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695


Implementation of Mohs micrographic surgery at the VA New York Manhattan Harbor Healthcare System eliminated need for re-excision and decreased time to treatment: A retrospective and prospective cohort study

Himeles, Jaclyn Rosenthal; Steuer, Alexa Beth; Sally, Rachel; Gutierrez, Daniel; Zampella, John G; Stevenson, Mary L; Carucci, John A; Lee, Nayoung
PMID: 38149943
ISSN: 1097-6787
CID: 5623592

Cutaneous Melanoma Incidence - Evidence of a Flattening Curve

Berk-Krauss, Juliana; Sharma, Medha; Polsky, David; Geller, Alan C
PMID: 38086518
ISSN: 1097-6787
CID: 5589212

Considerations Regarding Mohs Surgery for Early-Stage Merkel Cell Carcinoma-Reply

Cheraghlou, Shayan; Carucci, John A
PMID: 38506790
ISSN: 2168-6084
CID: 5640552

Metabolic targeting of cancer associated fibroblasts overcomes T-cell exclusion and chemoresistance in soft-tissue sarcomas

Broz, Marina T; Ko, Emily Y; Ishaya, Kristin; Xiao, Jinfen; De Simone, Marco; Hoi, Xen Ping; Piras, Roberta; Gala, Basia; Tessaro, Fernando H G; Karlstaedt, Anja; Orsulic, Sandra; Lund, Amanda W; Chan, Keith Syson; Guarnerio, Jlenia
T cell-based immunotherapies have exhibited promising outcomes in tumor control; however, their efficacy is limited in immune-excluded tumors. Cancer-associated fibroblasts (CAFs) play a pivotal role in shaping the tumor microenvironment and modulating immune infiltration. Despite the identification of distinct CAF subtypes using single-cell RNA-sequencing (scRNA-seq), their functional impact on hindering T-cell infiltration remains unclear, particularly in soft-tissue sarcomas (STS) characterized by low response rates to T cell-based therapies. In this study, we characterize the STS microenvironment using murine models (in female mice) with distinct immune composition by scRNA-seq, and identify a subset of CAFs we termed glycolytic cancer-associated fibroblasts (glyCAF). GlyCAF rely on GLUT1-dependent expression of CXCL16 to impede cytotoxic T-cell infiltration into the tumor parenchyma. Targeting glycolysis decreases T-cell restrictive glyCAF accumulation at the tumor margin, thereby enhancing T-cell infiltration and augmenting the efficacy of chemotherapy. These findings highlight avenues for combinatorial therapeutic interventions in sarcomas and possibly other solid tumors. Further investigations and clinical trials are needed to validate these potential strategies and translate them into clinical practice.
PMCID:10954767
PMID: 38509063
ISSN: 2041-1723
CID: 5640622

The Alopecia Areata Severity and Morbidity Index (ASAMI) Study: Results From a Global Expert Consensus Exercise on Determinants of Alopecia Areata Severity

