Xenophagy in Helicobacter pylori‐ and Epstein–Barr virus‐induced gastric cancer

Helicobacter pylori and Epstein–Barr virus (EBV) account for roughly 80% and 10%, respectively, of gastric carcinomas worldwide. Autophagy is an evolutionarily conserved and intricately regulated cellular process that involves the sequestration of cytoplasmic proteins and organelles into double‐membrane autophagosomes that eventually fuse with lysosomes for degradation of the engulfed content. Emerging evidence indicates that xenophagy, a form of selective autophagy, plays a crucial role in the pathogenesis of H. pylori‐ and EBV‐induced gastric cancer. Xenophagy specifically recognizes intracellular H. pylori and EBV and physically targets these pathogens to the autophagosomal–lysosomal pathway for degradation. In this connection, H. pylori or EBV‐induced dysregulation of autophagy may be causally linked to gastric tumourigenesis and therefore can be exploited as therapeutic targets. This review will discuss how H. pylori and EBV infection activate autophagy and how these pathogens evade recognition and degradation by the autophagic pathway. Elucidating the molecular aspects of H. pylori‐ and EBV‐induced autophagy will help us better understand the pathogenesis of gastric cancer and promote the development of autophagy modulators as antimicrobial agents. Published by John Wiley & Sons, Ltd     

Implementation of a novel population panel management curriculum among interprofessional health care trainees

Background

Gaps in chronic disease management have led to calls for novel methods of interprofessional, team-based care. Population panel management (PPM), the process of continuous quality improvement across groups of patients, is rarely included in health professions training for physicians, nurses, or pharmacists. The feasibility and acceptance of such training across different healthcare professions is unknown. We developed and implemented a novel, interprofessional PPM curriculum targeted to diverse health professions trainees.

Methods

The curriculum was implemented annually among internal medicine residents, nurse practitioner students and residents, and pharmacy residents co-located in a large, academic primary care site. Small groups of interprofessional trainees participated in supervised quarterly seminars focusing on chronic disease management (e.g., diabetes mellitus, hypertension, or chronic obstructive pulmonary disease) or processes of care (e.g., emergency department utilization for nonacute conditions or chronic opioid management). Following brief didactic presentations, trainees self-assessed their clinic performance using patient-level chart review, presented individual cases to interprofessional staff and faculty, and implemented subsequent feedback with their clinic team. We report data from 2011 to 2015. Program evaluation included post-session participant surveys regarding attitudes, knowledge and confidence towards PPM, ability to identify patients for referral to interprofessional team members, and major learning points from the session. Directed content analysis was performed on an open-ended survey question.

Results

Trainees (n?=?168) completed 122 evaluation assessments. Trainees overwhelmingly reported increased confidence in using PPM and increased knowledge about managing their patient panel. Trainees reported improved ability to identify patients who would benefit from multidisciplinary care or referral to another team member. Directed content analysis revealed that trainees viewed team members as important system resources (n?=?82).

Conclusions

Structured interprofessional training in PPM is both feasible and acceptable to trainees across multiple professions. Curriculum participants reported improved panel management skills, increased confidence in using PPM, and increased confidence in identifying candidates for interprofessional care. The curriculum could be readily exported to other programs and contexts.

     

Doppler echocardiographic measurement of pulmonary artery pressure from ductal Doppler velocities in the newborn

