bluuebunny/crossref_metadata_2025 huggingface dataset:
Tobacco and alcohol-induced epigenetic changes in oral carcinoma
Authors: Ghantous Yasmine , Schussel Juliana L. , Brait Mariana
Published: March 2018

Purpose of review

The present review aims to describe the epigenetic alterations observed in oral cancer linked to the exposure to alcohol and/or tobacco.

Recent findings

Recent findings emphasize the importance of epigenetics in oral cancer progression and in how risk factors (as tobacco and alcohol) affect the basal epigenetic profiles. Deeper techniques and detailed approaches allowed the perception that individual CG changes and even subtle changes may represent important epigenetic alterations resulting in expression changes and other carcinogenic consequences. New classes of epigenetic alterations including noncoding RNAs have been gaining attention.

Many epigenetic alterations have been described in oral carcinoma progression induced by tobacco and/or alcohol, including: promoter hypermethylation in genes with tumor suppressive activity, global (genome-wide) hypomethylation, change in methylation patterns throughout the genes, alteration in noncoding RNAs, and histones modifications. These changes represent progress in the knowledge of how these risk factors act in a molecular level. There is an urgent need for large independent studies to move these potential makers further and validate them to identify risk assessment, early diagnostic markers, and therapeutic targets, as well as to be the base for prevention and intervention strategies.
Managing seminomatous and nonseminomatous germ cell tumors
Authors: Chahoud Jad , Zhang Miao , Shah Amishi , Lin Sue-Hwa , Pisters Louis L. , Tu Shi-Ming
Published: March 2018

Purpose of review

In the present review, we summarize the recent developments in the management of germ cell tumors (GCTs).

Recent findings

Treatment-related acute and late-onset toxicity remains a key challenge in the management of GCTs, with recent evidence showing that the adverse health outcomes of etoposide and cisplatin for four cycles in comparison to bleomycin, etoposide, and cisplatin for three cycles appear to be similar. Recent data showed that multidisciplinary clinic approach and management in experienced academic centers were associated with improved overall survival in GCT patients. There are currently multiple conventional-dose chemotherapy options for salvage therapy in patients with refractory or recurrent disease. In addition, more efficacious high-dose chemotherapy regimens continue to be developed. The role of salvage conventional-dose chemotherapy versus high-dose chemotherapy is currently being investigated prospectively. Recent reports suggested that brentuximab vedotin could be a potential salvage option for cluster of differentiation 30 positive refractory GCTs. On the other hand the results of the first phase II clinical trial investigating pembrolizumab in refractory GCTs were disappointing showing no clinical activity.

Finally, deep exploration of the immune profile of GCTs using immunohistochemistry and gene expression profiling has identified that advanced GCT stage was associated with decreased T-cell and Natural killer-cell signatures, whereas T regulatory, neutrophil, mast cell, and macrophage signatures increased with advanced stage. Even though these results indicated that activated T-cell infiltration correlated with seminoma histology and good prognosis, and could be used in the future as a biomarker, this approach needs to be validated in a large cohort.

Remaining challenges to be addressed include minimizing therapeutic toxicity, and improving outcomes in patients with refractory/recurrent GCTs.
The evolving genomic landscape in urothelial cancer
Authors: Kujtan Lara , Hussain Arif , Subramanian Janakiraman , Masood Ashiq
Published: March 2018

Purpose of review

Recent advances in next-generation sequencing have allowed for detailed molecular analysis of urothelial carcinomas, with potentially significant clinical implications for personalized treatment. Our objective in this review is to highlight studies from the past year that have furthered the understanding of urothelial cancer genomics.

Recent findings

Recent studies by The Cancer Genome Atlas consortium further characterized urothelial carcinomas via molecular subtyping, and a schema was proposed to match each subtype with potential therapeutic implications. Molecular subtyping was also utilized in a separate analysis to determine which tumours benefit from neoadjuvant chemotherapy. Tumour characteristics were also explored pre and postneoadjuvant chemotherapy and a mutational signature associated with postcisplatin treatment was described. We also review a comprehensive analysis of upper tract urinary carcinomas published this past year.

Recent genomic analyses have revealed that the classification of urothelial carcinoma is much more complex than the traditional dichotomy of nonmuscle-invasive and muscle-invasive bladder cancers. Molecular subtyping has provided additional insights into prognoses and treatment options for these patients. Although molecular subtyping is not yet ready for implementation into clinical practice, these latest efforts offer an exciting opportunity to integrate such information into prospective clinical studies that may ultimately lead to improved treatment outcomes.
Lymphoid aggregates in desmoplastic melanoma have features of tertiary lymphoid structures
Authors: Stowman Anne M. , Hickman Alexandra W. , Mauldin Ileana S. , Mahmutovic Adela , Gru Alejandro A. , Slingluff Craig L.
Published: March 2018

