changes for body weight, body mass index, waist circumference, fasting insulin, glucose, and lipids (P’s > 0.300).

Implications/Conclusions

In the present study, adjunctive treatment of minocycline did not seem to improve body metabolism in patients with schizophrenia receiving risperidone. The implications for future studies were discussed.
Effects of Alcohol on the Pharmacokinetics of Blonanserin and N-Deethylated Blonanserin in Healthy Chinese Subjects
Authors: Deng Shuhua , Ni Xiaojia , Shang Dewei , Wang Zhanzhang , Zhang Ming , Hu Jinqing , Zhu Xiuqing , Lu Haoyang , Chen Yuqing , Zhang Yuefeng , Peng Huan , Wen Yuguan
Published: February 2018

Purpose/Background

Blonanserin is a novel antipsychotic drug approved for the treatment of schizophrenia in East Asia. The main objective of the present study was to investigate the effect of alcohol on the pharmacokinetic properties of blonanserin and its metabolite N-deethyl blonanserin in healthy Chinese male subjects under fasting conditions.

Methods/Procedures

The study was designed as a randomized, open-label, crossover clinical investigation in 10 male volunteers, each of whom received 2 treatments under fasted conditions: treatment A, blonanserin (8 mg) with water, and treatment B, blonanserin (8 mg) with alcohol (1 mL/kg).

Findings/Results

The average values of areas under the curve (AUCs) and mean peak plasma concentrations (C
max) were noticeably increased by alcohol consumption. In treatment A, average values of AUC0–24h, AUC0–∞, and C
max were 3178 ng/h/L, 3879 ng/h/L, and 492 ng/L for blonanserin, and 1932 ng/h/L, 4208 ng/h/L, and 137 ng/L for N-deethylated blonanserin, respectively. In treatment B, AUC0–∞ and C
max were both increased 2.4-fold for blonanserin and 1.4-fold and 1.7-fold, respectively, for N-deethylated blonanserin (P < 0.05). Compared with treatment A, clearance (Clz/F) of blonanserin and N-deethylated blonanserin decreased significantly (2.4-fold and 1.7-fold, respectively) in treatment B (P < 0.05). Alcohol delayed the absorption and reduced the clearance of blonanserin, leading to a 1.8-fold increase in the time to reach C
max (T
max) and half life time (t
1/2) (P < 0.05).

Implications/Conclusions

Alcohol increased the bioavailability of blonanserin and N-deethyl blonanserin in healthy subjects and the marked effect of alcohol on blonanserin bioavailability should be taken into consideration in deciding dosing schedules in clinical therapy.
The Antioxidant Effect of Rosmarinic Acid by Different Delivery Routes in the Animal Model of Noise-Induced Hearing Loss
Authors: Fetoni Anna R. , Eramo Sara Letizia Maria , Di Pino Antonella , Rolesi Rolando , Paciello Fabiola , Grassi Claudio , Troiani Diana , Paludetti Gaetano
Published: February 2018

Hypothesis:

Trans-tympanic Rosmarinic Acid (RA), as compared with the systemic administration, protects against noise-induced auditory hair cell and hearing losses in rats in vivo.

Background:

ROS production, lipoperoxidative damage, and an imbalance of antioxidant defences play a significant role in noise-induced hearing loss. Several molecules with antioxidant properties have been tested to restore redox homeostasis; however, drug delivery system represents a challenge for their effectiveness. In our model, acute and intense noise exposure induces hearing loss, hair cell death, and oxidative stress, with an increase in superoxide production and over-expression of lipid peroxidation in cochlear structures.

Methods:

RA was administrated in male Wistar rats by trans-tympanic (20 μl) and systemic (10 mg/kg) modality. In systemic administration, RA was injected 1 hour before noise exposure and once daily for the following 3 days. ABRs were measured before and at days 1, 3, 7, and 30 after noise exposure. Rhodamine-phalloidin staining, dihydroethidium and 8-isoprostane immunostainings were performed to assess and quantify outer hair cells loss, superoxide production, and lipid peroxidation in the different experimental groups.

Results:

Systemic RA administration significantly decreased noise-induced hearing loss and the improvement of auditory function was paralleled by a significant reduction in cochlear oxidative stress. The trans-tympanic modality of drug administration showed a similar degree of protection both at the functional and morphological levels.

Conclusion:

The effectiveness of RA given via trans-tympanic injection could be interesting for the future application of this minimally-invasive procedure in the treatment of ROS-induced hearing loss.
Immunotherapy for recurrent/metastatic head and neck cancer
Authors: Alfieri Salvatore , Cavalieri Stefano , Licitra Lisa
Published: February 2018

Purpose of review

In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less ‘immunogenic’ than other malignancies (e.g. melanoma), was field of application of several new immune agents. To date, the most important data regard drugs acting on PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) axis that is a crucial checkpoint used by tumor for immune escape. Our purpose is to summarize the results of these PD-1/PD-L1 inhibitors, outlining some critical points and few practical suggestions.

