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1.
Dysphagia ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935170

RESUMEN

Clinical implementation of evidence-based practice (EBP) tools is a healthcare priority. The Dynamic Grade of Swallowing Toxicity (DIGEST) is an EBP tool developed in 2016 for videofluoroscopy in head and neck (H&N) oncology with clinical implementation as a goal. We sought to examine: (1) feasibility of clinical implementation of DIGEST in a national comprehensive cancer center, and (2) fidelity of DIGEST adoption in real-world practice. A retrospective implementation evaluation was conducted in accordance with the STARI framework. Electronic health record (EHR) databases were queried for all consecutive modified barium swallow (MBS) studies conducted at MD Anderson Cancer Center from 2016 to 2021. Implementation outcomes included: feasibility as measured by DIGEST reporting in EHR (as a marker of clinical use) and fidelity as measured by accuracy of DIGEST reporting relative to the decision-tree logic (penetration-aspiration scale [PAS], residue, and Safety [S] and Efficiency [E] grades). Contextual factors examined included year, setting, cancer type, MBS indication, and provider. 13,055 MBS were conducted by 29 providers in 7,842 unique patients across the lifespan in diverse oncology populations (69% M; age 1-96 years; 58% H&N cancer; 10% inpatient, 90% outpatient). DIGEST was reported in 12,137/13,088 exams over the 6-year implementation period representing 93% (95% CI: 93-94%) adoption in all exams and 99% (95% CI: 98-99%) of exams excluding the total laryngectomy population (n = 730). DIGEST reporting varied modestly by year, cancer type, and setting/provider (> 91% in all subgroups, p < 0.001). Accuracy of DIGEST reporting was high for overall DIGEST (incorrect SE profile 1.6%, 200/12,137), DIGEST-safety (incorrect PAS 0.4% 51/12,137) and DIGEST-efficiency (incorrect residue 1.2%, 148/12,137). Clinical implementation of DIGEST was feasible with high fidelity in a busy oncology practice across a large number of providers. Adoption of the tool across the lifespan in diverse cancer diagnoses may motivate validation beyond H&N oncology.

2.
Food Microbiol ; 112: 104231, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36906319

RESUMEN

Bacillus cereus phylogenetic group III and IV strains are commonly associated with food products and cause toxin mediated foodborne diseases. These pathogenic strains have been identified from milk and dairy products, such as reconstituted infant formula and several cheeses. Paneer is a fresh, soft cheese originating from India that is prone to foodborne pathogen contamination, such as by Bacillus cereus. However, there are no reported studies of B. cereus toxin formation in paneer or predictive models quantifying growth of the pathogen in paneer under different environmental conditions. This study assessed enterotoxin-producing potential of B. cereus group III and IV strains, isolated from dairy farm environments, in fresh paneer. Growth of a four-strain cocktail of toxin-producing B. cereus strains was measured in freshly prepared paneer incubated at 5-55 °C and modelled using a one-step parameter estimation combined with bootstrap re-sampling to generate confidence intervals for model parameters. The pathogen grew in paneer between 10 and 50 °C and the developed model fit the observed data well (R2 = 0.972, RMSE = 0.321 log10 CFU/g). The cardinal parameters for B. cereus growth in paneer along with the 95% confidence intervals were: µopt 0.812 log10 CFU/g/h (0.742, 0.917); Topt is 44.177 °C (43.16, 45.49); Tmin is 4.405 °C (3.973, 4.829); Tmax is 50.676 °C (50.367, 51.144). The model developed can be used in food safety management plans and risk assessments to improve safety of paneer while also adding to limited information on B. cereus growth kinetics in dairy products.


