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1.
Small ; 20(27): e2307202, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38308381

RESUMO

Thin-films of metal-organic frameworks (MOFs) have widespread potential applications, especially with the emergence of glass-forming MOFs, which remove the inherent issue of grain boundaries and allow coherent amorphous films to be produced. Herein, it is established that atomic layer deposition (ALD) of zinc oxide lends excellent control over the thickness and localization of resultant polycrystalline and glass zeolitic imidazole framework-62 (ZIF-62) thin-films within tubular α-alumina supports. Through the reduction of the chamber pressure and dose times during zinc oxide deposition, the resultant ZIF-62 films are reduced from 38 µm to 16 µm, while the presence of sporadic ZIF-62 (previously forming as far as 280 µm into the support) is prevented. Furthermore, the glass transformation shows a secondary reduction in film thickness from 16 to 2 µm.

2.
Stem Cells ; 40(12): 1134-1148, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36056823

RESUMO

Cell manufacturing facilities need to define the potency of mesenchymal stromal cells (MSCs) as cellular therapeutics in advanced clinical trials or marketing approval. Since MSCs' mechanism of action in humans is not well defined, more than a single functional property of MSCs needs to be captured as a surrogate measure of potency utilizing assay matrix technologies. However, the current limitation is the sole investigation of MSC-mediated T-cell suppression as a surrogate measure of potency. We investigated the effect of MSCs on B-cell matrix responses to be incorporated into the assay matrix potency analytical system. Our results demonstrate that MSCs inhibit B-cell differentiation and block pan-antibody secretion upon activation of B cells in the PBMCs. In contrast, MSCs are inferior in blocking B-cell matrix responses when purified B cells are used. Mechanistic analysis has demonstrated that MSC-mediated inhibition of B-cell matrix responses is non-contact dependent and Tryptophan metabolic pathway plays a major role, akin to the mechanism of MSC-mediated T-cell suppression. MSCs also inhibit both T-cell and B-cell responses when both of these lymphoid populations are concurrently activated in the PBMCs. Secretome analysis of MSC and T/B cell-activated PBMC cocultures identified direct and inverse correlative matrix signatures between humoral antibody isotypes and secretory molecules. The current analysis of the combined and concomitant investigation of T-cell and B-cell matrix responses fulfills the potency assay matrix strategy by incorporating MSCs' interaction with more than a single inflammatory immune responder.


Assuntos
Leucócitos Mononucleares , Células-Tronco Mesenquimais , Humanos , Leucócitos Mononucleares/metabolismo , Medula Óssea , Linfócitos T , Técnicas de Cocultura , Células-Tronco Mesenquimais/metabolismo , Proliferação de Células , Células da Medula Óssea
3.
Molecules ; 28(3)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36771035

RESUMO

Angiotensin II (Ang II), a peptide hormone generated as part of the renin-angiotensin system, has been implicated in the pathophysiology of many cardiovascular diseases such as peripheral artery disease, heart failure, hypertension, coronary artery disease and other conditions. Liraglutide, known as an incretin mimetic, is one of the glucagon-like peptide-1 (GLP-1) receptor agonists, and has been proven to be effective in the treatment of cardiovascular disorders beyond adequate glycemic control. The objective of this review is to compile our recent experimental outcomes-based studies, and provide an overview the cardiovascular protection from liraglutide against Ang II- and pressure overload-mediated deleterious effects on the heart. In particular, the mechanisms of action underlying the inhibition of oxidative stress, vascular endothelial dysfunction, hypertension, cardiac fibrosis, left ventricular hypertrophy and heart failure with liraglutide are addressed. Thus, we support the notion that liraglutide continues to be a useful add-on therapy for the management of cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Hipertensão , Humanos , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Doenças Cardiovasculares/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Angiotensina II , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico
4.
Cereb Cortex ; 31(11): 5042-5055, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34165137

RESUMO

As our understanding of volitional motor function increases, it is clear that complex movements are the result of the interactions of multiple cortical regions rather than just the output properties of primary motor cortex. However, our understanding of the interactions among these regions is limited. In this study, we used the activity-dependent stimulation (ADS) technique to determine the short/long-term effects on network activity and neuroplasticity of intracortical connections. ADS uses the intrinsic neural activity of one region to trigger stimulations in a separate region of the brain and can manipulate neuronal connectivity in vivo. Our aim was to compare single-unit neuronal activity within premotor cortex (rostral forelimb area, [RFA] in rats) in response to ADS (triggered from RFA) and randomly-generated stimulation in the somatosensory area (S1) within single sessions and across 21 consecutive days of stimulation. We examined firing rate and correlation between spikes and stimuli in chronically-implanted healthy ambulatory rats during spontaneous and evoked activity. At the end of the treatment, we evaluated changes of synaptophysin expression. Our results demonstrated the ability of ADS to modulate RFA firing properties and to promote synaptogenesis in S1, strengthening the idea that this Hebbian-inspired protocol can be used to modulate cortical connectivity.


