Comparison of Retinal Imaging Techniques in Individuals with Pulmonary Artery Hypertension Using Vessel Generation Analysis.

(1) Background: Retinal vascular imaging plays an essential role in diagnosing and managing chronic diseases such as diabetic retinopathy, sickle cell retinopathy, and systemic hypertension. Previously, we have shown that individuals with pulmonary arterial hypertension (PAH), a rare disorder, exhibit unique retinal vascular changes as seen using fluorescein angiography (FA) and that these changes correlate with PAH severity. This study aimed to determine if color fundus (CF) imaging could garner identical retinal information as previously seen using FA images in individuals with PAH. (2) Methods: VESGEN, computer software which provides detailed vascular patterns, was used to compare manual segmentations of FA to CF imaging in PAH subjects (n = 9) followed by deep learning (DL) processing of CF imaging to increase the speed of analysis and facilitate a noninvasive clinical translation. (3) Results: When manual segmentation of FA and CF images were compared using VESGEN analysis, both showed identical tortuosity and vessel area density measures. This remained true even when separating images based on arterial trees only. However, this was not observed with microvessels. DL segmentation when compared to manual segmentation of CF images showed similarities in vascular structure as defined by fractal dimension. Similarities were lost for tortuosity and vessel area density when comparing manual CF imaging to DL imaging. (4) Conclusions: Noninvasive imaging such as CF can be used with VESGEN to provide an accurate and safe assessment of retinal vascular changes in individuals with PAH. In addition to providing insight into possible future clinical translational use.

Retinal vessel changes in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is classically considered an isolated small vessel vasculopathy of the lungs with peripheral pulmonary vascular obliteration. Systemic manifestations of PAH are increasingly acknowledged, but data remain limited. We hypothesized that retinal vascular changes occur in PAH. PAH subjects underwent retinal fluorescein angiography (FA) and routine disease severity measures were collected from the medical record. FA studies were analyzed using VESsel GENerational Analysis (VESGEN), a noninvasive, user-interactive computer software that assigns branching generation to large and small vessels. FAs from controls (n = 8) and PAH subjects (n = 9) were compared. The tortuosity of retinal arteries was higher in PAH subjects compared to unmatched controls (1.17, 95% confidence interval: [1.14, 1.20] in PAH vs. 1.13, 95% CI: [1.12, 1.14] in controls, p = 0.01). Venous tortuosity was higher and more variable in PAH (1.17, 95% CI: [1.14, 1.20]) compared to controls (1.13, 95% CI: [1.12, 1.15]), p = 0.02. PAH subjects without connective tissue disease had the highest degree of retinal tortuosity relative to controls (arterial, p = 0.01; venous, p = 0.03). Younger PAH subjects had greater retinal arterial tortuosity, which attenuated with age and was not observed in controls. Retinal vascular parameters correlated with some clinical measures of disease in PAH subjects. In conclusion, PAH subjects exhibit higher retinal vascular tortuosity. Retinal vascular changes may track with pulmonary vascular disease progression. Use of FA and VESGEN may facilitate early, noninvasive detection of PAH.

Lung Ultrasound for Diagnosing Patients with Severe Dyspnea and Acute Hypoxic Respiratory Failure.

Acute hypoxic respiratory failure can be caused by severe pneumonia, cardiogenic pulmonary edema (CPE), and acute respiratory distress syndrome (ARDS). Differentiating between these causes in critically ill patients can be challenging. Lung ultrasound (LUS) evaluation of acute respiratory failure has been developed and adopted only recently. LUS offers promise as a valuable clinical tool for the diagnosis and treatment of patients with severe dyspnea and acute hypoxic respiratory failure.

Pneumomediastinum in marijuana users: a retrospective review of 14 cases.

