Sustainability of an Opt-Out Electronic-Health Record-based Tobacco Treatment Consult Service at a large safety-net hospital: A 6-year Analysis.

INTRODUCTION: Our safety-net hospital implemented a hospital-based tobacco treatment intervention in 2016. We previously showed the intervention, an "opt-out" Electronic Health Record (EHR)-based Best Practice Alert (BPA)+order-set that triggers consultation to an inpatient Tobacco Treatment Consult (TTC) service for all patients who smoke, improves smoking abstinence. We now report on sustainability, 6 years after inception. METHODS: We analyzed data collected between July 2016-June 2022 of patients documented as 'currently smoking' in the EHR. Across the 6 years, we used Pearson's correlation analysis to compare Adoption (clinician acceptance of the BPA+order-set, thus generating consultation to the TTC service); Reach (number of consultations completed by the TTC service); and Effectiveness (receipt of pharmacotherapy orders between patients receiving and not receiving consultations). RESULTS: Among 39,558 adult admissions (July 2016-June 2022) with "currently smoking" status in the EHR for whom the BPA triggered, clinicians accepted the TTC order-set on 50.4% (19,932/39,558), though acceptance varied across services [e.g., Cardiology (71%) and Obstetrics-Gynecology (12%)]. The TTC service consulted on 17% (6779/39,558) of patients due to staffing constraints. Consultations ordered (r=-0.28, p=0.59) and completed (r= 0.45, p=0.37) remained stable over six-years. Compared to patients not receiving consultations, patients receiving consultations were more likely to receive pharmacotherapy orders overall (inpatient: 50.8% vs 35.1%, p<.0001; at discharge: 27.1% vs 10%, p<.0001) and in each year. CONCLUSIONS: The "opt-out" EHR-based TTC service is sustainable, though many did not receive consultations due to resource constraints. Healthcare systems should elevate priority of hospital-based tobacco treatment programs to increase reach to underserved populations. IMPLICATIONS: Our study shows that opt-out approaches that utilize the EHR are a sustainable approach to provide evidence-based tobacco treatment to all hospitalized individuals who smoke, regardless of readiness to stop smoking and clinical condition.

A Feasibility Study for a Novel Trans-infraorbital Canal Approach to the Maxillary Nerve in Pigs (Sus domesticus).

Experimental maxillofacial surgery is commonly performed in pigs; however, locoregional anesthesia of this area has not been described. This study evaluated the feasibility of a novel maxillary nerve block approach. In part I, cadavers were used to determine anatomic landmarks and assess maxillary nerve dye staining by using 0.03 mL kg-1 of a 1:10 mixture of commercial food dye and 0.5% bupivacaine. In part II, 10 additional pig cadavers underwent bilateral ultrasound-guided maxillary nerve blocks by using trans-infraorbital canal needle placement. The maxillary nerve was harvested and scored based on degree of staining (0 and 1, absent or incomplete staining; 2, staining; >1 cm circumferentially). Intracranial and intraconal spread of dye was evaluated. A Kruskal-Wallis test was used to compare infraorbital canal length estimated either externally via landmarks, internally via ultrasound, or actually measured after dissection. In 18 of 20 (90%) injections, successful staining (score = 2) of maxillary nerves was obtained for a nerve length of 2.4 ± 0.3 cm. Two of 20 cases (10%) had inadequate staining (score <2). At dissection of these 2 cases, the needle tip was observed to have collided with an unerupted tooth (third molar). No intracranial or intraconal spread of dye was observed. We detected no statistical differences between the estimated external, estimated internal, or actual dissection methods for measurement of infraorbital canal length (P = 0.3). Ultrasound-guided trans-infraorbital maxillary nerve block in pigs is a feasible technique, warranting further work to evaluate its in vivo efficacy and safety.

Image analysis comparison of nerve staining with food dye, methylene blue or tissue marker.