Assuntos
Córtex Motor , Animais , Estimulação Elétrica/métodos , Membro Anterior/fisiologia , Córtex Motor/fisiologia , Plasticidade Neuronal , Neurônios/fisiologia , Ratos
5.
J Stroke Cerebrovasc Dis ; 31(8): 106553, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35689934

RESUMO

OBJECTIVES: Nearly all data on mechanical thrombectomy for acute ischemic stroke is based on procedures performed on biplane angiography systems. However, thrombectomy may be performed on single-plane systems in situations of triage or limited resources. We present the first US study comparing the safety and effectiveness of mechanical thrombectomy performed on single-plane vs. biplane systems. METHODS AND METHODS: A retrospective review of a prospectively maintained database identified all patients treated with thrombectomy between July 2020 and July 2021 by a high-volume practice. Patients were dichotomized into those treated on single plane and biplane systems. Demographic, procedural, clinical and follow-up characteristics were compared. RESULTS: Of the 246 patients treated with mechanical thrombectomy, 70 (33%) and 141 (66%) patients were treated on SP and BP systems, respectively. No significant differences were detected in follow-up 'good functional outcome' (mRS ≤ 2; SP 51% vs BP 43%, p = 0.14), successful recanalization (SP 87% vs BP 88%, p = 0.72), intra-procedural vascular injury (SP 3% vs BP 2%, p = 0.96), or time from groin puncture to reperfusion (SP 24 min vs BP 26 min, p = 0.58). Additionally, no significant differences were detected in peri-procedural complications, fluoroscopy times or total radiation. Patients treated on single plane systems required significantly more contrast. CONCLUSIONS: Mechanical thrombectomy for acute ischemic stroke performed on single plane angiography systems is as safe and efficacious as when performed on biplane systems. Our results may have implications for increasing stroke care access, both domestically in underserved/rural areas and internationally when considering requirements for stroke care in lower-income countries.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Angiografia/efeitos adversos , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Trombectomia/efeitos adversos , Trombectomia/métodos , Resultado do Tratamento
6.
J Vasc Surg ; 73(1): 48-60.e1, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32437949

RESUMO

OBJECTIVE: Natural history studies of type B aortic dissection (TBAD) commonly report all-cause mortality. Our aim was to determine cause-specific mortality in TBAD and to evaluate the clinical characteristics associated with aorta-related and nonaorta-related mortality. METHODS: Clinical and administrative records were reviewed for patients with acute TBAD between 1995 and 2017. Demographics, comorbidities, presentation, and initial imaging findings were abstracted. Cause of death was ascertained through a multimodality approach using electronic health records, obituaries, social media, Social Security Death Index, and state mortality records. Causes of death were classified as aorta related, nonaorta related, or unknown. A Fine-Gray multivariate competing risk regression model for subdistribution hazard ratio was employed to analyze the association of clinical characteristics with aorta-related and nonaorta-related mortality. RESULTS: A total of 275 individuals met inclusion criteria (61.1 ± 13.7 years, 70.9% male, 68% white). Mean survival after discharge was 6.3 ± 4.7 years. Completeness of follow-up Clark C index was 0.87. All-cause mortality was 50.2% (n = 138; mean age, 70.1 ± 14.6 years) including an in-hospital mortality of 8.4%. Cause-specific mortality was aorta related, nonaorta related, and unknown in 51%, 43%, and 6%, respectively. Compared with patients with nonaorta-related mortality, patients with aorta-related mortality were younger at acute TBAD (69.5 ± 11.2 years vs 61.6 ± 15.5 years; P = .001), underwent more descending thoracic aortic repairs (19.4% vs 45.8%; P = .002), and had a shorter survival duration (5.7 ± 3.9 vs 3.4 ± 4.5 years; P = .002). There was clear variation in cause of death by each decade of life, with higher aorta-related mortality among those younger than 50 years and older than 70 years and a stepwise increase in nonaorta-related mortality with each increasing decade (P < .001). All-cause mortality at 1 year, 3 years, and 10 years was 15%, 24%, and 57%, respectively. After accounting for competing risks, the cumulative incidence of aorta-related mortality at 1 year, 3 years, and 10 years was 8.9%, 16.5%, and 27.2%, respectively, and that of nonaorta-related mortality was 2.7%, 7.2%, and 29%, respectively. A maximum descending thoracic aortic diameter >4 cm was associated with an increase in hazard of aorta-related mortality by 84% (subdistribution hazard ratio, 1.84; 95% confidence interval, 1.03-3.28) on multivariate competing risk regression analysis. CONCLUSIONS: TBAD is associated with high 10-year mortality. Those at risk for aorta-related mortality have a clinical phenotype different from that of individuals at risk for nonaorta-related mortality. This information is important for building risk prediction models that account for competing mortality risks and to direct optimal and individualized surgical and medical management of TBAD.


