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Eosinophilic Pustular Folliculitis in an HIV-Positive 63-Year-Old Male

Sikora, Michelle; Buontempo, Michael G; Ramachandran, Vignesh; Knutsen, Dorothy A; Meehan, Shane A; Hejazi, Emily Z; Caplan, Avrom S; Lo Sicco, Kristen I; Tattersall, Ian W
PMID: 38588935
ISSN: 1555-7162
CID: 5657272

Mpox in Children: 3 Cases

Frantzis, Irene; Ungar, Stephanie P; Soma, Vijaya L; Knutsen, Dorothy; Mazo, Dana; Zucker, Jason
Although the 2022 mpox outbreak mostly affected adults, its effect on children and adolescents was also substantial. In this report, we describe the clinical course and treatment of the first 3 known cases of mpox in children in New York City. These cases are instructive because they illustrate various routes of transmission, clinical presentations, and diagnostic challenges that differ from previous reports of mpox in endemic countries and previous mpox outbreaks. Of note is that each of the 3 patients received treatment with tecovirimat under an US Food and Drug Administration expanded access investigational new drug application and improved without exhibiting adverse reactions.
PMID: 38239109
ISSN: 1098-4275
CID: 5627642

Implementation and early outcomes of a telehealth visit model to deliver tecovirimat for mpox infection in New York City

Chan, Justin; DiTullio, David J; Pagan Pirallo, Patricia; Foote, Mary; Knutsen, Dorothy; Kottkamp, Angelica Cifuentes; McPherson, Tristan D; Mukherjee, Vikramjit; Pitts, Robert; Wallach, Andrew; Wong, Marcia; Mazo, Dana; Mgbako, Ofole
The 2022 mpox outbreak in New York City posed challenges to rapidly scaling up treatment capacity. We describe a telehealth treatment model launched during this outbreak that facilitated healthcare provider treatment capacity, and was able to adhere to a Centers for Disease Control and Prevention (CDC)-sponsored expanded access investigational new drug (EA-IND) protocol for tecovirimat. Sixty-nine patients were evaluated and prescribed tecovirimat for mpox through telehealth visits at NYC Health + Hospitals/Bellevue and NYU Langone Health from June to August 2022. Thirty-two (46.4%) were previously diagnosed with HIV. Forty-four (63.8%) reported full recovery, with the remainder lost to follow-up. Most patients (n = 60, 87.0%) attended at least one follow-up visit (either in person or through telehealth) after starting treatment. We observed favorable treatment outcomes, with no serious adverse events, hospitalizations, or deaths related to mpox. While equitable access to telehealth remains a limitation that needs to be addressed, this telehealth model enabled a rapid scale-up of tecovirimat prescription during the mpox outbreak, and should be considered as an important tool used to respond to future infectious disease outbreaks.
PMID: 37632124
ISSN: 1758-1109
CID: 5598892

Navigating the expanded access investigational new drug protocol for tecovirimat: Lessons learned from a public-private hospital partnership during the 2022 NYC mpox outbreak

Mgbako, Ofole; Chan, Justin; Pitts, Robert A.; Dilorenzo, Madeline A.; Knutsen, Dorothy; Mazo, Dana
During the 2022 mpox outbreak, tecovirimat was accessed through an expanded access investigational new drug (EA-IND) protocol. We leveraged a unique public/private hospital partnership in New York City to create a novel infrastructure to navigate the EA-IND's regulatory requirements and rapidly provide tecovirimat to patients.
ISSN: 2732-494x
CID: 5548652


Vy Anh Mai; Knutsen, Dorothy; Niyogi, Anjali
ISSN: 0884-8734
CID: 5267672


Knutsen, Dorothy; Blecker, Uwe; Anderson, Margot
ISSN: 0884-8734
CID: 5267682

HIV/AIDS patient migration in North-Central West Virginia

Knutsen, Dorothy A; Roidad, Nasira; Sarwari, Arif R; Coombs, Tabatha; Fisher, Melanie A
INTRODUCTION/BACKGROUND:Many HIV/AIDS patients rely on the Ryan White CARE Act, a federally-funded program to cover the costs of their medical care. The dispersal of this funding is dependent on a complex algorithm, which factors in the number of people that test positive for HIV in each state. However, demographic and migration studies have suggested that HIV/AIDS patients in rural America are first diagnosed in urban areas and then later moved to more rural areas. METHODS:The participant pool was identified from adult patients who have received care from the West Virginia University (WVU) Positive Health Clinic from January 1, 2004 to July 26, 2012 and knew the location where they had initially tested positive for HIV. RESULTS:The place of initial HIV diagnosis could be determined for 398 out of 433 patients and fewer than half (48%) were initially diagnosed in West Virginia. CONCLUSIONS:Because over half of the patients who are treated at WVU were initially tested outside of West Virginia, this could negatively impact the federal funding opportunities for our state through the Ryan White CARE Act using the current algorithm.
PMID: 23930557
ISSN: 0043-3284
CID: 5267662

Transgenic overexpression of keratinocyte-specific VEGF and Ang1 in combination promotes wound healing under nondiabetic but not diabetic conditions

