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1.
Neurocrit Care ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750393

RESUMEN

BACKGROUND: The Center for Medicare and Medicaid Services requires Organ Procurement Organizations (OPOs) to verify and document that any potential organ donor has been pronounced dead per applicable legal requirements of local, state, and federal laws. However, OPO practices regarding death by neurologic criteria (DNC) verification are not standardized, and little is known about their DNC verification processes. This study aimed to explore OPO practices regarding DNC verification in the United States. METHODS: An electronic survey was sent to all 57 OPOs in the United States from June to September 2023 to assess verification of policies and practices versus guidelines, concerns about policies and practices, processes to address concerns about DNC determination, and communication practices. RESULTS: Representatives from 12 OPOs across six US regions completed the entire survey; 8 of 12 reported serving > 50 referral hospitals. Most respondents (11 of 12) reported comparing their referral hospital's DNC policies with the 2010 American Academy of Neurology Practice Parameter and/or other (4 of 12) guidelines. Additionally, most (10 of 12) reported independently reviewing and verifying each DNC determination. Nearly half (5 of 12) reported concerns about guideline-discordant hospital policies, and only 3 of 12 thought all referral hospitals followed the 2010 American Academy of Neurology Practice Parameter in practice. Moreover, 9 of 12 reported concerns about clinician knowledge surrounding DNC determination, and most (10 of 12) reported having received referrals for patients whose DNC declaration was ultimately reversed. All reported experiences in which their OPO requested additional assessments (11 of 12 clinical evaluation, 10 of 12 ancillary testing, 9 of 12 apnea testing) because of concerns about DNC determination validity. CONCLUSIONS: Accurate DNC determination is important to maintain public trust. Nearly all OPO respondents reported a process to verify hospital DNC policies and practices with medical society guidelines. Many reported concerns about clinician knowledge surrounding DNC determination and guideline-discordant policies and practices. Educational and regulatory advocacy efforts are needed to facilitate systematic implementation of guideline-concordant practices across the country.

3.
J Clin Med ; 13(4)2024 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-38398345

RESUMEN

BACKGROUND: To examine the association between external ventricular drain (EVD) placement, critical care utilization, complications, and clinical outcomes in hospitalized adults with spontaneous subarachnoid hemorrhage (SAH). METHODS: A single-center retrospective study included SAH patients 18 years and older, admitted between 1 January 2014 and 31 December 2022. The exposure variable was EVD. The primary outcomes of interest were (1) early mortality (<72 h), (2) overall mortality, (3) improvement in modified-World Federation of Neurological Surgeons (m-WFNSs) grade between admission and discharge, and (4) discharge to home at the end of the hospital stay. We adjusted for admission m-WFNS grade, age, sex, race/ethnicity, intraventricular hemorrhage, aneurysmal cause of SAH, mechanical ventilation, critical care utilization, and complications within a multivariable analysis. We reported adjusted odds ratios (aORs) and 95% confidence intervals (CI). RESULTS: The study sample included 1346 patients: 18% (n = 243) were between the ages of 18 and 44 years, 48% (n = 645) were between the age of 45-64 years, and 34% (n = 458) were 65 years and older, with other statistics of females (56%, n = 756), m-WFNS I-III (57%, n = 762), m-WFNS IV-V (43%, n = 584), 51% mechanically ventilated, 76% White (n = 680), and 86% English-speaking (n = 1158). Early mortality occurred in 11% (n = 142). Overall mortality was 21% (n = 278), 53% (n = 707) were discharged to their home, and 25% (n = 331) improved their m-WFNS between admission and discharge. Altogether, 54% (n = 731) received EVD placement. After adjusting for covariates, the results of the multivariable analysis demonstrated that EVD placement was associated with reduced early mortality (aOR 0.21 [0.14, 0.33]), an improvement in m-WFNS grade (aOR 2.06 [1.42, 2.99]) but not associated with overall mortality (aOR 0.69 [0.47, 1.00]) or being discharged home at the end of the hospital stay (aOR 1.00 [0.74, 1.36]). EVD was associated with a higher rate of ventilator-associated pneumonia (aOR 2.32 [1.03, 5.23]), delirium (aOR 1.56 [1.05, 2.32]), and a longer ICU (aOR 1.33 [1.29;1.36]) and hospital length of stay (aOR 1.09 [1.07;1.10]). Critical care utilization was also higher in patients with EVD compared to those without. CONCLUSIONS: The study suggests that EVD placement in hospitalized adults with spontaneous subarachnoid hemorrhage (SAH) is associated with reduced early mortality and improved neurological recovery, albeit with higher critical care utilization and complications. These findings emphasize the potential clinical benefits of EVD placement in managing SAH. However, further research and prospective studies may be necessary to validate these results and provide a more comprehensive understanding of the factors influencing clinical outcomes in SAH.

