RESUMEN

Metastasis is a nonrandom process with varying degrees of organotropism-specific source-acceptor seeding. Understanding how patterns between source and acceptor tumors emerge remains a challenge in oncology. We hypothesize that organotropism results from the macronutrient niche of cells in source and acceptor organs. To test this, we constructed and analyzed a metastatic network based on 9303 records across 28 tissue types. We found that the topology of the network is nested and modular with scale-free degree distributions, reflecting organotropism along a specificity/generality continuum. The variation in topology is significantly explained by the matching of metastatic cells to their stoichiometric niche. Specifically, successful metastases are associated with higher phosphorus content in the acceptor compared to the source organ, due to metabolic constraints in proliferation crucial to the invasion of new tissues. We conclude that metastases are codetermined by processes at source and acceptor organs, where phosphorus content is a limiting factor orchestrating tumor ecology.

Asunto(s)

Ecosistema , Fósforo , Humanos , Línea Celular Tumoral , Metástasis de la Neoplasia

RESUMEN

BACKGROUND: Penile cancer accounts for less than 1% of male cancers in the United States. Localized disease, particularly T1 tumors are potentially curable with local therapy. We present the racial differences in survival outcomes for T1, penile cancer from the SEER database. METHODS: From 2004 to 2016 all men with T1, N0, M0 penile cancer in the SEER-18 database were included. Kaplan-Meier analysis and multivariable Cox-Regression analysis were conducted to investigate prognostic variables for cancer specific survival (CSS). RESULTS: A total of 4,406 men were identified with penile cancer; 1,941 men had T1 disease. The Kaplan-Meier (KM) analysis showed those with primary site surgery had better 5-year CSS compared to those without primary site surgery (P <.0001) and a significant difference in CSS based on race (P= 0.0078). On multivariable analysis, Hispanic individuals had worse CSS (HR 1.92; P = 0.0057) compared to the White men. Black men were also found to have a poor CSS however this was not statistically significant (HR 1.53, P = 0.118). Men with penile cancer who had either penectomy (HR 0.45; P = 0.006) or penile preservation surgery (HR 0.25; P< 0.001) had improved CSS. CONCLUSION: Racial disparities in CSS exist among men with in early-stage penile cancer. KM analysis showed significant differences in CSS by race and in those receiving primary site surgery. On multivariable analysis, the CSS is worse in Hispanic compared to White men. There is a trend towards worse CSS in Black men however this was not statistically significant.

Asunto(s)

Neoplasias del Pene , Humanos , Masculino , Hispánicos o Latinos , Estadificación de Neoplasias , Neoplasias del Pene/cirugía , Pronóstico , Factores Raciales , Programa de VERF , Estados Unidos/epidemiología , Blanco , Negro o Afroamericano

RESUMEN

There has been just over 30 years of experience in clinical intestine transplant. A rise in demand until 2007 with improving transplant outcomes preceded a subsequent fall in demand due, at least in part, to improvements in pretransplant care of patients with intestinal failure. Over the past 10 to 12 years, there has been no suggestion of an increase in demand and, particularly for adult transplant, there may be a continued trend toward fewer additions to the waiting list and fewer transplants, especially in those needing combined intestine-liver transplant. In addition, over the same period there has been no noticeable improvement in graft survival, with 1- and 5-year graft failure rates averaging 21.6% and 52.5%, respectively, for intestine-alone transplants and 28.6% and 47.2%, respectively, for combined intestine-liver allografts.

Asunto(s)

Trasplante de Hígado , Obtención de Tejidos y Órganos , Trasplantes , Adulto , Humanos , Estados Unidos/epidemiología , Intestinos/trasplante , Listas de Espera , Supervivencia de Injerto , Donantes de Tejidos

