Idiopathic Pericardial Effusions in Children: Workup and Final Diagnoses.

Pediatric idiopathic pericardial effusions are common and often have a prolonged clinical course. We hypothesized that these effusions have no standardized diagnostic workup, and ultimately have a final etiology not initially appreciated. To test these hypotheses, a hospital system-wide retrospective (1/1/1990-10/1/2019) cohort study of pericardial effusions in children (< 18 years) was conducted. Effusions were grouped by etiology and patients receiving an initial idiopathic diagnosis were further analyzed. Effusion size, diagnostic workup, final diagnosis, and time to resolution were abstracted. In total, 42/366 effusions were initially diagnosed as idiopathic. Workup was not standardized and included up to six laboratory tests including pericardial fluid analysis and infectious, metabolic, rheumatologic and thyroid workups. Treatment course involved 1 readmission in 24%, and > 1 readmission in 12%. Resolution of effusion occurred in 83% of patients within a median of 1 admission (range 1-4). Of those effusions initially deemed idiopathic, 12/42 (29%) were later found to have an underlying etiologic diagnosis including: autoimmune (7, 58%), neoplastic (2, 16%), infectious (2, 16%), and renal (1, 8%). Children initially diagnosed with idiopathic pericardial effusions have an underlying etiologic diagnosis 29% of the time, and a standardized workup may prevent delays in definitive diagnosis and treatment.

Concurrent Acute Appendicitis and Type III Appendiceal Intussusception: A Case Report.

Appendiceal intussusception is exceedingly rare. Although there are few case reports of concurrent ileocecal intussusception and acute appendicitis, to our knowledge, this is the first reported case of concurrent Type III appendiceal intussusception and acute appendicitis. We present the case of an 11-year-old male who underwent appendectomy with partial cecectomy for a Type III appendiceal intussusception with concurrent acute appendicitis.

Concurrent double aortic arch and circumflex aorta repair in a symptomatic child: a case report.

Double aortic arch with circumflex aorta is a rare type of vascular ring. Symptoms result from external compression of the trachea and esophagus. The best surgical approach for patients with double arch and circumflex aorta is debated, and options include the highly complex aortic uncrossing procedure. Herein we describe the surgical treatment of a patient with concurrent double aortic arch and circumflex aorta by division of the non-dominant arch and ligamentum arteriosum, plication and posterior tacking of the diverticulum of Kommerell. This left thoracotomy approach provided complete symptom resolution.

A shifting landscape: Practice patterns and outcomes of cystic fibrosis and non-cystic fibrosis pediatric lung transplantation.

BACKGROUND: New drugs may further decrease the need for lung transplant (LTx) in pediatric patients with cystic fibrosis (CF), but few studies highlight pediatric non-CF LTx characteristics and outcomes. METHODS: The ISHLT registry was used to report morbidity, graft failure, and survival for primary pediatric (<18 years) LTx performed 1990-2017. Recipient/donor characteristics and long-term outcomes were analyzed for CF and non-CF recipients. Survival was assessed using Kaplan-Meier curves. RESULTS: Of 2232 primary LTx, (43% in males), 918 (41%) were performed for non-CF indications; most commonly pulmonary hypertension (43%). Non-CF patients were younger (median age 11 vs. 15, p < .001), and more frequently on inotropes and/or extracorporeal membrane oxygenation (15% vs. 2.4%, p < .001) at transplant, compared to CF recipients. In-hospital major complications more commonly affected CF LTx recipients (57% vs. 48%, p = .003), but 30-day mortality was higher in the non-CF group (9% non-CF vs. 5% CF, p < .001). One-, five-, and ten-year mortality was 18%, 50%, and 65% for CF recipients, respectively, and 21%, 45%, and 58% for non-CF recipients (p = .01 at 10 years). Five-year survival was significantly better for non-CF females versus CF females (56% vs. 48%, p = .013), but was similar between groups for males (55% vs. 54%, p = .305). While age was a late outcomes risk factor, pulmonary hypertension and later transplants eras were protective. CONCLUSIONS: Early mortality is higher and late mortality is lower in non-CF LTx. Current non-CF LTx outcomes leave room for improvement. Further study is needed to evaluate the effects of center volume and pediatric-specific experience on outcomes.

Anesthetic and Analgesic Influence on Cancer Recurrence and Metastasis.

Cancer is one of the leading causes of death in the United States. Total resection of tumors can be curative; however, investigators have speculated that inflammatory, metabolic, neuroendocrine, and immunologic changes that occur perioperatively may be promoted or induced by anesthetics. The influence of anesthetic choice on cancer recurrence and metastasis has yet to be definitively linked. Retrospective, animal model, and in vitro studies investigating volatile anesthetics, local anesthetics, and intravenous analgesics have resulted in contradicting findings. Results ranged from no association between type of anesthetic used and cancer recurrence, to immune-protective effects inhibiting tumor cell growth, or immune-suppressive effects promoting tumor cell growth or metastasis. It has yet to be confirmed whether volatile anesthetics, intravenous anesthetics, and analgesics are causal factors for cancer metastasis or recurrence. There are increasing data suggesting the immunosuppressant effects of anesthesia can be circumvented by avoiding opioids and volatile anesthetics. Further evaluation is required to determine the implications of regional anesthesia and propofolbased total intravenous anesthesia on cancer recurrence. Several ongoing randomized controlled trials are studying this link. Changes to clinical practice cannot definitively be recommended until the results of these studies can be examined.

