Estrogens are disease modifiers in PAH. Even though female patients exhibit better right ventricular (RV) function than men, estrogen effects on RV function (a major determinant of survival in PAH) are incompletely characterized. We sought to determine whether sex differences exist in RV function in the SuHx model of PAH, whether hormone depletion in females worsens RV function, and whether E2 repletion improves RV adaptation. Furthermore, we studied the contribution of ERs in mediating E2's RV effects. SuHx-induced pulmonary hypertension (SuHx-PH) was induced in male and female Sprague-Dawley rats as well as OVX females with or without concomitant E2 repletion (75 μg·kg(-1)·day(-1)). Female SuHx rats exhibited superior CI than SuHx males. OVX worsened SuHx-induced decreases in CI and SuHx-induced increases in RVH and inflammation (MCP-1 and IL-6). E2 repletion in OVX rats attenuated SuHx-induced increases in RV systolic pressure (RVSP), RVH, and pulmonary artery remodeling and improved CI and exercise capacity (V̇o2max). Furthermore, E2 repletion ameliorated SuHx-induced alterations in RV glutathione activation, proapoptotic signaling, cytoplasmic glycolysis, and proinflammatory cytokine expression. Expression of ERα in RV was decreased in SuHx-OVX but was restored upon E2 repletion. RV ERα expression was inversely correlated with RVSP and RVH and positively correlated with CO and apelin RNA levels. RV-protective E2 effects observed in females were recapitulated in male SuHx rats treated with E2 or with pharmacological ERα or ERβ agonists. Our data suggest significant RV-protective ER-mediated effects of E2 in a model of severe PH.

The development of pulmonary hypertension (PH) requires multiple pulmonary vascular insults, yet the role of early oxygen therapy as an initial pulmonary vascular insult remains poorly defined. Here, we employ a two-hit model of PH, utilizing postnatal hyperoxia followed by adult hypoxia exposure, to evaluate the role of early hyperoxic lung injury in the development of later PH. Sprague-Dawley pups were exposed to 90% oxygen during postnatal days 0-4 or 0-10 or to room air. All pups were then allowed to mature in room air. At 10 wk of age, a subset of rats from each group was exposed to 2 wk of hypoxia (Patm = 362 mmHg). Physiological, structural, and biochemical endpoints were assessed at 12 wk. Prolonged (10 days) postnatal hyperoxia was independently associated with elevated right ventricular (RV) systolic pressure, which worsened after hypoxia exposure later in life. These findings were only partially explained by decreases in lung microvascular density. Surprisingly, postnatal hyperoxia resulted in robust RV hypertrophy and more preserved RV function and exercise capacity following adult hypoxia compared with nonhyperoxic rats. Biochemically, RVs from animals exposed to postnatal hyperoxia and adult hypoxia demonstrated increased capillarization and a switch to a fetal gene pattern, suggesting an RV more adept to handle adult hypoxia following postnatal hyperoxia exposure. We concluded that, despite negative impacts on pulmonary artery pressures, postnatal hyperoxia exposure may render a more adaptive RV phenotype to tolerate late pulmonary vascular insults.

Yttrium-90 (90Y) radioembolization is a treatment option for patients with metastatic colorectal cancer with unresectable liver metastases. We conducted a retrospective analysis to evaluate outcomes in 24 such patients who underwent 90Y radioembolization. We concluded that 90Y radioembolization is reasonable for select patients with unresectable hepatic metastases in the absence of other metastatic sites. Background Few patients with metastatic colorectal cancer (mCRC) are candidates for resection of their hepatic disease. Yttrium-90 (90Y) radioembolization has promise in the treatment of unresectable mCRC. We conducted retrospective study to assess the efficacy in patients with refractory mCRC who underwent 90Y radioembolization. Materials and methods Patients with unresectable mCRC with liver metastases treated at The Ohio State University were included in this analysis. Demographic data, carcinoembryonic antigen (CEA) values, observed toxicities, and information on prior therapies were collected. Response was assessed by RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Results Twenty-four patients (median age, 63 years) were included. Of the patients, 54% had extrahepatic disease; 67% had bilobar involvement. The patients had received a median of 3 prior therapies. No objective responses were observed. Five patients had a CEA response. Median PFS and OS were 3.9 months (95% CI, 2.4–4.8 months) and 8.9 months (95% CI, 4.2–16.7 months), respectively. Patients older than 65 years had improved PFS (4.6 vs. 2.4 months) and OS (14 vs. 5.5 months) vs. younger patients, likely due to receipt of 90Y treatment earlier in their disease course. The presence of extrahepatic disease and the absence of CEA response appeared negatively predictive of efficacy. Toxicities were expected and manageable. Conclusion 90Y radioembolization is active in select patients with refractory mCRC and with liver metastases, and is safe and well tolerated in the elderly. In patients with extensive extrahepatic disease, 90Y should be used in combination with chemotherapy. CEA may be a predictor of efficacy.

Physician compliance reporting can be used to improve ICU physician compliance with rounding checklists when prompters are unavailable. Improved physician compliance translated into decreased rates of Foley catheter, central venous catheter, and ventilator use. These results highlight the impact physician accountability can have on patient care in the ICU.