Citations

Context Additional reviews of diagnostic surgical and cytology cases have been shown to detect diagnostic discrepancies. Objective To develop, through a systematic review of the literature, recommendations for the review of pathology cases to detect or prevent interpretive diagnostic errors. Design The College of American Pathologists Pathology and Laboratory Quality Center in association with the Association of Directors of Anatomic and Surgical Pathology convened an expert panel to develop an evidence-based guideline to help define the role of case reviews in surgical pathology and cytology. A literature search was conducted to gather data on the review of cases in surgical pathology and cytology. Results The panel drafted 5 recommendations, with strong agreement from open comment period participants ranging from 87% to 93%. The recommendations are: (1) anatomic pathologists should develop procedures for the review of selected pathology cases to detect disagreements and potential interpretive errors; (2) anatomic pathologists should perform case reviews in a timely manner to avoid having a negative impact on patient care; (3) anatomic pathologists should have documented case review procedures that are relevant to their practice setting; (4) anatomic pathologists should continuously monitor and document the results of case reviews; and (5) if pathology case reviews show poor agreement within a defined case type, anatomic pathologists should take steps to improve agreement. Conclusions Evidence exists that case reviews detect errors; therefore, the expert panel recommends that anatomic pathologists develop procedures for the review of pathology cases to detect disagreements and potential interpretive errors, in order to improve the quality of patient care.

This quality improvement project demonstrates that RN Care Managers, in a chronic pain programme, can assess for a family history of substance abuse in 5–10 min. Information informs treatment based on specific high risk criteria. Benefits include heightened awareness of the genetic and environmental risks associated with a family history of substance abuse, an opportunity to participate in motivational interventions to prevent or minimize consequences of substance use disorders, and likely substantial overall health‐care cost savings.

Altered myocardial structure and function, secondary to chronically elevated blood pressure, are leading causes of heart failure and death. B-type natriuretic peptide (BNP), a guanylyl cyclase A agonist, is a cardiac hormone integral to cardiovascular regulation. Studies have demonstrated a causal relationship between reduced production or impaired BNP release and the development of human hypertension. However, the consequences of BNP insufficiency on blood pressure and hypertension-associated complications remain poorly understood. Therefore, the goal of this study was to create and characterize a novel model of BNP deficiency to investigate the effects of BNP absence on cardiac and renal structure, function, and survival. Genetic BNP deletion was generated in Dahl salt-sensitive rats. Compared with age-matched controls, BNP knockout rats demonstrated adult-onset hypertension. Increased left ventricular mass with hypertrophy and substantially augmented hypertrophy signaling pathway genes, developed in young adult knockout rats, which preceded hypertension. Prolonged hypertension led to increased cardiac stiffness, cardiac fibrosis, and thrombi formation. Significant elongation of the QT interval was detected at 9 months in knockout rats. Progressive nephropathy was also noted with proteinuria, fibrosis, and glomerular alterations in BNP knockout rats. End-organ damage contributed to a significant decline in overall survival. Systemic BNP overexpression reversed the phenotype of genetic BNP deletion. Our results demonstrate the critical role of BNP defect in the development of systemic hypertension and associated end-organ damage in adulthood.

Background Cardiac resynchronization therapy using bi‐ventricular pacing is proven effective in the management of heart failure (HF) with a wide QRS ‐complex. In the absence of QRS prolongation, however, device‐based resynchronization is reported unsuitable. As an alternative, the present study tests a regenerative cell‐based approach in the setting of narrow QRS ‐complex HF. Methods and Results Progressive cardiac dyssynchrony was provoked in a chronic transgenic model of stress‐triggered dilated cardiomyopathy. In contrast to rampant end‐stage disease afflicting untreated cohorts, stem cell intervention early in disease, characterized by mechanical dyssynchrony and a narrow QRS ‐complex, aborted progressive dyssynchronous HF and prevented QRS widening. Stem cell‐treated hearts acquired coordinated ventricular contraction and relaxation supporting systolic and diastolic performance. Rescue of contractile dynamics was underpinned by a halted left ventricular dilatation, limited hypertrophy, and reduced fibrosis. Reverse remodeling reflected a restored cardiomyopathic proteome, enforced at systems level through correction of the pathological molecular landscape and nullified adverse cardiac outcomes. Cell therapy of a dyssynchrony‐prone cardiomyopathic cohort translated prospectively into improved exercise capacity and prolonged survivorship. Conclusions In narrow QRS HF, a regenerative approach demonstrated functional and structural benefit, introducing the prospect of device‐autonomous resynchronization therapy for refractory disease.

