A simple echocardiographic prediction rule for hemodynamics in pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) has diverse causes with heterogeneous physiology compelling distinct management. Differentiating patients with primarily elevated pulmonary vascular resistance (PVR) from those with PH predominantly because of elevated left-sided filling pressure is critical. METHODS AND RESULTS: We reviewed hemodynamics, echocardiography, and clinical data for 108 patients seen at a referral PH clinic with transthoracic echocardiogram and right heart catheterization within 1 year. We derived a simple echocardiographic prediction rule to allow hemodynamic differentiation of PH attributed to pulmonary vascular disease (PH(PVD), defined as pulmonary artery wedge pressure [PAWP]≤15 mm Hg and PVR>3 WU). Age averaged 61.3±14.8 years, µPAWP and PVR were 16.4±7.1 mm Hg and 6.3±4.0 WU, respectively, and 52 (48.1%) patients fulfilled PH(PVD) hemodynamic criteria. The derived prediction rule ranged from -2 to +2 with higher scores suggesting higher probability of PH(PVD): +1 point for left atrial anterior-posterior dimension <3.2 cm; +1 for presence of a mid systolic notch or acceleration time <80 ms; -1 for lateral mitral E:e'>10; -1 for left atrial anterior-posterior dimension >4.2 cm. PVR increased stepwise with score (for -2, 0, and +2, µPVR were 2.5, 4.5, and 8.1 WU, respectively), whereas the inverse was true for pulmonary artery wedge pressure (corresponding µPAWP were 21.5, 16.5, and 10.4 mm Hg). Among subjects with complete data, the score had an area under the curve (AUC) of 0.921 for PH(PVD). A score ≥0 had 100% sensitivity and 69.3% positive predictive value for PH(PVD), with 62.3% specificity. No patients with a negative score had PH(PVD). Patients with a negative score and acceleration time >100 ms had normal PVR (µPVR=1.8 WU, range=0.7-3.2 WU). CONCLUSIONS: We present a simple echocardiographic prediction rule that accurately defines PH hemodynamics, facilitates improved screening and focused clinical investigation for PH diagnosis and management.

Impact of obesity on perioperative outcomes of minimally invasive esophagectomy.

BACKGROUND: Abnormal body mass index has been targeted as a predictor of complications after major surgery. The aim of this study was to review the impact of obesity on perioperative outcomes after minimally invasive esophagectomy. METHODS: This study was a single-institution retrospective review of patients undergoing minimally invasive esophagectomy for high-grade dysplasia or cancer of the esophagus between 1999 and 2004. A body mass index of 30 or greater was considered obese. Patients with a body mass index less than 18.5 were excluded because of the potentially adverse effects of malnutrition on outcomes. RESULTS: A total of 282 eligible patients were identified. There were 84 obese and 198 nonobese patients (mean body mass index = 34.5 versus 25.5; p < 0.0001). Preoperative demographics, comorbidities, and cancer status were similar, except for a higher prevalence of diabetes (p = 0.002), lower prevalence of peripheral vascular disease (p = 0.045), and lower prevalence of stage III disease in the obese group (p = 0.044). Operative time was significantly longer in obese patients (375 versus 301 minutes; p = 0.0001), and estimated blood loss was similar (433 versus 377 mL, obese versus nonobese, respectively). There were 5 (1.8%) overall 30-day perioperative mortalities, with no differences between the groups. Overall major (obese, 23 [27.5%] versus nonobese, 68 [34.3%]) and minor (obese, 23 [27.5%] versus nonobese, 65 [32.8%]) complication rates were also similar. Furthermore, there were no significant differences in any individual complications. There was no difference in median intensive care unit stay (obese, 1 day versus nonobese, 2 days) or overall hospital stay (obese, 7 days versus nonobese, 8 days). CONCLUSIONS: Obesity was associated with longer operative times. Our review suggests that obesity is not a risk factor for mortality, postoperative complications, or length of hospitalization after minimally invasive esophagectomy.

ERK activation following macrophage FcgammaR ligation leads to chromatin modifications at the IL-10 locus.

We have previously demonstrated that macrophages stimulated in the presence of immune complexes produce high levels of IL-10. We now examine the mechanism of IL-10 superinduction. We report that the enhanced production of IL-10 correlates with a rapid and enhanced activation of two MAPKs, ERK and p38. The inhibition of either ERK or p38 prevented IL-10 induction, indicating that both MAPKs were required for IL-10 synthesis. By chromatin immunoprecipitation assay, we demonstrate that activation of ERK leads to the phosphorylation of serine 10 on histone H3 at the il-10 gene, making the promoter more accessible to transcription factors generated in response to p38 activation. Inhibition of ERK activation prevented histone modifications, and decreased the binding of Sp1 and STAT3 to the IL-10 promoter. We conclude that the activation of ERK following FcgammaR ligation leads to a remodeling of the chromatin at the il-10 locus, making it more accessible to transcription factors. The rapid and transient regulation of transcription factor accessibility to the IL-10 promoter by MAPK activation represents a novel way that the production of this cytokine is regulated.