Desmoplastic melanomas (DM) have unique and challenging clinical presentations and histomorphology. A characteristic feature is the presence of scattered lymphoid aggregates. However, the nature of these aggregates is not defined. We hypothesized that they may be tertiary lymphoid structures (TLS), and may be associated with programmed death ligand 1 (PD-L1) expression. We searched our tissue database for ‘pure’ DMs and for scars as control tissues, collected clinical information, and reviewed H&E histology. We performed multispectral imaging after staining for CD8, CD20, PNAd, FoxP3, CD83, and Ki67, and assessed PD-L1 expression by immunohistochemistry. Pure DM samples were evaluable in 11 patients. All had desmoplastic stroma and lymphoid aggregates on H&E. The lymphoid aggregates of eight of the 11 (72%) DM samples and only three of the 11 scars contained features of TLS, defined as distinct clusters of B cells and CD8+ T cells, CD83+ dendritic cells in T-cell zones, and PNAd+ vasculature resembling high endothelial venules. PD-L1 was expressed by at least 1% of melanoma cells in six and by at least 5% of immune cells in 10 of the 11 DM samples. We found that most lymphoid aggregates in DM are organized, classical TLS. PD-L1 expression was detected in most cases and was highest in two cases of DM with TLS. However, low PD-L1 expression in some cases suggests that some DM cells may be unresponsive to interferon-γ. TLS support antigen presentation and T-cell responses in chronic inflammation and cancer. Their presence in DM likely reflects an adaptive immune response, which may be enhanced with immune therapies.
Polymorphous Sweat Gland Carcinoma: An Immunohistochemical and Molecular Study
Authors: Ronen Shira , Aguilera-Barrantes Irene , Giorgadze Tamara , Šteiner Petr , Grossmann Petr , Suster Saul
Published: March 2018

Polymorphous sweat gland carcinoma is an uncommon low-grade malignant adnexal tumor with a marked predilection for the distal extremities. Histologically, the lesions are characterized by a cellular proliferation showing a combination of growth patterns, including trabecular, solid, tubular, cribriform, or adenoid cystic and pseudopapillary. The immunohistochemical and molecular profile of these tumors has not yet been properly addressed. We have studied 3 cases of polymorphous sweat gland carcinoma using a broad panel of immunohistochemical markers including cytokeratin AE1/AE3, CK5/6, MOC31, p40, p63, p16, chromogranin, synaptophysin, CD56, MIB-1, estrogen receptor, progesterone receptor, androgen receptor, BER-EP4, smooth muscle actin, epithelial membrane antigen, carcinoembryonic antigen, CD117, S100 protein, HBME-1, DOG1, vimentin, and mammaglobin. We also examined for the MYB-NFIB fusion by fluorescent in situ hybridization (ISH) and for human papilloma virus by ISH. Our studies show that cytokeratin AE1/AE3, CK5/6, p40, p63, p16, chromogranin, and CD56 stains were positive in all 3 cases. All 3 cases were negative for MYB-NFIB fusion by fluorescent ISH which rules out adenoid cystic carcinoma. DNA ISH studies for high-risk human papilloma virus were negative in all cases. MIB-1 proliferation index was very high (30%–70% nuclear positivity), supporting a malignant phenotype. The positivity for chromogranin and CD56 suggests partial neuroendocrine differentiation. The differential diagnosis includes metastases from internal malignancies, basal cell carcinoma, and other benign and malignant adnexal neoplasms such as adenoid cystic carcinoma, ductal eccrine carcinoma, and microcystic carcinoma. Positivity for p16 in combination with chromogranin and CD56 may be potentially good markers for differentiating this tumor from other adnexal tumors.
Rare Variant of Agminated Spitz Nevi on a Hypopigmented Background and Segmental Distribution: Case Report and Review of Literature
Authors: Nevares-Pomales Oscar W. , Carrasquillo Osward Y. , Santiago-Vazquez Marely , Colon-Fontanez Francisco
Published: March 2018

Spitz nevus is a type of melanocytic nevus that can arise as a solitary lesion or as multiple lesions either disseminated or agminated (grouped) in different skin backgrounds (eg, grossly normal, hyperpigmented, or hypopigmented). Agminated Spitz nevi have been rarely reported and are even rarer in a background of hypopigmented skin. We present the case of a 2-month-old girl with multiple, grouped, dome-shaped, red papules arising on a hypopigmented patch with a segmental distribution. Biopsy of 2 lesions showed findings characteristic of Spitz nevus, confirming the diagnosis. We also review 4 other cases of agminated Spitz nevi arising on hypopigmented skin reported in the literature.
Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action
Authors: Prague Julia K. , Roberts Rachel E. , Comninos Alexander N. , Clarke Sophie , Jayasena Channa N. , Mohideen Pharis , Lin Vivian H. , Stern Theresa P. , Panay Nicholas , Hunter Myra S. , Webber Lorraine C. , Dhillo Waljit S.
Published: March 2018

Objective:

Seventy percent of postmenopausal women experience vasomotor symptoms, which can be highly disruptive and persist for years. Hormone therapy and other treatments have variable efficacy and/or side effects. Neurokinin B signaling increases in response to estrogen deficiency and has been implicated in hot flash (HF) etiology. We recently reported that a neurokinin 3 receptor (NK3R) antagonist reduces HF in postmenopausal women after 4 weeks of treatment. In this article we report novel data from that study, which shows the detailed time course of this effect.

Methods:

Randomized, double-blind, placebo-controlled, single-center, crossover trial of an oral NK3R antagonist (MLE4901) for vasomotor symptoms in women aged 40 to 62 years, experiencing ≥7 HF/24 hours some of which were reported as bothersome or severe (Clinicaltrials.gov NCT02668185). Thirty-seven women were randomized and included in an intention-to-treat analysis. To ascertain the therapeutic profile of MLE4901, a post hoc time course analysis was completed.

