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1.
Adv Drug Deliv Rev ; 210: 115331, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729264

RESUMO

Improving surgical resection outcomes for locally aggressive tumors is key to inducing durable locoregional disease control and preventing progression to metastatic disease. Macroscopically complete resection of the tumor is the standard of care for many cancers, including breast, ovarian, lung, sarcoma, and mesothelioma. Advancements in cancer diagnostics are increasing the number of surgically eligible cases through early detection. Thus, a unique opportunity arises to improve patient outcomes with decreased recurrence rates via intraoperative delivery treatments using local drug delivery strategies after the tumor has been resected. Of the current systemic treatments (e.g., chemotherapy, targeted therapies, and immunotherapies), immunotherapies are the latest approach to offer significant benefits. Intraoperative strategies benefit from direct access to the tumor microenvironment which improves drug uptake to the tumor and simultaneously minimizes the risk of drug entering healthy tissues thereby resulting in fewer or less toxic adverse events. We review the current state of immunotherapy development and discuss the opportunities that intraoperative treatment provides. We conclude by summarizing progress in current research, identifying areas for exploration, and discussing future prospects in sustained remission.

2.
bioRxiv ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617223

RESUMO

Hematopoietic dysfunction has been associated with a reduction in the number of active precursors. However, precursor quantification at homeostasis and under diseased conditions is constrained by the scarcity of available methods. To address this issue, we optimized a method for quantifying a wide range of hematopoietic precursors. Assuming the random induction of a stable label in precursors following a binomial distribution, the estimation depends on the inverse correlation between precursor numbers and the variance of precursor labeling among independent samples. Experimentally validated to cover the full dynamic range of hematopoietic precursors in mice (1 to 105), we utilized this approach to demonstrate that thousands of precursors, which emerge after modest expansion during fetal-to-adult transition, contribute to native and perturbed hematopoiesis. We further estimated the number of precursors in a mouse model of Fanconi Anemia, showcasing how repopulation deficits can be segregated into autologous (cell proliferation) and non-autologous causes (lack of precursor). Our results support an accessible and reliable approach for precursor quantification, emphasizing the contemporary perspective that native hematopoiesis is highly polyclonal.

3.
Death Stud ; : 1-12, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573792

RESUMO

To address gaps in bereavement services in the UK, a national charity offered free access to Grief Coach, a 12-month text message-based grief support program. To assess the feasibility and acceptability of the approach, this study examined program reach, retention, and user satisfaction. Over 4000 grievers enrolled in the program over 13.5 months; 6- and 12-month retention rates were 87.8% and 83.2%. Among individuals responding to a satisfaction survey (response rate = 55.9%), 94.8% rated the program as moderately or very helpful and 95.4% said it contributed to their sense of being supported in their grief. Common themes emerging from a qualitative analysis of the written comments were how the program helped with coping with the pain of grief and user appreciation of the program. Grief Coach may be a promising component of high-quality grief support to meet the needs of grieving people in the UK.

4.
Mol Carcinog ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558423

RESUMO

Epithelial ovarian cancers that are nonhomologous recombination deficient, as well as those that are recurrent and in a platinum-resistant state, have limited therapeutic options. The objectives of this study were to characterize the mechanism of action and investigate the therapeutic potential of a small molecule, VDX-111, against ovarian cancer. We examined the ability of VDX-111 to inhibit the growth of a panel of ovarian cancer cell lines, focusing on BRCA wild-type lines. We found that VDX-111 causes a dose-dependent loss of cell viability across ovarian cancer cell lines. Reverse phase protein array (RPPA) analysis was used to identify changes in cell signaling in response to VDX-111 treatment. An RPPA analysis performed on cells treated with VDX-111 detected changes in cell signaling related to autophagy and necroptosis. Immunoblots of OVCAR3 and SNU8 cells confirmed a dose-dependent increase in LC3A/B and RIPK1. Incucyte live cell imaging was used to measure cell proliferation and death in response to VDX-111 alone and with inhibitors of apoptosis, necroptosis, and autophagy. Annexin/PI assays suggested predominantly nonapoptotic cell death, while real-time kinetic imaging of cell growth indicated the necroptosis inhibitor, necrostatin-1, attenuates VDX-111-induced loss of cell viability, suggesting a necroptosis-dependent mechanism. Furthermore, VDX-111 inhibited tumor growth in patient-derived xenograft and syngeneic murine models. In conclusion, the cytotoxic effects of VDX-111 seen in vitro and in vivo appear to occur in a necroptosis-dependent manner and may promote an antitumor immune response.

