Juvenile dermatomyositis resembling late-stage Degos disease with gastrointestinal perforations successfully treated with combination of cyclophosphamide and rituximab: case-based review.

Dermatomyositis (DM) is a multi-system disease that results in chronic inflammation principally of the skin and striated muscle. Small blood vessel injury in the GI tract has been described in dermatomyositis, manifesting as bleeding, ulceration, pneumatosis intestinalis, and ultimately perforation. Recent histopathological studies have shown deposits in the capillaries of the skin, gastrointestinal tract, and brain of patients with dermatomyositis similar to that found in patients with Degos disease, suggesting these disease processes are closely related or represent varying degrees of severity on the same pathologic spectrum. We report a case of juvenile dermatomyositis (JDM) resembling late-stage Degos disease with gastrointestinal perforations successfully treated with combination rituximab and cyclophosphamide therapy. We systematically reviewed the literature detailing the medical and surgical treatments for gastrointestinal perforation in dermatomyositis, Degos-like dermatomyositis, and Degos disease. In addition to our case, as of October 2019, we identified 36 cases describing gastrointestinal perforation in patients with underlying dermatomyositis, 5 cases of Degos-like dermatomyositis and 17 cases of idiopathic Degos disease. Corticosteroid therapy was used widely for dermatomyositis and Degos-like dermatomyositis, while antiplatelet and anticoagulant medications were chiefly used for patients with idiopathic Degos disease. However, there were no cases that detailed the successful treatment of dermatomyositis or Degos disease with gastrointestinal perforation with rituximab alone or combined with cyclophosphamide. We report that rituximab, in combination with cyclophosphamide, can be used as a novel adjunctive therapy to successfully treat dermatomyositis with Degos-like gastrointestinal perforation.

Implementing a Novel Quality Improvement-Based Approach to Data Quality Monitoring and Enhancement in a Multipurpose Clinical Registry.

OBJECTIVE: To implement a quality improvement based system to measure and improve data quality in an observational clinical registry to support a Learning Healthcare System. DATA SOURCE: ImproveCareNow Network registry, which as of September 2019 contained data from 314,250 visits of 43,305 pediatric Inflammatory Bowel Disease (IBD) patients at 109 participating care centers. STUDY DESIGN: The impact of data quality improvement support to care centers was evaluated using statistical process control methodology. Data quality measures were defined, performance feedback of those measures using statistical process control charts was implemented, and reports that identified data items not following data quality checks were developed to enable centers to monitor and improve the quality of their data. PRINCIPAL FINDINGS: There was a pattern of improvement across measures of data quality. The proportion of visits with complete critical data increased from 72 percent to 82 percent. The percent of registered patients improved from 59 percent to 83 percent. Of three additional measures of data consistency and timeliness, one improved performance from 42 percent to 63 percent. Performance declined on one measure due to changes in network documentation practices and maturation. There was variation among care centers in data quality. CONCLUSIONS: A quality improvement based approach to data quality monitoring and improvement is feasible and effective.

Spinal cord astrocytoma: a unique presentation of abdominal pain.

A previously healthy male presented at age 5 years with recurrent abdominal pain that occurred diffusely. The pain was severe enough to cause episodic screaming, especially at night with spontaneous resolution. The patient was initially treated for constipation but when motor symptoms began to develop, imaging revealed the cause of his pain to be a spinal cord mass. The tumor was treated with steroids, and biopsy confirmed a grade II spinal cord astrocytoma. We describe this unusual presentation of a pediatric spinal cord astrocytoma and review the literature.

Management of Acute Pancreatitis in the Pediatric Population: A Clinical Report From the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas Committee.

BACKGROUND: Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed. METHODS: The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed. The authorship met to discuss the evidence, statements, and voted on recommendations. A consensus of at least 75% was required to approve a recommendation. RESULTS: The diagnosis of pediatric AP should follow the published INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE definitions (by meeting at least 2 out of 3 criteria: (1) abdominal pain compatible with AP, (2) serum amylase and/or lipase values ≥3 times upper limits of normal, (3) imaging findings consistent with AP). Adequate fluid resuscitation with crystalloid appears key especially within the first 24 hours. Analgesia may include opioid medications when opioid-sparing measures are inadequate. Pulmonary, cardiovascular, and renal status should be closely monitored particularly within the first 48 hours. Enteral nutrition should be started as early as tolerated, whether through oral, gastric, or jejunal route. Little evidence supports the use of prophylactic antibiotics, antioxidants, probiotics, and protease inhibitors. Esophago-gastro-duodenoscopy, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography have limited roles in diagnosis and management. Children should be carefully followed for development of early or late complications and recurrent attacks of AP. CONCLUSIONS: This clinical report represents the first English-language recommendations for the management of pediatric AP. Future aims should include prospective multicenter pediatric studies to further validate these recommendations and optimize care for children with AP.