Results:

By day 3 of treatment with MLE4901, HF frequency reduced by 72% (95% CI, −81.3 to −63.3%) compared with baseline (51 percentage point reduction compared with placebo, P < 0.0001); this effect size persisted throughout the 4-week dosing period. HF severity reduced by 38% compared with baseline by day 3 (95% CI, −46.1 to −29.1%) (P < 0.0001 compared with placebo), bother by 39% (95% CI, −47.5 to −30.1%) (P < 0.0001 compared with placebo), and interference by 61% (95% CI, −79.1 to −43.0%) (P = 0.0006 compared with placebo); all continued to improve throughout the 4-week dosing period (to −44%, −50%, and −70%, respectively by day 28, all P < 0.0001 compared with placebo).

Conclusions:

NK3R antagonism rapidly relieves vasomotor symptoms without the need for estrogen exposure.
Virtual Incision Pattern Planning using Three-Dimensional Images for Optimization of Syndactyly Surgery
Authors: Hoevenaren Inge A. , Vreeken Rinaldo D. , Verhulst Arico C. , Ulrich Dietmar J. O. , Maal Thomas J. J. , Wagner Till
Published: March 2018

Syndactyly is a congenital condition characterized by fusion of the fingers. If not treated correctly during infancy, syndactyly may hinder the normal development of hand function. Many surgical techniques have been developed, with the main goal to create a functional hand with the smallest number of operative corrections. Therefore, exact preoperative planning of the reconstructive procedure is essential. An imaging method commonly used for preoperative planning is 3-dimensional (3D) surface imaging. The goal of this study was to implement the use of this technique in hand surgery, by designing a virtual planning tool for a desyndactylization procedure based on 3D hand images. A 3D image of a silicon syndactyly model was made on which the incision pattern was virtually designed. A surgical template of this pattern was printed, placed onto the silicon model and delineated. The accuracy of the transfer from the virtual delineation toward the real delineation was calculated, resulting in a mean difference of 0.82 mm. This first step indicates that by using 3D images, a virtual incision pattern can be created and transferred back onto the patient successfully in an easy and accurate way by using a template. Thereafter, 3D hand images of 3 syndactyly patients were made, and individual virtual incision patterns were created. Each pattern was transferred onto the patient by using a 3D printed template. The resulting incision pattern needed minor modifications by the surgeon before the surgery was performed. Further research and validation are necessary to develop the virtual planning of desyndactylization procedures.
The stress regulator FKBP51: a novel and promising druggable target for the treatment of persistent pain states across sexes
Authors: Maiarù Maria , Morgan Oakley B. , Mao Tianqi , Breitsamer Michaela , Bamber Harry , Pöhlmann Max , Schmidt Mathias V. , Winter Gerhard , Hausch Felix , Géranton Sandrine M.
Published: March 2018

It is well established that FKBP51 regulates the stress system by modulating the sensitivity of the glucocorticoid receptor to stress hormones. Recently, we have demonstrated that FKBP51 also drives long-term inflammatory pain states in male mice by modulating glucocorticoid signalling at spinal cord level. Here, we explored the potential of FKBP51 as a new pharmacological target for the treatment of persistent pain across the sexes. First, we demonstrated that FKBP51 regulates long-term pain states of different aetiologies independently of sex. Deletion of FKBP51 reduced the mechanical hypersensitivity seen in joint inflammatory and neuropathic pain states in female and male mice. Furthermore, FKBP51 deletion also reduced the hypersensitivity seen in a translational model of chemotherapy-induced pain. Interestingly, these 3 pain states were associated with changes in glucocorticoid signalling, as indicated by the increased expression, at spinal cord level, of the glucocorticoid receptor isoform associated with glucocorticoid resistance, GRβ, and increased levels of plasma corticosterone. These pain states were also accompanied by an upregulation of interleukin-6 in the spinal cord. Crucially, we were able to pharmacologically reduce the severity of the mechanical hypersensitivity seen in these 3 models of persistent pain with the unique FKBP51 ligand SAFit2. When SAFit2 was combined with a state-of-the-art vesicular phospholipid gel formulation for slow release, a single injection of SAFit2 offered pain relief for at least 7 days. We therefore propose the pharmacological blockade of FKBP51 as a new approach for the treatment of persistent pain across sexes, likely in humans as well as rodents.
Dilute lidocaine suppresses ectopic neuropathic discharge in dorsal root ganglia without blocking axonal propagation: a new approach to selective pain control
Authors: Koplovitch Pini , Devor Marshall
Published: March 2018

Ectopic impulse discharge (ectopia) generated in the soma of afferent neurons in dorsal root ganglia (DRG) after nerve injury is believed to be a major contributor to neuropathic pain. The DRG is thus a prime interventional target. The process of electrogenesis (impulse generation) in the DRG is far more sensitive to systemically administered Na+channel blockers than the process of impulse propagation along sensory axons. It should therefore be possible to selectively suppress DRG ectopia with local application of membrane-stabilizing agents without blocking normal impulse traffic. Results from in vivo electrophysiological recordings in rats showed that epidural application of lidocaine to the DRG surface within the intervertebral foramen at 0.02% or 0.2% substantially suppresses electrogenesis in the DRG with only a modest blocking effect on impulse propagation through the foramen. Topically applied opiates and gamma aminobutyric acid, by contrast, blocked neither ongoing discharge nor spike through-conduction. This suggests that sustained intraforaminal delivery of dilute lidocaine, and by extension other membrane-stabilizing agents, is a potential new strategy for the control of chronic painful conditions in which ectopia in sensory ganglia is implicated as a key pain driver. Such conditions include postherpetic neuralgia, trigeminal neuralgia, phantom limb pain, complex regional pain syndrome, and radicular low back pain.
Reduced selective learning in patients with fibromyalgia vs healthy controls
Authors: Meulders Ann , Boddez Yannick , Blanco Fernando , Van Den Houte Maaike , Vlaeyen Johan W.S.
Published: March 2018

