Systematic Review of Intralesional Therapies for Cutaneous Warts.

Intralesional therapies are used for recalcitrant warts, but no Food and Drug Administration-approved treatment exists nor is there consensus regarding the most efficacious therapy. Therefore, this systematic review aims to summarize efficacy and adverse events reported in 62 randomized controlled trials (RCTs) of intralesional therapies for cutaneous warts. The most studied intralesional therapies included measles, mumps, rubella (MMR) vaccine (n = 24 studies), purified protein derivative (PPD) (n = 19 studies), vitamin D3 (n = 15 studies), and Candida antigen (n = 14 studies). Most studies included adult and pediatric patients or adults alone, with only 4 studies on pediatric patients alone. MMR vaccine was the most studied treatment (n = 853 patients). MMR had a complete response rate of 27-90%. The next most common treatment, PPD, had a complete response rate of 45-87%. Other treatments included Candida antigen and vitamin D3, with complete response rates of 25-84% and 40-96%, respectively. The most frequent side effects were injection-site reactions and flu-like symptoms. This systematic review represents a useful summary of intralesional therapy RCTs for clinician reference. This study also highlights the lack of large multi-institutional RCTs, despite many patients being treated for this widespread problem.

A retrospective cohort study of the efficacy of metronidazole in oral lichen planus.

Lichen planus (LP) is an inflammatory dermatosis with mucosal variants, including oral LP (OLP). OLP has a relapsing chronic course and may significantly affect a patient's quality of life. We analysed the efficacy of metronidazole as a treatment for OLP via a retrospective chart review of patients with a diagnosis of OLP seen at our institution over 10 years. Thirty patients with OLP were treated with metronidazole 500 mg twice daily. Most patients (n = 18; 60%) showed improvement with metronidazole, including 10 (33%) who experienced complete resolution of symptoms. Our results were limited by the retrospective nature of the review and the relatively small cohort size. Given the efficacy, mild side-effect profile and the less immunosuppressive nature of metronidazole vs. alternative systemic treatment options, metronidazole is a reasonable option to try in patients with symptomatic OLP who have failed topical treatment options.

Preoperative REM sleep is associated with complication development after colorectal surgery.

BACKGROUND: While total sleep duration and rapid eye movement (REM) sleep duration have been associated with long-term mortality in non-surgical cohorts, the impact of preoperative sleep on postoperative outcomes has not been well studied. METHODS: In this secondary analysis of a prospective observational cohort study, patients who recorded at least 1 sleep episode using a consumer wearable device in the 7 days before elective colorectal surgery were included. 30-day postoperative outcomes among those who did and did not receive at least 6 h of total sleep, as well as those who did and did not receive at least 1 h of rapid eye movement (REM) sleep, were compared. RESULTS: 34 out of 95 (35.8%) patients averaged at least 6 h of sleep per night, while 44 out of 82 (53.7%) averaged 1 h or more of REM sleep. Patients who slept less than 6 h had similar postoperative outcomes compared to those who slept 6 h or more. Patients who averaged less than 1 h of REM sleep, compared to those who achieved 1 h or more of REM sleep, had significantly higher rates of complication development (29.0% vs. 9.1%, P = 0.02), and return to the OR (10.5% vs. 0%, P = 0.04). After adjustment for confounding factors, increased REM sleep duration remained significantly associated with decreased complication development (increase in REM sleep from 50 to 60 min: OR 0.72, P = 0.009; REM sleep ≥ 1 h: OR 0.22, P = 0.03). CONCLUSION: In this cohort of patients undergoing elective colorectal surgery, those who developed a complication within 30 days were less likely to average at least 1 h of REM sleep in the week before surgery than those who did not develop a complication. Preoperative REM sleep duration may represent a risk factor for surgical complications; however additional research is necessary to confirm this relationship.

Wearable technology and the association of perioperative activity level with 30-day readmission among patients undergoing major colorectal surgery.