OBJECTIVE: Novel locoregional techniques use dye studies to confirm successful nerve targeting. The goal was to objectively quantify and compare nerve staining characteristics of dye mixtures commonly reported in the literature using image analysis software. STUDY DESIGN: Prospective, randomized cadaveric study. METHODS: Thirty-six brachial plexus nerves from unpreserved pig cadavers were randomized into three groups of 12: FD (1:10 mixture of blue food dye and bupivacaine 0.5%), MB (methylene blue 1%) and TM (0.1:10 mixture of blue tissue marker and lidocaine 2%). Nerves were immersed in dye for 1, 15, 30 or 60 minutes (n = 3 each). Images of nerves before immersion (baseline) and at each time point with epineurium intact (superficial staining) and after longitudinal bisection (deep staining) were processed using image analysis software. Color saturation values were divided into quartiles (dark, medium-dark, medium-light or light). Percentage of stained nerve area in each quartile was calculated and compared using two-way anova. RESULTS: Superficially, at minute 1, dark saturation covered 40% of nerve area in FD versus 19% in MB (p = 0.04) and 0% in TM (p < 0.0001). In bisected nerves, dark and medium-dark saturations occurred only in FD; medium-light saturation comprised anywhere from 4% to 22.5% over time in FD versus <1% at any time in MB (p = 1.000; p = 0.343; p = 0.383; p = 0.262). Deep staining was not found in TM at any point. CONCLUSION AND CLINICAL RELEVANCE: Food dye rapidly stains superficial and deep nerve layers. Based on these characteristics, investigators can choose the appropriate dye for their study.

Diagnostic accuracy of point-of-care ultrasound with artificial intelligence-assisted assessment of left ventricular ejection fraction.

Focused cardiac ultrasound (FoCUS) is becoming standard practice in a wide spectrum of clinical settings. There is limited data evaluating the real-world use of FoCUS with artificial intelligence (AI). Our objective was to determine the accuracy of FoCUS AI-assisted left ventricular ejection fraction (LVEF) assessment and compare its accuracy between novice and experienced users. In this prospective, multicentre study, participants requiring a transthoracic echocardiogram (TTE) were recruited to have a FoCUS done by a novice or experienced user. The AI-assisted device calculated LVEF at the bedside, which was subsequently compared to TTE. 449 participants were enrolled with 424 studies included in the final analysis. The overall intraclass coefficient was 0.904, and 0.921 in the novice (n = 208) and 0.845 in the experienced (n = 216) cohorts. There was a significant bias of 0.73% towards TTE (p = 0.005) with a level of agreement of 11.2%. Categorical grading of LVEF severity had excellent agreement to TTE (weighted kappa = 0.83). The area under the curve (AUC) was 0.98 for identifying an abnormal LVEF (<50%) with a sensitivity of 92.8%, specificity of 92.3%, negative predictive value (NPV) of 0.97 and a positive predictive value (PPV) of 0.83. In identifying severe dysfunction (<30%) the AUC was 0.99 with a sensitivity of 78.1%, specificity of 98.0%, NPV of 0.98 and PPV of 0.76. Here we report that FoCUS AI-assisted LVEF assessments provide highly reproducible LVEF estimations in comparison to formal TTE. This finding was consistent among senior and novice echocardiographers suggesting applicability in a variety of clinical settings.

Comparison of two sedation protocols, with and without analgesia, in pigs: Assessment of sedation end points and propofol requirements.

OBJECTIVE: To compare the effects of intramuscular premedication with a novel nonanalgesic [alfaxalone-midazolam-acepromazine (AMA)] and an analgesic [ketamine-midazolam-detomidine (KMD)] protocol on sedation end points and propofol requirements for induction of anesthesia in swine. STUDY DESIGN: Prospective experimental study. ANIMALS: A total of 27 Yorkshire cross gilts weighing approximately 30 kg. METHODS: Two sedation protocols, AMA and KMD, were compared. Time from intramuscular injection to ataxia, recumbency and nonresponsiveness to tactile stimulation was recorded. The propofol dose requirement for induction of general anesthesia and tracheal intubation, and any adverse events (paddling, twitching), were recorded. Data were tested for normality using a Shapiro-Wilk test. Propofol requirements were compared using a Student's t test. Times from injection to sedation end points were compared using a Mood's test, and significance was confirmed using a Kaplan-Meier curve with Wilcoxon test survival analysis. RESULTS: Sedation end points were reached significantly faster with KMD than with AMA. Nonresponsiveness occurred in 5 (0-16) and 9.5 (5-36) minutes for KMD and AMA, respectively (p = 0.011). No significant difference (p = 0.437) was found between propofol doses used in either group (KMD; 64.38 ± 5.98 mg, AMA; 72.00 ± 7.57 mg). More adverse events were noted with AMA (11/16 pigs) than with KMD (1/11 pigs). CONCLUSIONS AND CLINICAL RELEVANCE: In pigs, AMA can be used as a reliable sedation protocol. Frequency of adverse events and time to reach sedation end points between AMA and KMD differed, but the dose of propofol needed to induce general anesthesia was not significantly different.

