Citations

AbstractBackground/AimsInadequate bowel preparations can necessitate early repeat of colonoscopy and increased healthcare costs. Established risk factors for suboptimal bowel preparation are known, yet data are lacking in the specific subgroup of patients with decompensated cirrhosis. The primary aim of this study was to reduce inadequate bowel preparation rates in patients with decompensated cirrhosis undergoing evaluation for liver transplant via a quality improvement initiative targeting patient education.MethodsA total of 121 patients undergoing evaluation at our institution prior to implementation of the quality improvement initiative and 91 patients undergoing evaluation after implementation were included. The initiative was an educational intervention via a 6‐minute colonoscopy and split‐prep bowel preparation educational video during the initial liver transplantation evaluation visit for all patients with scheduled colonoscopy.ResultsInadequate bowel preparation was observed in 36 patients (29.8%) in the pre‐intervention period compared to 29 patients (31.9%) in the post‐intervention period. This corresponded to a lack of a significant difference in both single‐variable analysis and multivariable analysis. Of note, there was a significantly higher rate of inadequate bowel preparation as ascites worsened (P=.028).ConclusionPatient educational video failed to improve bowel preparations in patients undergoing colonoscopy with decompensated cirrhosis.

Goals: To perform an exploratory pilot study of all-trans retinoic acid (ATRA) combined with ursodeoxycholic acid (UDCA) in patients with primary sclerosing cholangitis (PSC). Background: PSC is a progressive disorder for which there is no accepted therapy. Studies in human hepatocyte cultures and in animal models of cholestasis indicate that ATRA might have beneficial effects in cholestatic disorders. Study: ATRA (45 mg/m2/d, divided and given twice daily) was combined with moderate-dose UDCA in patients with PSC who had incomplete response to UDCA monotherapy. The combination was administered for 12 weeks, followed by a 12-week washout in which patients returned to UDCA monotherapy. We measured alkaline phosphatase (ALP), alanine aminotransferase (ALT), bilirubin, cholesterol, bile acids, and the bile acid intermediate 7α-hydroxy-4-cholesten-3-one (C4) at baseline, week 12, and after washout. Results: Fifteen patients completed 12 weeks of therapy. The addition of ATRA to UDCA reduced the median serum ALP levels (277±211 to 243±225 U/L, P=0.09) although this, the primary endpoint, did not reach significance. In contrast, median serum ALT (76±55 to 46±32 U/L, P=0.001) and C4 (9.8±19 to 7.9±11 ng/mL, P=0.03) levels significantly decreased. After washout, ALP and C4 levels nonsignificantly increased, whereas ALT levels significantly increased (46±32 to 74±74, P=0.0006), returning to baseline. Conclusions: In this human pilot study, the combination of ATRA and UDCA did not achieve the primary endpoint (ALP); however, it significantly reduced ALT and the bile acid intermediate C4. ATRA appears to inhibit bile acid synthesis and reduce markers of inflammation, making it a potential candidate for further study in PSC (NCT 01456468).

ObjectiveTo systematically compare transthyretin with primary amyloid neuropathy to define their natural history and the underlying mechanisms for differences in phenotype and natural history.MethodsAll patients with defined amyloid subtype and peripheral neuropathy who completed autonomic testing and electromyography at Mayo Clinic Rochester between 1993 and 2013 were included. Medical records were reviewed for time of onset of defined clinical features. The degree of autonomic impairment was quantified using the composite autonomic severity scale. Comparisons were made between acquired and inherited forms of amyloidosis.ResultsOne hundred one cases of amyloidosis with peripheral neuropathy were identified, 60 primary and 41 transthyretin. Twenty transthyretin cases were found to have Val30Met mutations; 21 had other mutations. Compared to primary cases, transthyretin cases had longer survival, longer time to diagnosis, higher composite autonomic severity scale scores, greater reduction of upper limb nerve conduction study amplitudes, more frequent occurrence of weakness, and later non‐neuronal systemic involvement. Four systemic markers (cardiac involvement by echocardiogram, weight loss > 10 pounds, orthostatic intolerance, fatigue) in combination were highly predictive of poor survival in both groups.InterpretationThese findings suggest that transthyretin has earlier and greater predilection for neural involvement and more delayed systemic involvement. The degree and rate of systemic involvement is most closely related to prognosis. Ann Neurol 2016;80:401–411