BACKGROUND: The proliferation of wearable technology presents a novel opportunity for perioperative activity monitoring; however, the association between perioperative activity level and readmission remains underexplored. This study sought to determine whether physical activity data captured by wearable technology before and after colorectal surgery can be used to predict 30-day readmission. METHODS: In this prospective observational cohort study of adults undergoing elective major colorectal surgery (January 2018 to February 2019) at a single institution, participants wore an activity monitor 30 days before and after surgery. The primary outcome was return to baseline percentage, defined as step count on the day before discharge as a percentage of mean preoperative daily step count, among readmitted and non-readmitted patients. RESULTS: 94 patients had sufficient data available for analysis, of which 16 patients (17.0%) were readmitted within 30 days following discharge. Readmitted patients achieved a lower return to baseline percentage compared to patients who were not readmitted (median 15.1% vs. 31.8%; P = 0.004). On multivariable analysis adjusting for readmission risk and hospital length of stay, an absolute increase of 10% in return to baseline percentage was associated with a 40% decreased risk of 30-day readmission (odds ratio 0.60; P = 0.02). Analysis of the receiver operating characteristic curve identified 28.9% as an optimal return to baseline percent threshold for predicting readmission. CONCLUSIONS: Achieving a higher percentage of an individual's preoperative baseline activity level on the day prior to discharge after major colorectal surgery is associated with decreased risk of 30-day hospital readmission.

Preparedness Tested: Severe Cerebral Malaria Presenting as a High-Risk Person Under Investigation for Ebola Virus Disease at a US Hospital.

In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a "wet" person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.

Cortical RORß is required for layer 4 transcriptional identity and barrel integrity.

Retinoic acid-related orphan receptor beta (RORß) is a transcription factor (TF) and marker of layer 4 (L4) neurons, which are distinctive both in transcriptional identity and the ability to form aggregates such as barrels in rodent somatosensory cortex. However, the relationship between transcriptional identity and L4 cytoarchitecture is largely unknown. We find RORß is required in the cortex for L4 aggregation into barrels and thalamocortical afferent (TCA) segregation. Interestingly, barrel organization also degrades with age in wildtype mice. Loss of RORß delays excitatory input and disrupts gene expression and chromatin accessibility, with down-regulation of L4 and up-regulation of L5 genes, suggesting a disruption in cellular specification. Expression and binding site accessibility change for many other TFs, including closure of neurodevelopmental TF binding sites and increased expression and binding capacity of activity-regulated TFs. Lastly, a putative target of RORß, Thsd7a, is down-regulated without RORß, and Thsd7a knock-out alone disrupts TCA organization in adult barrels.

Wearable Technology in the Perioperative Period: Predicting Risk of Postoperative Complications in Patients Undergoing Elective Colorectal Surgery.