RESUMEN

Purpose: To evaluate clinicopathologic and treatment characteristics from a population-based cohort of penile cancer, with an emphasis in older adults, due to incomplete evidence to guide therapy in this age subgroup. Materials and Methods: Patients with malignant penile tumors diagnosed 2004-2016 were identified in the Surveillance, Epidemiology and End Results Program (SEER)-18 dataset. Demographic and treatment characteristics were obtained. Population was analyzed by age at diagnosis (<65 vs ≥65 years). We examined univariate associations between age groups with Chi-square analysis. To study survival, we calculated Kaplan-Meier survival curves, but due to the high number of competing events, we also performed a univariate competing risk analysis using the cumulative incidence function, and a multivariate analysis using the Fine-Gray method. We also described competing mortality due to penile cancer and other causes of death. Results: We included 3,784 patients. Median age was 68 years, 58.7% were aged ≥65. Older patients were less likely to have received chemotherapy (p<0.001), primary site surgery (p = 0.002), or therapeutic regional surgery (p <0.001). Median overall survival (OS) in patients <65 years was not reached (95% CI incalculable) vs 49 months in those ≥65 years (95% CI 45-53, p <0.0001). On univariate analysis, age was associated with a lower incidence of penile cancer death. On multivariate analysis, stage at diagnosis, and receipt of primary site surgery were associated with a higher incidence of penile cancer death. Estimated penile cancer-specific mortality was higher in patients <65 years in stages II-IV. Estimated mortality due to other causes was higher in older patients across all stages. Conclusions: Older patients are less likely to receive surgery, chemotherapy and radiotherapy for penile cancer. Primary surgical resection was associated with better penile cancer-specific mortality on multivariate analysis. Competing mortality risks are highly relevant when considering OS in older adults with penile cancer. Factors associated with undertreatment of older patients with penile cancer need to be studied, in order to develop treatment strategies tailored for this population.

RESUMEN

Animals rely on their ability to perform certain tasks sufficiently well to survive, secure mates and reproduce. Performance traits depend on morphology, and so morphological traits should predict performance, yet this relationship is often confounded by multiple competing performance demands. Males and females experience different selection pressures on performance, and the consequent sexual conflict over performance expression can either constrain performance evolution or drive sexual dimorphism in both size and shape. Furthermore, change in a single morphological trait may benefit some performance traits at the expense of others, resulting in functional trade-offs. Identifying general or sex-specific relationships between morphology and performance at the organismal level thus requires a multivariate approach, as individuals are products of both an integrated phenotype and the ecological environment in which they have developed and evolved. We estimated the multivariate morphology→performance gradient in wild-caught, green anoles (Anolis carolinensis) by measuring external morphology and forelimb and hindlimb musculature, and mapping these morphological traits to seven measured performance traits that cover the broad range of ecological challenges faced by these animals (sprint speed, endurance, exertion distance, climbing power, jump power, cling force and bite force). We demonstrate that males and females differ in their multivariate mapping of traits on performance, indicating that sex-specific ecological demands likely shape these relationships, but do not differ in performance integration.

Asunto(s)

Lagartos , Animales , Evolución Biológica , Fuerza de la Mordida , Femenino , Miembro Anterior , Miembro Posterior/anatomía & histología , Lagartos/anatomía & histología , Masculino , Caracteres Sexuales

RESUMEN

INTRODUCTION: Radiation therapy (XRT) has been investigated as a possible treatment for high-risk non-muscle invasive bladder cancer (NMIBC) with the goal of bladder preservation, especially with the ongoing Bacillus Calmette-Guerin (BCG) shortage. Yet, little is known about the clinical efficacy and the quality of evidence supporting XRT for NMIBC. Herein, we performed a systematic review and meta-analysis to evaluate XRT in the treatment of patients with high-risk NMIBC. METHODS: Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and Web of Science were searched for high-risk NMIBC (high grade T1, T1/Ta with associated risk features: carcinoma in-situ (CIS), multifocality, > 5cm in diameter, and/or multiple recurrences) treated with primary XRT. Outcomes evaluated were recurrence-free survival (RFS), cancer-specific-survival (CSS), overall survival (OS), and salvage cystectomy and progression to metastatic disease rates. A meta-analysis was performed to assess outcomes for XRT in NMIBC. RESULTS: Overall,13 studies including 746 patients met the search criteria. The 5-year rates of RFS, CSS and OS were 54% (95% CI = 38% - 70%), 86% (95% CI = 80% - 92%), and 72% (95% CI = 64% - 79%). Notably, 13% of patients proceeded to salvage radical cystectomy and 9% developed metastatic disease. All studies were of poor quality, comprising single institution and retrospective studies with only one clinical trial. CONCLUSION: XRT for high-risk NMIBC provides some degree of oncologic control, although distant progression was noted. In the setting of the low-quality evidence, a prospective clinical trial is needed to clearly define the risks and benefits of this approach.

