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Increasingly long and complex informed consents have yielded studies demonstrating comparatively low participant comprehension and satisfaction with traditional face-to-face approaches. In parallel, interest in electronic consents for clinical and research genomics has steadily increased, yet limited data are available for trio-based genomic discovery studies. We describe the design, development, implementation, and validation of an electronic iConsent application for trio-based genomic research deployed to support genomic studies of cerebral palsy. iConsent development incorporated stakeholder perspectives including researchers, patient advocates, institutional review board members, and genomic data-sharing considerations. The iConsent platform integrated principles derived from prior electronic consenting research and elements of multimedia learning theory. Participant comprehension was assessed in an interactive teachback format. The iConsent application achieved nine of ten proposed desiderata for effective patient-focused electronic consenting for genomic research. Overall, participants demonstrated high comprehension and retention of key human subjects' considerations. Enrollees reported high levels of satisfaction with the iConsent, and we found that participant comprehension, iConsent clarity, privacy protections, and study goal explanations were associated with overall satisfaction. Although opportunities exist to optimize iConsent, we show that such an approach is feasible, can satisfy multiple stakeholder requirements, and can realize high participant satisfaction and comprehension while increasing study reach.
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Highly conserved transport protein particle (TRAPP) complexes regulate subcellular trafficking pathways. Accurate protein trafficking has been increasingly recognized to be critically important for normal development, particularly in the nervous system. Variants in most TRAPP complex subunits have been found to lead to neurodevelopmental disorders with diverse but overlapping phenotypes. We expand on limited prior reports on TRAPPC6B with detailed clinical and neuroradiologic assessments, and studies on mechanisms of disease, and new types of variants. We describe 29 additional patients from 18 independent families with biallelic variants in TRAPPC6B. We identified seven homozygous nonsense (n = 12 patients) and eight canonical splice-site variants (n = 17 patients). In addition, we identified one patient with compound heterozygous splice-site/missense variants with a milder phenotype and one patient with homozygous missense variants. Patients displayed non-progressive microcephaly, global developmental delay/intellectual disability, epilepsy and absent expressive language. Movement disorders including stereotypies, spasticity and dystonia were also observed. Brain imaging revealed reductions in cortex, cerebellum and corpus callosum size with frequent white matter hyperintensity. Volumetric measurements indicated globally diminished volume rather than specific regional losses. We identified a reduced rate of trafficking into the Golgi apparatus and Golgi fragmentation in patient-derived fibroblasts that was rescued by wild-type TRAPPC6B. Molecular studies revealed a weakened interaction between mutant TRAPPC6B (c.454C>T, p.Q152*) and its TRAPP binding partner TRAPPC3. Patient-derived fibroblasts from the TRAPPC6B (c.454C>T, p.Q152*) variant displayed reduced levels of TRAPPC6B as well as other TRAPP II complex-specific members (TRAPPC9 and TRAPPC10). Interestingly, the levels of the TRAPPC6B homologue TRAPPC6A were found to be elevated. Moreover, co-immunoprecipitation experiments showed that TRAPPC6A co-precipitates equally with TRAPP II and TRAPP III, while TRAPPC6B co-precipitates significantly more with TRAPP II, suggesting enrichment of the protein in the TRAPP II complex. This implies that variants in TRAPPC6B may preferentially affect TRAPP II functions compared to TRAPP III functions. Finally, we assessed phenotypes in a Drosophila TRAPPC6B-deficiency model. Neuronal TRAPPC6B knockdown impaired locomotion and led to wing posture defects, supporting a role for TRAPPC6B in neuromotor function. Our findings confirm the association of damaging biallelic TRAPPC6B variants with microcephaly, intellectual disability, language impairments, and epilepsy. A subset of patients also exhibited dystonia and/or spasticity with impaired ambulation. These features overlap with disorders arising from pathogenic variants in other TRAPP subunits, particularly components of the TRAPP II complex. These findings suggest that TRAPPC6B is essential for brain development and function, and TRAPP II complex activity may be particularly relevant for mediating this function.