4.
Cureus ; 16(1): e52730, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38384632

RESUMEN

Background Managing neurocritical care patients encompasses many complex challenges, necessitating specialized care and continuous quality improvement efforts. In recent years, the focus on enhancing patient outcomes in neurocritical care may have led to the development of dedicated quality improvement programs. These programs are designed to systematically evaluate and refine care practices, aligning them with the latest clinical guidelines and research findings. Objective To describe the structure, processes, and outcomes of a dedicated Neurocritical Care Quality Improvement Program (NCC-QIP) at Harborview Medical Center, United States; a quaternary academic medical center, level I trauma, and a comprehensive stroke center. Materials and methods We describe the development of the NCC-QIP, its structure, function, challenges, and evolution. We examine our performance with several NCC-QI quality measures as proposed by the Joint Commission, the American Association of Neurology, and the Neurocritical Care Society, self-reported quality improvement (QI) concerns and QI initiatives undertaken because of the information obtained during our event/measure reporting process for patients admitted between 1/1/2014 and 06/30/2023. Results The NCC-QI reviewed data from 20,218 patients; mean age 57.9 (standard deviation 18.1) years, 56% (n=11,326) males, with acute ischemic stroke (AIS; 22.3%, n=4506), spontaneous intracerebral hemorrhage (ICH; 14.8%, n=2,996), spontaneous subarachnoid hemorrhage (SAH; 8.9%, n=1804), and traumatic brain injury (TBI; 16.6%, n=3352) among other admissions, 37.4% (n=7,559) were mechanically ventilated, and 13.6% (n=2,753) received an intracranial pressure monitor. The median intensive care unit length of stay was two days (Quartile 1-Quartile 3: 2-5 days), and the median hospital length of stay was seven days (Quartile 1-Quartile 3: 3-14 days); 53.9% (n=10,907) were discharged home while 11.4% (2,309) died. The three most commonly reported QI concerns were related to care coordination/communication/handoff (40.4%, n=283), medication-related concerns (14.9%, n=104), and equipment/devices-related concerns (11.7%, n=82). Hospital-acquired infections were in the form of ventilator-associated pneumonia (16.3%, n=419/2562), ventriculostomy catheter-associated infections (4%, n=102/2246), and deep venous thrombosis/pulmonary embolism (3.2%, n=647). The quality metrics documentation was as follows: nimodipine after SAH (99.8%, 1802/1810), Hunt and Hess score (36%, n=650/1804), and ICH score (58.4% n=1752/2996). In comparison, 72% (n=3244/4506) of patients with AIS had a documented National Institute of Health Stroke Scale. Admission Glasgow Coma Score was recorded in 99% of patients with SAH, ICH, and TBI. Educational modules were implemented in response to event reporting. Conclusion A dedicated NCC-QIP can be successfully implemented at a quaternary medical medical center. It is possible to monitor and review a large volume of neurocritical care patients, The three most reported NCC-QI concerns may be related to care coordination-communication/handoff, medication-related concerns, and equipment/devices-related complications. The documentation of illness severity scores and stroke measures depends upon the type of measure and ability to reliably and accurately abstract and can be challenging. The quality improvement process can be enhanced by educational modules that reinforce quality and safety.