Asunto(s)
Bacillus cereus , Bacillus , Humanos , Animales , Microbiología de Alimentos , Filogenia , Enterotoxinas , Leche/química
3.
Ann Surg ; 275(6): e752-e758, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33201090

RESUMEN

OBJECTIVE: The aim of this study was to obtain feedback from key stakeholders and end users to identify program strengths and weaknesses to plan for wider dissemination and implementation of the Virtual Acute Care for Elders (Virtual ACE) program, a novel intervention that improves outcomes for older surgical patients. BACKGROUND: Virtual ACE was developed to deliver evidence-based geriatric care without requiring daily presence of a geriatrician. Previous work demonstrated that Virtual ACE increased mobility and decreased delirium rates for surgical patients. METHODS: We conducted semi-structured interviews with 30 key stakeholders (physicians, nurses, hospital leadership, nurse managers, information technology staff, and physical/occupational therapists) involved in the implementation and use of the program. RESULTS: Our stakeholders indicated that Virtual ACE was extremely empowering for bedside nurses. The program helped nurses identify older patients who were at risk for a difficult postoperative recovery. Virtual ACE also gave them skills to manage complex older patients and more effectively communicate their needs to surgeons and other providers. Nurse managers felt that Virtual ACE helped them allocate limited resources and plan their unit staffing assignments to better manage the needs of older patients. The main criticism was that the Virtual ACE Tracker that displayed patient status was difficult to interpret and could be improved by a better design interface. Stakeholders also felt that program training needed to be improved to accommodate staff turnover. CONCLUSIONS: Although respondents identified areas for improvement, our stakeholders felt that Virtual ACE empowered them and provided effective tools to improve outcomes for older surgical patients.


Asunto(s)
Cuidados Críticos , Hospitales , Anciano , Humanos , Recursos Humanos
4.
J Surg Res ; 270: 437-443, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34798426

RESUMEN

BACKGROUND: Patients understandably have concerns about thyroidectomy scars. This study aimed to characterize patients' perceptions of their thyroidectomy scar before and up to 1-y after surgery. METHODS: Patients with papillary thyroid cancer (n = 83) completed semi-structured interviews before and at 2-wks, 6-Wk, 6-mo, and 1-y post-thyroidectomy. Interviews probed about scar concerns and appearance. Content analysis was used to identify themes. RESULTS: The majority of participants did not express concerns about scar appearance. When expressed, preoperative concerns often stemmed from previous surgery experiences or unease with neck incisions. Postoperatively, concerns about scar appearance decreased over time throughout the healing period with most patients being satisfied with their scar appearance by 6-mo after surgery. CONCLUSIONS: Patients with papillary thyroid cancer express few concerns about scar thyroidectomy appearance. Surgeons can reassure patients who have preoperative concerns that most patients are satisfied with their scar appearance by 6-mo after surgery.


Asunto(s)
Cicatriz , Neoplasias de la Tiroides , Cicatriz/etiología , Humanos , Satisfacción Personal , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/cirugía , Tiroidectomía/efectos adversos
5.
Cell Immunol ; 361: 104285, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33484943

RESUMEN

Myeloid derived suppressor cells (MDSCs) are a diverse collection of immune cells that suppress anti-tumor immune responses. Decreasing MDSCs accumulation in the tumor microenvironment could improve the anti-tumor immune response and improve immunotherapy. Here, we examine the impact of physiologically relevant thermal treatments on the accumulation of MDSCs in tumors in mice. We found that different temperature-based protocols, including 1) weekly whole-body hyperthermia, 2) housing mice at their thermoneutral temperature (TT, ~30 °C), and 3) housing mice at a subthermoneutral temperature (ST,~22 °C) while providing a localized heat source, each resulted in a reduction in MDSC accumulation and improved tumor growth control compared to control mice housed at ST, which is the standard, mandated housing temperature for laboratory mice. Additionally, we found that low dose ß-adrenergic receptor blocker (propranolol) therapy reduced MDSC accumulation and improved tumor growth control to a similar degree as the models that relieved cold stress. These results show that thermal treatments can decrease MDSC accumulation and tumor growth comparable to propranolol therapy.


