Background Variation in the gene encoding zinc finger binding protein 804A ( ZNF804A ) is associated with schizophrenia (SCZ) and bipolar disorder (BP). Evidence suggests that ZNF804A is a regulator ...of gene transcription and is present in nuclear and extranuclear compartments. However, a detailed examination of ZNF804A distribution and its neuronal functions has yet to be performed. Methods The localization of ZNF804A protein was examined in neurons derived from human neural progenitor cells (hNPCs), human induced pluripotent stem cells (hiPSCs) or in primary rat cortical neurons. Additionally, siRNA-mediated knockdown of ZNF804A was conducted to determine its role in neurite formation, maintenance of dendritic spine morphology and responses to activity-dependent stimulations. Results Endogenous ZNF804A protein localized to somato-dendritic compartments and co-localized with the putative synaptic markers in young neurons derived from hNPCs and hiPSCs. In mature rat neurons, Zfp804A, the homolog of ZNF804A, was present in a subset of dendritic spines and co-localized with synaptic proteins in specific nanodomains, as determined by superresolution microscopy. Interestingly, knockdown of ZNF804A attenuated neurite outgrowth in young neurons, an effect potentially mediated by reduced neuroligin-4 (NLGN4) expression. Furthermore, knockdown of ZNF804A in mature neurons resulted in the loss of dendritic spine density, and impaired responses to activity-dependent stimulation. Conclusions These data reveal a novel subcellular distribution for ZNF804A within somato-dendritic compartments and a nanoscopic organisation at excitatory synapses. Moreover, our results suggest that ZNF804A plays an active role in neurite formation, maintenance of dendritic spines and activity-dependent structural plasticity.
IMPORTANCE: Current evidence suggests that nonoperative management of uncomplicated appendicitis is safe, but overall effectiveness is determined by combining medical outcomes with the patient’s and ...family’s perspective, goals, and expectations. OBJECTIVE: To determine the effectiveness of patient choice in nonoperative vs surgical management of uncomplicated acute appendicitis in children. DESIGN, SETTING, AND PARTICIPANTS: Prospective patient choice cohort study in patients aged 7 to 17 years with acute uncomplicated appendicitis presenting at a single pediatric tertiary acute care hospital from October 1, 2012, through March 6, 2013. Participating patients and families gave informed consent and chose between nonoperative management and urgent appendectomy. INTERVENTIONS: Urgent appendectomy or nonoperative management entailing at least 24 hours of inpatient observation while receiving intravenous antibiotics and, on demonstrating improvement of symptoms, completion of 10 days of treatment with oral antibiotics. MAIN OUTCOMES AND MEASURES: The primary outcome was the 1-year success rate of nonoperative management. Successful nonoperative management was defined as not undergoing an appendectomy. Secondary outcomes included comparisons of the rates of complicated appendicitis, disability days, and health care costs between nonoperative management and surgery. RESULTS: A total of 102 patients were enrolled; 65 patients/families chose appendectomy (median age, 12 years; interquartile range IQR, 9-13 years; 45 male 69.2%) and 37 patients/families chose nonoperative management (median age, 11 years; IQR, 10-14 years; 24 male 64.9%). Baseline characteristics were similar between the groups. The success rate of nonoperative management was 89.2% (95% CI, 74.6%-97.0%) at 30 days (33 of 37 children) and 75.7% (95% CI, 58.9%-88.2%) at 1 year (28 of 37 children). The incidence of complicated appendicitis was 2.7% in the nonoperative group (1 of 37 children) and 12.3% in the surgery group (8 of 65 children) (P = .15). After 1 year, children managed nonoperatively compared with the surgery group had fewer disability days (median IQR, 8 5-18 vs 21 15-25 days, respectively; P < .001) and lower appendicitis-related health care costs (median IQR, $4219 $2514-$7795 vs $5029 $4596-$5482, respectively; P = .01). CONCLUSIONS AND RELEVANCE: When chosen by the family, nonoperative management is an effective treatment strategy for children with uncomplicated acute appendicitis, incurring less morbidity and lower costs than surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01718275
IMPORTANCE: The management of pilonidal disease continues to be a challenge due to high rates of recurrence and treatment-associated morbidity. OBSERVATIONS: There is a heterogeneous repertoire of ...treatment modalities used in the management of pilonidal disease and wide practice variation among clinicians. Available treatment options vary considerably in their level of invasiveness, associated morbidity and disability, risks of complications, and effectiveness at preventing disease recurrence. Conservative nonoperative management strategies, including persistent improved hygiene, depilation, and lifestyle modification, focus on disease prevention and minimization of disease activity. Epilation techniques using both laser and intense pulse light therapy are also used as primary and adjunct treatment modalities. Other nonoperative treatment modalities include phenol and fibrin injection to promote closure of pilonidal sinuses. The traditional operative management strategy for pilonidal disease involves excision of affected tissue paired with a variety of closure types including primary midline closure, primary off-midline closure techniques (ie, Karydakis flap, Limberg flap, Bascom cleft lift), and healing by secondary intention. There has been a recent shift toward more minimally invasive operative approaches including sinusectomy (ie, trephination or Gips procedure) and endoscopic approaches. Overall, the current evidence supporting the different treatment options is limited by study quality with inconsistent characterization of disease severity and use of variable definitions and reporting of treatment-associated outcomes across studies. CONCLUSIONS AND RELEVANCE: Pilonidal disease is associated with significant physical and psychosocial morbidity. Optimal treatments will minimize disease and treatment-associated morbidity. There is a need for standardization of definitions used to characterize pilonidal disease and its outcomes to develop evidence-based treatment algorithms.
