Primary Atriopathy in Mitral Valve Prolapse: Echocardiographic Evidence and Clinical Implications.

BACKGROUND: Prominent multi-scallop systolic leaflet displacement toward the left atrium (atrialization) is typically observed in bileaflet mitral valve prolapse (MVP) with mitral annular disjunction. We hypothesized that mitral leaflet atrialization is associated with an underlying left atrial (LA) myopathy characterized by progressive structural and functional abnormalities, irrespective of mitral regurgitation (MR) severity. METHODS: We identified 334 consecutive patients with MVP, no prior atrial fibrillation, and comprehensive clinical and echocardiographic data. LA function was assessed by LA reservoir strain, LA function index, and LA emptying fraction. We also classified the stage of LA remodeling based on LA enlargement and LA reservoir strain (stage 1: no remodeling; stage 2: mild remodeling; stage 3: moderate remodeling; and stage 4: severe remodeling). The primary end point was the composite risk of sudden arrhythmic death, heart failure hospitalization, or the new onset of atrial fibrillation. RESULTS: Bileaflet MVP with no or mild MR had a lower LA reservoir strain (P=0.04) and LA function index (P<0.001) compared with other MVP subtypes. In multivariable linear regression adjusted for cardiovascular risk factors and MR ≥moderate, bileaflet MVP remained significantly associated with lower LA function parameters (all P<0.05). There was a significant increase in the risk of events as the LA reservoir strain and LA remodeling stage increased (P<0.001). In multivariable analysis, stage 4 of LA remodeling remained significantly associated with a higher risk of events compared with stage 1 (hazard ratio, 6.09 [95% CI, 1.69-21.9]; P=0.006). CONCLUSIONS: In a large MVP registry, bileaflet involvement is associated with reduced LA function regardless of MR severity, suggesting a primary atriopathy in this MVP subtype. Abnormal LA function, particularly when assessed through a multiparametric approach, is linked to a higher risk of cardiovascular events and may improve risk stratification in MVP, even in those without significant MR.

Promoting interprofessional student outcomes through the narrative of an opioid use disorder survivor.

The inappropriate use of opioids is a national concern. Experts suggest a multifaceted, collaborative practice approach to reduce mortality rates in complex healthcare issues is effective. Before practice, students require education to address the development of interprofessional (IP) skills. The purpose of this mixed-methods cohort study was to identify changes in student self-perceived value of IP socialization skills and to explore student perceptions of IP engagement in the context of the opioid crisis, before and after a combined IP panel and focus group discussion using a healthcare professional's journey from addiction into recovery. Thirty-three pre-licensure healthcare students in Schools of Counseling, Nursing, Occupational Therapy, Pharmacy, and Physical Therapy assessed their IP experience using the Interprofessional Socialization and Valuing Scale (ISVS). The IP event included interactive discussions with a panel of healthcare providers, a pharmacist in recovery from opioid use disorder, and a local prescription drug awareness and prevention advocate. Significant differences occurred between pre and post ISVS scores in the perceived value of IP collaborative work. Results from the qualitative analysis revealed a need for student-driven self-reflection before the discussions evolved to address the perspectives of future practitioner, the patient, and the healthcare system. Creating a real-time, face-to-face interaction with a panel of healthcare practitioners, an opioid survivor in concert with a local prescription drug prevention advocate may be an effective means toward improving teaching IP value and progressing student outcomes toward IP skill attainment.

Favorable outcomes with de-escalated radiation therapy for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma.