Assuntos
Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/mortalidade , Dissecção Aórtica/mortalidade , Implante de Prótese Vascular/métodos , Procedimentos Endovasculares/métodos , Medição de Risco/métodos , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/cirurgia , Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/cirurgia , Causas de Morte/tendências , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Washington/epidemiologia
7.
J Pediatr ; 216: 95-100.e2, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610928

RESUMO

OBJECTIVE: To characterize the effects of a patent ductus arteriosus (PDA) on different organ blood flows in infants born preterm. STUDY DESIGN: Infants born preterm at ≤30 weeks of gestational age had daily echocardiography and Doppler assessments of middle cerebral artery, celiac artery, superior mesenteric (SMA), and renal arteries (RA) during the first postnatal week. Abnormal organ blood flow was defined as either reverse or absent diastolic flow, abnormally low mean or systolic velocities, or abnormally high pulsatility or resistance index. RESULTS: Twenty-five infants born very preterm (gestational age 27.0 ± 2.1 weeks) were enrolled. PDA presence at time of measurement increased the risk of abnormal organ blood flows (39% vs 8%, P < .001). Ductal diameter and left atrium-to-aortic root (LA/Ao) ratio correlated positively with resistance index (celiac artery, SMA, RA), and negatively with mean velocity (ductal diameter: SMA, RA; LA/Ao ratio: RA). A PDA >2.0 mm, LA/Ao ratio >1.4, and their combination were associated with 8.0 (95% CI 1.6-39.4)-, 6.7 (1.3-34.7)-, and 38.2 (3.2-455.5)-fold increase in risk of abnormal organ blood flow index, respectively. Abnormal descending aorta flow was detected in only 2% of measurements. CONCLUSIONS: Ductal size >2.0 mm and LA/Ao >1.4, especially in combination, are associated with a greater risk of abnormal organ blood flows. We suggest that Doppler assessment of the renal and superior mesenteric arteries are more likely to detect systemic hypoperfusion than the descending aorta.


Assuntos
Velocidade do Fluxo Sanguíneo , Débito Cardíaco , Permeabilidade do Canal Arterial/fisiopatologia , Permeabilidade do Canal Arterial/complicações , Ecocardiografia , Feminino , Idade Gestacional , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Estudos Prospectivos
8.
J Vasc Surg ; 70(4): 1115-1122, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30850292