Loyd, Candace M; Diaconu, Doina; Fu, Wen; Adams, Gregory N; Brandt, Erin; Knutsen, Dorothy A; Wolfram, Julie A; McCormick, Thomas S; Ward, Nicole L
VEGF and Angiopoietin (Ang)1 are growth factors that independently improve wound healing outcomes. Using a tet-repressible mouse model coupled with streptozotocin-induced diabetes, we examined wound healing in diabetic and nondiabetic mice engineered to overexpress keratinocyte-specific (K5) VEGF, Ang1 or Ang1-VEGF combined. All nondiabetic mice healed more rapidly than their diabetic counterparts; however overexpression of VEGF, Ang1 or the combination failed to improve wound closure under diabetic conditions. Conversely, under nondiabetic conditions, combining Ang1 and VEGF resulted in rapid wound closure. Molecular analyses of diabetic and nondiabetic K5-Ang1-VEGF skin revealed no differences in VEGF expression but an 80% decrease in Ang1 under diabetic conditions, suggesting an integral role for Ang1. Nondiabetic K5-Ang1 mice healed more quickly and had significant increases in granulation tissue and a 60% decrease in re-epithelialization 7 days after wounding. Furthermore, Ang1 stimulated primary mouse keratinocytes showed significantly less migration into a wound bed in an in vitro wound healing bioassay and had decreased pMAPK, pNFκB, pAkt, and pStat3 signaling. These data suggest that combined Ang1-VEGF overexpression cannot overcome diabetes-induced delays in wound healing but is efficacious under nondiabetic conditions possibly via Ang1-mediated delays in re-epithelialization and enhancement of granulation tissue formation, thereby allowing more rapid secondary intention healing.
PMID: 22295141
ISSN: 1936-2625
CID: 5267652

Cutaneous manipulation of vascular growth factors leads to alterations in immunocytes, blood vessels and nerves: Evidence for a cutaneous neurovascular unit

Ward, Nicole L; Hatala, Denise A; Wolfram, Julie A; Knutsen, Dorothy A; Loyd, Candace M
BACKGROUND:Skin cells produce soluble factors which influence keratinocyte proliferation, angiogenesis, nerve innervation and immunocyte response. OBJECTIVE:To test the hypothesis that epidermal-dermal interactions influence neural outgrowth, vascular survival, immunocyte recruitment and keratinocyte proliferation. METHODS:We genetically manipulated the epidermis to express excess vascular endothelial growth factor (VEGF) and/or angiopoietin-1 (Ang1) and then examined the epidermal and dermal phenotypes. We compared these findings with those occurring following overexpression of the Ang1 receptor Tie2 in endothelial cells or keratinocytes. RESULTS:Keratinocyte-overexpression of Ang1 resulted in increased epidermal thickness compared to control littermates. Keratinocyte-specific overexpression of Ang1 or VEGF increased dermal angiogenesis compared to control animals and combined Ang1-VEGF lead to further increases. Cutaneous leukocyte examination revealed increases in CD4(+) T cell infiltration in mice with keratinocyte-specific overexpression of Ang1, VEGF and Ang1-VEGF combined; in contrast only keratinocyte-specific Ang1 overexpression increased cutaneous F4/80(+) macrophage numbers. Interestingly, combined keratinocyte-derived Ang1-VEGF overexpression reduced significantly the number of F4/80(+) and Cd11c(+) cells compared to mice overexpressing epidermal Ang1 alone. Endothelial cell-specific Tie2 overexpression increased dermal angiogenesis but failed to influence the epidermal and immune cell phenotypes. Keratinocyte-specific Tie2 expressing mice had the highest levels of CD4(+), CD8(+) and CD11c(+) cell numbers and acanthosis compared to all animals. Finally, increases in the number of cutaneous nerves were found in all transgenic mice compared to littermate controls. CONCLUSION/CONCLUSIONS:These findings demonstrate that change to one system (vascular or epidermal) results in change to other cutaneous systems and suggest that individual molecules can exert effects on multiple systems.
PMID: 21129919
ISSN: 1873-569x
CID: 5267642

Keratinocyte but not endothelial cell-specific overexpression of Tie2 leads to the development of psoriasis

Wolfram, Julie A; Diaconu, Doina; Hatala, Denise A; Rastegar, Jessica; Knutsen, Dorothy A; Lowther, Abigail; Askew, David; Gilliam, Anita C; McCormick, Thomas S; Ward, Nicole L
Psoriasis is initiated and maintained through a multifaceted interplay between keratinocytes, blood vessels, gene expression, and the immune system. One previous psoriasis model demonstrated that overexpression of the angiopoietin receptor Tie2 in endothelial cells and keratinocytes led to the development of a psoriasiform phenotype; however, the etiological significance of overexpression in each cell type alone was unclear. We have now engineered two new mouse models whereby Tie2 expression is confined to either endothelial cells or keratinocytes. Both lines of mice have significant increases in dermal vasculature but only the KC-Tie2-overexpressing mice developed a cutaneous psoriasiform phenotype. These mice spontaneously developed characteristic hallmarks of human psoriasis, including extensive acanthosis, increases in dermal CD4(+) T cells, infiltrating epidermal CD8(+) T cells, dermal dendritic cells and macrophages, and increased expression of cytokines and chemokines associated with psoriasis, including interferon-gamma, tumor necrosis factor-alpha, and interleukins 1alpha, 6, 12, 22, 23, and 17. Host-defense molecules, cathelicidin, beta-defensin, and S100A8/A9, were also up-regulated in the hyperproliferative skin. All of the phenotypic traits were completely reversed without any scarring following repression of the transgene and were significantly improved following treatment with the anti-psoriasis systemic therapeutic, cyclosporin A. Therefore, confining Tie2 overexpression solely to keratinocytes results in a mouse model that meets the clinical, histological, immunophenotypic, biochemical, and pharmacological criteria required for an animal model of human psoriasis.
PMID: 19342373
ISSN: 1525-2191
CID: 5267632