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Article ; Online: JAK2 R683S Mutation Resulting in Dual Diagnoses of Chronic Eosinophilic Leukemia and Myelodysplastic/Myeloproliferative Overlap Syndrome.

Krah, Nathan M / Miotke, Laura / Li, Peng / Patel, Jay L / Bowen, Anneli R / Pomicter, Anthony D / Patel, Ami B

Journal of the National Comprehensive Cancer Network : JNCCN

2024 Volume 21, Issue 12, Page(s) 1218–1223

Abstract: A 66-year-old male presented with hypereosinophilia, thrombocytosis, extensive thrombosis refractory to direct oral anticoagulant therapy, and evidence of end-organ damage, including rash, splenic infarcts, and pulmonary infiltrates. Bone marrow biopsy ... ...

Abstract	A 66-year-old male presented with hypereosinophilia, thrombocytosis, extensive thrombosis refractory to direct oral anticoagulant therapy, and evidence of end-organ damage, including rash, splenic infarcts, and pulmonary infiltrates. Bone marrow biopsy revealed myeloid malignancy consistent with both chronic eosinophilic leukemia and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with SF3B1 mutation and thrombocytosis. Next-generation sequencing of the patient's eosinophils and neutrophil compartments revealed pathologic variants in EZH2 and SF3B1 in addition to a noncanonical JAK2 R683S mutation that has not been previously described in myeloproliferative disorders or other chronic myeloid neoplasms. These mutations were not present in the patient's lymphoid cell fraction, suggesting that the hematopoietic malignancy arose in a myeloid-committed progenitor cell. Based on this case and previous work from our group, we propose that noncanonical JAK2 mutations may permit signal transduction that biases toward eosinophilic differentiation in chronic myeloid neoplasms. Although the patient's blood counts initially responded to ruxolitinib and hydroxyurea, the response was not durable. Early referral for allogenic bone marrow transplant appears necessary to prevent long-term complications and disease progression in myeloid neoplasms with clonal hypereosinophilia driven by noncanonical JAK2 mutations.
MeSH term(s)	Male ; Humans ; Aged ; Diagnosis, Dual (Psychiatry) ; Myelodysplastic Syndromes/genetics ; Leukemia ; Myeloproliferative Disorders/diagnosis ; Myeloproliferative Disorders/genetics ; Myeloproliferative Disorders/therapy ; Thrombocytosis/diagnosis ; Thrombocytosis/genetics ; Thrombocytosis/pathology ; Mutation ; Eosinophilia ; Janus Kinase 2/genetics
Chemical Substances	JAK2 protein, human (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2)
Language	English
Publishing date	2024-01-12
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2250759-0
ISSN	1540-1413 ; 1540-1405
ISSN (online)	1540-1413
ISSN	1540-1405
DOI	10.6004/jnccn.2023.7068
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Zs.A 6365: Show issues

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Article ; Online: Electronic Cigarette Vape Exposure Exacerbates Post-Ischemic Outcomes in Female but Not in Male Rats.

Pradhyumnan, Hari / Patel, Shahil H / Furones-Alonso, Ofelia / Zhao, Weizhao / Bramlett, Helen M / Raval, Ami P

Stroke

2024 Volume 55, Issue 3, Page(s) 735–746

Abstract: Background: Nicotine-containing electronic cigarette (EC) vaping has become popular worldwide, and our understanding of the effects of vaping on stroke outcomes is elusive. Using a rat model of transient middle cerebral artery occlusion, the current ... ...