5.
Medicina (Kaunas) ; 60(2)2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38399591

RESUMEN

Background and Objectives: We analyzed delirium testing, delirium prevalence, critical care associations outcomes at the time of hospital discharge in patients with acute brain injury (ABI) due to acute ischemic stroke (AIS), non-traumatic subarachnoid hemorrhage (SAH), non-traumatic intraparenchymal hemorrhage (IPH), and traumatic brain injury (TBI) admitted to an intensive care unit. Materials and Methods: We examined the frequency of assessment for delirium using the Confusion Assessment Method for the intensive care unit. We assessed delirium testing frequency, associated factors, positive test outcomes, and their correlations with clinical care, including nonpharmacological interventions and pain, agitation, and distress management. Results: Amongst 11,322 patients with ABI, delirium was tested in 8220 (726%). Compared to patients 18-44 years of age, patients 65-79 years (aOR 0.79 [0.69, 0.90]), and those 80 years and older (aOR 0.58 [0.50, 0.68]) were less likely to undergo delirium testing. Compared to English-speaking patients, non-English-speaking patients (aOR 0.73 [0.64, 0.84]) were less likely to undergo delirium testing. Amongst 8220, 2217 (27.2%) tested positive for delirium. For every day in the ICU, the odds of testing positive for delirium increased by 1.11 [0.10, 0.12]. Delirium was highest in those 80 years and older (aOR 3.18 [2.59, 3.90]). Delirium was associated with critical care resource utilization and with significant odds of mortality (aOR 7.26 [6.07, 8.70] at the time of hospital discharge. Conclusions: In conclusion, we find that seven out of ten patients in the neurocritical care unit are tested for delirium, and approximately two out of every five patients test positive for delirium. We demonstrate disparities in delirium testing by age and preferred language, identified high-risk subgroups, and the association between delirium, critical care resource use, complications, discharge GCS, and disposition. Prioritizing equitable testing and diagnosis, especially for elderly and non-English-speaking patients, is crucial for delivering quality care to this vulnerable group.


Asunto(s)
Lesiones Encefálicas , Delirio , Accidente Cerebrovascular Isquémico , Humanos , Anciano , Delirio/diagnóstico , Delirio/epidemiología , Delirio/etiología , Alta del Paciente , Accidente Cerebrovascular Isquémico/complicaciones , Cuidados Críticos , Unidades de Cuidados Intensivos , Lesiones Encefálicas/complicaciones , Hospitales
7.
Front Immunol ; 14: 1109759, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37720229

RESUMEN

Introduction: Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells, which mediate host immunity to microbial infection by recognizing metabolite antigens derived from microbial riboflavin synthesis presented by the MHC-I-related protein 1 (MR1). Namely, the potent MAIT cell antigens, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), form via the condensation of the riboflavin precursor 5-amino-6-D-ribitylaminouracil (5-A-RU) with the reactive carbonyl species (RCS) methylglyoxal (MG) and glyoxal (G), respectively. Although MAIT cells are abundant in humans, they are rare in mice, and increasing their abundance using expansion protocols with antigen and adjuvant has been shown to facilitate their study in mouse models of infection and disease. Methods: Here, we outline three methods to increase the abundance of MAIT cells in C57BL/6 mice using a combination of inflammatory stimuli, 5-A-RU and MG. Results: Our data demonstrate that the administration of synthetic 5-A-RU in combination with one of three different inflammatory stimuli is sufficient to increase the frequency and absolute numbers of MAIT cells in C57BL/6 mice. The resultant boosted MAIT cells are functional and can provide protection against a lethal infection of Legionella longbeachae. Conclusion: These results provide alternative methods for expanding MAIT cells with high doses of commercially available 5-A-RU (± MG) in the presence of various danger signals.


Asunto(s)
Células T Invariantes Asociadas a Mucosa , Humanos , Animales , Ratones , Ratones Endogámicos C57BL , Adyuvantes Inmunológicos , Piruvaldehído , Riboflavina
8.
J Clin Med ; 12(11)2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37298001