Evaluation of transpulmonary ultrasound dilution cardiac output in piglets: accuracy, precision and trending ability with room temperature injectate.

OBJECTIVE: Transpulmonary ultrasound dilution (TPUD) is a minimally invasive technique to measure cardiac output (CO) using a 1 mL kg-1 isotonic 37 °C saline injectate indicator. The objective was to evaluate the performance of TPUD using a room temperature saline injectate. STUDY DESIGN: Prospective experimental trial. ANIMALS: A total of seven anesthetized male Yorkshire piglets. METHODS: Piglets aged 1 month and weighing 7.7-9.0 kg were anesthetized with detomidine-ketamine-hydromorphone-isoflurane and a pulmonary artery flow probe (PAFP) placed via a median sternotomy. The thoracic cavity remained open during measurement of CO by PAFP and TPUD. The TPUD indicators of 1 mL kg-1 0.9% saline at 37 °C and 20 °C were compared during infusions of phenylephrine and dobutamine, blood withdrawal and replacement. Bias, limits of agreement (LoAs) and percentage error (PE) between each iteration of PAFP and TPUD were measured with Bland-Altman plots. Trending ability via concordance, angular bias and radial LoA were compared. RESULTS: Bland-Altman plots showed negligible bias with varying LoAs. PEs of 22% and 38% were found for 37 °C and 20 °C saline injectates, respectively. In the four-quadrant plots, the concordance rate was 94% and 100% for measurements obtained with 37 °C and 20 °C saline injectates, respectively. Angular bias for both were < ±5 °, with radial LoA < ±7 °. CONCLUSIONS: TPUD was accurate when using 1 mL kg-1 of isotonic saline at 37 °C in a range of CO within 0.2-0.8 L minute-1, and it reliably tracked positive and negative changes in CO. Room temperature (20 °C) indicator was less accurate but equally able to track direction of changes in CO. CLINICAL RELEVANCE: The use of room temperature injectates allows an easy, readily available clinical application of TPUD CO monitoring while preserving the trending ability of the monitor.

Pirfenidone in Progressive Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

Background: The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax convened to update clinical practice guidelines for interstitial lung disease (ILD). Objective: To conduct a systematic review to evaluate existing ILD literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic pirfenidone. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using pirfenidone to treat patients with PPF. Data Extraction: Mortality, disease progression, lung function, and adverse event data were extracted. Meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation Working Group approach was used to assess the quality of evidence. Synthesis: Two studies met inclusion criteria. Meta-analyses revealed that changes in forced vital capacity (FVC) percent predicted (mean difference [MD], 2.3%; 95% confidence interval [CI], 0.5-4.1%), the FVC in milliliters (MD, 100.0 ml; 95% CI, 98.1-101.9 ml), and the 6-minute-walk distance in meters (MD, 25.2 m; 95% CI, 8.3-42.1 m) all favored pirfenidone over placebo. The changes in the diffusing capacity of the lung for carbon monoxide (DLCO) in millimoles per kilopascal per minute (MD, 0.40 mmol/kPa/min; 95%, CI 0.10-0.70 mmol/kPa/min) and risk of DLCO declining more than 15% (relative risk [RR], 0.27; 95% CI, 0.08-0.95) also favored pirfenidone. The risks of gastrointestinal discomfort (RR, 1.83; 95% CI, 1.29-2.60) and photosensitivity (RR, 4.88; 95% CI, 1.09-21.83) were higher with pirfenidone. The quality of the evidence was low or very low according to the Grading of Recommendations, Assessment, Development and Evaluation criteria, depending on the outcome. Conclusions: Pirfenidone use in patients with PPF is associated with a statistically significant decrease in disease progression and with protection of lung function. However, there is very low certainty in the estimated effects because of limitations in the available evidence. Primary Source of Funding: Funded by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.