5.
Int Forum Allergy Rhinol ; 14(4): 850-852, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37646427

RESUMO

KEY POINTS: CRS patients treated with medical management have improvement in ETD symptoms as reflected by lower ETDQ-7 scores However, appropriate CRS medical management may be limited in ability to significantly improve, or resolve, ETD.


Assuntos
Otopatias , Tuba Auditiva , Rinossinusite , Sinusite , Humanos , Estudos Prospectivos , Sinusite/tratamento farmacológico , Otopatias/tratamento farmacológico , Otopatias/diagnóstico , Doença Crônica
6.
Eur Arch Otorhinolaryngol ; 281(1): 489-496, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37906366

RESUMO

PURPOSE: The objective of this study was to determine concerns of otolaryngology patients regarding health-related social media usage. METHODS: A total of 372 otolaryngology patients were asked to report their level of concern (on a scale of "not at all", "a little", "somewhat", or "highly" concerned) regarding health-related social media usage as it pertained to risk of "loss of privacy or anonymity related to your health condition", "reliability of disease/treatment information", and "reliability of physician reviews/recommendations". Demographics and social media usage patterns (on Facebook, Instagram, Twitter, TikTok or other platforms) were compared to concerns about health-related social media usage. RESULTS: The level of concern was highest for reliability of disease/treatment information and least for loss of privacy/anonymity (p < 0.001). Concern about loss of privacy/anonymity was associated with age over 25 years (OR = 3.12, 95%CI 1.66-5.86, p < 0.001) and negatively with daily use of Twitter (OR = 0.54, 95%CI 0.30-0.96, p = 0.035). Concern about reliability of disease/treatment information was negatively associated with Medicare insurance (OR = 0.57, 95%CI 0.35-0.93, p = 0.024), which is available to adults aged ≥65 years, and concern over reliability of physician reviews/recommendations was associated with patients identifying their race as Asian, American Indian and other (OR = 3.16, 95%CI 1.22-8.19, p = 0.018). CONCLUSIONS: The greatest concern about health-related social media usage is related to reliability of disease/treatment information, though notably less among patients with Medicare who represent adults of age 65 years or older. Concerns over loss of privacy/anonymity and reliability of physician reviews/recommendations are also prevalent and associated with patient demographics. These concerns may constrain utilization of social media for healthcare purposes, which highlights the importance of reliable sources of information.


Assuntos
Otolaringologia , Médicos , Mídias Sociais , Adulto , Humanos , Idoso , Estados Unidos , Reprodutibilidade dos Testes , Medicare
7.
Artigo em Inglês | MEDLINE | ID: mdl-37788156

RESUMO

BACKGROUND: Existing patient-reported outcome measures (PROMs) for chronic rhinosinusitis (CRS) use a variety of recall periods and response scales to assess CRS symptom burden. Global perspectives of CRS patients regarding optimal recall periods and response scales for CRS PROMs are unknown. METHODS: This was a multi-center, cross-sectional study recruiting 461 CRS patients from sites across the United States, Saudi Arabia, New Zealand, and Austria. Participants chose which CRS symptom recall period (1 day, 2 weeks, 1 month, >1 month) was most reflective of their current disease state and upon which to best base treatment recommendations (including surgery). Participants also chose which of six response scales (one visual analogue scale and five Likert scales ranging from four to eight items) was easiest to use, understand, and preferred. RESULTS: A plurality of participants (40.0%) felt their CRS symptoms' current state was best reflected by a 1-month recall period. However, most patients (56.9%) preferred treatment recommendations to be determined by symptoms experienced over a >1 month period. The four- and five-item Likert scales were the easiest to understand (26.0% and 25.4%, respectively) and use (23.4% and 26.7%, respectively). The five-item (26.4% rating it most preferred and 70.9% rating it preferred) and four-item Likert (22.3% rating it most preferred and 56.4% rating it preferred) response scales were most preferred. CONCLUSION: Future PROMs for CRS should consider assessment of symptoms over a 1-month period and use a four- or five-item Likert response scale to reflect global patient preferences. These findings also inform interpretation of current CRS PROMs.