Impaired selective fear learning has been advanced as a core mechanism involved in excessive spreading of protective responses such as pain-related fear and avoidance leading to disability in chronic pain conditions. Using the litmus test for selective learning effects, the blocking procedure, we tested the hypothesis that patients with fibromyalgia (FM) show less selective threat learning than healthy controls (HCs). We introduce a novel selective learning task based around a clinical diary scenario. On a trial-by-trial basis, participants rated whether they expected certain situations (A, B, Z, and X) in the diary of a fictive FM patient would trigger pain in that patient. The procedure did not involve any experimental pain induction because the verbal outcomes “pain” or “no pain” were used. During the elemental acquisition phase, one situation was followed by “pain” (A+, eg, “Kim slept badly, and reports pain”), whereas another situation was followed by “no pain” (Z−, eg, “Kim was stressed, and reports no pain”). During the compound acquisition phase, another situation (X), referred to as the blocked stimulus, was presented in compound with a previously pain-eliciting situation and also paired with “pain” (AX+, eg, Kim slept badly” and “Kim has vacuumed,” and reports pain). Simultaneously, a novel situation was introduced and also followed by “pain” (B+). Within-group comparisons showed blocking (ie, significant difference between B and X) in the HCs, but not in the patients with FM. This study is the first in directly assessing differences in selective learning between patients with FM and HCs using a blocking procedure.
Bilateral Cochlear Implantation Versus Bimodal Hearing in Patients With Functional Residual Hearing: A Within-subjects Comparison of Audiologic Performance and Quality of Life
Authors: Yawn Robert J. , O’Connell Brendan P. , Dwyer Robert T. , Sunderhaus Linsey W. , Reynolds Susan , Haynes David S. , Gifford René H.
Published: March 2018

Objective:

Evaluate performance and quality of life changes after sequential bilateral cochlear implantation in patients with preoperative residual hearing functioning in a bimodal hearing configuration.

Study Design:

Retrospective analysis using within-subjects repeated measures design.

Setting:

Tertiary otologic center.

Patients:

Twenty-two adult patients with bilateral sensorineural hearing loss who used bimodal hearing before second cochlear implant (CI) meeting the following criteria: 1) preoperative residual hearing (≤80 dB HL at 250 Hz) in the ear to be implanted, 2) implantation with current CI technology (2013–2016), 3) consonant-nucleus-consonant (CNC) speech recognition testing in the bimodal condition preoperatively and bilateral CI condition postoperatively.

Intervention:

Cochlear implantation.

Main Outcome Measures:

CNC and AzBio sentence scores in quiet and noise (+5 SNR). Subjective measures of communication difficulty and sound quality were also administered.

Results:

Twenty-two patients (mean 64 yr, 68% men) were included. At an average follow-up of 11.8 months, CNC scores in the bilateral CI condition (mean 63%, standard deviation [SD] = 22) were significantly better than preoperative bimodal scores with repeated measures analysis (mean 55%, SD = 22) (p = 0.03). AzBio scores in quiet were also higher with bilateral CI (mean 76%, SD = 24) compared with bimodal listening (mean 69%, SD = 29) (p = 0.0007). Global abbreviated profile of hearing aid benefit (APHAB) and overall speech, spatial, and qualities of hearing (SSQ) scores exhibited significant improvement following bilateral implantation (p = 0.006 for both analyses).

Conclusions:

For patients using a bimodal hearing configuration with substantial residual hearing in the non-CI ear, bilateral cochlear implantation yields improved audiologic performance and better subjective quality of life, irrespective of the ability to preserve acoustic hearing during the second sided implantation.
Cystic fibrosis transmembrane conductance regulator modulators: precision medicine in cystic fibrosis
Authors: Burgener Elizabeth B. , Moss Richard B.
Published: March 2018

Purpose of review

The aim of this study was to describe the newest development in cystic fibrosis (CF) care, CF transmembrane conductance regulator (CFTR) modulator therapies.

Recent findings

Phase II results showing CFTR modulator triple therapies are more effective than current CFTR modulators.

