Ventilator-induced Lung Injury Promotes Inflammation within the Pleural Cavity.

Mechanical ventilation contributes to the morbidity and mortality of patients in intensive care, likely through the exacerbation and dissemination of inflammation. Despite the proximity of the pleural cavity to the lungs and exposure to physical forces, little attention has been paid to its potential as an inflammatory source during ventilation. Here, we investigate the pleural cavity as a novel site of inflammation during ventilator-induced lung injury. Mice were subjected to low or high tidal volume ventilation strategies for up to 3 hours. Ventilation with a high tidal volume significantly increased cytokine and total protein levels in BAL and pleural lavage fluid. In contrast, acid aspiration, explored as an alternative model of injury, only promoted intraalveolar inflammation, with no effect on the pleural space. Resident pleural macrophages demonstrated enhanced activation after injurious ventilation, including upregulated ICAM-1 and IL-1ß expression, and the release of extracellular vesicles. In vivo ventilation and in vitro stretch of pleural mesothelial cells promoted ATP secretion, whereas purinergic receptor inhibition substantially attenuated extracellular vesicles and cytokine levels in the pleural space. Finally, labeled protein rapidly translocated from the pleural cavity into the circulation during high tidal volume ventilation, to a significantly greater extent than that of protein translocation from the alveolar space. Overall, we conclude that injurious ventilation induces pleural cavity inflammation mediated through purinergic pathway signaling and likely enhances the dissemination of mediators into the vasculature. This previously unidentified consequence of mechanical ventilation potentially implicates the pleural space as a focus of research and novel avenue for intervention in critical care.

A systematic critical appraisal of clinical practice guidelines of antithrombotic agents in gastrointestinal endoscopy using the AGREE II tool.

BACKGROUND AND AIM: The quality of clinical practice guidelines (CPGs) for the management of antithrombotic agents in patients undergoing gastrointestinal (GI) endoscopy has not been systematically appraised. The goal of this study was to evaluate the methodological quality of CPGs for the management of antithrombotic agents in periendoscopic period published within last 6 years. METHODS: A systematic search of PubMed and Embase databases was performed to identify eligible CPGs published between January 1, 2016, and April 14, 2022, addressing the management of antithrombotic agents in the periendoscopic period. The quality of the CPG was independently assessed by six reviewers using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Domain scores were considered of sufficient quality when > 60% and of good quality when > 80%. RESULTS: The search yielded 343 citations, of which seven CPGs published by the gastroenterology associations in Asia (n = 3), Europe (n = 2), and North America (n = 2) were included for the critical appraisal. The overall median score for the AGREE II domains was 93% (interquartile range [IQR] 11%) for scope and purpose, 79% (IQR 61%) for stakeholder involvement, 79% (IQR 36%) for rigor of development, 100% (IQR 14%) for clarity of presentation, 32% (IQR 36%) for applicability, 93% (IQR 29%) for editorial independence, and 86% (IQR 29%) for overall assessment. CONCLUSIONS: The findings show that the overall methodological quality of the CPGs for the management of antithrombotic agents in the periendoscopic period varies across the domains. There is significant scope for improvement in the methodological rigor and applicability of CPGs.

Clinical practice, decision-making, and use of clinical decision support systems in invasive mechanical ventilation: a narrative review.

Invasive mechanical ventilation is a key supportive therapy for patients on intensive care. There is increasing emphasis on personalised ventilation strategies. Clinical decision support systems (CDSS) have been developed to support this. We conducted a narrative review to assess evidence that could inform device implementation. A search was conducted in MEDLINE (Ovid) and EMBASE. Twenty-nine studies met the inclusion criteria. Role allocation is well described, with interprofessional collaboration dependent on culture, nurse:patient ratio, the use of protocols, and perception of responsibility. There were no descriptions of process measures, quality metrics, or clinical workflow. Nurse-led weaning is well-described, with factors grouped by patient, nurse, and system. Physician-led weaning is heterogenous, guided by subjective and objective information, and 'gestalt'. No studies explored decision-making with CDSS. Several explored facilitators and barriers to implementation, grouped by clinician (facilitators: confidence using CDSS, retaining decision-making ownership; barriers: undermining clinician's role, ambiguity moving off protocol), intervention (facilitators: user-friendly interface, ease of workflow integration, minimal training requirement; barriers: increased documentation time), and organisation (facilitators: system-level mandate; barriers: poor communication, inconsistent training, lack of technical support). One study described factors that support CDSS implementation. There are gaps in our understanding of ventilation practice. A coordinated approach grounded in implementation science is required to support CDSS implementation. Future research should describe factors that guide clinical decision-making throughout mechanical ventilation, with and without CDSS, map clinical workflow, and devise implementation toolkits. Novel research design analogous to a learning organisation, that considers the commercial aspects of device design, is required.

