108 results on '"M, Kuruvilla"'
Search Results
2. Data from Maximal Activation of Apoptosis Signaling by Cotargeting Antiapoptotic Proteins in BH3 Mimetic–Resistant AML and AML Stem Cells
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Michael Andreeff, Phuong K. Morrow, Xiaoyue Chen, Paul E. Hughes, Elias J. Jabbour, Marina Konopleva, Venkata L. Battula, Duncan H. Mak, Xiangmeng Wang, Vinitha M. Kuruvilla, Vivian Ruvolo, Qi Zhang, Wenjing Tao, Po Yee Mak, and Bing Z. Carter
- Abstract
MCL-1 is known to play a major role in resistance to BCL-2 inhibition, but the contribution of other BCL-2 family proteins has not been fully explored. We, here, demonstrate the ineffectiveness of MCL-1 inhibitor AMG176 in venetoclax-resistant, and conversely, of venetoclax in AMG176-resistant acute myelogenous leukemia (AML). Like cells with acquired resistance to venetoclax, cells with acquired resistance to AMG176 express increased MCL-1. Both cells with acquired resistance to venetoclax and to AMG176 express increased levels of BCL-2 and BCL-2A1, decreased BAX, and/or altered levels of other BCL-2 proteins. Cotargeting BCL-2 and MCL-1 was highly synergistic in AML cell lines with intrinsic or acquired resistance to BH3 mimetics or engineered to genetically overexpress BCL-2 or BCL-2A1 or downregulate BAX. The combination effectively eliminated primary AML blasts and stem/progenitor cells resistant to or relapsed after venetoclax-based therapy irrespective of mutations and cytogenetic abnormalities. Venetoclax and AMG176 combination markedly suppressed antiapoptotic BCL-2 proteins and AML stem/progenitor cells and dramatically extended mouse survival (median 336 vs. control 126 days; P < 0.0001) in a patient-derived xenograft (PDX) model developed from a venetoclax/hypomethylating agent therapy-resistant patient with AML. However, decreased BAX levels in the bone marrow residual leukemia cells after 4-week combination treatment may represent a resistance mechanism that contributed to their survival. Enhanced antileukemia activity was also observed in a PDX model of monocytic AML, known to be resistant to venetoclax therapy. Our results support codependence on multiple antiapoptotic BCL-2 proteins and suppression of BAX as mechanisms of AML resistance to individual BH3 mimetics. Cotargeting of MCL-1 and BCL-2 eliminates otherwise apoptosis-resistant cells.
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- 2023
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3. Table S1 from Selective Inhibition of the Second Bromodomain of BET Family Proteins Results in Robust Antitumor Activity in Preclinical Models of Acute Myeloid Leukemia
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Yu Shen, Marina Konopleva, Warren M. Kati, Keith F. McDaniel, Daniel H. Albert, Michael Boyiadzis, Kathleen A. Dorritie, Neal C. Goodwin, Jenny Rowe, Terrance J. Magoc, Sriram S. Shanmugavelandy, Gaurav Mehta, Debra C. Ferguson, Lina Han, Antonio Cavazos, Qi Zhang, Tamar Uziel, Paul Hessler, Weiguo Feng, Zheng Zha, Xin Lu, Lloyd T. Lam, Vinitha M. Kuruvilla, Emily J. Faivre, Richard J. Bellin, Joshua P. Plotnik, Mai H. Bui, Xiaoli Huang, Xiaoyu Lin, Tianyu Cai, and Lu Zhang
- Abstract
Primary patient sample information
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- 2023
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4. Supplementary Figure from Maximal Activation of Apoptosis Signaling by Cotargeting Antiapoptotic Proteins in BH3 Mimetic–Resistant AML and AML Stem Cells
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Michael Andreeff, Phuong K. Morrow, Xiaoyue Chen, Paul E. Hughes, Elias J. Jabbour, Marina Konopleva, Venkata L. Battula, Duncan H. Mak, Xiangmeng Wang, Vinitha M. Kuruvilla, Vivian Ruvolo, Qi Zhang, Wenjing Tao, Po Yee Mak, and Bing Z. Carter
- Abstract
Supplementary Figure from Maximal Activation of Apoptosis Signaling by Cotargeting Antiapoptotic Proteins in BH3 Mimetic–Resistant AML and AML Stem Cells
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- 2023
- Full Text
- View/download PDF
5. Supplementary Data from Maximal Activation of Apoptosis Signaling by Cotargeting Antiapoptotic Proteins in BH3 Mimetic–Resistant AML and AML Stem Cells
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Michael Andreeff, Phuong K. Morrow, Xiaoyue Chen, Paul E. Hughes, Elias J. Jabbour, Marina Konopleva, Venkata L. Battula, Duncan H. Mak, Xiangmeng Wang, Vinitha M. Kuruvilla, Vivian Ruvolo, Qi Zhang, Wenjing Tao, Po Yee Mak, and Bing Z. Carter
- Abstract
Supplementary Data from Maximal Activation of Apoptosis Signaling by Cotargeting Antiapoptotic Proteins in BH3 Mimetic–Resistant AML and AML Stem Cells
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- 2023
- Full Text
- View/download PDF
6. Supplementary Data from Selective Inhibition of the Second Bromodomain of BET Family Proteins Results in Robust Antitumor Activity in Preclinical Models of Acute Myeloid Leukemia
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Yu Shen, Marina Konopleva, Warren M. Kati, Keith F. McDaniel, Daniel H. Albert, Michael Boyiadzis, Kathleen A. Dorritie, Neal C. Goodwin, Jenny Rowe, Terrance J. Magoc, Sriram S. Shanmugavelandy, Gaurav Mehta, Debra C. Ferguson, Lina Han, Antonio Cavazos, Qi Zhang, Tamar Uziel, Paul Hessler, Weiguo Feng, Zheng Zha, Xin Lu, Lloyd T. Lam, Vinitha M. Kuruvilla, Emily J. Faivre, Richard J. Bellin, Joshua P. Plotnik, Mai H. Bui, Xiaoli Huang, Xiaoyu Lin, Tianyu Cai, and Lu Zhang
- Abstract
Supplementary figure and table legends
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- 2023
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7. Data from Selective Inhibition of the Second Bromodomain of BET Family Proteins Results in Robust Antitumor Activity in Preclinical Models of Acute Myeloid Leukemia
- Author
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Yu Shen, Marina Konopleva, Warren M. Kati, Keith F. McDaniel, Daniel H. Albert, Michael Boyiadzis, Kathleen A. Dorritie, Neal C. Goodwin, Jenny Rowe, Terrance J. Magoc, Sriram S. Shanmugavelandy, Gaurav Mehta, Debra C. Ferguson, Lina Han, Antonio Cavazos, Qi Zhang, Tamar Uziel, Paul Hessler, Weiguo Feng, Zheng Zha, Xin Lu, Lloyd T. Lam, Vinitha M. Kuruvilla, Emily J. Faivre, Richard J. Bellin, Joshua P. Plotnik, Mai H. Bui, Xiaoli Huang, Xiaoyu Lin, Tianyu Cai, and Lu Zhang
- Abstract
Dual bromodomain BET inhibitors that bind with similar affinities to the first and second bromodomains across BRD2, BRD3, BRD4, and BRDT have displayed modest activity as monotherapy in clinical trials. Thrombocytopenia, closely followed by symptoms characteristic of gastrointestinal toxicity, have presented as dose-limiting adverse events that may have prevented escalation to higher dose levels required for more robust efficacy. ABBV-744 is a highly selective inhibitor for the second bromodomain of the four BET family proteins. In contrast to the broad antiproliferative activities observed with dual bromodomain BET inhibitors, ABBV-744 displayed significant antiproliferative activities largely although not exclusively in cancer cell lines derived from acute myeloid leukemia and androgen receptor positive prostate cancer. Studies in acute myeloid leukemia xenograft models demonstrated antitumor efficacy for ABBV-744 that was comparable with the pan-BET inhibitor ABBV-075 but with an improved therapeutic index. Enhanced antitumor efficacy was also observed with the combination of ABBV-744 and the BCL-2 inhibitor, venetoclax compared with monotherapies of either agent alone. These results collectively support the clinical evaluation of ABBV-744 in AML (Clinical Trials.gov identifier: NCT03360006).
