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New medicines are urgently required to treat the fatal neuromuscular disease Duchenne muscular dystrophy (DMD). Dimethyl fumarate (DMF) is a potent immunomodulatory small molecule nuclear erythroid 2-related factor 2 activator with current clinical utility in the treatment of multiple sclerosis and psoriasis that could be effective for DMD and rapidly translatable. Here, we tested 2 weeks of daily 100 mg/kg DMF versus 5 mg/kg standard-care prednisone (PRED) treatment in juvenile mdx mice with early symptomatic DMD. Both drugs modulated seed genes driving the DMD disease program and improved force production in fast-twitch muscle. However, only DMF showed pro-mitochondrial effects, protected contracting muscles from fatigue, improved histopathology, and augmented clinically compatible muscle function tests. DMF may be a more selective modulator of the DMD disease program than PRED, warranting follow-up longitudinal studies to evaluate disease-modifying impact.

BACKGROUND A patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO’s ability to predict clinical response to gastrointestinal (GI) cancers.METHODS We generated PDOs from primary and metastatic lesions of patients with GI cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma. We compared PDO response with the observed clinical response for donor patients to the same treatments.RESULTS We report an approximately 80% concordance rate between PDO and donor tumor response. Importantly, we found a profound influence of culture media on PDO phenotype, where we showed a significant difference in response to standard-of-care chemotherapies, distinct morphologies, and transcriptomes between media within the same PDO cultures.CONCLUSION While we demonstrate a high concordance rate between donor tumor and PDO, these studies also showed the important role of culture media when using PDOs to inform treatment selection and predict response across a spectrum of GI cancers.TRIAL REGISTRATION Not applicable.FUNDING The Joan F. & Richard A. Abdoo Family Fund in Colorectal Cancer Research, GI Cancer program of the Mayo Clinic Cancer Center, Mayo Clinic SPORE in Pancreatic Cancer, Center of Individualized Medicine (Mayo Clinic), Department of Laboratory Medicine and Pathology (Mayo Clinic), Incyte Pharmaceuticals and Mayo Clinic Hepatobiliary SPORE, University of Minnesota-Mayo Clinic Partnership, and the Early Therapeutic program (Department of Oncology, Mayo Clinic).

Nonalcoholic fatty liver disease (NAFLD) is a range of pathologies arising from fat accumulation in the liver in the absence of excess alcohol use or other causes of liver disease. Its complications include cirrhosis and liver failure, hepatocellular carcinoma, and eventual death. NAFLD is the most common cause of liver disease globally and is estimated to affect nearly one-third of individuals in the United States. Despite knowledge that the incidence and prevalence of NAFLD are increasing, the pathophysiology of the disease and its progression to cirrhosis remain insufficiently understood. The molecular pathogenesis of NAFLD involves insulin resistance, inflammation, oxidative stress, and endoplasmic reticulum stress. Better insight into these molecular pathways would allow for therapies that target specific stages of NAFLD. Preclinical animal models have aided in defining these mechanisms and have served as platforms for screening and testing of potential therapeutic approaches. In this review, we will discuss the cellular and molecular mechanisms thought to contribute to NAFLD, with a focus on the role of animal models in elucidating these mechanisms and in developing therapies. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorders (AUD) are prevalent and often go untreated. Patients are commonly screened for AUD in primary care, but existing treatment programs are failing to meet demand. Digital therapeutics include novel mobile app-based treatment approaches which may be cost-effective treatment options to help fill treatment gaps. The goal of this study was to identify implementation needs and workflow design considerations for integrating digital therapeutics for AUD into primary care. Methods: We conducted qualitative interviews with clinicians, care delivery leaders, and implementation staff (n = 16) in an integrated healthcare delivery system in the United States. All participants had experience implementing digital therapeutics for depression or substance use disorders in primary care. Interviews were designed to gain insights into adaptations needed to optimize existing clinical processes, workflows, and implementation strategies for use with alcohol-focused digital therapeutics. Interviews were recorded and transcribed and then analyzed using a rapid analysis process and affinity diagramming. Results: Qualitative themes were well represented across health system staff roles. Participants were enthusiastic about digital therapeutics for AUD, anticipated high patient demand for such a resource, and made suggestions for successful implementation. Key insights regarding the implementation of digital therapeutics for AUD and unhealthy alcohol use from our data include: (1) implementation strategy selection must be driven by digital therapeutic design and target population characteristics, (2) implementation strategies should seek to minimize burden on clinicians given the large numbers of patients with AUD who are likely to be interested in and eligible for digital therapeutics, and (3) digital therapeutics should be offered alongside many other treatment options to accommodate individual patients' AUD severity and treatment goals. Participants also expressed confidence that previous implementation strategies used with other digital therapeutics such as clinician training, electronic health record supports, health coaching, and practice facilitation would be effective for the implementation of digital therapeutics for AUD. Conclusions: The implementation of digital therapeutics for AUD would benefit from careful consideration of the target population. Optimal integration requires tailoring workflows to meet anticipated patient volume and designing workflow and implementation strategies to meet the unique needs of patients with varying AUD severity. Contributions to the literature: Provides insights regarding the best ways to implement app-based treatments for alcohol use disorder (AUD) in primary care. Represents the perspectives of a variety of stakeholders including care delivery leaders, clinicians, and implementation staff. Identifies the following recommendations to improve the implementation of digital therapeutics for AUD: (1) plan for high patient volume, (2) support teams during implementation, and (3) account for individual patient needs. [ABSTRACT FROM AUTHOR]

Background: Ventriculitis usually occurs as the result of infection and results in the inflammation of the ependymal lining of the ventricular system. Mortality rates remain high despite treatment. Case Description: We present the case of a 66-year-old man who presented with altered mental status and progressively became comatose. He was found to have fulminant ventriculitis due to a ruptured intracranial abscess. He was treated with bilateral IRRAflow® catheter (IRRAS, Stockholm, Sweden) placement through which continuous irrigation with vancomycin was initiated. Conclusion: This treatment was safe and led to improvement in the patient's neurologic examination, imaging findings, and cerebrospinal fluid profiles. [ABSTRACT FROM AUTHOR]

The treatment of severe frostbite injury has undergone rapid development in the past 30 years with many different diagnostic and treatment options now available. However, there is currently no consensus on the best method for management of this disease process. At our institution, we have designed a protocol for severe frostbite injury that includes diagnosis, medical treatment, wound cares, therapy, and surgery. This study assess the efficacy of our treatment since its implementation six years ago. During this time, all patients with severe frostbite injury were included in prospective observational trial of the protocol. We found that this protocol results in significant tissue salvage with over 80.7% of previously ischemic tissue becoming viable and not requiring amputation. We also were able to improve our center's efficiency over the course of six years and now our current average time from rapid rewarming to delivery of thrombolytics is under six hours. [ABSTRACT FROM AUTHOR]

The canonical pathway is rapid, transient, and involves immune and inflammatory responses, whereas the noncanonical pathway is a slower, sustained response that often controls developmental processes including B-cell maturation.[7],[8] Deregulation of the NF- B pathway has been described in a variety of B-cell malignancies, including Hodgkin lymphoma, MALT lymphoma, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and multiple myeloma. On initial workup, a positron emission tomography (PET) and/or computed tomography (CT) showed a large left paraspinal pelvic mass and a left supragluteal mass with moderate fludeoxyglucose (FDG) uptake. Marginal zone lymphoma (MZL) is a heterogenous group of low-grade B-cell lymphomas that harbor various genetic alterations. Case 2 The patient was a 67-year-old female who underwent biopsy of an eyelid lesion (Figs 3A-C), which showed a dense infiltrate of B lymphocytes and plasma cells, and was diagnosed with ocular extranodal MZL of mucosa-associated lymphoid tissue (MALT lymphoma). [Extracted from the article]