Asunto(s)

Neoplasias de la Vejiga Urinaria/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

INTRODUCTION: With growing support of perioperative chemotherapy for upper tract urothelial carcinoma (UTUC), current biopsy methods are challenging, and little is known as to the degree to which patients would appropriately receive neoadjuvant chemotherapy (NAC) from biopsy alone. Herein, we sought to assess the rates of appropriate clinical use of NAC and identify clinicopathologic factors associated with aggressive UTUC amongst patients undergoing radical nephroureterectomy (RNU) for clinically localized disease. METHODS: From 2004 to 2013, we identified all treatment naïve patients diagnosed with clinically localized, high grade UTUC (cTa-4Nx) who underwent RNU from the National Cancer Database (NCDB). Pathologic criteria for NAC (pT2-4N0,x; pTanyN1) from RNU represented the primary outcome. Bivariate and multivariable analyses were utilized to identify covariates associated with primary outcome to determine appropriate use of NAC. RESULTS: During the study interval, 5,362 patients were diagnosed with clinically localized UTUC and underwent RNU. Overall, 49.1% of patients presented with an unknown primary tumor stage (Tx) and 24.5% had invasive UTUC from biopsy. On multivariable analysis, upper tract tumor size was associated with invasive UTUC eligible for NAC (all P < 0.05). Amongst patients with cTx UTUC from biopsy, half of patients had pathologic noninvasive UTUC (pTa,is,1) from RNU and would be overtreated with NAC. CONCLUSION: Significant uncertainty persists in assigning primary upper tract tumor depth and represents a key barrier to widespread implementation of NAC for patients with high grade UTUC. Further research is needed to more accurately determine clinical criteria to identify patients for NAC.

Asunto(s)

Terapia Neoadyuvante/métodos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Anciano , Femenino , Humanos , Masculino , Estadificación de Neoplasias

RESUMEN

Cancer is a singular cellular state, the emergence of which destabilises the homeostasis reached through the evolution to multicellularity. We present the idea that the onset of the cellular disobedience to the metazoan functional and structural architecture, known as the cancer phenotype, is triggered by changes in the cell's external environment that occur with ageing: what ensues is a breach of the social contract of multicellular life characteristic of metazoans. By integrating old ideas with new evidence, we propose that with ageing the environmental information that maintains a multicellular organisation is eroded, rewiring internal processes of the cell, and resulting in an internal shift towards an ancestral condition resulting in the pseudo-multicellular cancer phenotype. Once that phenotype emerges, a new local social contract is built, different from the homeostatic one, leading to tumour formation and the foundation of a novel local ecosystem.

Asunto(s)

Evolución Biológica , Neoplasias , Envejecimiento , Animales , Ecosistema , Humanos , Neoplasias/genética , Fenotipo

RESUMEN

Colonization of the upper respiratory tract with Streptococcus pneumoniae is the precursor of pneumococcal pneumonia and invasive disease. Following exposure, however, it is unclear which human immune mechanisms determine whether a pathogen will colonize. We used a human challenge model to investigate host-pathogen interactions in the first hours and days following intranasal exposure to Streptococcus pneumoniae. Using a novel home sampling method, we measured early immune responses and bacterial density dynamics in the nose and saliva after volunteers were experimentally exposed to pneumococcus. Here, we show that nasal colonization can take up to 24 h to become established. Also, the following two distinct bacterial clearance profiles were associated with protection: nasal clearers with immediate clearance of bacteria in the nose by the activity of pre-existent mucosal neutrophils and saliva clearers with detectable pneumococcus in saliva at 1 h post challenge and delayed clearance mediated by an inflammatory response and increased neutrophil activity 24 h post bacterial encounter. This study describes, for the first time, how colonization with a bacterium is established in humans, signifying that the correlates of protection against pneumococcal colonization, which can be used to inform design and testing of novel vaccine candidates, could be valid for subsets of protected individuals. IMPORTANCE: Occurrence of lower respiratory tract infections requires prior colonization of the upper respiratory tract with a pathogen. Most bacterial infection and colonization studies have been performed in murine and in vitro models due to the current invasive sampling methodology of the upper respiratory tract, both of which poorly reflect the complexity of host-pathogen interactions in the human nose. Self-collecting saliva and nasal lining fluid at home is a fast, low-cost, noninvasive, high-frequency sampling platform for continuous monitoring of bacterial encounter at defined time points relative to exposure. Our study demonstrates for the first time that, in humans, there are distinct profiles of pneumococcal colonization kinetics, distinguished by speed of appearance in saliva, local phagocytic function, and acute mucosal inflammatory responses, which may either recruit or activate neutrophils. These data are important for the design and testing of novel vaccine candidates.