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- 2023
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8. Maximal activation of apoptosis signaling by co-targeting anti-apoptotic proteins in BH3 mimetic-resistant AML and AML stem cells
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Bing Z. Carter, Po Yee Mak, Wenjing Tao, Qi Zhang, Vivian Ruvolo, Vinitha M. Kuruvilla, Xiangmeng Wang, Duncan H. Mak, Venkata L. Battula, Marina Konopleva, Elias J. Jabbour, Paul E. Hughes, Xiaoyue Chen, Phuong K. Morrow, and Michael Andreeff
- Subjects
Cancer Research ,Stem Cells ,Apoptosis ,Bridged Bicyclo Compounds, Heterocyclic ,Article ,Leukemia, Myeloid, Acute ,Mice ,Oncology ,Proto-Oncogene Proteins c-bcl-2 ,Biomimetic Materials ,hemic and lymphatic diseases ,Cell Line, Tumor ,Animals ,Humans ,Myeloid Cell Leukemia Sequence 1 Protein ,Apoptosis Regulatory Proteins ,bcl-2-Associated X Protein - Abstract
MCL-1 is known to play a major role in resistance to BCL-2 inhibition, but the contribution of other BCL-2 family proteins has not been fully explored. We, here, demonstrate the ineffectiveness of MCL-1 inhibitor AMG176 in venetoclax-resistant, and conversely, of venetoclax in AMG176-resistant acute myelogenous leukemia (AML). Like cells with acquired resistance to venetoclax, cells with acquired resistance to AMG176 express increased MCL-1. Both cells with acquired resistance to venetoclax and to AMG176 express increased levels of BCL-2 and BCL-2A1, decreased BAX, and/or altered levels of other BCL-2 proteins. Cotargeting BCL-2 and MCL-1 was highly synergistic in AML cell lines with intrinsic or acquired resistance to BH3 mimetics or engineered to genetically overexpress BCL-2 or BCL-2A1 or downregulate BAX. The combination effectively eliminated primary AML blasts and stem/progenitor cells resistant to or relapsed after venetoclax-based therapy irrespective of mutations and cytogenetic abnormalities. Venetoclax and AMG176 combination markedly suppressed antiapoptotic BCL-2 proteins and AML stem/progenitor cells and dramatically extended mouse survival (median 336 vs. control 126 days; P < 0.0001) in a patient-derived xenograft (PDX) model developed from a venetoclax/hypomethylating agent therapy-resistant patient with AML. However, decreased BAX levels in the bone marrow residual leukemia cells after 4-week combination treatment may represent a resistance mechanism that contributed to their survival. Enhanced antileukemia activity was also observed in a PDX model of monocytic AML, known to be resistant to venetoclax therapy. Our results support codependence on multiple antiapoptotic BCL-2 proteins and suppression of BAX as mechanisms of AML resistance to individual BH3 mimetics. Cotargeting of MCL-1 and BCL-2 eliminates otherwise apoptosis-resistant cells.
- Published
- 2022
9. Abstract A24: Targeting mitochondrial metabolism following Induction Chemotherapy eradicates Acute Myeloid Leukemia at the level of Minimal Residual Disease
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Natalia Baran, Lina Han, Lucille Stuani, Antonio Cavazos, Laurie M. Cooper, Cassandra L. Ramage, Vinitha M. Kuruvilla, Qi Zhang, Marie Sabatier, Emeline Boet, Jason P. Gay, Ningping Feng, Lokesh Battula, Emeline Chu-Van, Florence Castelli, Martin Carrol, Sergej Konoplev, Beenu Thakral, Hagop M. Kantarjian, Naval Daver, Joseph Marszalek, Michael Andreeff, Jean-Emmanuel Sarry, and Marina Konopleva
- Subjects
General Medicine - Abstract
Acute myeloid leukemia (AML) stem cells (AMLSCs) are thought to be responsible for disease initiation, chemoresistance and treatment failure. AMLSCs and residual cytarabine (AraC)-resistant AML cells (constituting minimal residual disease, MRD) were shown to be highly dependent on mitochondrial function for survival and thus are vulnerable to pharmacological blockade of the oxidative phosphorylation (OXPHOS) (Farge et al. Cancer Discov, 2017). Efficacy of OXPHOS inhibitor IACS-010759 was previously reported, demonstrating potent inhibition of mitochondrial complex I, OXPHOS suppression and growth inhibition of AML cells (Molina, et al. Nat Med, 2018). Here we evaluated OXPHOS dependency of AML MRD cells and determined impact of OXPHOS blockade on residual AML cells surviving standard chemotherapy (Doxorubicin/AraC, DA). Our results demonstrated that AML cell lines treated with AraC or DA induced accumulation of reactive oxygen species, mitochondrial superoxides, increased mitochondrial mass and mitochondrial membrane potential. AraC- and DA-based therapies in vitro were significantly potentiated by IACS-010759. OxPhos dependency shown as a significantly increased basal and maximal oxygen consumption rate after AraC and DA treatment, was fully inhibited by OxPhos inhibitor, leading to a total mitochondrial collapse. OxPhos inhibition in combination with DA consolidated reduction of viable cell number, induction of apoptosis and differentiation in cell lines and in AraC-resistant primary patient samples. Next, the efficacy of IACS-010759 together with DA chemotherapy was evaluated in several chemotherapy-sensitive and -resistant animal models in vivo. DA/IACS-010759 combination significantly reduced leukemia burden and significantly extended survival in OCI-AML3/Luc/GFP model and in FLT3-ITD+ AML PDX model. In the latter, IACS-010759 led to reduction of leukemia burden, and delayed leukemia recurrence when administered post completion of DA. At the single-cell level, CyTOF analysis demonstrated that this combination reduced frequency of CD34+CD38lowCD123+AML LSCs and has superior efficacy to facilitate differentiation of immature subpopulations. Furthermore, addition of IACS-010759 to DA extended survival of mice inoculated with chemoresistant PDX AML models. Finally, IACS-010759 administered during consolidation phase significantly extended mice survival compared to standard of care arm, supporting clinical utility of OXPHOS inhibitors in AML. In conclusion, our findings indicate that chemotherapy fosters mitochondrial respiration in AML, which could be abrogated by OXPHOS inhibitor at the LSCs and MRD level, in vitro and in vivo. Our data advocate for combining mitochondrial targeting strategies with chemotherapy as a part of induction and consolidation treatment for improved control of MRD, eradication of AMLSC and extended response duration. Citation Format: Natalia Baran, Lina Han, Lucille Stuani, Antonio Cavazos, Laurie M. Cooper, Cassandra L. Ramage, Vinitha M. Kuruvilla, Qi Zhang, Marie Sabatier, Emeline Boet, Jason P. Gay, Ningping Feng, Lokesh Battula, Emeline Chu-Van, Florence Castelli, Martin Carrol, Sergej Konoplev, Beenu Thakral, Hagop M. Kantarjian, Naval Daver, Joseph Marszalek, Michael Andreeff, Jean-Emmanuel Sarry, Marina Konopleva. Targeting mitochondrial metabolism following Induction Chemotherapy eradicates Acute Myeloid Leukemia at the level of Minimal Residual Disease [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr A24.
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- 2023
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10. P401 PATIENT SATISFACTION WITH TELEMEDICINE SERVICES IN ALLERGY: AN INSTITUTIONAL SURVEY
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K. Lanier, M. Kuruvilla, and Jennifer Shih
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Telemedicine ,Quality management ,business.industry ,education ,Immunology ,Telehealth ,Patient satisfaction ,Family medicine ,Pandemic ,medicine ,Immunology and Allergy ,Allergists ,Medical diagnosis ,business ,Allergy clinic - Abstract
Introduction: Telemedicine across the United States has steadily expanded over the past five years, however, adoption of these services by the allergist community has been minimal until the SARS-CoV2 pandemic Telehealth in allergy has expeditiously expanded in recent months, prompting ongoing quality improvement This study investigates patient satisfaction with telemedicine services during the SARS-CoV2 pandemic Methods: Our study measured patient satisfaction with a cloud-based telemedicine platform at a university-affiliated adult allergy clinic during the SARS-CoV2 pandemic We surveyed all consenting patients seen in the first two months using a questionnaire-based satisfaction survey with IRB exemption Results: A total of 297 patients were seen over two months 58% completed the questionnaire;the most common primary diagnoses were asthma and immune deficiency Overall, 88% of patients rated their comfort seeing a doctor via telemedicine as 10, and 92 5% felt that their doctor explained their condition in an easily understood manner 79% strongly agreed that connecting their telehealth appointments was easy 44% would choose telemedicine over in-person care even after the pandemic, while 76% would strongly recommend telemedicine services to others 40% percent strongly agreed that seeing a doctor using telemedicine was just as good as seeing a doctor in person Notably, Caucasian patients were 18 45 times more likely to feel comfortable seeing the doctor using telemedicine as compared to Hispanic patients Conclusion: This survey highlights perceived deficiencies in telemedicine services offered by allergists Further studies could elucidate factors to improve the telemedicine experience in allergy - so it more closely resembles in-person experiences
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- 2020
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11. A selective BCL-X
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Sajid, Khan, Xuan, Zhang, Dongwen, Lv, Qi, Zhang, Yonghan, He, Peiyi, Zhang, Xingui, Liu, Dinesh, Thummuri, Yaxia, Yuan, Janet S, Wiegand, Jing, Pei, Weizhou, Zhang, Abhisheak, Sharma, Christopher R, McCurdy, Vinitha M, Kuruvilla, Natalia, Baran, Adolfo A, Ferrando, Yong-Mi, Kim, Anna, Rogojina, Peter J, Houghton, Guangcun, Huang, Robert, Hromas, Marina, Konopleva, Guangrong, Zheng, and Daohong, Zhou
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Blood Platelets ,Sulfonamides ,Aniline Compounds ,bcl-X Protein ,Antineoplastic Agents ,Thrombocytopenia ,Article ,Gene Expression Regulation, Neoplastic ,Mice ,Von Hippel-Lindau Tumor Suppressor Protein ,Proteolysis ,Animals ,Heterografts ,Humans - Abstract
BCL-XL is a well-validated cancer target. However, the on-target and dose-limiting thrombocytopenia limits the use of BCL-XL inhibitors such as ABT263 as safe and effective anticancer agents. To reduce the toxicity of ABT263, we converted it into DT2216, a BCL-XL proteolysis targeting chimera (PROTAC), that targets BCL-XL to the Von Hippel-Lindau (VHL) E3 ligase for degradation. We found that DT2216 was more potent against various BCL-XL-dependent leukemia and cancer cells but significantly less toxic to platelets than ABT263 in vitro because VHL is poorly expressed in platelets. In vivo, DT2216 effectively inhibits the growth of several xenograft tumors as a single agent or in combination with other chemotherapeutic agents, without causing significant thrombocytopenia. These findings demonstrate the potential to use PROTAC technology to reduce on-target drug toxicities and rescue the therapeutic potential of previously undruggable targets. Furthermore, DT2216 may be developed as a safe first-in-class anticancer agent targeting BCL-XL.