,; Moussa, Anthony; Bennett, Michaela; Wall, Dmitri; Meah, Nekma; York, Katherine; Bokhari, Laita; Asfour, Leila; Rees, Huw; Abraham, Leonardo Spagnol; Asz-Sigall, Daniel; Basmanav, Fitnat Buket; Bergfeld, Wilma; Betz, Regina C; Bhoyrul, Bevin; Blume-Peytavi, Ulrike; Callender, Valerie; Chitreddy, Vijaya; Combalia, Andrea; Cotsarelis, George; Craiglow, Brittany; Dhurat, Rachita; Donovan, Jeff; Doroshkevich, Andrei; Eisman, Samantha; Farrant, Paul; Ferrando, Juan; Gadzhigoroeva, Aida; Green, Jack; Grimalt, Ramon; Harries, Matthew; Hordinsky, Maria; Irvine, Alan; Jolliffe, Victoria; Kaiumov, Spartak; King, Brett; Lee, Joyce; Lee, Won-Soo; Li, Jane; Lortkipanidze, Nino; McMichael, Amy; Mesinkovska, Natasha Atanaskova; Messenger, Andrew; Mirmirani, Paradi; Olsen, Elise; Orlow, Seth J; Ovcharenko, Yuliya; Piraccini, Bianca Maria; Pirmez, Rodrigo; Rakowska, Adriana; Reygagne, Pascal; Rudnicka, Lidia; Corralo, David Saceda; Senna, Maryanne; Shapiro, Jerry; Sharma, Pooja; Siliuk, Tatiana; Starace, Michela; Suchonwanit, Poonkiat; Takwale, Anita; Tosti, Antonella; Vañó-Galván, Sergio; Visser, Willem I; Vogt, Annika; Wade, Martin; Yip, Leona; Zhou, Cheng; Sinclair, Rodney
IMPORTANCE/UNASSIGNED:Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact. OBJECTIVE/UNASSIGNED:To explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI). EVIDENCE REVIEW/UNASSIGNED:A total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds. The first 2 sessions took place via a text-based web application following the Delphi study design. The final round took place virtually among participants via video conferencing software on April 30, 2022. FINDINGS/UNASSIGNED:Of all invited experts, 64 completed the first survey round (global representation: Africa [4.7%], Asia [9.4%], Australia [14.1%], Europe [43.8%], North America [23.4%], and South America [4.7%]; health care setting: public [20.3%], private [28.1%], and both [51.6%]). A total of 58 specialists completed the second round, and 42 participated in the final video conference meeting. Overall, consensus was achieved in 96 of 107 questions. Several factors, independent of the Severity of Alopecia Tool score, were identified as potentially worsening AA severity outcomes. These factors included a disease duration of 12 months or more, 3 or more relapses, inadequate response to topical or systemic treatments, rapid disease progression, difficulty in cosmetically concealing hair loss, facial hair involvement (eyebrows, eyelashes, and/or beard), nail involvement, impaired quality of life, and a history of anxiety, depression, or suicidal ideation due to or exacerbated by AA. Consensus was reached that the Alopecia Areata Investigator Global Assessment scale adequately classified the severity of scalp hair loss. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This eDelphi survey study, with consensus among global experts, identified various determinants of AA severity, encompassing not only scalp hair loss but also other outcomes. These findings are expected to facilitate the development of a multicomponent severity tool that endeavors to competently measure various disease impact. The findings are also anticipated to aid in identifying candidates for current and emerging systemic treatments. Future research must incorporate the perspectives of patients and the public to assign weight to the domains recognized in this project as associated with AA severity.
PMID: 38324292
ISSN: 2168-6084
CID: 5632682

High-volume facilities are significantly more likely to use guideline-adherent systemic immunotherapy for metastatic Merkel cell carcinoma: implications for cancer care regionalization

Cheraghlou, Shayan; Pahalyants, Vartan; Jairath, Neil K; Doudican, Nicole A; Carucci, John A
Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a high rate of mortality. While still relatively rare, the incidence of MCC has been rapidly rising in the US and around the world. Since 2017, two immunotherapeutic drugs, avelumab and pembrolizumab, have been FDA-approved for the treatment of metastatic MCC and have revolutionized outcomes for MCC. However, real-world outcomes can differ from clinical trial data, and the adoption of novel therapeutics can be gradual. We aimed to characterize the treatment practices and outcomes of patients with metastatic MCC across the US. A retrospective cohort study of adult cases of MCC in the National Cancer Database diagnosed from 2004 to 2019 was performed. Multivariable logistic regressions to determine the association of a variety of patient, tumor, and system factors with likelihood of receipt of systemic therapies were performed. Univariate Kaplan-Meier and multivariable Cox survival regressions were performed. We identified 1017 cases of metastatic MCC. From 2017 to 2019, 54.2% of patients received immunotherapy. This increased from 45.1% in 2017 to 63.0% in 2019. High-volume centers were significantly more likely to use immunotherapy (odds ratio 3.235, p = 0.002). On univariate analysis, patients receiving systemic immunotherapy had significantly improved overall survival (p < 0.001). One-, 3-, and 5-year survival was 47.2% (standard error [SE] 1.8%), 21.8% (SE 1.5%), and 16.5% (SE 1.4%), respectively, for patients who did not receive immunotherapy versus 62.7% (SE 3.5%), 34.4% (SE 3.9%), and 23.6% (SE 4.4%), respectively, for those who did (Fig. 1). In our multivariable survival regression, receipt of immunotherapy was associated with an approximately 35% reduction in hazard of death (hazard ratio 0.665, p < 0.001; 95% CI 0.548-0.808). Our results demonstrate that the real-world survival advantage of immunotherapy for metastatic MCC is similar to clinical trial data. However, many patients with metastatic disease did not receive this guideline-recommended therapy in our most recent study year, and use of immunotherapy is higher at high-volume centers. This suggests that regionalization of care to high-volume centers or dissemination of their practices, may ultimately improve patient survival.
PMID: 38349538
ISSN: 1432-069x
CID: 5635292