A Systematic Review of Antibiotic Prophylaxis for Delayed Sternal Closure in Children.

Antibiotic prophylaxis following delayed sternal closure in pediatric cardiac surgery is not standardized. We systematically reviewed relevant literature published between 1990 and 2019 to aid future trial design. Patient characteristics, antimicrobial prophylaxis regimens, and postoperative incidence of infection were collected. Twenty-eight studies described 36 different regimens in over 3,000 patients. There were 11 single-drug regimens and 25 multidrug regimens. Cefazolin-only was the most common regimen (9/36, 25%). The overall incidence of surgical site infection was 7.5% (217/2,910 patients) and bloodstream infection was 7.4% (123/1,667 patients). In the 2010s, multidrug regimens were associated with a significantly lower incidence of both surgical site infections (4.6% vs. 20%, P < .001) and bloodstream infections (6.0% vs. 50%, P < .001) compared to single-drug regimens.

Surgery for Dysphagia Lusoria in Children.

Aberrant right subclavian artery, or arteria lusoria, is a common congenital anomaly of the aortic arch and may be associated with dysphagia. Surgical treatment, particularly in children, remains controversial. Current surgical interventions include supraclavicular and thoracotomy approaches, as well as hybrid endovascular techniques. However, these techniques have significant limitations and varying degrees of success. This case report describes a 2-site operation whereby the arteria lusoria is transected via a left thoracotomy and subsequently re-implanted into the right common carotid artery via a median sternotomy. This approach has provided complete symptom resolution for dysphagia lusoria in 2 children.

Clade X: A Pandemic Exercise.

Clade X was a day-long pandemic tabletop exercise conducted by the Johns Hopkins Center for Health Security on May 15, 2018, in Washington, DC. In this report, we briefly describe the exercise development process and focus principally on the findings and recommendations that arose from this project.

Outbreaks of Hepatitis A in US Communities, 2017-2018: Firsthand Experiences and Operational Lessons From Public Health Responses.

Objectives. To identify and analyze common challenges from multiple US communities affected by the hepatitis A epidemic beginning in March 2017, and to identify operational lessons to support preparedness for similar future public health emergencies.Methods. We conducted semistructured interviews with health officials from 9 city or county health departments to collect the firsthand experience of public health responders. We collected data from January to October 2018 via teleconference. Key informants, whom we purposefully sampled, were senior public health officials who were directly involved in outbreak response or in preparing for potential hepatitis A outbreaks in their communities.Results. Several themes emerged during these discussions, including common challenges and solutions pertaining to sanitation and hygiene infrastructure, hepatitis A vaccination, health workforce availability and surge capacity, communication and stigma, and partnerships and coordination with local law enforcement and other stakeholders.Conclusions. By generating key, evidence-based operational lessons, this study can inform response activities in localities currently experiencing outbreaks as well as community preparedness for possible future outbreaks due to the presence of similar at-risk populations.

ACVR1C/SMAD2 signaling promotes invasion and growth in retinoblastoma.

Retinoblastoma is the most common intraocular cancer in children. While the primary tumor can often be treated by local or systemic chemotherapy, metastatic dissemination is generally resistant to therapy and remains a leading cause of pediatric cancer death in much of the world. In order to identify new therapeutic targets in aggressive tumors, we sequenced RNA transcripts in five snap frozen retinoblastomas which invaded the optic nerve and five which did not. A three-fold increase was noted in mRNA levels of ACVR1C/ALK7, a type I receptor of the TGF-ß family, in invasive retinoblastomas, while downregulation of DACT2 and LEFTY2, negative modulators of the ACVR1C signaling, was observed in most invasive tumors. A two- to three-fold increase in ACVR1C mRNA was also found in invasive WERI Rb1 and Y79 cells as compared to non-invasive cells in vitro. Transcripts of ACVR1C receptor and its ligands (Nodal, Activin A/B, and GDF3) were expressed in six retinoblastoma lines, and evidence of downstream SMAD2 signaling was present in all these lines. Pharmacological inhibition of ACVR1C signaling using SB505124, or genetic downregulation of the receptor using shRNA potently suppressed invasion, growth, survival, and reduced the protein levels of the mesenchymal markers ZEB1 and Snail. The inhibitory effects on invasion, growth, and proliferation were recapitulated by knocking down SMAD2, but not SMAD3. Finally, in an orthotopic zebrafish model of retinoblastoma, a 55% decrease in tumor spread was noted (p = 0.0026) when larvae were treated with 3 µM of SB505124, as compared to DMSO. Similarly, knockdown of ACVR1C in injected tumor cells using shRNA also resulted in a 54% reduction in tumor dissemination in the zebrafish eye as compared to scrambled shRNA control (p = 0.0005). Our data support a role for the ACVR1C/SMAD2 pathway in promoting invasion and growth of retinoblastoma.

