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1.
Clin Case Rep ; 12(6): e8997, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38799529

RESUMO

We report a case of Staphylococcus aureus subcapsular splenic abscess and associated empyema after recent commencement of tocilizumab, masquerading as musculoskeletal pain. This highlights the importance of considering unusual underlying infections in patients on tocilizumab.

2.
NPJ Digit Med ; 7(1): 103, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671232

RESUMO

The integration of robotics in surgery has increased over the past decade, and advances in the autonomous capabilities of surgical robots have paralleled that of assistive and industrial robots. However, classification and regulatory frameworks have not kept pace with the increasing autonomy of surgical robots. There is a need to modernize our classification to understand technological trends and prepare to regulate and streamline surgical practice around these robotic systems. We present a systematic review of all surgical robots cleared by the United States Food and Drug Administration (FDA) from 2015 to 2023, utilizing a classification system that we call Levels of Autonomy in Surgical Robotics (LASR) to categorize each robot's decision-making and action-taking abilities from Level 1 (Robot Assistance) to Level 5 (Full Autonomy). We searched the 510(k), De Novo, and AccessGUDID databases in December 2023 and included all medical devices fitting our definition of a surgical robot. 37,981 records were screened to identify 49 surgical robots. Most surgical robots were at Level 1 (86%) and some reached Level 3 (Conditional Autonomy) (6%). 2 surgical robots were recognized by the FDA to have machine learning-enabled capabilities, while more were reported to have these capabilities in their marketing materials. Most surgical robots were introduced via the 510(k) pathway, but a growing number via the De Novo pathway. This review highlights trends toward greater autonomy in surgical robotics. Implementing regulatory frameworks that acknowledge varying levels of autonomy in surgical robots may help ensure their safe and effective integration into surgical practice.

3.
BMJ Case Rep ; 17(3)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514158

RESUMO

Flecainide is a Vaughan Williams class 1c antiarrhythmic used to treat supraventricular and ventricular arrhythmias. It has been described as a rare cause for increased pacemaker capture thresholds. We describe a report of a patient, in her early 80s, presenting with tachy-brady syndrome on a background of permanent atrial fibrillation. She was treated with metoprolol and flecainide by her private cardiologist. Permanent right ventricular chamber pacing was recommended for her slow heart rate. At insertion of her single chamber pacemaker, she was noted to have elevated capture thresholds despite appropriate lead positioning. A flecainide level was elevated at 1.1 µg/mL, and it was subsequently ceased. This was associated with a rapid improvement in her capture threshold. Flecainide should be considered as a cause for elevated pacing thresholds at the time of implant. Particular care should be taken for at-risk groups such as the elderly and patients with renal impairment.


Assuntos
Fibrilação Atrial , Marca-Passo Artificial , Feminino , Humanos , Idoso , Flecainida/efeitos adversos , Antiarrítmicos/efeitos adversos , Marca-Passo Artificial/efeitos adversos , Fibrilação Atrial/etiologia , Bradicardia/etiologia , Estimulação Cardíaca Artificial
4.
JMIR Hum Factors ; 11: e55246, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38421708