Radiation fields for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have shrunk over time; involved-site radiation therapy (ISRT) has replaced extended-field radiation therapy (EFRT) and involved-field radiation therapy (IFRT), but this has not been validated. The role of systemic therapy is unclear. We reviewed 71 stage I/II NLPHL patients and assessed progression-free survival (PFS), overall survival (OS), locoregional disease-free survival, and distant disease-free survival (DDFS). Median patient age was 39 years, and 61% had stage II disease. Thirty-six (51%) received radiation therapy (RT) only, 6 (8%) received systemic therapy only, and 29 (41%) received both. More patients receiving combined therapy had B symptoms (P = .035) and stage II disease (P = .001). In the RT-only group, 9 (25%) received EFRT, 13 (36%) received IFRT, and 14 (39%) received ISRT; in the combined-modality group, 3 (10%) received EFRT, 7 (24%) received IFRT, and 19 (66%) received ISRT. After a median follow-up of 6.2 years, 15 patients relapsed (13 distant, 2 locoregional). Five-year PFS and OS rates were 86% and 96% and did not differ by treatment. In the RT-only group, follow-up was shorter in the ISRT cohort (2.6 years vs 17.9 years [EFRT] and 8.5 years [IFRT], P < .01), but 5-year PFS did not differ by field size (P = .20). Locoregional control rates were 100% for the RT-only and combined groups, and corresponding 5-year DDFS rates were 93% and 95% (P = .95). Eight patients (11%) experienced a second malignancy (1 within RT field). Six patients died (1 from lymphoma). Use of limited ISRT fields does not appear to increase the risk of locoregional relapse, even when RT is given as single-modality therapy.

Encouraging activity for R-CHOP in advanced stage nodular lymphocyte-predominant Hodgkin lymphoma.

Nodular lymphocyte Hodgkin lymphoma (NLPHL) is a rare disease for which the optimal therapy is unknown. We hypothesized that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) could decrease rates of relapse and transformation. We retrospectively reviewed patients with NLPHL diagnosed between 1995 and 2015 confirmed by central pathologic review. Fifty-nine had sufficient treatment and follow-up data for analysis. We described progression-free survival (PFS), overall survival (OS), and histologic transformation according to treatment strategy and explored prognostic factors for PFS and OS. The median age at diagnosis was 41 years; 75% were male, and 61% had a typical growth pattern. Twenty-seven patients were treated with R-CHOP with an overall response rate of 100% (complete responses 89%). The median follow-up was 6.7 years, and the estimated 5- and 10-year PFS rates for patients treated with R-CHOP were 88.5% (95% confidence interval [CI], 68.4% to 96.1%) and 59.3 (95% CI, 25.3% to 89.1%), respectively. Excluding patients with histologic transformation at diagnosis, the 5-year cumulative incidence of histologic transformation was 2% (95% CI, 87% to 100%). No patient treated with R-CHOP experienced transformation. A high-risk score from the German Hodgkin Study Group was adversely prognostic for OS (P = .036), whereas male sex and splenic involvement were adversely prognostic for PFS (P = .006 and .002, respectively) but not OS. Our data support a potential role for R-CHOP in patients with NLPHL. Larger prospective trials are needed to define the optimal chemotherapy regimen.

Muscle Viability Revisited: Are We Removing Normal Muscle? A Critical Evaluation of Dogmatic Debridement.

PURPOSE: Determination of muscle viability during debridement is a subjective process with significant consequences. Evaluating muscle color, consistency, contractility, and capacity to bleed (the 4 Cs) was established by a study performed half a century ago. This work reinvestigates the utility of the 4 Cs using current histopathologic techniques. METHODS: After institutional review board approval, 36 biopsies were prospectively collected at a level-1 trauma center from 20 patients undergoing a debridement for open fracture (81%), compartment syndrome (11%), infection (5%), or crush injury (3%). Surgeons graded the biopsies using the 4 Cs, and provided their overall impression as healthy, borderline, or dead. Blinded pathological analysis was performed on each specimen. A correlation between the 4 Cs and surgeon impression with histopathological diagnosis was sought through a univariate statistical analysis. RESULTS: The surgeon's impression was dead muscle in 25 specimens, borderline in 10, and healthy in 1. Pathological analysis of the 35 specimens considered as dead or borderline muscle by the surgeon demonstrated normal muscle or mild interstitial inflammation in 21 specimens (60%). Color (P = 0.07), consistency (P = 0.12), contractility (P = 0.51), capacity to bleed (P = 0.07), and surgeon impression (P = 0.50) were unable to predict histologic appearance. CONCLUSIONS: Neither the 4 Cs nor the surgeon's impression correlate with histological findings regarding muscle viability. In 72% of specimens, the treating surgeon's gross assessment differed from the histopathologic appearance. Although the fate of the debrided muscle remains unclear if left in situ, these results raise questions regarding current practices, including the possibility that surgeons are debriding potentially viable muscle. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Cell lineage distribution atlas of the human stomach reveals heterogeneous gland populations in the gastric antrum.