RESUMEN

We examined the associations between the Neurological Pupillary Index (NPi) and disposition at hospital discharge in patients admitted to the neurocritical care unit with acute brain injury (ABI) due to acute ischemic stroke (AIS), spontaneous intracerebral hemorrhage (sICH), aneurysmal subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI). The primary outcome was discharge disposition (home/acute rehabilitation vs. death/hospice/skilled nursing facility). Secondary outcomes were tracheostomy tube placement and transition to comfort measures. Among 2258 patients who received serial NPi assessments within the first seven days of ICU admission, 47.7% (n = 1078) demonstrated NPi ≥ 3 on initial and final assessments, 30.1% (n = 680) had initial NPI < 3 that never improved, 19% (n = 430) had initial NPi ≥ 3, which subsequently worsened to <3 and never recovered, and 3.1% (n = 70) had initial NPi < 3, which improved to ≥3. After adjusting for age, sex, admitting diagnosis, admission Glasgow Coma Scale score, craniotomy/craniectomy, and hyperosmolar therapy, NPi values that remained <3 or worsened from ≥3 to <3 were associated with poor outcomes (adjusted odds ratio, aOR 2.58, 95% CI [2.03; 3.28]), placement of a tracheostomy tube (aOR 1.58, 95% CI [1.13; 2.22]), and transition to comfort measures only (aOR 2.12, 95% CI [1.67; 2.70]). Our study suggests that serial NPi assessments during the first seven days of ICU admission may be helpful in predicting outcomes and guiding clinical decision-making in patients with ABI. Further studies are needed to evaluate the potential benefit of interventions to improve NPi trends in this population.

9.
Artículo en Inglés | MEDLINE | ID: mdl-36941123

RESUMEN

BACKGROUND: We report adherence to 6 Anesthesiology Performance Improvement and Reporting Exchange (ASPIRE) quality metrics (QMs) relevant to patients undergoing decompressive craniectomy or endoscopic clot evacuation after spontaneous supratentorial intracerebral hemorrhage (sICH). METHODS: In this retrospective observational study, we describe adherence to the following ASPIRE QMs: acute kidney injury (AKI-01); mean arterial pressure < 65 mm Hg for less than 15 minutes (BP-03); myocardial injury (CARD-02); treatment of high glucose (> 200 mg/dL, GLU-03); reversal of neuromuscular blockade (NMB-02); and perioperative hypothermia (TEMP-03). RESULT: The study included 95 patients (70% male) with median (interquartile range) age 55 (47 to 66) years and ICH score 2 (1 to 3) undergoing craniectomy (n=55) or endoscopic clot evacuation (n=40) after sICH. In-hospital mortality attributable to sICH was 23% (n=22). Patients with American Society of Anesthesiologists physical status class 5 (n=16), preoperative reduced glomerular filtration rate (n=5), elevated cardiac troponin (n=21) and no intraoperative labs with high glucose (n=71), those who were not extubated at the end of the case (n=62) or did not receive a neuromuscular blocker given (n=3), and patients having emergent surgery (n=64) were excluded from the analysis for their respective ASPIRE QM based on predetermined ASPIRE exclusion criteria. For the remaining patients, the adherence to ASPIRE QMs were: AKI-01, craniectomy 34%, endoscopic clot evacuation 1%; BP-03, craniectomy 72%, clot evacuation 73%; CARD-02, 100% for both groups; GLU-03, craniectomy 67%, clot evacuation 100%; NMB-02, clot evacuation 79%, and; TEMP-03, clot evacuation 0% with hypothermia. CONCLUSION: This study found variable adherence to ASPIRE QMs in sICH patients undergoing decompressive craniectomy or endoscopic clot evacuation. The relatively high number of patients excluded from individual ASPIRE metrics is a major limitation.

10.
Cell Death Dis ; 14(2): 111, 2023 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-36774342

RESUMEN

Cell death mechanisms in T lymphocytes vary according to their developmental stage, cell subset and activation status. The cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are largely unknown. Here we report that MAIT cells express key necroptotic machinery; receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) protein, in abundance. Despite this, we discovered that the loss of RIPK3, but not necroptotic effector MLKL or apoptotic caspase-8, specifically increased MAIT cell abundance at steady-state in the thymus, spleen, liver and lungs, in a cell-intrinsic manner. In contrast, over the course of infection with Francisella tularensis, RIPK3 deficiency did not impact the magnitude of the expansion nor contraction of MAIT cell pools. These findings suggest that, distinct from conventional T cells, the accumulation of MAIT cells is restrained by RIPK3 signalling, likely prior to thymic egress, in a manner independent of canonical apoptotic and necroptotic cell death pathways.