A Comparison of Long-Term Outcomes in Patients Managed With Venovenous Extracorporeal Membrane Oxygenation in the First and Second Waves of the COVID-19 Pandemic in the United Kingdom.

OBJECTIVES: Early studies of venovenous extracorporeal membrane oxygenation (ECMO) in COVID-19 have revealed similar outcomes to historical cohorts. Changes in the disease and treatments have led to differences in the patients supported on venovenous ECMO in the first and second waves. We aimed to compare these two groups in both the acute and follow-up phase. DESIGN: Retrospective single-center cohort study comparing mortality at censoring date (November 30, 2021) and decannulation, patient characteristics, complications and lung function and quality of life (QOL-by European Quality of Life 5 Dimensions 3 Level Version) at first follow-up in patients supported on venovenous ECMO between wave 1 and wave 2 of the COVID-19 pandemic. SETTING: Critical care department of a severe acute respiratory failure service. PATIENTS: Patients supported on ECMO for COVID-19 between wave 1 (March 17, 2020, to August 31, 2020) and wave 2 (January 9, 2020, to May 25, 2021). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three patients were included in our analysis. Survival at censoring date (χ 2 , 6.35; p = 0.012) and decannulation (90.4% vs 70.0%; p < 0.001) was significantly lower in the second wave, while duration of ECMO run was longer (12.0 d [18.0-30.0 d] vs 29.5 d [15.5-58.3 d]; p = 0.005). Wave 2 patients had longer application of noninvasive ventilation (NIV) prior to ECMO and a higher frequency of barotrauma. Patient age and NIV use were independently associated with increased mortality (odds ratio 1.07 [1.01-1.14]; p = 0.025 and 3.37 [1.12-12.60]; p = 0.043, respectively). QOL and lung function apart from transfer coefficient of carbon monoxide corrected for hemoglobin was similar at follow-up across the waves. CONCLUSIONS: Most patients with COVID-19 supported on ECMO in both waves survived in the short and longer term. At follow-up patients had similar lung function and QOL across the two waves. This suggests that ECMO has an ongoing role in the management of a carefully selected group of patients with COVID-19.

Quantitative single photon emission computed tomography derived standardized uptake values on 99mTc-PYP scan in patients with suspected ATTR cardiac amyloidosis.

Technetium-99 pyrophosphate scintigraphy (99mTc-PYP) provides qualitative and semiquantitative diagnosis of ATTR cardiac amyloidosis (ATTR-CA) using the Perugini scoring system and heart/contralateral heart ratio (H/CL) on planar imaging. Standardized uptake values (SUV) with quantitative single photon emission computed tomography (xSPECT/CT) can offer superior diagnostic accuracy and quantification through precise myocardial contouring that enhances assessment of ATTR-CA burden. We examined the correlation of xSPECT/CT SUVs with Perugini score and H/CL ratio. We also assessed SUV correlation with cardiac magnetic resonance (CMR), echocardiographic, and baseline clinical characteristics. Retrospective review of 78 patients with suspected ATTR-CA that underwent 99mTc-PYP scintigraphy with xSPECT/CT. Patients were grouped off Perugini score (Grade 0-1 and Grade 2-3), H/CL ratio (≥ 1.5 and < 1.5). Two cohorts were also created: myocardium SUVmax > 1.88 and ≤ 1.88 at 1-hour based off an AUC curve with 1.88 showing the greatest sensitivity and specificity. Cardiac SUV retention index was calculated as [SUVmax myocardium/SUVmax vertebrae] × SUVmax paraspinal muscle. Primary outcome was myocardium SUVmax at 1-hour correlation with Perugini grades, H/CL ratio, CMR, and echocardiographic data. Higher Perugini Grades corresponded with higher myocardium SUVmax values, especially when comparing Perugini Grade 3 to Grade 2 and 1 (3.03 ± 2.1 vs 0.59 ± 0.97 and 0.09 ± 0.2, P < 0.001). Additionally, patients with H/CL ≥ 1.5 had significantly higher myocardium SUVmax compared to patients with H/CL ≤ 1.5 (2.92 ± 2.18 vs 0.35 ± 0.60, P < 0.01). Myocardium SUVmax at 1-hour strongly correlated with ECV (r = 0.91, P = 0.001), pre-contrast T1 map values (r = 0.66, P = 0.037), and left ventricle mass index (r = 0.80, P = 0.002) on CMR. SUVs derived from 99mTc-PYP scintigraphy with xSPECT/CT provides a discriminatory and quantitative method to diagnose and assess ATTR-CA burden. These findings strongly correlate with CMR.