Asunto(s)
Calor/uso terapéutico , Células Supresoras de Origen Mieloide/inmunología , Neoplasias/inmunología , Antagonistas Adrenérgicos beta/farmacología , Animales , Línea Celular Tumoral , Femenino , Respuesta al Choque Térmico/fisiología , Calefacción/métodos , Hipertermia Inducida/métodos , Inmunoterapia/métodos , Masculino , Ratones , Ratones Endogámicos BALB C , Células Supresoras de Origen Mieloide/metabolismo , Células Supresoras de Origen Mieloide/fisiología , Microambiente Tumoral/inmunología
6.
BMC Med Res Methodol ; 21(1): 142, 2021 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-34238247

RESUMEN

BACKGROUND: Standard practice for conducting systematic reviews (SRs) is time consuming and involves the study team screening hundreds or thousands of citations. As the volume of medical literature grows, the citation set sizes and corresponding screening efforts increase. While larger team size and alternate screening methods have the potential to reduce workload and decrease SR completion times, it is unknown whether investigators adapt team size or methods in response to citation set sizes. Using a cross-sectional design, we sought to understand how citation set size impacts (1) the total number of authors or individuals contributing to screening and (2) screening methods. METHODS: MEDLINE was searched in April 2019 for SRs on any health topic. A total of 1880 unique publications were identified and sorted into five citation set size categories (after deduplication): < 1,000, 1,001-2,500, 2,501-5,000, 5,001-10,000, and > 10,000. A random sample of 259 SRs were selected (~ 50 per category) for data extraction and analysis. RESULTS: With the exception of the pairwise t test comparing the under 1000 and over 10,000 categories (median 5 vs. 6, p = 0.049) no statistically significant relationship was evident between author number and citation set size. While visual inspection was suggestive, statistical testing did not consistently identify a relationship between citation set size and number of screeners (title-abstract, full text) or data extractors. However, logistic regression identified investigators were significantly more likely to deviate from gold-standard screening methods (i.e. independent duplicate screening) with larger citation sets. For every doubling of citation size, the odds of using gold-standard screening decreased by 15 and 20% at title-abstract and full text review, respectively. Finally, few SRs reported using crowdsourcing (n = 2) or computer-assisted screening (n = 1). CONCLUSIONS: Large citation set sizes present a challenge to SR teams, especially when faced with time-sensitive health policy questions. Our study suggests that with increasing citation set size, authors are less likely to adhere to gold-standard screening methods. It is possible that adjunct screening methods, such as crowdsourcing (large team) and computer-assisted technologies, may provide a viable solution for authors to complete their SRs in a timely manner.


Asunto(s)
Colaboración de las Masas , Estudios Transversales , Humanos , Tamizaje Masivo , Proyectos de Investigación , Revisiones Sistemáticas como Asunto
7.
Ann Plast Surg ; 87(1): 73-79, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34133367

RESUMEN

BACKGROUND: Migraine surgery has been shown to be efficacious, but nuanced effects of surgery on pain and individuals' lives remain incompletely understood. Surgery may be performed at a single or multiple "primary" sites. The aims of this study were to investigate patient perceptions following single-site surgery and compare themes in patients undergoing single-site surgery with those from a previously published conceptual framework generated with patients undergoing multisite surgery. METHODS: Patients who underwent single-site headache surgery participated in open-ended interviews at least 1 year after surgery. Participants (n = 14) had undergone either occipital, temporal, or nasoseptal site surgery. A multidisciplinary team analyzed transcripts. Recurring themes were identified and compared and contrasted to those observed in patients who underwent multiple-site surgery (n = 15) in a previous study (Plast Reconstr Surg 2019;144(4):956-964). RESULTS: Similar recurring themes emerged from the single-site cohort, and the conceptual framework was applicable to all participants. Two new themes emerged from the single-site analysis. First, 5 of 14 participants described being "migraine-free" postoperatively, a finding not observed in the multisite group. Second, several individuals described financial benefits after surgery, via decreased prescription medication requirements, raises at work, and improved productivity. CONCLUSIONS: Single-site headache surgery appears to positively impact patients' lives in ways that support and expand upon previously published outcomes. Patients undergoing surgery at a single site may be more likely to experience a "pain-free" state, which may relate to the underlying pathophysiology of chronic headache. The effect of surgery on finances appears to be an outcome of interest to patients, which should be explored further.