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- 2019
12. A003 DIRECT AMOXICILLIN CHALLENGE WITHOUT PRELIMINARY SKIN TESTING FOR PEDIATRIC PATIENTS WITH LOW-RISK PENICILLIN ALLERGY SYMPTOMS
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M. Kuruvilla, Jennifer Shih, K. Patel, and Laura A Wang
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Immunology ,medicine ,Immunology and Allergy ,Penicillin allergy ,Amoxicillin ,business ,Dermatology ,medicine.drug - Published
- 2019
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13. Power Monitoring and Theft Detection System using IoT
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Rejin V Jose, Adrin Denny, R Meenal, Kevin M Kuruvilla, and Renoy Roy
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History ,Computer science ,business.industry ,Computer security ,computer.software_genre ,Computer Science Applications ,Education ,Power (physics) ,Electric power transmission ,Work (electrical) ,The Internet ,Real-time data ,Electricity ,business ,Internet of Things ,computer ,Gsm module - Abstract
Electricity thefts are increasing every year across domestic as well as industrial domains which affect the economic status of the country. Various wireless communication systems are available to detect the power theft, but lacks the required infrastructure needed to employ them. The project’s aim is to design a system to monitor the power consumed by load and to detect and eliminate the power theft in transmission lines and energy meters. This work is also focused on communicating the theft information to Electricity Board (EB) through IoT. As a network of devices is connected like sensors it has the ability to exchange real time information through internet. In this project Raspberry Pi is utilized to detect power theft and send command to GSM module which sends the theft information message to EB. The implementation of this system will help save large amount of electricity.
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- 2019
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14. DIRECT ORAL AMOXICILLIN CHALLENGE WITHOUT PRELIMINARY SKIN TESTING IN PATIENTS WITH REPORTED PENICILLIN ALLERGY
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N. Scanlon and M. Kuruvilla
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Public health ,Immunology ,Penicillin allergy ,Amoxicillin ,Rash ,Penicillin ,Delayed hypersensitivity ,Internal medicine ,medicine ,Immunology and Allergy ,In patient ,medicine.symptom ,Prospective cohort study ,business ,medicine.drug - Abstract
Introduction 10% of hospitalized patients report penicillin allergy; studies indicate that ∼98% are not truly allergic. Unconfirmed penicillin allergy labels pose public health risks, and evaluation is recommended to improve antibiotic stewardship. While the most widely accepted protocol is penicillin skin testing (PST) followed by oral amoxicillin challenge, time constraints and resources may preclude this. Recent literature supports the safety and efficacy of direct oral amoxicillin challenge in low-risk individuals. Methods We retrospectively evaluated data and oral challenge outcomes from adult patients in clinic with a penicillin allergy label over a 6-month period. Direct oral amoxicillin challenge was recommended in patients with history of benign rash, benign somatic symptoms, or unknown history associated with last penicillin exposure more than 12 months ago. Those with severe reactions or reactions within 12 months of evaluation were not challenged. Patients were monitored for 60 minutes following challenge. Results Of 355 encounters, 14% of patients had a penicillin allergy label. 76% of those met inclusion criteria. Penicillin-associated reactions varied, and 88% reported reactions more than 10 years prior. 8% of patients were de-labeled based on history alone. 53% of patients offered amoxicillin challenge consented, and none developed immediate, or to our knowledge, delayed hypersensitivity reactions. 15% of patients developed subjective and self-limited symptoms not deemed to constitute true IgE-mediated reactions. Conclusions This study adds to the accumulating body of evidence supporting the safety and efficacy of direct provocative challenge without preliminary skin testing to exclude penicillin allergy in low-risk individuals. Larger prospective studies are necessary to confirm these observations. Outcomes of Patients with Penicillin Allergy Labels
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- 2018
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15. A Study of Character Association in Small Cardamom (Elettaria cardamomum Maton)
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K. J. Madhusoodanan, T. K. Hrideek, V. V. Radhakrishnan, K. M. Kuruvilla, J. Thomas, and K. V. Mohanan
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Horticulture ,Character (mathematics) ,food.ingredient ,food ,Agronomy ,Elettaria cardamomum ,Biology - Published
- 2007
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16. Subcutaneous Panniculitis like T Cell Lymphoma associated with erythromelalgia
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P M Kuruvilla, J Varghese, J Thomas, and B V Maramattom
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Male ,medicine.medical_specialty ,Pathology ,Panniculitis ,Skin Neoplasms ,Treatment outcome ,subcutaneous panniculitis like T cell lymphoma ,lcsh:Medicine ,Lymphoma, T-Cell ,Diagnosis, Differential ,Young Adult ,Erythromelalgia ,Subcutaneous Panniculitis-Like T-Cell Lymphoma ,Antineoplastic Combined Chemotherapy Protocols ,Skin Ulcer ,medicine ,Humans ,Small Fiber Neuropathy ,Cyclophosphamide ,Secondary erythromelalgia ,Erthromelalgia ,business.industry ,secondary erythromelalgia ,lcsh:R ,Febrile illness ,General Medicine ,Exanthema ,medicine.disease ,Dermatology ,Rash ,Lymphoma ,Treatment Outcome ,SPTCL ,Doxorubicin ,Vincristine ,Prednisone ,medicine.symptom ,business - Abstract
Erythromelalgia is a rare disorder that simulates a small fiber neuropathy and patients often have painful erythematous extremities during episodes. It is of two types: A primary or inherited form that is sometimes associated with a Na channel mutation or a secondary disorder associated with an underlying systemic disorder. We present a 19-year-old boy who presented to us with erythromelalgia and a febrile illness with systemic rash. Detailed work-up revealed another unusual condition: Subcutaneous panniculitis like T cell lymphoma (SPTCL). This is the first report of an association of erythromelalgia with SPTCL.
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- 2014
17. Renal function tests in lithium treated patients - a controlled study
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M, Kuruvilla, K, Kuruvilla, and C K, Jacob
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Original Article - Abstract
SUMMARY Results of renal function tests done on 36 patients on prophylactic lithium treatment are compared with those of 28 age matched individuals, also being treated for affective disorders but exposed only to neuroleptics and/or tricyclic antidepressants. 25% of the lithium treated patients had A.D.H. resistant concentration dysfunction resulting in polyuria and polydypsia. Serum lithium levels had a significant positive correlation with the daily urine volume and a significant negative correlation with the 12 hour urine specific gravity. No relationship was found between the total amount of lithium consumed or the duration of lithium treatment and the urine volume. Though a higher proportion of the lithium treated patients had proteinuria, it was only of a mild degree. Glomerular Filteration Rate and renal tubular hydrogen ion excretion were normal in both the test and control groups.
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- 2011
18. Disease concomitance in psoriasis: A clinical study of 61 cases
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E, Alexander, J, Pinto, G S, Pal, N, Kamath, and M, Kuruvilla
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Concomitant diseases ,lcsh:Dermatology ,Psoriasis ,lcsh:RL1-803 - Abstract
Sixty-one patients with psoriasis were studied for concomitant diseases and compared with 61 age and sex-matched controls. Concomitant cutaneous diseases most often seen with psoriasis were lichen simplex chronicus (16.3%), verruca vulgaris (9.8%) and me Iasina (4.9%). Of the systemic disorders, diabetes showed the highest frequency (13.1%) followed by hypertension (8.1%). Two patients had HIV infection (3.2%). Both the patients had severe and atypical lesions.
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- 2001
19. Methicillin resistant staphylococcus aureus (MRSA) in skin isolates from hospital acquired infections
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A M, Sajna, M, Kuruvilla, S, Shenoy, and G K, Bhat
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Eighty-four isolates of Staphylococcus aureus (S.aureus) obtained from nosocomial infections were screened for methicillin resistance, which was found to be about 40.47%. This indicates a rising trend in the incidence of MRSA over the previous years. Early detection of resistant strains as well as prudent use of antibiotics can help to combat the global problem of resistance.
