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1.
Transplantation ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33795598

RESUMO

BACKGROUND: Ruxolitinib, a JAK1/2 inhibitor, is used to treat chronic graft-versus-host-disease (cGVHD) in adult allogeneic hematopoietic stem cell transplant patients, but experience in children is limited, perhaps due to lack of pediatric dosing information. In this report we describe our pediatric and young adult dosing strategy experience in cGVHD. METHODS: Ruxolitinib was administered orally at 5mg twice daily for children ≥25kg or 2.5mg twice daily if <25kg. The dose was halved with concurrent azole administration and increased to a maximum of 10mg twice daily if tolerated. Responses were evaluated using the 2014 NIH consensus criteria. Phosphorylation of lymphocyte STAT5 following dosing, a surrogate of JAK inhibition, was evaluated by flow cytometry. RESULTS: Twenty patients with a median age 14.6 years (range 5-26 years) received ruxolitinib for severe (n=9) and moderate (n=11) cGVHD. Median steroid dose was 0.5mg/kg/day (range 0.08-1.5mg/kg/day) at ruxolitinib initiation. Two patients with moderate cGVHD achieved a complete response (CR), while 12 patients achieved a partial response (PR) at a median of 48 days (range 17-98 days) from first ruxolitinib dose, for an overall response rate of 70%. Eleven patients are maintaining their PRs. pSTAT5 on lymphocytes was absent or decreased (0-6% events) in 5 evaluated patients, suggesting adequate inhibition. Three patients discontinued ruxolitinib due to neutropenia, thrombocytopenia, or elevated alanine aminotransferase. Four patients developed bacterial infections, and three experienced symptomatic viral infections. Two patients died from complications related to progressive severe cGVHD. CONCLUSION: Ruxolitinib using our dosing strategy demonstrates promise for treating cGVHD in children.Supplemental Visual Abstract; http://links.lww.com/TP/C202.

2.
J Immunother Cancer ; 9(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33722907

RESUMO

BACKGROUND: Oncolytic viruses reduce tumor burden in animal models and have generated promising results in clinical trials. However, it is likely that oncolytic viruses will be more effective when used in combination with other therapies. Current therapeutic approaches, including chemotherapeutics, come with dose-limiting toxicities. Another option is to combine oncolytic viruses with immunotherapeutic approaches. METHODS: Using experimental models of metastatic 4T1 breast cancer and ID8 ovarian peritoneal carcinomatosis, we examined natural killer T (NKT) cell-based immunotherapy in combination with recombinant oncolytic vesicular stomatitis virus (VSV) or reovirus. 4T1 mammary carcinoma cells or ID8 ovarian cancer cells were injected into syngeneic mice. Tumor-bearing mice were treated with VSV or reovirus followed by activation of NKT cells via the intravenous administration of autologous dendritic cells loaded with the glycolipid antigen α-galactosylceramide. The effects of VSV and reovirus on immunogenic cell death (ICD), cell viability and immunogenicity were tested in vitro. RESULTS: VSV or reovirus treatments followed by NKT cell activation mediated greater survival in the ID8 model than individual therapies. The regimen was less effective when the treatment order was reversed, delivering virus treatments after NKT cell activation. In the 4T1 model, VSV combined with NKT cell activation increased overall survival and decreased metastatic burden better than individual treatments. In contrast, reovirus was not effective on its own or in combination with NKT cell activation. In vitro, VSV killed a panel of tumor lines better than reovirus. VSV infection also elicited greater increases in mRNA transcripts for proinflammatory cytokines, chemokines, and antigen presentation machinery compared with reovirus. Oncolytic VSV also induced the key hallmarks of ICD (calreticulin mobilization, plus release of ATP and HMGB1), while reovirus only mobilized calreticulin. CONCLUSION: Taken together, these results demonstrate that oncolytic VSV and NKT cell immunotherapy can be effectively combined to decrease tumor burden in models of metastatic breast and ovarian cancers. Oncolytic VSV and reovirus induced differential responses in our models which may relate to differences in virus activity or tumor susceptibility.