Vascular Inflammation, Cancer, and Cardiovascular Diseases.

PURPOSE OF REVIEW: Cancer and cardiovascular disease are among the leading causes of morbidity and mortality in the USA. Cancer and cardiovascular disease have inflammatory underpinnings that have been associated with both the development and progression of these disease states. RECENT FINDINGS: Inflammatory signaling has been found to be a critical event in both cardiovascular disease and cancer formation and progression. Further, many chemotherapeutic agents potentiate inflammation exacerbating existing cardiovascular disease or leading to its presence. The exact mechanisms of these interactions remain poorly understood. The proinflammatory milieu observed in both cancer and cardiovascular disease likely plays an important role in the development and potentiation of both conditions. Further evaluation of this relationship will be critical in the development of new diagnostic and therapeutic modalities.

Enhancing European Management of Analgesia, Sedation, and Delirium: A Multinational, Prospective, Interventional Before-After Trial.

BACKGROUND: The objective of this study was to analyze the impact of a structured educational intervention on the implementation of guideline-recommended pain, agitation, and delirium (PAD) assessment. METHODS: This was a prospective, multinational, interventional before-after trial conducted at 12 intensive care units from 10 centers in Germany, Austria, Switzerland, and the UK. Intensive care units underwent a 6-week structured educational program, comprising online lectures, instructional videos, educational handouts, and bedside teaching. Patient-level PAD assessment data were collected in three 1-day point-prevalence assessments before (T1), 6 weeks after (T2), and 1 year after (T3) the educational program. RESULTS: A total of 430 patients were included. The rate of patients who received all three PAD assessments changed from 55% (107/195) at T1 to 53% (68/129) at T2, but increased to 73% (77/106) at T3 (p = 0.003). The delirium screening rate increased from 64% (124/195) at T1 to 65% (84/129) at T2 and 77% (82/106) at T3 (p = 0.041). The pain assessment rate increased from 87% (170/195) at T1 to 92% (119/129) at T2 and 98% (104/106) at T3 (p = 0.005). The rate of sedation assessment showed no signficiant change. The proportion of patients who received nonpharmacological delirium prevention measures increased from 58% (114/195) at T1 to 80% (103/129) at T2 and 91% (96/106) at T3 (p < 0.001). Multivariable regression revealed that at T3, patients were more likely to receive a delirium assessment (odds ratio [OR] 2.138, 95% confidence interval [CI] 1.206-3.790; p = 0.009), sedation assessment (OR 4.131, 95% CI 1.372-12.438; p = 0.012), or all three PAD assessments (OR 2.295, 95% CI 1.349-3.903; p = 0.002) compared with T1. CONCLUSIONS: In routine care, many patients were not assessed for PAD. Assessment rates increased significantly 1 year after the intervention. Clinical trial registration ClinicalTrials.gov: NCT03553719.

Intranasal spray of cubosomal tizanidine hydrochloride for brain targeting: in vitro and in vivo characterisation.

Tizanidine HCl (TH) is used as first-line therapy for the treatment of muscular spasm. The intranasal cubosomal delivery system of TH for site-specific delivery, i.e. CNS was developed. Cubosomes of TH were prepared using glyceryl monooleate (GMO) as a lipid, poloxamer 407 as stabiliser, and ethanol and polyethylene glycol 200 as co-solvent. Optimised cubosomes of TH were characterised for vesicle size, zeta potential, % drug entrapment, and mucin binding efficiency, which were found to be 50.22 nm, -6.39 mV, 69.28%, and 42.12%. It is also evaluated for CRYO-FESEM, CRYO-TEM, SAXS, residual solvent content, and in vitro drug release. Ex vivo permeation was also conducted at 7.4 and it indicates that almost 93.66% drug was diffused from a formulation in 6 h. Histopathological study of the optimised TH cubosomes suggests that the prepared formulation is non-toxic to the nasal mucosa. Pharmacokinetic and brain distribution study indicates targeted action of the formulated TH cubosomes.