RESUMO

OBJECTIVE: Management of abdominal aortic aneurysms (AAA) has undergone considerable advances over the last two decades. Our aim was to evaluate AAA-related mortality trends in Washington State over a 21-year period and to assess variation in AAA-related mortality by sex, race, and county over the same time period. We hypothesized that a significant decrease in AAA-related mortality in Washington State would be noted. METHODS: Death certificate records were obtained from the Washington State Department of Health from 1996 to 2016. Records in which AAA was listed as an underlying or associated cause of death were selected for analysis. Age-standardized mortality rates for each year were calculated using the 2016 Washington State population as the standard. Mortality trends were compared by sex and race using linear regression. County-specific age-standardized ruptured AAA (rAAA) mortality rates were compared using a Kruskal-Wallis test. RESULTS: Of the 1,014,039 deaths occurring in Washington State during the study period, 4438 (0.4%) had AAA listed as an underlying or associated cause of death (66.1% male; 94.8% white; mean age at death, 79.4 ± 9.3 years). In 64.1% of the cases, AAA was listed as the underlying cause of death. AAA-related mortality rates decreased by 62.1% over the 21 years from 5.8 to 2.2 deaths per 100,000. Notably, there was a statistically significant decrease in rAAA-related mortality rates (from 3.2 to 0.95 per 100,000, a decrease of 0.12 deaths/100,000/year; 95% confidence interval, 0.11-0.14; r2 = 0.95). Men had a significantly steeper decrease in age-standardized AAA-related mortality rates with a 55% decrease (from 6.5 to 3.0 per 100,000) vs a 41% decrease (2.4 to 1.4 per 100,000) among women. Men were younger at the time of death than women (78.1 ± 9.4 years vs 81.9 ± 8.6 years, respectively; P < .001). Individuals who were white had a significantly steeper decrease in age-standardized AAA-related mortality rates with a 53% decrease (from 5.3 to 2.5 per 100,000) compared with a 13% decrease among individuals who were nonwhite (from 1.5 to 1.3 per 100,000). Age-standardized rAAA-related mortality rates varied by county (P < .001). CONCLUSIONS: Age-standardized AAA-related mortality rate has decreased in Washington State between 1996 and 2016, with a notable decrease in the rAAA-related mortality rate. The decrease in AAA-related mortality rates varied by sex and race. Additionally, rAAA-related mortality rates differed between counties. These observations are a first step toward regional population assessments. Future work to understand the sources of variation can influence public health interventions on a state level.


Assuntos
Aneurisma da Aorta Abdominal/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/etnologia , Causas de Morte/tendências , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Distribuição por Sexo , Fatores de Tempo , Washington/epidemiologia , Adulto Jovem
9.
Eur J Pediatr ; 176(3): 293-300, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28091777

RESUMO

Ultrasonography (US) has been shown to be effective for verifying endotracheal tube (ETT) position in adults but has been less studied in infants and children. We review the literature regarding US for ETT positioning in the pediatric population. A literature search was conducted using the Ovid and MEDLINE databases with search terms regarding US relating to ETT intubation and positioning in infants and children. Most studies in neonates and infants used the midsagittal suprasternal view. Studies reported >80% visualization of the ETT tip by US, and US interpretation of the ETT position correlated with the XR position in 73-100% of cases. Studies of older children used the suprasternal views, substernal views, and mid-axillary intercostal views. US appears comparable to XR and capnography in determining ETT position in this population. CONCLUSION: US for ETT verification appears to be well tolerated in infants and children and may augment determination of proper ETT position in combination with other ETT verification modalities. Further studies are needed regarding technique and training. What is Known: • Point-of-care ultrasonography is realizing increased availability and use in several pediatric specialties. • Ultrasonography has been shown to be effective for verifying ETT position in adults but have been less studied in infants and children. What is New: • Ultrasonography for endotracheal tube verification appears to be well tolerated in infants and children. • Ultrasonography may augment determination of proper endotracheal tube position in combination with other verification modalities such as radiography and capnography in the pediatric population.


Assuntos
Intubação Intratraqueal/métodos , Ultrassonografia de Intervenção , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Intubação Intratraqueal/efeitos adversos , Sistemas Automatizados de Assistência Junto ao Leito
10.
Am J Perinatol ; 34(7): 627-632, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28030872

RESUMO

Objective Ultrasonography (US) has been shown to be effective for verifying endotracheal tube (ETT) position in adults and older children but has been less studied in the neonates and infants. The literature regarding US utility for ETT positioning in this population is reviewed. Study Design A literature search was conducted using the EMBASE, Google Scholar, MEDLINE, Ovid, and Scopus databases with search terms regarding US relating to ETT intubation and positioning in neonates and infants. Result Nine relevant studies were included for review. All studies report > 80% visualization of the ETT tip by US. US interpretation of the ETT position correlated with the radiography position in 73 to 100% of cases when the ETT tip was visible. There were variations in technique, sonographer, and sonographer training between studies. Conclusion US appears to be well tolerated by neonates and infants and may augment the determination of proper ETT position. Further studies are needed regarding optimal technique and sonographer training.