3.
Atherosclerosis ; 321: 1-7, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33582446

RESUMO

BACKGROUND AND AIMS: Identifying patient subgroups with cardiovascular disease (CVD) at highest risk for recurrent events remains challenging. Angiographic features may provide incremental value in risk prediction beyond clinical characteristics. METHODS: We included all cardiac catheterization patients from the Duke Databank for Cardiovascular Disease with significant coronary artery disease (CAD; 07/01/2007-12/31/2012) and an outpatient follow-up visit with a primary care physician or cardiologist in the same health system within 3 months post-catheterization. Follow-up occurred for 3 years for the primary major adverse cardiovascular event endpoint (time to all-cause death, myocardial infarction [MI], or stroke). A multivariable model to predict recurrent events was developed based on clinical variables only, then adding angiographic variables from the catheterization. Next, we compared discrimination of clinical vs. clinical plus angiographic risk prediction models. RESULTS: Among 3366 patients with angiographically-defined CAD, 633 (19.2%) experienced cardiovascular events (death, MI, or stroke) within 3 years. A multivariable model including 18 baseline clinical factors and initial revascularization had modest ability to predict future atherosclerotic cardiovascular disease events (c-statistic = 0.716). Among angiographic predictors, number of diseased vessels, left main stenosis, left anterior descending stenosis, and the Duke CAD Index had the highest value for secondary risk prediction; however, the clinical plus angiographic model only slightly improved discrimination (c-statistic = 0.724; delta 0.008). The net benefit for angiographic features was also small, with a relative integrated discrimination improvement of 0.05 (95% confidence interval: 0.03-0.08). CONCLUSIONS: The inclusion of coronary angiographic features added little incremental value in secondary risk prediction beyond clinical characteristics.

4.
Circ Cardiovasc Qual Outcomes ; 14(3): e007187, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33596663

RESUMO

BACKGROUND: Health status assessment is essential for documenting the benefit of transcatheter aortic valve replacement (TAVR) or transcatheter mitral valve repair on patients' symptoms, function, and quality of life. Health status can also be a powerful marker for subsequent clinical outcomes, but its prognostic importance around the time of both TAVR and transcatheter mitral valve repair has not been fully defined. METHODS: Among 73 699 patients who underwent transfemoral TAVR or transcatheter mitral valve repair between 2011 and 2018 (mean age, 81.9±7.0 years, 53% men, 92% TAVR), we constructed sequential models examining the association of health status (as assessed with the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score; KCCQ-OS) at baseline, 30 days, change from baseline to 30 days, and combinations of these assessments with death and heart failure (HF) hospitalization from 30 days to 1 year. RESULTS: Although higher baseline KCCQ-OS and 30-day KCCQ-OS scores were each associated with lower risk of death and HF hospitalization (in individual models and in a model including both measures), the 30-day KCCQ-OS was most predictive (death: hazard ratio, 0.89 per 5-point increase [95% CI, 0.89-0.90]; HF hospitalization: hazard ratio, 0.91 [95% CI, 0.90-0.91]). The 30-day KCCQ-OS also was most predictive when included in a separate model with change in KCCQ from baseline to 30 days. Similar findings were noted for the outcomes of death and of HF hospitalization, unadjusted and adjusted for patient factors. All interaction terms between procedure type and KCCQ were not significant, suggesting that health status provided similar prognostic information in both procedures. CONCLUSIONS: The patient's assessment of their health status immediately before and 30 days after TAVR and transcatheter mitral valve repair is associated with subsequent risk of death and HF hospitalization, with the 30-day assessment being most strongly associated with outcomes. Our findings support the routine use of KCCQ data as a prognostic tool.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33605695

RESUMO

INTRODUCTION: Never-frozen liquid plasma (LQP) was found to reduce component waste, decrease healthcare expenses, and have a superior hemostatic profile compared to fresh frozen plasma (FFP). Although transfusing LQP in hemorrhaging patients has become more common, its clinical effectiveness remains to be explored. This study aims to examine outcomes of trauma patients transfused with LQP compared to thawed FFP. METHODS: Adult (≥18 years) trauma patients receiving early (≤4 hours) plasma transfusions were identified in the Trauma Quality Improvement Program 2017. Patients were stratified into those receiving LQP vs. FFP. Propensity-score matching in a 1:2 ratio was performed. Primary outcome measures were mortality and time to first plasma unit transfusion. Secondary outcome measures were major complications and hospital length of stay (LOS). RESULTS: A total of 107 adult trauma patients receiving LQP were matched to 214 patients receiving FFP. Mean age was 48±19 years, 73% were male, and median ISS was 27 [23-41]. A total of 42% of patients were in shock, 22% had penetrating injuries, and 31% required surgical intervention for hemorrhage control. Patients received a median of 4 [2,6] units of PRBC, 2 [1,3] units of LQP or FFP, and 1 [0,1] unit of platelets. The median time to the first LQP unit transfused was significantly shorter compared to the first FFP unit transfused (54 [28-79] vs. 98 [59-133] minutes; p<0.001). Rates of 24-hour mortality (2.8 vs. 3.7%; p=0.664) and in-hospital mortality (16.8 vs. 20.1%; p=0.481) were not different between the LQP and FFP groups. Similarly, there was no difference in major complications (15.9 vs. 21.5%; p=0.233) and hospital LOS (12 [6-21] vs. 12 [6-23] days; p=0.826). CONCLUSION: LQP is safe and effective in resuscitating trauma patients. LQP has the potential to expand our transfusion armamentarium given its longer storage time and immediate availability. STUDY TYPE: Prognostic. LEVEL OF EVIDENCE: III.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33605704