8.
Gynecol Oncol ; 178: 161-169, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37890345

RESUMO

OBJECTIVE: This study assessed the efficacy, safety, and health-related quality of life (HRQoL) of the treatment regimen of dostarlimab, a programmed death-1 inhibitor, combined with niraparib, a poly (ADP-ribose) polymerase inhibitor, in patients with BRCA wild type (BRCAwt) recurrent platinum-resistant ovarian cancer (PROC) who had previously received bevacizumab treatment. METHODS: This Phase II, open-label, single-arm, multicenter study, conducted in the USA, enrolled patients with recurrent PROC to receive niraparib and dostarlimab until disease progression or unacceptable toxicity (up to 3 years). A preplanned interim futility analysis was performed after the first 41 patients had undergone ≥1 radiographic evaluation (approximately 9 weeks from the first treatment). RESULTS: The prespecified interim futility criterion was met and the study was therefore terminated. For the 41 patients assessed, the objective response rate (ORR) was 7.3% (95% confidence interval: 1.5-19.9); no patients achieved a complete response, 3 patients (7.3%) achieved a partial response (duration of response; 3.0, 3.8, and 9.2 months, respectively), and 9 patients (22.0%) had stable disease. In total, 39 patients (95.1%) experienced a treatment-related adverse event, but no new safety issues were observed. HRQoL, assessed using FOSI, or Functional Assessment of Cancer Therapy - Ovarian Symptom Index scores, worsened over time compared with baseline scores. CONCLUSIONS: The study was terminated due to the observed ORR at the interim futility analysis. This highlights a need for effective therapies in treating patients with recurrent BRCAwt PROC.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/induzido quimicamente , Qualidade de Vida , Carcinoma Epitelial do Ovário/tratamento farmacológico , Antineoplásicos/uso terapêutico , Indazóis/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico
9.
J Immunother Cancer ; 11(6)2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37295818

RESUMO

Advanced gynecologic cancers have historically lacked effective treatment options. Recently, immune checkpoint inhibitors (ICIs) have been approved by the US Food and Drug Administration for the treatment of cervical cancer and endometrial cancer, offering durable responses for some patients. In addition, many immunotherapy strategies are under investigation for the treatment of earlier stages of disease or in other gynecologic cancers, such as ovarian cancer and rare gynecologic tumors. While the integration of ICIs into the standard of care has improved outcomes for patients, their use requires a nuanced understanding of biomarker testing, treatment selection, patient selection, response evaluation and surveillance, and patient quality of life considerations, among other topics. To address this need for guidance, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline. The Expert Panel drew on the published literature as well as their own clinical experience to develop evidence- and consensus-based recommendations to provide guidance to cancer care professionals treating patients with gynecologic cancer.


Assuntos
Neoplasias dos Genitais Femininos , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias dos Genitais Femininos/terapia , Imunoterapia , Qualidade de Vida , Resultado do Tratamento , Neoplasias do Colo do Útero/etiologia
10.
Laryngoscope ; 133(12): 3492-3498, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37334783

RESUMO

OBJECTIVE: Receiving instruments from surgical technicians during endoscopic laryngeal and airway microsurgery (ELAM) has challenges including repeated, expeditious handling of delicate instruments and passing them to the surgeon's hand opposite of where the surgical assistant is standing. Optimizing this interaction may reduce surgical errors and improve operative efficiency. METHODS: A proprietary ELAM instrument holder was attached to both sides of the operating room bed. The device consisted of an articulating arm with custom silicone inserts mounted on a tray (storing up to three endoscopic instruments). ELAM cases were randomized to be performed either with (device) or without the holder (control). Using custom software, instrument pass time (IPT), instrument drop rate (IDR), and communication errors (eg handing incorrect instruments) were manually recorded. Qualitative use metrics relating to overall device satisfaction were also obtained. RESULTS: Data were collected from 25 device and 23 control cases among three different laryngologists. Average IPT was nearly three times quicker for the device (0.80 s, n = 1175 passes) compared with controls (2.09 s, n = 1208 passes) [p < 0.001]. IPT interquartile range was five times higher for control (1.65 s) versus device cases (0.42 s). IDR was not significantly different [p = 0.48]; however, device cases had significantly lower communication errors compared to control cases [p = 0.01]. Surgeons and surgical assistants were similarly satisfied with the device on a 5-point Likert scale (mean: 4.2/5, standard deviation: 0.92). CONCLUSION: The proposed endoscopic instrument holder can improve ELAM operative workflow by reducing instrument passing time and variability without increasing IDR. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3492-3498, 2023.