Objective: Proximal ischial hamstring avulsion injuries are relatively uncommon. As such, the management of these injuries is often highly variable. Consensus agreement is lacking for the indications for repair, along with the operative technique, and post-operative rehabilitation. The purpose of this study was to survey surgeons who treat proximal hamstring avulsion injuries to identify current trends in the management of this injury. Methods: After IRB approval, a 46-question cross-sectional survey was distributed using a secure electronic survey portal. The survey sought to determine surgeon experience, diagnostic preferences, treatment patterns, surgical indications/technique, perceived patient outcomes, surgical complications, as well as post-operative management and rehab protocols. Surveys were completed electronically and anonymously, with invitations distributed to members of the American Orthopedic Society for Sports Medicine (AOSSM) and Arthroscopy Association of Canada (AAC). Results: A total of 108 surgeons who manage proximal hamstring injuries completed the survey. Most respondents (77%) treat one to five of these injuries per year. MRI was the preferred imaging modality to confirm diagnosis. Despite 98% of respondents indicating that there was a role for surgical management of proximal hamstring avulsions, operative treatment was reportedly undertaken in only 50% of cases seen by each respondent. The top three reported surgical indications were: number of tendons involved (most important factor = 42%, second most = 26%, third most = 13%), amount of tendon retraction (28%, 41%, 16%), and patient activity level (16%, 18%, 24%). Conclusion: Based on the practice patterns of the surgeons who completed the survey, there is continued disparity in the management of proximal hamstring avulsions. A lack of agreement exists with regards to surgical indications, operative technique, and post-operative protocols. Most striking is the rate of non-operative treatment and perceived rate of poor outcomes within this cohort. Future research should focus on objective evaluation of non-operative management, and additional variables involved in surgical treatment and post-operative rehabilitation. [ABSTRACT FROM AUTHOR]

Objectives  This study is aimed to report the largest independent case series of spontaneous otogenic pneumocephalus (SOP) and review its pathophysiology, clinical presentation, and treatment. Design  Four patients underwent a middle cranial fossa approach for repair of the tegmen tympani and tegmen mastoideum. A comprehensive review of the literature regarding this disease entity was performed. Setting  U.S. tertiary academic medical center. Participants:  Patients presenting to the lead author's clinic or to the emergency department with radiographic evidence of SOP. Symptoms included headache, otalgia, and neurologic deficits. Main Outcome Measures  Patients were assessed for length of stay, postoperative length of stay, and neurologic outcome. Three of four patients returned to their neurologic baseline following repair. Results  Four patients were successfully managed via a middle cranial fossa approach to repairing the tegmen mastoideum. Conclusion  The middle cranial fossa approach is an effective strategy to repair defects of the tegmen mastoideum. SOP remains a clinically rare disease, with little published information on its diagnosis and treatment. [ABSTRACT FROM AUTHOR]

As antimicrobial resistance increases, it is crucial to develop new treatment strategies to counter the emerging threat. In this paper, we consider combination therapies involving conventional antibiotics and debridement, coupled with a novel anti-adhesion therapy, and their use in the treatment of antimicrobial resistant burn wound infections. Our models predict that anti-adhesion–antibiotic–debridement combination therapies can eliminate a bacterial infection in cases where each treatment in isolation would fail. Antibiotics are assumed to have a bactericidal mode of action, killing bacteria, while debridement involves physically cleaning a wound (e.g. with a cloth); removing free bacteria. Anti-adhesion therapy can take a number of forms. Here we consider adhesion inhibitors consisting of polystyrene microbeads chemically coupled to a protein known as multivalent adhesion molecule 7, an adhesin which mediates the initial stages of attachment of many bacterial species to host cells. Adhesion inhibitors competitively inhibit bacteria from binding to host cells, thus rendering them susceptible to removal through debridement. An ordinary differential equation model is developed and the antibiotic-related parameters are fitted against new in vitro data gathered for the present study. The model is used to predict treatment outcomes and to suggest optimal treatment strategies. Our model predicts that anti-adhesion and antibiotic therapies will combine synergistically, producing a combined effect which is often greater than the sum of their individual effects, and that anti-adhesion–antibiotic–debridement combination therapy will be more effective than any of the treatment strategies used in isolation. Further, the use of inhibitors significantly reduces the minimum dose of antibiotics required to eliminate an infection, reducing the chances that bacteria will develop increased resistance. Lastly, we use our model to suggest treatment regimens capable of eliminating bacterial infections within clinically relevant timescales. [ABSTRACT FROM AUTHOR]

This research draws upon the interpersonal-psychological theory of suicide in the development of the LEAP intervention, a web-based selective preventive suicide intervention targeting cognitions of perceived burdensomeness toward others. The pilot randomized controlled trial consisted of 80 adolescents (68.8% female, 65.8% Hispanic) 13-19 of age years who were randomly assigned to either the LEAP intervention or a psychoeducational control condition. Participants completed baseline, posttreatment, and 6-week follow-up assessments. All participants reported high levels of satisfaction with the program. Findings on outcome variables differed across intent-to-treat analyses and treatment completer analyses. Intent-totreat analysis yielded no significant between-condition differences in perceived burdensomeness at posttreatment or follow-up. Treatment completer analyses revealed significant between-condition differences on outcome variables such that participants who completed the LEAP intervention showed significantly lower perceived burdensomeness scores at postintervention and significantly lower perceived burdensomeness, thwarted belongingness, and depressive symptom scores at follow-up as compared to participants in the control condition. No significant differences in suicidal ideation were found between conditions. These findings support the promise of the LEAP intervention as a brief, web-based selective preventive intervention for reducing perceived burdensomeness among adolescents who complete the intervention. This study provides evidence that perceived burdensomeness can be modified via a psychosocial intervention. Future research is needed to identify ways to enhance adolescent engagement with and completion of the intervention. [ABSTRACT FROM AUTHOR]

Antibiotic resistance has been demonstrated during the entire duration of antibiotic use even before medical utilization. Increasing resistance within virtually all microbes continues to be a problem. Infection with antibiotic resistant microbes has demonstrated significantly increased morbidity, death, and health-care-associated costs. Given increasing antibiotic resistance, multiple novel agents and approaches are being investigated, including antimicrobial lipids. Sphingosine and ceramide have been demonstrated to play a pivotal role in the innate immunity of the epidermis, oral mucosa, and respiratory epithelium; their role is being investigated currently in uroepithelium. Ceramide has been shown to be pivotal in the regulation of mammalian defense against Pseudomonas aeruginosa and Staphylococcus aureus pathogens commonly encountered in pneumonia. On the other hand, sphingosine appears to be equally pivotal and directly involved in pathogenic defense and has been demonstrated to "rescue" mammals from P. aeruginosa infections. Within this review, we will discuss the role of sphingolipids within innate immunity, pathogen invasion, and bacterial infection. We will discuss the antimicrobial activity of sphingosine and possibility for commercial use as an antimicrobial in the post-antibiotic era. [ABSTRACT FROM AUTHOR]