The ductal flow velocities in 37 newborns (group 1: persistent pulmonary hypertension [n = 16], transient tachypnea [n = 3], other [n = 2]; group 2: respiratory distress syndrome [n = 16]) were prospectively evaluated by Doppler ultrasound for the purpose of deriving systolic pulmonary artery pressures. Maximal tricuspid regurgitant Doppler velocity in 21 of these patients was used to validate the pulmonary artery pressures derived from ductal flow velocities. There was a significant linear correlation between tricuspid regurgitant Doppler velocity and pulmonary artery systolic pressure derived from ductal Doppler velocities in patients with unidirectional (pure left to right or pure right to left) ductal shunting (p less than 0.001, r = 0.95, SEE 8) and in those with bidirectional shunting (p less than 0.001, r = 0.95, SEE 4.5). Systolic pulmonary artery pressure in group 1 (67 +/- 13 mm Hg) was significantly higher than that in group 2 (39 +/- 10 mm Hg) (p less than 0.001). In those with bidirectional shunting, duration of right to left shunting less than 60% of systole was found when pulmonary artery pressure was systemic or less, whereas duration greater than or equal to 60% was associated with suprasystemic pulmonary artery pressures. Serial changes in pulmonary artery systolic pressure, reflected by changes in ductal Doppler velocities, correlated with clinical status in persistent pulmonary hypertension of the newborn. Persistently suprasystemic pulmonary artery pressure was associated with death in five group 1 patients. It is concluded that ductal Doppler velocities can be reliably utilized to monitor the course of pulmonary artery systolic pressures in newborns.     

Percutaneous cholecystostomy: an alternative to surgical cholecystostomy for acute cholecystitis?

Emergency percutaneous cholecystostomy was successfully performed in 39 of 40 attempted procedures in 37 hospitalized patients with possible acute cholecystitis. All cholecystostomies were performed with ultrasound guidance and preferentially with the transhepatic route, and all but four were performed at the patient's bedside. The patients had been hospitalized an average of 27 days before the procedure. Twenty-two of the 37 patients (59%) eventually died during hospitalization because of other medical or surgical problems. Only minor complications related to percutaneous cholecystostomy placement occurred in this series: catheter dislodgment without sequelae (n = 2) and significant abdominal pain (n = 2). Technical problems included guide-wire buckling during catheter insertion (n = 1) and failed attempted cholecystostomy (n = 1). Percutaneous cholecystostomy is a safe alternative to surgical cholecystostomy in the treatment of patients suspected of having acute cholecystitis.     

Factors Associated with Nodal Pathologic Complete Response Among Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Results of CALGB 40601 (HER2+) and 40603 (Triple-Negative) (Alliance)

Annals of Surgical Oncology - De-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) requires careful patient selection. We seek to determine predictors of nodal pathologic complete...     

Post‐mastectomy Radiotherapy for pT3N0 Breast Cancers: A Retrospective,Multi‐Institution Review

The role of post‐mastectomy radiotherapy for pT3N0 breast cancers remains undefined. The purpose of this study was to report institutional outcomes for women with pT3N0 breast cancers treated with and without post‐mastectomy radiotherapy. We collected data from two large tumor registries on pT3N0 breast cancers diagnosed between 1985 and 2014. Kaplan–Meier estimates were used to analyze freedom from local‐regional recurrence (FFLR), relapse free survival, and overall survival. This analysis identified 93 women with pT3N0 breast cancers. Of these, 53 received post‐mastectomy radiotherapy and 40 did not. Median follow‐up was 6.2 years and 5.3 years in the non‐post‐mastectomy radiotherapy and post‐mastectomy radiotherapy cohorts, respectively. Women not undergoing post‐mastectomy radiotherapy were more likely to be diagnosed in the 1980s and 1990s and were less likely to receive systemic therapies than women receiving post‐mastectomy radiotherapy (p < 0.05). There was a trend toward increased FFLR in the women receiving post‐mastectomy radiotherapy (p = 0.15). FFLR in the post‐mastectomy radiotherapy cohort was 98% at both 5 and 10 years. For women not receiving post‐mastectomy radiotherapy, FFLR was 88% at both 5 and 10 years. Women not receiving post‐mastectomy radiotherapy in our study had an isolated local‐regional failure rate of 12% at 10 years, despite receiving inferior systemic treatment by current standards. Local‐regional control after post‐mastectomy radiotherapy for pT3N0 breast cancers was excellent. Further research is needed to define post‐mastectomy radiotherapy indications for this patient population when receiving chemotherapy and endocrine therapy in line with current guidelines.