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Distonía , Epilepsia , Discapacidad Intelectual , Microcefalia , Trastornos del Neurodesarrollo , Animales , Humanos , Microcefalia/genética , Discapacidad Intelectual/genética , Proteínas de Transporte Vesicular/genética , Trastornos del Neurodesarrollo/genética , Epilepsia/genéticaRESUMEN
BACKGROUND: Mutations in the NMDA receptor are known to disrupt glutamatergic signaling crucial for early neurodevelopment, often leading to severe global developmental delay/intellectual disability, epileptic encephalopathy, and cerebral palsy phenotypes. Both seizures and movement disorders can be highly treatment-refractory. RESULTS: We describe a targeted ABA n-of-1 treatment trial with intrathecal MgSO4, rationally designed based on the electrophysiologic properties of this gain of function mutation in the GRIN1 NMDA subunit. CONCLUSION: Although the invasive nature of the trial necessitated a short-term, non-randomized, unblinded intervention, quantitative longitudinal neurophysiologic monitoring indicated benefit, providing class II evidence in support of intrathecal MgSO4 for select forms of GRIN disorders.
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Discapacidad Intelectual , Magnesio , Humanos , Discapacidad Intelectual/genética , Magnesio/metabolismo , Mutación/genética , Proteínas del Tejido Nervioso/genética , Receptores de N-Metil-D-Aspartato/genética , Convulsiones/genética , Estudios de Casos Únicos como AsuntoRESUMEN
In the evolving modern era of neuromodulation for movement disorders in adults and children, much progress has been made recently characterizing the human motor network (MN) with potentially important treatment implications. Herein is a focused review of relevant resting state fMRI functional and effective connectivity of the human motor network across the lifespan in health and disease. The goal is to examine how the transition from functional connectivity to dynamic effective connectivity may be especially informative of network-targeted movement disorder therapies, with hopeful implications for children.
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BACKGROUND: KCNMA1-linked channelopathy is a rare movement disorder first reported in 2005. Paroxysmal non-kinesigenic dyskinesia (PNKD) in KCNMA1-linked channelopathy is the most common symptom in patients harboring the KCNMA1-N999S mutation. PNKD episodes occur up to hundreds of times daily with significant morbidity and limited treatment options, often in the context of epilepsy. CASES: We report 6 cases with the KCNMA1-N999S variant treated with lisdexamfetamine (0.7-1.25 mg/kg/day), a pro-drug of dextroamphetamine. Data were collected retrospectively from interviews and chart review. Parent-reported daily PNKD episode counts were reduced under treatment, ranging from a 10-fold decrease to complete resolution. CONCLUSION: Our findings suggest that lisdexamfetamine is an effective therapy for PNKD3 (KCNMA1-associated PNKD). Treatment produced dramatic reductions in debilitating dyskinesia episodes, without provocation or exacerbation of other KCNMA1-associated symptoms such as seizures.
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Opsoclonus-myoclonus-ataxia syndrome is a rare neuroimmunologic disorder typically presenting in previously healthy infants and toddlers. It is characterized by a clinical triad of (1) erratic saccadic intrusions; (2) myoclonus and/or ataxia; (3) behavioral features, typified by developmental plateauing, irritability and insomnia. About half of cases are associated with an underlying neuroblastoma and diagnostic imaging is essential once OMAS is suspected. A thorough workup, including serum, urine, and cerebrospinal fluid studies is critical to identify underlying biomarkers of OMAS itself or neuroblastoma. Historically, many children had relatively poor long-term outcomes, with residual neurologic and/or neuropsychiatry sequelae typical. More recent concepts have emphasized combined immunotherapy regimens that offer hope for better outcomes in children with this remarkable, challenging disease.
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Neuroblastoma , Trastornos de la Motilidad Ocular , Síndrome de Opsoclonía-Mioclonía , Ataxia/terapia , Progresión de la Enfermedad , Humanos , Lactante , Neuroblastoma/complicaciones , Neuroblastoma/terapia , Síndrome de Opsoclonía-Mioclonía/terapiaRESUMEN
OBJECTIVE: To quantify the association of pubic symphysis separation with mode of delivery and follow the resolution of this physiologic separation in the postpartum period. METHODS: Prospective observational cohort study that recruited two cohorts of primiparous women: those undergoing vaginal and cesarean delivery (45 and 46 patients, respectively). Chart review collected intrapartum factors. Patients were followed with serial anterior-posterior radiographs within 48 hours of delivery and at 6, 12, and 24 weeks postpartum, to evaluate the extent of pubic symphysis separation. Differences between the two cohorts in intrapartum factors were assesses as was pubic symphysis separation at each time point. RESULTS: Mean age of women was 25.8 (SD 5.1) years, and 56% were White. Mean birth weight was 3.5 (SD 0.52) kg. Mean immediate postpartum pubic symphysis separation was 7.6 (SD 2.2) mm and did not differ between groups, at 7.18 mm for vaginal delivery versus 8.04 mm for cesarean delivery (CD; P = 0.08). Pubic symphysis separation was not significantly different for CD with and without labour. Black race and obesity were associated with increased pubic symphysis separation. No intrapartum events were related to extent of separation. Normalization of pregnancy pubic symphysis separation to 4-5 mm occurred by 6 weeks postpartum. Separation of >10mm and <15mm occurred in 10 of the 91 women and occurred after vaginal and cesarean delivery. The widest pubic symphysis separation was observed in 3 patients after vaginal delivery. CONCLUSION: Physiological pubic symphysis separation occursduring pregnancy and regresses postpartum with minimal effects from labour and delivery. Cesarean deliverydoes not prevent physiological pubic symphysis separation.