RESUMO

BACKGROUND: Low back pain (LBP) is a costly global health condition that affects individuals of all ages and genders. Physical therapy (PT) is a commonly used and effective intervention for the management of LBP and incorporates movement assessment and therapeutic exercise. A newly developed wearable, fabric-based sensor system, Motion Tape, uses novel sensing and data modeling to measure lumbar spine movements unobtrusively and thus offers potential benefits when used in conjunction with PT. However, physical therapists' acceptance of Motion Tape remains unexplored. OBJECTIVE: The primary aim of this research study was to evaluate physical therapists' acceptance of Motion Tape to be used for the management of LBP. The secondary aim was to explore physical therapists' recommendations for future device development. METHODS: Licensed physical therapists from the American Physical Therapy Association Academy of Leadership Technology Special Interest Group participated in this study. Overall, 2 focus groups (FGs; N=8) were conducted, in which participants were presented with Motion Tape samples and examples of app data output on a poster. Informed by the Technology Acceptance Model, we conducted semistructured FGs and explored the wearability, usefulness, and ease of use of and suggestions for improvements in Motion Tape for PT management of LBP. FG data were transcribed and analyzed using rapid qualitative analysis. RESULTS: Regarding wearability, participants perceived that Motion Tape would be able to adhere for several days, with some variability owing to external factors. Feedback was positive for the low-profile and universal fit, but discomfort owing to wires and potential friction with clothing was of concern. Other concerns included difficulty with self-application and potential skin sensitivity. Regarding usefulness, participants expressed that Motion Tape would enhance the efficiency and specificity of assessments and treatment. Regarding ease of use, participants stated that the app would be easy, but data management and challenges with interpretation were of concern. Physical therapists provided several recommendations for future design improvements including having a wireless system or removable wires, customizable sizes for the tape, and output including range of motion data and summary graphs and adding app features that consider patient input and context. CONCLUSIONS: Several themes related to Motion Tape's wearability, usefulness, and ease of use were identified. Overall, physical therapists expressed acceptance of Motion Tape's potential for assessing and monitoring low back posture and movement, both within and outside clinical settings. Participants expressed that Motion Tape would be a valuable tool for the personalized treatment of LBP but highlighted several future improvements needed for Motion Tape to be used in practice.


Assuntos
Dor Lombar , Fisioterapeutas , Dispositivos Eletrônicos Vestíveis , Feminino , Humanos , Masculino , Grupos Focais , Pesquisa Qualitativa , Movimento (Física) , Dor Lombar/diagnóstico
5.
Nat Immunol ; 25(1): 41-53, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38036767

RESUMO

Bacille Calmette-Guérin (BCG) vaccination can confer nonspecific protection against heterologous pathogens. However, the underlying mechanisms remain mysterious. We show that mice vaccinated intravenously with BCG exhibited reduced weight loss and/or improved viral clearance when challenged with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 B.1.351) or PR8 influenza. Protection was first evident between 14 and 21 d post-vaccination and lasted ∼3 months. Notably, BCG induced a biphasic innate response and robust antigen-specific type 1 helper T cell (TH1 cell) responses in the lungs. MyD88 signaling was essential for innate and TH1 cell responses, and protection against SARS-CoV-2. Depletion of CD4+ T cells or interferon (IFN)-γ activity before infection obliterated innate activation and protection. Single-cell and spatial transcriptomics revealed CD4-dependent expression of IFN-stimulated genes in lung myeloid and epithelial cells. Notably, BCG also induced protection against weight loss after mouse-adapted SARS-CoV-2 BA.5, SARS-CoV and SHC014 coronavirus infections. Thus, BCG elicits integrated organ immunity, where CD4+ T cells feed back on tissue myeloid and epithelial cells to imprint prolonged and broad innate antiviral resistance.


Assuntos
Imunidade Adaptativa , Vacina BCG , Animais , Camundongos , Humanos , Retroalimentação , Vacinação , Redução de Peso , Antivirais , Imunidade Inata
6.
Eur J Investig Health Psychol Educ ; 13(9): 1738-1750, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37754465