Gastrointestinal considerations related to youth sports and the young athlete.

Young athletes, though often healthy, can carry a variety of symptoms that may impede their participation in sports or other activities. Typically we might think of musculoskeletal and respiratory problems primarily, however disorders of the gastrointestinal (GI) tract must also be considered. In some instances musculoskeletal complaints may bring to light activity of an underlying GI condition as is the case with inflammatory bowel disease. Gastrointestinal symptoms in the young athlete can be quite significant and a nuisance for participation. We aim to describe and discuss treatment options of a few conditions targeted specifically for your young athlete both that arise specifically from athletic participation and those GI disorders that are chronic in nature whose presence must not be neglected in the athlete.

Engineering Structurally Interacting RNA (sxRNA).

RNA-based three-way junctions (3WJs) are naturally occurring structures found in many functional RNA molecules including rRNA, tRNA, snRNA and ribozymes. 3WJs are typically characterized as resulting from an RNA molecule folding back on itself in cis but could also form in trans when one RNA, for instance a microRNA binds to a second structured RNA, such as a mRNA. Trans-3WJs can influence the final shape of one or both of the RNA molecules and can thus provide a means for modulating the availability of regulatory motifs including potential protein or microRNA binding sites. Regulatory 3WJs generated in trans represent a newly identified regulatory category that we call structurally interacting RNA or sxRNA for convenience. Here we show that they can be rationally designed using familiar cis-3WJ examples as a guide. We demonstrate that an sxRNA "bait" sequence can be designed to interact with a specific microRNA "trigger" sequence, creating a regulatable RNA-binding protein motif that retains its functional activity. Further, we show that when placed downstream of a coding sequence, sxRNA can be used to switch "ON" translation of that sequence in the presence of the trigger microRNA and the amount of translation corresponded with the amount of microRNA present.

Anti-TNFα therapy for inflammatory bowel diseases is associated with Epstein-Barr virus lytic activation.

Anti-TNFα therapy, known to suppress T-cell immunity, is increasingly gaining popularity for treatment of autoimmune diseases including inflammatory bowel diseases (IBD). T-cell suppression increases the risk of B-cell EBV-lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is essential for development of EBV-lymphomas and there have been reports of EBV-lymphomas in patients treated with anti-TNFα therapy, we investigated if patients treated with anti-TNFα antibodies demonstrate greater EBV-lytic activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely on anti-TNFα therapy compared to 3 control groups (10 IBD patients not on immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and 10 healthy subjects) were examined for the percentage of T-cells, EBV load and EBV-lytic transcripts. Patients on anti-TNFα therapy had significantly fewer T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic genes of all kinetic classes compared to controls. Furthermore, exposure of EBV-infected B-cell lines to anti-TNFα antibodies resulted in increased levels of BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch. Thus, IBD patients treated with anti-TNFα antibodies have greater EBV loads likely due to enhanced EBV-lytic gene expression and anti-TNFα antibodies may be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay the groundwork for additional scientific and clinical investigation into the effects of anti-TNFα therapy on the life cycle of EBV, a ubiquitous oncovirus that causes lymphomas in the setting of immunocompromise.

Response to mercaptopurine for refractory autoimmune cytopenias in children.

BACKGROUND: Several treatment strategies are available for children with severe immune thrombocytopenic purpura (ITP) and other immune cytopenias refractory to initial therapies. 6-Mercaptopurine (6MP) is one option, however it has not been well studied in children, especially as a single agent, and no pediatric case series have been reported since 1970. PATIENTS AND METHODS: We reviewed the experience at our institution over 8 years, using 6MP as a steroid sparing treatment for children with ITP, auto-immune hemolytic anemia (AIHA) or Evans syndrome. A total of 29 pediatric patients were treated with 6MP from 2000 to 2007. RESULTS: Response was defined as a rise in hemoglobin by at least 1.5 g/dl and to a level of 10 g/dl or greater in patients treated for anemia, or a platelet count >or=50 x 10(9)/L in patients treated for thrombocytopenia. We found an overall response rate of 83% among all patients. Fourteen percent of patients stopped drug because of side effects. CONCLUSIONS: These results suggest that 6MP can be an effective single-agent treatment for refractory immune cytopenias in children. Prospective studies are warranted to determine long-term efficacy and toxicity and to more clearly define patient populations most likely to respond.