Asunto(s)
Células T Invariantes Asociadas a Mucosa , Humanos , Necrosis/metabolismo , Células T Invariantes Asociadas a Mucosa/metabolismo , Muerte Celular , Hígado/metabolismo , Proteínas Quinasas/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo
11.
Neurol Clin Pract ; 12(5): 336-343, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36380895

RESUMEN

Background and Objective: To examine the verification of a referring hospital's practice of determining death by neurologic criteria (DNC) by an organ procurement organization (OPO) pursuant to the Center for Medicaid and Medicare Services rule §486.344(b). Methods: In this retrospective cohort study, we examined prevalence and factors associated with deviations from acceptable DNC standards, the performance of additional ancillary testing requested by the OPO, resolution of concerns about deviations between referring hospitals and the OPO, and interactions between referring hospitals and the OPO. Results: The OPO reviewed DNC processes for 645 adult potential organ donors from 64 referral hospitals. Concerns about practice deviations from acceptable standards were identified by the OPO's medical director (also a practicing neurointensivist) on call in 19% (n = 120) and were related to clinical prerequisites (27.2%, n = 49), clinical examination (23.9%, n = 67), and apnea testing (25.3%, n = 97). The top 3 concerns were apnea test results not meeting PCO2 targets (6.7%, n = 43), errors in documentation of the clinical examination (5.3%, n = 34), and potential confounding effects of CNS depressants (2.5%, n = 16). Compared with the "no medical director concerns" group which includes all patients, where the coordinator felt that DNC determination met all the conditions on the checklist, medical director concerns were less likely to occur in hospitals with a dedicated neurocritical care unit (odds ratio [OR] 0.33, 95% CI 0.17-0.66, p < 0.001), prevalent across hospitals independent of whether their policies conformed to updated DNC guidelines (OR 0.92, 95% CI 0.57-1.45, p = 0.720). The OPO requested additional ancillary testing (6%, n = 41) when clinical prerequisites were not met (OR 12.7, 95% CI 4.29-33.5), p < 0.001). Resolution of concerns and organ donation was achieved in 99.4% (n = 641). Four patients were rejected as brain-dead donors because of the presence of cerebral blood flow on the nuclear medicine perfusion test. Referring hospitals requested support from the OPO regarding the determination of DNC (10%, n = 64) and declaring physicians were reported to lack knowledge about the institutional DNC policy (4%, n = 23). Discussion: Ongoing review of institutional DNC standards and adherence to those standards is an urgent unmet need. Both referring hospitals and OPOs jointly carry responsibility for preventing errors in DNC leading up to organ recovery.

12.
Transplant Proc ; 54(8): 2075-2081, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36357226

RESUMEN

Patients on the transplant waiting list continue to have a significant wait time as organ supply remains low. Many initiatives have been undertaken in the last few years to attempt to increase the organ allograft supply. As organ procurement organizations have attempted to increase their procurement of organs from deceased donors, emphasis has been placed on avoidance of injury to organs during procurement. To analyze the success of this attention, data were collected from 29 of 57 organ procurement organizations in the United States. Data collection was from November 2017 to January 2020. Total injury rate ranged from 6% (donation after brain death) to 8.4% (donation after circulatory death). Level 3 injuries, those resulting in loss of the allograft, ranged from 1.1% in donation after brain death to 1.6% in donation after circulatory death. The most likely injured organ resulting in loss of viability (level 3 injury) during procurement was the right kidney. We noted that among donors with procurement injuries, a higher number had no previous abdominal surgery and there were more injuries noted from attending surgeons (compared to trainees). Deceased donor procurement organ injuries, though rare, lead to substantial loss of transplantable organs every year. Given that the United Network for Organ Sharing has recorded >10,000 deceased donors yearly for the past few years, such injuries can result in hundreds of transplantable organs lost. In this article we detailed the incidence and degree of injury and some variables that may be associated with these injuries.