RESUMEN

OBJECTIVE: To evaluate risk factors for hepatic artery thrombosis (HAT) and examine the long-term outcomes of graft and patient survival after HAT in pediatric recipients of liver transplantation. STUDY DESIGN: Using multicenter data from the Society of Pediatric Liver Transplantation, Kaplan-Meier and Cox regression analyses were performed on first-time pediatric (aged <18 years) liver transplant recipients (n = 3801) in the US and Canada between 1995 and 2016. RESULTS: Of children undergoing their first liver transplantation, 7.4% developed HAT within the first 90 days of transplantation and, of those who were retransplanted, 20.7% developed recurrent HAT. Prolonged warm ischemia times increased the odds of developing HAT (OR, 1.11; P = .02). Adolescents aged 11-17 years (OR, 0.53; P = .03) and recipients with split, reduced, or living donor grafts had decreased odds of HAT (OR, 0.59; P < .001 compared with whole grafts). Fifty percent of children who developed HAT developed graft failure within the first 90 days of transplantation (adjusted hazard ratio, 11.87; 95% CI, 9.02-15.62) and had a significantly higher post-transplant mortality within the first 90 days after transplantation (adjusted hazard ratio, 6.18; 95% CI, 4.01-9.53). CONCLUSIONS: These data from an international registry demonstrate poorer long-term graft and patient survival in pediatric recipients whose post-transplant course is complicated by HAT. Notably, recipients of technical variant grafts had lower odds of HAT compared with whole liver grafts.

Asunto(s)

Arteria Hepática , Hepatopatías/cirugía , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/epidemiología , Trombosis/epidemiología , Adolescente , Factores de Edad , Canadá , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Incidencia , Lactante , Hepatopatías/etiología , Hepatopatías/mortalidad , Masculino , Oportunidad Relativa , Complicaciones Posoperatorias/diagnóstico , Factores de Riesgo , Tasa de Supervivencia , Trombosis/diagnóstico , Estados Unidos

RESUMEN

Recent advances in animal tracking technology have ushered in a new era in biologging. However, the considerable size of many sophisticated biologging devices restricts their application to larger animals, whereas older techniques often still represent the state-of-the-art for studying small vertebrates. In industrial applications, low-power wireless sensor networks (WSNs) fulfill requirements similar to those needed to monitor animal behavior at high resolution and at low tag mass. We developed a wireless biologging network (WBN), which enables simultaneous direct proximity sensing, high-resolution tracking, and long-range remote data download at tag masses of 1 to 2 g. Deployments to study wild bats created social networks and flight trajectories of unprecedented quality. Our developments highlight the vast capabilities of WBNs and their potential to close an important gap in biologging: fully automated tracking and proximity sensing of small animals, even in closed habitats, at high spatial and temporal resolution.