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- 2010
20. Pattern of skin diseases in Bantwal Taluq, Dakshina Kannada
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M, Kuruvilla, K S, Sridhar, P, Kumar, and G S, Rao
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A survey was conducted to find out the pattern of skin diseases among patients who attended the fortnightly medical camp held in Bantwal Taluq, a rural area. Infective disorders were found in 42.68% and non infective in 41.58%. Among the infective disorders fungal infections were most common (24.08%). Among the non infective dermatoses eczemas were most common (33.93%). On comparing the proportional infectivity rate of infectious diseases among males and females it was found that in scabies males were more affected than females.
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- 2010
21. POEMS syndrome associated with plasmacytoma of the clivus: 'Time discovers the truth'
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P M Kuruvilla, J Varghese, J Thomas, and B V Maramattom
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Pathology ,medicine.medical_specialty ,organomegaly ,lcsh:Medicine ,Case Report ,Organomegaly ,plasmacytoma ,Clivus ,immune system diseases ,hemic and lymphatic diseases ,Edema ,monoclonal protein ,medicine ,Papilledema ,POEMS syndrome ,Castleman′s disease ,business.industry ,lcsh:R ,Castleman's disease ,General Medicine ,medicine.disease ,endocrinopathy ,and skin changes (POEMS) ,medicine.anatomical_structure ,Peripheral neuropathy ,Plasmacytoma ,polyneuropathy ,medicine.symptom ,business ,Polyneuropathy - Abstract
Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is characterized by the presence of a monoclonal plasma cell disorder, peripheral neuropathy, and one or more of the following features: Osteosclerotic myeloma, Castleman′s disease (angiofollicular lymph node hyperplasia), increased levels of serum vascular endothelial growth factor (VEGF), organomegaly, endocrinopathy, edema, typical skin changes, and papilledema. [1] Solitary plasmacytomas most frequently occur in the bone but can also be found in soft tissues (extramedullary plasmacytoma). [2] We report a case that showed a rare association of POEMS syndrome with a plasmacytoma of the clivus.
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- 2016
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22. Cutaneous manifestations of non-Hodgkin's lymphoma
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S S, Kumar, M, Kuruvilla, G S, Pai, and M, Dinesh
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Thirty-two confirmed cases of non -Hodgkin's lymphoma (NHL) were examined for cutaneous manifestations for a period of 2 years from November 1998 in KMC Hospital Attavar, Mangalore. Cutaneous manifestations in the study group were compared to a control group of 32 patients. Specific infiltrates were present in all (5/5) CTCL patients and one out of twenty-seven patients with low grade NHL. Morphologically they presented as papules, plaques, nodules and erythroderma. Infective conditions seen in the study group were superficial fungal (7/32) and viral infections (2/ 32). Non-infective conditions were acquired ichthyosis (10/32), generalised pruritus (5/32), insect bite reaction (1/32) and drug eruption (1/32). When compared to control patients only acquired ichthyosis and generalised pruritus were found to be statistically significant. The study group also showed changes due to chemotherapy like diffuse alopecia (24/29), bluish pigmentation of proximal part of nail (4/29), localised pigmentation of palms and soles (1 /29), diffuse pigmentation at injection site (1 /29), pigmentation at scar site (1 /29) and stomatitis (4/29).
- Published
- 2007
23. Prognostic factors for recurrence and cosmesis in 393 patients after radiation therapy for early mammary carcinoma
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O E Streeter, A R Rao, A R Kagan, Myron Wollin, M A Tedeschi, H Nussbaum, M. C. Ryoo, B. L. Hintz, A M Kuruvilla, and M A Tomé
- Subjects
Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Mammary gland ,Urology ,Breast Neoplasms ,medicine ,Adjuvant therapy ,Carcinoma ,Humans ,Radiology, Nuclear Medicine and imaging ,Breast ,Aged ,Aged, 80 and over ,Radiotherapy ,business.industry ,Cosmesis ,Cancer ,Radiotherapy Dosage ,Middle Aged ,Ductal carcinoma ,Prognosis ,medicine.disease ,Surgery ,Radiation therapy ,Carcinoma, Intraductal, Noninfiltrating ,medicine.anatomical_structure ,Female ,Neoplasm Recurrence, Local ,business ,Mastectomy - Abstract
Between 1978 and 1985, 393 of 2,765 (14%) patients with operable cancer of the breast (clinical stage T0-3N0-2M0) were irradiated after excisional biopsy and staging axillary dissection. Of 77 patients with microscopic axillary metastases, 68 received systemic adjuvant therapy. Treatment failed locally in 26 cases, and there were seven patients with distant metastasis. The three major factors for increased local treatment failure were (a) age below 40 years (P = .003), (b) negative estrogen receptor assay result (P = .03), and (c) failure to deliver a radiation boost dose when tumor was present at the margin of the specimen (P = .002). The size of the tumor, the nodal status, the progesterone receptor assay result, and the presence of ductal carcinoma in situ mixed with infiltrating carcinoma did not show a significant influence on local recurrence. In 274 of 393 (70%) patients, cosmesis was evaluated. The four major factors affecting cosmesis favorably were (a) utilization of a wedge (P less than .0001); (b) treatment of two fields a day (P less than .0001); (c) failure to use a separate treatment port to the regional lymph nodes, so as to avoid field junctions (P = .0003); and (d) small size of specimen (less than 50 cm2) (P = .0171). A second or third cancer was found in 39 of the 393 (10%) patients; contralateral breast cancer was the most common form (n = 23), followed by genitourinary cancer (n = 5). The most frequent complication was arm edema (6%).
- Published
- 1989
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24. Karyotypic and electrophoretic studies on taro and its origin
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Avtar Singh and K. M. Kuruvilla
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Strain (biology) ,fungi ,food and beverages ,Karyotype ,Plant Science ,Horticulture ,Gel electrophoresis of proteins ,Biology ,Colocasia esculenta ,Electrophoresis ,Genotype ,Botany ,Genetics ,Leaf size ,Ploidy ,Agronomy and Crop Science - Abstract
Karyotypes and electrophoretic pattern of 15 strains of taro were studied. Strains collected from the northeast India hill state, Meghalaya were diploids and triploids whereas those from the plains of south India were diploids and of north India was a triploid. The diploids had 2n=28 and triploids showed 2n=42 chromosomes. The wild taro had the most asymmetrical karyotype. The protein content varied from 4.2 to 11.4 mg/g dry wt. The maximum protein content was found in a triploid strain 8 (11.4 mg/g dry wt) and minimum in the wild taro (4.2 mg/g dry wt). The number of protein bands was 7 in the wild taro (diploid) and 12 in one of the cultivated triploid strain. Meghalaya strains showed great variation with respect to leaf size and tuber shape and size. All the strains have diverged at morphological, karyotypic and genotypic levels. It is suggested that taro might have originated in the north-eastern India.
- Published
- 1981
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25. Power Monitoring and Theft Detection System using IoT.
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R Meenal, Kevin M Kuruvilla, Adrin Denny, Rejin V Jose, and Renoy Roy
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- 2019
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26. Patient and physician perspectives on disease burden in chronic spontaneous urticaria: A real-world US survey.
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Mosnaim G, Patil D, Kuruvilla M, Hetherington J, Keal A, and Mehlis S
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- Humans, Female, Male, Adult, Middle Aged, Cross-Sectional Studies, United States epidemiology, Surveys and Questionnaires, Physicians psychology, Severity of Illness Index, Chronic Urticaria drug therapy, Quality of Life, Cost of Illness
- Abstract
Background: Chronic spontaneous urticaria (CSU) is frequently associated with severe disease-related symptoms that negatively affect quality of life, but patients and physicians may differ in their opinion on CSU burden., Objective: To describe the clinical and humanistic burden associated with CSU and level of agreement between patient and physician perceptions of disease burden and treatment satisfaction., Methods: This cross-sectional, survey-based study of US physicians and their adult patients with CSU included data collected in the Adelphi CSU Disease Specific Programme from 2020 to 2021. Overall, 1082 patient record forms completed by 110 physicians (including 40 allergists/immunologists, 50 dermatologists, and 20 primary care physicians) and 474 matched patient-reported questionnaires were included. Paired physician-patient records were used to determine agreement on disease burden and treatment satisfaction., Results: Patients with CSU often experienced physician-reported itching (66%) and hives (49%) and had a history of angioedema (23%). Although current CSU severity had largely improved since diagnosis, many patients and physicians continued to report moderate/severe current disease symptoms (46% and 30%, respectively). Moderate/severe disease had greater impacts on quality of life, sleep, work impairment, and treatment satisfaction than mild disease. Most patients and physicians agreed on symptom severity (61%-74%), with disagreement largely due to physicians underreporting severity relative to patients. Patient/physician agreement on treatment satisfaction was highest with mild CSU severity (82%), mild hive severity (80%), and omalizumab or other biologic treatment (87%)., Conclusion: Moderate/severe CSU was associated with greater disease burden and lower treatment satisfaction than mild CSU. Physicians more frequently underreported CSU severity compared with their patients., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2025
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27. Clinical burden, treatment, and disease control in patients with chronic spontaneous urticaria: Real-world evidence.