Abstract	Background: Nicotine-containing electronic cigarette (EC) vaping has become popular worldwide, and our understanding of the effects of vaping on stroke outcomes is elusive. Using a rat model of transient middle cerebral artery occlusion, the current exploratory study aims to evaluate the sex-dependent effects of EC exposure on brain energy metabolism and stroke outcomes. Methods: Adult Sprague-Dawley rats of both sexes were randomly assigned to air/EC vapor (5% nicotine Juul pods) exposure for 16 nights, followed by randomization into 3 cohorts. The first cohort underwent exposure to air/EC preceding randomization to transient middle cerebral artery occlusion (90 minutes) or sham surgery, followed by survival for 21 days. During the survival period, rats underwent sensorimotor and Morris water maze testing. Subsequently, brains were collected for histopathology. A second cohort was exposed to air/EC after which brains were collected for unbiased metabolomics analysis. The third cohort of animals was exposed to air/EC and received transient middle cerebral artery occlusion/sham surgery, and brain tissue was collected 24 hours later for biochemical analysis. Results: In females, EC significantly increased ( Conclusions: Even brief EC exposure over 2 weeks impacts brain energy metabolism, exacerbates infarction, and worsens poststroke cognitive deficits in working memory more in female than male rats.
MeSH term(s)	Humans ; Adult ; Rats ; Male ; Female ; Animals ; Vaping ; Rats, Sprague-Dawley ; Nicotine/adverse effects ; Electronic Nicotine Delivery Systems ; Infarction, Middle Cerebral Artery/metabolism
Chemical Substances	Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2024-02-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	80381-9
ISSN	1524-4628 ; 0039-2499 ; 0749-7954
ISSN (online)	1524-4628
ISSN	0039-2499 ; 0749-7954
DOI	10.1161/STROKEAHA.123.046101
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Zs.A 448: Show issues

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Article: Evolving Coronary Stent Technologies - A Glimpse Into the Future.

Patel, Smeet / Patel, Kalpen B / Patel, Zeel / Konat, Ashwati / Patel, Ami / Doshi, Jinish S / Chokshi, Priyank / Patel, Divya / Sharma, Kamal / Amdani, MohmadSabir M / Shah, Darshini B / Dholu, Urva / Patel, Merik

Cureus

2023 Volume 15, Issue 3, Page(s) e35651

Abstract: One of the most widely accepted forms of treatment for coronary artery disease (CAD) is the implementation of stents into the vessel. This area of research is constantly evolving, ranging from bare-metal stents through drug-eluting stents and, more ... ...

Abstract	One of the most widely accepted forms of treatment for coronary artery disease (CAD) is the implementation of stents into the vessel. This area of research is constantly evolving, ranging from bare-metal stents through drug-eluting stents and, more recently, approaching bioresorbable stents and polymer-free stents. This article reviews the evolution of all these devices and emphasizes how they might be further evolved to provide an optimal coronary stent and overcome unsolved challenges in stent development. We thoroughly evaluated a number of published studies in order to advance coronary stent technologies. Additionally, we looked for various literature that highlighted the inadequacies of the coronary stents that are currently available and how they might be modified to create the optimum coronary stent. Coronary stents have significantly improved clinical outcomes in interventional cardiology, but there are still a number of drawbacks, including an persisted risk of thrombosis due to endothelial injury and in-stent restenosis. Gene eluting stents (GES) and customized coronary stents with self-reporting stent sensors are appealing alternatives to existing stent approaches. Considering the adequacy of these gene eluting stents (GES), customized coronary stents produced by novel 4D printing technologies and integrated self-reporting stent sensors should be assumed for anticipating future advancements to optimal coronary stent devices; however, more interventional evidence is required to determine the future prospects of these stent innovations.
Language	English
Publishing date	2023-03-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.35651
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Article: A Case of Sustained Viral Shedding of Mpox With Ocular Involvement Resulting in Vision Loss.

Speiser, Lisa J / Wonnaparhown, Alex M / Blair, Janis / Shah, Ami / Patel, Dharmendra R / McCullough, Ann E / Nicolasora, Nelson / Khalsa, Ann M / Orenstein, Robert / Vikram, Holenarasipur R / Huang, Vivian / Seville, Maria Teresa

Open forum infectious diseases

2023 Volume 11, Issue 1, Page(s) ofad632

Abstract: Mpox, caused by infection ... ...

Abstract	Mpox, caused by infection with
Language	English
Publishing date	2023-12-14
Publishing country	United States
Document type	Case Reports
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofad632
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Article ; Online: A Perspective on Hormonal Contraception Usage in Central Nervous System Injury.

Pradhyumnan, Hari / Perez, Gina G / Patel, Shahil H / Blaya, Meghan O / Bramlett, Helen M / Raval, Ami P

Journal of neurotrauma

2023 Volume 41, Issue 5-6, Page(s) 541–551

Abstract: Naturally occurring life stages in women are associated with changes in the milieu of endogenous ovarian hormones. Women of childbearing age may be exposed to exogenous ovarian hormone(s) because of their use of varying combinations of estrogen and ... ...