Nintedanib in Progressive Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

Background: The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax convened to update clinical practice guidelines for interstitial lung disease (ILD). Objective: To conduct a systematic review to evaluate existing ILD literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic nintedanib. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using nintedanib to treat patients with PPF. Data Extraction: Mortality, disease progression, and adverse event data were extracted, and meta-analyses performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Synthesis: Two relevant studies were selected. The annual decline in forced vital capacity was less in the nintedanib arm in the overall study population (mean difference [MD], 107 ml/yr; 95% confidence interval [CI], 65.4 to 148.5 ml/yr) and in the subgroups with usual interstitial pneumonia (UIP) pattern of pulmonary fibrosis (MD, 128.2 ml/yr; 95% CI, 70.8 to 185.6 ml/yr), non-UIP patterns of pulmonary fibrosis (MD, 75.3 ml/yr; 95% CI, 15.5 to 135.0 ml/yr), fibrotic connective tissue disease-related ILD (MD, 106.2 ml/yr; 95% CI, 10.6 to 201.9 ml/yr), fibrotic idiopathic nonspecific interstitial pneumonia (MD, 141.7 ml/yr; 95% CI, 46.0 to 237.4 ml/yr), and fibrotic occupational ILD (MD, 252.8 ml/yr; 95% CI, 79.2 to 426.5 ml/yr), but not fibrotic hypersensitivity pneumonitis (MD, 72.9 ml/yr; 95% CI, -8.9 to 154.7 ml/yr), fibrotic sarcoidosis (MD, -20.5 ml/yr; 95% CI, -337.1 to 296.1 ml/yr), or unclassified fibrotic ILD (MD, 68.5 ml/yr; 95% CI, -31.3 to 168.4 ml/yr) when compared with placebo. Gastrointestinal side effects were common. Quality of evidence for the outcomes ranged from very low to moderate GRADE. Conclusions: Nintedanib use in patients with PPF is associated with a statistically significant decrease in disease progression but increase in gastrointestinal side effects regardless of the radiographic pattern of pulmonary fibrosis. However, limitations in the available evidence lead to low certainty in these effect estimates and make definitive conclusions about the differential effects by subtype of ILD difficult to determine. Primary Source of Funding: Funded by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.

Transbronchial Lung Cryobiopsy in Patients with Interstitial Lung Disease: A Systematic Review.

Rationale: In 2018, a systematic review evaluating transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD) was performed to inform American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guidelines on the diagnosis of idiopathic pulmonary fibrosis. Objectives: To perform a new systematic review to inform updated guidelines. Methods: Medline, Excerpta Medica Database, and the Cochrane Central Register of Controlled Trials (CCTR) were searched through June 2020. Studies that enrolled patients with ILD and reported the diagnostic yield or complication rates of TBLC were selected for inclusion. Data was extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the grading of recommendations, assessment, development, and evaluation approach. Results: Histopathologic diagnostic yield (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBLC was 80% (95% confidence interval [CI], 76-83%) in patients with ILD. TBLC was complicated by bleeding and pneumothorax in 30% (95% CI, 20-41%) and 8% (95% CI, 6-11%) of patients, respectively. Procedure-related mortality, severe bleeding, prolonged air leak, acute exacerbation, respiratory failure, and respiratory infection were rare. The quality of the evidence was very low owing to the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results. Conclusions: Very low-quality evidence indicated that TBLC has a diagnostic yield of approximately 80% in patients with ILD, with manageable complications.

Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.