Assuntos
Intubação Intratraqueal/métodos , Traqueia/diagnóstico por imagem , Ultrassonografia/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Sistemas Automatizados de Assistência Junto ao Leito/estatística & dados numéricos
11.
Am J Perinatol ; 33(6): 525-30, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26692205

RESUMO

Objective Central catheters (CCs) are routinely used in the neonatal intensive care unit (NICU). Ultrasonography (US) has been advocated as a procedural adjunct for CC placement to better localize catheter tip position (CTP), minimize radiation exposure, and decrease procedural burden. This review evaluates the clinical benefit, practical considerations for implementation, and limitations of US for CC placement in the NICU. Study Design A literature search was conducted using the Pubmed and Ovid databases with search terms regarding the ultrasound modality relating to CCs in infants and neonates. Results Five studies regarding US-guided CC insertions and seven studies describing postinsertion US were determined pertinent to this review's objective and discussed. Conclusions At this time, the literature seems insufficient to recommend US as a replacement for radiography for CTP confirmation; however, US-guidance during insertion followed by radiographic verification can decrease line manipulations and repeat radiographs. Postinsertion assessments by US can better determine the CTP and guide repositioning decisions, reducing the likelihood of malposition and potential complications, and may be more practical for many NICUs. However, it is unclear how much training and experience is necessary to deem an individual competent for reliable and clinically beneficial bedside US evaluations.


Assuntos
Cateterismo Venoso Central/métodos , Ecocardiografia/estatística & dados numéricos , Cateterismo Venoso Central/efeitos adversos , Catéteres , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/organização & administração , Exposição à Radiação , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
J Pediatr Hematol Oncol ; 36(2): e125-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23689288

RESUMO

BACKGROUND: Burkitt lymphoma (BL) is an aggressive, rapidly proliferating neoplasm of B-cell origin. A late recurrence should be investigated to differentiate whether it is a true relapse or a de novo lymphoma as this has therapeutic implications. OBSERVATIONS: We report an HIV-negative white male individual, who at the age of 14 presented with recurrent BL in the abdomen occurring 6 years after successful treatment. Analysis of VDJ rearrangement showed marked dissimilarity in clonal peaks between the 2 tumors, suggesting that each tumor was associated with separate origins. The second tumor was treated as a de novo BL, and the patient remained in complete remission 2 years from recurrence without any evidence of the disease. CONCLUSION: We present a case with 2 distinct BLs verified by the VDJ rearrangement analysis in a non-HIV infected individual. Our case supports the finding that a genetically discrete BL can be treated as if it were a new tumor, thereby reducing chemotherapeutic burden and treatment-related morbidity associated with the regimens for relapsed or refractory disease. Analysis of VDJ rearrangement seems to be a reliable assessment of tumor clonality.


Assuntos
Linfoma de Burkitt/genética , Cadeias Pesadas de Imunoglobulinas/genética , Segunda Neoplasia Primária/genética , Recombinação V(D)J/genética , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Citometria de Fluxo , Humanos , Masculino , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/tratamento farmacológico , Reação em Cadeia da Polimerase
13.
World Neurosurg ; 176: 35-42, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37059357

RESUMO

INTRODUCTION: Spine surgery has undergone significant changes in approach and technique. With the adoption of intraoperative navigation, minimally invasive spinal surgery (MISS) has arguably become the gold standard. Augmented reality (AR) has now emerged as a front-runner in anatomical visualization and narrower operative corridors. In effect, AR is poised to revolutionize surgical training and operative outcomes. Our study examines the current literature on AR-assisted MISS, synthesizes findings, and creates a narrative highlighting the history and future of AR in spine surgery. MATERIAL AND METHODS: Relevant literature was gathered using the PubMed (Medline) database from 1975 to 2023. Pedicle screw placement models were the primary intervention in AR. These were compared to the outcomes of traditional MISS RESULTS: We found that AR devices on the market show promising clinical outcomes in preoperative training and intraoperative use. Three prominent systems were as follows: XVision, HoloLens, and ImmersiveTouch. In the studies, surgeons, residents, and medical students had opportunities to operate AR systems, showcasing their educational potential across each phase of learning. Specifically, one facet described training with cadaver models to gauge accuracy in pedicle screw placement. AR-MISS exceeded free-hand methods without unique complications or contraindications. CONCLUSIONS: While still in its infancy, AR has already proven beneficial for educational training and intraoperative MISS applications. We believe that with continued research and advancement of this technology, AR is poised to become a dominant player within the fundamentals of surgical education and MISS operative technique.