CFTR modulator therapy targets the protein defective in CF and boosts its function, but the drug must match mutation pathobiology. Ivacaftor, a CFTR potentiator, was the first modulator approved in 2012, with impressive improvement in lung function and other measures of disease in patients with gating and other residual function mutations (∼10% of CF patients). In 2015, the combination of lumacaftor, a CFTR corrector, and ivacaftor was approved for patients homozygous for the F508del mutation (∼40–50% of the CF population) with positive but less impressive clinical response and 10–20% incidence of intolerance. A next-generation CFTR corrector, tezacaftor, with ivacaftor equally effective and better tolerated than lumacaftor, has also received US Food and Drug Administration approval. Novel CFTR correctors, entering Phase 3 trials in triple modulator combination with tezacaftor-ivacaftor, appear substantially more effective for patients who are homozygous for the F508del mutation and can provide benefit for patients with a single F508del mutation. This offers promise of effective CFTR modulator therapy for nearly 90% of CF patients.
Useful References in Pediatric Cardiac Intensive Care: The 2017 Update*
Authors: Uzark Karen C. , Costello John M. , DeSena Holly C. , Thiagajaran Ravi , Smith-Parrish Melissa , Gist Katja M.
Published: March 2018

Objectives:

Pediatric cardiac intensive care continues to evolve, with rapid advances in knowledge and improvement in clinical outcomes. In the past, the Board of Directors of the Pediatric Cardiac Intensive Care Society created and subsequently updated a list of sentinel references focused on the care of critically ill children with congenital and acquired heart disease. The objective of this article is to provide clinicians with a compilation and brief summary of updated and useful references that have been published since 2012.

Data Selection:

Pediatric Cardiac Intensive Care Society members were solicited via a survey sent out between March 20, 2017, and April 28, 2017, to provide important references that have impacted clinical care. The survey was sent to approximately 523 members. Responses were received from 45 members, of which some included multiple references.

Data Extraction:

Following review of the list of references, and removing editorials, references were compiled by the first and last author. The final list was submitted to members of the society’s Research Briefs Committee, who ranked each publication.

Data Synthesis:

Rankings were compiled and the references with the highest scores included. Research Briefs Committee members ranked the articles from 1 to 3, with one being highly relevant and should be included and 3 being less important and should be excluded. Averages were computed, and the top articles included in this article. The first (K.C.U.) and last author (K.M.G.) reviewed and developed summaries of each article.

Conclusions:

This article contains a compilation of useful references for the critical care of children with congenital and acquired heart disease published in the last 5 years. In conjunction with the prior version of this update in 2012, this article may be used as an educational reference in pediatric cardiac intensive care.
Variability in Antibiotic Use Across PICUs*
Authors: Brogan Thomas V. , Thurm Cary , Hersh Adam L. , Gerber Jeffrey S. , Smith Michael J. , Shah Samir S. , Courter Joshua D. , Patel Sameer J. , Parker Sarah K. , Kronman Matthew P. , Lee Brian R. , Newland Jason G.
Published: March 2018

Objectives:

To characterize and compare antibiotic prescribing across PICUs to evaluate the degree of variability.

Design:

Retrospective analysis from 2010 through 2014 of the Pediatric Health Information System.

Setting:

Forty-one freestanding children’s hospital.

Subjects:

Children aged 30 days to 18 years admitted to a PICU in children’s hospitals contributing data to Pediatric Health Information System.

Interventions:

To normalize for potential differences in disease severity and case mix across centers, a subanalysis was performed of children admitted with one of the 20 All Patient Refined-Diagnosis Related Groups and the seven All Patient Refined-Diagnosis Related Groups shared by all PICUs with the highest antibiotic use.

Results:

The study included 3,101,201 hospital discharges from 41 institutions with 386,914 PICU patients. All antibiotic use declined during the study period. The median-adjusted antibiotic use among PICU patients was 1,043 days of therapy/1,000 patient-days (interquartile range, 977–1,147 days of therapy/1,000 patient-days) compared with 893 among non-ICU children (interquartile range, 805–968 days of therapy/1,000 patient-days). For PICU patients, the median adjusted use of broad-spectrum antibiotics was 176 days of therapy/1,000 patient-days (interquartile range, 152–217 days of therapy/1,000 patient-days) and was 302 days of therapy/1,000 patient-days (interquartile range, 220–351 days of therapy/1,000 patient-days) for antimethicillin-resistant Staphylococcus aureus agents, compared with 153 days of therapy/1,000 patient-days (interquartile range, 130–182 days of therapy/1,000 patient-days) and 244 days of therapy/1,000 patient-days (interquartile range, 203–270 days of therapy/1,000 patient-days) for non-ICU children. After adjusting for potential confounders, significant institutional variability existed in antibiotic use in PICU patients, in the 20 All Patient Refined-Diagnosis Related Groups with the highest antibiotic usage and in the seven All Patient Refined-Diagnosis Related Groups shared by all 41 PICUs.

Conclusions:

The wide variation in antibiotic use observed across children’s hospital PICUs suggests inappropriate antibiotic use.
The Effects of a Motorized Aquatic Treadmill Exercise Program on Muscle Strength, Cardiorespiratory Fitness, and Clinical Function in Subacute Stroke Patients
Authors: Lee So Young , Im Sang Hee , Kim Bo Ryun , Han Eun Young
Published: March 2018

Objective

The aim of this study was to assess whether the effects of a motorized aquatic treadmill exercise program improve the isometric strength of the knee muscles, cardiorespiratory fitness, arterial stiffness, motor function, balance, functional outcomes, and quality of life in subacute stroke patients.

Design

Thirty-two patients were randomly assigned to 4-wk training sessions of either aquatic therapy (n = 19) or land-based aerobic exercise (n = 18). Isometric strength was measured using an isokinetic dynamometer. Cardiopulmonary fitness was evaluated using a symptom-limited exercise tolerance test and by measuring brachial ankle pulse wave velocity. Moreover, motor function (Fugl-Meyer Assessment [FMA] and FMA-lower limb [FMA-LL]), balance (Berg Balance Scale [BBS]), Activities of daily living (Korean version of the Modified Barthel Index [K-MBI]), and quality of life (EQ-5D index) were examined.