OBJECTIVE: The glands of the stomach body and antral mucosa contain a complex compendium of cell lineages. In lower mammals, the distribution of oxyntic glands and antral glands define the anatomical regions within the stomach. We examined in detail the distribution of the full range of cell lineages within the human stomach. DESIGN: We determined the distribution of gastric gland cell lineages with specific immunocytochemical markers in entire stomach specimens from three non-obese organ donors. RESULTS: The anatomical body and antrum of the human stomach were defined by the presence of ghrelin and gastrin cells, respectively. Concentrations of somatostatin cells were observed in the proximal stomach. Parietal cells were seen in all glands of the body of the stomach as well as in over 50% of antral glands. MIST1 expressing chief cells were predominantly observed in the body although individual glands of the antrum also showed MIST1 expressing chief cells. While classically described antral glands were observed with gastrin cells and deep antral mucous cells without any parietal cells, we also observed a substantial population of mixed type glands containing both parietal cells and G cells throughout the antrum. CONCLUSIONS: Enteroendocrine cells show distinct patterns of localisation in the human stomach. The existence of antral glands with mixed cell lineages indicates that human antral glands may be functionally chimeric with glands assembled from multiple distinct stem cell populations.

Ovarian tumor-derived ectopic hyperprolactinemia.

To describe extreme hyperprolactinemia originating from a pituitary adenoma in the wall of an ovarian dermoid. This is a description of an unusual case and a review of ectopic prolactin production. Ectopic production of prolactin is a rare condition that has been reported in isolated organ system pathology including ovaries. An ovarian dermoid is a benign neoplasm that has the potential for active unregulated endocrine function. Hyperprolactinemia can result from functioning lactotrophs found in ovarian dermoids and can lead to clinical sequelae. Definitive treatment of the condition requires surgical removal of the functioning endocrine tissue. Extreme hyperprolactinemia caused by a pituitary tumor located within a dermoid has not been reported before. We present a case of profound hyperprolactinemia originating from a pituitary adenoma found in the wall of an ovarian dermoid and give a broad overview of the condition and literature. Ectopic prolactin production should always be considered in symptomatic patients found to have elevated serum levels and no findings on brain imaging.

Distinguishing Ménétrier's disease from its mimics.

OBJECTIVE: Ménétrier's disease (MD) is a rare hypertrophic gastropathy characterised by giant rugal folds, hypochlorhydria, protein loss and a classic constellation of symptoms (nausea, vomiting, abdominal pain and peripheral oedema). It is considered a clinical diagnosis that may at times be difficult to establish. Firm diagnostic criteria for MD are proposed by delineating the clinicopathological features that best differentiate MD from its mimics. METHOD: 48 patients referred to Vanderbilt University Medical Center for consideration of enrolment in a clinical trial of treatment of patients with MD with cetuximab were evaluated for a definitive diagnosis by assessing the clinical presentation, pertinent laboratory values and histopathological features. RESULTS: MD was confirmed in 25 of the 48 patients (52%). The remaining 23 patients were considered to be mimics of MD, the most common diagnoses being gastric polyps or polyposis syndromes (13/23, 57%). Gastric slides were available from 40 of the 48 patients for detailed histological analysis (22/25 MD and 18/23 non-MD). Foveolar hyperplasia, glandular tortuosity and dilation, and a marked reduction in parietal cell number were present in all 22 cases of MD. Lamina propria smooth muscle hyperplasia and oedema characterised most cases (18/22 and 19/22, respectively). More than half had prominent eosinophils (11/22) and/or plasma cells (12/22) in the lamina propria. The clinical presentation of patients with MD was characterised by significantly younger age of onset, male predominance and increased vomiting compared with non-MD patients, and a lower prevalence of anaemia compared with MD patients with polyps. There was a trend towards increased frequency of peripheral oedema in patients with MD compared with non-MD patients. CONCLUSIONS: MD is most accurately diagnosed by clinicohistopathological analysis including oesophagogastroduodenoscopy with gastric pH, appropriate laboratory tests (complete blood count, serum albumin, serum gastrin, Helicobacter pylori and cytomegalovirus serology) and full-thickness mucosal biopsy of the involved gastric mucosa.