RESUMO

INTRODUCTION: Nonoperative management of acute calculous cholecystitis (ACC) in the frail geriatric population is underexplored. The aim of our study was to examine long-term outcomes of frail geriatric patients with ACC treated with cholecystectomy compared to initial nonoperative management. METHODS: We conducted a 2017 analysis of the Nationwide Readmissions Database and included frail geriatric (≥65 years) patients with ACC. Frailty was assessed using the 5-factor modified frailty index (mFI). Patients were stratified into those undergoing cholecystectomy at index admission (OP) vs. those managed with non-operative intervention (NOP). The NOP group was further subdivided into those who received antibiotics only, and those who received percutaneous drainage. Primary outcomes were procedure-related complications in the OP group and 6-month failure of NOP (readmission with cholecystitis). Secondary outcomes were mortality and overall hospital length of stay (LOS). RESULTS: A total of 53,412 geriatric patients with ACC were identified, 51.0% of whom were frail: 16,791 (61.6%) in OP group and 10,472 (38.4%) in NOP group (3,256 had percutaneous drainage, 7,216 received antibiotics only). Patients were comparable in age (76±7 vs. 77±8 years;p=0.082) and mFI (0.47 vs. 0.48;p=0.132). Procedure-related complications in the OP group was 9.3% and 6-month failure of NOP was 18.9%. Median time to failure of NOP management was 36[12-78] days. Mortality was higher in the frail NOP group (5.2 vs. 3.2%;p<0.001). The NOP group had more days of hospitalization (8[4-15] vs. 5[3-10];p<0.001). Both receiving antibiotics only (OR 1.6 [1.3-2.0]; p<0.001) and receiving percutaneous drainage (OR 1.9 [1.7-2.2]; p<0.001) were independently associated with increased mortality. CONCLUSION: One in five patients failed NOP and subsequently had complicated hospital stays. Non-operative management of frail elderly ACC patients may be associated with significant morbidity and mortality. LEVEL OF EVIDENCE: Level III Prognostic.

8.
Blood Adv ; 5(1): 1-11, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33570619

RESUMO

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication of hematopoietic stem cell transplantation (HSCT). A single-center prospective screening study has shown that the incidence of TA-TMA is much higher than prior retrospective studies that did not systematically screen. These data have not been replicated in a multicenter study. Our objective was to determine the incidence and risk factors for TA-TMA and compare outcomes of pediatric HSCT patients with and without TA-TMA. Patients were prospectively screened for TA-TMA at participating centers using a simple to implement and inexpensive strategy from the start of the preparative regimen through day +100. TA-TMA was diagnosed if ≥4 of 7 laboratory/clinical markers diagnostic for TA-TMA were present concurrently or if tissue histology showed TA-TMA. A total of 614 patients (359 males; 58%) received prospective TA-TMA screening at 13 pediatric centers. TA-TMA was diagnosed in 98 patients (16%) at a median of 22 days (interquartile range, 14-44) posttransplant. Patients with TA-TMA had significantly increased bloodstream infections (38% [37/98] vs 21% [107/51], P ≤ .001), mean total hospitalization days (68; 95% confidence interval [CI], 63-74 vs 43; 95% CI, 41-45; P ≤ .001), and number of days spent in the intensive care unit (10.1; 95% CI, 6.4-14; vs 1.6; 95% CI, 1.1-2.2; P ≤ .001) in the first 100 days after HSCT compared with patients without TA-TMA. Overall survival was significantly higher in patients without TA-TMA (93%; 490/516) compared with patients with TA-TMA (78%; 76/98) (P ≤ .001). These data support the need for systematic screening for TA-TMA and demonstrate the feasibility and efficacy of an easy to implement strategy to do so.