Assuntos
Laringoscópios , Laringe , Humanos , Instrumentos Cirúrgicos , Endoscopia , Laringe/cirurgia , Salas Cirúrgicas
11.
Clin Transl Med ; 13(7): e1244, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37386762

RESUMO

BACKGROUND: The intersection of synthetic biology and biomaterials promises to enhance safety and efficacy in novel therapeutics. Both fields increasingly employ Boolean logic, which allows for specific therapeutic outputs (e.g., drug release, peptide synthesis) in response to inputs such as disease markers or bio-orthogonal stimuli. Examples include stimuli-responsive drug delivery devices and logic-gated chimeric antigen receptor (CAR) T cells. In this review, we explore recent manuscripts highlighting the potential of synthetic biology and biomaterials with Boolean logic to create novel and efficacious living therapeutics. MAIN BODY: Collaborations in synthetic biology and biomaterials have led to significant advancements in drug delivery and cell therapy. Borrowing from synthetic biology, researchers have created Boolean-responsive biomaterials sensitive to multiple inputs including pH, light, enzymes and more to produce functional outputs such as degradation, gel-sol transition and conformational change. Biomaterials also enhance synthetic biology, particularly CAR T and adoptive T cell therapy, by modulating therapeutic immune cells in vivo. Nanoparticles and hydrogels also enable in situ generation of CAR T cells, which promises to drive down production costs and expand access to these therapies to a larger population. Biomaterials are also used to interface with logic-gated CAR T cell therapies, creating controllable cellular therapies that enhance safety and efficacy. Finally, designer cells acting as living therapeutic factories benefit from biomaterials that improve biocompatibility and stability in vivo. CONCLUSION: By using Boolean logic in both cellular therapy and drug delivery devices, researchers have achieved better safety and efficacy outcomes. While early projects show incredible promise, coordination between these fields is ongoing and growing. We expect that these collaborations will continue to grow and realize the next generation of living biomaterial therapeutics.


Assuntos
Materiais Biocompatíveis , Biologia Sintética , Animais , Materiais Biocompatíveis/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos , Sistemas de Liberação de Medicamentos , Imunoterapia Adotiva , Mamíferos
12.
Otolaryngol Clin North Am ; 56(2): 371-388, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37030949

RESUMO

Dysphagia is a common functional outcome following treatment of laryngeal cancer. Despite curative advances in both nonsurgical and surgical approaches, preserving and optimizing swallowing function is critical. Understanding the nature and severity of dysphagia depending on initial tumor staging and treatment modality and intensity is crucial. This chapter explores current evidence on the acute and chronic impacts of treatments for laryngeal cancer on swallow function, as well as the medical and nonmedical management of dysphagia in this population.


Assuntos
Transtornos de Deglutição , Neoplasias Laríngeas , Humanos , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/patologia , Deglutição , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Laringectomia/efeitos adversos , Terapia Combinada
13.
Cancer Res Commun ; 3(2): 309-324, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36860657

RESUMO

The importance of the immune microenvironment in ovarian cancer progression, metastasis, and response to therapies has become increasingly clear, especially with the new emphasis on immunotherapies. To leverage the power of patient-derived xenograft (PDX) models within a humanized immune microenvironment, three ovarian cancer PDXs were grown in humanized NBSGW (huNBSGW) mice engrafted with human CD34+ cord blood-derived hematopoietic stem cells. Analysis of cytokine levels in the ascites fluid and identification of infiltrating immune cells in the tumors demonstrated that these humanized PDX (huPDX) established an immune tumor microenvironment similar to what has been reported for patients with ovarian cancer. The lack of human myeloid cell differentiation has been a major setback for humanized mouse models, but our analysis shows that PDX engraftment increases the human myeloid population in the peripheral blood. Analysis of cytokines within the ascites fluid of huPDX revealed high levels of human M-CSF, a key myeloid differentiation factor as well as other elevated cytokines that have previously been identified in ovarian cancer patient ascites fluid including those involved in immune cell differentiation and recruitment. Human tumor-associated macrophages and tumor-infiltrating lymphocytes were detected within the tumors of humanized mice, demonstrating immune cell recruitment to tumors. Comparison of the three huPDX revealed certain differences in cytokine signatures and in the extent of immune cell recruitment. Our studies show that huNBSGW PDX models reconstitute important aspects of the ovarian cancer immune tumor microenvironment, which may recommend these models for preclinical therapeutic trials. Significance: huPDX models are ideal preclinical models for testing novel therapies. They reflect the genetic heterogeneity of the patient population, enhance human myeloid differentiation, and recruit immune cells to the tumor microenvironment.