Background and purpose Many studies demonstrate that both kyphoplasty and vertebroplasty are superior to conservative therapy in the treatment of osteoporotic vertebral body compression fractures. We performed a systematic review and meta-analysis of studies comparing the outcomes of vertebroplasty and kyphoplasty, which included prospective non-randomized, retrospective comparative, and randomized studies. Materials and methods We searched MEDLINE, EMBASE, and the Web of Science databases for studies of kyphoplasty versus vertebroplasty from 1 January 1990 to 30 November 2014 and compared the following outcomes: procedure characteristics, pain and disability improvement, complications and anatomic outcomes. A subgroup analysis was performed comparing pain outcomes based on the risk of bias. Results 29 studies enrolling 2838 patients (1384 kyphoplasty and 1454 vertebroplasty) were included. 16 prospective non-randomized studies, 10 retrospective comparative studies, and 3 randomized controlled studies were included. No significant differences were found in mean pain scores between the two groups postoperatively (2.9±1.5 kyphoplasty vs 2.9±1.7 vertebroplasty, p=0.39) and at 12 months (2.7±1.8 kyphoplasty vs 3.2±1.8 vertebroplasty, p=0.64). No significant differences were found in disability postoperatively (34.7±7.1 kyphoplasty group vs 36.3±7.8 vertebroplasty group, p=0.74) or at 12 months (28.3±16 kyphoplasty group vs 29.6±13.9 vertebroplasty group, p=0.70). Kyphoplasty was associated with lower odds of new fractures (p=0.06), less extraosseous cement leakage (p<0.01), and greater reduction in kyphotic angle (p<0.01). Conclusions No significant difference was found between vertebroplasty and kyphoplasty in short- and long-term pain and disability outcomes. Further studies are needed to better determine if any particular subgroups of patients would benefit more from vertebroplasty or kyphoplasty in the treatment of vertebral body compression fractures.

Abstract Background: Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms, and selected mature B-cell neoplasms is reported. Method: Data on 4,979 cases and 4,752 controls from nine American/European studies from the InterLymph consortium (1988–2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI). Results: Obesity (BMI ≥ 30 kg/m2) was associated with DLBCL risk [OR = 1.33; 95% confidence interval (CI), 1.02–1.73], as was TNF-308GA+AA (OR = 1.24; 95% CI, 1.07–1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost 2-fold relative to those of normal weight and TNF-308GG (OR = 1.93; 95% CI, 1.27–2.94), with a RERI of 0.41 (95% CI, −0.05–0.84; Pinteraction = 0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected. Conclusions: Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk. Impact: Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G&gt;A in the pathogenesis of lymphoma. Cancer Epidemiol Biomarkers Prev; 24(7); 1061–70. ©2015 AACR.

Although evidence of the protective immunity conferred by B‐1b cells (CD19+B220+IgMhiMac1+CD5−) has been established, the mechanisms governing the maintenance and activation of B‐1b cells following pathogen encounter remain unclear. B cell–activating factor (BAFF) and a proliferation‐inducing ligand (APRIL) mediate their function in mature B cells through the BAFF receptor (BAFFR) and transmembrane activator and CAML interactor (TACI). BAFFR‐deficient mice have lower numbers of B‐1b cells, and this reduction is directly proportional to BAFFR levels. The generation of B‐1b cells is also dependent on the strength of B cell receptor (BCR) signaling. Mice with impaired BCR signaling, such as X‐linked immunodeficient (xid) mice, have B‐1b cell deficiency, indicating that both BCR‐ and BAFFR‐mediated signaling are critical for B‐1b cell homeostasis. Borrelia hermsii induces expansion and persistence of B‐1b cells in xid mice, and these B‐1b cells provide a heightened protective response. Toll‐like receptor (TLR)–mediated stimulation of xid B cells results in a significant increase in TACI expression and restoration of TACI‐mediated functions. The activation of TLR signaling by B. hermsii and BCR/TLR costimulation–mediated upregulation of BAFFR and TACI on B‐1b cells suggests that B‐1b cell maintenance and function following bacterial exposure may depend on BAFFR‐ and TACI‐mediated signaling. In fact, the loss of both BAFFR and TACI results in a greater impairment in anti‐B. hermsii responses compared to deficiency of BAFFR or TACI alone.