Restoration of cardiac progenitor cells after myocardial infarction by self-proliferation and selective homing of bone marrow-derived stem cells

Tissue-specific progenitor cells contribute to local cellular regeneration and maintain organ function. Recently, we have determined that cardiac side-population (CSP) cells represent a distinct cardiac progenitor cell population, capable of in vitro differentiation into functional cardiomyocytes. The response of endogenous CSP to myocardial injury, however, and the cellular mechanisms that maintain this cardiac progenitor cell pool in vivo remain unknown. In this report we demonstrate that local progenitor cell proliferation maintains CSP under physiologic conditions, with little contribution from extracardiac stem cell sources. Following myocardial infarction in adult mice, however, CSP cells are acutely depleted, both within the infarct and noninfarct areas. CSP pools are subsequently reconstituted to baseline levels within 7 days after myocardial infarction, through both proliferation of resident CSP cells, as well as through homing of bone marrow-derived stem cells (BMC) to specific areas of myocardial injury and immunophenotypic conversion of BMC to adopt a CSP phenotype. We, therefore, conclude that following myocardial injury, cardiac progenitor cell populations are acutely depleted and are reconstituted to normal levels by both self-proliferation and selective homing of BMC. Understanding and enhancing such processes hold enormous potential for therapeutic myocardial regeneration.     

A critical review of the diagnosis and management of Barrett's esophagus: the AGA Chicago Workshop

BACKGROUND & AIMS: The diagnosis and management of Barrett's esophagus (BE) are controversial. We conducted a critical review of the literature in BE to provide guidance on clinically relevant issues. METHODS: A multidisciplinary group of 18 participants evaluated the strength and the grade of evidence for 42 statements pertaining to the diagnosis, screening, surveillance, and treatment of BE. Each member anonymously voted to accept or reject statements based on the strength of evidence and his own expert opinion. RESULTS: There was strong consensus on most statements for acceptance or rejection. Members rejected statements that screening for BE has been shown to improve mortality from adenocarcinoma or to be cost-effective. Contrary to published clinical guidelines, they did not feel that screening should be recommended for adults over age 50, regardless of age or duration of heartburn. Members were divided on whether surveillance prolongs survival, although the majority agreed that it detects curable neoplasia and can be cost-effective in selected patients. The majority did not feel that acid-reduction therapy reduces the risk of esophageal adenocarcinoma but did agree that nonsteroidal antiinflammatory drugs are associated with a cancer risk reduction and are of promising (but unproven) value. Participants rejected the notion that mucosal ablation with acid suppression prevents adenocarcinoma in BE but agreed that this may be an appropriate strategy in a subgroup of patients with high-grade dysplasia. CONCLUSIONS: Based on this review of BE, the opinions of workshop members on issues pertaining to screening and surveillance are at variance with published clinical guidelines.     

Enhancing Usability of Appointment Reminders: Qualitative Interviews of Patients Receiving Care in the Veterans Health Administration

BackgroundNo-shows are a persistent and costly problem in all healthcare systems. Because forgetting is a common cause of no-shows, appointment reminders are widely used. However, qualitative research examining appointment reminders and how to improve them is lacking.ObjectiveTo understand how patients experience appointment reminders as part of intervention development for a pragmatic trial of enhanced appointment reminders.DesignQualitative content analysisParticipantsTwenty-seven patients at a single Department of Veterans Affairs hospital and its satellite clinicsApproachWe conducted five waves of interviews using rapid qualitative analysis, in each wave continuing to ask veterans about their experience of reminders. We double-coded all interviews, used deductive and inductive content analysis to identify themes, and selected quotations that exemplified three themes (limitations, strategies, recommendations).Key ResultsInterviews showed four limitations on the usability of current appointment reminders which may contribute to no-shows: (1) excessive information within reminders; (2) frustrating telephone systems when calling in response to an appointment reminder; (3) missing or cryptic information about clinic logistics; and (4) reminder fatigue. Patients who were successful at keeping appointments often used specific strategies to optimize the usability of reminders, including (1) using a calendar; (2) heightening visibility; (3) piggybacking; and (4) combining strategies. Our recommendations to enhance reminders are as follows: (1) mix up their content and format; (2) keep them short and simple; (3) add a personal touch; (4) include specifics on clinic location and contact information; (5) time reminders based on the mode of delivery; and (6) hand over control of reminders to patients.ConclusionsAppointment reminders are vital to prevent no-shows, but their usability is not optimized for patients. There is potential for healthcare systems to modify several aspects of the content, timing, and delivery of appointment reminders to be more effective and patient-centered.Electronic supplementary materialThe online version of this article (10.1007/s11606-020-06183-5) contains supplementary material, which is available to authorized users.KEY WORDS: access to care, no-shows, missed appointments, reminder, military veterans     