Desmoplasia is associated with decreased cytotoxic and helper T cells and increased T cell exhaustion in cutaneous squamous cell carcinoma

Hirakawa, Yuka; Zhan, Qian; Essien, Sernah; Yu, Kenneth K; Murad, Fadi; Piris, Adriano; Ramsey, Matthew R; Schatton, Tobias; Carucci, John A; Schmults, Chrysalyne D
PMID: 38309575
ISSN: 1523-1747
CID: 5627062

Treatment of Merkel Cell Carcinoma With Mohs Micrographic Surgery Is Associated With Shorter Delays to Surgery in the United States

Cheraghlou, Shayan; Jairath, Neil K; Carucci, John A; Criscito, Maressa C
PMID: 37861352
ISSN: 1524-4725
CID: 5633012

An update on private equity acquisitions in dermatology, 2013 to 2022

Agarwal, Aneesh; Orlow, Seth J
PMID: 37863202
ISSN: 1097-6787
CID: 5614262

Kinase Insert Domain Receptor Q472H Pathogenic Germline Variant Impacts Melanoma Tumor Growth and Patient Treatment Outcomes

Ibrahim, Milad; Illa-Bochaca, Irineu; Fa"™ak, Faisal; Monson, Kelsey R.; Ferguson, Robert; Lyu, Chen; Vega-Saenz de Miera, Eleazar; Johannet, Paul; Chou, Margaret; Mastroianni, Justin; Darvishian, Farbod; Kirchhoff, Tomas; Zhong, Judy; Krogsgaard, Michelle; Osman, Iman
Background: We previously reported a higher incidence of a pathogenic germline variant in the kinase insert domain receptor (KDR) in melanoma patients compared to the general population. Here, we dissect the impact of this genotype on melanoma tumor growth kinetics, tumor phenotype, and response to treatment with immune checkpoint inhibitors (ICIs) or targeted therapy. Methods: The KDR genotype was determined and the associations between the KDR Q472H variant (KDR-Var), angiogenesis, tumor immunophenotype, and response to MAPK inhibition or ICI treatment were examined. Melanoma B16 cell lines were transfected with KDR-Var or KDR wild type (KDR-WT), and the differences in tumor kinetics were evaluated. We also examined the impact of KDR-Var on the response of melanoma cells to a combination of VEGFR inhibition with MAPKi. Results: We identified the KDR-Var genotype in 81/489 (37%) patients, and it was associated with a more angiogenic (p = 0.003) and immune-suppressive tumor phenotype. KDR-Var was also associated with decreased PFS to MAPKi (p = 0.022) and a trend with worse PFS to anti-PD1 therapy (p = 0.06). KDR-Var B16 murine models had increased average tumor volume (p = 0.0027) and decreased CD45 tumor-infiltrating lymphocytes (p = 0.0282). The anti-VEGFR treatment Lenvatinib reduced the tumor size of KDR-Var murine tumors (p = 0.0159), and KDR-Var cells showed synergistic cytotoxicity to the combination of dabrafenib and lenvatinib. Conclusions: Our data demonstrate a role of germline KDR-Var in modulating melanoma behavior, including response to treatment. Our data also suggest that anti-angiogenic therapy might be beneficial in patients harboring this genotype, which needs to be tested in clinical trials.
SCOPUS:85182244291
ISSN: 2072-6694
CID: 5629852