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Diástasis de la Sínfisis Pubiana , Sínfisis Pubiana , Adulto , Cesárea , Parto Obstétrico , Femenino , Humanos , Embarazo , Estudios Prospectivos , Sínfisis Pubiana/diagnóstico por imagen , Diástasis de la Sínfisis Pubiana/diagnóstico por imagen , Diástasis de la Sínfisis Pubiana/epidemiologíaRESUMEN
OBJECTIVE: To determine whether mutations reported for ZDHHC15 can cause mixed neurodevelopmental disorders, we performed both functional studies on variant pathogenicity and ZDHHC15 function in animal models. METHODS: We examined protein function of 4 identified variants in ZDHHC15 in a yeast complementation assay and locomotor defects of loss-of-function genotypes in a Drosophila model. RESULTS: Although we assessed multiple patient variants, only 1 (p.H158R) affected protein function. We report a patient with a diagnosis of hypotonic cerebral palsy, autism, epilepsy, and intellectual disability associated with this bona fide damaging X-linked variant. Features include tall forehead with mild brachycephaly, down-slanting palpebral fissures, large ears, long face, facial muscle hypotonia, high-arched palate with dental crowding, and arachnodactyly. The patient had mild diminished cerebral volume, with left-sided T2/FLAIR hyperintense periatrial ovoid lesion. We found that loss-of-function mutations in orthologs of this gene cause flight and coordinated movement defects in Drosophila. CONCLUSIONS: Our findings support a functional expansion of this gene to a role in motor dysfunction. Although ZDHHC15 mutations represent a rare cause of neurodevelopmental disability, candidate variants need to be carefully assessed before pathogenicity can be determined.
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In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.
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Parálisis Cerebral/genética , Proteínas F-Box/genética , Tubulina (Proteína)/genética , Proteínas Supresoras de Tumor/genética , beta Catenina/genética , Animales , Parálisis Cerebral/patología , Ciclina D/genética , Citoesqueleto/genética , Drosophila/genética , Exoma/genética , Matriz Extracelular/genética , Femenino , Adhesiones Focales/genética , Predisposición Genética a la Enfermedad , Genoma Humano/genética , Humanos , Masculino , Mutación/genética , Neuritas/metabolismo , Neuritas/patología , Factores de Riesgo , Análisis de Secuencia de ADN , Transducción de Señal/genética , Secuenciación del Exoma , Proteína de Unión al GTP rhoB/genéticaRESUMEN
Several populations of the amphipod, Hyalella azteca, have developed resistance to pyrethroid insecticides due to non-target exposure, but the dominance of the resistance trait is unknown. The current study investigated the dominance level of point mutations in natural populations of insecticide-resistant H. azteca and determined whether H. azteca from different clades with and without resistant alleles can hybridize and produce viable offspring. A parent generation (P0) of non-resistant homozygous wild type H. azteca was crossbred with pyrethroid-resistant homozygous mutant animals and the tolerance of the filial 1 (F1) generation to the pyrethroid insecticide, permethrin, was measured. Then the genotypes of the F1 generation was examined to assure heterozygosity. The resistant parents had permethrin LC50 values that ranged from 52 to 82 times higher than the non-resistant animals and both crossbreeding experiments produced heterozygous hybrid offspring that had LC50 values similar to the non-resistant H. azteca parent. Dominance levels calculated for each of the crosses showed values close to 0, confirming that the L925I and L925V mutations were completely recessive. The lack of reproduction by hybrids of the C x D breeding confirmed that these clades are reproductively isolated and therefore introgression of adaptive alleles across these clades is unlikely. Potential evolutionary consequences of this selection include development of population bottlenecks, which may arise leading to fitness costs and reduced genetic diversity of H. azteca.