Placental expression of soluble fms-like tyrosine kinase 1 is increased in singletons and twin pregnancies with intrauterine growth restriction

OBJECTIVE: Intrauterine growth restriction (IUGR) is characterized by decreased placental perfusion. Low oxygen has been shown to increase soluble fms-like tyrosine kinase 1 (sFlt-1) expression in the human placenta. The objective of this study was to examine sFlt-1 expression in different types of IUGR pregnancies, including early-onset severe cases characterized by abnormal umbilical and uterine artery Doppler and discordant IUGR twins in which the normal cotwin represents the optimal control because both placentas share the same uterine environment. PATIENTS: Placentas from four subgroups were collected: early severe IUGR with umbilical artery absent end diastolic flow (n = 19), small for gestational age with normal uterine and umbilical artery Doppler (n = 11), severely growth-restricted dichorionic and monochorionic twins with abnormal umbilical artery Doppler (n = 9), preeclamptic twins (n = 3), and age-matched normal singletons (n = 19) and twin controls (n = 8). RESULTS: Expression of sFlt-1 mRNA and protein was significantly increased in IUGR placentas compared with small for gestational age and normal control placentas. sFlt-1 expression levels were also significantly greater in the small IUGR twin placentas from discordant twin pregnancies compared with the normal cotwin. In preeclamptic twins, sFlt-1 expression was increased in only one of the two placentas. CONCLUSIONS: Our results demonstrate that sFlt-1 expression is increased in severe IUGR placentas with abnormal umbilical artery Doppler of singletons and also in discordant IUGR twins. Reduced placental perfusion may contribute to the increased expression of sFlt-1 in IUGR pregnancies. Our data are compatible with differential sFlt-1 expression in placentas from discordant twins.     

Jejunoileal transplantation

This study was designed to determine if extrinsic innervation and intrinsic neural continuity with the duodenum (neuroenteric physiologic pathways disrupted during intestinal transplantation) modulate the characteristics of interdigestive motor activity in the canine small bowel. Five dogs served as neurally intact controls (group 1) and 10 dogs (group 2) underwent a model of jejunal autotransplantation involvingin situ neural isolation of the jejunoileum. Fasting duodenal and jejunal motor activity was recorded on-line to a microcomputer using closely spaced duodenal and jejunal manometry catheters. Characteristics of global motor patterns, the migrating motor complex (MMC), and local motor patterns, including individual contractions and grouped clustered contractions, were determined. Neural isolation of the jejunoileum disrupted coordination of duodenal and jejunal phase III activity, increased the variability of cycling of the MMC, decreased the period of the jejunal MMC, and increased motility indices in the neurally isolated jejunum. In contrast, single pressure waves and clustered contractions in the neurally isolated jejunum were not altered significantly in incidence or direction, distance, or velocity of spread.In situ neural isolation of the jejunoileum leads to temporal dissociation of the MMC between the transplanted segment (jejunum) and the duodenum but does not appear to alter markedly the characteristics of local contractile activity as measured by individual or grouped contractions. The occurrence of interdigestive jejunal motor patterns and the local organization of individual and grouped small intestinal contractions are not controlled by extrinsic innervation or intrinsic neural continuity with the duodenum.     

Protocol driven palliative care consultation: Outcomes of the ENABLE CHF-PC pilot study

Background

Little has been reported about protocol-driven outpatient palliative care consultation (OPCC) for advanced heart failure (HF).