Introduction: Inhaled marijuana has been infrequently identified as a potential risk factor for the development of spontaneous pneumomediastinum (SPM), a rare finding of free air in the mediastinum likely caused by barotrauma during breathing manoeuvres. The mechanism of inhalation drug use is often not ascertained by physicians, thus little is known about how different smoking techniques precipitate pulmonary injury. We aimed to evaluate the frequency of marijuana use in patients with non-traumatic pneumomediastinum over a 12-month period, identifying additional relevant clinical features or risk factors, and determining the extent to which clinicians record smoking techniques. Methods: We performed a retrospective chart review over a 1-year period, identifying patients presenting to the hospital with a diagnosis of pneumomediastinum in the absence of trauma, malignancy or iatrogenic cause. Results: We identified 21 cases, 14 of which (66.7%) were associated with marijuana use, average age was 22.5 years (range 18-30), with male predominance (64.2%). Daily or more use was reported in 50% of cases. Concurrent risk factors including vomiting (57.1%) and coughing (42.9%) were commonly present. The mechanism of smoking was described in only two cases (14.3%). Discussion: Inhaled marijuana may be an underappreciated risk factor for the development of SPM, caused by air leakage around the bronchovascular sheaths during successive inhalation through a high-resistance smoking apparatus or forced exhalation against a closed glottis. Physicians should be aware of this association in order to provide appropriate counselling. Further research is needed to direct the safe use of smoking devices and techniques.

Lower DHEA-S levels predict disease and worse outcomes in post-menopausal women with idiopathic, connective tissue disease- and congenital heart disease-associated pulmonary arterial hypertension.

High oestradiol (E2) and low dehydroepiandrosterone-sulfate (DHEA-S) levels are risk factors for pulmonary arterial hypertension (PAH) in men, but whether sex hormones are related to PAH in women is unknown.Post-menopausal women aged ≥55 years with PAH were matched by age and body mass index to women without cardiovascular disease. Plasma sex hormone levels were measured by immunoassay.Lower levels of DHEA-S (p<0.001) and higher levels of E2 (p=0.02) were associated with PAH. In PAH cases (n=112), lower DHEA-S levels were associated with worse haemodynamics (all p<0.01) and more right ventricular dilatation and dysfunction (both p=0.001). Lower DHEA-S levels were associated with shorter 6-min walking distance (6MWD) (p=0.01) and worse functional class (p=0.004). Each Ln(1 µg·dL-1) decrease in DHEA-S was associated with a doubling in the risk of death (hazard ratio 2.0, 95% CI 1.5-2.7; p<0.001). Higher levels of E2 were associated with shorter 6MWD (p=0.03) and worse functional class (p=0.01).High E2 and low DHEA-S levels are associated with the risk and severity of PAH in post-menopausal women. Hormonal modulation should be studied as a treatment strategy in PAH.

Pulmonary Arterial Hypertension and the Sex Hormone Paradox.

PURPOSE OF REVIEW: Prevalence and outcome differences between women and men with pulmonary arterial hypertension (PAH) raise questions about the role of sex hormones in disease pathobiology. This review will summarize the current understanding of sex and sex hormone pathways and their influence on heart-lung function in health and in disease. RECENT FINDINGS: Female sex has been shown to be a risk factor for the development of PAH, but women have improved survival compared to men with PAH. These paradoxical observations are likely driven in part by complex sex hormone signaling and processing pathways and their interaction with the pulmonary vasculature and the right ventricle. These relationships may vary depending on an individual's underlying sex, age, and/or genetic substrate. The study of the connections between sex, sex hormones, the pulmonary circulation, and the right ventricle may improve our understanding of disease epidemiology and outcomes and lead to new treatment strategies for PAH.

5-fluorouracil induced cardiotoxicity: review of the literature.

5-fluorouracil (5-FU) is a key chemotherapeutic agent in the treatment of many gastrointestinal tract adenocarcinomas. Despite its proven therapeutic efficacy, 5-FU also possesses several undesired cardiac toxicities, including coronary vasospasm, coronary thrombosis, cardiomyopathy, and sudden cardiac death. This review addresses the incidence, mechanisms of action, clinical presentation, risk stratification, and management of 5-FU associated cardiotoxicity; it also highlights the importance of careful pre-administration cardiac risk stratification and close monitoring during and after drug administration.