Cardiovascular effects of the post-COVID-19 condition.

Throughout the COVID-19 pandemic, the new clinical entity of the post-COVID-19 condition, defined as a multisystemic condition of persistent symptoms following resolution of an acute severe acute respiratory syndrome coronavirus 2 infection, has emerged as an important area of clinical focus. While this syndrome spans multiple organ systems, cardiovascular complications are often the most prominent features. These include, but are not limited to, myocardial injury, heart failure, arrhythmias, vascular injury/thrombosis and dysautonomia. As the number of individuals with the post-COVID-19 condition continues to climb and overwhelm medical systems, summarizing existing information and knowledge gaps in the complex cardiovascular effects of the post-COVID-19 condition has become critical for patient care. In this Review, we explore the current state of knowledge of the post-COVID-19 condition and identify areas where additional research is warranted. This will provide a framework for better understanding the cardiovascular manifestations of the post-COVID-19 condition with a focus on pathophysiology, diagnosis and management.

Pleural Epithelioid Hemangioendothelioma: An Ultrarare Cause for Recurrent Pleural Effusion Managed With Trametinib and Pazopanib.

Epithelioid hemangioendothelioma (EHE) is an extremely rare sarcoma of vascular origin. Primary pleural involvement is extremely under-reported and tends to have a more aggressive course. We report a case of pleural EHE in a Caucasian female in her 50s with a two-month history of dyspnea and chest pain. Investigations, including video-assisted thoracoscopy, revealed extensive pleural scarring and inflammation. Management with trametinib and pazopanib led to a stable disease course, reduction in the frequency of pleural effusion recurrence, and improvement in cancer-related pain.

Prognostic value of left ventricular global longitudinal strain in transcatheter edge-to-edge repair for chronic primary mitral regurgitation.

AIMS: Left ventricular global longitudinal strain (LVGLS) is a known outcome predictor in transcatheter edge-to-edge repair (TEER) for functional mitral regurgitation (MR). We aimed to assess its prognostic yield in the setting of TEER for chronic primary MR. METHODS AND RESULTS: We conducted a single-centre, retrospective analysis of 323 consecutive patients undergoing isolated, first-time procedures. Stratified by baseline LVGLS quartiles (≤-19%, -18.9% to -16%, -15.9% to -12%, >-12%), the cohort was evaluated for the primary composite outcome of all-cause mortality or heart failure hospitalizations, as well as secondary endpoints consisting of mitral reinterventions and the persistence of significant residual MR and/or functional disability-all along the first year after intervention. Subjects with worse (i.e. less negative) LVGLS exhibited higher comorbidity, more advanced HF, and elevated procedural risk. Post-TEER, those belonging to the worst LVGLS quartile group sustained increased mortality (16.9% vs. 6.3%, Log-Rank P = 0.005, HR 1.75, 95% CI 1.08-4.74, P = 0.041) and, when affected by LV dysfunction/dilatation, more primary outcome events (21.1% vs. 11.5%, Log-Rank P = 0.037, HR 1.68, 95% CI 1.02-5.46, P = 0.047). No association was demonstrated between baseline LVGLS and other endpoints. Upon exploratory analysis, 1-month post-procedural LVGLS directly correlated with and was worse than its baseline counterpart by 1.6%, and a more impaired 1-month value-but not the presence/extent of deterioration-conferred heightened risk for the primary outcome. CONCLUSION: TEER for chronic primary MR is feasible, safe, and efficacious irrespective of baseline LVGLS. Yet, worse baseline LVGLS forecasts a less favourable post-procedural course, presumably reflecting a higher-risk patient profile.

Preprocedural transthoracic echocardiography for predicting outcomes of transcatheter edge-to-edge repair for chronic primary mitral regurgitation.