Asunto(s)

Quirópteros , Monitoreo del Ambiente/métodos , Tecnología de Sensores Remotos/métodos , Tecnología Inalámbrica , Animales , Conducta Animal , Quirópteros/fisiología , Ecosistema , Suministros de Energía Eléctrica , Monitoreo del Ambiente/instrumentación , Femenino , Alemania , Masculino , Panamá , Conducta Social , Análisis Espacio-Temporal , Clima Tropical , Vertebrados

RESUMEN

Some nonhuman animals form adaptive long-term cooperative relationships with nonkin that seem analogous in form and function to human friendship [1-4]. However, it remains unclear how these bonds initially form, especially when they entail investments of time and energy. Theory suggests individuals can reduce the risk of exploitation by initially spreading out smaller cooperative investments across time [e.g., 5] or partners [6], then gradually escalating investments in more cooperative partnerships [7]. Despite its intuitive appeal, this raising-the-stakes model [7] has gained surprisingly scarce empirical support. Although human strangers do "raise the stakes" when making bids in cooperation games [8], there has been no clear evidence for raising the stakes during formation of social bonds in nature. Existing studies are limited to cooperative interactions with severe power asymmetries (e.g., the cleaner-client fish mutualism [9]) or snapshots of a single behavior within established relationships (grooming in primates [10-13]). Raising the stakes during relationship formation might involve escalating to more costly behaviors. For example, individuals could "test the waters" by first clustering for warmth (no cost), then conditionally grooming (low cost), and eventually providing coalitionary support (high cost). Detecting such a pattern requires introducing random strangers and measuring the emergence of natural helping behaviors that vary in costs. We performed this test by tracking the emergence of social grooming and regurgitated food donations among previously unfamiliar captive vampire bats (Desmodus rotundus) over 15 months. We found compelling evidence that vampire bats selectively escalate low-cost grooming before developing higher-cost food-sharing relationships.

Asunto(s)

Quirópteros/psicología , Conducta Cooperativa , Conducta Alimentaria , Animales , Femenino , Masculino , Panamá

RESUMEN

OBJECTIVE: To evaluate disease-specific and age-related factors contributing to health-related quality of life (HRQOL). in children with intestinal failure. STUDY DESIGN: A prospective study of HRQOL was performed in a regional intestinal rehabilitation program. Parent-proxy Pediatric Quality of Life Inventory surveys were administered annually to families of 91 children with intestinal failure over a 6-year period. Survey data was stratified by age and compared with pediatric HRQOL data in healthy and chronically ill populations. Linear mixed-effect models using multivariable regression were constructed to identify associations with HRQOL. RESULTS: A total of 180 surveys were completed by 91 children and their families. HRQOL scores were lowest for children ages 5-7 years (P < .001) and 8-12 years (P < .01), and these changes were primarily related to school dimension scores. In multivariable regression, age of 5 years and older and developmental delay were independently associated with lower HRQOL scores. The trend toward lower HRQOL scores parallels reference data from healthy and chronically ill children, although patients with intestinal failure scored lower than both populations at school age. CONCLUSIONS: Children with intestinal failure experience lower parent-proxy HRQOL scores in the 5-7 and 8-12 year age groups primarily related to school dimension scores. Multicenter data to validate these findings and identify interventions to improve QOL for children with intestinal failure are needed.

Asunto(s)

Enterocolitis Necrotizante/psicología , Gastrosquisis/psicología , Calidad de Vida , Síndrome del Intestino Corto/psicología , Distribución por Edad , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Discapacidades del Desarrollo , Femenino , Humanos , Lactante , Masculino , Padres/psicología , Estudios Prospectivos , Encuestas y Cuestionarios

RESUMEN

Rationale: Pneumococcal pneumonia remains a global health problem. Colonization of the nasopharynx with Streptococcus pneumoniae (Spn), although a prerequisite of infection, is the main source of exposure and immunological boosting in children and adults. However, our knowledge of how nasal colonization impacts on the lung cells, especially on the predominant alveolar macrophage (AM) population, is limited. Objectives: Using a controlled human infection model to achieve nasal colonization with 6B serotype, we investigated the effect of Spn colonization on lung cells. Methods: We collected BAL from healthy pneumococcal-challenged participants aged 18–49 years. Confocal microscopy and molecular and classical microbiology were used to investigate microaspiration and pneumococcal presence in the lower airways. AM opsonophagocytic capacity was assessed by functional assays in vitro, whereas flow cytometry and transcriptomic analysis were used to assess further changes on the lung cellular populations. Measurements and Main Results: AMs from Spn-colonized individuals exhibited increased opsonophagocytosis to pneumococcus (11.4% median increase) for approximately 3 months after experimental pneumococcal colonization. AMs also had increased responses against other bacterial pathogens. Pneumococcal DNA detected in the BAL samples of Spn-colonized individuals were positively correlated with nasal pneumococcal density (r=0.71; P=0.029). Similarly, AM heightened opsonophagocytic capacity was correlated with nasopharyngeal pneumococcal density (r=0.61, P=0.025). Conclusions: Our findings demonstrate that nasal colonization with pneumococcus and microaspiration prime AMs, leading to brisker responsiveness to both pneumococcus and unrelated bacterial pathogens. The relative abundance of AMs in the alveolar spaces, alongside their potential for nonspecific protection, render them an attractive target for novel vaccines.

