Citations

Abstract Goals consist of determining 5-year prevalence and recurrence of methadone-related delirium (MRD), along with causes, treatments, and outcomes. Sample comprised 81 patients in methadone maintenance treatment. Criteria for MRD encompassed delirium with high methadone serum levels plus alleviation of delirium upon lowering methadone serum levels. MRD occurred in 14 cases who had 25 episodes. MRD precipitants included physician prescribing (i.e., excessive methadone or medications slowing methadone metabolism), drug misuse, and renal-fluid alterations. Social affiliation (housing with family, intimate partner) reduced MRD; employment increased MRD. Recovery occurred in 23/25 episodes of MRD; two episodes progressed to dementia. Obtaining serum methadone levels fostered prompt recognition.

AbstractBackgroundIneffective esophageal motility (IEM) is a heterogenous minor motility disorder diagnosed when ≥50% ineffective peristaltic sequences (distal contractile integral <450 mm Hg cm s) coexist with normal lower esophageal sphincter relaxation (integrated relaxation pressure < upper limit of normal) on esophageal high‐resolution manometry (HRM). Ineffective esophageal motility is not consistently related to disease states or symptoms and may be seen in asymptomatic healthy individuals.PurposeA 1‐day symposium of esophageal experts reviewed existing literature on IEM, and this review represents the conclusions from the symposium. Severe IEM (>70% ineffective sequences) is associated with higher esophageal reflux burden, particularly while supine, but milder variants do not progress over time or consistently impact quality of life. Ineffective esophageal motility can be further characterized using provocative maneuvers during HRM, especially multiple rapid swallows, where augmentation of smooth muscle contraction defines contraction reserve. The presence of contraction reserve may predict better prognosis, lesser reflux burden and confidence in a standard fundoplication for surgical management of reflux. Other provocative maneuvers (solid swallows, standardized test meal, rapid drink challenge) are useful to characterize bolus transit in IEM. No effective pharmacotherapy exists, and current managements target symptoms and concurrent reflux. Novel testing modalities (baseline and mucosal impedance, functional lumen imaging probe) show promise in elucidating pathophysiology and stratifying IEM phenotypes. Specific prokinetic agents targeting esophageal smooth muscle need to be developed for precision management.

Abstract Objectives Given the increased complexity of molecular and cytogenetic testing (MOL-CG), the Society for Hematopathology Education Committee (SH-EC) was interested in determining what the current expectations are for MOL-CG education in hematopathology (HP) fellowship training. Methods The SH-EC sent a questionnaire to HP fellowship program directors (HP-PDs) covering MOL-CG training curricula, test menus, faculty background, teaching, and sign-out roles. These findings were explored via a panel-based discussion at the 2018 SH-EC meeting for HP-PDs. Results HP fellows are expected to understand basic principles, nomenclature, and indications for and limitations of testing. Interpretation of common assays is within that scope, but not necessarily proficiency in technical troubleshooting of testing or analysis of complex raw data. Conclusions The consensus was that HP fellows should understand the components of MOL-CG testing necessary to incorporate those results into an accurate, clinically relevant, and integrated HP report.

Background: Professional baseball pitchers are at high risk for tears of the ulnar collateral ligament (UCL) of the elbow, often requiring surgical reconstruction. Despite acceptable published return-to-play outcomes, multiple techniques and graft types have been described. Purpose: This study compares UCL reconstruction (UCLR) outcomes based on tunnel configuration and graft type. Study Design: Cohort study; Level of evidence, 3. Methods: After approval from our institutional review board and Major League Baseball (MLB), 566 professional baseball pitchers who underwent UCLR between 2010 and 2014 were identified and included. The following patient characteristics were analyzed: age, pitching role (starter vs reliever), level of play (MLB vs Minor League Baseball [MiLB]), and throwing side dominance. Surgical factors analyzed included reconstruction technique, graft type, and concomitant procedures. Primary outcome measures consisted of the ability to return to play at any level (RTP), ability to return to the same level of play (RSL), time to return, subsequent elbow injuries, and need for subsequent or revision elbow surgery. The effects of patient and surgical factors on outcomes were analyzed using multivariate linear and logistic regression modeling. Results: The RTP rate was 79.9%, and the RSL rate was 71.2%. Grafts used to reconstruct the UCL included the palmaris longus autograft (n = 361, 63.7%), the gracilis autograft (n = 135, 23.8%), and other grafts (n = 70, 12.5%). Surgical techniques utilized were the docking technique (n = 171, 30.2%), the modified Jobe technique (n = 290, 51.2%), and other techniques (n = 105, 18.6%). There were no significant differences in the time to RTP or RSL based on reconstruction technique or graft type. RTP rates were similar for the docking versus modified Jobe technique (80.1% vs 82.4%, respectively; P = .537) and for the 2 primary graft types (83.1% for palmaris longus vs 80.7% for gracilis; P = .596). The rate of subsequent elbow surgery was 10.5% for the docking technique versus 14.8% for the modified Jobe technique ( P = .203), and the rate of revision UCLR was 2.9% versus 6.2% for the docking versus modified Jobe technique, respectively ( P = .128). Significant trends toward an increasing use of the palmaris longus autograft ( P = .023) and the docking technique ( P = .006) were observed. MLB pitchers were more likely than MiLB pitchers to RTP ( P < .001) and RSL ( P < .001), but they required a longer time to return (mean difference, 35 days; P = .039) and had a higher likelihood of subsequent elbow (odds ratio [OR], 3.58 [95% CI, 2.06-6.23]; P < .001) and forearm injuries (OR, 5.70 [95% CI, 1.99-16.30]; P = .004) but not subsequent elbow surgery. No specific variables correlated with the rates of subsequent elbow surgery or revision UCLR in the multivariate analysis. The use of concomitant ulnar nerve transposition did not affect outcomes. Conclusion: Surgical outcomes in professional baseball players are not significantly influenced by UCLR technique or graft type. There was a high rate (46.3%) of subsequent throwing elbow injuries. MLB pitchers were more likely to RTP and RSL, but they had a higher frequency of subsequent elbow and forearm injuries than MiLB pitchers. Both the docking technique and the palmaris longus autograft are increasing in popularity among surgeons treating professional baseball players.