Asunto(s)
Trastornos de Cefalalgia , Trastornos Migrañosos , Estudios de Cohortes , Cefalea/etiología , Humanos , Trastornos Migrañosos/cirugía , Recurrencia
8.
J Surg Res ; 248: 82-89, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31874319

RESUMEN

BACKGROUND: Strong patient engagement is often associated with better postoperative outcomes and reduced risk of dangerous and expensive complications for the patient. Our goal with this project is to define a new model specifically for surgical patient engagement to guide future work to improve patient outcomes. METHODS: Open-ended qualitative interviews were conducted with 38 postoperative patients, analyzed using the conventional content analysis method, and coded with NVivo 11. Patients from either a safety net or private hospital in the Houston area between the ages of 18 and 70 y were recruited after surgery for either thyroid, parathyroid, colon, or rectal cancer, inflammatory bowel disease, and diverticulitis. Pregnant and incarcerated patients in addition to those with postoperative complications or interview time frames greater than 4 wk postoperatively were excluded. RESULTS: Of patients completing the Patient Activation Measure, 98% obtained a score of 3 or 4, indicating optimal levels of activation despite differences in socio-economic status. Upon analysis of coded transcripts, four main themes of "self-efficacy," "resilience," "transitional agency," and "enabling agency," in addition to a fifth emergency rescue activator, "family and social support," were discovered as "drivers" of patient engagement. CONCLUSIONS: A novel model of patient engagement specific to surgical patients is necessary because of the unique recovery track they endure. Our new model can be used to develop interventions for these patients to improve their engagement and thereby their outcomes.


Asunto(s)
Participación del Paciente/psicología , Periodo Posoperatorio , Procedimientos Quirúrgicos Operativos/rehabilitación , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Resiliencia Psicológica , Autoeficacia , Apoyo Social
9.
J Theor Biol ; 462: 171-183, 2019 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-30385312

RESUMEN

Darwinian fitness is maximised at a temperature below Topt, but what this temperature is remains unclear. By linking our previous work on the Biokinetic Spectrum for Temperature with a model for temperature-dependent biological growth rate we obtain a plausible value for such a temperature. We find this approach reveals considerable commonalities in how life responds to temperature with implications that follow in evolution, physiology and ecology. We described a data set consisting of 17,021 observations of temperature-dependent population growth rates from 2411 bacterial, archaeal and eukaryal strains. We fitted a thermodynamic model to describe the strains' temperature-dependent growth rate curves that assumed growth was limited by a single rate-limiting enzyme. We defined Umes as an empirical measure of the temperature at which strains grew as fast and also as efficiently as possible. We propose that Darwinian fitness is optimised at Umes by trading-off growth rate and physiological efficiency. Using the full data set we calculated the Biokinetic Spectrum for Temperature (BKST): the distribution of temperature-dependent growth rates for each temperature. We used quantile regression to fit alternative models to the BKST to obtain quantile curves. A quantile is a value that contains a particular proportion of the data. The quantile curves suggested commonalities in temperature-dependencies spanning taxa and ecotype, consistent with the single rate-limiting enzyme concept. We showed that on the log scale, the slopes of the quantile curves were the same as the slopes of the thermodynamic model growth curves at Umes. This was true for Bacteria, Archaea, and Eukarya, and across other conditions (pH, water activity, metabolic type and trophic type). We showed that the quantile curves were the loci of the temperatures and growth rates that optimised Darwinian fitness for each strain at a given temperature-dependence and independently of other conditions. The quantile curves for Archaea and Bacteria shared a number of similarities attributable to the influence of the properties of water on protein folding. Other implications have impact on evolutionary biology, ecology, and physiology. The model predicts the existence of eurythermic strains that grow with about equal efficiency over a broad temperature range. These strains will have higher evolutionary rates with lower mutational costs that are independent of environmental conditions, a factor likely to have been significant during the Precambrian if the early Earth was warmer than today. The model predicts that random mutations are likely to result in shifts along the quantile curves and not across them. It predicts that some psychrophiles will be capable of performing well under climate change, and that selection will favour faster growth rates as the temperature increases. Last, it predicts trade-offs between growth rate and soma production, so that temperature-dependence, and possibly Darwinian fitness, remain constant over a broad temperature range and growth rates.