Assuntos
Neoplasias Ovarianas , Cavidade Peritoneal , Humanos , Camundongos , Animais , Feminino , Xenoenxertos , Ascite , Neoplasias Ovarianas/terapia , Citocinas , Microambiente Tumoral
14.
Laryngoscope ; 133(12): 3279-3284, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36971228

RESUMO

OBJECTIVE: To determine the impact of comorbid migraine on quality of life (QOL) in chronic rhinosinusitis (CRS). METHODS: A total of 213 adult patients with CRS were recruited. All participants completed the 22-item Sinonasal Outcome Test (SNOT-22), from which total and validated nasal, ear/facial pain, sleep, and emotional subdomain scores were calculated, and the 5-dimension EuroQol general health questionnaire (EQ-5D), from which the visual analogue scale (VAS) and health utility value (HUV) were calculated. The presence of comorbid migraine was determined by a score of ≥4 on the 5-item Migraine Screen Questionnaire (MS-Q). RESULTS: Of the participants, 36.2% were screened positive for having comorbid migraine. The mean SNOT-22 score was 64.9 (SD: 18.7) in participants with migraine and 41.5 (SD: 21.1) in participants without migraine (p < 0.001). The mean EQ-5D VAS and HUV were 60.2 (SD: 21.9) and 0.69 (SD: 0.18), respectively, in participants with migraine and 71.4 (SD: 19.4) and 0.84 (SD: 0.13), respectively, in participants without migraine (p < 0.001 for both). Higher ear/facial pain (OR = 1.22, 95% CI: 1.10-1.36, p < 0.001) and sleep (OR = 1.11, 95% CI: 1.04-1.18, p = 0.002) SNOT-22 subdomain scores were positively associated with migraine. The SNOT-22 item scores related to dizziness, reduced concentration, and facial pain, in descending order, were most associated with migraine. The presence of nasal polyps (OR = 0.24, 95% CI: 0.07 - 0.80, p = 0.020) was negatively associated with migraine. CONCLUSION: Comorbid migraine may be relatively common amongst CRS patients, and its presence is associated with significantly worse QOL. Dizziness as a symptom in CRS patients may be particularly indicative of migraine. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3279-3284, 2023.


Assuntos
Rinite , Sinusite , Adulto , Humanos , Qualidade de Vida , Tontura/complicações , Rinite/complicações , Rinite/epidemiologia , Rinite/diagnóstico , Doença Crônica , Sinusite/complicações , Sinusite/diagnóstico , Dor Facial
15.
Cureus ; 15(1): e34086, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36843722

RESUMO

Preeclampsia is a type of hypertensive disorder of pregnancy that can cause significant maternal and perinatal morbidity and mortality. Hypertension and proteinuria are the keystones of the disease, though systemic end-organ dysfunction may follow. The pathogenesis is multifactorial, with known influences by placental, vascular, renal, and immunological dysfunction. This is a case of preeclampsia complicated by preterm delivery and antepartum intracerebral hemorrhage secondary to aneurysm rupture, presenting as dull headaches and blurry vision, commonly associated with severe features.

16.
Laryngoscope ; 133(9): 2116-2121, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36373871

RESUMO

OBJECTIVE: To determine factors associated with social media usage for finding a doctor or seeking medical advice among otolaryngology patients. METHODS: Cross-sectional study of 361 patients visiting our clinics. All participants were asked if they were aware social media may be used to find doctors and if they had ever done so, and also if they were aware social media could be used to get advice about a medical condition or its treatment and if they had ever done so. Demographic characteristics were examined for association with affirmative answers to these questions. RESULTS: Facebook was the most used social media platform with 50.7% using Facebook daily. Over 50% of participants were aware social media could be used to find a doctor or seek medical advice. Daily use of Facebook was associated with using social media for finding a doctor (OR = 2.57, 95%CI: 1.41-4.67, p = 0.002) and seeking medical advice (OR = 1.72, 95%CI: 1.09-2.71, p = 0.020). Having Medicare was associated with using social media to find a doctor (OR = 2.20, 95%CI: 1.15-4.21, p = 0.017), whereas Medicaid was associated with using social media for medical advice (OR = 1.99, 95%CI: 1.08-3.67, p = 0.027). CONCLUSION: A majority of otolaryngology patients may be aware of health care applications of social media, with Facebook being the dominant platform, and Medicare insurance identifying patients who may most use social media in this manner. There is also an indication that social determinants of health, as reflected by Medicaid insurance, may be associated with using social media to seek medical advice. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2116-2121, 2023.