Recent findings

Nivolumab was recently approved by main regulatory agencies as second-line treatment for platinum-refractory R/M HNSCC. In the same setting, pembrolizumab was approved by FDA. Atezolizumab and durvalumab have already showed similar benefit in phase Ia and II studies, respectively.

Anti-PD1/PD-L1 agents are new effective therapies in R/M HNSCC. Their combination with conventional/novel compounds, as well as a better selection of responding patients, could lead to improve current results.
Leukocyte Telomere Length and Pancreatic Cancer Risk
Authors: Antwi Samuel O. , Petersen Gloria M.
Published: February 2018

Many risk factors have been firmly established for pancreatic cancer (PC), but the molecular processes by which known risk factors influence susceptibility to PC are not clear. There has been a recent upsurge of interest in the role of telomere length (TL), the protective DNA sequence repeats at chromosome ends, in pancreatic carcinogenesis. Given this heightened interest, we performed an in-depth, focused, and up-to-date review of the epidemiological evidence linking leukocyte TL (LTL) with PC risk. We searched MEDLINE, Embase, and the Cochrane Library databases for all published studies on LTL and PC risk, up to May 2017. Five studies were identified for review: 4 nested case-control studies and 1 retrospective case-control study. Two studies found opposite associations between LTL and PC risk: 1 found a dose-response positive association and the other found a dose-response inverse association. Two studies also found a “U-shaped” association, whereas another reported a weak nonlinear relationship. We offer potential reasons for the conflicting findings including variation in study design, biospecimen characteristics, and differences in interlaboratory measurements of TL. Future studies should carefully control for risk factors of PC that are associated also with telomere attrition and investigate the role of genetic variation in TL maintenance.
Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Fonseca Annabelle L. , Kirkwood Kimberly , Kim Michael P. , Maitra Anirban , Koay Eugene J.
Published: February 2018

The incidence of intraductal papillary mucinous neoplasms (IPMNs) has been increasing over the past decade, mainly owing to increased awareness and the increased use of cross-sectional imaging. The Sendai and Fukuoka consensus guidelines provide us with clinical management guidelines and algorithms; however, the clinical management of IPMNs continues to be challenging. Our incomplete understanding of the natural history of the disease, and the events and pathways that permit progression to adenocarcinoma, result in difficulties predicting which tumors are high risk and will progress to invasive disease. In this review, we summarize the current management guidelines and describe ongoing efforts to more clearly stratify IPMNs by risk of malignancy and identify IPMNs with malignant potential or ongoing malignant transformation.
Utility of Echocardiography as Screening for Late-onset Anthracycline-induced Cardiotoxicity in Pediatric Cancer Survivors: Observations from the First Decade After End of Therapy
Authors: Moke Diana J. , Schubert Lynn E. , Sun Heather Y. , Printz Beth F. , Dietz Andrew C.
Published: February 2018

Current screening guidelines are available for anthracycline-induced cardiotoxicity. However, the utility of echocardiogram screening for late-onset anthracycline cardiotoxicity especially in the decade immediately after end of therapy is debatable. A retrospective chart review of patients seen in the Thriving after Cancer Clinic at Rady Children’s Hospital January 2006 to December 2013 was performed. Treatment data, echocardiogram results, cardiology referral notes and cardiac medication data were abstracted from anthracycline-exposed survivors. Descriptive and univariate comparative statistics were performed. Of 368 patients (45% female, median 5.3 y old at diagnosis [range 0 to 18.3], median 5.0 y from end of therapy [EOT] [range 0 to 18.2]), a total of 4 patients (10-year cumulative incidence after EOT 1.3%; 95% confidence interval, 0.1%-19.7%) required cardiac medication for late-onset cardiotoxicity (>1 y after EOT). Those requiring medication for late-onset cardiotoxicity were exposed to more anthracyclines than survivors without cardiotoxicity (median, 360 mg/m2 [range, 300 to 375 mg/m2] vs. 182 mg/m2 [range, 26 to 515 mg/m2], P=0.009). None had neck or chest radiation. In this population, medication initiation for late-onset anthracycline cardiotoxicity was limited predominantly to the first 3 years after EOT, with the next >13 years after EOT. These findings add to the growing body of literature assessing current guidelines to inform improvements in screening practices of survivorship providers.
Retroperitoneal Angiomatoid Fibrous Histiocytoma Presenting as a Recurrent Spontaneous Retroperitoneal Hemorrhage in a 9-Year-Old Boy
Authors: Slack Jonathan C. , Sanchez-Glanville Carlos , Steele MacGregor , Wong Andrew L. , Bründler Marie-Anne
Published: February 2018