Asunto(s)
Aptitud Genética , Modelos Biológicos , Temperatura , Archaea , Bacterias , Evolución Biológica , Eucariontes , Cinética
10.
J Surg Res ; 244: 324-331, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31306889

RESUMEN

BACKGROUND: Thyroid cancer patients report unmet needs after diagnosis. However, little is known about their specific needs. Therefore, we sought to characterize the needs of patients with thyroid cancer before undergoing surgery. MATERIAL AND METHODS: We conducted semistructured interviews with 32 patients with papillary thyroid cancer after their preoperative surgical consultation. Data were analyzed using thematic content analysis. RESULTS: The central need of patients with thyroid cancer was a strong patient-surgeon relationship characterized by informational and emotional support, and respect for the patient as a person. Patients preferred disease- and treatment-related information to be individualized and to take into account aspects of their daily life. They wanted adequate time for asking questions with thoughtful answers tailored to their case. Patients additionally desired emotional support from the surgeon characterized by empathy and validation of their cancer experience. They particularly wanted surgeons to address their fears and anxiety. Patients also highly valued the surgeons' ability to see beyond their disease and acknowledge them as a unique person with respect to their occupation, psychosocial state, and other individual characteristics. When surgeons met patients' needs, they felt reassured, comfortable with their cancer diagnosis, and prepared for treatment. Suboptimal support increased patients' anxiety particularly when they felt the surgeon minimized their concerns. CONCLUSIONS: Preoperatively, patients with thyroid cancer desire a strong patient-surgeon relationship. They rely on the surgeon to provide adequate informational and emotional support and respect them as individuals. In turn, patients feel reassured and prepared for treatment.


Asunto(s)
Necesidades y Demandas de Servicios de Salud , Relaciones Médico-Paciente , Cuidados Preoperatorios , Investigación Cualitativa , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/cirugía , Adulto , Emociones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cirujanos , Cáncer Papilar Tiroideo/psicología , Neoplasias de la Tiroides/psicología
11.
Dysphagia ; 34(3): 325-332, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30232550

RESUMEN

Pharyngeal high-resolution manometry (HRM) is at a point of entry into speech-language pathologist (SLP) clinical practice. However, the demographic characteristics of SLPs who are early adopters of HRM are unclear; perspectives of early adopters may shape how the technology is received by the field at large. We hypothesized that younger SLPs, those working in outpatient settings, those with a strong knowledge base in HRM, and those with experience in other types of instrumentation are more likely to have interest in adopting HRM. We surveyed the population of board-certified SLPs (BCS-S; n = 262) with a 33% response rate (n = 78). Firth logistic regression was used to determine differences in those expressing interest in adopting HRM into future practice (n = 28) and those who did not (n = 45) from the analytic sample of 73 respondents. The best fitting model predicted that SLPs: (1) with training in more types of instrumentation; and (2) believing they could explain the HRM procedure to a patient were more likely to plan to adopt pharyngeal HRM into regular clinical practice. Experience with a variety of instrumentation techniques may encourage SLPs to use new forms of technology. Knowledge of early adopter demographics will allow for development of targeted trainings and determination of HRM implementation barriers. Identification of a clinician sub-group more likely to adopt other new technologies in the future may also be possible.


Asunto(s)
Manometría/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Patología del Habla y Lenguaje/estadística & datos numéricos , Adulto , Femenino , Humanos , Masculino , Manometría/métodos , Persona de Mediana Edad , Faringe , Patología del Habla y Lenguaje/métodos
12.
Dysphagia ; 34(2): 170-178, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30382385

RESUMEN

High-resolution manometry (HRM) objectively measures swallowing-related pressures in the pharynx and esophagus. It has been used in many research applications, but it is unclear how HRM is perceived amongst speech-language pathologists (SLP) as it enters into clinical practice. The purpose of this study was to explore SLP perceptions of clinical HRM use. Based on qualitative data collected at four focus groups held at two national conferences and a survey based on open-ended questions, we found broad consensus among those queried regarding how HRM's objective and targeted data could enhance diagnosis and drive treatments. However, we found less consensus among SLPs regarding which patients may and may not benefit, as well as when in the clinical process HRM would best supplement existing technologies, showing a need for further research. These findings highlight how SLPs can be motivated to adopt new clinical technologies if they see a patient-centered benefit and underscore the need for continued SLP education on pharyngeal HRM.