RESUMO

BACKGROUND: The World Health Organization (WHO) warns that vaccine hesitancy is an ongoing major global health threat. While vaccination against severe acute respiratory syndrome coronavirus (SARS-CoV-2) proves to be an effective strategy in protecting against the disease, vaccine hesitancy represents a major barrier to stopping the spread of the virus. Willingness for vaccination can be influenced by several factors, including education level and health literacy. Although several studies demonstrate the value of video educational programs in improving coronavirus disease 2019 (COVID-19) vaccine knowledge and acceptance, no studies to date have evaluated if race, gender, and other demographic factors impact the influence of an educational video on COVID-19 vaccine knowledge and hesitancy among university students in the United States (U.S.). AIMS: This study was conducted to determine the impact of an educational video on U.S. university undergraduate students' COVID-19 vaccine perception and acceptance. It also aims to evaluate whether demographic factors affect the influence of the video. METHODS: An online survey was used to measure perceived understanding and acceptance of COVID-19 vaccines before and after viewing a video regarding the effectiveness and safety of COVID-19 vaccinations. The impact of demographic factors on the Video Influence Score was analyzed. KEY RESULTS: After viewing the video, respondents' (n = 285) perceived awareness and acceptance of COVID-19 vaccines significantly increased (p < 0.05). In addition, gender, political party affiliation, age, study major, and influenza vaccination history did not significantly impact the Video Influence Score (p > 0.05). However, African American/Black respondents (3.81 ± 4.24) were significantly more influenced by the video compared to respondents of other races (p < 0.05), such as White/Caucasian (1.91 ± 3.75), Hispanic/Latino (0.17 ± 3.67), Asian (0.29 ± 1.53), and Indigenous American (0.64 ± 2.52). CONCLUSIONS: This study suggests the potential impact of an educational video on COVID-19 vaccine perception and acceptance among university students. Despite limitations such as a modest survey response rate, this study provides valuable insight concerning the influential factors affecting vaccine acceptance in diverse student populations. Future studies are warranted to explore how student response to vaccine educational videos may vary depending on students' racial and cultural backgrounds. IMPLICATIONS: A targeted educational video to promote vaccine acceptance is a valuable tool for public health campaigns to combat vaccine hesitancy. The study also highlights the importance of tailoring interventions to specific demographic groups such as considering racial factors to maximize the impact of educational interventions on vaccine attitudes.

7.
Proc Natl Acad Sci U S A ; 120(20): e2302191120, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37155869

RESUMO

Circular RNAs (circRNAs) are a class of RNAs commonly found across eukaryotes and viruses, characterized by their resistance to exonuclease-mediated degradation. Their superior stability compared to linear RNAs, combined with previous work showing that engineered circRNAs serve as efficient protein translation templates, make circRNA a promising candidate for RNA medicine. Here, we systematically examine the adjuvant activity, route of administration, and antigen-specific immunity of circRNA vaccination in mice. Potent circRNA adjuvant activity is associated with RNA uptake and activation of myeloid cells in the draining lymph nodes and transient cytokine release. Immunization of mice with engineered circRNA encoding a protein antigen delivered by a charge-altering releasable transporter induced innate activation of dendritic cells, robust antigen-specific CD8 T cell responses in lymph nodes and tissues, and strong antitumor efficacy as a therapeutic cancer vaccine. These results highlight the potential utility of circRNA vaccines for stimulating potent innate and T cell responses in tissues.


Assuntos
Imunização , RNA Circular , Camundongos , Animais , RNA Circular/genética , RNA Circular/metabolismo , Imunização/métodos , Linfócitos T CD8-Positivos , Vacinação/métodos , Adjuvantes Imunológicos , RNA/genética , RNA/metabolismo , Antígenos/metabolismo , Camundongos Endogâmicos C57BL
8.
Proc Natl Acad Sci U S A ; 120(16): e2217864120, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37043533

RESUMO

Aberrant activity of cyclin-dependent kinase (Cdk5) has been implicated in various neurodegenerative diseases. This deleterious effect is mediated by pathological cleavage of the Cdk5 activator p35 into the truncated product p25, leading to prolonged Cdk5 activation and altered substrate specificity. Elevated p25 levels have been reported in humans and rodents with neurodegeneration, and the benefit of genetically blocking p25 production has been demonstrated previously in rodent and human neurodegenerative models. Here, we report a 12-amino-acid-long peptide fragment derived from Cdk5 (Cdk5i) that is considerably smaller than existing peptide inhibitors of Cdk5 (P5 and CIP) but shows high binding affinity toward the Cdk5/p25 complex, disrupts the interaction of Cdk5 with p25, and lowers Cdk5/p25 kinase activity. When tagged with a fluorophore (FITC) and the cell-penetrating transactivator of transcription (TAT) sequence, the Cdk5i-FT peptide exhibits cell- and brain-penetrant properties and confers protection against neurodegenerative phenotypes associated with Cdk5 hyperactivity in cell and mouse models of neurodegeneration, highlighting Cdk5i's therapeutic potential.