RAND appropriateness panel to determine the applicability of UK guidelines on the management of acute respiratory distress syndrome (ARDS) and other strategies in the context of the COVID-19 pandemic.

BACKGROUND: COVID-19 has become the most common cause of acute respiratory distress syndrome (ARDS) worldwide. Features of the pathophysiology and clinical presentation partially distinguish it from 'classical' ARDS. A Research and Development (RAND) analysis gauged the opinion of an expert panel about the management of ARDS with and without COVID-19 as the precipitating cause, using recent UK guidelines as a template. METHODS: An 11-person panel comprising intensive care practitioners rated the appropriateness of ARDS management options at different times during hospital admission, in the presence or absence of, or varying severity of SARS-CoV-2 infection on a scale of 1-9 (where 1-3 is inappropriate, 4-6 is uncertain and 7-9 is appropriate). A summary of the anonymised results was discussed at an online meeting moderated by an expert in RAND methodology. The modified online survey comprising 76 questions, subdivided into investigations (16), non-invasive respiratory support (18), basic intensive care unit management of ARDS (20), management of refractory hypoxaemia (8), pharmacotherapy (7) and anticoagulation (7), was completed again. RESULTS: Disagreement between experts was significant only when addressing the appropriateness of diagnostic bronchoscopy in patients with confirmed or suspected COVID-19. Adherence to existing published guidelines for the management of ARDS for relevant evidence-based interventions was recommended. Responses of the experts to the final survey suggested that the supportive management of ARDS should be the same, regardless of a COVID-19 diagnosis. For patients with ARDS with COVID-19, the panel recommended routine treatment with corticosteroids and a lower threshold for full anticoagulation based on a high index of suspicion for venous thromboembolic disease. CONCLUSION: The expert panel found no reason to deviate from the evidence-based supportive strategies for managing ARDS outlined in recent guidelines.

Cardiogenic shock in autoimmune rheumatologic diseases: an insight on etiologies, management, and treatment outcomes.

Autoimmune rheumatological disorders are known to have an increased risk for cardiovascular diseases including coronary artery disease (CAD), myocarditis, pericarditis, valvulopathy, and in consequence cardiogenic shock. Data on cardiogenic shock in rheumatological diseases are scarce; however, several reports have highlighted this specific entity. We sought to review the available literature and highlight major outcomes and the management approaches in each disease. Systematic literature search, including PubMed, Ovid/Medline, Cochrane Library, and Web of Science, was conducted between January 2000 and December 2009. We reviewed all cases reporting cardiogenic shock with rheumatologic conditions, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Takayasu's arteritis (TA), granulomatosis with polyangiitis (GPA), giant cell arteritis (GCA), and antiphospholipid syndrome (APS). We selected 45 papers reporting a total of 48 cases. Mean age was 39 ± 7.3 years and 68.8% were females. Most common rheumatologic conditions associated with cardiogenic shock were SLE (31%), GPA (23%), TA (14.6%), APA (10.4%), and RA (8.3%). Cardiogenic shock was found to be caused by eosinophilic myocarditis in 58% of cases, CAD in 19% of cases, and valvulopathy in 6% of cases. Most patient required high-dose steroids and second immunosuppressant therapy. Mechanical circulatory supported was required in 23 cases, IABP in 16 cases, and ECMO in 12 cases. Complete recovery occurred in 37 patients while 9 patients died and 2 required heart transplant. Responsible for two-thirds of cases, eosinophilic myocarditis should be suspected in young cardiogenic shock patients with underlying rheumatologic conditions. Lupus and GPA are the two most common conditions.

Secreted Extracellular Cyclophilin A Is a Novel Mediator of Ventilator-induced Lung Injury.