BACKGROUND: The implementation of protocolized care pathways has resulted in major improvements in surgical outcomes. Additional gains will require focused efforts to alter preexisting risk. Prehabilitation programs provide a promising avenue for risk reduction. OBJECTIVE: This study used wearable technology to monitor activity levels before colorectal surgery to evaluate the impact of preoperative activity on postoperative outcomes. DESIGN: This was a prospective nonrandomized observational study. SETTINGS: The study was conducted at a large academic medical center. PATIENTS: Patients undergoing elective colorectal surgery from January 2018 to February 1, 2019, were included. MAIN OUTCOME MEASURES: Patients were trained in the usage of wearable activity-tracking devices and instructed to wear the device for 30 days before surgery. Patients were stratified as active (≥5000 steps per day) and inactive (<5000 steps per day) based on preoperative step counts. Univariate analyses compared postoperative outcomes. Multivariable regression models analyzed the impact of preoperative activity on postoperative complications, adjusting for each patient's baseline risk as calculated using the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator. Models were rerun without the addition of activity and the predictive ability of the models compared. RESULTS: Ninety-nine patients were included, with 40 (40.4%) classified as active. Active patients experienced fewer overall complications (11/40 (27.5%) vs 33/59 (55.9%); p = 0.005) and serious complications (2/40 (5%) vs 12/59 (20.3%); p = 0.032). Increased preoperative activity was associated with a decreased risk of any postoperative complication (OR = 0.386; p = 0.0440) on multivariable analysis. The predictive ability of the models for complications and serious complications was improved with the addition of physical activity. LIMITATIONS: The study was limited by its small sample size and single institution. CONCLUSIONS: There is significant room for improvement in baseline preoperative activity levels of patients undergoing colorectal surgery, and poor activity is associated with increased postoperative complications. These data will serve as the basis for an interventional trial investigating whether wearable devices help improve surgical outcomes through a monitored preoperative exercise program. See Video Abstract at http://links.lww.com/DCR/B145. TECNOLOGÍA PORTÁTIL EN EL PERÍODO PERIOPERATORIO: PREDICCIÓN DEL RIESGO DE COMPLICACIONES POSTOPERATORIAS EN PACIENTES SOMETIDOS A CIRUGÍA COLORRECTAL ELECTIVA: La implementación de vías de atención protocolizadas ha dado lugar a importantes mejoras en los resultados quirúrgicos. Para obtener más beneficios será necesario realizar esfuerzos concentrados para modificar el riesgo preexistente. Los programas de rehabilitación proporcionan una vía prometedora para la reducción del riesgo.Este estudio utilizó tecnología portátil para monitorear los niveles de actividad antes de la cirugía colorrectal para evaluar el impacto de la actividad preoperatoria en los resultados postoperatorios.Estudio observacional prospectivo no aleatorizado.Gran centro médico académico.Pacientes sometidos a cirugía colorrectal electiva desde enero de 2018 hasta el 1 de febrero de 2019.Los pacientes fueron entrenados en el uso de dispositivos portátiles para el seguimiento de la actividad y se les indicó usar el dispositivo durante 30 días antes de la cirugía. Los pacientes fueron estratificados como activos (> 5000 pasos / día) e inactivos (<5000 pasos / día) en base a los recuentos de pasos preoperatorios. Los análisis univariados compararon los resultados postoperatorios. Los modelos de regresión multivariable analizaron el impacto de la actividad preoperatoria en las complicaciones postoperatorias, ajustando el riesgo de referencia de cada paciente según lo calculado utilizando la Calculadora de riesgo quirúrgico del Programa Nacional de Mejora de la Calidad Quirúrgica del Colegio Americano de Cirujanos. Los modelos se volvieron a ejecutar sin agregar actividad, y se comparó la capacidad de predicción de los modelos.Noventa y nueve pacientes fueron incluidos con 40 (40.4%) clasificados como activos. Los pacientes activos experimentaron menos complicaciones generales [11/40 (27,5%) frente a 33/59 (55,9%); p = 0,005] y complicaciones graves [2/40 (5%) frente a 12/59 (20,3%); p = 0,032]. El aumento de la actividad preoperatoria se asoció con una disminución del riesgo de cualquier complicación postoperatoria (OR 0.386, p = 0.0440) en el análisis multivariable. La capacidad predictiva de los modelos para complicaciones y complicaciones graves mejoró con la adición de actividad física.Tamaño de muestra pequeño, una sola institución.Existe un margen significativo para mejorar los niveles basales de actividad preoperatoria de los pacientes de cirugía colorrectal, y la escasa actividad se asocia con mayores complicaciones postoperatorias. Estos datos servirán de base para un ensayo intervencionista que investigue si los dispositivos portátiles ayudan a mejorar los resultados quirúrgicos a través de un programa de ejercicio preoperatorio monitoreado. Consulte Video Resumen en http://links.lww.com/DCR/B145.

An integrative analysis of regional gene expression profiles in the human brain.