INTRODUCTION AND OBJECTIVES: Limited data exist on the prognostic usefulness of transthoracic echocardiography preceding MitraClip for chronic primary mitral regurgitation (MR). We evaluated the predictive ability of transthoracic echocardiography in this setting. METHODS: A total of 410 patients (median age, 83 years, 60.7% males) were included in the study. The primary outcome was the 1-year composite of all-cause mortality or heart failure hospitalization. Secondary endpoints encompassed individual elements of the primary outcome, the persistence of significant functional impairment or above-moderate MR at 1 year, and above-mild MR at 1-month. RESULTS: The only parameter associated with the risk of the primary outcome was a ventricular end systolic diameter index of ≥2.1 cm/m2, corresponding to the cohort's 4th quartile (HR, 2.44; 95%CI, 1.09-4.68; P=.022). Concurrently, higher left atrial volume index (LAVi) and a mid-diastolic medial-lateral mitral annular diameter (MAD) equal to or above the cohort's median of 32.2mm were linked to a higher probability of death and heart failure hospitalization, respectively. LAVi of ≥ 60mL/m2, above-mild mitral annular calcification, and above-moderate tricuspid regurgitation conferred higher odds of functional class III-IV or above-moderate MR persistence. All variables except LAVi and MAD, as well as indexed mid-diastolic medial-lateral MAD of ≥ 20.2mm/m2 and mitral effective regurgitant orifice area of ≥ 0.40 cm2, were associated with greater-than-mild MR at 1 month. CONCLUSIONS: Preprocedural increased indexed left heart dimensions, mainly left ventricular end-systolic diameter index, MAD, mitral annular calcification, mitral effective regurgitant orifice area, and tricuspid regurgitation mark a less favorable course post-MitraClip for chronic primary MR.

Implications of Mitral Annular Disjunction in Patients Undergoing Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation.

BACKGROUND: Little is known about mitral transcatheter edge-to-edge repair (TEER) in patients with mitral annular disjunction (MAD). OBJECTIVES: The authors sought to explore TEER for degenerative mitral regurgitation (MR) according to MAD status. METHODS: We retrospectively analyzed 271 consecutive patients (median age 82 [Q1-Q3: 75-88] years, 60.9% men) undergoing an isolated, first-ever TEER for whom there were viewable preprocedural echocardiograms. Stratified by MAD status at baseline, the cohort was evaluated for all-cause mortality, heart failure hospitalizations, and mitral reinterventions-the composite of which constituted the primary outcome-as well as functional capacity and residual MR, all along the first postprocedural year. RESULTS: Individuals with (n = 62, 22.9%) vs without MAD had more extensive prolapse and larger valve dimensions. Although the former's procedures were longer, utilizing more devices per case, technical success rate and residual MR were comparable. MAD presence was associated with higher mortality risk (HR: 2.64; 95% CI: 1.82-5.52; P = 0.014), and increased MAD length-with lower odds of functional class ≤II (OR: 0.65; 95% CI: 0.47-0.88; P = 0.006). Among 47 MAD patients with retrievable 1-month data, MAD regressed in 91.5% and by an overall 50% (Q1-Q3: 22%-100%) compared with baseline (P < 0.001). A greater MAD shortening conferred attenuated risk for the primary outcome. CONCLUSIONS: In our experience, TEER for degenerative MR accompanied by MAD was feasible and safe; however, its postprocedural course was somewhat less favorable. MAD shortening following TEER was observed in most patients and proved prognostically beneficial.

Computer versus human-expert ranking of posterior pole vascular tortuosity and dilation using retinal vessel maps generated from bedside optical coherence tomography: a proof-of-concept study.

Semiautomated computer software (ie, ROPtool) can trace and analyze optical coherence tomography (OCT)-generated retinal vessel maps for plus/pre-plus disease with high reliability and accuracy. This proof-of-concept study found that ROPtool can reliably rank OCT-generated vessel maps for tortuosity and combined tortuosity/dilation, which correlated well with human-expert rankings and clinical examination.

The Evolving Role of Echocardiography During the Coronavirus Disease 2019 Pandemic.

Coronavirus disease 2019 (COVID-19) has been associated with a wide spectrum of cardiovascular manifestations. Since the beginning of the pandemic, echocardiography has served as a valuable tool for triaging, diagnosing and managing patients with COVID-19. More recently, speckle-tracking echocardiography has been shown to be effective in demonstrating subclinical myocardial dysfunction that is often not detected in standard echocardiography. Echocardiographic findings in COVID-19 patients include left or right ventricular dysfunction, including abnormal longitudinal strain and focal wall motion abnormalities, valvular dysfunction and pericardial effusion. Additionally, some of these echocardiographic abnormalities have been shown to correlate with biomarkers and adverse clinical outcomes, suggesting an additional prognostic value of echocardiography. With increasing evidence of cardiac sequelae of COVID-19, the use of echocardiography has expanded to patients with cardiopulmonary symptoms after recovery from initial infection. This article aims to highlight the available echocardiographic tools and to summarize the echocardiographic findings across the full spectrum of COVID-19 disease and their correlations with biomarkers and mortality.

Quantitative comparison of blood vessel changes after treatment of retinopathy of prematurity with laser versus bevacizumab.