Results

There were no intergroup differences between demographic and clinical characteristics at baseline (P > 0.05). The results shows significant improvements in peak oxygen consumption (P = 0.02), maximal isometric strength of the bilateral knee extensors (P < 0.01) and paretic knee flexors (P = 0.01), FMA (P = 0.03), FMA-LL (P = 0.01), BBS (P = 0.01), K-MBI (P < 0.01), and EQ-5D index (P = 0.04) after treatment in the aquatic therapy group. However, only significant improvements in maximal isometric strength in the knee extensors (P = 0.03) and flexors (P = 0.04) were found within the aquatic therapy group and control group.

Conclusions

Water-based aerobic exercise performed on a motorized aquatic treadmill had beneficial effect on isometric muscle strength in the lower limb.

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CME Objectives

Upon completion of this article, the reader should be able to: (1) Articulate the rationale for including walking on an aquatic treadmill in the rehabilitation of subacute stroke patients; (2) Describe the beneficial effects of a motorized aquatic treadmill exercise program in the rehabilitation of subacute stroke patients; and (3) Determine the appropriate indications for incorporating a motorized aquatic treadmill exercise program in the rehabilitation of subacute stroke patients.

Level: Advanced

Accreditation

The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Interactions Between Stress and Sex in Microbial Responses Within the Microbiota-Gut-Brain Axis in a Mouse Model
Authors: Tsilimigras Matthew C.B. , Gharaibeh Raad Z. , Sioda Michael , Gray Laura , Fodor Anthony A. , Lyte Mark
Published: March 2018

Objective

Animal models are frequently used to examine stress response, but experiments seldom include females. The connection between the microbiota-gut-brain axis and behavioral stress response is investigated here using a mixed-sex mouse cohort.

Methods

CF-1 mice underwent alternating days of restraint and forced swim for 19 days (malen= 8, femalen= 8) with matching numbers of control animals at which point the 16S rRNA genes of gut microbiota were sequenced. Mixed linear models accounting for stress status and sex with individuals nested in cage to control for cage effects evaluated these data. Murine behaviors in elevated plus-maze, open-field, and light/dark box were investigated.

Results

Community-level associations with sex, stress, and their interaction were significant. Males had higher microbial diversity than females (p= .025). Of the 638 operational taxonomic units detected in at least 25% of samples, 94 operational taxonomic units were significant: 31 (stress), 61 (sex), and 34 (sex-stress interaction). Twenty of the 39 behavioral measures were significant for stress, 3 for sex, and 6 for sex-stress. However, no significant associations between behavioral measures and specific microbes were detected.

Conclusions

These data suggest sex influences stress response and the microbiota-gut-brain axis and that studies of behavior and the microbiome therefore benefit from consideration of how sex differences drive behavior and microbial community structure. Host stress resilience and absence of associations between stress-induced behaviors with specific microbes suggests that hypothalamic-pituitary-adrenal axis activation represents a threshold for microbial influence on host behavior. Future studies are needed in examining the intersection of sex, stress response, and the microbiota-gut-brain axis.
High Medication Possession Ratios Associated With Greater Risk of Virologic Failure Among Youth Compared With Adults in a Nigerian Cohort
Authors: Ahonkhai Aimalohi A. , Banigbe Bolanle , Adeola Juliet , Bassett Ingrid V. , Idigbe Ifeoma , Okonkwo Prosper , Freedberg Kenneth A. , Regan Susan , Losina Elena
Published: March 2018

Background:

Medication possession ratio (MPR) is widely used as a measure of adherence to antiretroviral therapy (ART). Many adolescents and young adults (AYA) experience ART adherence challenges. Our objective was to determine whether the relationship between MPR and virologic failure (VF) is consistent between AYA and older adults in Nigeria.

Methods:

We conducted a retrospective study of AYA (aged 15–25 years) and adults (aged >25 years) who initiated ART between January 2009 and December 2012 at 10 university-affiliated HIV clinics in Nigeria. We used multivariate generalized linear models to assess the relationship between age, MPR (ART doses dispensed)/(days since ART initiation), and risk of VF (HIV RNA >1000 copies/mL) in the 1st year on ART.

Results:

The cohort included 1508 AYA and 11,376 older adults. VF was more common in AYA than older adults (30% vs. 24% P < 0.01). Overall, 74% of patients had optimal, 16% suboptimal, and 9% poor adherence (MPR >94%, 80%–94%, and <80%, respectively). AYA attended fewer pharmacy-only visits than older adults (5 vs. 6, P < 0.001). Higher MPR was associated with decreased rate of VF (80%–94%, accounting rate of return 0.57; >94% accounting rate of return 0.43, P < 0.001 vs. MPR <80%). Among those with optimal adherence by MPR, 26% of AYA had VF, a risk that was 20% higher than for older adults with optimal adherence (P < 0.001).

Conclusions:

In this Nigerian cohort, MPRs were high overall, and there was a strong association between low MPR and risk of VF. Nonetheless, 26% of AYA with high MPRs still had VF. Understanding the discrepancy between MPR and viral suppression in AYA is an important priority.
Evaluation of the Efficacy of Different Concentrations of Dextrose Prolotherapy in Temporomandibular Joint Hypermobility Treatment
Authors: Mustafa Rawand , Güngörmüş Metin , Mollaoğlu Nur
Published: March 2018

Purpose:

The aim of this study was to compare and evaluate the efficacy of different concentrations of dextrose prolotherapy for the treatment of temporomandibular joint (TMJ) hypermobility.