Studies reported a strong genetic correlation between the Big Five personality traits and major depressive disorder (MDD). Moreover, personality traits are thought to be associated with response to antidepressants treatment that might partly be mediated by genetic factors. In this study, we examined whether polygenic scores (PGSs) derived from the Big Five personality traits predict treatment response and remission in patients with MDD who were prescribed selective serotonin reuptake inhibitors (SSRIs). In addition, we performed meta-analyses of genome-wide association studies (GWASs) on these traits to identify genetic variants underpinning the cross-trait polygenic association. The PGS analysis was performed using data from two cohorts: the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS, n = 529) and the International SSRI Pharmacogenomics Consortium (ISPC, n = 865). The cross-trait GWAS meta-analyses were conducted by combining GWAS summary statistics on SSRIs treatment outcome and on the personality traits. The results showed that the PGS for openness and neuroticism were associated with SSRIs treatment outcomes at p < 0.05 across PT thresholds in both cohorts. A significant association was also found between the PGS for conscientiousness and SSRIs treatment response in the PGRN-AMPS sample. In the cross-trait GWAS meta-analyses, we identified eight loci associated with (a) SSRIs response and conscientiousness near YEATS4 gene and (b) SSRI remission and neuroticism eight loci near PRAG1, MSRA, XKR6, ELAVL2, PLXNC1, PLEKHM1, and BRUNOL4 genes. An assessment of a polygenic load for personality traits may assist in conjunction with clinical data to predict whether MDD patients might respond favorably to SSRIs. [ABSTRACT FROM AUTHOR]

Abstract: In this case series, we report seven immunized healthy children without underlying immunodeficiency who presented with herpes zoster that correlated with varicella‐zoster vaccination site. The morphology of the lesions included erythematous papules, pseudovesicles, and plaques, with associated pain in two and pruritus in three patients; systemic symptoms ranged from none to low‐grade fevers, upper respiratory symptoms, and joint pain. These cases highlight the clinical, diagnostic, and therapeutic implications of herpes zoster in vaccinated children. [ABSTRACT FROM AUTHOR]

The cancer anorexia cachexia syndrome is a systemic metabolic disorder characterized by the catabolism of stored nutrients in skeletal muscle and adipose tissue that is particularly prevalent in nonsmall cell lung cancer (NSCLC). Loss of skeletal muscle results in functional impairments and increased mortality. The aim of the present study was to characterize the changes in systemic metabolism in a genetically engineered mouse model of NSCLC. We show that a portion of these animals develop loss of skeletal muscle, loss of adipose tissue, and increased inflammatory markers mirroring the human cachexia syndrome. Using noncachexic and fasted animals as controls, we report a unique cachexia metabolite phenotype that includes the loss of peroxisome proliferatoractivated receptor-α (PPARα) -dependent ketone production by the liver. In this setting, glucocorticoid levels rise and correlate with skeletal muscle degradation and hepatic markers of gluconeogenesis. Restoring ketone production using the PPARα agonist, fenofibrate, prevents the loss of skeletal muscle mass and body weight. These results demonstrate how targeting hepatic metabolism can prevent muscle wasting in lung cancer, and provide evidence for a therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background Esthesioneuroblastomas (ENB) are uncommon and data regarding outcomes are often limited to single-institution series. The National Cancer Database (NCDB), which contains outcomes information from treatment centers across the United States, represents an opportunity to evaluate outcomes for rare diseases such as ENB across multiple institutions. Methods The NCDB was queried for location codes corresponding to the nasal cavity and paranasal sinuses and the histology code for ENB. Multivariate analyses were performed to evaluate for contributing factors to overall survival. Results A total of 1225 patients with ENB met the inclusion criteria. The 5-year overall survival was 76.2% (95% confidence interval [CI], 73.4-79.0%). Overall survival was associated with Kadish stage, grade, treatment sequence, margin status, Charlson/Deyo score, age, and gender ( p < 0.05). Multivariate analysis demonstrated that, compared with surgery alone, surgery followed by radiation without chemotherapy had improved all-cause mortality (odds ratio [OR], 0.61; 95% CI, 0.40-0.95). Surgery with chemotherapy alone was associated with increased odds of all-cause mortality (OR, 4.86; 95% CI, 2.31-10.25). Multivariate subanalysis for Kadish stages A and B demonstrated no difference in survival between surgery and surgery followed by radiation, but surgery followed by chemoradiation had worse overall survival (OR, 3.03; 95% CI, 1.07-8.56). For Kadish stage C, surgery followed by radiation had improved overall survival compared with surgery alone (OR, 0.44; 95% CI, 0.24-0.81). Conclusion The most common treatment for ENB is surgery followed by radiation, which is associated with the highest overall survival. The role of adjunctive chemotherapy needs to be re-evaluated in further studies. [ABSTRACT FROM AUTHOR]

Aims: Right ventricular (RV) pacing can impair left ventricular (LV) function. When timed with native RV activation, LV-only pacing may cause greater improvements in LV function than biventricular pacing. This study compared the chronic effects of cardiac resynchronization therapy (CRT) on LV mechanics between biventricular pacing and LV-only pacing in patients with normal atrioventricular (AV) conduction.Methods and Results: The Adaptive CRT (aCRT) algorithm provides LV-only pacing timed with native RV activation when the AV interval is normal (≤200 ms during sinus rhythm). We studied patients from the aCRT trial with normal AV conduction at their baseline visit and compared changes in cardiac function after 12 months of treatment with conventional biventricular or mostly (≥80%) LV-only pacing. Speckle tracking echocardiography was used to assess LV myocardial strain before and after treatment. Despite similar improvements in Packer's clinical composite scores and LV volumes, LV-only paced patients (n = 70) had a greater improvement in LV ejection fraction (8.5 ± 11.3% vs. 5.5 ± 10.3%, P = 0.038) and global LV radial strain (6.3 ± 8.6% vs. 4.0 ± 10.1%, P = 0.046) than those randomized to biventricular pacing (n = 91). Strain was improved to a greater extent near the RV pacing lead, in septal and apical regions (P < 0.05 for both regions), in patients receiving LV-only pacing.Conclusion: In heart failure patients with normal AV conduction, LV-only pacing timed with native RV activation may result in greater improvements in LV ejection fraction and myocardial strain compared with biventricular pacing due to better apical and septal function. [ABSTRACT FROM AUTHOR]

Background Off-label use of topical ophthalmologic formulations for treatment of rhinologic disease is cited in recent literature and is anecdotally prevalent among practicing otolaryngologists. Steroids, antibiotics, and other drugs designed for ocular use have subjective clinical efficacy in the nose and sinuses, but their specific effects on the ciliated epithelium are less well defined. This study examines 9 commercially available ophthalmologic drug formulations for effects on ciliary motility in sinonasal cultures, in an effort to characterize their utility as topical therapies for sinonasal diseases. Methods Ophthalmologic solutions were tested on human sinonasal cultures grown at an air-liquid interface. Baseline ciliary beat frequency (CBF) was recorded and compared with CBF changes in the 20 minutes after drug addition. Substances were categorized by degree of ciliostimulation or cilioinhibition. Results All ophthalmologic solutions tested had only moderate effects on CBF during the 20-minute experimental period, with no solutions causing overt ciliostasis. Azithromycin, neomycin, and olopatadine were slightly ciliostimulatory, whereas levofloxacin, tobramycin, dexamethasone, azelastine, and prednisolone acetate were cilioinhibitory. Ciprofloxacin elicited moderate cilioinhibition that progressed to ciliostimulation. Conclusion All solutions tested appear to have moderate effects on ciliated cell surfaces for a period of time typical of mucociliary clearance (10 to 20 minutes). Both active drugs and excipients can play a role in ciliary modulation, and specific formulations can show unique or unexpected properties. Any other individual ophthalmologic solutions to be used in a nasal drug delivery system should be tested in this manner to evaluate potential ciliary effects before clinical use. [ABSTRACT FROM AUTHOR]