A randomized outpatient trial of a decision-support information technology tool.

BACKGROUND: Decision-support information technology is often adopted to improve clinical decision making, but it is rarely rigorously evaluated. Congress mandated the evaluation of Problem-Knowledge Couplers (PKC Corp, Burlington, Vt), a decision-support tool proposed for the Department of Defense's new health information network. METHODS: This was a patient-level randomized trial conducted at 2 military practices. A total of 936 patients were allocated to the intervention group and 966 to usual care. Couplers were applied before routine ambulatory clinic visits. The primary outcome was quality of care, which was assessed based on the total percentage of any of 24 health care quality process measures (opportunities to provide evidence-based care) that were fulfilled. Secondary outcomes included medical resources consumed within 60 days of enrollment and patient and provider satisfaction. RESULTS: There were 4639 health care opportunities (2374 in the Coupler group and 2265 in the usual-care group), with no difference in the proportion of opportunities fulfilled (33.9% vs 30.7%; P = .12). Although there was a modest improvement in performance on screening/preventive measures, it was offset by poorer performance on some measures of acute care. Coupler patients used more laboratory and pharmacy resources than usual-care patients (logarithmic mean difference, 71 dollars). No difference in patient satisfaction was observed between groups, and provider satisfaction was mixed. CONCLUSION: This study provides no strong evidence to support the utility of this decision-support tool, but it demonstrates the value of rigorous evaluation of decision-support information technology.

Plant based HIV-1 vaccine candidate: Tat protein produced in spinach.

The HIV-1 Tat protein has been recently explored as a prospective vaccine candidate with broad, subtype non-specific action. We approached the problem of delivery of Tat through the mucosal route by expressing Tat in an edible plant. The tat gene was assembled from synthetic overlapping oligonucleotides, and was subsequently cloned into a plant virus-based vector tobacco mosaic virus (TMV). Spinach plants inoculated with the Tat-producing constructs were collected and fed to mice 7-14 days post inoculation. DNA vaccinations were performed using a gene gun. Codon optimization of the Tat gene expressed in spinach plants resulted in several-fold yield increase as detected in immunoblots, and did not cause severe symptoms in inoculated plants. Mice were fed with the Tat-producing or control vector-inoculated spinach. After three feedings, 1 week apart, 1g per mice, no differences were detected in the growth rate or behavior of the animals fed with these three types of spinach. None of the animals developed measurable Tat antibodies. Following DNA vaccination, however, mice having previously received oral Tat developed higher antibody titers to Tat than did the controls, with the titers peaking at 4 weeks post-vaccination. Codon optimization allows production of up to 300-500 microg of Tat antigen per 1 g of leaf tissue in spinach using a plant virus-based expression system. The plant produced Tat does not seem to have any apparent adverse effect on mice growth or behavior, when fed with spinach for 4 weeks. ELISA data suggested that oral Tat primed for the development of Tat antibodies when mice were subsequently vaccinated with plasmid DNA designed for Tat expression.