Patients and Methods:

A prospective, randomized clinical trial including patients with subluxation or dislocation was performed. The study comprised 40 patients. Patients were randomly divided into 4 groups: control group, 10% dextrose, 20% dextrose, and 30% dextrose group. Patients in all groups received injections into 4 different areas of each TMJ in 4 sessions at monthly intervals. Visual analog scale of TMJ pain intensity, maximum mouth opening (MMO), joint sounds, and frequency of luxations were recorded preoperatively and postoperatively after 1 month of last injection. The collected data were then statistically analyzed.

Results:

Each group showed postoperatively significant improvement in TMJ pain, significant decrease in both MMO and joint sound. Besides that, TMJ locking was not observed in any patient during the follow-up period. There were no statistically significant differences throughout the study intervals between the groups.

Conclusion:

It was concluded that there was no significant difference between control group and dextrose groups and there is no superiority of any concentration of dextrose over the others in TMJ prolotherapy, and all treatment procedures were efficient in improvement of clinical symptoms related to TMJ hypermobility. If dextrose is used as a proliferant, it can be said that 10% dextrose can be sufficient in TMJ hypermobility treatment.
Interventions to Reduce Intraoperative Costs
Authors: Childers Christopher P. , Showen Amy , Nuckols Teryl , Maggard-Gibbons Melinda
Published: March 2018

Objective:

The aim of this study was to systematically review the risks and benefits of interventions designed to reduce intraoperative costs.

Summary Background Data:

Episode-based payments shift financial risk from insurers onto hospitals and providers. The operating room (OR) is a resource dense environment and there is growing interest in identifying ways to reduce intraoperative costs while maintaining patient safety.

Methods:

We searched PubMed, Cochrane, and CINAHL for articles published between 2001 and March 2017 that assessed interventions designed to reduce intraoperative costs. We grouped interventions into 6 categories: standardization of instruments, switching to reusable instruments or removing instruments from trays, wound closure comparisons, cost feedback to surgeons, head-to-head instrument trials, and timely arrival of surgeon to the OR.

Results:

Of 43 included studies, 12 were randomized trials and 31 were observational studies. Gross cost estimates ranged from −$413 (losses) to $3154 (savings) per operation, with only 2 studies reporting losses; however, studies had significant methodologic limitations related to cost data. Studies evaluating standardization and cost feedback were the most robust with estimated cost savings between $38 and $732/case, with no change in OR time, length of stay, or adverse events.

Conclusions:

Almost all studies assessing interventions to reduce intraoperative costs have demonstrated cost savings with no apparent increase in adverse effects. Methodologic limitations, especially related to cost data, weaken the reliability of these estimates for most intervention categories. However, hospitals seeking to reduce costs may be able to do so safely by standardizing operative instruments or providing cost feedback to surgeons.
Emergency Computed Tomography Predicts Caustic Esophageal Stricture Formation
Authors: Bruzzi Matthieu , Chirica Mircea , Resche-Rigon Matthieu , Corte Helene , Voron Thibault , Sarfati Emile , Zagdanski Anne-Marie , Cattan Pierre
Published: March 2018

Background:

Endoscopy is the best predictor of stricture formation after caustic ingestion.

Objective:

Our aim was to compare the accuracy of emergency computed tomography (CT) and endoscopy in predicting risks of esophageal stricture.

Methods:

We describe a CT classification of esophageal caustic injuries: Grade I show normal esophagus; Grade IIa display internal enhancement of the esophageal mucosa and enhancement of the outer wall conferring a “target” aspect; Grade IIb present as a fine rim of external esophageal wall enhancement. In 152 patients (56 males, median age 45) who underwent esophageal preservation after caustic ingestion we compared the accuracy of the CT and endoscopic (Zargar) classifications in predicting esophageal stricture.

Results:

On endoscopy esophageal injuries were classified as grade 1 (n = 50; 33%), grade 2a (n = 11; 7%), grade 2b (n = 19; 13%), grade 3a (n = 14; 9%), and grade 3b (n = 58; 38%). On CT, 47 (31%) patients had grade I, 47 (31%) had grade IIa and 58 (38%) had grade IIb esophageal injuries. Fifty-six (37%) patients developed esophageal strictures. The risk of esophageal stricture formation was 0%, 17%, and 83%, for grade I, IIa, and IIb CT injuries and 0, 0, 28, 50, and 76% for endoscopic grade 1, 2a, 2b, and 3a and 3b injuries, respectively. ROC curve analysis at 120 days after ingestion showed that CT outperformed endoscopy in predicting stricture formation (AUC: 85.1 [95% CI, 74.9–95.3] vs 77.8 [95% CI, 66.5–89.0], P = 0.047) and did just as well as a combined CT-endoscopy algorithm (AUC: 85.8 [95% CI, 76.5–95.0] vs 85.1 [95% CI, 74.9–95.3], P = 0.73).