Abstract	Naturally occurring life stages in women are associated with changes in the milieu of endogenous ovarian hormones. Women of childbearing age may be exposed to exogenous ovarian hormone(s) because of their use of varying combinations of estrogen and progesterone hormones-containing oral contraceptives (OC; also known as "the pill"). If women have central nervous system (CNS) injury such as spinal cord injury (SCI) and traumatic brain injury (TBI) during their childbearing age, they are likely to retain their reproductive capabilities and may use OC. Many deleterious side effects of long-term OC use have been reported, such as aberrant blood clotting and endothelial dysfunction that consequently increase the risk of myocardial infarction, venous thromboembolism, and ischemic brain injury. Although controversial, studies have suggested that OC use is associated with neuropsychiatric ramifications, including uncontrollable mood swings and poorer cognitive performance. Our understanding about how the combination of endogenous hormones and OC-conferred exogenous hormones affect outcomes after CNS injuries remains limited. Therefore, understanding the impact of OC use on CNS injury outcomes needs further investigation to reveal underlying mechanisms, promote reporting in clinical or epidemiological studies, and raise awareness of possible compounded consequences. The goal of the current review is to discuss the impacts of CNS injury on endogenous ovarian hormones and vice-versa, as well as the putative consequences of exogenous ovarian hormones (OC) on the CNS to identify potential gaps in our knowledge to consider for future laboratory, epidemiological, and clinical studies.
MeSH term(s)	Female ; Humans ; Hormonal Contraception ; Trauma, Nervous System ; Central Nervous System ; Brain Injuries, Traumatic ; Estrogens
Chemical Substances	Estrogens
Language	English
Publishing date	2023-12-21
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2023.0219
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Zs.A 2016: Show issues

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Article ; Online: Impact of menopause-associated frailty on traumatic brain injury.

Sinder, Sophie B / Sharma, Sabrina V / Shirvaikar, Isha S / Pradhyumnan, Hari / Patel, Shahil H / Cabeda Diaz, Indy / Perez, Gina G / Bramlett, Helen M / Raval, Ami P

Neurochemistry international

2024 Volume 176, Page(s) 105741

Abstract: Navigating menopause involves traversing a complex terrain of hormonal changes that extend far beyond reproductive consequences. Menopausal transition is characterized by a decrease in estradiol-17β (E2), and the impact of menopause resonates not only in ...

Abstract	Navigating menopause involves traversing a complex terrain of hormonal changes that extend far beyond reproductive consequences. Menopausal transition is characterized by a decrease in estradiol-17β (E2), and the impact of menopause resonates not only in the reproductive system but also through the central nervous system, musculoskeletal, and gastrointestinal domains. As women undergo menopausal transition, they become more susceptible to frailty, amplifying the risk and severity of injuries, including traumatic brain injury (TBI). Menopause triggers a cascade of changes leading to a decline in muscle mass, accompanied by diminished tone and excitability, thereby restricting the availability of irisin, a crucial hormone derived from muscles. Concurrently, bone mass undergoes reduction, culminating in the onset of osteoporosis and altering the dynamics of osteocalcin, a hormone originating from bones. The diminishing levels of E2 during menopause extend their influence on the gut microbiota, resulting in a reduction in the availability of tyrosine, tryptophan, and serotonin metabolites, affecting neurotransmitter synthesis and function. Understanding the interplay between menopause, frailty, E2 decline, and the intricate metabolisms of bone, gut, and muscle is imperative when unraveling the nuances of TBI after menopause. The current review underscores the significance of accounting for menopause-associated frailty in the incidence and consequences of TBI. The review also explores potential mechanisms to enhance gut, bone, and muscle health in menopausal women, aiming to mitigate frailty and improve TBI outcomes.
Language	English
Publishing date	2024-04-14
Publishing country	England
Document type	Journal Article
ZDB-ID	283190-9
ISSN	1872-9754 ; 0197-0186
ISSN (online)	1872-9754
ISSN	0197-0186
DOI	10.1016/j.neuint.2024.105741
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Zs.A 1610: Show issues

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Article ; Online: Clonal hematopoiesis in patients with HIV and cancer.