Current therapies for treatment-indicated (type 1) retinopathy of prematurity mainly consist of laser photocoagulation and intravitreal anti-vascular endothelial growth factor (eg, bevacizumab) injection. The first visible signs of acute-phase regression are typically vascular, including decreased plus disease. Using a semiautomated computer program, we quantitatively compared posterior pole vascular changes following treatment with laser versus bevacizumab and found that in the first month following treatment, vascular dilation and tortuosity significantly decreased following either treatment modality, but tortuosity decreased earlier and faster after bevacizumab.

Rank correlation inferences for clustered data with small sample size.

This paper develops methods to test for associations between two variables with clustered data using a U-Statistic approach with a second-order approximation to the variance of the parameter estimate for the test statistic. The tests that are presented are for clustered versions of: Pearsons χ 2 test, the Spearman rank correlation and Kendall's τ for continuous data or ordinal data and for alternative measures of Kendall's τ that allow for ties in the data. Shih and Fay use the U-Statistic approach but only consider a first-order approximation. The first-order approximation has inflated significance level in scenarios with small sample sizes. We derive the test statistics using the second-order approximations aiming to improve the type I error rates. The method applies to data where clusters have the same number of measurements for each variable or where one of the variables may be measured once per cluster while the other variable may be measured multiple times. We evaluate the performance of the test statistics through simulation with small sample sizes. The methods are all available in the R package cluscor.

Semi-automated vessel analysis of en face posterior pole vessel maps generated from optical coherence tomography for diagnosis of plus or pre-plus disease.

En face retinal vessel maps generated from bedside optical coherence tomography (OCT) can show posterior pole vascular tortuosity and dilation (ie, plus/pre-plus disease). In this proof-of-concept study, we found that ROPtool could trace OCT-generated retinal vessel maps with high reliability and accuracy for detecting plus or pre-plus disease.

Bortezomib treatment for refractory nontuberculous mycobacterial infection in the setting of interferon gamma autoantibodies.

Interferon-γ autoantibodies increase the risk of disseminated nontuberculous mycobacterial infections. Addition of rituximab to antibiotics accelerates and improves outcomes, but refractory infections can occur due to persistent production of autoantibodies. We combined bortezomib with rituximab to reduce autoantibodies leading to clinical and radiographic improvement in infection.

Prophylactic laser versus continued surveillance after initial bevacizumab treatment for retinopathy of prematurity.

Guidelines on managing infants after initial anti-vascular endothelial growth factor (VEGF) treatment (eg, bevacizumab) for retinopathy of prematurity (ROP) are limited. We found that following initial bevacizumab treatment for ROP, prophylactically lasering infant eyes before hospital discharge reduced the number and duration of outpatient ROP screening examinations compared with following infants, per current United States (US) ROP screening guidelines.

Quantitatively comparing weekly changes in retinal vascular characteristics of eyes eventually treated versus not treated for retinopathy of prematurity.

PURPOSE: To quantitatively compare retinal vascular characteristics over time in eyes eventually treated versus not treated for retinopathy of prematurity (ROP), using ROPtool analysis of narrow-field retinal images. METHODS: This longitudinal study used prospectively collected narrow-field retinal images of infants screened for ROP, prior to treatment, if needed. Images were analyzed using a methodology that combines quadrant-level measures from several images of the same eye. For the longitudinal analysis, one examination per postmenstrual age (PMA) was included per eye. We compared the following ROPtool indices and their change per week between eyes eventually treated versus not treated for ROP: tortuosity index (TI), dilation index (DI), sum of adjusted indices (SAI), and tortuosity-weighted plus (TWP). Analysis was performed on three levels: eye (mean value/eye), quadrant (highest quadrant value/eye), and blood vessel (highest blood vessel value/eye). RESULTS: Of 832 examinations (99 infants), 745 images (89.5%) had 3-4 quadrants analyzable by ROPtool. On the eye level, ROPtool indices differed between eyes eventually treated versus not treated at PMA of 33-35 and 37 weeks for TI, SAI, and TWP, and at PMA of 33-34 and 37 weeks for DI (P ≤ 0.0014), and change per week differed between eyes eventually treated versus not treated only for SAI at PMA of 32 weeks (P < 0.001). CONCLUSIONS: Quantitative analysis of retinal vascular characteristics using ROPtool can help predict eventual need for treatment for ROP as early as 32 weeks PMA. ROPtool index values were more useful than change in these indices to predict eyes that would eventually need treatment for ROP.

A Brief History of OLEDs-Emitter Development and Industry Milestones.