Background and purpose Radiotherapy (RT) to the primary nasopharyngeal tumor is frequently offered to patients with metastatic nasopharyngeal carcinoma (mNPC). However, only limited data exist to support RT in this setting. We used the National Cancer Database (NCDB) to evaluate outcomes for mNPC patients receiving chemotherapy with and without local RT. Methods The NCDB was queried for patients with mNPC with synchronous metastatic disease at diagnosis who received chemotherapy. Overall survival (OS) was analyzed using the Kaplan–Meier method, Cox proportional hazards models, and propensity score-matched analyses. Results From 2004 to 2013, 718 cases were identified (39% chemotherapy-alone, 61% chemotherapy + RT). At a median follow-up of 4.4 years, RT was associated with improved survival on univariate analysis (median OS 21.4 vs 15.5 months; 5-year OS 28% vs 10%; p < 0.001) and multivariate analyses (HR, 0.61; CI, 0.51–0.74; p < 0.001). Propensity score analysis with matched baseline characteristics demonstrated a similar OS advantage with RT (HR, 0.68; CI, 0.55–0.84; p < 0.001). The benefits of RT remained consistent in models controlling for single vs multi-organ metastases and anatomic sites of metastatic involvement. RT dose was an independent prognostic factor as both a continuous and categorical variable, with OS benefits observed among patients receiving ≥50 Gy. Long-term survival of >10 years was only observed in the RT cohort. Conclusions This analysis supports strategies incorporating local RT with chemotherapy for mNPC. Prospective trials evaluating RT integration for mNPC are warranted. [ABSTRACT FROM AUTHOR]

Objectives: Baseline and post-concussion neurocognitive testing is useful in managing concussed athletes. Attention deficit hyperactivity disorder (ADHD) and stimulant medications are recognized as potential modifiers of performance on neurocognitive testing by the Concussion in Sport Group. Our goal was to assess whether individuals with ADHD perform differently on post-concussion testing and if this difference is related to the use of stimulants. Methods: Retrospective case-control study in which 4373 athletes underwent baseline and post-concussion testing using the ImPACT battery. 277 athletes self-reported a history of ADHD, of which, 206 reported no stimulant treatment and 69 reported stimulant treatment. Each group was matched with participants reporting no history of ADHD or stimulant use on several biopsychosocial characteristics. Non-parametric tests were used to assess ImPACT composite score differences between groups. Results: Participants with ADHD had worse verbal memory, visual memory, visual motor speed, and reaction time scores than matched controls at baseline and post-concussion, all withp ≤ .001 and |r|≥ 0.100. Athletes without stimulant treatment had lower verbal memory, visual memory, visual motor speed, and reaction time scores than controls at baseline (p ≤ 0.01, |r|≥ 0.100 [except verbal memory,r = −0.088]) and post-concussion (p = 0.000, |r|> 0.100). Athletes with stimulant treatment had lower verbal memory (Baseline:p = 0.047,r = −0.108; Post-concussion:p = 0.023,r = −0.124) and visual memory scores (Baseline:p = 0.013,r = −0.134; Post-concussion:p = 0.003,r = −0.162) but equivalent visual motor speed and reaction time scores versus controls at baseline and post-concussion. Conclusions: ADHD-specific baseline and post-concussion neuropsychological profiles, as well as stimulant medication status, may need to be considered when interpreting ImPACT test results. Further investigation into the effects of ADHD and stimulant use on recovery from sport-related concussion (SRC) is warranted. [ABSTRACT FROM PUBLISHER]

Background: The present study sought to identify trajectories of depressive symptoms in adolescence and emerging adulthood using a school-based sample of adolescents assessed over a five-year period. The study also examined whether bully and cyberbully victimization and perpetration significantly predicted depressive symptom trajectories.Method: Data from a sample of 1042 high school students were examined. The sample had a mean age of 15.09 years (SD=.79), was 56.0% female, and was racially diverse: 31.4% Hispanic, 29.4% White, and 27.9% African American. Data were examined using growth mixture modeling.Results: Four depressive symptoms trajectories were identified, including those with a mild trajectory of depressive symptoms, an increasing trajectory of depressive symptoms, an elevated trajectory of depressive symptoms, and a decreasing trajectory of depressive symptoms. Results indicated that bully victimization and cyberbully victimization differentially predicted depressive symptoms trajectories across adolescence, though bully and cyberbully perpetration did not.Limitations: Limitations include reliance on self-reports of bully perpetration and a limited consideration of external factors that may impact the course of depression.Conclusions: These findings may inform school personnel in identifying students' likely trajectory of depressive symptoms and determining where depression prevention and treatment services may be needed. [ABSTRACT FROM AUTHOR]

Severe frostbite is associated with high levels of morbidity through loss of digits or limbs. The aim of this study was to examine the salvage rate following severe frostbite injury. Frostbite patients from 2006 to 2014 were identified in the prospectively maintained database at a single urban burn and trauma center. Patients with imaging demonstrating a lack of blood flow in limbs/digits were included in the analysis (N = 73). The Hennepin Frostbite Score was used to quantify frostbite injury and salvage. This score provides a single value to assess each individual patient's salvage rate. The majority of patients with perfusion deficits were male (80%) with an average age of 42 years (range 11-83 years). Patients requiring amputation tended to be older (P = .002), have more tissue impacted by frostbite (P < .001), and experienced a longer time from rewarming to thrombolytic therapy (P = .001). A majority of patients (62%) received thrombolytic treatment. The percentage of patients requiring amputation was lower and the salvage rate was higher in patients treated with thrombolytics; however, the differences failed to reach statistical significance (P = .092 and P = .061, respectively). The rate of salvage decreases as the time from rewarming to thrombolytic therapy increases. Regression analysis demonstrates an additional 26.8% salvage loss with each hour of delayed treatment (P = .006). When the amount of tissue at risk for amputation is included in the model, each hour delay in thrombolytic treatment results in a 28.1% decrease in salvage (P = .011). This study demonstrates a significant decrease in limb/digit salvage with each hour of delayed administration of thrombolytics in patients with severe frostbite. [ABSTRACT FROM AUTHOR]

Purpose: To review the literature on femoroacetabular impingement (FAI) treatment outcomes, specifically focusing on potential pre-operative radiographic parameters that may provide prognostic information regarding outcomes following surgical management.Methods: A comprehensive review of computerized literature databases (Medline Ovid and PubMed) was performed, searching for articles reporting on FAI treatment outcomes. A single reviewer screened titles, abstracts and performed full-text reviews of eligible studies. The references of these studies were further screened for additional potentially relevant studies. A total of 243 studies were reviewed, with 18 meeting inclusion criteria.Results: Thirteen arthroscopic studies reported on 1556 patients, with clinical improvement in 35-92 % of patients and associated failure rates of 12-71 %. Five open surgical studies reported on 238 patients with clinical improvement in 65-95 % of patients and associated failure rates of 0-35 %. Both arthroscopic and open studies identified inferior outcomes with pre-operative radiographic findings of an elevated Tönnis grade (grade 2 or higher), joint space <2 mm, lateral centre-edge angle (LCEA) <20° and incomplete femoral osteoplasty.Conclusion: Pre-operative radiographic findings of osteoarthritis (Tönnis grade 2/3, <2 mm joint space) or dysplasia (LCEA < 20°) should be considered relative contraindications to joint preservation surgery as outcomes are worse among these patients and associated with a higher risk of conversion to total hip arthroplasty. Care should also be taken to perform a thorough femoral osteoplasty to reduce the risk of failure and need for revision surgery.Level Of Evidence: III. [ABSTRACT FROM AUTHOR]

