Cryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses.

Cryptosporidium infects gastrointestinal epithelium and is a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. There are no vaccines and no fully effective therapy available for the infection. Type II and III interferon (IFN) responses are important determinants of susceptibility to infection but the role for type I IFN response remains obscure. Cryptosporidium parvum virus 1 (CSpV1) is a double-stranded RNA (dsRNA) virus harbored by Cryptosporidium spp. Here we show that intestinal epithelial conditional Ifnar1-/- mice (deficient in type I IFN receptor) are resistant to C. parvum infection. CSpV1-dsRNAs are delivered into host cells and trigger type I IFN response in infected cells. Whereas C. parvum infection attenuates epithelial response to IFN-γ, loss of type I IFN signaling or inhibition of CSpV1-dsRNA delivery can restore IFN-γ-mediated protective response. Our findings demonstrate that type I IFN signaling in intestinal epithelial cells is detrimental to intestinal anti-C. parvum defense and Cryptosporidium uses CSpV1 to activate type I IFN signaling to evade epithelial antiparasitic response.

Elevations in End-Tidal CO 2 With CO 2 Use During Pediatric Endoscopy With Airway Protection: Is This Physiologically Significant?

BACKGROUND: Inflation of the gastrointestinal lumen is vital for proper visualization during endoscopy. Air, insufflated via the endoscope, is gradually being replaced with carbon dioxide (CO 2 ) in many centers, with the intention of minimizing post-procedural discomfort due to retained gas. Recent studies suggest that the use of CO 2 during pediatric esophagogastroduodenoscopy (EGD) with an unprotected airway is associated with transient elevations in exhaled CO 2 (end-tidal CO 2 , EtCO 2 ), raising safety concerns. One possible explanation for these events is eructation of insufflation gas from the stomach. OBJECTIVES: To distinguish eructated versus absorbed CO 2 by sampling EtCO 2 from a protected airway with either laryngeal mask airway (LMA) or endotracheal tube (ETT), and to observe for changes in minute ventilation (MV) to exclude hypoventilation events. METHODS: Double-blinded, randomized clinical trial of CO 2 versus air insufflation for EGD with airway protection by either LMA or ETT. Tidal volume, respiratory rate, MV, and EtCO 2 were automatically recorded every minute. Cohort demographics were described with descriptive characteristics. Variables including the percent of children with peak, transient EtCO 2 ≥ 60 mmHg were compared between groups. RESULTS: One hundred ninety-five patients were enrolled for 200 procedures. Transient elevations in EtCO 2 of ≥60 mmHg were more common in the CO 2 group, compared to the air group (16% vs 5%, P = 0.02), but were mostly observed with LMA and less with ETT. Post-procedure pain was not different between groups, but flatulence was reported more with air insufflation ( P = 0.004). CONCLUSION: Transient elevations in EtCO 2 occur more often with CO 2 than with air insufflation during pediatric EGD despite protecting the airway with an LMA or, to a lesser degree, with ETT. These elevations were not associated with changes in MV. Although no adverse clinical effects from CO 2 absorption were observed, these findings suggest that caution should be exercised when considering the use of CO 2 insufflation, especially since the observed benefits of using this gas were minimal.

Recurrent Gastrointestinal Bleed Due to Small Bowel Vascular Malformation in a Patient with Turner Syndrome Diagnosed with Surgically Assisted Push Enteroscopy.

BACKGROUND Obscure gastrointestinal bleeding accounts for approximately 5% of all cases of gastrointestinal bleeding and the most frequent site is the small bowel. Turner syndrome (TS) is a genetic disorder of the second X chromosome in females. The association between gastrointestinal vascular malformations and Turner syndrome has been described in some case reports. Vascular malformation in Turner's syndrome can vary from asymptomatic to severe recurrent GI bleeds, but data on diagnosis and management of these patients are lacking. CASE REPORT A 14-year-old girl with TS presented with recurrent symptomatic melena. The initial work-up included a negative upper endoscopy, negative bidirectional endoscopies, and a video capsule endoscopy (VCE) that demonstrated large amount of blood and small erythematous lesion in the small bowel without active bleeding, and a negative Meckel scan. CT angiography was remarkable for prominent left lower mesenteric blood vessels, and a single-balloon enteroscopy demonstrated prominent vasculature throughout the small bowel. A a clip was placed at the site of a questionable bleed. The patient underwent a surgically assisted push enteroscopy due to recurrent bleeding; findings were consistent with diffuse vascular malformations. She was started on tranexamic acid and later transitioned to estrogen therapy without further reports of GI bleeding, anemia, or adverse effects from treatment 6 months after initial presentation. CONCLUSIONS Small bowel bleeding can be life-threating, and evidence-based guidelines in children are needed. Turner syndrome is associated with gastrointestinal vascular malformations, and suspicion for this diagnosis should be high for these patients when presenting with gastrointestinal bleeding. Estrogen might be an effective therapy in TS adolescent patients in the setting of diffuse vascular malformations (DVM).

Pott's Puffy Tumor in an Inflammatory Bowel Disease Patient on Anti-TNF Therapy.

BACKGROUND Anti-TNF-alpha therapies were the first class of biologics to be used in treatment of moderate to severe IBD. Immunosuppression status that develops from using anti-TNF-a therapies increases the risk of serious and opportunistic infections. We present here a rare case of serious infection that developed in an IBD patient while on anti-TNF therapy. CASE REPORT Our patient was a 14-year-old boy with a history of chronic sinusitis and ulcerative colitis who had been on infliximab therapy for the last 3 years. He presented with facial swelling and worsening constant frontal headache. Imaging showed frontal scalp subgaleal abscess, mild frontal calvarial early osteomyelitis, bilateral preseptal cellulitis, and acute and chronic paranasal sinus disease. He was treated with intravenous antibiotics and underwent sinus surgery with incision and drainage of the forehead abscess. He recovered well and resumed his infliximab infusions 3 weeks after the surgery. CONCLUSIONS PPT is a serious complication of untreated sinusitis. IBD patients on biologics can have higher risk of developing such complications because of their decreased ability to fight infections. Although the risk of serious infections declines significantly after the first year of using biologics, physicians should keep a low threshold for investigating symptomatic patients for serious infections, as they require prompt intervention. Despite the potential complications from using biologics, the benefits of this therapy in IBD patients outweigh the risks.