Catheter Ablation for Atrial Arrhythmias in Patients With CABackgroundCardiac amyloidosis (CA) is associated with increased atrial arrhythmias risk. The efficacy/safety of catheter‐based ablation therapy in patients with CA has not been adequately assessed.Methods and ResultsAll diagnosed CA patients who underwent atrial arrhythmia ablation therapy from 1995 to 2015 were reviewed. Arrhythmia recurrence, NYHA symptoms, and mortality were recorded. A total of 26 patients with CA and atrial arrhythmias were included; there were 7 light‐chain (AL), 17 wild‐type transthyretin (ATTRwt), and 2 mutated transthyretin (ATTRm) amyloidosis patients in total. Of which 13 underwent atrial arrhythmia ablation (CA‐A) and 13 underwent AV nodal ablation (CA‐AVN). In the CA‐A group, there were: 3 with atrial fibrillation (AF); 6 with atrial flutter (AFL); 2 with AF/AFL; and 2 with atrial tachycardia (AT). One‐year and 3‐year recurrence‐free survival were 75% and 60%, respectively. NYHA symptom improvement 6 months postablation was observed in both CA‐A and CA‐AVN groups: 7/10 (70%) and 4/8 (50%), respectively. Eleven patients with CA died (8 in CA‐AVN group vs. 3 in CA‐A group).ConclusionsCatheter‐based ablation for patients with CA appears to provide important symptomatic relief. However, mortality from the underlying disease remains a significant issue for the amyloid light‐chain subtype.

Abstract Innate lymphoid cells (ILCs) are a new family of immune cells that play important roles in innate immunity in mucosal tissues, and in the maintenance of tissue and metabolic homeostasis. Recently, group 2 ILCs (ILC2s) were found to promote the development and effector functions of Th2-type CD4+ T cells by interacting directly with T cells or by activating dendritic cells, suggesting a role for ILC2s in regulating adaptive immunity. However, our current knowledge on the role of ILCs in humoral immunity is limited. In this study, we found that ILC2s isolated from the lungs of naive BALB/c mice enhanced the proliferation of B1- as well as B2-type B cells and promoted the production of IgM, IgG1, IgA, and IgE by these cells in vitro. Soluble factors secreted by ILC2s were sufficient to enhance B cell Ig production. By using blocking Abs and ILC2s isolated from IL-5–deficient mice, we found that ILC2-derived IL-5 is critically involved in the enhanced production of IgM. Furthermore, when adoptively transferred to Il7r−/− mice, which lack ILC2s and mature T cells, lung ILC2s promoted the production of IgM Abs to a polysaccharide Ag, 4-hydroxy-3-nitrophenylacetyl Ficoll, within 7 d of airway exposure in vivo. These findings add to the growing body of literature regarding the regulatory functions of ILCs in adaptive immunity, and suggest that lung ILC2s promote B cell production of early Abs to a respiratory Ag even in the absence of T cells.

AbstractBackgroundDiagnosis of suspected basal cell carcinoma (BCC) is typically confirmed with incisional biopsy before referral to final surgery.ObjectiveTo investigate the clinical confidence and accuracy of physicians making a diagnosis of BCC based on dermoscopic and reflectance confocal microscopy (RCM) features.MethodsThis study was designed as a simulation to determine the certainty and willingness to refer to surgery without previous biopsy confirmation of BCC. Study subjects were identified with suspected BCC. Dermoscopic and RCM lesion images were obtained before biopsy. Eight clinicians with various expertise levels blindly interpreted these images and chose among four hypothetical treatment options: definite BCC, refer directly to surgery without biopsy; other malignancy, perform biopsy for diagnosis; uncertain diagnosis, perform biopsy; benign, do not biopsy. Decisions for treatment were based on dermoscopic images alone and, subsequently, on dermoscopic and RCM images combined.ResultsThe sensitivity for referral to surgery without biopsy was 67.6% with the use of dermoscopy; the positive predictive value (PPV) was 97.0%. Adding RCM increased the sensitivity to 76.5% and the PPV to 98.6%.ConclusionsDermoscopy provides a high PPV for BCC. The addition of RCM to dermoscopy increases diagnostic sensitivity, particularly in less experienced dermoscopists. Physician behavior might be different if actual referrals were made for surgery without biopsy.