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Riedl MA, Patil D, Rodrigues J, Kuruvilla M, Raftery T, Pivneva I, Doran J, Voegel A, Signorovitch J, and Yosipovitch G
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- Humans, Male, Female, Adult, Middle Aged, Prevalence, Incidence, Cost of Illness, United States epidemiology, Adrenal Cortex Hormones therapeutic use, Young Adult, Aged, Adolescent, Immunosuppressive Agents therapeutic use, Immunosuppressive Agents economics, Urticaria drug therapy, Urticaria epidemiology, Urticaria economics, Histamine Antagonists therapeutic use, Chronic Urticaria drug therapy, Chronic Urticaria epidemiology, Chronic Urticaria economics, Health Care Costs statistics & numerical data
- Abstract
Background: Chronic spontaneous urticaria (CSU) is an unpredictable inflammatory skin condition with substantial clinical burden that affects 0.23% to 0.78% of the US population., Objective: To describe the incidence and prevalence of patients with a record of CSU diagnosis, treatment patterns, disease control, and clinical and economic burden in a US cohort of patients with CSU., Methods: Adults with a record of CSU diagnosis within the US HealthVerity claims database were eligible. Age- and gender-adjusted prevalence/incidence rates were calculated for January 2017 to December 2022. Clinical characteristics were described during the 1 year before CSU diagnosis (baseline) and the time after (follow-up). Proxy events representing uncontrolled CSU (any record of prescriptions for corticosteroids, biologics, or immunosuppressants [excluding all antihistamines and over-the-counter medication] or any CSU-related inpatient admissions or emergency department or urgent care visits) were used to identify patients with uncontrolled CSU. Health care resource utilization (HCRU) and health care costs were described., Results: Overall, 200,298 patients were followed-up for a median of 2.3 years after diagnosis. Estimated cumulative prevalence of diagnosed CSU was 0.57% (women: 0.80%; men: 0.32%). The average annual incidence rate was 0.08%. Corticosteroids were the most prescribed treatment during follow-up among the 166,195 patients prescribed at least 1 treatment (94.3%). Proxy events were observed in 59.1% of the patients. HCRU and health care costs increased from baseline in patients with uncontrolled CSU during follow-up., Conclusion: Of patients with CSU who were prescribed treatment, more than 50% experienced uncontrolled CSU, which was associated with increased HCRU and health care costs., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2025
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28. Pneumonia Detection from Chest X-Ray Images Using Deep Learning and Transfer Learning for Imbalanced Datasets.
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Alshanketi F, Alharbi A, Kuruvilla M, Mahzoon V, Siddiqui ST, Rana N, and Tahir A
- Abstract
Pneumonia remains a significant global health challenge, necessitating timely and accurate diagnosis for effective treatment. In recent years, deep learning techniques have emerged as powerful tools for automating pneumonia detection from chest X-ray images. This paper provides a comprehensive investigation into the application of deep learning for pneumonia detection, with an emphasis on overcoming the challenges posed by imbalanced datasets. The study evaluates the performance of various deep learning architectures, including visual geometry group (VGG), residual networks (ResNet), and Vision Transformers (ViT) along with strategies to mitigate the impact of imbalanced dataset, on publicly available datasets such as the Chest X-Ray Images (Pneumonia) dataset, BRAX dataset, and CheXpert dataset. Additionally, transfer learning from pre-trained models, such as ImageNet, is investigated to leverage prior knowledge for improved performance on pneumonia detection tasks. Our investigation extends to zero-shot and few-shot learning experiments on different geographical regions. The study also explores semi-supervised learning methods, including the Mean Teacher algorithm, to utilize unlabeled data effectively. Experimental results demonstrate the efficacy of transfer learning, data augmentation, and balanced weight in addressing imbalanced datasets, leading to improved accuracy and performance in pneumonia detection. Our findings emphasize the importance of selecting appropriate strategies based on dataset characteristics, with semi-supervised learning showing particular promise in leveraging unlabeled data. The findings highlight the potential of deep learning techniques in revolutionizing pneumonia diagnosis and treatment, paving the way for more efficient and accurate clinical workflows in the future., Competing Interests: Declarations Institutional Review Board Statement Not applicable. Informed Consent Not applicable. Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)
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- 2024
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29. Tipping the Scales: Indiscriminate Use of Interval Scales to Rate Diverse Dysarthric Features.
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Stipancic KL, Whelan BM, Laur L, Zhao Y, Rohl A, Choi I, and Kuruvilla-Dugdale M
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- Humans, Female, Reproducibility of Results, Middle Aged, Aged, Adult, Male, Observer Variation, Aged, 80 and over, Dysarthria diagnosis, Dysarthria physiopathology, Dysarthria etiology, Parkinson Disease physiopathology, Parkinson Disease complications, Speech Intelligibility, Severity of Illness Index, Speech Production Measurement methods
- Abstract
Purpose: Error related to incorrect use of rating scales is problematic in the assessment and treatment of dysarthria. The main purpose of this project was to determine scale fit for cardinal speech features of hypokinetic dysarthria. A secondary aim was to determine rater reliability for the two different scales explored., Method: Forty-three speakers with Parkinson's disease (PD) and 25 neurologically healthy control talkers were recorded reading sentences from the Speech Intelligibility Test. Twenty-two healthy female listeners used both an equal appearing interval (EAI) scale and a direct magnitude estimation (DME) scale to rate five perceptual speech features (i.e., overall speech severity, articulatory imprecision, reduced loudness, short rushes of speech, and monotony) from these recordings. Regression analyses were used to determine the linearity of the relationship between the means of the EAI and DME ratings. Inter- and intrarater reliability was calculated using intraclass correlation coefficients and Spearman's correlation coefficients, respectively, for both EAI and DME ratings., Results: There was a linear relationship between EAI and DME means for monotony, indicating it is a metathetic dimension. Curvilinear relationships were observed between the EAI and DME means for the other four features, indicating prothetic dimensions. Intra- and interrater reliability values were similar for EAI and DME ratings., Discussion: Overall, results of this work suggest that DME is the best fit for scaling several hypokinetic dysarthria features, and not the conventionally used EAI scale. Prothetic dimensions best scaled by DME include overall speech severity, articulatory imprecision, reduced loudness, and short rushes of speech. Monotony was the only feature found to be a metathetic dimension and would be best scaled using EAI or DME. Findings call for rethinking the widespread use of EAI scales for rating perceptual features as part of the assessment and treatment of motor speech disorders.
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- 2024
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30. Experimental laboratory models as tools for understanding modifiable dementia risk.
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Sinclair D, Canty AJ, Ziebell JM, Woodhouse A, Collins JM, Perry S, Roccati E, Kuruvilla M, Leung J, Atkinson R, Vickers JC, Cook AL, and King AE
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- Humans, Animals, Risk Factors, Disease Models, Animal, Dementia prevention & control
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Experimental laboratory research has an important role to play in dementia prevention. Mechanisms underlying modifiable risk factors for dementia are promising targets for dementia prevention but are difficult to investigate in human populations due to technological constraints and confounds. Therefore, controlled laboratory experiments in models such as transgenic rodents, invertebrates and in vitro cultured cells are increasingly used to investigate dementia risk factors and test strategies which target them to prevent dementia. This review provides an overview of experimental research into 15 established and putative modifiable dementia risk factors: less early-life education, hearing loss, depression, social isolation, life stress, hypertension, obesity, diabetes, physical inactivity, heavy alcohol use, smoking, air pollution, anesthetic exposure, traumatic brain injury, and disordered sleep. It explores how experimental models have been, and can be, used to address questions about modifiable dementia risk and prevention that cannot readily be addressed in human studies. HIGHLIGHTS: Modifiable dementia risk factors are promising targets for dementia prevention. Interrogation of mechanisms underlying dementia risk is difficult in human populations. Studies using diverse experimental models are revealing modifiable dementia risk mechanisms. We review experimental research into 15 modifiable dementia risk factors. Laboratory science can contribute uniquely to dementia prevention., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
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- 2024
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31. Disease burden and predictors associated with non-response to antihistamine-based therapy in chronic spontaneous urticaria.
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Soong W, Patil D, Pivneva I, Signorovitch J, Wells MA, Balp MM, and Kuruvilla M
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Background: H1-antihistamines (H1AH) are the first-line treatment for chronic spontaneous urticaria (CSU), but 50% of patients have inadequate disease control at standard doses., Objective: To assess the comorbidity burden and healthcare resource utilization (HRU) associated with non-response to H1AH-based treatments; to identify predictors of non-response., Methods: Optum® de-identified Electronic Health Record dataset (2007-2020) was used to identify adult patients with CSU who initiated a H1AH, alone or in combination with other oral non-biologics (index treatment). Based on twelve-month treatment patterns observed after index treatment initiation, patients were categorized as responders (continued index treatment or had only 1 next H1AH treatment without corticosteroids) or non-responders (continued corticosteroids or had 2 or more treatment switches). Patient characteristics and HRU were assessed in the 12 months before (baseline) and ≥12 months after (follow-up) index treatment initiation. Baseline predictors associated with non-response were identified using machine learning., Results: There were 17 062 patients who met inclusion criteria, and 14824 (86.9%) were classified as non-responders. A higher proportion of non-responders had records of CSU-related symptoms, comorbidities, polypharmacy, and certain laboratory tests than responders at baseline. A higher proportion of non-responders than responders visited an allergist or dermatologist during follow-up (59.5% vs 53.0%). Non-responders had a larger increase in hospitalizations (15.7% vs -2.4%) than responders during follow-up vs baseline. Predictors of non-response included index and baseline treatment classes, types of specialists seen, chronic pulmonary disease, depression, and female sex., Conclusion: A large proportion of CSU patients treated with H1AH-based therapies had uncontrolled disease, contributing to increased HRU and patient burden. Non-responders had more comorbidities and HRU at baseline and follow-up, with steep increases in follow-up hospitalizations relative to baseline, highlighting an urgent need for early disease control., Competing Interests: WS has served on Research, Consultant and Advisory Boards for Novartis, Regeneron, Sanofi, Genentech, AstraZeneca, and Amgen, and Speaker's Bureau for Regeneron, Sanofi, AstraZeneca, and Amgen. DP, MAW, and MK are employees of Novartis Pharmaceuticals Corporation. MMB is an employee of Novartis Pharma AG. IP and JS are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Novartis Pharmaceuticals Corporation, which funded the development and conduct of this study and manuscript., (© 2023 The Authors.)