Gillis, Nancy / Dickey, Brittney L / Colin-Leitzinger, Christelle / Tang, Yi-Han / Putney, Ryan M / Mesa, Tania E / Yoder, Sean J / Suneja, Gita / Spivak, Adam M / Patel, Ami B / Extermann, Martine / Giuliano, Anna R / Teng, Mingxiang / Kresovich, Jacob / Berglund, Anders / Coghill, Anna E

The Journal of infectious diseases

2024

Abstract: Background: Cancer-related deaths for people living with HIV (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and ... ...

Abstract	Background: Cancer-related deaths for people living with HIV (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH. Methods: We conducted a retrospective study to compare the prevalence and clinical outcomes of CH in PWH and people without HIV (PWoH) and cancer. Included in the study were PWH and similar PWoH based on tumor site, age, tumor sequence, and cancer treatment status. Biological aging was also measured using epigenetic methylation clocks. Results: In 136 patients with cancer, PWH had twice the prevalence of CH compared to similar PWoH (23% vs 11%, p=0.07). After adjusting for patient characteristics, PWH were four-times more likely to have CH than PWoH (OR 4.1, 95% CI 1.3-13.9, p=0.02). The effect of CH on survival was most pronounced in PWH, who had a 5-year survival rate of 38% if they had CH (vs 59% if no CH), compared to PWoH who had a 5-year survival rate of 75% if they had CH (vs 83% if no CH). Conclusion: This study provides the first evidence that PWH may have a higher prevalence of CH than PWoH with the same cancers. CH may be an independent biological aging risk factor contributing to inferior survival for PWH and cancer.
Language	English
Publishing date	2024-04-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiae212
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Uh II Zs.50: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 445: Show issues

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Article ; Online: Trisomy 21 and Coronavirus Disease 2019 in Pediatric Patients.

Newman, Alexander M / Jhaveri, Ravi / Patel, Ami B / Tan, Tina Q / Toia, Jacqueline M / Arshad, Mehreen

The Journal of pediatrics

2020 Volume 228, Page(s) 294–296

Abstract: We present 4 pediatric patients with trisomy 21 (T21) and associated comorbidities who developed coronavirus disease 2019 requiring hospitalization. A review of the literature revealed that comorbidities associated with T21 may predispose patients to ... ...

Abstract	We present 4 pediatric patients with trisomy 21 (T21) and associated comorbidities who developed coronavirus disease 2019 requiring hospitalization. A review of the literature revealed that comorbidities associated with T21 may predispose patients to severe disease. Children with T21 should be considered high risk and monitored carefully if infected with severe acute respiratory syndrome coronavirus 2.
MeSH term(s)	Adolescent ; COVID-19/complications ; COVID-19/epidemiology ; Comorbidity ; Disease Susceptibility ; Down Syndrome/complications ; Down Syndrome/epidemiology ; Hospitalization ; Humans ; Infant ; Male ; Risk Factors ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-08-27
Publishing country	United States
Document type	Case Reports
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2020.08.067
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Article ; Online: Antiplatelet Therapy and Bleeding Outcomes With CYP2C19 Genotyping.

Coons, James C / Stevenson, James M / Patel, Ami / Smith, A J Conrad / Prebehalla, Linda / Empey, Philip E

Journal of cardiovascular pharmacology and therapeutics

2022 Volume 27, Page(s) 10742484221143246

Abstract: Purpose: The impact of antiplatelet therapy with availability of CYP2C19 genotyping on bleeding in a real-world setting has not been extensively studied.: Methods: Prospective, single-center, cohort study conducted between December 2015 and October ... ...