Assuntos
Realidade Aumentada , Parafusos Pediculares , Cirurgia Assistida por Computador , Humanos , Vértebras Lombares/cirurgia , Cirurgia Assistida por Computador/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
15.
Curr Stem Cell Rep ; 8(2): 72-92, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35502223

RESUMO

Purpose of Review: Cryopreservation and its associated freezing and thawing procedures-short "freeze-thawing"-are among the final steps in economically viable manufacturing and clinical application of diverse cellular therapeutics. Translation from preclinical proof-of-concept studies to larger clinical trials has indicated that these processes may potentially present an Achilles heel to optimal cell product safety and particularly efficacy in clinical trials and routine use. Recent Findings: We review the current state of the literature on how cryopreservation of cellular therapies has evolved and how the application of this technique to different cell types is interlinked with their ability to engraft and function upon transfer in vivo, in particular for hematopoietic stem and progenitor cells (HSPCs), their progeny, and therapeutic cell products derived thereof. We also discuss pros and cons how this may differ for non-hematopoietic mesenchymal stromal/stem cell (MSC) therapeutics. We present different avenues that may be crucial for cell therapy optimization, both, for hematopoietic (e.g., effector, regulatory, and chimeric antigen receptor (CAR)-modified T and NK cell based products) and for non-hematopoietic products, such as MSCs and induced pluripotent stem cells (iPSCs), to achieve optimal viability, recovery, effective cell dose, and functionality of the cryorecovered cells. Summary: Targeted research into optimizing the cryopreservation and freeze-thawing routines and the adjunct manufacturing process design may provide crucial advantages to increase both the safety and efficacy of cellular therapeutics in clinical use and to enable effective market deployment strategies to become economically viable and sustainable medicines.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36712473

RESUMO

Objective: To compare clinical outcomes associated with appropriate and inappropriate management of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) among inpatients with neurogenic bladder (NB). Design: Multicenter, retrospective cohort. Setting: The study was conducted across 4 Veterans' Affairs hospitals. Participants: The study included veterans with NB due to spinal cord injury or disorder (SCI/D), multiple sclerosis (MS), or Parkinson's disease (PD) hospitalized between January 1, 2017, and December 31, 2018, with diagnosis of ASB or UTI. Interventions: In a medical record review, we classified ASB and UTI diagnoses and treatments as appropriate or inappropriate based on national guidelines. Main outcome measures: Frequencies of Clostridioides difficile infection, acute kidney injury, 90-day hospital readmission, postculture length-of-stay (LOS), and multidrug-resistant organisms in subsequent urine cultures were compared between those who received appropriate and inappropriate management. Results: We included 170 encounters with ASB (30%) or UTI (70%) diagnoses occurring for 166 patients. Overall, 86.1% patients were male, 47.6% had SCI/D and 77.6% used bladder catheters. All ASB encounters had appropriate diagnoses, and 96.1% had appropriate treatment. In contrast, 37 UTI encounters (31.1%) had inappropriate diagnoses and 61 (51.3%) had inappropriate treatment, including 30 encounters with true ASB. Among patients with SCI/D or MS, appropriate ASB or UTI diagnosis was associated with a longer postculture LOS (median, 14 vs 7.5 days; P = .02). We did not detect any significant associations between appropriate versus inappropriate diagnosis and treatment and other outcomes. Conclusions: Almost one-third of UTI diagnoses and half of treatments in hospitalized patients with NB are inappropriate. Opportunities exist to improve ASB and UTI management in patients with NB to minimize inappropriate antibiotic use.