Organic light-emitting diodes (OLEDs) have come a long way ever since their first introduction in 1987 at Eastman Kodak. Today, OLEDs are especially valued in the display and lighting industry for their promising features. As one of the research fields that equally inspires and drives development in academia and industry, OLED device technology has continuously evolved over more than 30 years. OLED devices have come forward based on three generations of emitter materials relying on fluorescence (first generation), phosphorescence (second generation), and thermally activated delayed fluorescence (third generation). Furthermore, research in academia and industry toward the fourth generation of OLEDs is in progress. Excerpts from the history of green, orange-red, and blue OLED emitter development on the side of academia and milestones achieved by key players in the industry are included in this report.

Disease Relapse After Drug-Free Remission in Ocular Mucous Membrane Pemphigoid.

PURPOSE: To quantitate the risk of relapse of ocular and extraocular disease among patients with mucous membrane pemphigoid (MMP) who had undergone drug-free remission. DESIGN: Retrospective, comparative, interventional case series. METHODS: There were 167 patients with biopsy-proven MMP who were seen at the Wilmer Eye Institute between November 1984 and December 2019. Among the 167 patients, 119 patients had ocular involvement and 103 of those patients received systemic treatment for MMP. The main outcome measures were the incidence of ocular remission, incidence rate of disease relapse after remission, and risk factors for disease relapse. RESULTS: Over a median follow-up time of 7 years, 74 of 103 treated patients (71.8%) experienced drug-free remission (incidence rate = 0.28/person-year [PY], 95% confidence interval [CI] 0.22-0.35/PY). Most patients (80/103, 77.7%) received cyclophosphamide therapy. Thirteen of the 74 patients (17.6%) had disease relapse after remission: 4 with ocular disease only, 4 with extraocular disease only, and 5 with both. The rate relapse of ocular MMP was 0.020/PY (95% CI 0.009-0.038/PY), and the rate of relapse of MMP at any site (ocular or extraocular site) was 0.029/PY (95% CI 0.015-0.050/PY). The use of cyclophosphamide was associated with a greater chance of remission (hazard ratio [HR] = 3.84, P < .0001) and a lower risk of relapse (HR = 0.32, P = .05) compared with other immunosuppressive drugs except for rituximab. Five patients experienced drug-free remission after rituximab therapy and none of them had relapse (median follow-up after remission = 3.6 years). When use of cyclophosphamide or rituximab was compared with all other treatments, the risk of MMP relapse at any site (HR = 0.17, P = .02) and of ocular MMP (HR = 0.11, P = .007) were significantly lower. CONCLUSIONS: Rates of relapse of MMP after drug-free remission are low but not zero; therefore, monitoring of patients remains necessary. Relapses were not observed among those patients treated with rituximab who had remission; however, follow-up duration in those patients was shorter than the whole MMP cohort and the sample size was small.

Natural History and Evolution of Anti-Interferon-γ Autoantibody-Associated Immunodeficiency Syndrome in Thailand and the United States.

BACKGROUND: The natural history of anti-interferon-γ (IFN-γ) autoantibody-associated immunodeficiency syndrome is not well understood. METHODS: Data of 74 patients with anti-IFN-γ autoantibodies at Srinagarind Hospital, Thailand, were collected annually (median follow-up duration, 7.5 years). Annual data for 19 patients and initial data for 4 patients with anti-IFN-γ autoantibodies at the US National Institutes of Health were collected (median follow-up duration, 4.5 years). Anti-IFN-γ autoantibody levels were measured in plasma samples. RESULTS: Ninety-one percent of US patients were of Southeast Asian descent; there was a stronger female predominance (91%) in US than Thai (64%) patients. Mycobacterium abscessus (34%) and Mycobacterium avium complex (83%) were the most common nontuberculous mycobacteria in Thailand and the United States, respectively. Skin infections were more common in Thailand (P = .001), whereas bone (P < .0001), lung (P = .002), and central nervous system (P = .03) infections were more common in the United States. Twenty-four percent of Thai patients died, most from infections. None of the 19 US patients with follow-up data died. Anti-IFN-γ autoantibody levels decreased over time in Thailand (P < .001) and the United States (P = .017), with either cyclophosphamide (P = .01) or rituximab therapy (P = .001). CONCLUSIONS: Patients with anti-IFN-γ autoantibodies in Thailand and the United States had distinct demographic and clinical features. While titers generally decreased with time, anti-IFN-γ autoantibody disease had a chronic clinical course with persistent infections and death. Close long-term surveillance for new infections is recommended.

Incidence and Clinical Characteristics of Ocular Involvement in Mucous Membrane Pemphigoid.