Rationale: Mechanical ventilation is a mainstay of intensive care but contributes to the mortality of patients through ventilator-induced lung injury. eCypA (extracellular CypA [cyclophilin A]) is an emerging inflammatory mediator and metalloproteinase inducer, and the gene responsible for its expression has recently been linked to coronavirus disease (COVID-19). Objectives: To explore the involvement of eCypA in the pathophysiology of ventilator-induced lung injury. Methods: Mice were ventilated with a low or high Vt for up to 3 hours, with or without blockade of eCypA signaling, and lung injury and inflammation were evaluated. Human primary alveolar epithelial cells were exposed to in vitro stretching to explore the cellular source of eCypA, and CypA concentrations were measured in BAL fluid from patients with acute respiratory distress syndrome to evaluate the clinical relevance. Measurements and Main Results: High-Vt ventilation in mice provoked a rapid increase in soluble CypA concentration in the alveolar space but not in plasma. In vivo ventilation and in vitro stretching experiments indicated the alveolar epithelium as the likely major source. In vivo blockade of eCypA signaling substantially attenuated physiological dysfunction, macrophage activation, and MMPs (matrix metalloproteinases). Finally, we found that patients with acute respiratory distress syndrome showed markedly elevated concentrations of eCypA within BAL fluid. Conclusions: CypA is upregulated within the lungs of injuriously ventilated mice (and critically ill patients), where it plays a significant role in lung injury. eCypA represents an exciting novel target for pharmacological intervention.

Managing Harlequin Syndrome in VA-ECMO - do not forget the right ventricle.

Harlequin Syndrome (also known as North-South Syndrome) is a complication of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) that can occur when left ventricular function starts to recover. While most commonly due to continued impaired gas exchange in the lungs, we present a case caused by right ventricular dysfunction, successfully managed by conversion of the ECMO circuit to a veno-veno-arterial (VV-A) configuration.

Cardiovascular Imaging in Cardio-Oncology: The Role of Echocardiography and Cardiac MRI in Modern Cardio-Oncology.

Cardiovascular (CV) events are an increasingly common limitation of effective anticancer therapy. Over the last decade imaging has become essential to patients receiving contemporary cancer therapy. Herein we discuss the current state of CV imaging in cardio-oncology. We also provide a practical apparatus for the use of imaging in everyday cardiovascular care of oncology patients to improve outcomes for those at risk for cardiotoxicity, or with established cardiovascular disease. Finally, we consider future directions in the field given the wave of new anticancer therapies.

Readmission-free period and in-hospital mortality at the time of first readmission in acute heart failure patients-NRD-based analysis of 40,000 heart failure readmissions.

The 30-day readmission rates, predictors, and outcomes for acute heart failure (AHF) patients are well published, but data beyond 30 days and the association between readmission-free period (RFP) and in-hospital readmission-related mortality remain unknown. We queried the National Readmission Database to analyze comparative outcomes of AHF. Patients were divided into three groups based on their RFP: group 1 (1-30 days), group 2 (31-90 days), and group 3 (91-275 days). AHF cases and clinical variables were identified using ICD-9 codes. The primary outcome was in-hospital mortality at the time of readmission. A total of 39,237 unplanned readmissions occurred within 275 days; 15,181 within group 1, 11,925 within group 2, and 12,131 within group 3. In-hospital mortality in groups 1, 2, and 3 were 7.4%, 5.1%, and 4.1% (p < 0.001). Group 1 had higher percentages of patients with cardiogenic shock (1.3% vs. 0.9% vs. 0.9%; p < 0.001), acute kidney injury (30.2% vs. 25.9% vs. 24.0%; p < 0.001), dialysis use (8.6% vs. 7.5% vs. 6.9%; p < 0.001), and non-ST elevation myocardial infarction (4.4% vs. 3.8% vs. 3.6%; p < 0.001), but there was no statistical difference among the three groups for ST-elevation myocardial infarction, percutaneous coronary intervention (PCI), or ventricular assist device use at the time of index admission. However, group 3 had higher PCI (1.7%) compared with groups 1 and 2 (p < 0.001). In multivariable logistic regression, groups 2 and 3 had odd ratio of 0.70 and 0.55, respectively, for in-hospital mortality compared with group 1. Longer RFP is associated with decreased risk of in-hospital mortality at the time of first readmission.

Etiologies and predictors of readmission among obese and morbidly obese patients admitted with heart failure.