Assuntos
Quinase 5 Dependente de Ciclina , Peptídeos , Camundongos , Animais , Humanos , Quinase 5 Dependente de Ciclina/metabolismo , Fosforilação , Peptídeos/metabolismo , Fragmentos de Peptídeos/metabolismo , Fenótipo
9.
Nat Immunol ; 23(12): 1788-1798, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36316475

RESUMO

Systems vaccinology has defined molecular signatures and mechanisms of immunity to vaccination. However, comparative analysis of immunity to different vaccines is lacking. We integrated transcriptional data of over 3,000 samples, from 820 adults across 28 studies of 13 vaccines and analyzed vaccination-induced signatures of antibody responses. Most vaccines induced signatures of innate immunity and plasmablasts at days 1 and 7, respectively, after vaccination. However, the yellow fever vaccine induced an early transient signature of T and B cell activation at day 1, followed by delayed antiviral/interferon and plasmablast signatures that peaked at days 7 and 14-21, respectively. Thus, there was no evidence for a 'universal signature' that predicted antibody response to all vaccines. However, accounting for the asynchronous nature of responses, we defined a time-adjusted signature that predicted antibody responses across vaccines. These results provide a transcriptional atlas of immunity to vaccination and define a common, time-adjusted signature of antibody responses.


Assuntos
Formação de Anticorpos , Vacinas , Adulto , Humanos , Formação de Anticorpos/genética , Perfilação da Expressão Gênica/métodos , Vacinação , Imunidade Inata , Anticorpos Antivirais
10.
Sci Adv ; 8(39): eabo4662, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36170369

RESUMO

DNA double-strand breaks (DSBs) are linked to neurodegeneration and senescence. However, it is not clear how DSB-bearing neurons influence neuroinflammation associated with neurodegeneration. Here, we characterize DSB-bearing neurons from the CK-p25 mouse model of neurodegeneration using single-nucleus, bulk, and spatial transcriptomic techniques. DSB-bearing neurons enter a late-stage DNA damage response marked by nuclear factor κB (NFκB)-activated senescent and antiviral immune pathways. In humans, Alzheimer's disease pathology is closely associated with immune activation in excitatory neurons. Spatial transcriptomics reveal that regions of CK-p25 brain tissue dense with DSB-bearing neurons harbor signatures of inflammatory microglia, which is ameliorated by NFκB knockdown in neurons. Inhibition of NFκB in DSB-bearing neurons also reduces microglia activation in organotypic mouse brain slice culture. In conclusion, DSBs activate immune pathways in neurons, which in turn adopt a senescence-associated secretory phenotype to elicit microglia activation. These findings highlight a previously unidentified role for neurons in the mechanism of disease-associated neuroinflammation.


Assuntos
Quebras de DNA de Cadeia Dupla , Microglia , Animais , Antivirais/metabolismo , DNA/metabolismo , Humanos , Camundongos , Microglia/metabolismo , NF-kappa B/metabolismo , Neurônios/metabolismo
11.
Pharmacy (Basel) ; 10(5)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36136836