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- 2023
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32. Improving Perceptual Speech Ratings: The Effects of Auditory Training on Judgments of Dysarthric Speech.
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Stipancic KL, Golzy M, Zhao Y, Pinkerton L, Rohl A, and Kuruvilla-Dugdale M
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- Humans, Dysarthria therapy, Judgment, Reproducibility of Results, Speech Intelligibility, Speech Production Measurement, Speech Perception, Amyotrophic Lateral Sclerosis, Parkinson Disease complications
- Abstract
Purpose: Auditory training has been shown to reduce rater variability in perceptual voice assessment. Because rater variability is also a central issue in the auditory-perceptual assessment of dysarthria, this study sought to determine if training produces a meaningful change in rater reliability, criterion validity, and scaling magnitude of four features: overall speech impairment, articulatory imprecision, monotony, and slow rate., Method: Forty-four nonexperts randomized to training and nontraining listener groups completed a pretest and posttest. Only the former group underwent auditory training between pre- and posttests. For both testing and training, listeners rated samples from speakers with amyotrophic lateral sclerosis (ALS), speakers with Parkinson's disease (PD), and neurologically healthy control speakers using separate visual analog scales (VASs) for each of the four features. Intraclass correlation coefficients were used to compare inter- and intrarater reliability between pre- and posttest for both listener groups. For criterion validity, severity ratings from the two nonexpert listener groups were compared to those of two experienced listeners for all four features. To determine changes in scaling magnitude, raw VAS scores for each feature were compared from pre- to posttest within the two nonexpert listener groups. Scaling changes were also compared between the two listener groups for the pre- and posttest conditions., Results and Conclusions: In the training group, a meaningful improvement in interrater reliability was observed for some features in all three speaker groups, but not in the nontraining group. In contrast, for intrarater reliability, in the nontraining group, a meaningful improvement was observed for many features in all three speaker groups, but only for PD monotony and slow rate in the training group. All ratings from the nonexpert listeners were valid except for monotony. Raw VAS scores did not meaningfully change from pre- to posttest for any of the features, but there was a trend toward lower scores posttraining, mainly for the ALS samples. Modifications to the auditory training paradigm to further improve reliability and validity, along with future goals for optimizing training, are discussed.
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- 2023
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33. Articulatory Performance in Dysarthria: Using a Data-Driven Approach to Estimate Articulatory Demands and Deficits.
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Kuruvilla-Dugdale M and Mefferd AS
- Abstract
This study pursued two goals: (1) to establish range of motion (ROM) demand tiers (i.e., low, moderate, high) specific to the jaw (J), lower lip (LL), posterior tongue (PT), and anterior tongue (AT) for multisyllabic words based on the articulatory performance of neurotypical talkers and (2) to identify demand- and disease-specific articulatory performance characteristics in talkers with amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). J, LL, PT, and AT movements of 12 talkers with ALS, 12 talkers with PD, and 12 controls were recorded using electromagnetic articulography. Vertical ROM, average speed, and movement duration were measured. Results showed that in talkers with PD, J and LL ROM were already significantly reduced at the lowest tier whereas PT and AT ROM were only significantly reduced at moderate and high tiers. In talkers with ALS, J ROM was significantly reduced at the moderate tier whereas LL, PT, and AT ROM were only significantly reduced at the highest tier. In both clinical groups, significantly reduced J and LL speeds could already be observed at the lowest tier whereas significantly reduced AT speeds could only be observed at the highest tier. PT speeds were already significantly reduced at the lowest tier in the ALS group but not until the moderate tier in the PD group. Finally, movement duration, but not ROM or speed performance, differentiated between ALS and PD even at the lowest tier. Results suggest that articulatory deficits vary with stimuli-specific motor demands across articulators and clinical groups.
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- 2022
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34. Isolated REM sleep behaviour disorder: current diagnostic procedures and emerging new technologies.
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Bramich S, King A, Kuruvilla M, Naismith SL, Noyce A, and Alty J
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- Humans, Polysomnography, Neurodegenerative Diseases diagnosis, Parkinson Disease, REM Sleep Behavior Disorder diagnosis, Sleep Wake Disorders
- Abstract
Isolated REM sleep behaviour disorder (iRBD) is characterised by dream enactment behaviours, such as kicking and punching while asleep, and vivid/violent dreams. It is now acknowledged as a prodromal phase of neurodegenerative disease-approximately 80% of people with iRBD will develop dementia with Lewy Bodies, Parkinson's disease or another degenerative brain disease within 10 years. It is important that neurologists and other clinicians understand how to make an early accurate diagnosis of iRBD so that affected people can have the opportunity to take part in clinical trials. However, making a diagnosis can be clinically challenging due to a variety of reasons, including delayed referral, symptom overlap with other disorders, and uncertainty about how to confirm a diagnosis. Several methods of assessment are available, such as clinical interview, screening questionnaires and video polysomnography or 'sleep study'. This review aims to support clinical neurologists in assessing people who present with symptoms suggestive of iRBD. We describe the usefulness and limitations of each diagnostic method currently available in clinical practice, and present recent research on the utility of new wearable technologies to assist with iRBD diagnosis, which may offer a more practical assessment method for clinicians. This review highlights the importance of thorough clinical investigation when patients present with suspected iRBD and emphasises the need for easier access to diagnostic procedures for accurate and early diagnosis., (© 2022. The Author(s).)
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- 2022
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35. The drug efflux pump MDR1 promotes intrinsic and acquired resistance to PROTACs in cancer cells.
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Kurimchak AM, Herrera-Montávez C, Montserrat-Sangrà S, Araiza-Olivera D, Hu J, Neumann-Domer R, Kuruvilla M, Bellacosa A, Testa JR, Jin J, and Duncan JS
- Subjects
- Animals, Humans, Mice, Drug Resistance, Lapatinib, Protein Kinase Inhibitors, Proteolysis, Proteomics, Proto-Oncogene Proteins p21(ras), Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics
- Abstract
Proteolysis-targeting chimeras (PROTACs) are a promising new class of drugs that selectively degrade cellular proteins of interest. PROTACs that target oncogene products are avidly being explored for cancer therapies, and several are currently in clinical trials. Drug resistance is a substantial challenge in clinical oncology, and resistance to PROTACs has been reported in several cancer cell models. Here, using proteomic analysis, we found intrinsic and acquired resistance mechanisms to PROTACs in cancer cell lines mediated by greater abundance or production of the drug efflux pump MDR1. PROTAC-resistant cells were resensitized to PROTACs by genetic ablation of ABCB1 (which encodes MDR1) or by coadministration of MDR1 inhibitors. In MDR1-overexpressing colorectal cancer cells, degraders targeting either the kinases MEK1/2 or the oncogenic mutant GTPase KRAS
G12C synergized with the dual epidermal growth factor receptor (EGFR/ErbB)/MDR1 inhibitor lapatinib. Moreover, compared with single-agent therapies, combining MEK1/2 degraders with lapatinib improved growth inhibition of MDR1-overexpressing KRAS-mutant colorectal cancer xenografts in mice. Together, our findings suggest that concurrent blockade of MDR1 will likely be required with PROTACs to achieve durable protein degradation and therapeutic response in cancer.- Published
- 2022
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36. The co-adsorption of thymohydroquinone dimethyl ether (THQ) and coumarin present in the aqueous extract of Ayapana triplinervis on mild steel and its protection in hydrochloric acid up to 323 K: computational and physicochemical studies.