Asunto(s)
Trastornos de Deglución/diagnóstico , Manometría/estadística & datos numéricos , Patología del Habla y Lenguaje/métodos , Adulto , Deglución , Esófago/fisiopatología , Femenino , Grupos Focales , Humanos , Masculino , Manometría/métodos , Percepción , Faringe/fisiopatología , Presión , Investigación Cualitativa , Valores de Referencia
13.
J Surg Res ; 221: 69-76, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29229155

RESUMEN

BACKGROUND: Patient engagement is challenging to define and operationalize. Qualitative analysis allows us to explore patient perspectives on this topic and establish themes. A game theoretic signaling model also provides a framework through which to further explore engagement. METHODS: Over a 6-mo period, thirty-eight interviews were conducted within 6 wk of discharge in patients undergoing thyroid, parathyroid, or colorectal surgery. Interviews were transcribed, anonymized, and analyzed using the NVivo 11 platform. A signaling model was then developed depicting the doctor-patient interaction surrounding the patient's choice to reach out to their physician with postoperative concerns based upon the patient's perspective of the doctor's availability. This was defined as "engagement". We applied the model to the qualitative data to determine possible causations for a patient's engagement or lack thereof. A private hospital's and a safety net hospital's populations were contrasted. RESULTS: The private patient population was more likely to engage than their safety-net counterparts. Using our model in conjunction with patient data, we determined possible etiologies for this engagement to be due to the private patient's perceived probability of dealing with an available doctor and apparent signals from the doctor indicating so. For the safety-net population, decreased access to care caused them to be less willing to engage with a doctor perceived as possibly unavailable. CONCLUSIONS: A physician who understands these Game Theory concepts may be able to alter their interactions with their patients, tailoring responses and demeanor to fit the patient's circumstances and possible barriers to engagement.


Asunto(s)
Teoría del Juego , Modelos Teóricos , Participación del Paciente , Cuidados Posoperatorios/psicología , Periodo Posoperatorio , Adulto , Anciano , Femenino , Hospitales Privados , Humanos , Masculino , Persona de Mediana Edad , Proveedores de Redes de Seguridad
14.
Int J Hyperthermia ; 34(2): 135-143, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29498310

RESUMEN

Stress in patients and pre-clinical research animals plays a critical role in disease progression Activation of the sympathetic nervous system (SNS) by stress results in secretion of the catecholamines epinephrine (Epi) and norepinephrine (NE) from the adrenal gland and sympathetic nerve endings. Adrenergic receptors for catecholamines are present on immune cells and their activity is affected by stress and the accompanying changes in levels of these neurotransmitters. In this short review, we discuss how this adrenergic stress impacts two categories of immune responses, infections and autoimmune diseases. Catecholamines signal primarily through the ß2-adrenergic receptors present on innate and adaptive immune cells which are critical in responding to infections caused by pathogens. In general, this adrenergic input, particularly chronic stimulation, suppresses lymphocytes and allows infections to progress. On the other hand, insufficient adrenergic control of immune responses allows progression of several autoimmune diseases.


Asunto(s)
Autoinmunidad/inmunología , Enfermedades Transmisibles/inmunología , Sistema Nervioso Simpático/fisiopatología , Humanos
18.
Cell Mol Immunol ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902348