RESUMO

The coronavirus disease 2019 pandemic created a major shift in learning modalities in the Advanced Pharmacy Practice Experience program. This descriptive study aimed to evaluate preceptor and student perceptions of remote learning experiences and student practice readiness upon completion of remote rotations. Preceptors and students who participated in partial to full remote experiential rotations between 17 August 2020 and 26 March 2021 were invited to complete an on-line survey. A cross-sectional survey consisted of closed-ended questions using a 5-point Likert scale assessing perception on adaptability, effectiveness of remote learning in advancing practice knowledge and skills, and confidence in students' practice readiness. A total of 29 preceptors and 43 students completed the survey (response rates of 67% and 57%, respectively). Approximately 70% of the remote rotations were practice-based, with ambulatory care representing the most frequently reported rotation by preceptors (38%) and students (28%). A high level of confidence in preceptor perception of their ability to adapt and provide effective remote experiences (average 4.28) matched with the students' high level of confidence with their preceptors' abilities (86% agree or strongly agree). Upon the completion of remote rotations, both preceptors and students felt confident in student practice readiness based on student ability to design and initiate individualized patient care plans or complete projects using evidence-based resources (79% and 86%, respectively). Most preceptors (69%) reported that students achieved the rotation objectives at the same level as students engaged in-person experiences. The limitations of remote learning included the absence of direct interactions. Overall, both preceptors and students reported achieving practice readiness with remote experiential learning experiences and felt the remote activities should be continued post-pandemic.

12.
J Acquir Immune Defic Syndr ; 91(4): 390-396, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35952358

RESUMO

BACKGROUND: There is no established cryptococcal antigen (CrAg) screening guideline for people with HIV who are antiretroviral therapy experienced but have poor virologic control. We assessed factors associated with CrAg screening and describe missed opportunities for earlier testing. SETTING: Ambulatory clinics affiliated with Montefiore Medical Center, Bronx, NY. METHODS: This was a retrospective chart review of CrAg screening among asymptomatic people with HIV with absolute CD4 counts 200 cells/mm 3 and HIV viral loads (VLs) > 200 copies/mL receiving HIV care from 2015 to 2020. We used Cox proportional hazards regression to identify predictors of screening, including longitudinal CD4 count and HIV VL as time-varying covariables. Among cases of diagnosed cryptococcosis, we assessed for opportunities for earlier diagnosis. RESULTS: Screening CrAg was performed in 2.9% of 2201 individuals meeting the inclusion criteria. Compared with those not screened, those who were screened had a shorter duration of HIV infection (0.09 vs. 5.1 years; P = 0.001) and lower absolute CD4 counts (12 vs. 24 cells/mm 3 ; P < 0.0001). In a multivariable model stratified by median HIV duration, CD4 < 100 [hazard ratio (HR), 7.07; 95% confidence interval (CI): 2.43 to 20.6], VL > 10,000 (HR, 15.0; 95% CI: 4.16 to 54.0), and a shorter duration of HIV infection (HR, 0.60; 95% CI: 0.42 to 0.86) were associated with screening for those with HIV < 5 years. Among those diagnosed with cryptococcosis (n = 14), 6 individuals had an ambulatory visit in the preceding 6 months but did not undergo screening. CONCLUSION: CrAg screening was infrequently performed in this at-risk population. Those with a longer duration of HIV infection were less likely to undergo CrAg screening, highlighting potential missed opportunities for earlier diagnosis.


Assuntos
Criptococose , Cryptococcus , Infecções por HIV , Meningite Criptocócica , Humanos , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Estudos Retrospectivos , Antígenos de Fungos , Contagem de Linfócito CD4 , Criptococose/diagnóstico , Programas de Rastreamento , Meningite Criptocócica/diagnóstico
13.
NPJ Vaccines ; 7(1): 55, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606518