Objective:Femoroacetabular impingement (FAI) has been increasingly recognized in cutting sports including soccer, hockey and football. More recently, the prevalence among overhead athletes has also been recognized. The purpose of this study was to review impingement patterns, return-to-play rates and clinical outcome following arthroscopic treatment of FAI among high-level baseball players. Methods:Between 2010 and 2014, 70 competitive baseball players (86 hips; age 22.4 ± 4.5 years) were identified. Demographics and return-to-play rates were recorded. Patient-reported outcome scores, including the Modified Harris Hip Score (mHHS), the Hip Outcome Score-Activity of Daily Living (HOS-ADL), the Sport-specific Subscale (HOS-SSS), and the International Hip Outcome Tool (iHOT-33), were collected pre-operatively at 6 months and 1year (n = 34, 49% of cohort). Results:The cohort included professional (27.1%), college (57.1%), high-school (8.6%) and club-team athletes (7.1%). Infielder (37.5%), pitcher (22.9%) and catcher (16.7%) were the most common positions. Average follow-up was 16.8 months (range 12.1–34.2). There was no relationship between playing position and impingement pattern (p ≥ 0.459), or between symptom laterality and handedness, batting position or playing position (p ≥ 0.179). One patient required revision surgery (infection). Return to sport rate was 88%, at a mean of 8.6 ± 4.2 months, with 97.7% returning at/above their pre-injury level of play. There was significant improvement in all outcome measures: mHHS (60.1 ± 11.9 to 93 ± 9.5), HOS-ADL (71.3 ± 16.7 to 96.3 ± 3.6), HOS-SSS (51.3 ± 24.8 to 92.3 ± 8.2) and iHOT-33 (40.7 ± 19.9 to 85.9 ± 14) (p < 0.001). Conclusion:Arthroscopic treatment of FAI in competitive baseball players resulted in high return-to-play rates at short-term follow-up, with significant improvements in clinical outcome scores. [ABSTRACT FROM PUBLISHER]

The aim of this study was to identify structural and functional brain changes that accompanied the transition from chronic (CM; ≥15 headache days/month) to episodic (EM; <15 headache days/month) migraine following prophylactic treatment with onabotulinumtoxinA (BoNT-A). Specifically, we examined whether CM patients responsive to prophylaxis (responders; n 11), as evidenced by a reversal in = disease status (defined by at least a 50% reduction in migraine frequency and <15 headache days/month), compared to CM patients whose migraine frequency remained unchanged (non-responders; n 12), showed differences in cortical thickness using = surface-based morphometry. We also investigated whether areas showing group differences in cortical thickness displayed altered resting-state functional connectivity (RS-FC) using seed-to-voxel analyses. Migraine characteristics measured across groups included disease duration, pain intensity and headache frequency. Patient reports of headache frequency over the 4 weeks prior to (pre-treatment) and following (post- treatment) prophylaxis were compared (post minus pre) and this measure served as the clinical endpoint that determined group assignment. All patients were scanned within 2 weeks of the post-treatment visit. Results revealed that responders showed significant cortical thickening in the right primary somatosensory cortex (SI) and anterior insula (aINS), and left superior temporal gyrus (STG) and pars opercularis (ParsOp) compared to non-responders. In addition, disease duration was negatively correlated with cortical thickness in fronto-parietal and temporo-occipital regions in responders but not non-responders, with the exception of the primary motor cortex (MI) that showed the opposite pattern; disease duration was positively associated with MI cortical thickness in responders versus non-responders. Our seed-based RS-FC analyses revealed anti-correlations between the SI seed and lateral occipital (LOC) and dorsomedial prefrontal cortices (DMPFC) in responders, whereas non- responders showed increased connectivity between the ParsOp seed and LOC. Overall, our findings revealed distinct morphometric and functional brain changes in CM patients that reverted to EM following prophylactic treatment compared to CM patients that showed no change in disease status. Elucidating the CNS changes involved in disease reversal may be critical to discovering interventions that prevent or slow the progression of CM. Such changes may aid in the evaluation of treatments as well as provide markers for disease "de-chronification". [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are noncoding RNAs that modulate cellular gene expression, primarily at the post-transcriptional level. We sought to examine the functional role of miR-155 in a model of viral-induced neuroinflammation.Methods: Acute encephalomyelitis and immune-mediated demyelination were induced by intracranial injection with the neurotropic JHM strain of mouse hepatitis virus (JHMV) into C57BL/6 miR-155 (+/+) wildtype (WT) mice or miR-155 (-/-) mice. Morbidity and mortality, viral load and immune cell accumulation in the CNS, and spinal cord demyelination were assessed at defined points post-infection. T cells harvested from infected mice were used to examine cytolytic activity, cytokine activity, and expression of certain chemokine receptors. To determine the impact of miR-155 on trafficking, T cells from infected WT or miR-155 (-/-) mice were adoptively transferred into RAG1 (-/-) mice, and T cell accumulation into the CNS was assessed using flow cytometry. Statistical significance was determined using the Mantel-Cox log-rank test or Student's T tests.Results: Compared to WT mice, JHMV-infected miR-155 (-/-) mice developed exacerbated disease concomitant with increased morbidity/mortality and an inability to control viral replication within the CNS. In corroboration with increased susceptibility to disease, miR-155 (-/-) mice had diminished CD8(+) T cell responses in terms of numbers, cytolytic activity, IFN-γ secretion, and homing to the CNS that corresponded with reduced expression of the chemokine receptor CXCR3. Both IFN-γ secretion and trafficking were impaired in miR-155 (-/-) , virus-specific CD4(+) T cells; however, expression of the chemokine homing receptors analyzed on CD4(+) cells was not affected. Except for very early during infection, there were not significant differences in macrophage infiltration into the CNS between WT and miR-155 (-/-) JHMV-infected mice, and the severity of demyelination was similar at 14 days p.i. between WT and miR-155 (-/-) JHMV-infected mice.Conclusions: These findings support a novel role for miR-155 in host defense in a model of viral-induced encephalomyelitis. Specifically, miR-155 enhances antiviral T cell responses including cytokine secretion, cytolytic activity, and homing to the CNS in response to viral infection. Further, miR-155 can play either a host-protective or host-damaging role during neuroinflammation depending on the disease trigger. [ABSTRACT FROM AUTHOR]

Objective: To systematically search the literature for trials evaluating luminal toxin-binding agents (LTBAs) for Clostridium difficile infection (CDI). Methods: A systematic search was conducted utilizing PubMed and International Pharmaceutical Abstracts with the following terms: anion-exchange resins, C difficile, cholestyramine, tolevamer, and colestipol. Articles were included if published in the English language and reported clinical outcomes of more than 5 adult humans with CDI treated with LTBAs. Results: Nearly all clinical trials evaluated LTBA as monotherapy for CDI and LTBAs are inferior to standard therapy. In contemporary practice, LTBAs are employed as adjunctive or sequential therapy for which there is a paucity of data. Some data suggest potential efficacy for recurrent CDI. Current guidelines for CDI assert LTBAs are contraindicated due to drug–drug interactions with vancomycin. However, the impact of this interaction on clinical outcomes has not been evaluated, and it is unknown whether higher doses of vancomycin or separating the administration of LTBAs from vancomycin would mitigate this interaction. Conclusion: LTBA monotherapy is inferior to vancomycin and metronidazole for CDI. Some data indicate possible benefit in reducing recurrent CDI, but outcomes with adjunctive and/or sequential LTBAs are unavailable. Further studies are needed to investigate the role of LTBAs for CDI. [ABSTRACT FROM AUTHOR]

