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Recent studies have focused on the contribution of capillary endothelial TRPV4 channels to pulmonary pathologies, including lung edema and lung injury. However, in pulmonary hypertension (PH), small pulmonary arteries are the focus of the pathology, and endothelial TRPV4 channels in this crucial anatomy remain unexplored in PH. Here, we provide evidence that TRPV4 channels in endothelial cell caveolae maintain a low pulmonary arterial pressure under normal conditions. Moreover, the activity of caveolar TRPV4 channels is impaired in pulmonary arteries from mouse models of PH and PH patients. In PH, up-regulation of iNOS and NOX1 enzymes at endothelial cell caveolae results in the formation of the oxidant molecule peroxynitrite. Peroxynitrite, in turn, targets the structural protein caveolin-1 to reduce the activity of TRPV4 channels. These results suggest that endothelial caveolin-1-TRPV4 channel signaling lowers pulmonary arterial pressure, and impairment of endothelial caveolin-1-TRPV4 channel signaling contributes to elevated pulmonary arterial pressure in PH. Thus, inhibiting NOX1 or iNOS activity, or lowering endothelial peroxynitrite levels, may represent strategies for restoring vasodilation and pulmonary arterial pressure in PH.

Catecholamine-resistant postoperative vasoplegic syndrome (PVS) lacks effective treatment modalities. Synthetic angiotensin II was recently approved for the treatment of vasodilatory shock; however, its use in PVS is not well described. We report outcomes in six patients receiving angiotensin II for the treatment of isolated PVS. All patients achieved their MAP goal and the majority showed improvement in lactate and background catecholamine dose; however, variables of perfusion changed discordantly. Three of six patients survived to hospital discharge. [ABSTRACT FROM AUTHOR]

Rationale: Patients with autoimmune lymphoproliferative syndrome (ALPS), a disorder of impaired lymphocyte apoptosis, often undergo radiographic chest imaging to evaluate the presence and progression of lymphadenopathy. These images often lead to parenchymal and interstitial lung findings of unclear clinical significance.Objectives: To characterize the pulmonary findings associated with ALPS and to determine if lung abnormalities present on computed tomographic (CT) imaging of the chest correlate with infection or functional status.Methods: Patients with lung abnormalities observed on chest CT scans were retrospectively identified from the largest known ALPS cohort. Lung computed tomography findings were characterized and correlated with medical records, bronchoalveolar lavage, biopsy, and lung function.Measurements and Main Results: CT images of the chest were available for 234 (92%) of 255 of the patients with ALPS. Among patients with a chest CT scan, 18 (8%) had lung abnormalities on at least one CT scan. Fourteen (78%) of those 18 were classified as having ALPS with undetermined genetic defect. Most patients (n = 16 [89%]) with lung lesions were asymptomatic. However, two (11%) of them had associated dyspnea and/or desaturation on room air. Immunosuppressive treatment was administered for lung disease in nine (50%) cases, and all were followed for clinical outcomes.Conclusions: Patients with ALPS can develop chest radiographic findings with protean manifestations that may mimic pulmonary infection. Management of patients with ALPS with incidental lung lesions identified by CT imaging should be guided by clinical correlation. Symptomatic patients may benefit from chest CT imaging and lesion biopsy to exclude infection and guide administration of immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Purpose To describe the Plan-Do-Study-Act (PDSA) methodology utilized by a multidisciplinary team to address the discordance between ordering and administration of dexmedetomidine for sleep hygiene in the intensive care unit (ICU). Summary The addition of sleep hygiene as an indication for the use of dexmedetomidine at University of Virginia (UVA) Health led to discordance between the medication orders in the electronic medical record and the subsequent administration of dexmedetomidine. A multidisciplinary team implemented interventions that included modifying the order panel, streamlining the institutional formulary, developing institutional practice guidelines, and providing education to healthcare team members. After completion of the first PDSA cycle, the mean number of discordant order elements decreased to 1.96 out of 5 possible order elements from an initial 2.5 out of 5 elements before the interventions, meeting the aim to reduce the mean to less than 2. There was a significant decrease in the discordance in the duration of infusion (discordant for 14 of 30 orders before the interventions vs 1 of 28 orders after the interventions, P = 0.0002) but a significant increase in the discordance in the titration dose (discordant for 13 of 30 orders before the interventions vs 24 of 28 orders after the interventions, P < 0.0001). Other discordant order elements including the starting dose, maximum rate, and titration interval time decreased in frequency after the interventions, although the differences were not statistically significant. The interventions made during the first PDSA cycle are anticipated to lead to an estimated cost savings of up to $180,000 per year within the UVA Health system. Conclusion The multidisciplinary team utilizing a PDSA method to modify the order panel, streamline the institutional formulary, develop institutional practice guidelines, and provide education to healthcare team members was effective at reducing overall discordance between order intent and administration of dexmedetomidine for sleep hygiene in the ICU. [ABSTRACT FROM AUTHOR]