RESUMO

Adjuvants enhance the magnitude and the durability of the immune response to vaccines. However, there is a paucity of comparative studies on the nature of the immune responses stimulated by leading adjuvant candidates. In this study, we compared five clinically relevant adjuvants in mice-alum, AS03 (a squalene-based adjuvant supplemented with α-tocopherol), AS37 (a TLR7 ligand emulsified in alum), CpG1018 (a TLR9 ligand emulsified in alum), O/W 1849101 (a squalene-based adjuvant)-for their capacity to stimulate immune responses when combined with a subunit vaccine under clinical development. We found that all four of the adjuvant candidates surpassed alum with respect to their capacity to induce enhanced and durable antigen-specific antibody responses. The TLR-agonist-based adjuvants CpG1018 (TLR9) and AS37 (TLR7) induced Th1-skewed CD4+ T cell responses, while alum, O/W, and AS03 induced a balanced Th1/Th2 response. Consistent with this, adjuvants induced distinct patterns of early innate responses. Finally, vaccines adjuvanted with AS03, AS37, and CpG1018/alum-induced durable neutralizing-antibody responses and significant protection against the B.1.351 variant 7 months following immunization. These results, together with our recent results from an identical study in non-human primates (NHPs), provide a comparative benchmarking of five clinically relevant vaccine adjuvants for their capacity to stimulate immunity to a subunit vaccine, demonstrating the capacity of adjuvanted SARS-CoV-2 subunit vaccines to provide durable protection against the B.1.351 variant. Furthermore, these results reveal differences between the widely-used C57BL/6 mouse strain and NHP animal models, highlighting the importance of species selection for future vaccine and adjuvant studies.

14.
Curr Opin Immunol ; 77: 102189, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35588691

RESUMO

Development of effective vaccines is a critical global health priority. Stimulating antigen-specific B and T cells to elicit long-lasting protection remains the central paradigm of vaccinology. Adjuvants are components that enhance vaccine immunogenicity by targeting specific innate immune receptors and pathways. Recent data highlight the capacity of adjuvants to induce durable epigenetic reprogramming of the innate immune system to engender heightened resistance against pathogens. This raises the prospect of developing epigenetic adjuvants that, in addition to stimulating robust T and B cell responses, convey broad protection against diverse pathogens by training the innate immune system. In this review, we discuss our emerging understanding of the various vaccines and adjuvants and their effects on durable reprogramming of the innate immune response, their putative mechanisms of action, and the promise and challenges of developing epigenetic adjuvants as a universal vaccine strategy.


Assuntos
Adjuvantes Imunológicos , Vacinas , Adjuvantes Imunológicos/farmacologia , Epigênese Genética , Humanos , Sistema Imunitário , Imunidade Inata
15.
Nat Immunol ; 23(4): 543-555, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35288714

RESUMO

Despite the success of the BNT162b2 mRNA vaccine, the immunological mechanisms that underlie its efficacy are poorly understood. Here we analyzed the innate and adaptive responses to BNT162b2 in mice, and show that immunization stimulated potent antibody and antigen-specific T cell responses, as well as strikingly enhanced innate responses after secondary immunization, which was concurrent with enhanced serum interferon (IFN)-γ levels 1 d following secondary immunization. Notably, we found that natural killer cells and CD8+ T cells in the draining lymph nodes are the major producers of this circulating IFN-γ. Analysis of knockout mice revealed that induction of antibody and T cell responses to BNT162b2 was not dependent on signaling via Toll-like receptors 2, 3, 4, 5 and 7 nor inflammasome activation, nor the necroptosis or pyroptosis cell death pathways. Rather, the CD8+ T cell response induced by BNT162b2 was dependent on type I interferon-dependent MDA5 signaling. These results provide insights into the molecular mechanisms by which the BNT162b2 vaccine stimulates immune responses.