Impact of stent deployment procedural factors on long-term effectiveness and safety of sirolimus-eluting stents (final results of the multicenter prospective STLLR trial)

Drug-eluting stent failures were associated with various clinical factors. However, the clinical impact of stent deployment technique was unknown. This study was designed to evaluate the frequency and impact of suboptimal percutaneous coronary intervention on long-term outcomes of 1,557 patients treated with sirolimus-eluting stents (SESs) in 41 US hospitals. All steps of the interventional procedure were scrutinized by an independent core laboratory to determine the occurrence of geographic miss (GM). GM included longitudinal (LGM; injured or diseased segment not covered by SES) or axial GM (balloon-artery size ratio <0.9 or >1.3) mismatches. Patients with and without GM were stratified (GM vs no-GM group). Patients, investigators, and the independent clinical event adjudication committee were blind to study group assignments. The primary end point was 1-year target-vessel revascularization (TVR) rate. Incidences and predictors of GM and safety outcomes were secondary end points. GM occurred in 943 patients (66.5%): 47.6% had LGM, 35.2% had axial GM, and 16.5% had both. One-year TVR rates were 5.1% in the GM group versus 2.5% in the no-GM group (p=0.025). TVR was 6.1% in the LGM versus 2.6% in the no-LGM subgroups (p=0.001). The association of GM with 1-year TVR was independent of clinical or anatomic factors (hazard ratio 2.0, 95% confidence interval 1.0 to 4.02, p=0.05). There was a 3-fold increase in myocardial infarction rates associated with GM (2.4% vs 0.8%; p=0.04). In conclusion, GM occurred frequently during SES implantation and was associated with increased risk of TVR and myocardial infarction at 1 year. These results emphasized the need for improvement in contemporary percutaneous coronary intervention practices and technologies.     

Anxiety and depression after coronary artery bypass graft surgery: most get better, some get worse

BACKGROUND: To target interventions, patients at risk for poor outcomes after a cardiac event need to be identified. We investigated trajectories of anxiety and depression after coronary artery bypass graft surgery (CABGS) and identified patients at risk of persistent or worsening anxiety and depression. METHODS: A consecutive sample of 184 patients on the waiting list for CABGS at The Royal Melbourne Hospital completed self-report questionnaires before surgery, and at 2 and 6 months postsurgery. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Growth mixture modelling identified trajectories of anxiety and depression. RESULTS: Two possible trajectories emerged for anxiety, whereas three trajectories emerged for depression. Most patients (92%) followed a trajectory of minor presurgical anxiety that remitted in 6 months after CABGS, with the remainder (8%) following a trajectory of major anxiety that remitted in the same period. Minor remitted depression was also common (72% patients). Two less common depression trajectories indicated worsening or unresolved depression. One trajectory began with major presurgical depression that partially remitted by 6 months (14% patients) and the other began with minor presurgical depression that worsened by 6 months (14% patients). Unpartnered patients, smokers, those with presurgical anxiety, high cholesterol, angina, more severe disease or having repeat CABGS were at increased risk for a poor depression trajectory. CONCLUSION: Although initial anxiety and depression resolved or lessened for most patients, some patients experienced persistent or worsening depression after CABGS. Interventions can be targeted toward 'at risk' patients.     

Perioperative bridging therapy with unfractionated heparin or low-molecular-weight heparin in patients with mechanical prosthetic heart valves on long-term oral anticoagulants (from the REGIMEN Registry)

Patients with mechanical prosthetic heart valves require long-term oral anticoagulant therapy (OAT). During the temporary interruption of OAT, bridging anticoagulant therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) is recommended. This prespecified subgroup analysis from REGIMEN-a large, prospective, multicenter registry-compared UFH (n = 73) and LMWH (n = 172) as bridging anticoagulation in patients with mechanical heart valves on long-term OAT. Patient demographics and co-morbidities were generally similar between groups. There were more bileaflet valves in the LMWH group (67.4% vs 43.8%, p = 0.0005), but no differences in valve positions between groups. The LMWH group was less likely to undergo major surgery (33.7% vs 58.9%, p = 0.0002) and cardiothoracic surgery (7.6% vs 19.2%, p = 0.008), and to receive intraprocedural anticoagulants or thrombolytics (4.1% vs 13.7%, p = 0.007). Major adverse event rates (5.5% vs 10.3%, p = 0.23) and major bleeds (4.2% vs 8.8%, p = 0.17) were similar in the LMWH and UFH groups, respectively; 1 arterial thromboembolic event occurred in each group. More LMWH-bridged patients were treated as outpatients or discharged from the hospital in <24 hours (68.6% vs 6.8%, p <0.0001). Multivariate logistic analysis found no significant differences in major bleeds and major composite adverse events when adjusting for cardiothoracic or major surgery between groups. In conclusion, for patients with mechanical prosthetic heart valves on long-term OAT, mostly outpatient-based LMWH bridging therapy appears to be feasible for selected procedures, is as safe as UFH, and is associated with a low arterial thromboembolic rate.