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Anfípodos , Insecticidas/análisis , Piretrinas , Contaminantes Químicos del Agua/análisis , Animales , Hibridación Genética , Resistencia a los Insecticidas , PermetrinaRESUMEN
Enteroviruses are a common cause of respiratory and gastrointestinal illness, and multiple subtypes, including poliovirus, can cause neurologic disease. In recent years, enterovirus D68 (EV-D68) has been associated with serious neurologic illnesses, including acute flaccid myelitis (AFM), frequently preceded by respiratory disease. A cluster of 11 suspect cases of pediatric AFM was identified in September 2016 in Phoenix, AZ. To determine if these cases were associated with EV-D68, we performed multiple genomic analyses of nasopharyngeal (NP) swabs and cerebrospinal fluid (CSF) material from the patients, including real-time PCR and amplicon sequencing targeting the EV-D68 VP1 gene and unbiased microbiome and metagenomic sequencing. Four of the 11 patients were classified as confirmed cases of AFM, and an additional case was classified as probable AFM. Real-time PCR and amplicon sequencing detected EV-D68 virus RNA in the three AFM patients from which NP swabs were collected, as well as in a fourth patient diagnosed with acute disseminated encephalomyelitis, a disease that commonly follows bacterial or viral infections, including enterovirus. No other obvious etiological causes for AFM were identified by 16S or RNA and DNA metagenomic sequencing in these cases, strengthening the likelihood that EV-D68 is an etiological factor. Herpes simplex viral DNA was detected in the CSF of the fourth case of AFM and in one additional suspect case from the cluster. Multiple genomic techniques, such as those described here, can be used to diagnose patients with suspected EV-D68 respiratory illness, to aid in AFM diagnosis, and for future EV-D68 surveillance and epidemiology.IMPORTANCE Enteroviruses frequently result in respiratory and gastrointestinal illness; however, multiple subtypes, including poliovirus, can cause severe neurologic disease. Recent biennial increases (i.e., 2014, 2016, and 2018) in cases of non-polio acute flaccid paralysis have led to speculations that other enteroviruses, specifically enterovirus D68 (EV-D68), are emerging to fill the niche that was left from poliovirus eradication. A cluster of 11 suspect cases of pediatric acute flaccid myelitis (AFM) was identified in 2016 in Phoenix, AZ. Multiple genomic analyses identified the presence of EV-D68 in the majority of clinical AFM cases. Beyond limited detection of herpesvirus, no other likely etiologies were found in the cluster. These findings strengthen the likelihood that EV-D68 is a cause of AFM and show that the rapid molecular assays developed for this study are useful for investigations of AFM and EV-D68.
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Enfermedades Virales del Sistema Nervioso Central/epidemiología , Enfermedades Virales del Sistema Nervioso Central/virología , Análisis por Conglomerados , Enterovirus Humano D/clasificación , Enterovirus Humano D/aislamiento & purificación , Mielitis/epidemiología , Mielitis/virología , Enfermedades Neuromusculares/epidemiología , Enfermedades Neuromusculares/virología , Filogenia , Arizona/epidemiología , Líquido Cefalorraquídeo/virología , Enterovirus Humano D/genética , Humanos , Epidemiología Molecular , Nasofaringe/virología , ARN Viral/genética , ARN Viral/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Peripheral diagnostics for Alzheimer's disease (AD) continue to be developed. Diagnostics capable of detecting AD before the onset of symptoms are particularly desirable, and, given the fact that early detection is imperative for alleviating long-term symptoms of the disease, methods which enable detection in the earliest stages are urgently needed. Saliva testing is non-invasive, and saliva is easy to acquire. A simple, non-invasive saliva test can potentially be used as an adjunct to diagnose AD during its earliest stages. METHODS: Salivary levels of beta amyloid 42 (Aß42) were quantitated with enzyme-linked immunosorbent-type assays. Fifteen AD patients (7 men, mean age 77.8 ± 1.8 years, mean Mini-Mental State Examination [MMSE] score 19.0 ± 1.3) and 7 normal controls (2 men, mean age 60.4 ± 4.7 years, mean MMSE 29.0 ± 0.4) were enrolled. RESULTS: Salivary Aß42 levels were significantly higher in AD patients than in controls (51.7 ± 1.6 pg/mL for AD and 21.1 ± 0.3 pg/mL for controls, p < 0.001). Based on these results, saliva testing appears to be a promising method for detecting AD during its critical early stages.