AbstractThere is an association between Helicobacter pylori infection and immune thrombocytopenia (ITP), and few studies have suggested that eradicative treatment of H. pylori infection may improve platelet counts in patients with ITP. Conventional treatments for ITP include immunosuppressive agents, and more recently thrombopoietic agents. However, based on clinical reports of association between H. pylori and ITP, several medical societies increasingly suggest detection and eradication of H. pylori as a treatment for ITP. In this article, we reappraise recent medical literature to determine the effectiveness of platelet response after treatment of H. pylori infection in patients with ITP. We searched two online databases (MEDLINE and Google Scholar) for full articles published between January 2008 and May 2018, and found a total of 11 studies that presented data and outcomes of treatment of H. pylori infection in ITP patients. All the studies administered triple therapy (amoxicillin 500 mg, clarithromycin 250 mg and a proton-pump inhibitor each given twice daily for either 7- or 14-day course) for eradication of H. pylori. Median overall platelet response ranged from 27 to 69.2% with a complete response rate ranging from 0 to 65.4% and a partial response rate ranging from 0 to 29.4%. Although there is variability in the effectiveness between different populations, it appears to be of benefit to ITP patients with concomitant H. pylori infection when treated with triple therapy. However, further studies to understand the pathogenesis of H. pylori-associated ITP is necessary for the development of new therapeutic approaches for ITP.

Abstract Aging leads to increased cellular senescence and is associated with decreased potency of tissue‐specific stem/progenitor cells. Here, we have done an extensive analysis of cardiac progenitor cells (CPCs) isolated from human subjects with cardiovascular disease, aged 32–86 years. In aged subjects (>70 years old), over half of CPCs are senescent (p16 INK4A , SA‐β‐gal, DNA damage γH2AX, telomere length, senescence‐associated secretory phenotype [SASP]), unable to replicate, differentiate, regenerate or restore cardiac function following transplantation into the infarcted heart. SASP factors secreted by senescent CPCs renders otherwise healthy CPCs to senescence. Elimination of senescent CPCs using senolytics abrogates the SASP and its debilitative effect in vitro. Global elimination of senescent cells in aged mice (INK‐ATTAC or wild‐type mice treated with D + Q senolytics) in vivo activates resident CPCs and increased the number of small Ki67‐, EdU‐positive cardiomyocytes. Therapeutic approaches that eliminate senescent cells may alleviate cardiac deterioration with aging and restore the regenerative capacity of the heart.

Cellular senescence results in cell cycle arrest with secretion of cytokines, chemokines, growth factors, and remodeling proteins (senescence-associated secretory phenotype; SASP) that have autocrine and paracrine effects on the tissue microenvironment. SASP can promote remodeling, inflammation, infectious susceptibility, angiogenesis, and proliferation, while hindering tissue repair and regeneration. While the role of senescence and the contributions of senescent cells are increasingly recognized in the context of aging and a variety of disease states, relatively less is known regarding the portfolio and influences of senescent cells in normal lung growth and aging per se or in the induction or progression of lung diseases across the age spectrum such as bronchopulmonary dysplasia, asthma, chronic obstructive pulmonary disease, or pulmonary fibrosis. In this review, we introduce concepts of cellular senescence, the mechanisms involved in the induction of senescence, and the SASP portfolio that are relevant to lung cells, presenting the potential contribution of senescent cells and SASP to inflammation, hypercontractility, and remodeling/fibrosis: aspects critical to a range of lung diseases. The potential to blunt lung disease by targeting senescent cells using a novel class of drugs (senolytics) is discussed. Potential areas for future research on cellular senescence in the lung are identified.