The relationship between severity of obesity and outcomes in heart failure (HF) has long been under debate. We studied index HF admissions from the 2013-14 National Readmission Database. Admissions were separated into three weight-based categories: non-obese (Non-Ob), obese (Ob), and morbidly obese (Morbid-Ob) to analyze hospital mortality and readmission at 30 days and 6 months. We investigated etiologies and predictors of 30-day readmission among these weight categories. We studied a total of 578,213 patients of whom 3.0% died during index hospitalization (Non-Ob 3.3% vs. Ob 1.9% vs. Morbid-Ob 1.9%; p < 0.01). Non-Ob comprised 79.5%, Ob 9.9%, and Morbid-Ob 10.6% of patients. Morbid-Ob patients were the youngest among age categories and more likely to be female. In-hospital mortality during readmission at 30 days and 6 months was significantly lower among Morbid-Ob and Ob compared with Non-Ob patients (all p < 0.01). Thirty-day readmission among Morbid-Ob was lower than Non-Ob and higher than Ob patients (19.6% vs. 20.5% vs. 18.6%, respectively; p < 0.01). Morbid-Ob patients were less likely to be readmitted for cardiovascular etiologies compared with both Ob and Non-Ob (45.0% vs. 50.3% vs. 50.6%; p < 0.01). Multivariable regression analysis revealed that Ob (adjusted odds ratio 0.84, 95% confidence intervals 0.82-0.86) and Morbid-Ob (aOR 0.83, 95% CI 0.81-0.85) were independently associated with lower 30-day readmission. Readmission at 6 months was highest among Morbid-Ob followed by Non-Ob and Ob (51.1% vs. 50.2% vs. 49.1%, p < 0.01). Morbid-Ob and Ob patients experience lower in-hospital mortality during index HF admission and during readmission with 30 days or 6 months compared with Non-Ob. Morbid-Ob patients experience greater readmission at 6 months despite the lower rate at 30 days post discharge. Morbid-Ob patients are most likely to be readmitted for non-cardiovascular causes.

Gender-based outcomes of impeller pumps percutaneous ventricular assist devices.

BACKGROUND: There is paucity of data focusing on females' outcomes after the use of impeller pumps percutaneous ventricular assist devices (IPVADs). METHODS: Patients who received IPVADs during the period of October 1st, 2015-December 31, 2017, were identified from the United States National Readmission Database. A 1:1 propensity score matching was used to compare the outcomes between females and males. RESULTS: A total of 19,278 (Female = 5,456; Male = 13,822) patients were included in the current analysis. After propensity score matching and among all-comers who were treated with IPVADs, females had higher in-hospital major adverse events (MAEs) (38 vs. 32.6%, p < .01), mortality (31 vs. 28%, p < .01), vascular complications (3.3 vs. 2.1%, p < .01), major bleeding (7.8 vs. 4.8%, p < .01), nonhome discharges (21.6 vs. 16.3%; p < .01), and longer length of stay (7 days [IQR 2-12] vs. 6 days [IQR 2-12], p = .02) with higher 30-day readmission rate compared to males (20.5 vs.16.4%, p < .01). Furthermore, among patients who received the IPVADs for high-risk percutaneous coronary intervention (HRPCI), females continued to have worse MAEs, which was driven by high rates of major bleeding. However, among patients who received IPVADs for cardiogenic shock (CS) the outcomes of females and males were comparable. CONCLUSIONS: Among all-comers who received IPVADs, females suffered higher morbidity and mortality compared to males. Higher morbidity driven mainly by higher rates of major bleeding was seen among females who received IPVADs for the hemodynamic support during HRPCI and comparable outcomes were observed when the IPVADs were used for CS.

Sex-stratified analysis of the safety of percutaneous left atrial appendage occlusion.

OBJECTIVES AND BACKGROUND: There is insufficient current evidence about whether sex impacts outcomes of percutaneous left atrial appendage occlusion (LAAO). The aim of this study was to investigate the association between sex and short-term outcomes of LAAO. METHODS: Patients who were hospitalized and underwent LAAO from October 2015 to December 2017 in the National Readmission Database were queried. The primary endpoint of interest was major in-hospital adverse events. Secondary endpoints included, 30-day readmission rate, nonhome discharge, and cost of hospitalization. Propensity score matching (1:1) was performed to compare the outcomes among women and men. RESULTS: A total of 9,281 patients were included in the current analysis [women = 3,659 (39%); men = 5,622 (61%)]. Comparing women to men, women had lower prevalence of diabetes mellitus (30.6% vs 35.7%, p < .01), heart failure (28.6% vs 30.8%, p = .03), vascular disease (55.5% vs 69.6%, p < .01) and renal failure (18.3% vs 21.2%, p < .01), and higher CHA2 DS2 VASc score (5 [IQR4-6] vs 4 [IQR3-6], p < .01). After propensity-score matching, women had higher rate of major in-hospital adverse events (2.8% vs 1.9%; p < .01), and nonhome discharges (11.4% vs 6.7%; p < .01). Additionally, 30-day readmission rate was higher among women (10% vs 8.6%, p = .03). CONCLUSION: Among hospitalized patients undergoing LAAO, women carry higher risk for major in-hospital adverse events, nonhome discharge, and 30-day readmission rates.