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor that typically presents in children and young adults. Occurrence outside of the extremities and the head and neck region is exceedingly rare. We report the case of a 9-year-old boy who presented with recurrent retroperitoneal hemorrhage initially thought to be a manifestation of an underlying bleeding disorder. After comprehensive diagnostic work-up, including multiple negative biopsies, the patient underwent surgical resection of an extensively hemorrhagic intramuscular mass and to date remains well. Pathologic examination confirmed AFH with EWSR1 gene rearrangement. This first documented report of an AFH in a retroperitoneal location in a child highlights the diagnostic difficulties and clinical challenges of AFH arising in an atypical location.
Anemia in Adolescents and Young Adult Patients With Congenital Heart Disease
Authors: Rodríguez-Hernández Juan L. , Rodríguez-González Fayna , Martínez-Quintana Efrén
Published: February 2018

Introduction:

Despite anemia in acquired heart disease being a common problem, little is known in patients with congenital heart disease (CHD).

Methods:

In total, 544 consecutive stable noncyanotic CHD patients were studied to determine demographic, clinical, and analytic parameters. Anemia was defined as a condition in which hemoglobin concentration was <13 g/dL in male individuals and <12 g/dL in female individuals.

Results:

In total, 49 (9%) CHD patients had anemia. Patients with complex anatomy had the highest prevalence of anemia (33%). The median hemoglobin concentration was 14.4 (13.5 to 15.6) mg/dL. Of the total anemic CHD patients, 21 of 49 (43%) were microcytic (mean corpuscular volume <84 fL) and 46 of 49 (94%) had a mean corpuscular volume under 95 fL. Oral anticoagulation, oral antiaggregation, diuretic treatment, and having valve prostheses or cardiovascular risk factors, such as arterial hypertension or diabetes mellitus, did not reach statistical significance between anemic and nonanemic CHD patients. Multivariate analyses determined as risk factors for anemia a worse New York Heart Association functional class (patients in class >II/IV) (odds ratio [OR], 8.37; 95% confidence interval [CI], 1.69-41.35), N-terminal proB-type natriuretic peptide levels >125 pg/mL (OR, 7.90; 95% CI, 2.88-21.69), and apoferritn levels below 15 ng/mL (OR, 0.21; 95% CI, 0.09-0.50). The Kaplan-Meier survival analysis showed no significant differences in mortality between anemic and nonanemic CHD patients (P=0.143).

Conclusions:

The incidence of anemia in CHD patients is similar to that of the normal population and iron deficiency anemia accounts for most of the cases. There were no significant differences in mortality between CHD patients with and without anemia.
A Congenital Case of Ependymoblastoma: A Rare and Aggressive Brain Tumor
Authors: Grassham Courtney D. , Rady Sara , Foster Kimberly , SantaCruz Karen S. , Kuttesch John F. , Maxwell Jessie R.
Published: February 2018

Congenital brain tumors are rare, representing <2% of all childhood brain tumors. Of these, ependymoblastoma is a profoundly aggressive embryonal brain tumor that is included in the diagnostic entity known as an embryonal tumor with multilayered rosettes. This report of a congenital ependymoblastoma diagnosed at birth aims to highlight how much remains unknown about embryonal tumor with multilayered rosettes and the devastating prognosis of this condition. Despite recent advancements made in identifying molecular targets for therapy, this tumor continues to have a high rate of recurrence with few successful treatment options, especially when diagnosed in the newborn period.
How Do Patients Respond to Genetic Testing for Age-related Macular Degeneration?
Authors: McCarty Catherine A. , Fuchs Michael J. , Lamb Allan , Conway Pat
Published: February 2018

SIGNIFICANCE

The American Academy of Ophthalmology currently recommends against routine genetic testing for complex diseases such as age-related macular degeneration (AMD). The results of this study demonstrate that patients are very interested in predictive genetic testing for AMD, find the information useful, and make behavioral changes as a result of the information.

PURPOSE

The goal of this project was to conduct a pilot AMD genomic medicine study.

METHODS

Eligible patients were aged 50 to 65 years with no personal history of AMD. DNA samples were genotyped for five single-nucleotide polymorphisms (SNPs) in the CFH gene, one SNP in the ARMS-2 gene, one SNP in the C3 gene, and one SNP in the mitochondrial ND2 gene. A risk score was calculated utilizing a model based on odds ratios, lifetime risk of advanced AMD and known population prevalence of genotype, haplotype, and smoking risk. The study optometrist provided the patient's risk score and counseling for personal protective behaviors. Telephone interviews were conducted 1 to 3 months after the counseling visit.