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Rani At J, Thomas A, Kuruvilla M, Arshad M, and Joseph A
- Abstract
This study evaluates the corrosion inhibition property of the aqueous and alcoholic leaf extracts of the medicinal plant Ayapana triplinervis . The major components in the extracts are thymohydroquinone dimethyl ether (THQ) and coumarin. It is clear from the weight-loss studies that the water extract of the leaves (AYW) is superior to the alcoholic extract (AYA) in terms of offering corrosion inhibition. The 96% efficiency of 4% (v/v) AYW in 0.5 N HCl at room temperature changes to 84.62% at 323 K. The mixed-type inhibition behaviour of AYW shows slight dominance in the anodic direction. Studies suggest the multilayer adsorption of phytochemicals on the metal surface and that the adsorption follows the Temkin model. Theoretical studies using DFT and BIOVIA Materials Studio investigations establish THQ as a good inhibitor with high adsorption characteristics. Even though the concentration of coumarin in the extract is low, its presence in the extract facilitates the adsorption of THQ on the metal surface, which is evident from the MD simulation study. The changes in the surface topography and elemental composition of the metal specimen in the inhibited and uninhibited solution are monitored by SEM and EDX spectral studies. XPS data support the presence of both THQ and coumarin on the metal surface and the existence of co-ordinate bonding between the metal's d orbital and the O atoms of THQ. Theoretical and experimental studies support the mixed mode of adsorption of THQ as physisorption followed by chemisorption., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)
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- 2022
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37. Detection of Newly Secreted Antibodies Predicts Nonrecurrence in Primary Clostridioides difficile Infection.
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Haddad NS, Nozick S, Kim G, Ohanian S, Kraft CS, Rebolledo PA, Wang Y, Wu H, Bressler A, Le SNT, Kuruvilla M, Runnstrom MC, Ramonell RP, Cannon LE, Lee FE, and Daiss JL
- Subjects
- Biomarkers, Culture Media, Humans, Immunoglobulin A, Immunoglobulin G, Recurrence, Bacterial Toxins, Clostridioides difficile, Clostridium Infections epidemiology
- Abstract
Within 8 weeks of primary Clostridioides difficile infection (CDI), as many as 30% of patients develop recurrent disease with the associated risks of multiple relapses, morbidity, and economic burden. There are no clear clinical correlates or validated biomarkers that can predict recurrence during primary infection. This study demonstrated the potential of a simple test for identifying hospitalized CDI patients at low risk for disease recurrence. Forty-six hospitalized CDI patients were enrolled at Emory University Hospitals. Samples of serum and a novel matrix from circulating plasmablasts called "medium-enriched for newly synthesized antibodies" (MENSA) were collected during weeks 1, 2, and 4. Antibodies specific for 10 C. difficile antigens were measured in each sample. Among the 46 C. difficile-infected patients, 9 (19.5%) experienced recurrence within 8 weeks of primary infection. Among the 37 nonrecurrent patients, 23 (62%; 23/37) had anti-C. difficile MENSA antibodies specific for any of the three toxin antigens: TcdB-CROP, TcdBvir-CROP, and/or CDTb. Positive MENSA responses occurred early (within the first 12 days post-symptom onset), including six patients who never seroconverted. A similar trend was observed in serum responses, but they peaked later and identified fewer patients (51%; 19/37). In contrast, none (0%; 0/9) of the patients who subsequently recurred after hospitalization produced antibodies specific for any of the three C. difficile toxin antigens. Thus, patients with a negative early MENSA response against all three C. difficile toxin antigens had a 19-fold greater relative risk of recurrence. MENSA and serum levels of immunoglobulin A (IgA) and/or IgG antibodies for three C. difficile toxins have prognostic potential. These immunoassays measure nascent immune responses that reduce the likelihood of recurrence thereby providing a biomarker of protection from recurrent CDI. Patients who are positive by this immunoassay are unlikely to suffer a recurrence. Early identification of patients at risk for recurrence by negative MENSA creates opportunities for targeted prophylactic strategies that can reduce the incidence, cost, and morbidity due to recurrent CDI.
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- 2022
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38. Contrast study in umbilical venous line extravasation.
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Kamupira SR, Tarr JD, and Kuruvilla M
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- Device Removal, Equipment Failure Analysis methods, Humans, Infant, Newborn, Infant, Premature, Male, Prosthesis Fitting methods, Treatment Outcome, Vascular Access Devices adverse effects, Catheterization, Peripheral adverse effects, Catheterization, Peripheral instrumentation, Catheterization, Peripheral methods, Extravasation of Diagnostic and Therapeutic Materials blood, Extravasation of Diagnostic and Therapeutic Materials diagnosis, Extravasation of Diagnostic and Therapeutic Materials physiopathology, Extravasation of Diagnostic and Therapeutic Materials therapy, Radiography, Abdominal methods, Umbilical Veins diagnostic imaging
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2022
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39. What is allergic fungal sinusitis: A call to action.
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Kim J, Makary CA, Roland LT, Kuruvilla M, Lam K, Smith KA, Magliocca KR, Wise SK, Toskala E, Fermin JM, Pashley CH, Levy JM, and Luong AU
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- Chronic Disease, Humans, Mycoses diagnosis, Mycoses microbiology, Sinusitis diagnosis, Sinusitis microbiology, Sinusitis therapy
- Published
- 2022
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40. Utilizing Predictive Inflammatory Markers for Guiding the Use of Biologicals in Severe Asthma.
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Runnstrom M, Pitner H, Xu J, Lee FE, and Kuruvilla M
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Asthma is a chronic respiratory disease characterized by chronic airway inflammation and airflow obstruction. Up to ten percent of asthmatics have severe asthma, and many remain uncontrolled despite optimal medical management. With our increased understanding of the heterogeneity of asthma and its complex pathophysiology, several biomarkers have been developed and in the recent past, several biologic therapies for severe asthma have been developed and are now in widespread use. Although these biological agents have shown great benefit in treating severe asthma, not all patients respond equally well, and some do not derive any benefit. As much of the current literature of these medications have not assessed biomarkers or have used different cutoffs, it is often challenging to decide the best medication for an individual patient. Here, we review common asthma subtypes, current available biologic therapies for asthma, the clinical application of currently available type 2 biomarkers, as well as summarizing the evidence on how patient characteristics and biomarkers can help with choosing the optimal biologic for a patient that has the highest likelihood of success., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Runnstrom et al.)
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- 2022
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41. Diagnosis of Streptococcus pneumoniae infection using circulating antibody secreting cells.
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Kyu S, Ramonell RP, Kuruvilla M, Kraft CS, Wang YF, Falsey AR, Walsh EE, Daiss JL, Paulos S, Rajam G, Wu H, Velusamy S, and Lee FE
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Young Adult, Antibodies, Bacterial blood, Antibody-Producing Cells cytology, Antibody-Producing Cells immunology, Diagnostic Tests, Routine methods, Immunoassay methods, Pneumococcal Infections diagnosis, Pneumococcal Infections immunology, Streptococcus pneumoniae immunology
- Abstract
Background: Streptococcus pneumoniae infections cause morbidity and mortality worldwide. A rapid, simple diagnostic method could reduce the time needed to introduce definitive therapy potentially improving patient outcomes., Methods: We introduce two new methods for diagnosing S. pneumoniae infections by measuring the presence of newly activated, pathogen-specific, circulating Antibody Secreting Cells (ASC). First, ASC were detected by ELISpot assays that measure cells secreting antibodies specific for signature antigens. Second, the antibodies secreted by isolated ASC were collected in vitro in a novel matrix, MENSA (media enriched with newly synthesized antibodies) and antibodies against S. pneumoniae antigens were measured using Luminex immunoassays. Each assay was evaluated using blood from S. pneumoniae and non-S. pneumoniae-infected adult patients., Results: We enrolled 23 patients with culture-confirmed S. pneumoniae infections and 24 controls consisting of 12 non-S. pneumoniae infections, 10 healthy donors and two colonized with S. pneumoniae. By ELISpot assays, twenty-one of 23 infected patients were positive, and all 24 controls were negative. Using MENSA samples, four of five S. pneumoniae-infected patients were positive by Luminex immunoassays while all five non-S. pneumoniae-infected patients were negative., Conclusion: Specific antibodies produced by activated ASC may provide a simple diagnostic for ongoing S. pneumoniae infections. This method has the potential to diagnose acute bacterial infections., Competing Interests: FEHL is the founder of Micro-Bplex, Inc, serves on the scientific board of Be Bio Pharma, and is a recipient of grants from the Bill and Melinda Gates Foundation and Genentech, Inc. FEHL has also served as a consultant for Astra Zeneca. FEHL and JLD are co-inventors of the patented MENSA technology. The MENSA patent is assigned to MicroB-plex, Inc. ARF is a recipient of grants from Pfizer, AstraZeneca, BioFire, Janssen and has served on DSMB for Novavax. EEW is a recipient of grants from Pfizer, Janssen, Merck and has served on DSMB for GSK. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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- 2021
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42. Virtual interprofessional chronic cough clinic: An efficient and appealing approach to a complex problem.
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Kuruvilla M, Hatcher J, Shelly S, Dixit AN, Gillespie AI, VanNostrand K, Saikawa E, Jain A, and Klein AM
- Subjects
- Chronic Disease, Humans, Patient Satisfaction, Cough therapy, Telemedicine
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- 2021
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43. Dupilumab improves alcohol tolerance in aspirin-exacerbated respiratory disease.
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Arnold M, Kuruvilla M, Levy JM, and Xu J
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Ethanol adverse effects, Interleukin-4 Receptor alpha Subunit, Anti-Inflammatory Agents therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Asthma, Aspirin-Induced drug therapy, Alcohol Drinking
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- 2021
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44. COVID-19 in a series of patients with aspirin-exacerbated respiratory disease.