17.
J Perinat Med ; 39(1): 47-50, 2011 01.
Artigo em Inglês | MEDLINE | ID: mdl-20979447

RESUMO

OBJECTIVE: To evaluate whether National Institute of Child Health and Human Health and Development (NICHD) fetal heart rate categories were predictive of neonatal survival in periviable pregnancies. METHODS: We reviewed the charts of 57 infants delivered at 23 and 24 weeks' gestation. Fetal heart rate tracings were evaluated following the NICHD 2008 criteria, using the acceleration height of 10 bpm and duration of 10 s. Multiple logistic regression analyses were performed using survival, fetal morbidities, and cord pH <7.1 as dependent variables. Independent variables included fetal heart rate category, mode of delivery, resuscitation, and histological chorioamnionitis. Outcomes of infants delivered at 23 and 24 weeks were also compared. RESULTS: In 23-week pregnancies, fetal heart rate category 2 was associated with improved short-term survival compared to category 3 (OR 1.3, 95% CI 0.11-15.7). Cesarean delivery and histological chorioamnionitis were not predictive of survival [(OR 0.5, 95% CI 0.04-7.1, and OR 0.4, 95% CI 0.02-6.85), respectively]. Long-term survival for infants born at 23 and 24 weeks was 8% and 56%, respectively. CONCLUSIONS: The NICHD fetal heart rate category during labor may be associated with survival for infants born at 23 and 24 weeks of gestation. Cesarean delivery was not associated with improved survival.


Assuntos
Viabilidade Fetal , Idade Gestacional , Frequência Cardíaca Fetal , Algoritmos , Feminino , Humanos , National Institute of Child Health and Human Development (U.S.) , Valor Preditivo dos Testes , Gravidez , Estados Unidos
18.
Crit Care Explor ; 3(1): e0313, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33458681

RESUMO

To develop and characterize a machine learning algorithm to discriminate acute respiratory distress syndrome from other causes of respiratory failure using only ventilator waveform data. DESIGN: Retrospective, observational cohort study. SETTING: Academic medical center ICU. PATIENTS: Adults admitted to the ICU requiring invasive mechanical ventilation, including 50 patients with acute respiratory distress syndrome and 50 patients with primary indications for mechanical ventilation other than hypoxemic respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pressure and flow time series data from mechanical ventilation during the first 24-hours after meeting acute respiratory distress syndrome criteria (or first 24-hr of mechanical ventilation for non-acute respiratory distress syndrome patients) were processed to extract nine physiologic features. A random forest machine learning algorithm was trained to discriminate between the patients with and without acute respiratory distress syndrome. Model performance was assessed using the area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value. Analyses examined performance when the model was trained using data from the first 24 hours and tested using withheld data from either the first 24 hours (24/24 model) or 6 hours (24/6 model). Area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value were 0.88, 0.90, 0.71, 0.77, and 0.90 (24/24); and 0.89, 0.90, 0.75, 0.83, and 0.83 (24/6). CONCLUSIONS: Use of machine learning and physiologic information derived from raw ventilator waveform data may enable acute respiratory distress syndrome screening at early time points after intubation. This approach, combined with traditional diagnostic criteria, could improve timely acute respiratory distress syndrome recognition and enable automated clinical decision support, especially in settings with limited availability of conventional diagnostic tests and electronic health records.

19.
Clin Neurophysiol ; 131(11): 2527-2536, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32927206

RESUMO

OBJECTIVE: To investigate the diagnostic utility of high frequency oscillations (HFOs) via scalp electroencephalogram (EEG) in infantile spasms. METHODS: We retrospectively analyzed interictal slow-wave sleep EEGs sampled at 2,000 Hz recorded from 30 consecutive patients who were suspected of having infantile spasms. We measured the rate of HFOs (80-500 Hz) and the strength of the cross-frequency coupling between HFOs and slow-wave activity (SWA) at 3-4 Hz and 0.5-1 Hz as quantified with modulation indices (MIs). RESULTS: Twenty-three patients (77%) exhibited active spasms during the overnight EEG recording. Although the HFOs were detected in all children, increased HFO rate and MIs correlated with the presence of active spasms (p < 0.001 by HFO rate; p < 0.01 by MIs at 3-4 Hz; p = 0.02 by MIs at 0.5-1 Hz). The presence of active spasms was predicted by the logistic regression models incorporating HFO-related metrics (AUC: 0.80-0.98) better than that incorporating hypsarrhythmia (AUC: 0.61). The predictive performance of the best model remained favorable (87.5% accuracy) after a cross-validation procedure. CONCLUSIONS: Increased rate of HFOs and coupling between HFOs and SWA are associated with active epileptic spasms. SIGNIFICANCE: Scalp-recorded HFOs may serve as an objective EEG biomarker for active epileptic spasms.


Assuntos
Ondas Encefálicas/fisiologia , Encéfalo/fisiopatologia , Couro Cabeludo/fisiopatologia , Espasmos Infantis/diagnóstico , Mapeamento Encefálico/métodos , Eletroencefalografia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Espasmos Infantis/fisiopatologia
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