Asunto(s)
Muerte Encefálica , Obtención de Tejidos y Órganos , Humanos , Estados Unidos , Donantes de Tejidos , Riñón , Recolección de Datos
13.
J Exp Med ; 219(9)2022 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-36018322

RESUMEN

Mucosal-associated invariant T (MAIT) cells detect microbial infection via recognition of riboflavin-based antigens presented by the major histocompatibility complex class I (MHC-I)-related protein 1 (MR1). Most MAIT cells in human peripheral blood express CD8αα or CD8αß coreceptors, and the binding site for CD8 on MHC-I molecules is relatively conserved in MR1. Yet, there is no direct evidence of CD8 interacting with MR1 or the functional consequences thereof. Similarly, the role of CD8αα in lymphocyte function remains ill-defined. Here, using newly developed MR1 tetramers, mutated at the CD8 binding site, and by determining the crystal structure of MR1-CD8αα, we show that CD8 engaged MR1, analogous to how it engages MHC-I molecules. CD8αα and CD8αß enhanced MR1 binding and cytokine production by MAIT cells. Moreover, the CD8-MR1 interaction was critical for the recognition of folate-derived antigens by other MR1-reactive T cells. Together, our findings suggest that both CD8αα and CD8αß act as functional coreceptors for MAIT and other MR1-reactive T cells.


Asunto(s)
Células T Invariantes Asociadas a Mucosa , Receptores de Antígenos de Linfocitos T alfa-beta , Antígenos , Antígenos CD8 , Linfocitos T CD8-positivos , Antígenos de Histocompatibilidad Clase I , Humanos , Antígenos de Histocompatibilidad Menor
14.
Anesthesiology ; 137(2): 137-150, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35819863

RESUMEN

SUMMARY: For the task of estimating a target benchmark dose such as the ED50 (the dose that would be effective for half the population), an adaptive dose-finding design is more effective than the standard approach of treating equal numbers of patients at a set of equally spaced doses. Up-and-down is the most popular family of dose-finding designs and is in common use in anesthesiology. Despite its widespread use, many aspects of up-and-down are not well known, implementation is often misguided, and standard, up-to-date reference material about the design is very limited. This article provides an overview of up-and-down properties, recent methodologic developments, and practical recommendations, illustrated with the help of simulated examples. Additional reference material is offered in the Supplemental Digital Content.


Asunto(s)
Proyectos de Investigación , Relación Dosis-Respuesta a Droga , Humanos
15.
J Leukoc Biol ; 112(4): 717-732, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35704477

RESUMEN

Mucosal-associated invariant T (MAIT) cells are innate-like, unconventional T cells that are present in peripheral blood and mucosal surfaces. A clear understanding of how MAIT cells in the mucosae function and their role in host immunity is still lacking. Therefore, our aim was to investigate MAIT cell distribution and their characteristics in the gastrointestinal (GI) mucosal tissue based on Vα7.2+ CD161hi identification. We showed that Vα7.2+ CD161hi T cells are present in both intraepithelial layer and lamina propriae of the GI mucosa, but have different abundance at each GI site. Vα7.2+ CD161hi T cells were most abundant in the duodenum, but had the lowest reactivity to MR1-5-OP-RU tetramers when compared with Vα7.2+ CD161hi T cells at other GI tissue sites. Striking discrepancies between MR1-5-OP-RU tetramer reactive cells and Vα7.2+ CD161hi T cells were observed along each GI tissue sites. Vα7.2+ CD161hi TCR repertoire was most diverse in the ileum. Similar dominant profiles of TRBV usage were observed among peripheral blood, duodenum, ileum, and colon. Some TRBV chains were detected at certain intestinal sites and not elsewhere. The frequency of peripheral blood Vα7.2+ CD161hi T cells correlated with mucosal Vα7.2+ CD161hi T cells in lamina propriae ileum and lamina propriae colon. The frequency of peripheral blood Vα7.2+ CD161hi T cells in Helicobacter pylori-infected individuals was significantly lower than uninfected individuals, but this was not observed with gastric Vα7.2+ CD161hi T cells. This study illustrates the biology of Vα7.2+ CD161hi T cells in the GI mucosa and provides a basis for understanding MAIT cells in the mucosa and MAIT-related GI diseases.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Células T Invariantes Asociadas a Mucosa , Humanos , Membrana Mucosa , Receptores de Antígenos de Linfocitos T , Ribitol/análogos & derivados , Uracilo/análogos & derivados
16.
Immunol Cell Biol ; 100(7): 547-561, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35514192

