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Chromosome-scale construction along with evolution in the tetraploid Salvia splendens (Lamiaceae) genome.
BACKGROUND Different variables are playing a role in prognosis of acute heart failure. OBJECTIVES Our purpose was to create and validate a risk score to predict mortality in patients with a first episode of acute heart failure during the first 2 months after the first hospitalization. DESIGN This was a prospective cohort study. PARTICIPANTS We recruited patients diagnosed with a first episode of acute heart failure. MAIN MEASURES We collected data on sociodemographic characteristics; medical history; symptoms; precipitating factors; signs and symptoms of congestion; echocardiographic parameters; aetiology; vital signs and laboratory findings; and response to initial treatment (yes/no). A Cox proportional hazard regression model was built with mortality during the first 2 months after the index episode as the dependent variable. A risk score is presented. KEY RESULTS The mortality rate during the first 2 months after a first episode of heart failure was 5%. Age, systolic blood pressure, serum sodium, ejection fraction and blood urea nitrogen were selected in the internal validation, as was right ventricular failure. A risk score was developed. Both the model and the score showed good discrimination and calibration properties when applied to an independent cohort. CONCLUSIONS Our ESSIC-FEHF risk score showed excellent properties in the derivation cohort and also in a cohort from a different time period. This score is expected to help decision making in patients diagnosed with heart failure for the first time. A 35-year-old woman with progressive decrease of vision in both eyes and with no other associated symptoms, manifested as the only antecedent, the death of her brother due to amyloidosis. The visual acuity was counting fingers at 30 centimetres in the right eye and 20/70 in the left eye. In ophthalmoscopy of the right eye, a white, homogeneous vitreous, that was difficult to assess in detail, was observed, and in the left eye a whitish vitreous with band-like opacities in the cortical region. Vitrectomy was performed in the right eye, and a study with specific stains showed positive for amyloid material. A case is reported of amyloidosis diagnosed with specific stains in a vitreous sample for which the initial and only manifestation was the presence of vitreous opacities. The processing of these samples should be considered in patients with family history, early vitreous opacities, negative results of systemic biopsy, or atypical course of the disease. In a number of mouse models of hereditary deafness, therapeutic transgene delivery to the cochlea and vestibular organs using adeno-associated viral vectors (AAVs) has shown striking rescue of hearing and balance. However, only a subset of AAV capsids have shown efficacy in transducing both inner hair cells and outer hair cells, and it is also not clear which of these can be translated to treatment of human inner ear. We recently reported efficient transgene expression of a GFP reporter in a non-human primate cochlea, in both inner and outer hair cells, following injection of the AAV9 capsid variant PHP.B via the round window membrane (RWM). However efficiency was poor at a lower dose. To further define the transduction potential of AAV9-PHP.B, we have performed a dosing study in the cynomolgus monkey and assessed vector-encoded GFP expression. Three animals were injected in both ears and four doses were tested. We describe a transmastoid surgical approach needed to access the RWM of this common primate model. We found that AAV9-PHP.B transduced nearly 100% of both IHCs and OHCs, from base to apex, at the higher doses (3.5 × 1011 and 7 × 1011 vector genomes). However, at lower doses there was a steep reduction in viral transduction. Thus, AAV9-PHP.B efficiently transduces the IHCs and OHCs of nonhuman primates, and should be considered as an AAV capsid for inner ear gene therapy in humans. PURPOSE Randomized controlled trials (RCT) in pediatric appendicitis remain limited, and the robustness of available evidence is unknown. The aim of this study was to determine the fragility of results in pediatric appendicitis RCTs. METHODS A systematic search of Embase and MEDLINE was performed. Eligible studies were two-armed RCTs that included at least one statistically significant dichotomous outcome, had parallel-group allocation, and assessed pediatric patients (0-17) with a primary diagnosis of appendicitis. The Fragility Index (FI) for one statistically significant outcome per trial was calculated using a Fisher's exact test, with statistical significance set at p  less then  0.05. RESULTS Six studies were identified for inclusion. Studies included a median of 103 patients (interquartile range [IQR] 86-127), with a median of 18 (IQR 4.5-41.25) events for analyzed outcomes. The primary outcome variable was included in analysis for 4(67%) studies. The median FI across studies was 3 (IQR 0.75-4.25), with results ranging from 0 to 5. Results indicate that overall, converting 3 patients from non-events to events in a single trial arm would change the significant dichotomous outcome to nonsignificant. CONCLUSION The fragility of results in RCTs in pediatric appendicitis should be considered before clinical practice is changed. Investigators should consider reporting the FI alongside study results, as p-values alone may be misleading. TYPE OF STUDY Randomized Controlled Trial. LEVEL OF EVIDENCE Level I. BACKGROUND/PURPOSE Children with inflammatory bowel disease (IBD) have increased risk for venous thromboembolism (VTE). We sought to determine incidence and risk factors for postoperative VTE in a multicenter cohort of pediatric patients undergoing colorectal resection for IBD. METHODS Retrospective review of children ≤18 years who underwent colorectal resection for IBD from 2010 to 