Browsing by Author "Prohaska, Clare C."

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    Human Endogenous Retrovirus, SARS-CoV-2, and HIV Promote PAH via Inflammation and Growth Stimulation
    (MDPI, 2023-04-18) Wang, Desheng; Gomes, Marta T.; Mo, Yanfei; Prohaska, Clare C.; Zhang, Lu; Chelvanambi, Sarvesh; Clauss, Matthias A.; Zhang, Dongfang; Machado, Roberto F.; Gao, Mingqi; Bai, Yang; Medicine, School of Medicine
    Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease characterized by the progressive elevation of pulmonary arterial pressures. It is becoming increasingly apparent that inflammation contributes to the pathogenesis and progression of PAH. Several viruses are known to cause PAH, such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human endogenous retrovirus K(HERV-K), and human immunodeficiency virus (HIV), in part due to acute and chronic inflammation. In this review, we discuss the connections between HERV-K, HIV, SARS-CoV-2, and PAH, to stimulate research regarding new therapeutic options and provide new targets for the treatment of the disease.
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    "If We Manage Early, We Can Get It Right": A Descriptive Study of Healthcare Workers' Experiences Managing Sepsis at a Kenyan Referral Hospital
    (Springer Nature, 2025-02-14) Srour, Maria; Ali, Shamim; Hodge, Matthew; Kwobah, Charles; McHenry, Megan; Etling, Mary Ann; Nafiseh, Amira; Khan, Babar; Prohaska, Clare C.; Navuluri, Neelima; Medicine, School of Medicine
    Background and objectives: Sepsis and septic shock are conditions of high mortality across the globe. Despite the efforts of the Surviving Sepsis Campaign, improvements in outcomes for patients with sepsis and septic shock have been mostly seen in high-income countries (HICs), leaving low- and middle-income countries (LMICs) to bear most of the global disease burden. This paper utilizes a socio-ecological model to describe the lived experiences of local healthcare workers treating sepsis and septic shock at a large referral hospital in Western Kenya. These perspectives shed light on barriers and strengths in care, gaps in knowledge, and areas of high-yield improvement. Materials and methods: This is a descriptive analysis focused on providers caring for patients with sepsis and septic shock. Twenty-seven interviews with a wide variety of purposively sampled patient-facing and ancillary medical staff were performed. Concurrent thematic analysis took place as interviews were being conducted. The concept presented was inductively and deductively reasoned and analyzed using a socio-ecological framework. We chose to present three levels of influence on the individual provider. Results: We present our results using a socio-ecological model. At the health system level, we found that most patients do not have healthcare coverage, which drives up out-of-pocket expenses for individuals. At the hospital level, capacity limits, particularly personnel shortages and small intensive care unit (ICU) spaces, influence care. At the interdisciplinary level, relationships between providers and other members of the healthcare team can present challenges. Lastly, these system-, hospital-, and interdisciplinary-level challenges make guideline adherence difficult and not always feasible for individual providers. Conclusions: To our knowledge, this is the first study to give voice to local providers treating patients with sepsis at a referral center in Western Kenya. By presenting findings in the socio-ecological model, we are able to organize potential interventions for the improvement of care at various levels. We found high-yield areas for improving care including establishing clear protocols for task assignments and communication, increasing the number of trained personnel both in the general wards and in the ICU, and, on a broader scale, advocating for expanded healthcare coverage for all Kenyans. This work provides a framework for further investigation into elements of sepsis care and the creation of locally relevant treatment guidelines in sub-Saharan Africa and across LMICs.
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    RASA3 is a candidate gene in sickle cell disease-associated pulmonary hypertension and pulmonary arterial hypertension
    (Wiley, 2023-04-01) Prohaska, Clare C.; Zhang, Xu; Schwantes‐An, Tae‐Hwi L.; Stearman, Robert S.; Hooker, Stanley; Kittles, Rick A.; Aldred, Micheala A.; Lutz, Katie A.; Pauciulo, Michael W.; Nichols, William C.; Desai, Ankit A.; Gordeuk, Victor R.; Machado, Roberto F.; Medicine, School of Medicine
    Pulmonary hypertension (PH) is associated with significant morbidity and mortality. RASA3 is a GTPase activating protein integral to angiogenesis and endothelial barrier function. In this study, we explore the association of RASA3 genetic variation with PH risk in patients with sickle cell disease (SCD)-associated PH and pulmonary arterial hypertension (PAH). Cis-expression quantitative trait loci (eQTL) were queried for RASA3 using whole genome genotype arrays and gene expression profiles derived from peripheral blood mononuclear cells (PBMC) of three SCD cohorts. Genome-wide single nucleotide polymorphisms (SNPs) near or in the RASA3 gene that may associate with lung RASA3 expression were identified, reduced to 9 tagging SNPs for RASA3 and associated with markers of PH. Associations between the top RASA3 SNP and PAH severity were corroborated using data from the PAH Biobank and analyzed based on European or African ancestry (EA, AA). We found that PBMC RASA3 expression was lower in patients with SCD-associated PH as defined by echocardiography and right heart catheterization and was associated with higher mortality. One eQTL for RASA3 (rs9525228) was identified, with the risk allele correlating with PH risk, higher tricuspid regurgitant jet velocity and higher pulmonary vascular resistance in patients with SCD-associated PH. rs9525228 associated with markers of precapillary PH and decreased survival in individuals of EA but not AA. In conclusion, RASA3 is a novel candidate gene in SCD-associated PH and PAH, with RASA3 expression appearing to be protective. Further studies are ongoing to delineate the role of RASA3 in PH.
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    Regional Variation in Methamphetamine-associated Pulmonary Arterial Hypertension: Who’d Better Call Saul?
    (American Thoracic Society, 2021) Prohaska, Clare C.; Machado, Roberto F.; Medicine, School of Medicine
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    The different facets of sickle cell disease-related pulmonary hypertension
    (Wolters Kluwer, 2021) Prohaska, Clare C.; Machado, Roberto F.; Medicine, School of Medicine
    Purpose of review: Sickle cell disease (SCD), one of the most common genetic diseases in the world, is characterized by repeated episodes of hemolysis and vaso-occlusion. Hemolytic anemia is a risk factor for the development of pulmonary hypertension, and currently SCD-related pulmonary hypertension is classified as World Health Organization group 5 pulmonary hypertension. Patients with SCD-related pulmonary hypertension have unique hemodynamics, multiple comorbidities, and distinct phenotypes that may contribute to the development of pulmonary hypertension. Recent findings: SCD-related pulmonary hypertension is defined as a mean pulmonary artery pressure >20 mmHg, a pulmonary artery occlusion pressure ≤15 mmHg and relatively low pulmonary vascular resistance (>2 Wood units) rather than the traditional definition of ≥3 Wood units, an important distinction due to a baseline high-cardiac output state in the setting of chronic anemia and low vascular resistance. Diastolic dysfunction is frequently identified in this patient population and right heart catheterization is essential to determine if combined pre- and postcapillary pulmonary hypertension is present. Thromboembolism is common among patients with SCD, and screening for chronic thromboembolic pulmonary hypertension is essential. Data regarding advanced therapies are limited. Primary treatment options include targeting correction of their primary hemoglobinopathy as well as aggressive management of underlying comorbid conditions. Summary: SCD-related pulmonary hypertension is common among patients with SCD and is associated with increased mortality. A high index of suspicion is warranted during evaluation to identify all potential factors that may be contributing to disease.