RESUMEN

Mixing of pigs into new social groups commonly induces aggressive interactions that result in skin lesions on the body of the animals. The relationship between skin lesions and aggressive behavioral interactions in group-housed pigs can be analyzed within the framework of social genetic effects (SGE). This study incorporates the quantification of aggressive interactions between pairs of animals in the modeling of SGE for skin lesions in different regions of the body in growing pigs. The dataset included 792 pigs housed in 59 pens. Skin lesions in the anterior, central, and caudal regions of the body were counted 24 h after pig mixing. Animals were video-recorded for 9 h postmixing and trained observers recorded the type and duration of aggressive interactions between pairs of animals. The number of seconds that pairs of pigs spent engaged in reciprocal fights and unilateral attack behaviors were used to parametrize the intensity of social interactions (ISI). Three types of models were fitted: direct genetic additive model (DGE), traditional social genetic effect model (TSGE) assuming uniform interactions between dyads, and an intensity-based social genetic effect model (ISGE) that used ISI to parameterize SGE. All models included fixed effects of sex, replicate, lesion scorer, weight at mixing, premixing lesion count, and the total time that the animal spent engaged in aggressive interactions (reciprocal fights and unilateral attack behaviors) as a covariate; a random effect of pen; and a random direct genetic effect. The ISGE models recovered more direct genetic variance than DGE and TSGE, and the estimated heritabilities (h^D2) were highest for all traits (P < 0.01) for the ISGE with ISI parametrized with unilateral attack behavior. The TSGE produced estimates that did not differ significantly from DGE (P > 0.5). Incorporating the ISI into ISGE, even in a small dataset, allowed separate estimation of the genetic parameters for direct and SGE, as well as the genetic correlation between direct and SGE (rs), which was positive for all lesion traits. The estimates from ISGE suggest that if behavioral observations are available, selection incorporating SGE may reduce the consequences of aggressive behaviors after mixing pigs.

Asunto(s)

Bienestar del Animal , Conducta Animal , Porcinos/fisiología , Agresión , Animales , Femenino , Masculino , Modelos Genéticos , Fenotipo , Piel/lesiones , Porcinos/genética

RESUMEN

BACKGROUND: Closed reduction (CR) is a common treatment for infantile developmental dysplasia of the hip. The purpose of this observational, prospective, multicenter study was to determine the early outcomes following CR. METHODS: Prospectively collected data from an international multicenter study group was analyzed for patients treated from 2010 to 2014. Baseline demographics, clinical exam, radiographic/ultrasonographic data, and history of previous orthotic treatment were assessed. At minimum 1-year follow-up, failure was defined as an IHDI grade 3 or 4 hip and/or need for open reduction. The incidence of avascular necrosis (AVN), residual dysplasia, and need for further surgery was assessed. RESULTS: A total of 78 patients undergoing CR for 87 hips were evaluated with a median age at initial reduction of 8 months (range, 1 to 20 mo). Of these, 8 hips (9%) were unable to be closed reduced initially. At most recent follow-up (median 22 mo; range, 12 to 36 mo), 72/79 initially successful CRs (91%) remained stable. The likelihood of failure was unaffected by initial clinical reducibility of the hip (P=0.434), age at initial CR (P=0.897), or previous treatment in brace (P=0.222). Excluding those hips that failed initial CR, 18/72 hips (25%) developed AVN, and the risk of osteonecrosis was unaffected by prereduction reducibility of the hip (P=0.586), age at CR (P=0.745), presence of an ossific nucleus (P=0.496), or previous treatment in brace (P=0.662). Mean acetabular index on most recent radiographs was 25 degrees (±6 degrees), and was also unaffected by any of the above variables. During the follow-up period, 8/72 successfully closed reduced hips (11%) underwent acetabular and/or femoral osteotomy for residual dysplasia. CONCLUSIONS: Following an initially successful CR, 9% of hips failed reduction and 25% developed radiographic AVN at early-term follow-up. History of femoral head reducibility, previous orthotic bracing, and age at CR did not correlate with success or chances of developing AVN. Further follow-up of this prospective, multicenter cohort will be necessary to establish definitive success and complication rates following CR for infantile developmental dysplasia of the hip. LEVEL OF EVIDENCE: Level II-prospective observational cohort.

