Alta Bates Summit Medical Center

Background: Quality-of-life (OQL) is recognized as a proven benefit of atrial fibrillation (AF) ablation. The DEEP trial (NCT02393885) showed safety (6.7%) and efficacy (71.8%) of an epicardial-endocardial hybrid ablation (HA) approach with left atrial appendage exclusion (LAAE) for non-paroxysmal AF; results were consistent with two randomized trials comparing HA+LAAE to catheter ablation (CA). Limited data exist on QOL after HA+LAAE. Goal: To evaluate QOL changes from baseline to 12-months post-HA+LAAE in the DEEP trial. Methods: DEEP is a 17-site prospective, international, single arm trial. Key eligibility: adults with non-paroxysmal AF, left atrial diameter ≤5.5cm, failed class I/III anti-arrhythmic drugs, and ≤2 prior failed CA. Stage 1 was thoracoscopic radiofrequency epicardial ablation to isolate the pulmonary veins and left atrial posterior wall, and LAAE. Stage 2 was endocardial mapping and touchup ablation. QOL was measured via the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire at baseline and 12-months post-HA+LAAE. AFEQT yields scores from 0 to 100 (0 as complete disability and 100 as no disability) and includes an overall and four subscale scores. A 5-point AFEQT change is clinically important. Mean differences with 95% CIs were calculated; p-values are from paired t-tests. Results: Of 85 patients, 82 completed both baseline and 12-month AFEQT. The mean change in overall score was 30.1 ± 19.8 (95% CI: 25.8-34.5; median 29.5, min, max: -15.4, 78.2; p<0.0001) (Figure). The greatest improvement was in the Treatment Satisfaction subscale with a mean score of 53.2 ± 29.9 (95% CI: 46.6-59.7; median 58.3, min, max: 0.0, 100.0; p<0.0001), followed by Treatment Concern, Daily Activities, and Symptoms subscale scores. All mean improvements from baseline exceeded a clinically meaningful 5-point change. Conclusion: In the DEEP trial, HA+LAAE resulted in patient-reported QOL improvements at 12-months post-procedure.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disease caused by Aspergillus fumigatus (Af), prevalent in persons with cystic fibrosis (CF) or asthma. In ABPA, Af proteases drive a T-helper cell-2 (Th2)-mediated allergic immune response leading to inflammation that contributes to permanent lung damage. Corticosteroids and antifungals are the mainstays of therapies for ABPA. However, their long-term use has negative sequelae. The treatment of patients with CF (pwCF) has been revolutionized by the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Pharmacological improvement in CFTR function with highly effective elexacaftor/tezacaftor/ivacaftor (ETI) provides unprecedented improvements in lung function and other clinical outcomes of pwCF. The mechanism behind the improvement in patient outcomes is a continued topic of investigation as our understanding of the role of CFTR function evolves. As ETI therapy gains traction in CF management, understanding its potential impact on ABPA, especially on the allergic immune response pathways and Af infection becomes increasingly crucial for optimizing patient outcomes. This literature review aims to examine the extent of these findings and expand our understanding of the already published research focusing on the intersection between ABPA therapeutic approaches in CF and the rapid impact of the evolving CFTR modulator landscape. While our literature search yielded limited reports specifically focusing on the role of CFTR modulator therapy on CF-ABPA, findings from epidemiologic and retrospective studies suggest the potential for CFTR modulator therapies to positively influence pulmonary outcomes by addressing the underlying pathophysiology of CF-ABPA, especially by decreasing inflammatory response and Af colonization. Thus, this review highlights the promising scope of CFTR modulator therapy in decreasing the overall prevalence and incidence of CF-ABPA.

Background and AimsCrohn’s disease [CD] is a debilitating, inflammatory condition affecting the gastrointestinal tract. There is no cure and sustained clinical and endoscopic remission is achieved by fewer than half of patients with current therapies. The immunoregulatory function of the vagus nerve, the ‘inflammatory reflex’, has been established in patients with rheumatoid arthritis and biologic-naive CD. The aim of this study was to explore the safety and efficacy of vagus nerve stimulation in patients with treatment-refractory CD, in a 16-week, open-label, multicentre, clinical trial.MethodsA vagus nerve stimulator was implanted in 17 biologic drug-refractory patients with moderately to severely active CD. One patient exited the study pre-treatment, and 16 patients were treated with vagus nerve stimulation [4/16 receiving concomitant biologics] during 16 weeks of induction and 24 months of maintenance treatment. Endpoints included clinical improvement, patient-reported outcomes, objective measures of inflammation [endoscopic/molecular], and safety.ResultsThere was a statistically significant and clinically meaningful decrease in CD Activity Index at Week 16 [mean ± SD: -86.2 ± 92.8, p = 0.003], a significant decrease in faecal calprotectin [-2923 ± 4104, p = 0.015], a decrease in mucosal inflammation in 11/15 patients with paired endoscopies [-2.1 ± 1.7, p = 0.23], and a decrease in serum tumour necrosis factor and interferon-γ [46–52%]. Two quality-of-life indices improved in 7/11 patients treated without biologics. There was one study-related severe adverse event: a postoperative infection requiring device explantation.ConclusionsNeuroimmune modulation via vagus nerve stimulation was generally safe and well tolerated, with a clinically meaningful reduction in clinical disease activity associated with endoscopic improvement, reduced levels of faecal calprotectin and serum cytokines, and improved quality of life.