Postoperative scar appearance is often a significant concern among patients, with many seeking advice from their surgeons regarding scar minimization. Numerous products are available that claim to decrease postoperative scar formation and improve wound healing. These products attempt to create an ideal environment for wound healing by targeting the three phases of wound healing: inflammation, proliferation, and remodeling. With that said, preoperative interventions, such as lifestyle modifications and optimization of medical comorbidities, and intraoperative interventions, such as adherence to meticulous operative techniques, are equally important for ideal scarring. In this article, the authors review the available options in postoperative scar management, addressing the benefits of multimodal perioperative intervention. Although numerous treatments exist, no single modality has been proven superior over others. Therefore, each patient should receive a personalized treatment regimen to optimize scar management. [ABSTRACT FROM AUTHOR]

There is insufficient evidence to recommend a specific protocol for treatment of infantile spasms (IS) and a lack of standardization among, and even within, institutions. Twice-daily dosing (for the first two weeks) of high-dose natural ACTH for IS is used by many centers and recommended by the National Infantile Spasms Consortium (NISC). Conversely, it is our practice to use once-daily dosing of high-dose natural ACTH for IS. In order to determine the effectiveness of our center's practice, we retrospectively reviewed 57 cases over the past four years at Boston Children's Hospital (BCH). We found that 70% of infants were spasm-free at 14 days from ACTH initiation and 54% continued to be spasm-free at 3-month follow-up. Electroencephalogram showed resolution of hypsarrhythmia (when present on the pretreatment EEG) in all responders. Additionally, once-daily dosing of ACTH was well tolerated. We performed a meta-analysis to compare our results against the reports of published literature using twice-daily high-dose ACTH for treatment of IS. The meta-analysis revealed that our results were comparable to previously published outcomes using twice-daily ACTH administration for IS treatment. Our experience shows that once-daily dosing of ACTH is effective for treatment of IS. If larger prospective trials can confirm our findings, it would obviate the need for additional painful injections, simplify the schedule, and support a universal standardized protocol. [ABSTRACT FROM AUTHOR]

The spinal cord is unable to regenerate after injury largely due to growth-inhibition by an inflammatory response to the injury that fails to resolve, resulting in secondary damage and cell death. An approach that prevents inhibition by attenuating the inflammatory response and promoting its resolution through the transition of macrophages to anti-inflammatory phenotypes is essential for the creation of a growth permissive microenvironment. Viral gene delivery to induce the expression of anti-inflammatory factors provides the potential to provide localized delivery to alter the host inflammatory response. Initially, we investigated the effect of the biomaterial and viral components of the delivery system to influence the extent of cell infiltration and the phenotype of these cells. Bridge implantation reduces antigen-presenting cell infiltration at day 7, and lentivirus addition to the bridge induces a transient increase in neutrophils in the spinal cord at day 7 and macrophages at day 14. Delivery of a lentivirus encoding IL-10, an anti-inflammatory factor that inhibits immune cell activation and polarizes the macrophage population towards anti-inflammatory phenotypes, reduced neutrophil infiltration at both day 7 and day 28. Though IL-10 lentivirus did not affect macrophages number, it skewed the macrophage population toward an anti-inflammatory M2 phenotype and altered macrophage morphology. Additionally, IL-10 delivery resulted in improved motor function, suggesting reduced secondary damage and increased sparing. Taken together, these results indicate that localized expression of anti-inflammatory factors, such as IL-10, can modulate the inflammatory response following spinal cord injury, and may be a key component of a combinatorial approach that targets the multiple barriers to regeneration and functional recovery. [ABSTRACT FROM AUTHOR]

Purpose To develop a nomogram for femtosecond laser astigmatic keratotomy (AK) to treat post-keratoplasty astigmatism. Setting Three academic medical centers. Design Retrospective interventional case series. Methods A review of post-keratoplasty femtosecond laser AK was performed. Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, manifest refraction, and keratometry were recorded preoperatively and 1, 3, 6, and 12 months postoperatively. The location, length, depth, and diameter of the AK incisions were recorded, and the surgically induced astigmatic correction was related to these variables using regression analysis. Results One hundred forty femtosecond laser AK procedures were performed after penetrating keratoplasty (PKP) (n = 129) or deep anterior lamellar keratoplasty (DALK) (n =11), with 89 procedures (80 PKP, 9 DALK) included in the analysis. The mean CDVA improved from 20/59 (0.47 logMAR ± 0.38 [SD]) preoperatively to 20/45 (0.35 ± 0.31 logMAR) postoperatively ( P = .013) (n = 46). The mean keratometric astigmatism decreased from 8.26 ± 2.90 diopters (D) preoperatively to 3.62 ± 2.59 D postoperatively ( P < .0001) (n = 89). The mean refractive cylinder decreased from 6.77 ± 2.80 D preoperatively to 2.85 ± 2.57 D postoperatively ( P < .0001) (n = 69). A nomogram for femtosecond laser AK to treat post-keratoplasty astigmatism was generated using regression analysis. Conclusions Femtosecond laser AK significantly improved UDVA and CDVA and significantly reduced keratometric astigmatism and refractive cylinder after keratoplasty. The nomogram generated should improve the accuracy of post-keratoplasty femtosecond laser AK. Financial Disclosure None of the authors has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Alloplastic facial implants have a wide range of uses to achieve the appropriate facial contour. A variety of materials such as metals, polymers, ceramics and synthetic injectable fillers are available to the reconstructive and aesthetic surgeon. Besides choosing the right surgical technique and the adequate material, the surgeon must be prepared to treat complications. Infection is an uncommon but serious complication that can cause displeasing consequences for the patient. There are few references in literature regarding treatment and management of facial implant-related infections. This study aims to discuss the role of biofilm in predisposing alloplastic materials to infection, to provide a review of literature, to describe our own institutional experience, and to define a patient care pathway for facial implant-associated infection. [ABSTRACT FROM AUTHOR]

Case: Multiple cases of modular femoral component failure involving fatigue at the modular stem junction have been reported following revision total hip arthroplasty. In the present report, we describe what we believe to be the first case of catastrophic failure involving the Biomet Arcos revision system. The failure involved a young patient with an elevated body mass index and proximal bone deficiency. Conclusion: The possibility of this failure mechanism must be weighed against the potential advantages of modular cementless stems when planning for complex hip arthroplasty, especially in the young, active patient. [ABSTRACT FROM AUTHOR]

Objectives To examine the risk of community-acquired pneumonia ( CAP) associated with the use of anticholinergic medications in elderly adults. Design Nested case-control study. Setting A regional Medicare Advantage healthcare plan (2009-2010). Participants Participants were Medicare Advantage Plan enrollees aged 65 and older with at least one inpatient and one outpatient claim with no history of CAP between January 1 and June 30, 2009. Cases were identified as enrollees with an incident diagnosis of CAP, between July 1, 2009, and December 31, 2010 (n = 291). Four age- and sex-matched controls (n = 1,164) were identified per case using incidence density sampling. Measurements Anticholinergic prescription 30 days preceding the event date was the primary exposure. Anticholinergic exposure was defined based on the Anticholinergic Drug Scale ( ADS). A conditional logistic regression model stratified on matched case-control sets was used, with exposure to a Level 1, 2, or 3 anticholinergic on the ADS as the main independent variable; CAP as the main outcome variable; and risk factors for CAP as additional explanatory variables. Results After controlling for risk factors, overall use of anticholinergic medications was significantly associated with risk of pneumonia (odds ratio (OR) = 1.65, 95% confidence interval (CI) = 1.20-2.28). The risk of pneumonia remained significant across the different exposure periods, although use of higher-level (ADS Level 2 or 3) anticholinergics was not associated with pneumonia risk (OR = 1.16, 95% CI = 0.70-1.96). Conclusion Overall use of anticholinergic medications, but not higher-level drugs, was associated with greater risk of CAP compared to no use after controlling for other factors. More research is needed to better understand the role of potent anticholinergic medications on pneumonia risk in elderly adults. [ABSTRACT FROM AUTHOR]