Assuntos
Linfócitos T CD8-Positivos , Vacinas , Imunidade Adaptativa , Animais , Vacina BNT162 , Humanos , Imunidade Inata , Camundongos , Vacinas Sintéticas , Vacinas de mRNA
16.
Nat Commun ; 13(1): 549, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-35087093

RESUMO

Adjuvants hold great potential in enhancing vaccine efficacy, making the understanding and improving of adjuvants critical goals in vaccinology. The TLR7/8 agonist, 3M-052, induces long-lived humoral immunity in non-human primates and is currently being evaluated in human clinical trials. However, the innate mechanisms of 3M-052 have not been fully characterized. Here, we perform flow cytometry, single cell RNA-seq and ATAC-seq to profile the kinetics, transcriptomics and epigenomics of innate immune cells in murine draining lymph nodes following 3M-052-Alum/Ovalbumin immunization. We find that 3M-052-Alum/OVA induces a robust antiviral and interferon gene program, similar to the yellow fever vaccine, which is known to confer long-lasting protection. Activation of myeloid cells in dLNs persists through day 28 and single cell analysis reveals putative TF-gene regulatory programs in distinct myeloid cells and heterogeneity of monocytes. This study provides a comprehensive characterization of the transcriptomics and epigenomics of innate populations in the dLNs after vaccination.


Assuntos
Adjuvantes Imunológicos/química , Imunidade Humoral/imunologia , Imunidade Inata , Vacinas Atenuadas/imunologia , Imunidade Adaptativa , Adjuvantes Imunológicos/farmacologia , Compostos de Alúmen , Animais , Anticorpos Antivirais/imunologia , Epigenômica , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Imunização , Glicoproteínas de Membrana/agonistas , Camundongos , Camundongos Endogâmicos C57BL , Monócitos , Células Mieloides , Ovalbumina , Receptor 7 Toll-Like/agonistas , Receptor 8 Toll-Like/agonistas , Vacinação
17.
Blood ; 138(26): 2799-2809, 2021 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-34724566

RESUMO

Immune aplastic anemia (AA) features somatic loss of HLA class I allele expression on bone marrow cells, consistent with a mechanism of escape from T-cell-mediated destruction of hematopoietic stem and progenitor cells. The clinical significance of HLA abnormalities has not been well characterized. We examined the somatic loss of HLA class I alleles and correlated HLA loss and mutation-associated HLA genotypes with clinical presentation and outcomes after immunosuppressive therapy in 544 AA patients. HLA class I allele loss was detected in 92 (22%) of the 412 patients tested, in whom there were 393 somatic HLA gene mutations and 40 instances of loss of heterozygosity. Most frequently affected was HLA-B*14:02, followed by HLA-A*02:01, HLA-B*40:02, HLA-B*08:01, and HLA-B*07:02. HLA-B*14:02, HLA-B*40:02, and HLA-B*07:02 were also overrepresented in AA. High-risk clonal evolution was correlated with HLA loss, HLA-B*14:02 genotype, and older age, which yielded a valid prediction model. In 2 patients, we traced monosomy 7 clonal evolution from preexisting clones harboring somatic mutations in HLA-A*02:01 and HLA-B*40:02. Loss of HLA-B*40:02 correlated with higher blood counts. HLA-B*07:02 and HLA-B*40:01 genotypes and their loss correlated with late-onset of AA. Our results suggest the presence of specific immune mechanisms of molecular pathogenesis with clinical implications. HLA genotyping and screening for HLA loss may be of value in the management of immune AA. This study was registered at clinicaltrials.gov as NCT00001964, NCT00061360, NCT00195624, NCT00260689, NCT00944749, NCT01193283, and NCT01623167.


Assuntos
Anemia Aplástica/genética , Genes MHC Classe I , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Mutação , Adolescente , Adulto , Alelos , Anemia Aplástica/imunologia , Evolução Clonal , Feminino , Deleção de Genes , Expressão Gênica , Antígenos HLA-A/imunologia , Antígenos HLA-B/imunologia , Humanos , Imunidade , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Am J Health Syst Pharm ; 78(18): 1732-1738, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-33948622