Antacid Medication and Antireflux Surgery in Patients with Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia with impaired survival. Previous guidelines recommend antacid medication to improve respiratory outcomes in patients with IPF. Objectives: This systematic review was undertaken during the development of an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guideline. The clinical question was, "Should patients with IPF who have documented abnormal gastroesophageal reflux (GER) with or without symptoms of GER disease 1) be treated with antacid medication or 2) undergo antireflux surgery to improve respiratory outcomes?" Methods: Medline, Embase, the Cochrane Central Register of Controlled Trials, and the gray literature were searched through June 30, 2020. Studies that enrolled patients with IPF and 1) compared antacid medication to placebo or no medication or 2) compared antireflux surgery to no surgery were selected. Meta-analyses were performed when possible. Outcomes included disease progression, mortality, exacerbations, hospitalizations, lung function, respiratory symptoms, GER severity, and adverse effects/complications. Results: For antacid medication, when two studies were aggregated, there was no statistically significant effect on disease progression, defined as a 10% or more decline in FVC, more than 50-m decline in 6-minute walking distance, or death (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.76-1.03). A separate study that could not be included in the meta-analysis found no statistically significant effect on disease progression when defined as a 5% or more decline in FVC or death (RR, 1.10; 95% CI, 1.00-1.21) and an increase in disease progression when defined as a 10% or more decline in FVC or death (RR, 1.28; 95% CI, 1.08-1.51). For antireflux surgery, there was also no statistically significant effect on disease progression (RR, 0.29; 95% CI, 0.06-1.26). Neither antacid medications nor antireflux surgery was associated with improvements in the other outcomes. Conclusions: There is insufficient evidence to conclude that antacid medication or antireflux surgery improves respiratory outcomes in patients with IPF, most of whom had not had abnormal GER confirmed. Well-designed and adequately powered prospective studies with objective evaluation for GER are critical to elucidate the role of antacid medication and antireflux surgery for respiratory outcomes in patients with IPF.

Use of a Genomic Classifier in Patients with Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

Background: Usual interstitial pneumonia (UIP) is the histopathologic hallmark of idiopathic pulmonary fibrosis (IPF), the prototypical interstitial lung disease (ILD). Diagnosis of IPF requires that a typical UIP pattern be identified by using high-resolution chest computed tomography or lung sampling. A genomic classifier for UIP has been developed to predict histopathologic UIP by using lung samples obtained through bronchoscopy. Objective: To perform a systematic review to evaluate genomic classifier testing in the detection of histopathologic UIP to inform new American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guidelines. Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched through June 2020. Data Extraction: Data were extracted from studies that enrolled patients with ILD and reported the use of genomic classifier testing. Synthesis: Data were aggregated across studies via meta-analysis. The quality of the evidence was appraised by using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results: Genomic classifier testing had a sensitivity of 68% (95% confidence interval [CI], 55-73%) and a specificity of 92% (95% CI, 81-95%) in predicting the UIP pattern in ILD. Confidence in an IPF diagnosis increased from 43% to 93% in one cohort and from 59% to 89% in another cohort. Agreement levels in categorical IPF and non-IPF diagnoses measured by using a concordance coefficient were 0.75 and 0.64 in the two cohorts. The quality of evidence was moderate for test characteristics and very low for both confidence and agreement. Conclusions: Genomic classifier testing predicts histopathologic UIP in patients with ILD with a specificity of 92% and improves diagnostic confidence; however, sensitivity is only 68%, and testing is not widely available.

Pulmonary Arterial Hypertension in Patients Infected with the Human Immunodeficiency Virus.

It is important to recognize and treat human immunodeficiency virus-associated pulmonary arterial hypertension (HIV-PAH) because of the associated morbidity and mortality. With the introduction of antiretroviral therapies (ART), improved survival has changed the focus of treatment management from immunodeficiency-related opportunistic infections to chronic cardiovascular complications, including HIV-PAH. The 2018 6th World Symposium of Pulmonary Hypertension recommended a revised definition of PAH that might result in a greater number of patients with HIV-PAH; however, the implication of this change is not yet clear. Here, we review the current literature on the diagnosis, management, and outcomes of patients with HIV-PAH.

Pulmonary Tumor Thrombotic Microangiopathy as a Cause of Pulmonary Hypertension.