RESUMEN

Mucosal-associated invariant T (MAIT) cells are a major subset of innate-like T cells mediating protection against bacterial infection through recognition of microbial metabolites derived from riboflavin biosynthesis. Mouse MAIT cells egress from the thymus as two main subpopulations with distinct functions, namely, T-bet-expressing MAIT1 and RORγt-expressing MAIT17 cells. Previously, we reported that inducible T-cell costimulator and interleukin (IL)-23 provide essential signals for optimal MHC-related protein 1 (MR1)-dependent activation and expansion of MAIT17 cells in vivo. Here, in a model of tularemia, in which MAIT1 responses predominate, we demonstrate that IL-12 and IL-23 promote MAIT1 cell expansion during acute infection and that IL-12 is indispensable for MAIT1 phenotype and function. Furthermore, we showed that the bias toward MAIT1 or MAIT17 responses we observed during different bacterial infections was determined and modulated by the balance between IL-12 and IL-23 and that these responses could be recapitulated by cytokine coadministration with antigen. Our results indicate a potential for tailored immunotherapeutic interventions via MAIT cell manipulation.


Asunto(s)
Infecciones Bacterianas , Células T Invariantes Asociadas a Mucosa , Animales , Citocinas , Antígenos de Histocompatibilidad Clase I/metabolismo , Interleucina-12 , Interleucina-23 , Ratones
17.
J Neurosurg Anesthesiol ; 34(1): e34-e39, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32149890

RESUMEN

INTRODUCTION: The exposure of anesthesiologists to organ recovery procedures and the anesthetic technique used during organ recovery has not been systematically studied in the United States. METHODS: A retrospective cohort study was conducted on all adult and pediatric patients who were declared brain dead between January 1, 2008, and June 30, 2019, and who progressed to organ donation at Harborview Medical Center. We describe the frequency of directing anesthetic care by attending anesthesiologists, anesthetic technique, and donor management targets during organ recovery. RESULTS: In a cohort of 327 patients (286 adults and 41 children), the most common cause of brain death was traumatic brain injury (51.1%). Kidneys (94.4%) and liver (87.4%) were the most common organs recovered. On average, each year, an attending anesthesiologist cared for 1 (range: 1 to 7) brain-dead donor during organ retrieval. The average anesthetic time was 127±53.5 (mean±SD) minutes. Overall, 90% of patients received a neuromuscular blocker, 63.3% an inhaled anesthetic, and 33.9% an opioid. Donor management targets were achieved as follows: mean arterial pressure ≥70 mm Hg (93%), normothermia (96%), normoglycemia (84%), urine output >1 to 3 mL/kg/h (61%), and lung-protective ventilation (58%). CONCLUSIONS: During organ recovery from brain-dead organ donors, anesthesiologists commonly administer neuromuscular blockers, inhaled anesthetics, and opioids, and strive to achieve donor management targets. While infrequently being exposed to these cases, it is expected that all anesthesiologists be cognizant of the physiological perturbations in brain-dead donors and achieve physiological targets to preserve end-organ function. These findings warrant further examination in a larger multi-institutional cohort.


Asunto(s)
Anestésicos , Muerte Encefálica , Adulto , Encéfalo , Niño , Humanos , Estudios Retrospectivos , Donantes de Tejidos , Estados Unidos
18.
Anesth Analg ; 132(3): 761-769, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-32665465