Assuntos
Otolaringologia , Mídias Sociais , Idoso , Humanos , Estados Unidos , Estudos Transversais , Medicare , Atenção à Saúde
17.
J Int Neuropsychol Soc ; 29(5): 459-471, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36062528

RESUMO

OBJECTIVE: Smartphones have the potential for capturing subtle changes in cognition that characterize preclinical Alzheimer's disease (AD) in older adults. The Ambulatory Research in Cognition (ARC) smartphone application is based on principles from ecological momentary assessment (EMA) and administers brief tests of associative memory, processing speed, and working memory up to 4 times per day over 7 consecutive days. ARC was designed to be administered unsupervised using participants' personal devices in their everyday environments. METHODS: We evaluated the reliability and validity of ARC in a sample of 268 cognitively normal older adults (ages 65-97 years) and 22 individuals with very mild dementia (ages 61-88 years). Participants completed at least one 7-day cycle of ARC testing and conventional cognitive assessments; most also completed cerebrospinal fluid, amyloid and tau positron emission tomography, and structural magnetic resonance imaging studies. RESULTS: First, ARC tasks were reliable as between-person reliability across the 7-day cycle and test-retest reliabilities at 6-month and 1-year follow-ups all exceeded 0.85. Second, ARC demonstrated construct validity as evidenced by correlations with conventional cognitive measures (r = 0.53 between composite scores). Third, ARC measures correlated with AD biomarker burden at baseline to a similar degree as conventional cognitive measures. Finally, the intensive 7-day cycle indicated that ARC was feasible (86.50% approached chose to enroll), well tolerated (80.42% adherence, 4.83% dropout), and was rated favorably by older adult participants. CONCLUSIONS: Overall, the results suggest that ARC is reliable and valid and represents a feasible tool for assessing cognitive changes associated with the earliest stages of AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/psicologia , Smartphone , Reprodutibilidade dos Testes , Cognição , Biomarcadores/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Disfunção Cognitiva/psicologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano
18.
JACC Cardiovasc Imaging ; 15(11): 1944-1955, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36357136

RESUMO

BACKGROUND: Patients with suspected cardiac sarcoidosis frequently undergo fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging to assess disease activity at baseline and after treatment initiation. OBJECTIVES: This study investigated the effect of immunosuppressive therapy and biopsy status to achieve complete treatment response (CTR), partial treatment response (PTR), or no response (NR) on myocardial FDG-PET/CT. METHODS: This study analyzed 83 patients with suspected cardiac sarcoidosis (aged 53 ± 1.8 years, 71% were male, 69% were White, 61% had a history of biopsy-confirmed sarcoidosis) who were treatment naive, had evidence of myocardial FDG at baseline, and underwent repeat PET imaging after treatment initiation. CTR was graded visually, and PTR/NR were measured both visually and quantitatively using the total glycolytic activity. Patients were also evaluated for the occurrence of death, sustained ventricular arrhythmias, and heart failure admissions. RESULTS: Overall, 59 patients (71%) achieved CTR/PTR (30%/41%) at follow-up scan (P = 0.04). Total glycolytic activity and visual estimate of PTR/NR had excellent agreement (κ = 0.86 [95% CI: 0.72-0.99]; P < 0.0001). In patients receiving prednisone only, the highest rates of CTR/PTR were observed in patients initiated on moderate or high dose (P < 0.01). In a regression model, moderate prednisone start dose (P = 0.03) was more strongly associated with achieving CTR/PTR than was high prednisone start dose. However, the latter patients were tapered faster between start dose and follow-up scan (P < 0.01). After a median follow-up of 4.7 (IQR: 3.1-7.8) years, patients who were biopsy-proven (vs non-biopsy-proven; P = 0.029) and with preserved left ventricular function (P = 002) were less likely to experience major adverse cardiac events. Outcomes based on treatment response status (CTR vs PTR vs NR; P = 0.23) were not significantly different. CONCLUSIONS: Among patients with suspected sarcoidosis and evidence of myocardial inflammation, treatment response by serial FDG-PET was variable, but a favorable response was more common when using moderate-to-high intensity prednisone dose. Biopsy-proven individuals and those with preserved systolic function were less likely to experience adverse outcomes during follow-up.