RESULTS

One hundred one subjects (85%) participated in the genetic testing; 78 (77.2%) were female. Follow-up interviews were conducted with 94 participants (93.1%). More than half (n = 48) of the participants said that they were motivated to participate in the study because they had a family member with AMD or another eye or genetic disorder. Despite low risk levels, many participants reported making changes as a result of the genetic testing. Twenty-seven people reported making specific changes, including wearing sunglasses and brimmed hat and taking vitamin supplements. Another 16 people said that they were already doing the recommended activities, including wearing glasses, quitting smoking, and/or taking vitamins.

CONCLUSIONS

Interest in genetic testing for future risk of AMD was high in this population and resulted in support to continue current health behaviors or incentive to improve behaviors related to eye health.
What Is the Nature of the Reach and Grasp Deficit in Wet Age-related Macular Degeneration?
Authors: Corveleyn Xavier , Lenoble Quentin , Szaffarczyk Sébastien , Tran Thi Ha Chau , Boucart Muriel
Published: February 2018

SIGNIFICANCE

Vision is paramount for motor actions directed toward objects. Vision allows not only the identification of objects and their shape and spatial location, but also the adaptation of our movement when it arrives on the object. These findings show that vision deficits, as in age-related macular degeneration (AMD), can lead to reaching and grasping deficits.

PURPOSE

Few studies have investigated reaching and grasping in patients with AMD. They showed a deficit in the execution of motor actions in people with AMD, even though these people do not mention difficulties in their daily lives. The purpose of this study was to understand the nature of impairments in motor actions in patients.

METHODS

We compared performance in two reach-and-grasp tasks determined by whether the participants (16 people with wet AMD and 17 age-matched control subjects) had time to look at the object before reaching and grasping it.

RESULTS

The results show that the kinematic parameters of reach-and-grasp movements do not differ between groups when participants are provided time to look at the object before the movement. In contrast, performance in terms of movement duration, acceleration time, time to reach the maximum grip aperture, and the maximum velocity differ between patients and control subjects when the object is displayed immediately before the movement.

CONCLUSIONS

The motor perturbations observed in people with AMD in previous studies seem to result from difficulties in target identification rather than from visuomotor deficits.
Evaluation of Vasopressin for Vasoplegic Shock in Patients With Preoperative Left Ventricular Dysfunction After Cardiac Surgery: A Propensity-Score Analysis
Authors: Cheng Yongqing , Pan Tuo , Ge Min , Chen Tao , Ye Jiaxin , Lu Lichong , Chen Cheng , Zong Qiuyan , Ding Yi , Wang Dongjin
Published: February 2018

Purpose:

Postoperative vasoplegic shock after cardiac surgery seems to be a frequent complication with poor outcomes. We hypothesized that vasopressin may increase the risk of poor outcomes in patients with preoperative Left Ventricular Dysfunction (pLVD) rather than norepinephrine. The aim of this study was to assess whether vasopressin is superior to norepinephrine to improve outcomes in patients with pLVD after cardiac surgery.

Methods:

This retrospective cohort study included 1,156 patients with postoperative vasoplegic shock (mean arterial pressure <65 mmHg resistant to fluid challenge and cardiac index >2.20 L/min m2) and pLVD (left ventricular ejection fraction ≤35%, left ventricular end-diastolic diameter ≥60 mm, New York Heart Association ≥III) from 2007 to 2017. To address any indicated biases, we derived a propensity score predicting the functions of vasopressin (0.02–0.07 U/min) and norepinephrine (10–60 μg/min) on postoperative vasoplegic shock. The primary outcomes were 30-day mortality, mechanical ventilation more than 48 h, cardiac reoperation, extracorporeal membrane oxygenation, stroke, and acute kidney injury, whereas the secondary outcomes included infection, septic shock, atrial fibrillation and ventricular arrhythmias.

Results:

There were 338 patients (169 vasopressin and169 norepinephrine) with a similar risk profile in propensity score-matched cohort. In propensity-matched patients, the primary outcomes of vasopressin and norepinephrine showed no significant difference (50.89% vs. 58.58%, P = 0.155). However, compared with norepinephrine, secondary outcomes of vasopressin were increased due to the high rate of atrial fibrillation (11.83% vs. 20.12%, P = 0.038) and ventricular arrhythmias (14.20% vs. 24.85%, P = 0.014).

Conclusions:

Compared with norepinephrine, vasopressin could not improve the postoperative outcomes in patients with pLVD after cardiac surgery. Vasopressin should be cautious to be used as a first-line vasopressor agent in postcardiac vasoplegic shock.