In summary, characteristic histologic features of UIP can be identified on TBB specimens more often than previously appreciated. TBB may be more useful in confirming UIP than previously recognized.
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Pulmonary arterial vascular smooth muscle (PAVSM) cell proliferation is a key pathophysiological component of vascular remodeling in pulmonary arterial hypertension (PAH) for which cellular and molecular mechanisms are poorly understood. The goal of our study was to determine the role of mammalian target of rapamycin (mTOR) in PAVSM cell proliferation, a major pathological manifestation of vascular remodeling in PAH. Our data demonstrate that chronic hypoxia promoted mTOR(Ser-2481) phosphorylation, an indicator of mTOR intrinsic catalytic activity, mTORC1-specific S6 and mTORC2-specific Akt (Ser-473) phosphorylation, and proliferation of human and rat PAVSM cells that was inhibited by siRNA mTOR. PAVSM cells derived from rats exposed to chronic hypoxia (VSM-H cells) retained increased mTOR(Ser-2481), S6, Akt (Ser-473) phosphorylation, and DNA synthesis compared to cells from normoxia-exposed rats. Suppression of mTORC2 signaling with siRNA rictor, or inhibition of mTORC1 signaling with rapamycin and metformin, while having little effect on other complex activities, inhibited VSM-H and chronic hypoxia-induced human and rat PAVSM cell proliferation. Collectively, our data demonstrate that up-regulation of mTOR activity and activation of both mTORC1 and mTORC2 are required for PAVSM cell proliferation induced by in vitro and in vivo chronic hypoxia and suggest that mTOR may serve as a potential therapeutic target to inhibit vascular remodeling in PAH.
OBJECTIVE: To assess outcomes of medication abortion provided through telemedicine compared with standard medication abortion at Planned Parenthood health centers in four U.S. states. METHODS: In this retrospective cohort study, we analyzed electronic health records for patients receiving telemedicine compared with standard medication abortion at 26 health centers in Alaska, Idaho, Nevada, and Washington from April 2017 to March 2018. All patients had on-site ultrasound scans, laboratory testing, and counseling and provided informed consent before meeting with the clinician. Telemedicine patients met with a clinician by secure videoconference platform; standard patients met with a clinician in person. We also reviewed adverse event reports submitted during this period. Study outcomes included ongoing pregnancy, receipt of or referral for aspiration procedure, and clinically significant adverse events. To compare outcomes between the telemedicine and standard groups, we performed logistic regression accounting for gestational age and health center clustering. RESULTS: A total of 5,952 patients underwent medication abortion (738 telemedicine and 5,214 standard). Mean gestational age was 50.4 days for telemedicine patients compared with 48.9 days for standard patients (prevalence ratio 1.02; 95% CI 1.00–1.03). We had outcome data for 4,456 (74.9%) patients; follow-up within 45 days of abortion was lower among telemedicine patients (60.3%) than standard patients (76.9%) (prevalence ratio 0.83; 95% CI 0.78–0.88). Among patients with follow-up data, ongoing pregnancy was less common among telemedicine patients (2/445, 0.5%) than standard patients (71/4,011, 1.8%) (adjusted odds ratio [OR] 0.23; 95% CI 0.14–0.39). Aspiration procedures were less common among telemedicine patients (6/445, 1.4%) than standard patients (182/4,011, 4.5%) (adjusted OR 0.28; 95% CI 0.17–0.46). Fewer than 1% of patients in each group reported clinically significant adverse events. No deaths were reported. CONCLUSION: Findings from this study conducted across geographically diverse settings support existing evidence that outcomes for medication abortion provided through telemedicine are comparable with standard provision of medication abortion. Differences in observed outcomes may be due to differential follow-up between groups.
Pulmonary arterial hypertension (PAH) is a rare disease which is characterized by increased pulmonary vascular resistance and right heart failure. Recent discoveries in disease pathophysiology have been translated into effective therapies tested in clinical trials. The studies which have led to the regulatory board approval of therapies for PAH have focused on surrogate and intermediate end points, thought to reflect quantity and quality of life, respectively. However, validation of many of these surrogates is incomplete. It is also unknown which indicators of function or long-term survival should be used to formulate decisions regarding addition, discontinuation, or combination of therapies. Identification of suitable end points would therefore not only help investigators design appropriate clinical trials, but also assist clinicians in caring for patients with PAH. Hemodynamic, cardiac imaging, plasma biomarkers, and exercise testing hold some promise as potential surrogate end points for PAH. Functional status and quality of life assessments may also have important roles. Future studies should validate the most promising surrogate markers, so that patients, clinicians, subjects, and investigators may benefit from the advantages they confer on clinical care and on clinical trials.The past several years have yielded an explosion of randomized clinical trials (RCTs) of several new medical therapies for pulmonary arterial hypertension (PAH). The hopes for these and all treatments for potentially fatal diseases are 1) to improve how a patient feels or functions and/ or 2) to prolong survival. While simply stated, the assessment of progress towards these goals may be quite complex [1][2][3][4][5][6].New PAH therapies have gained regulatory board approval based on studies with intermediate and surrogate end points as primary outcomes, believed to reflect the impact of these drugs on quality of life (QOL) and survival, respectively. While hemodynamic, plasma, cardiac imaging, exercise, functional, and QOL parameters are promising candidates, the reliability and validity of these measures are not clearly established. In addition, there are no RCTs addressing the use of such end points in guiding management decisions in PAH, such as changing, intensifying, escalating, or combining therapies. Despite this lack of evidence, clinicians who
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