Microtubule Inhibitors and Cardiotoxicity.

PURPOSE OF REVIEW: Cancer and heart disease are the leading causes of mortality in the USA. Advances in cancer therapies, namely, the development and use of chemotherapeutic agents alone or in combination, are becoming increasingly prevalent. RECENT FINDINGS: Many chemotherapeutic agents have been associated with adverse cardiovascular manifestations. The mechanisms of these sequelae remain incompletely understood. In particular, microtubule inhibitor (MTI) agents have been related to the development of heart failure, myocardial ischemia, and conduction abnormalities. At present, there are no guidelines for patients undergoing MTI therapy as it pertains to both preventative and mitigatory strategies for cardiovascular complications. We conducted a literature review focusing on content related to the use of MTIs and their effect on the cardiovascular system. MTIs have been associated with various forms of cardiotoxicity, and fatal cardiotoxicities are rare. The most well-described cardiotoxicities are brady- and tachyarrhythmias. The co-administration of anthracycline-based agents with MTIs can increase the risk of cardiotoxicity.

Pulmonary Angiopathy in Severe COVID-19: Physiologic, Imaging, and Hematologic Observations.

Rationale: Clinical and epidemiologic data in coronavirus disease (COVID-19) have accrued rapidly since the outbreak, but few address the underlying pathophysiology.Objectives: To ascertain the physiologic, hematologic, and imaging basis of lung injury in severe COVID-19 pneumonia.Methods: Clinical, physiologic, and laboratory data were collated. Radiologic (computed tomography (CT) pulmonary angiography [n = 39] and dual-energy CT [DECT, n = 20]) studies were evaluated: observers quantified CT patterns (including the extent of abnormal lung and the presence and extent of dilated peripheral vessels) and perfusion defects on DECT. Coagulation status was assessed using thromboelastography.Measurements and Results: In 39 consecutive patients (male:female, 32:7; mean age, 53 ± 10 yr [range, 29-79 yr]; Black and minority ethnic, n = 25 [64%]), there was a significant vascular perfusion abnormality and increased physiologic dead space (dynamic compliance, 33.7 ± 14.7 ml/cm H2O; Murray lung injury score, 3.14 ± 0.53; mean ventilatory ratios, 2.6 ± 0.8) with evidence of hypercoagulability and fibrinolytic "shutdown". The mean CT extent (±SD) of normally aerated lung, ground-glass opacification, and dense parenchymal opacification were 23.5 ± 16.7%, 36.3 ± 24.7%, and 42.7 ± 27.1%, respectively. Dilated peripheral vessels were present in 21/33 (63.6%) patients with at least two assessable lobes (including 10/21 [47.6%] with no evidence of acute pulmonary emboli). Perfusion defects on DECT (assessable in 18/20 [90%]) were present in all patients (wedge-shaped, n = 3; mottled, n = 9; mixed pattern, n = 6).Conclusions: Physiologic, hematologic, and imaging data show not only the presence of a hypercoagulable phenotype in severe COVID-19 pneumonia but also markedly impaired pulmonary perfusion likely caused by pulmonary angiopathy and thrombosis.

Unilateral intrusion in a medically complex patient using an orthodontic mini-implant: A case report.

Orthognathic surgery offers a predictable treatment option for patients with skeletal discrepancies and corresponding dental malocclusions. In cases where surgery is not advised due to significant medical co-morbidity, the orthodontist must approach the treatment using different mechanical modalities. Orthodontic mini-implants can be a valuable adjunct in these cases. We describe a case where a palatal mini-implant was used during orthodontic treatment in a patient with a complex capillary malformation, which precluded surgical correction.