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Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides/análisis , Biomarcadores/análisis , Diagnóstico Precoz , Saliva/química , Anciano , Anciano de 80 o más Años , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Biocidal products are mixtures of one or more active substances (a.s.) and a broad range of formulation additives. There is regulatory guidance currently under development that will specify how the combined effects of the a.s. and any relevant formulation additives shall be considered in the environmental risk assessment of biocidal products. The default option is a component-based approach (CBA) by which the toxicity of the product is predicted from the toxicity of 'relevant' components using concentration addition. Hence, unequivocal and practicable criteria are required for identifying the 'relevant' components to ensure protectiveness of the CBA, while avoiding unnecessary workload resulting from including by default components that do not significantly contribute to the product toxicity. The present study evaluated a set of different criteria for identifying 'relevant' components using confidential information on the composition of 21 wood preservative products. Theoretical approaches were complemented by experimentally testing the aquatic toxicity of seven selected products. RESULTS: For three of the seven tested products, the toxicity was underestimated for the most sensitive endpoint (green algae) by more than factor 2 if only the a.s. were considered in the CBA. This illustrated the necessity of including at least some additives along with the a.s. Considering additives that were deemed 'relevant' by the tentatively established criteria reduced the underestimation of toxicity for two of the three products. A lack of data for one specific additive was identified as the most likely reason for the remaining toxicity underestimation of the third product. In three other products, toxicity was overestimated by more than factor 2, while prediction and observation fitted well for the seventh product. Considering all additives in the prediction increased only the degree of overestimation. CONCLUSIONS: Supported by theoretical calculations and experimental verifications, the present study developed criteria for the identification of CBA-relevant components in a biocidal product. These criteria are based on existing criteria stated in the regulation for classification, labelling and packaging of substances. The CBA was found sufficiently protective and reliable for the tested products when applying the here recommended criteria. The lack of available aquatic toxicity data for some of the identified relevant components was the main reason for underestimation of product toxicity.
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A majority of cervical cancers are caused by human papillomavirus (HPV); however, HPV-negative cervical cancers exist and, though rare, are more aggressive. No prior reports examine HPV-negative cancer of the cervix in a female pseudohermaphrodite with congenital adrenal hyperplasia (CAH). This is a case of a 78-year-old phenotypic male with hypospadias and absent testicles who presented with urinary retention and urosepsis. He was diagnosed with a pelvic mass on imaging and with a female mosaic karyotype (45,X/47,XXX/46 XX). He was taken to the operating room and found to have a rare form of HPV-negative cervical cancer: gastric-type adenocarcinoma (GAS). This study examines the presentation, management, and outcome of a GAS cervical cancer in a patient with a known lack of HPV exposure secondary to the unique anatomy of female pseudohermaphrodism.
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Pyrethroid-resistant Hyalella azteca with voltage-gated sodium channel mutations have been identified at multiple locations throughout California. In December 2013, H. azteca were collected from Mosher Slough in Stockton, CA, USA, a site with reported pyrethroid (primarily bifenthrin and cyfluthrin) sediment concentrations approximately twice the 10-d LC50 for laboratory-cultured H. azteca. These H. azteca were shipped to Southern Illinois University Carbondale and have been maintained in pyrethroid-free culture since collection. Even after 22 months in culture, resistant animals had approximately 53 times higher tolerance to permethrin than non-resistant laboratory-cultured H. azteca. Resistant animals held in culture also lacked the wild-type allele at the L925 locus, and had non-synonymous substitutions that resulted in either a leucine-isoleucine or leucine-valine substitution. Additionally, animals collected from the same site nearly three years later were again resistant to the pyrethroid permethrin. When resistant animals were compared to non-resistant animals, they showed lower reproductive capacity, lower upper thermal tolerance, and the data suggested greater sensitivity to, 4, 4'-dichlorodiphenyltrichloroethane (DDT), copper (II) sulfate, and sodium chloride. Further testing of the greater heat and sodium chloride sensitivity of the resistant animals showed these effects to be unrelated to clade association. Fitness costs associated with resistance to pyrethroids are well documented in pest species (including mosquitoes, peach-potato aphids, and codling moths) and we believe that H. azteca collected from Mosher Slough also have fitness costs associated with the developed resistance.