The wrist and hand are essential in the placement of the upper extremity in a functional position for grasp, pinch, and release activities. This depends on the delicate balance between the extrinsic and intrinsic muscles of the wrist and hand. Spasticity alters this equilibrium, limiting the interaction of the upper limb with the environment. Classically, pediatric patients with upper limb spasticity present with a flexed wrist, thumb-in-palm, and flexed finger posture. These contractures are typically secondary to spasticity of the extrinsic flexor muscles of the wrist and hand and intrinsic muscles of the thumb and digits. Tendon release, lengthening, or transfer procedures may help correct the resultant abnormal postures. A total wrist arthrodesis with or without proximal row carpectomy may help address the severely flexed wrist deformity. With proper diagnosis, a well-executed surgical plan, and a consistent hand rehabilitation regimen, successful surgical outcomes can be achieved. [ABSTRACT FROM AUTHOR]

Background: Custom cutting guides (CCGs; sometimes called patient-specific instrumentation [PSI]) in total knee arthroplasty (TKA) use preoperative three-dimensional imaging to fabricate cutting blocks specific to a patient's native anatomy.Questions/purposes: The purposes of this study were to determine if CCGs (1) improve clinical outcomes as measured by UCLA activity, SF-12, and Oxford knee scores; and (2) coronal mechanical alignment versus standard alignment guides.Methods: This was a retrospective cohort study of patients undergoing primary TKA using the same cruciate-retaining, cemented TKA system between January 2009 and April 2012. Patients were included if they were candidates for a unilateral, cruciate-retaining TKA and met other prespecified criteria; patients were allowed to self-select either an MRI-based CCG procedure or standard TKA. Ninety-seven of 120 (80.8%) patients in the standard and 104 of 124 (83.9%, p = 0.5) in the CCG cohort with a minimum of 1-year followup were available for analysis. The first 95 patients in the standard (mean followup, 3 years; range, 1-4 years) and CCG (mean followup, 2 years; range, 1-4 years) cohorts were compared. The alignment goal for all TKAs was a hip-knee-ankle (HKA) angle of 0°. UCLA, SF-12, and Oxford knee scores were collected preoperatively and at each patient's most recent followup visit. Postoperative, rotationally controlled coronal scout CT scans were used to measure HKA alignment. Independent-sample t-tests and chi-square tests were used for comparisons with a p value ≤ 0.05 considered significant.Results: At the most recent followup, no differences were present between the two cohorts for range of motion (114° ± 14° in CCG versus 115° ± 15° in standard, p = 0.7), UCLA (6 ± 2 in CCG versus 6 ± 2 in standard, p = 0.7), SF-12 physical (44 ± 12 in CCG versus 41 ± 12 in standard, p = 0.07), or Oxford knee scores (39 ± 9 in CCG versus 37 ± 10 in standard, p = 0.1). No differences were present for the incremental improvement in the UCLA (1 ± 4 in CCG versus 1 ± 3 in standard, p = 0.5), SF-12 physical (12 ± 20 in CCG versus 11 ± 21, p = 0.8), or Oxford knee scores (16 ± 9 in CCG versus 19 ± 10 in standard, p = 0.1) from preoperatively to postoperatively. There was no difference in the percentage of outliers for alignment (23% in standard versus 31% in CCG with HKA outside of 0° ± 3°; p = 0.2) between the two cohorts.Conclusions: At a mean followup of greater than 2 years, CCGs fail to demonstrate any advantages in validated knee outcome measure scores or coronal alignment as measured by CT scan versus the use of standard instrumentation in TKA. The clinical benefit of CCGs must be proven before continued implementation of this technology.Level Of Evidence: Level III, retrospective controlled study. [ABSTRACT FROM AUTHOR]

Zygomycosis is a rare invasive opportunistic fungal infection that occurs in the setting of hematologic malignancies, chemotherapy-induced neutropenia, and immunosuppressive therapies. We report the first case of disseminated appendiceal zygomycosis due to Absidia spp. in a neutropenic patient who initially presented as acute appendicitis. A 63-year-old woman with acute myeloid leukemia presented as acute appendicitis while receiving induction chemotherapy and ultimately succumbed to overwhelming disseminated zygomycosis. Initial symptoms included loose stools and right lower abdominal pain unresponsive to broad-spectrum antibiotics. Clinical examination and cross-sectional imaging suggested acute appendicitis. The final diagnosis was established by histological evaluations of the ileocecectomy specimen, which showed angioinvasive fungal organisms within the necrotic appendiceal wall with characteristics typical of zygomycetes. Fungal cultures demonstrated Absidia spp. The patient was treated with amphotericin B but expired in the setting of fungal sepsis. A diagnosis of a fungal infection, including zygomycosis, should be considered in all chemotherapy-induced neutropenic patients who present with symptoms of acute appendicitis. A high index of clinical suspicion with prompt histologic and culture diagnosis of zygomycosis may reduce the high mortality and morbidity associated with zygomycosis of the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Objective: Selective serotonin reuptake inhibitors (SSRIs) are the first line of treatment for depression. Among the SSRIs, paroxetine has strong anticholinergic properties and may lead to increased risk of adverse cognitive outcomes among elderly patients. This study evaluated the comparative risk of dementia associated with use of paroxetine and other SSRIs among elderly nursing home patients.Methods: A retrospective cohort study using propensity score matching was conducted with 2007-2010 Minimum Data Set-linked Medicare data. The study population included elderly nursing home patients with depression who were new users of SSRIs. Patients were followed for a maximum of two years after index SSRI use. The risk of dementia was modeled by using a robust Cox proportional hazards model to account for clustering within matched users of paroxetine and other SSRIs.Results: The unmatched cohort included 19,952 new users of SSRIs; 1,898 used paroxetine, and 18,054 used other SSRIs. In the propensity-matched cohort of 3,796 patients, the unadjusted incidence of dementia was 7.5% for users of paroxetine and 8.6% for users of other SSRIs. There was no difference in the risk of dementia for users of paroxetine or other SSRIs. These study findings remained robust in multiple sensitivity analyses involving various measures of dementia.Conclusions: Compared with use of other SSRIs, use of paroxetine was not associated with higher risk of dementia among elderly nursing home patients with depression. Future studies are needed to evaluate the impact of paroxetine on other cognition measures. [ABSTRACT FROM AUTHOR]