Conclusion:

Emergency CT outperforms endoscopy in predicting esophageal stricture formation after caustic ingestion. Emergency endoscopy evaluation after caustic ingestion is not indispensable.
Feeder density enhances house finch disease transmission in experimental epidemics
Authors: Moyers Sahnzi C. , Adelman James S. , Farine Damien R. , Thomason Courtney A. , Hawley Dana M.
Published: March 2018

Anthropogenic food provisioning of wildlife can alter the frequency of contacts among hosts and between hosts and environmental sources of pathogens. Despite the popularity of garden bird feeding, few studies have addressed how feeders influence host contact rates and disease dynamics. We experimentally manipulated feeder density in replicate aviaries containing captive, pathogen-naive, groups of house finches (
Haemorhous mexicanus
) and continuously tracked behaviours at feeders using radio-frequency identification devices. We then inoculated one bird per group with
Mycoplasma gallisepticum
(Mg), a common bacterial pathogen for which feeders are fomites of transmission, and assessed effects of feeder density on house finch behaviour and pathogen transmission. We found that pathogen transmission was significantly higher in groups with the highest density of bird feeders, despite a significantly lower rate of intraspecific aggressive interactions relative to the low feeder density groups. Conversely, among naive group members that never showed signs of disease, we saw significantly higher concentrations of Mg-specific antibodies in low feeder density groups, suggesting that birds in low feeder density treatments had exposure to subclinical doses of Mg. We discuss ways in which the density of garden bird feeders could play an important role in mediating the intensity of Mg epidemics.

This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife'.
Health hazards to wild birds and risk factors associated with anthropogenic food provisioning
Authors: Lawson Becki , Robinson Robert A. , Toms Mike P. , Risely Kate , MacDonald Susan , Cunningham Andrew A.
Published: March 2018

Provision of supplementary food for wild birds at garden feeding stations is a common, large-scale and year-round practice in multiple countries including Great Britain (GB). While these additional dietary resources can benefit wildlife, there is a concomitant risk of disease transmission, particularly when birds repeatedly congregate in the same place at high densities and through interactions of species that would not normally associate in close proximity. Citizen science schemes recording garden birds are popular and can integrate disease surveillance with population monitoring, offering a unique opportunity to explore inter-relationships between supplementary feeding, disease epidemiology and population dynamics. Here, we present findings from a national surveillance programme in GB and note the dynamism of endemic and emerging diseases over a 25-year period, focusing on protozoal (finch trichomonosis), viral (Paridae pox) and bacterial (passerine salmonellosis) diseases with contrasting modes of transmission. We also examine the occurrence of mycotoxin contamination of food residues in bird feeders, which present both a direct and indirect (though immunosuppression) risk to wild bird health. Our results inform evidence-based mitigation strategies to minimize anthropogenically mediated health hazards, while maintaining the benefits of providing supplementary food for wild birds.

This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.
Winter feeding of elk in the Greater Yellowstone Ecosystem and its effects on disease dynamics
Authors: Cotterill Gavin G. , Cross Paul C. , Cole Eric K. , Fuda Rebecca K. , Rogerson Jared D. , Scurlock Brandon M. , du Toit Johan T.
Published: March 2018

Providing food to wildlife during periods when natural food is limited results in aggregations that may facilitate disease transmission. This is exemplified in western Wyoming where institutional feeding over the past century has aimed to mitigate wildlife–livestock conflict and minimize winter mortality of elk (
Cervus canadensis
). Here we review research across 23 winter feedgrounds where the most studied disease is brucellosis, caused by the bacterium
Brucella abortus
. Traditional veterinary practices (vaccination, test-and-slaughter) have thus far been unable to control this disease in elk, which can spill over to cattle. Current disease-reduction efforts are being guided by ecological research on elk movement and density, reproduction, stress, co-infections and scavengers. Given the right tools, feedgrounds could provide opportunities for adaptive management of brucellosis through regular animal testing and population-level manipulations. Our analyses of several such manipulations highlight the value of a research–management partnership guided by hypothesis testing, despite the constraints of the sociopolitical environment. However, brucellosis is now spreading in unfed elk herds, while other diseases (e.g. chronic wasting disease) are of increasing concern at feedgrounds. Therefore experimental closures of feedgrounds, reduced feeding and lower elk populations merit consideration.

This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.
Consequences of resource supplementation for disease risk in a partially migratory population
Authors: Brown Leone M. , Hall Richard J.
Published: March 2018

Anthropogenic landscape features such as urban parks and gardens, landfills and farmlands can provide novel, seasonally reliable food sources that impact wildlife ecology and distributions. In historically migratory species, food subsidies can cause individuals to forgo migration and form partially migratory or entirely sedentary populations, eroding a crucial benefit of migration: pathogen avoidance through seasonal abandonment of transmission sites and mortality of infected individuals during migration. Since many migratory taxa are declining, and wildlife populations in urban areas can harbour zoonotic pathogens, understanding the mechanisms by which anthropogenic resource subsidies influence infection dynamics and the persistence of migration is important for wildlife conservation and public health. We developed a mathematical model for a partially migratory population and a vector-borne pathogen transmitted at a shared breeding ground, where food subsidies increase the nonbreeding survival of residents. We found that higher resident nonbreeding survival increased infection prevalence in residents and migrants, and lowered the fraction of the population that migrated. The persistence of migration may be especially threatened if residency permits emergence of more virulent pathogens, if resource subsidies reduce costs of infection for residents, and if infection reduces individual migratory propensity.

This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.