RESUMEN

BACKGROUND: This survey assessed satisfaction with the practice environment among physicians who have completed fellowship training in critical care medicine (CCM) as recognized by the American Board of Anesthesiology (and are members of the American Society of Anesthesiology) and evaluated the perceived effectiveness of training programs in preparing fellows for critical care practice. METHODS: A cross-sectional online survey composed of 39 multiple choice and open-ended questions was administered between August and December 2018 to all members of the American Society of Anesthesiologists (ASA) who self-identified as being CCM trained. The survey instrument was developed and revised in an iterative fashion by ASA committee on CCM and the Society for Education in Anesthesia (SEA). Survey results were analyzed using a mixed-method approach. RESULTS: Three hundred fifty-three of the 1400 anesthesiologists who self-identified to the ASA as having CCM training (25.2%) completed the survey. Most were men (72.3%), board certified in CCM (98.7%), and had practiced a median of 5 years. Half of the respondents rated their training as "excellent." A total of 70.6% described currently working in academic centers with 53.6% providing care in open surgical intensive care units (ICUs). Most anesthesiologist intensivists (75%) spend at least 25% of their clinical time providing ICU care (versus clinical anesthesia). A total of 89% of the respondents were involved in educational activities, 60% reported being in administrative leadership roles, and 37% engaged in scholarly activity. Areas of dissatisfaction included fatigue, lack of collegiality or respect, lack of research training, decreased job satisfaction, and burnout. Analysis suggested moderate levels of job satisfaction (49%), work-life balance (52%), and high levels of burnout (74%). A significant contributor to burnout was with a perception of lack of respect (P = .005) in the work environment. Burnout was not significantly associated with gender or duration of practice. Qualitative analysis of the open-ended responses also identified these 3 variables as major themes. CONCLUSIONS: This survey of CCM-trained anesthesiologists described a high rate of board certification, practice in academic settings, and participation in resident education. Areas of dissatisfaction with an anesthesia/critical care practice included burnout, work/life balance, and lack of respect. These results may increase recruitment of anesthesiologists into critical care and inform strategies to improve satisfaction with anesthesia critical care practice, fellowship training.


Asunto(s)
Anestesiólogos/educación , Anestesiología/educación , Cuidados Críticos , Satisfacción en el Trabajo , Adulto , Anciano , Actitud del Personal de Salud , Agotamiento Profesional/etiología , Competencia Clínica , Estudios Transversales , Femenino , Encuestas de Atención de la Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Consejos de Especialidades , Equilibrio entre Vida Personal y Laboral , Lugar de Trabajo
19.
Int J Crit Illn Inj Sci ; 10(Suppl 1): 17-20, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33376685

RESUMEN

INTRODUCTION: Hypothermic machine perfusion (HMP) has been established as an efficacious method for preserving kidney allografts from deceased donors in clinical trials, but little data are available on the effectiveness of HMP in real-world settings. We examined factors associated with HMP use and clinical outcomes in a real-world organ procurement organization setting. METHODS: We conducted a retrospective cohort study of the Lifecenter Northwest organ procurement database from 2010 to 2015, linked to the United Network of Organ Sharing outcomes database. We examined HMP utilization, and our primary outcomes were delayed graft function (DGF) and graft survival, using multivariable Poisson and Cox regression models. RESULTS: Among 1729 deceased-donor kidneys, 797 (46%) were preserved with HMP. Higher donor age, region of procurement, and donation type were associated with HMP use. HMP was associated with a 37% decreased risk of DGF (adjusted relative risk 0.63, 95% confidence interval [CI]: 0.51-0.78), with no effect on 1-year graft survival (adjusted hazard ratio 0.83, 95% CI: 0.38-1.80). CONCLUSION: Variation exists in the utilization of HMP for deceased donor kidneys. HMP reduced the risk for DGF, but was not associated with improvements in long-term graft survival.

20.
Front Immunol ; 11: 1845, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33013835

RESUMEN

Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells that recognize the evolutionarily conserved major histocompatibility complex (MHC) class I-like antigen-presenting molecule known as MHC class I related protein 1 (MR1). Since their rise from obscurity in the early 1990s, the study of MAIT cells has grown substantially, accelerating our fundamental understanding of these cells and their possible roles in immunity. In the context of recent advances, we review here the relationship between MR1, antigen, and TCR usage among MAIT and other MR1-reactive T cells and provide a speculative discussion.


Asunto(s)
Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Menor/inmunología , Células T Invariantes Asociadas a Mucosa/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Animales , Humanos , Activación de Linfocitos/inmunología
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