Objective: To examine the prevalence and predictors of potentially inappropriate anticholinergic medication use in older adults with dementia.Design: A cross-sectional study.Setting: United States, 2009-2010.Participants: Medical Expenditure Panel Survey household component participants aged 65 years or older identified as having dementia and using potentially inappropriate anticholinergic medication.Main Outcome Measures: Prevalence and predictors of potentially inappropriate anticholinergic medication use as per the updated 2012 American Geriatrics Society Beers criteria.Results: A total of 3.78 million older adult patients (95% confidence interval [CI] 3.17 million to 4.38 million) were identified as having dementia, for an overall prevalence of 4.81%. Of those patients, an estimated 1.02 million (95% CI 0.70 million to 1.30 million) were reported to use potentially inappropriate anticholinergic medications, for an overall prevalence of 26.95% (95% CI 20.10% to 33.79%). The most frequently prescribed drugs were oxybutynin, solifenacin, paroxetine, tolterodine, promethazine, and cyclobenzaprine. Multivariable logistic analysis revealed that those patients with the need characteristics of self-reported anxiety, mood disorders, and "fair/poor" general health status had increased odds of potentially inappropriate anticholinergic use, while patients with the predisposing characteristic of being aged 75-84 years had decreased odds of potentially inappropriate anticholinergic use.Conclusion: More than one in four older adults with dementia were found to use potentially inappropriate anticholinergics. Given the adverse cognitive effects of these medications, there is a strong need to monitor and optimize their use in older adult patients with dementia. [ABSTRACT FROM AUTHOR]

Rationale: Vitamin D deficiency, often defined by total serum 25-hydroxyvitamin D (25[OH]D) <20 ng/ml, is common in critically ill patients, with associations with increased mortality and morbidity in the intensive care unit. Correction of vitamin D deficiency in critical illness has been recommended, and ongoing clinical trials are investigating the effect of repletion on patient outcome. The biologically active amount of 25(OH)D depends on the concentration and protein isoform of vitamin D-binding protein (VDBP), which is also an acute-phase reactant affected by inflammation and injury.Objectives: We performed a secondary analysis of a cohort of critically ill children in which we reported a high rate of vitamin D deficiency, to examine how VDBP level and genotype would impact vitamin D status.Methods: We prospectively enrolled 511 children admitted to the pediatric intensive care unit over a 12-month period.Measurements and Main Results: We measured serum VDBP in 479 children. We genotyped single nucleotide polymorphisms rs7041 and rs4588 in the VDBP gene (GC) to determine haplotypes GC1F, GC1S, and GC2 in 178 subjects who consented, then calculated bioavailable 25(OH)D from serum 25(OH)D, VDBP, albumin, and GC haplotype. The median serum VDBP level was 159 μg/ml (interquartile range, 108-221), lower than has been reported in healthy children. Factors predicting lower levels in multivariate analysis included age <1 year, nonwhite race, being previously healthy, 25(OH)D <20 ng/ml and greater illness severity. In the subgroup that was genotyped, GC haplotype had the strongest association with VDBP level; carriage of one additional copy of GC1S was associated with a 37.5% higher level (95% confidence interval, 31.9-44.8; P < 0.001). Bioavailable 25(OH)D was also inversely associated with illness severity (r = -0.24, P < 0.001), and ratio to measured total 25(OH)D was variable and related to haplotype.Conclusions: Physiologic deficiency of 25(OH)D in critical illness may be more difficult to diagnose, given that lower VDBP levels increase bioavailability. Treatment studies conducted on the basis of total 25(OH)D level, without consideration of VDBP concentration and genotype, may increase the risk of falsely negative results. [ABSTRACT FROM AUTHOR]

The World Health Organization and collaborating agencies have set the goal of eliminating dog-mediated human rabies by 2030. Building on experience with rabies endemic countries, we constructed a user-friendly tool to help public health officials plan the resources needed to achieve this goal through mass vaccination of dogs. [ABSTRACT FROM AUTHOR]

Non-suicidal self-injury (NSSI), the intentional damage to body tissue without the intent to die, is a prevalent public health problem in the U.S. and around the world. The current study sought to identify intrapersonal (emotional reactivity) and interpersonal (emotional expressiveness to others) correlates of NSSI in order to provide insight into how to best tailor prevention and treatment efforts. Four hundred and forty nine college students were surveyed about various psychological characteristics as well as engagement in NSSI. Results indicated that those who have difficulty expressing emotions are at an increased risk for NSSI even after controlling for depressive symptoms and that emotional expressiveness acts as a partial mediator between depression and NSSI. Emotional expressiveness should be a target of treatment among people who engage in NSSI. [ABSTRACT FROM AUTHOR]

Background Multiple studies have detailed promising smile restoration following gracilis free muscle transfer for facial reanimation but information detailing the potential complications is lacking. The aim of this study is to systematically review the literature to evaluate the reported complication rate associated with this procedure. We also aim to determine the most common occurring complications. Methods The PubMed, Embase, and Web of Science databases were queried with multiple search strategies for published articles between January 1950 and February 2013 that detailed gracilis free muscle transfer for facial reanimation. Title, abstract, and full text review was performed. Complications were defined as any reported, identifiable adverse outcome that required an alteration in treatment for correction. Results The literature search yielded 62 studies of gracilis free muscle transfer for facial reanimation. Overall, 36 articles (58%) reported whether or not a complication had occurred. The overall complication rate based on pooled proportions was 9.6% and the most commonly occurring complications were postoperative hematoma (3.6%) and infection (3.5%). Conclusions Our data suggests that complications after gracilis free muscle transfer for facial reanimation may be underreported and this complex procedure may in fact be associated with significant adverse outcomes as high as 9.6%. [ABSTRACT FROM AUTHOR]

Inflammatory responses are essential for the clearance of pathogens and the repair of injured tissues; however, if these responses are not properly controlled chronic inflammation can occur. Chronic inflammation is now recognized as a contributing factor to many age-associated diseases including metabolic disorders, arthritis, neurodegeneration, and cardiovascular disease. Due to the connection between chronic inflammation and these diseases, it is essential to understand underlying mechanisms behind this process. In this review, factors that contribute to chronic inflammation are discussed. Further, we emphasize the emerging roles of microRNAs (miRNAs) and other noncoding RNAs (ncRNA) in regulating chronic inflammatory states, making them important future diagnostic markers and therapeutic targets. Copyright Line: © 2015 The Authors BioEssays Published by Wiley-VCH Verlag GmbH & Co. KGaA. [ABSTRACT FROM AUTHOR]

Background. The impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis (PM) in US children is unknown. We compared the serotype distribution, antibiotic susceptibility, hospital course, and outcomes of children with PM 3 years before and 3 years after the introduction of PCV13. Methods. We identified patients =18 years of age with PM at 8 children's hospitals in the United States. Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. Clinical data were abstracted from medical records. Patients were divided into 3 subgroups: pre-PCV13 (2007-2009), transitional year (2010), and post-PCV13 (2011-2013). Categorical variables were analyzed by the ?2 test and continuous variables by the Mann--Whitney U test. Results. During the study period, 173 of 1207 episodes (14%) of invasive pneumococcal disease were identified as PM; 76 of 645 (12%) were during 2007-2009 and 69 of 394 (18%) during 2011-2013 (50% increase; P = .03). The proportion of PCV13 serotype cases decreased from 54% in 2007-2009 to 27% in 2011-2013 (P = .001). Non-PCV13 serotype cases represented 73% of the isolates in 2011-2013. Isolates with ceftriaxone minimum inhibitory concentration =1 µg/mL decreased (13% to 3%) from 2007-2009 to 2011-2013 (P = .03). No significant differences were identified for hospital course or outcome, with the exception that a greater proportion of patients had subdural empyema and hemiparesis in 2011-2013. Conclusions. After the introduction of PCV13, the number of cases of PM in children remained unchanged compared with 2007-2009, although the proportion of PCV13 serotypes decreased significantly. Serotype 19A continued to be the most common serotype in 2011-2013. Antibiotic resistance decreased significantly. Morbidity and case-fatality rate due to PM remain substantial. [ABSTRACT FROM AUTHOR]