Comparative diagnostic accuracy of EUS needles in solid pancreatic masses: a network meta-analysis.

Background and study aims Endoscopic ultrasound (EUS)-guided tissue sampling is the standard of care for diagnosing solid pancreatic lesions. While many two-way comparisons between needle types have been made in randomized controlled trials (RCTs), it is unclear which size and type of needle offers the best probability of diagnosis. We therefore performed a network meta-analysis (NMA) to compare different sized and shaped needles to rank the diagnostic performance of each needle. Methods We searched MEDLINE, EMBASE and Cochrane Library databases through August, 2020 for RCTs that compared the diagnostic accuracy of EUS fine-needle aspiration (FNA) and biopsy (FNB) needles in solid pancreatic masses. Using a random-effects NMA under the frequentist framework, RCTs were analyzed to identify the best needle type and sampling technique. Performance scores (P-scores) were used to rank the different needles based on pooled diagnostic accuracy. The NMA model was used to calculate pairwise relative risk (RR) with 95 % confidence intervals. Results Review of 2577 studies yielded 29 RCTs for quantitative synthesis, comparing 13 different needle types. All 22G FNB needles had an RR > 1 compared to the reference 22G FNA (Cook) needle. The highest P-scores were seen with the 22G Medtronic FNB needle (0.9279), followed by the 22G Olympus FNB needle (0.8962) and the 22G Boston Scientific FNB needle (0.8739). Diagnostic accuracy was not significantly different between needles with or without suction. Conclusions In comparison to FNA needles, FNB needles offer the highest diagnostic performance in sampling pancreatic masses, particularly with 22G FNB needles.

Graft-vs-Host Disease Colitis After Lung Transplant.

Graft-vs-host disease, characteristically a major complication of allogenic hematopoietic stem cell transplantation, is rare after solid organ transplantation. We report a 50-year-old man who presented with abdominal pain, vomiting, and diarrhea shortly after bilateral lung transplantation. Colonoscopy with biopsy revealed diffuse severe active colitis with ulceration and crypt apoptosis consistent with graft-vs-host disease colitis. The diagnosis was confirmed by the presence of donor lymphocytes in the peripheral blood. His symptoms were refractory to corticosteroids but responded to the addition of infliximab and extracorporeal photophoresis. He remained in remission 17 months later.

Factors Associated With Recurrence of Barrett's Esophagus After Radiofrequency Ablation.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) is effective treatment for Barrett's esophagus (BE). However, some patients have recurrence after complete eradication of intestinal metaplasia (CEIM). We investigated the incidence of and factors associated with BE recurrence, with or without neoplasia, after RFA and CEIM using data from the national Veterans Affairs (VA) healthcare system. METHODS: We performed a retrospective cohort study of Veterans with BE treated by RFA from 2005 through 2016 with follow-up endoscopy. Subjects were followed until BE recurrence, neoplasia, death until October 2016. CEIM, BE recurrence, and factors associated with recurrence were identified by review of medical records. We calculated incidence rates of BE recurrence, with and without neoplasia, after CEIM and identified predictors using Cox proportional hazards models. RESULTS: We identified 430 Veterans with BE who were treated with RFA; of these 337 achieved CEIM (78.4%). Most were men (98.6%), White (83.7%), and 66.0% had baseline dysplasia. Of those with CEIM, 98 patients (29.1%) had recurrence of BE during a total 906.0 patient-years of follow-up (median 1.9 years) after CEIM (incidence, 10.8%/patient-year). Dysplasia developed in 20 patients (2.2%/patient-year) and cancer in 3 patients (0.3%/patient-year). Baseline dysplasia (hazard ratio [HR], 1.71; 95% CI, 1.03-2.84) and long-segment BE (HR, 1.59; 95% CI, 1.01-2.51) increased risk of BE recurrence whereas treatment at high-volume RFA facilities reduced risk of BE recurrence (for quartile 4 vs quartile 1: HR, 0.19; 95% CI, 0.05-0.68). CONCLUSIONS: In a nationwide VA system study of outcomes of RFA for BE, we associated baseline dysplasia, long-segment BE, and treatment at low-volume RFA centers with recurrence of BE after CEIM. The findings call for performing these procedures in high-volume centers.

Fyn Kinase Regulates Microglial Neuroinflammatory Responses in Cell Culture and Animal Models of Parkinson's Disease.

Sustained neuroinflammation mediated by resident microglia is recognized as a key pathophysiological contributor to many neurodegenerative diseases, including Parkinson's disease (PD), but the key molecular signaling events regulating persistent microglial activation have yet to be clearly defined. In the present study, we examined the role of Fyn, a non-receptor tyrosine kinase, in microglial activation and neuroinflammatory mechanisms in cell culture and animal models of PD. The well-characterized inflammogens LPS and TNFα rapidly activated Fyn kinase in microglia. Immunocytochemical studies revealed that activated Fyn preferentially localized to the microglial plasma membrane periphery and the nucleus. Furthermore, activated Fyn phosphorylated PKCδ at tyrosine residue 311, contributing to an inflammogen-induced increase in its kinase activity. Notably, the Fyn-PKCδ signaling axis further activated the LPS- and TNFα-induced MAP kinase phosphorylation and activation of the NFκB pathway, implying that Fyn is a major upstream regulator of proinflammatory signaling. Functional studies in microglia isolated from wild-type (Fyn(+/+)) and Fyn knock-out (Fyn(-/-)) mice revealed that Fyn is required for proinflammatory responses, including cytokine release as well as iNOS activation. Interestingly, a prolonged inflammatory insult induced Fyn transcript and protein expression, indicating that Fyn is upregulated during chronic inflammatory conditions. Importantly, in vivo studies using MPTP, LPS, or 6-OHDA models revealed a greater attenuation of neuroinflammatory responses in Fyn(-/-) and PKCδ (-/-) mice compared with wild-type mice. Collectively, our data demonstrate that Fyn is a major upstream signaling mediator of microglial neuroinflammatory processes in PD. SIGNIFICANCE STATEMENT: Parkinson's disease (PD) is a complex multifactorial disease characterized by the progressive loss of midbrain dopamine neurons. Sustained microglia-mediated neuroinflammation has been recognized as a major pathophysiological contributor to chronic degenerative processes in PD; however, the key molecular signaling mechanisms underlying microglial activation are not entirely clear. Herein, we identified a novel role for the non-receptor tyrosine kinase Fyn in regulating neuroinflammatory responses in microglia. Our data clearly suggest that the Fyn-PKCδ signaling axis acts as a major upstream signaling mediator of the sustained neuroinflammatory processes in cell culture and animal models of PD. Our finding has important clinical significance to PD because it identifies Fyn as a potential translational target for intervention of progressive neurodegenerative processes in PD.