RESUMO

PURPOSE: To describe the innovative teaching practices, tools, and resources for remote learning developed by a school of pharmacy with a decentralized experiential program to empower and support preceptors in response to the coronavirus disease 2019 (COVID-19) pandemic. SUMMARY: As the pandemic has continued, there have been significant shifts in pharmacy workflow, staffing, and patient care delivery. Pharmacy students are slowly being reintegrated into these learning environments. Although preceptors are willing and eager to teach, many lack the resources, tools, and support to create remote learning experiences at their facilities. The University of the Pacific Thomas J. Long School of Pharmacy has a decentralized experiential education model in which faculty regional coordinators with clinical practices and diverse expertise are disseminated throughout California. This model allowed us to collaborate and understand preceptor needs from a local level. We created a preceptor COVID-19 guidance document, introduced innovative virtual playbooks to pivot up to 100% remote rotations, and promoted the layered learning model to integrate pharmacy residents into the remote teaching space. Communication and flexibility are key to ensure student and preceptor safety while maintaining high-quality advanced pharmacy practice experiences and preserving patient-student relationships in telehealth. CONCLUSION: Overall, we successfully created innovative solutions and leveraged our decentralized experiential model to meet the teaching and learning demands during an unanticipated crisis. We continue to adapt and plan to assess the effectiveness of the tools by administering surveys of preceptors and pharmacy students.


Assuntos
COVID-19 , Educação em Farmácia , Farmácia , Estudantes de Farmácia , Currículo , Humanos , Assistência ao Paciente , Preceptoria , SARS-CoV-2
19.
J Pharm Pract ; 34(5): 814-817, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33622074

RESUMO

PURPOSE: Amantadine is commonly used to treat Parkinson's disease. A case of myoclonus and asterixis was associated with amantadine is reported. CASE SUMMARY: An 80-year-old man with Parkinson's disease diagnosed in 2015 was started on amantadine for treatment of progressive tremor and orofacial dyskinesias induced by levodopa. He took amantadine 100mg orally daily for 7 days, then increased to 100mg twice a day thereafter. The patient complained of "worsening tremor" after 9 days and amantadine was decreased to 100mg daily. After 1 month on this dose, the patient reported that his "tremor" persisted and experienced visual hallucinations. His examination demonstrated diffuse myoclonus throughout his extremities and trunk, as well as asterixis when attempting to stand or holding his arms antigravity. Laboratory testing for renal and hepatic failure was unrevealing. Amantadine was reduced to 50mg daily for 4 days and then discontinued. Myoclonus resolved 3 days after discontinuation of amantadine. CONCLUSION: While amantadine-induced myoclonus is rare, health care providers should be vigilant in monitoring for signs and symptoms of myoclonus following amantadine initiation.


Assuntos
Mioclonia , Doença de Parkinson , Idoso de 80 Anos ou mais , Amantadina/efeitos adversos , Alucinações , Humanos , Levodopa , Masculino , Mioclonia/induzido quimicamente , Mioclonia/diagnóstico
20.
JCI Insight ; 6(4)2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33476300

RESUMO

Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as a treatment for coronavirus disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200 mL of CCP with a spike protein IgG titer ≥ 1:2430 (median 1:47,385) within 72 hours of admission with propensity score-matched controls cared for at a medical center in the Bronx, between April 13 and May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroid use, and anticoagulation use. There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared with matched controls, CCP recipients less than 65 years had 4-fold lower risk of mortality and 4-fold lower risk of deterioration in oxygenation or mortality at day 28. For CCP recipients, pretransfusion spike protein IgG, IgM, and IgA titers were associated with mortality at day 28 in univariate analyses. No adverse effects of CCP were observed. Our results suggest CCP may be beneficial for hospitalized patients less than 65 years, but data from controlled trials are needed to validate this finding and establish the effect of aging on CCP efficacy.


Assuntos
Anticorpos Neutralizantes/administração & dosagem , Anticorpos Antivirais/administração & dosagem , COVID-19/terapia , SARS-CoV-2/imunologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/virologia , Feminino , Mortalidade Hospitalar , Humanos , Imunização Passiva/métodos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Glicoproteína da Espícula de Coronavírus/imunologia , Resultado do Tratamento , Soroterapia para COVID-19
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