Background This study reports national estimates of population characteristics and outcomes for patients with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and evaluates the ...relationships between hospital volume and outcomes. Methods Patients admitted within 30 days of life who had International Classification of Diseases, 9th Edition, Clinical Modification diagnosis and procedure codes relevant to EA/TEF during 1999−2012 were identified with the Pediatric Health Information System database. Baseline demographics, comorbidities, and postoperative outcomes, including predictors of in-hospital mortality, were examined up to 2 years after EA/TEF repair. Results We identified 3,479 patients with EA/TEF treated at 43 children's hospitals; 37% were premature and 83.5% had ≥1 additional congenital anomaly, with cardiac anomalies (69.6%) being the most prevalent. Within 2 years of discharge, 54.7% were readmitted, 5.2% had a repeat TEF ligation, 11.4% had a repeat operation for their esophageal reconstruction, and 11.7% underwent fundoplication. In-hospital mortality was 5.4%. Independent predictors of mortality included lower birth weight, congenital heart disease, other congenital anomalies, and preoperative mechanical ventilation. There was no relationship between hospital volume and mortality or repeat TEF ligation. Conclusion This study describes population characteristics and outcomes, including predictors of in-hospital mortality, in EA/TEF patients treated at children's hospitals across the United States. Across these hospitals, rates of mortality or repeat TEF ligation were not dependent on hospital volume.
Results from a clinical trial of moxifloxacin for treating uncomplicated appendicitis provide support for its continued use. Patients with uncomplicated appendicitis should be allowed to decide ...whether to take oral antibiotics or undergo surgery.
Abstract Infants with minor abusive injuries are at risk for more serious abusive injury, including abusive head trauma (AHT). Our study objective was to determine if children with AHT had prior ...opportunities to detect abuse and to describe the opportunities. All AHT cases from 7/1/2009 to 12/31/2011 at four tertiary care children's hospitals were included. A prior opportunity was defined as prior evaluation by either a medical or child protective services (CPS) professional when the symptoms and/or referral could be consistent with abuse but the diagnosis was not made and/or an alternate explanation was given and accepted. Two-hundred-thirty-two children with AHT were identified; median age (IQR) was 5.40 (3.30, 14.60) months. Ten percent (22/232) died. Of the 232 patients diagnosed with AHT, 31% (n = 73) had a total of 120 prior opportunities. Fifty-nine children (25%) had at least one prior opportunity to identify abuse in a medical setting, representing 98 prior opportunities. An additional 14 (6%) children had 22 prior opportunities through previous CPS involvement. There were no differences between those with and without a prior opportunity based on age, gender, race, insurance, mortality, or institution. Children with prior opportunities in a medical setting were more likely to have chronic subdural hemorrhage (48 vs. 17%, p < 0.01) and healing fractures (31 vs. 19%, p = 0.05). The most common prior opportunities included vomiting 31.6% (38/120), prior CPS contact 20% (24/120), and bruising 11.7% (14/120). Improvements in earlier recognition of AHT and subsequent intervention might prevent additional injuries and reduce mortality.
•Shared decision-making is critical to patient-centered care in pediatric surgery.•Shared decision-making can be performed effectively in a high acuity surgical setting in children.•Treatment choice ...requires timely, informed decisions that allow for incorporation of personal values, and preferences.•Nonoperative management of uncomplicated appendicitis is an effective treatment alternative that maybe preferred by families.
Nonoperative management (NOM) of uncomplicated appendicitis is a safe and effective treatment alternative to surgery that may be preferred by some families. Surgery and NOM differ significantly in their associated risks and benefits. Choosing a treatment for acute appendicitis requires patients and their caregivers to make timely, informed decisions that allow for incorporation of personal perspectives, values, and preferences. This article will address the concept of shared decision-making and establish its role in patient-centered care. It will demonstrate the effectiveness of shared decision-making in a high acuity surgical setting for children and highlight how the choice for management of acute appendicitis may be impacted by patients’ and families’ individualized circumstances and values.
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