Evaluating the frequency of operational research conducted during the 2014-2016 West Africa Ebola epidemic.

INTRODUCTION: The West Africa Ebola epidemic of 2014-2016 was the largest Ebola outbreak on record, and thousands of individuals were involved in the response, including local and national governments, as well as numerous philanthropic and other non-governmental organizations. A number of after-action reports and other reviews of the global response to the epidemic routinely pointed out key challenges, including gaps in operational research. METHODS: To determine the extent to which operational research studies were conducted during the 2014-2016 West Africa Ebola epidemic, a quantitative analysis of the literature published during and immediately after the epidemic was conducted. The goal was to identify the proportion of all Ebola-related publications released regarding the epidemic that addressed operational aspects of the response. It was also sought to describe, at a general level, the sorts of studies that were published during the epidemic, with the goal of increasing understanding of whether additional efforts are needed to encourage the conduct and dissemination of operational studies during future public health crises. RESULTS: Among the 3681 publications on Ebola published between the World Health Organization announcement of the Ebola outbreak in March 2014 and the end of 2017, 109 (3%) were determined to be operational research publications. Among these, 64 (58%) were published after the World Health Organization initially declared the outbreak over on January 14, 2016, reflecting the time delay of sharing operational lessons with the broader preparedness and response community. DISCUSSION: Improved sharing of firsthand, operational knowledge from practitioners who respond to outbreaks is critical for improving preparedness activities and informing the development of sound, effective policies that support ongoing and future preparedness efforts. Based on the results from this review, we propose several policy and programmatic innovations that could facilitate knowledge sharing during future outbreaks.

Roles for Interleukin 17 and Adaptive Immunity in Pathogenesis of Colorectal Cancer.

Sporadic colorectal cancer is one of the most common and lethal cancers worldwide. The locations and functions of immune cells in the colorectal tumor microenvironment are complex and heterogeneous. T-helper (Th)1 cell-mediated responses against established colorectal tumors are associated with better outcomes of patients (time of relapse-free or overall survival), whereas Th17 cell-mediated responses and production of interleukin 17A (IL17A) have been associated with worse outcomes of patients. Tumors that develop in mouse models of colorectal cancer are rarely invasive and differ in many ways from human colorectal tumors. However, these mice have been used to study the mechanisms by which Th17 cells and IL17A promote colorectal tumor initiation and growth, which appear to involve their direct effects on colon epithelial cells. Specific members of the colonic microbiota may promote IL17A production and IL17A-producing cell functions in the colonic mucosa to promote carcinogenesis. Increasing our understanding of the interactions between the colonic microbiota and the mucosal immune response, the roles of Th17 cells and IL17 in these interactions, and how these processes are altered during colon carcinogenesis, could lead to new strategies for preventing or treating colorectal cancer.

Safety Assessment of Endovascular Treatment of Cerebral Aneurysms in Patients with Fibromuscular Dysplasia.

BACKGROUND: The prevalence of cerebral aneurysms is increased in fibromuscular dysplasia (FMD). The presence of FMD may serve as discouragement to elective endovascular aneurysm treatment. Outcomes of endovascular intervention for aneurysms through vessels affected by FMD have not been reported. METHODS: A prospectively maintained database of patients undergoing intracranial embolization was reviewed for patients with FMD who underwent endovascular aneurysm treatment. RESULTS: A total of 1,025 patients were screened and 31 (3.0%) had cerebrovascular FMD. These patients underwent a total of 43 embolization procedures; 27 of these procedures were performed through an affected vessel. All but 1 patient were female and the average age was 62 years. "String-of-pearls"-type FMD was the most common subtype (90%). The internal carotid arteries were more commonly affected (65%) than the vertebral arteries (48%). All patients underwent treatment of cerebral aneurysms, most of which (87%) were incidentally discovered; 6 patients (19%) also had incidental vessel dissection. The average aneurysm size was 7.1 mm. The morphology was saccular in 93% of the cases, and 86% were in the anterior circulation. The most commonly performed treatment was flow diversion (67%), in the majority of cases by pipeline embolization. Other procedures performed were coiling (19%), stent-coiling (12%), and intrasaccular flow disruption (2%). All but 1 procedure (98%) were successful. There were no major complications; 1 patient experienced a transient ischemic attack. Follow-up angiography was performed in 88% of the cases, without evidence for disease progression after treatment. The average time to last angiographic follow-up was 17 months (±13). CONCLUSIONS: Elective embolization of intracranial aneurysms can be performed safely through vessels affected by FMD.