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Anfípodos/efectos de los fármacos , Insecticidas/toxicidad , Nitrilos/toxicidad , Piretrinas/toxicidad , Contaminantes Químicos del Agua/toxicidad , Anfípodos/fisiología , Animales , Resistencia a Medicamentos , Femenino , Insecticidas/análisis , Masculino , Permetrina/toxicidad , Contaminantes Químicos del Agua/análisisRESUMEN
The recent discovery of pyrethroid-resistant Hyalella azteca populations in California, USA suggests there has been significant exposure of aquatic organisms to these terrestrially-applied insecticides. Since resistant organisms are able to survive in relatively contaminated habitats they may experience greater pyrethroid bioaccumulation, subsequently increasing the risk of those compounds transferring to predators. These issues were evaluated in the current study following toxicity tests in water with permethrin which showed the 96-h LC50 of resistant H. azteca (1670 ng L-1) was 53 times higher than that of non-resistant H. azteca (31.2 ng L-1). Bioaccumulation was compared between resistant and non-resistant H. azteca by exposing both populations to permethrin in water and then measuring the tissue concentrations attained. Our results indicate that resistant and non-resistant H. azteca have similar potential to bioaccumulate pyrethroids at the same exposure concentration. However, significantly greater bioaccumulation occurs in resistant H. azteca at exposure concentrations non-resistant organisms cannot survive. To assess the risk of pyrethroid trophic transfer, permethrin-dosed resistant H. azteca were fed to fathead minnows (Pimephales promelas) for four days, after which bioaccumulation of permethrin and its biotransformation products in fish tissues were measured. There were detectable concentrations of permethrin in fish tissues after they consumed dosed resistant H. azteca. These results show that bioaccumulation potential is greater in organisms with pyrethroid resistance and this increases the risk of trophic transfer when consumed by a predator. The implications of this study extend to individual fitness, populations and food webs.
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Anfípodos/metabolismo , Cyprinidae/metabolismo , Insecticidas/metabolismo , Permetrina/metabolismo , Contaminantes Químicos del Agua/metabolismo , Anfípodos/efectos de los fármacos , Animales , California , Cadena Alimentaria , Resistencia a los Insecticidas , Insecticidas/análisis , Insecticidas/toxicidad , Permetrina/análisis , Permetrina/toxicidad , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
STUDY OBJECTIVE: To evaluate the ability of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator to predict discharge to postacute care and perioperative complications in gynecologic oncology patients undergoing minimally invasive surgery (MIS). DESIGN: A retrospective chart review (Canadian Task Force classification II-1). SETTING: A university hospital. PATIENTS: All patients undergoing MIS on the gynecologic oncology service from January 1, 2009, to December 30, 2013. INTERVENTIONS: Surgical procedures were reviewed, and appropriate Common Procedural Terminology codes were assigned. Twenty-one preoperative risk factors were abstracted from the chart and entered into the ACS NSQIP surgical risk calculator. The predicted risk of discharge to postacute care and 8 additional postoperative complications were calculated and recorded. Actual postoperative complications were abstracted from the medical record. The association between the calculated risk and the actual outcome was determined using logistic regression. The ability of the calculator to accurately predict a particular event was assessed using the c-statistic and Brier score. MEASUREMENTS AND MAIN RESULTS: Of the 876 patients reviewed, a majority underwent hysterectomy (71.6%), with almost half of those patients undergoing additional cancer staging procedures (34.8%). Although the calculator was a poor predictor of postoperative complications, it was a strong predictor for discharge to postacute care (c-statistic = 0.91, Brier score = 0.02) with an odds ratio of 2.31 (95% confidence interval, 1.65-3.25; p < .0001). CONCLUSION: The ACS NSQIP surgical risk calculator does not accurately predict postoperative complications or length of stay in gynecologic oncology patients undergoing MIS. Although it was a strong predictor of need for discharge to postacute care, it vastly overestimated the number of patients requiring this service. Therefore, the calculator's risk score for discharge to postacute care may be considered during preoperative counseling but should not be a predictor of whether or not the patient should proceed with surgery.