Pulmonary tumor thrombotic microangiopathy is a rare entity, often diagnosed postmortem. We describe a patient with signs and symptoms of pulmonary hypertension secondary to metastatic cholangiocarcinoma with invasion of the myocardium and pulmonary vasculature, and highlight the diagnostic challenges and therapeutic limitations of this disease. (Level of Difficulty: Intermediate.).

Treatment of pulmonary hypertension in patients with Hereditary Hemorrhagic Telangiectasia - A case series and systematic review.

RATIONALE: Pulmonary Arterial Hypertension (PAH), a rare complication of HHT is associated with poor outcome. There are no trials to date that have investigated whether pulmonary vasodilator therapy improves hemodynamics or survival in this disease. OBJECTIVE: To determine whether pulmonary vasodilator therapy improves survival, exercise capacity, or hemodynamics in HHT patients with pre-capillary PH. METHODS: We performed a before-and-after observational study on a multicenter cohort of subjects with HHT-PAH who received intravenous prostanoid therapy. We then conducted a systematic review, searching Medline and EMBASE through December 2019. Studies that enrolled HHT-PAH subjects and reported treatment outcomes were selected. PROSPERO #158179. RESULTS: Twenty-one articles were selected. Studies were before-and-after observational studies, case reports, and case series. Among all subjects with HHT-PAH, both mPAP (65 ± 19 pre-treatment vs 51 ± 16 mmHg post-treatment p = 0.04) and PVR (12 ± 6 pre-treatment vs 8 ± 4 WU post-treatment p = 0.01) improved with treatment. The mPAP improved with either oral (57 ± 17 pre-treatment versus 44 ± 13 mmHg post-treatment, p = 0.03) or intravenous (80 ± 15 pre-treatment versus 64 ± 16 mmHg post-treatment, p = 0.017) therapy. PVR also improved with either oral (10 ± 4 pre-treatment versus 6 ± 3 WU post-treatment, p = 0.004) or intravenous (17 ± 5 pre-treatment versus 10 ± 4 WU post-treatment, p = 0.04) therapy. Survival among HHT-PAH patients who received oral or intravenous therapy was not different (p = 0.2). Unadjusted survival among HHT-PAH patients was longer than that of IPAH patients (p = 0.008). There was no difference in side effects among HHT-PAH patient who received oral or intravenous therapy (p = 0.1). CONCLUSION: Pulmonary vasodilator therapy is effective in improving hemodynamics of subjects with HHT-PAH and was not associated with increased risk of side effects.

Intentional suspected suicide exposures by poisoning among adolescents from 2009 to 2018 reported to the Georgia Poison Center and compared nationally.

This retrospective chart review aimed to report the incidence and characteristics of intentional suspected suicide among 13- to 19-year-olds reported to the Georgia Poison Center (GPC) and compared nationally from 2009 to 2018. Of the 19 733 cases reported to the GPC, 74.9% were females. The total number of cases more than doubled from 2009 to 2018, increasing annually by 10%. Majority (90.1%) of the cases occurred in the home, and 60.4% of the cases resulted in either no effect or minor effect. More than half (66.5%) of the cases involved only one substance. Pharmaceuticals made up 94.5% of the substances used, with analgesics accounting for 42.10% and antidepressants at 20.77%. A significant difference was found in substances used between males and females (P < .001). Females were more likely to use analgesics (45.17% vs 32.90%), and males were more likely to use sedatives/hypnotics/antipsychotics (20.45% vs 13.58%). While the majority of the GPC patients were females, the GPC was more likely to have fewer female patients (74.7% vs 75.7%) and more male patients (25.3% vs 24.3%) than other poison centers. Intentional suspected suicide exposures by poisoning are on the rise and higher among females, demonstrating a need for strengthened intervention and prevention strategies.

Proteomic Analysis and Cell Viability of Nine Amnion, Chorion, Umbilical Cord, and Amniotic Fluid-Derived Products.