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White AA, Cahill KN, Jerschow E, Kuruvilla M, Sehanobish E, Bensko J, Laidlaw TM, and Levy JM
- Subjects
- Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Aspirin adverse effects, Humans, SARS-CoV-2, Asthma, Aspirin-Induced diagnosis, Asthma, Aspirin-Induced drug therapy, COVID-19, Respiratory Tract Diseases, Sinusitis
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- 2021
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45. Articulatory Correlates of Stress Pattern Disturbances in Talkers With Dysarthria.
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Kim D, Kuruvilla-Dugdale M, de Riesthal M, Jones R, Bagnato F, and Mefferd A
- Subjects
- Articulation Disorders, Humans, Speech Intelligibility, Tongue, Amyotrophic Lateral Sclerosis complications, Dysarthria etiology
- Abstract
Purpose Reduced stress commonly occurs in talkers with Parkinson's disease (PD), whereas excessive and equal stress is frequently associated with dysarthria of talkers with amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). This study sought to identify articulatory impairment patterns that underlie these two impaired stress patterns. We further aimed to determine if talkers with the same stress pattern disturbance but different diseases (ALS and MS) exhibit disease-specific articulatory deficits. Method Fifty-seven talkers participated in the study-33 talkers with dysarthria and 24 controls. Talkers with dysarthria were grouped based on their medical diagnosis: PD ( n = 15), ALS ( n = 10), MS ( n = 8). Participants repeated target words embedded in a carrier phrase. Kinematic data were recorded using electromagnetic articulography. Duration, displacement, peak speed, stiffness, time-to-peak speed, and parameter c were extracted for the initial lower lip opening stroke of each target word, which was either stressed or unstressed. Results Stress effects were significant for all kinematic measures across groups except for stiffness and time-to-peak speed, which were nonsignificant in ALS. For comparisons with controls, more kinematic measures significantly differed in the ALS group than in the PD and MS groups. Additionally, ALS and MS showed mostly similar articulatory impairment patterns. Conclusions In general, significant stress effects were observed in talkers with dysarthria. However, stress-specific between-group differences in articulatory performance, particularly displacement, may explain the perceptual impression of disturbed stress patterns. Furthermore, similar findings for ALS and MS suggest that articulatory deficits underlying similar stress pattern disturbances are not disease-specific.
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- 2021
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46. Novel immunoassay for diagnosis of ongoing Clostridioides difficile infections using serum and medium enriched for newly synthesized antibodies (MENSA).
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Haddad NS, Nozick S, Kim G, Ohanian S, Kraft C, Rebolledo PA, Wang Y, Wu H, Bressler A, Le SNT, Kuruvilla M, Cannon LE, Lee FE, and Daiss JL
- Subjects
- Antibodies, Bacterial immunology, Antigens, Bacterial immunology, Antigens, Bacterial metabolism, Case-Control Studies, Cell Culture Techniques, Clostridioides difficile immunology, Clostridium Infections blood, Clostridium Infections microbiology, Culture Media metabolism, Female, Humans, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Male, Middle Aged, Recombinant Proteins immunology, Recombinant Proteins metabolism, Antibodies, Bacterial analysis, Clostridioides difficile isolation & purification, Clostridium Infections diagnosis, Serologic Tests methods
- Abstract
Background: Clostridioides difficile infections (CDI) have been a challenging and increasingly serious concern in recent years. While early and accurate diagnosis is crucial, available assays have frustrating limitations., Objective: Develop a simple, blood-based immunoassay to accurately diagnose patients suffering from active CDI., Materials and Methods: Uninfected controls (N = 95) and CDI patients (N = 167) were recruited from Atlanta area hospitals. Blood samples were collected from patients within twelve days of a positive CDI test and processed to yield serum and PBMCs cultured to yield medium enriched for newly synthesized antibodies (MENSA). Multiplex immunoassays measured Ig responses to ten recombinant C. difficile antigens., Results: Sixty-six percent of CDI patients produced measurable responses to C. difficile antigens in their serum or MENSA within twelve days of a positive CDI test. Fifty-two of the 167 CDI patients (31%) were detectable in both serum and MENSA, but 32/167 (19%) were detectable only in MENSA, and 27/167 (16%) were detectable only in serum., Discussion: We describe the results of a multiplex immunoassay for the diagnosis of ongoing CDI in hospitalized patients. Our assay resolved patients into four categories: MENSA-positive only, serum-positive only, MENSA- and serum-positive, and MENSA- and serum-negative. The 30% of patients who were MENSA-positive only may be accounted for by nascent antibody secretion prior to seroconversion. Conversely, the serum-positive only subset may have been more advanced in their disease course. Immunocompromise and misdiagnosis may have contributed to the 34% of CDI patients who were not identified using MENSA or serum immunoassays., Importance: While there was considerable overlap between patients identified through MENSA and serum, each method detected a distinctive patient group. The combined use of both MENSA and serum to detect CDI patients resulted in the greatest identification of CDI patients. Together, longitudinal analysis of MENSA and serum will provide a more accurate evaluation of successful host humoral immune responses in CDI patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2021
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47. In reply: Aspirin desensitization for aspirin-exacerbated respiratory disease in the era of biologics: Clinical perspective.
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Levy JM and Kuruvilla M
- Subjects
- Aspirin adverse effects, Desensitization, Immunologic, Humans, Asthma, Aspirin-Induced therapy, Biological Products
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- 2021
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48. Absence of Iodinated Contrast Hypersensitivity and Characterization of Gadolinium Utilization in an Interventional Pain Population.
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Kalangara J, Lanier K, Beckworth WJ, and Kuruvilla M
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- Drug Hypersensitivity etiology, Gadolinium adverse effects, Humans, Incidence, Pain complications, Retrospective Studies, Contrast Media adverse effects, Drug Hypersensitivity epidemiology, Injections, Epidural adverse effects, Injections, Epidural methods, Iodine adverse effects
- Abstract
Background: Iodinated contrast media (ICM) allergy labels pose a unique clinical problem for the interventional pain physician due to the drawbacks of gadolinium for enhancement during pain procedures, as well as the reluctance to add to the cumulative steroid burden with steroid premedication. However, the risks of ICM hypersensitivity specific to this setting have not been previously described., Methods: We aimed to describe the incidence of ICM-induced hypersensitivity during the performance of epidural injections in a large healthcare system. We also sought to characterize preexisting ICM allergy labels and how these affected consequent gadolinium utilizations in this population., Results: 6,471 epidural pain procedures requiring contrast enhancement were performed during the 18-month study period. There were no reported contrast-induced hypersensitivity reactions in this time. 108 patients (1.6%) had a preexisting ICM allergy; a shellfish/seafood allergy was recorded in 118 patients (1.82%), and 51 charts (0.78%) were labeled with "iodine" allergy. 183 individuals received gadolinium for enhancement during epidural steroid injections. 96.7% of gadolinium utilization occurred in the context of preexisting allergy labels in the electronic medical record. Of note, 20 patients (18.5%) with ICM allergy labels also received iodinated contrast, and this was uneventful in all cases., Conclusion: Our results suggest that ICM-associated hypersensitivity is very rare during epidural procedures and the incidence is significantly lower than expected based on reaction rates during intravascular administration. This may be related to both dose as well as route of administration. The establishment of a protocol for safe workup of ICM allergy labels would be useful in optimizing pain procedures., (© 2020 World Institute of Pain.)
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- 2021
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49. Approach to Perioperative Anaphylaxis in 2020: Updates in Diagnosis and Management.
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Kalangara J, Vanijcharoenkarn K, Lynde GC, McIntosh N, and Kuruvilla M
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- Female, History, 21st Century, Humans, Male, Anaphylaxis diagnosis, Anaphylaxis therapy, Perioperative Period adverse effects
- Abstract
Purpose of Review: The goal of the paper is to review the epidemiology, pathogenesis, diagnosis, and manifestations of perioperative anaphylaxis (POA). We seek to review the most common culprits of POA and different diagnostic modalities for evaluation., Recent Findings: Specific IgE testing has a limited role in POA evaluation due to lack of widespread availability and low sensitivity. Basophil activation testing is complementary to skin tests and can assist NMBA sensitivity diagnosis in complex cases. In the past years, there has been an exponential increase in suspected teicoplanin allergic reactions in the European Union. Chlorhexidine is also being increasingly implicated as a culprit in POA. Multiple classes of perioperative medications cause POA. Diagnostic modalities available include skin testing with nonirritating concentrations, basophil activation tests, specific IgE, and drug provocation testing. An accurate record and critical analysis of perioperative events is more important than isolated test results. Future studies evaluating the pathophysiology of these reactions and other therapeutic strategies, such as targeting the MRGPRX2 receptor, are needed.
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- 2021
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50. Patient satisfaction and utilization of telemedicine services in allergy: An institutional survey.
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Lanier K, Kuruvilla M, and Shih J
- Subjects
- Humans, Patient Satisfaction, Surveys and Questionnaires, Hypersensitivity diagnosis, Hypersensitivity epidemiology, Hypersensitivity therapy, Telemedicine
- Published
- 2021
- Full Text
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