Asunto(s)

Necrosis de la Cabeza Femoral , Fémur , Luxación Congénita de la Cadera , Procedimientos Ortopédicos , Osteotomía , Cuidados Posteriores/métodos , Cuidados Posteriores/estadística & datos numéricos , Femenino , Fémur/anomalías , Fémur/diagnóstico por imagen , Fémur/cirugía , Necrosis de la Cabeza Femoral/epidemiología , Necrosis de la Cabeza Femoral/etiología , Luxación Congénita de la Cadera/diagnóstico por imagen , Luxación Congénita de la Cadera/cirugía , Humanos , Incidencia , Lactante , Masculino , Procedimientos Ortopédicos/efectos adversos , Procedimientos Ortopédicos/instrumentación , Procedimientos Ortopédicos/métodos , Procedimientos Ortopédicos/estadística & datos numéricos , Osteotomía/métodos , Osteotomía/estadística & datos numéricos , Estudios Prospectivos , Radiografía/métodos , Reoperación/métodos , Reoperación/estadística & datos numéricos , Resultado del Tratamiento

RESUMEN

OBJECTIVE: To examine the characteristics and outcomes of a multicenter patient cohort with indeterminate pediatric acute liver failure (IND-PALF) and with aplastic anemia with acute hepatitis treated with corticosteroids. STUDY DESIGN: Retrospective study of patients age 1-17 years with IND-PALF and aplastic anemia with acute hepatitis who presented between 2009 and 2018 to 1 of 4 institutions and were treated with corticosteroids for presumed immune dysregulation. RESULTS: Of 28 patients with IND-PALF (median of 4.0 years of age [range 1-16] and 71% male) 71% (n = 20) were treated with 0.5-4 mg/kg/day of intravenous methylprednisolone, and 8 patients received 10 mg/kg/day followed by a taper. By 21 days postcorticosteroid initiation, 14 patients (50%) underwent liver transplantation, 13 patients (46%) recovered with their native liver, and 1 patient (4%) died. Patients who recovered with their native liver received a median of 139 days (range 19-749) of corticosteroid therapy, with a median of 12 days (range 1-240) to international normalized ratio ≤1.2. Patients with aplastic anemia with acute hepatitis (n = 6; median of 9.5 years of age [range 1-12], 83% male), received 1-2 mg/kg/day of methylprednisolone for a median of 100 days (range 63-183), and all recovered with their native liver. One patient with IND-PALF and 2 patients with aplastic anemia with acute hepatitis developed a serious infection within 90 days postcorticosteroid initiation. CONCLUSIONS: Many patients with IND-PALF or aplastic anemia with acute hepatitis that were treated with corticosteroids improved, but survival with native liver may not be different from historical reports. A randomized controlled trial exploring the benefits and risks of steroid therapy is needed before it is adopted broadly.

Asunto(s)

Anemia Aplásica/complicaciones , Glucocorticoides/uso terapéutico , Hepatitis/complicaciones , Fallo Hepático Agudo/complicaciones , Fallo Hepático Agudo/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Enfermedad Aguda , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD161+CD8+ T cell clusters were significantly lower in colonized than in noncolonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide–specific and total plasmablasts in blood. Moreover, increased responses of blood mucosa-associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell populations.