2016 was performed at four children's hospitals. Primary outcome was VTE that occurred between surgery and last follow-up. Factors associated with VTE were determined using univariable and multivariable analyses. RESULTS Two hundred seventy-six patients were included with median age 15 years [13,17]. Forty-two children (15%) received perioperative VTE chemoprophylaxis, and 88 (32%) received mechanical prophylaxis. DVT occurred in 12 patients (4.3%) at a median of 14 days postoperatively [8,147]. Most were portomesenteric (n = 9, 75%) with the remaining catheter-associated DVTs in extremities (n = 3, 25%). There was no association with chemoprophylaxis (p > 0.99). On Cox regression, emergent procedure [HR 18.8, 95%CI 3.18-111], perioperative plasma transfusion [HR 25.1, 95%CI 2.4-259], and postoperative infectious complication [HR 10.5, 95%CI 2.63-41.8] remained predictive of DVT. CONCLUSION Less than 5% of pediatric IBD patients developed postoperative VTE. Chemoprophylaxis was not protective but rarely used. Patients with risk factors identified in this study should be monitored or given prophylaxis for VTE. LEVEL OF EVIDENCE Treatment Study, Level III. PURPOSE The identification of urachal remnants is occurring more in infancy. Despite evidence that nonoperative management is effective, operative management remains common and has a high complication rate. We sought to determine if the complication rate after urachal resection is associated with age. METHODS Patients undergoing urachal remnant resection were identified from ACS NSQIP Pediatric from 2013 to 2017. Exclusion criteria included emergent operations, contaminated wounds, and any additional procedures. Patients were compared based on complication rates, need for reoperation or readmission, and length of stay. RESULTS A complication occurred in 16 of 476 patients (3.3%), 6 (1.3%) had reoperation, and 11 (2.3%) were readmitted. The median age for patients requiring reoperation was lower (0.1 years) than those not (1.3 years; p = 0.004). The median age of those readmitted was lower (0.4 years) than those not (1.4 years, p = 0.03), and a weak trend of longer length of stay in younger patients was identified (ρ = -0.16, p  less then  0.001). CONCLUSIONS Operative management of younger patients resulted in greater risk of reoperation, readmission, and longer length of stay. Given that nonoperative management is effective, it may be of benefit to delay resection of urachal remnants to after 1 year of age. STUDY TYPE Treatment study. LEVEL OF EVIDENCE Level III. In response to the ongoing opioid epidemic, many surgeons who care for children have reflected upon current practices and the history of our own prescribing. In this editorial review, we provide a brief summary of the origins of opioid use in medicine and surgery, we describe how the ongoing opioid epidemic specifically impacts children and adolescents, and we explore contemporary efforts underway to facilitate evidence-based opioid prescribing. Resources for pediatric surgeons including national guidelines related to safe opioid prescribing and web-based toolkits that may be used to implement change locally are highlighted. The goal of the present manuscript is to introduce opioid stewardship as a guiding principle in pediatric surgery. LEVEL OF EVIDENCE LEVEL V (Expert opinion). AIMS To illustrate the construction of statistical control charts and show their potential application to analysis of outcomes in children's surgery. PATIENTS AND METHODS Two datasets recording outcomes following esophageal atresia repair and intestinal resection for Crohn's disease maintained by the author were used to construct four types of charts. The effects of altering the target signal, the alarm signal and the limits are illustrated. The dilemmas in choice of target rate are described. Simulated data illustrate the advantages over hypothesis testing. RESULTS The charts show the author's institutional leak rate for esophageal atresia repair may be within acceptable limits, but that this is dependent on the target set. The desirable target is contentious. The leak rate for anastomoses following intestinal resection for Crohn's disease leak is also within acceptable limits when compared to published experience, but may be deteriorating. The charts are able to detect deteriorating levels of performance well before hypothesis testing would suggest a systematic problem with outcomes. CONCLUSIONS Statistical process control charts can provide surgeons with early warning of systematic poor performance. They are robust to volume-outcome influences, since the outcome is tested sequentially after each procedure or patient. They have application in a specialty with low frequencies of operations such as children's surgery. TYPE OF STUDY Diagnostic test. LEVEL OF EVIDENCE Level II. Crown All rights reserved.PURPOSE Sun-exposure can cause health problems, including melanoma and nonmelanoma skin cancer, especially in Australia where the incidence of skin cancer is particularly high. Childhood cancer survivors (CCSs) have an augmented risk due to previous cancer history and treatment. Despite recommendations advising sun protection, CCSs may be placing themselves at risk. We considered daily summer sun-exposure in an Australian cohort of CCSs and in community reference groups, and identified factors associated with sun-exposure in these populations. METHODS Summer sun-exposure data were collected on 471 CCSs (119 parents of survivors aged less then 16, and 352 survivors aged ≥16) and a reference group of 470 participants from the community (155 parents of children aged less then 16, and 355 adults aged ≥16). Survivors completed paper questionnaires and the reference groups completed an online survey. Medical records confirmed survivors' clinical information. Ordinal logistic regressions identified factors associated with daily summer sun-exposure.
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