RESUMEN

Myeloid-derived suppressor cells (MDSCs) are a main driver of immunosuppression in tumors. Understanding the mechanisms that determine the development and immunosuppressive function of these cells could provide new therapeutic targets to improve antitumor immunity. Here, using preclinical murine models, we discovered that exportin 1 (XPO1) expression is upregulated in tumor MDSCs and that this upregulation is induced by IL-6-induced STAT3 activation during MDSC differentiation. XPO1 blockade transforms MDSCs into T-cell-activating neutrophil-like cells, enhancing the antitumor immune response and restraining tumor growth. Mechanistically, XPO1 inhibition leads to the nuclear entrapment of ERK1/2, resulting in the prevention of ERK1/2 phosphorylation following the IL-6-mediated activation of the MAPK signaling pathway. Similarly, XPO1 blockade in human MDSCs induces the formation of neutrophil-like cells with immunostimulatory functions. Therefore, our findings revealed a critical role for XPO1 in MDSC differentiation and suppressive functions; exploiting these new discoveries revealed new targets for reprogramming immunosuppressive MDSCs to improve cancer therapeutic responses.

19.
Nat Commun ; 15(1): 2803, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555305

RESUMEN

Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlate with poor outcomes in hematologic malignancies. Here, we identify that MDSC mitochondrial fitness controls the efficacy of doxorubicin chemotherapy in a preclinical lymphoma model. Mechanistically, we show that triggering STAT3 signaling via ß2-adrenergic receptor (ß2-AR) activation leads to improved MDSC function through metabolic reprograming, marked by sustained mitochondrial respiration and higher ATP generation which reduces AMPK signaling, altering energy metabolism. Furthermore, induced STAT3 signaling in MDSCs enhances glutamine consumption via the TCA cycle. Metabolized glutamine generates itaconate which downregulates mitochondrial reactive oxygen species via regulation of Nrf2 and the oxidative stress response, enhancing MDSC survival. Using ß2-AR blockade, we target the STAT3 pathway and ATP and itaconate metabolism, disrupting ATP generation by the electron transport chain and decreasing itaconate generation causing diminished MDSC mitochondrial fitness. This disruption increases the response to doxorubicin and could be tested clinically.


Asunto(s)
Neoplasias Hematológicas , Células Supresoras de Origen Mieloide , Succinatos , Humanos , Glutamina/metabolismo , Neoplasias Hematológicas/metabolismo , Adenosina Trifosfato/metabolismo , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Doxorrubicina/metabolismo
20.
J Man Manip Ther ; 32(1): 96-110, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38104312

RESUMEN

OBJECTIVE: The International Consortium on Manual Therapies (ICMT) is a grassroots interprofessional association open to any formally trained practitioner of manual therapy (MT) and basic scientists promoting research related to the practice of MT. Currently, MT research is impeded by professions' lack of communication with other MT professions, biases, and vernacular. Current ICMT goals are to minimize these barriers, compare MT techniques, and establish an interprofessional MT glossary. METHODS: Practitioners from all professions with training in manual therapies were encouraged by e-mail and website to participate (www.ICMTConferene.org). Video conferences were conducted at least bimonthly for 2.5 years by profession-specific and interprofessional focus groups (FGs). Members summarized scopes of practice, technique descriptions, associated mechanisms of action (MOA), and glossary terms. Each profession presented their work to the interprofessional FG to promote dialogue, understanding and consensus. Outcomes were reported and refined at numerous public events. RESULTS: Focus groups with representatives from 5 MT professions, chiropractic, massage therapy, osteopathic, physical therapy and structural integration identified 17 targeting osseous structures and 49 targeting nonosseous structures. Thirty-two techniques appeared distinct to a specific profession, and 13 were used by more than 1. Comparing descriptions identified additional commonalities. All professions agreed on 4 MOA categories for MT. A glossary of 280 terms and definitions was consolidated, representing key concepts in MT. Twenty-one terms were used by all MT professions and basic scientists. Five terms were used by MT professions exclusive of basic scientists. CONCLUSION: Outcomes suggested a third to a half of techniques used in MT are similar across professions. Additional research is needed to better define the extent of similarity and how to consistently identify those approaches. Ongoing expansion and refinement of the glossary is necessary to promote descriptive clarity and facilitate communication between practitioners and basic scientists.


Asunto(s)
Quiropráctica , Manipulaciones Musculoesqueléticas , Medicina Osteopática , Médicos Osteopáticos , Humanos , Modalidades de Fisioterapia
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