Abstract	Purpose: The impact of antiplatelet therapy with availability of CYP2C19 genotyping on bleeding in a real-world setting has not been extensively studied. Methods: Prospective, single-center, cohort study conducted between December 2015 and October 2019 with 1-year follow-up. Patients underwent percutaneous coronary intervention (PCI), CYP2C19 genotyping, and received P2Y12 inhibitor therapy. The primary outcome was time to first bleed of any severity using Bleeding Academic Research Consortium criteria. Secondary outcomes included time to first major bleed and rates of antiplatelet switching. Results: The primary outcome occurred in 697 of 2091 (33%) participants at a median of 15 days. Major bleeding occurred in 176 (8%) of patients. Compared to clopidogrel, treatment with ticagrelor or prasugrel was associated with increased risk of any bleeding (adjusted HR [aHR] 2.04, 95% CI 1.69-2.46). For patients without CYP2C19 no function alleles, treatment with prasugrel or ticagrelor was associated with increased risk of any bleeding (aHR 2.31, 95% CI 1.83-2.90). Similar associations were observed for major bleeding. No difference in ischemic events was observed. Among patients discharged on ticagrelor or prasugrel, 199 (36%) were de-escalated to clopidogrel within 1 year. De-escalation was more likely after a bleed if patients did not have a no function allele (35.9% vs 19.1%; Conclusion: Bleeding is common in post-PCI patients on antiplatelet therapy. Patients on high potency agents had higher bleeding risk in the population at-large and in non-carriers of CYP2C19 no function alleles. Genotype-guided antiplatelet de-escalation should be further explored in prospective studies.
Language	English
Publishing date	2022-12-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	1329372-2
ISSN	1940-4034 ; 1074-2484
ISSN (online)	1940-4034
ISSN	1074-2484
DOI	10.1177/10742484221143246
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Zs.A 4895: Show issues

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Article ; Online: Differences in epigenetic age by HIV status among patients with a non-AIDS defining cancer.

Dickey, Brittney L / Putney, Ryan M / Suneja, Gita / Kresovich, Jacob K / Spivak, Adam M / Patel, Ami B / Teng, Mingxiang / Extermann, Martine / Giuliano, Anna R / Gillis, Nancy / Berglund, Anders / Coghill, Anna E

AIDS (London, England)

2023 Volume 37, Issue 13, Page(s) 2049–2057

Abstract: Objective: People with HIV (PWH) are living longer and experiencing higher numbers of non-AIDS-defining cancers (NADC). Epigenetic aging biomarkers have been linked to cancer risk, and cancer is now a leading cause of death in PWH, but these biomarkers ... ...

Abstract	Objective: People with HIV (PWH) are living longer and experiencing higher numbers of non-AIDS-defining cancers (NADC). Epigenetic aging biomarkers have been linked to cancer risk, and cancer is now a leading cause of death in PWH, but these biomarkers have not been investigated in PWH and cancer. Design: In order to compare epigenetic age by HIV status, HIV-uninfected participants were matched to PWH by reported age, tumor site, tumor sequence number, and cancer treatment status. Methods: DNA from blood was assayed using Illumina MethylationEPIC BeadChip, and we estimated immune cell composition and aging from three epigenetic clocks: Horvath, GrimAge, and epiTOC2. Age acceleration by clock was computed as the residual from the expected value, calculated using linear regression, for each study participant. Comparisons across HIV status used the Wilcoxon rank sum test. Hazard ratios and 95% confidence intervals for the association between age acceleration and survival in PWH were estimated with Cox regression. Results: Among 65 NADC participants with HIV and 64 without, biological age from epiTOC2 ( P < 0.0001) and GrimAge ( P = 0.017) was significantly higher in PWH. Biological age acceleration was significantly higher in PWH using epiTOC2 ( P < 0.01) and GrimAge ( P < 0.0001), with the difference in GrimAge remaining statistically significant after adjustment for immune cell composition. Among PWH, GrimAge acceleration was significantly associated with increased risk of death (hazard ratio 1.11; 95% confidence interval (CI) 1.04-1.18). Conclusion: We observed a higher epigenetic age in PWH with a NADC diagnosis compared with their HIV-uninfected counterparts, as well as a significant association between this accelerated biological aging and survival for patients diagnosed with a NADC.
MeSH term(s)	Humans ; HIV Infections/complications ; Acquired Immunodeficiency Syndrome/complications ; Aging ; Neoplasms/genetics ; Neoplasms/complications ; Epigenesis, Genetic
Language	English
Publishing date	2023-07-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0000000000003661
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