OBJECTIVE: Amnion products are used in various musculoskeletal surgeries and as injections for joint pain with conflicting reports of cell viability and protein contents. The objective of this study was to determine the full proteome and examine cell viability in 9 commercial amnion products using an unbiased bottom-up shotgun proteomics approach and confocal microscopy. DESIGN: Products were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and searched against a UniProt Homo sapiens database. Relative protein abundance was determined for each sample. Based on proteomics results, lumican was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis was performed for interleukin-1 receptor antagonist (IL-1Ra) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2). Cell viability was determined by calcein AM (live) and ethidium homodimer (dead) staining and confocal microscopy. RESULTS: Proteomic analysis revealed 919 proteins in the nine products. Proteins were primarily collagens, keratin, and albumin. Lumican, a small leucine-rich proteoglycan (SLRP) was found in all samples. Western blot analysis for IL-1Ra and TIMP-2 indicated presence of both proteins, with nonspecific antibody binding also present in all samples. No live cells were identified in any product. CONCLUSIONS: Several novel proteins were identified through proteomics that might impart the beneficial effects of amnion products, including SLRPs, collagens, and regulators of fibroblast activity. IL-1Ra and TIMP-2 were identified, but concentrations measured by ELISA may be falsely increased due to nonspecific antibody binding. The concept that the amnion tissues provide live cells to aid in tissue regeneration cannot be supported by the findings of this study.

Lung megakaryocytes display distinct transcriptional and phenotypic properties.

Megakaryocytes (MKs) are responsible for platelet biogenesis, which is believed to occur canonically in adult bone marrow (BM) and in the fetal liver during development. However, emerging evidence highlights the lung as a previously underappreciated residence for MKs that may contribute significantly to circulating platelet mass. Although a diversity of cells specific to the BM is known to promote the maturation and trafficking of MKs, little investigation into the impact of the lung niche on the development and function of MKs has been done. Here, we describe the application of single-cell RNA sequencing, coupled with histological, ploidy, and flow cytometric analyses, to profile primary MKs derived from syngeneic mouse lung and hematopoietic tissues. Transcriptional profiling demonstrated that lung MKs have a unique signature distinct from their hematopoietic counterparts, with lung MKs displaying enrichment for maturation markers, potentially indicating a propensity for more efficient platelet production. Reciprocally, fetal lung MKs also showed the robust expression of cytokines and growth factors that are known to promote lung development. Lastly, lung MKs possess an enrichment profile skewed toward roles in immunity and inflammation. These findings highlight the existence of a lung-specific MK phenotype and support the notion that the lung plays an independent role in the development and functional maturation of MKs. The immune phenotype displayed by lung MKs also introduces their potential role in microbial surveillance and antigen presentation.

Long-term outcomes of epoprostenol therapy in sarcoid associated pulmonary hypertension.

Sarcoidosis-Associated Pulmonary Hypertension (SAPH) is a common finding in patients with chronic sarcoidosis and is associated with increased mortality. The optimal treatment for SAPH is not known; however, therapies approved for Group 1 pulmonary hypertension have improved hemodynamics and functional status. Prostanoids, including epoprostenol, have been therapeutic in short-term studies of SAPH, but long-term efficacy is unknown. In this study, we evaluated the long-term effect of epoprostenol therapy in 12 patients with SAPH. Hemodynamic assessment after an average of 4.1 years of epoprostenol therapy demonstrated significant improvement in mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output; furthermore, patients demonstrated improved NYHA functional class. To evaluate further the long-term effect of epoprostenol, we compared survival of SAPH patients to a cohort of hemodynamically matched patients from the same center treated with epoprostenol for Idiopathic Pulmonary Arterial Hypertension (IPAH). Interestingly, there was no difference in survival, despite the additional systemic disease burden of the SAPH subjects. Subgroup analysis by Scadding stage demonstrated that Scadding stages 1-3 had improved survival compared to Scadding stage 4. These observations suggest that epoprostenol is an effective long-term therapy for patients with SAPH; it improves hemodynamics, functional class, and provides survival similar to that seen in a hemodynamically-matched cohort of IPAH patients. Furthermore, we identify a subgroup of SAPH patients (nonfibrotic lung disease Scadding 1-3) who may derive significant benefit from prostanoid therapy. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 184-191).