Purpose: To describe the risk of developing ocular mucous membrane pemphigoid (MMP) or a new extraocular site of MMP, and to identify risk factors for new involvement. Methods: Retrospective chart review of 162 biopsy-proven MMP patients. Results: At presentation, 109 of 162 MMP patients (67.3%) had ocular involvement and 53 patients did not. Of the 53 patients without ocular involvement at presentation followed up to 22 years, the risk of developing ocular MMP was 0.014 per person-year (PY, 95% confidence interval [CI]: 0.005/PY, 0.034/PY). The risk of developing any new location of extraocular MMP was 0.020/PY (95% CI: 0.007/PY, 0.043/PY). Smoking was a risk factor for developing an additional extraocular MMP location (hazard ratio [HR] = 4.09, p = 0.04). Conclusions: Patients presenting with extraocular MMP are at risk for developing ocular MMP, and all MMP patients are at risk for developing secondary extraocular MMP locations, although the rates were low.

Comparison of Access to Eye Care Appointments Between Patients With Medicaid and Those With Private Health Care Insurance.

Importance: Although low-income populations have more eye problems, whether they face greater difficulty obtaining eye care appointments is unknown. Objective: To compare rates of obtaining eye care appointments and appointment wait times for those with Medicaid vs those with private insurance. Design, Setting, and Participants: In this prospective, cohort study conducted from January 1, 2017, to July 1, 2017, researchers made telephone calls to a randomly selected sample of vision care professionals in Michigan and Maryland stratified by neighborhood (urban vs rural) and professional type (ophthalmologist vs optometrist) to request the first available appointment. Appointments were sought for an adult needing a diabetic eye examination and a child requesting a routine eye examination for a failed vision screening. Researchers called each practice twice, once requesting an appointment for a patient with Medicaid and the other time for a patient with Blue Cross Blue Shield (BCBS) insurance, and asked whether the insurance was accepted and, if so, when the earliest available appointment could be scheduled. Main Outcomes and Measures: Rate of successfully made appointments and mean wait time for the first available appointment. Results: A total of 603 telephone calls were made to 330 eye care professionals (414 calls [68.7%] to male and 189 calls [31.3%] to female eye care professionals). The sample consisted of ophthalmologists (303 [50.2%]) and optometrists (300 [49.8%]) located in Maryland (322 [53.4%]) and Michigan (281 [46.6%]). The rates of successfully obtaining appointments among callers were 61.5% (95% CI, 56.0%-67.0%) for adults with Medicaid and 79.3% (95% CI, 74.7%-83.9%) for adults with BCBS (P < .001) and 45.4% (95% CI, 39.8%-51.0%) for children with Medicaid and 62.5% (95% CI, 57.1%-68.0%) for children with BCBS (P < .001). Mean wait time did not vary significantly between the BCBS and Medicaid groups for both adults and children. Adults with Medicaid had significantly decreased odds of receiving an appointment compared with those with BCBS (odds ratio [OR], 0.41; 95% CI, 0.28-0.59; P < .001) but had increased odds of obtaining an appointment if they were located in Michigan vs Maryland (OR, 2.40; 95% CI, 1.49-3.87; P < .001) or with an optometrist vs an ophthalmologist (OR, 1.91; 95% CI, 1.31-2.79; P < .001). Children with Medicaid had significantly decreased odds of receiving an appointment compared with those with BCBS (OR, 0.41; 95% CI, 0.28-0.60; P < .001) but had increased odds of obtaining an appointment if they were located in Michigan vs Maryland (OR, 1.68; 95% CI, 1.04-2.73; P = .03) or with an optometrist vs an ophthalmologist (OR, 8.00; 95% CI, 5.37-11.90; P < .001). Conclusions and Relevance: Callers were less successful in trying to obtain eye care appointments with Medicaid than with BCBS, suggesting a disparity in access to eye care based on insurance status, although confounding factors may have contributed to this finding. Improving access to eye care professionals for those with Medicaid may improve health outcomes and decrease health care spending in the long term.

Production of Stealthin C Involves an S-N-Type Smiles Rearrangement.

The kinamycin family of aromatic polyketide natural products contains an atypical angucycline ring system substituted with a diazo group. The enzymatic chemistry involved in constructing both of these structural features has been largely unexplored. Here we report the in vivo and in vitro production of seongomycin, a shunt product from this pathway, and stealthin C, a proposed biosynthetic precursor to the kinamycins. We show that a single enzyme, the flavin-dependent monooxygenase AlpJ, can generate these metabolites from N-acetyl-l-cysteine and l-cysteine, respectively, and that the synthesis of stealthin C likely proceeds via a nonenzymatic S-N-type Smiles rearrangement. This unexpected route to stealthin C reveals a distinct approach to install aromatic amino groups in metabolites and raises questions about the intermediacy of this species in kinamycin production.