Studies of the brain's transcriptome have become prominent in recent years, resulting in an accumulation of datasets with somewhat distinct attributes. These datasets, which are often analyzed only in isolation, also are often collected with divergent goals, which are reflected in their sampling properties. While many researchers have been interested in sampling gene expression in one or a few brain areas in a large number of subjects, recent efforts from the Allen Institute for Brain Sciences and others have focused instead on dense neuroanatomical sampling, necessarily limiting the number of individual donor brains studied. The purpose of the present work is to develop methods that draw on the complementary strengths of these two types of datasets for study of the human brain, and to characterize the anatomical specificity of gene expression profiles and gene co-expression networks derived from human brains using different specific technologies. The approach is applied using two publicly accessible datasets: (1) the high anatomical resolution Allen Human Brain Atlas (AHBA, Hawrylycz et al., 2012) and (2) a relatively large sample size, but comparatively coarse neuroanatomical dataset described previously by Gibbs et al. (2010). We found a relatively high degree of correspondence in differentially expressed genes and regional gene expression profiles across the two datasets. Gene co-expression networks defined in individual brain regions were less congruent, but also showed modest anatomical specificity. Using gene modules derived from the Gibbs dataset and from curated gene lists, we demonstrated varying degrees of anatomical specificity based on two classes of methods, one focused on network modularity and the other focused on enrichment of expression levels. Two approaches to assessing the statistical significance of a gene set's modularity in a given brain region were studied, which provide complementary information about the anatomical specificity of a gene network of interest. Overall, the present work demonstrates the feasibility of cross-dataset analysis of human brain microarray studies, and offers a new approach to annotating gene lists in a neuroanatomical context.

Object-centered reference frames in depth as revealed by induced motion.

An object-centric reference frame is a spatial representation in which objects or their parts are coded relative to others. The existence of object-centric representations is supported by the phenomenon of induced motion, in which the motion of an inducer frame in a particular direction induces motion in the opposite direction in a target dot. We report on an experiment made with an induced motion display where a degree of slant is imparted to the inducer frame using either perspective or binocular disparity depth cues. Critically, the inducer frame oscillates perpendicularly to the line of sight, rather than moving in depth. Participants matched the perceived induced motion of the target dot in depth using a 3D rotatable rod. Although the frame did not move in depth, we found that subjects perceived the dot as moving in depth, either along the slanted frame or against it, when depth was given by perspective and disparity, respectively. The presence of induced motion is thus not only due to the competition among populations of planar motion filters, but rather incorporates 3D scene constraints. We also discuss this finding in the context of the uncertainty related to various depth cues, and to the locality of representation of reference frames.

An informatics approach to integrating genetic and neurological data in speech and language neuroscience.

A number of heritable disorders impair the normal development of speech and language processes and occur in large numbers within the general population. While candidate genes and loci have been identified, the gap between genotype and phenotype is vast, limiting current understanding of the biology of normal and disordered processes. This gap exists not only in our scientific knowledge, but also in our research communities, where genetics researchers and speech, language, and cognitive scientists tend to operate independently. Here we describe a web-based, domain-specific, curated database that represents information about genotype-phenotype relations specific to speech and language disorders, as well as neuroimaging results demonstrating focal brain differences in relevant patients versus controls. Bringing these two distinct data types into a common database ( http://neurospeech.org/sldb ) is a first step toward bringing molecular level information into cognitive and computational theories of speech and language function. One bridge between these data types is provided by densely sampled profiles of gene expression in the brain, such as those provided by the Allen Brain Atlases. Here we present results from exploratory analyses of human brain gene expression profiles for genes implicated in speech and language disorders, which are annotated in our database. We then discuss how such datasets can be useful in the development of computational models that bridge levels of analysis, necessary to provide a mechanistic understanding of heritable language disorders. We further describe our general approach to information integration, discuss important caveats and considerations, and offer a specific but speculative example based on genes implicated in stuttering and basal ganglia function in speech motor control.