Assuntos
Cardiomiopatias , Miocardite , Sarcoidose , Humanos , Masculino , Feminino , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Prednisona , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/patologia , Valor Preditivo dos Testes , Sarcoidose/diagnóstico por imagem , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia , Tomografia por Emissão de Pósitrons/métodos , Terapia de Imunossupressão
19.
J Am Coll Emerg Physicians Open ; 3(5): e12819, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36172306

RESUMO

Objectives: The objective of this study was to evaluate the performance of non-targeted hepatitis C virus (HCV) screening in emergency departments (EDs) and other healthcare settings in terms of patients identified with HCV infection and linked to HCV care. Methods: In the Southern Appalachian region of the United States, we developed non-targeted HCV screening and linkage-to-care programs in 10 institutions at different healthcare settings, including EDs, outpatient clinics, and inpatient units. Serum samples were tested for HCV antibodies, and if positive, reflexed to HCV ribonucleic acid (RNA) testing as a confirmatory test for active infection. Patients with positive RNA tests were contacted to link them to HCV care. Results: Between 2017 and 2019, among 195,152 patients screened for HCV infection, 16,529 (8.5%) were positive by antibody testing, 10,139 (5.2% of screened patients and 61.3% of patients positive by antibody test) were positive by RNA testing, and 5778 (3.0% of screened patients and 57.0% of patients positive by RNA test) were successfully linked to HCV care. Among 83,645 patients screened in EDs, 9060 (10.8%) were positive by HCV antibody, and 5243 (6.3%) were positive by RNA test. Among patients positive by RNA testing, linkage to care was lower for patients screened in the ED (44.1%) compared with outpatient clinics (67.6%) (P < 0.01) and inpatient units (50.9%) (P < 0.01). Conclusions: Non-targeted HCV screening in acute care settings can identify large numbers of people with HCV infection. To optimize the utility of these screening programs, future work is needed to develop best practices that consistently link these patients to HCV care.

20.
Poult Sci ; 101(10): 102055, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35973350

RESUMO

The presence of meat quality defects is increasing in the turkey industry. While the main strategy for mitigating these issues is through improved housing, management, and slaughter conditions, it may be possible to incorporate meat quality into a turkey breeding strategy with the intent to improve meat quality. Before this can occur, it is important to describe the current state of turkey meat quality as well as the correlations among the different meat quality traits and important production traits. The main objective of the present study was to provide a descriptive analysis of 8 different meat quality traits for turkey breast meat from 3 different purebred lines (A, B, and C), and their correlation with a selection of production traits. Using a total of 7,781 images, the breast meat (N = 590-3,892 birds depending on trait) was evaluated at 24 h postmortem for color (L*, a*, b*), pH, and physiochemical characteristics (drip loss, cooking loss, shear force). Descriptive statistics (mean and standard deviation) and Pearson correlations were computed to describe the relationships among traits within each genetic line. A one-factor ANOVA and post hoc t-test were conducted for each trait and between each of the genetic lines. We found significant differences between genetic lines for some color traits (L* and a*), pHinitial, drip loss, and cooking loss. The lightest line in weight (line B) had meat that was the lightest (L*) in color. The heaviest line (line C) had meat that was less red (a*) with a higher pHinitial and greater cooking loss. Unfavorable correlations between production traits and meat quality were also found for each of the genetic lines where increases in production (e.g., body weight, growth rate) resulted in meat that was lighter and redder in color and in some cases (line B and C), with an increased moisture loss. The results of this study provide an important benchmark for turkey meat quality in purebred lines and provide an updated account of the relationships between key production traits and meat quality. Although the magnitude of these correlations is low, their cumulative effect on meat quality can be more significant especially with continued selection pressure on growth and yield.


Assuntos
Galinhas , Carne , Animais , Culinária , Fenótipo , Perus/genética
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