This chapter offers diverse images that provide an overview on diverticular disease of the colon and aims to provide a synopsis through pictures and illustrations rather than through text. Diverticular disease is the terminology used to describe asymptomatic diverticulosis, an often incidental finding. Clinical manifestations of diverticulosis include acute uncomplicated diverticulitis, symptomatic uncomplicated diverticular disease, segmental colitis associated with diverticulosis, and diverticular bleeding. Several factors contribute to the pathogenesis of diverticular disease, including structural and functional changes in the connective tissue, colonic motility with more phasic contractions, and alternations in the enteric nervous system with decreased neural density and increased fibrosis in the myenteric plexus. The diagnosis of diverticular disease usually requires endoscopic and radiological modalities, with computed tomography being the standard of care for the diagnosis.

Background and Objective: In Ethiopia, birth asphyxia causes ~30% of all neonatal deaths and 11–31% of deaths among neonates delivered in healthcare facilities that have breathing difficulty at birth. This study aimed to examine the impact of low-dose, high-frequency (LDHF) training for introducing a nurse-led neonatal advanced life support (NALS) service in a tertiary care hospital in Ethiopia.Methods: Through a retrospective cohort study, a total of 12,001 neonates born post-implementation of the NALS service (between June 2017 and March 2019) were compared to 2,066 neonates born before its implementation (between June 2016 and September 2016). Based on when the neonates were born, they were divided into six groups (groups A to F). All deliveries occurred in the inpatient Labor and Delivery Unit (LDU) at St. Paul's Hospital Millennium Medical College. The number of neonatal deaths in the LDU, neonatal intensive care unit (NICU) admission rate, and proportion of neonates with normal axillary temperature (36.5–37.5°C) within the first hour of life were evaluated. Data were analyzed using the χ2 test, and p-values < 0.05 were considered statistically significant. Following the implementation of the NALS service, semi-structured interviews with key stakeholders were conducted to evaluate their perception of the service; the interviews were recorded, transcribed, and coded for thematic analysis.Results: There was a decrease in the proportion of neonates who died in the LDU (from 3.5 to 1%) during the immediate post-implementation period, followed by a sustained decrease over the study period (p < 0.001). The change in the NICU admission rate (from 22.8 to 21.2%) was insignificant (p = 0.6) during this initial period. However, this was followed by a significant sustained decrease (7.8% in group E and 9.8% in group F, p < 0.001). The proportion of newborns with normal axillary temperature improved from 46.2% during the initial post-implementation period to 87.8% (p < 0.01); this proportion further increased to 99.8%. The program was perceived positively by NALS team members, NICU care providers, and hospital administrators.Conclusion: In resource-limited settings, LDHF training for neonatal resuscitation improves the neonatal resuscitation skills and management of delivery room attendants.

The Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification of diverticulosis and diverticular disease (DD) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement on this classification in an international endoscopists community setting. A total of 96 doctors (82.9% endoscopists) independently scored a set of DD endoscopic videos. The percentages of overall agreement on DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of interrater agreement. Overall agreement in using DICA was 91.8% with a free-marginal kappa of 88% (95% CI 80-95). The overall agreement levels were: DICA 1, 85.2%; DICA 2, 96.5%; DICA 3, 99.5%. The free marginal κ was: DICA 1 = 0.753, DICA 2 = 0.958, DICA 3 = 0.919. The agreement about the main endoscopic items was 83.4% (k 67%) for diverticular extension, 62.6% (k 65%) for number of diverticula for each district, 86.8% (k 82%) for presence of inflammation, and 98.5 (k 98%) for presence of complications. The overall interrater agreement in this study ranges from good to very good. DICA score is a simple and reproducible endoscopic scoring system for diverticulosis and DD.