9.
Blood Adv ; 5(1): 250-261, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33570643

RESUMO

Fanconi anemia (FA) is a complex genetic disorder associated with progressive marrow failure and a strong predisposition to malignancy. FA is associated with metabolic disturbances such as short stature, insulin resistance, thyroid dysfunction, abnormal body mass index (BMI), and dyslipidemia. We studied tryptophan metabolism in FA by examining tryptophan and its metabolites before and during the stress of hematopoietic stem cell transplant (HSCT). Tryptophan is an essential amino acid that can be converted to serotonin and kynurenine. We report here that serotonin levels are markedly elevated 14 days after HSCT in individuals with FA, in contrast to individuals without FA. Kynurenine levels are significantly reduced in individuals with FA compared with individuals without FA, before and after HSCT. Most peripheral serotonin is made in the bowel. However, serotonin levels in stool decreased in individuals with FA after transplant, similar to individuals without FA. Instead, we detected serotonin production in the skin in individuals with FA, whereas none was seen in individuals without FA. As expected, serotonin and transforming growth factor ß (TGF-ß) levels were closely correlated with platelet count before and after HSCT in persons without FA. In FA, neither baseline serotonin nor TGF-B correlated with baseline platelet count (host-derived platelets), only TGF-B correlated 14 days after transplant (blood bank-derived platelets). BMI was negatively correlated with serotonin in individuals with FA, suggesting that hyperserotonemia may contribute to growth failure in FA. Serotonin is a potential therapeutic target, and currently available drugs might be beneficial in restoring metabolic balance in individuals with FA.

10.
Chem Commun (Camb) ; 57(7): 919-922, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33393538

RESUMO

The regioselective γ-C-H amination of the side-chain of saturated 2-alkyl nitrogen heterocycles is reported, proceeding through a sulfamide-directed 1,6-radical translocation. The practicality of this rapid access to 1,3-diamines is highlighted in a short synthesis of the alkaloid tetraponerine T8 and non-natural analogues.

11.
J Am Heart Assoc ; 10(2): e016835, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33432843

RESUMO

Background Evidence-based therapies are generally underused for cardiovascular risk reduction; however, less is known about contemporary patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Methods and Results Pharmacy and medical claims data from within Anthem were queried for patients with established atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Using an index date of April 18, 2018, we evaluated the proportion of patients with a prescription claim for any of the 3 evidence-based therapies on, or covering, the index date ±30 days: high-intensity statin, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and sodium glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist. The potential benefit of achieving 100% adoption of all 3 evidence-based therapies was simulated using pooled treatment estimates from clinical trials. Of the 155 958 patients in the sample, 24.7% were using a high-intensity statin, 53.1% were using an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and 9.9% were using either an sodium glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonists. Overall, only 2.7% of the population were covered by prescriptions for all 3 evidence-based therapies, and 37.4% were on none of them. Over a 12-month period, 70.6% of patients saw a cardiologist, while only 18% saw an endocrinologist. Increasing the use of evidence-based therapies to 100% over 3 years of treatment could be expected to reduce 4546 major atherosclerotic cardiovascular events (myocardial infarction, stroke, or cardiovascular death) in eligible but untreated patients. Conclusions Alarming gaps exist in the contemporary use of evidence-based therapies in this large population of insured patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. These data provide a call to action for patients, providers, industry, regulators, professional societies, and payers to close these gaps in care.

12.
Pediatr Blood Cancer ; 68(4): e28891, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33442960

RESUMO

BACKGROUND: Accurate risk stratification of Langerhans cell histiocytosis (LCH) is essential as management can range from conservative in single system, low risk for central nervous system (CNS) involvement lesions to intensive chemotherapy for multisystem or high-risk disease. Additionally, being able to differentiate metabolically active from inactive lesions is essential for both prognostic reasons and to avoid potentially unnecessary treatment. METHODS: A retrospective review was performed on all patients with histopathology-confirmed LCH at Cincinnati Children's Hospital Medical Center (CCHMC) between 2009 and 2019. RESULTS: One hundred seven positron emission tomography (PET)/computerized tomography (CT) images were included in the review. A discrepancy between PET/CT and conventional imaging occurred on 53 occasions. On 13 occasions, increased uptake was observed on PET in an area with no identifiable lesion on conventional imaging. On 40 occasions, lesions were found on conventional imaging where no increased uptake was observed on PET. On eight skeletal surveys, three other radiographs, four diagnostic CTs, five localization CTs, and one bone scan, no lesion was identified in an area with increased fluorodeoxyglucose (FDG) uptake. This occurred exclusively in bone. On nine skeletal surveys, one other radiograph, four diagnostic CTs, six localization CTs, 19 magnetic resonance imaging (MRI) scans, and one bone scan, a lesion was identified in a location without increased FDG uptake. This occurred in bone, CNS, and lungs. CONCLUSION: F-18-FDG PET/CT is vital in the evaluation of LCH lesions given its ability to detect LCH lesions not detectable on conventional imaging modalities, as well as its ability to distinguish metabolically active from inactive disease. MRI and diagnostic CT are still useful adjunctive tests for identification of CNS and lung lesions.

13.
Chem Commun (Camb) ; 57(5): 599-602, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33345263

RESUMO

Regioselective and stereospecific directed C-H arylation of simple amine substrates, and cyclisation, delivered 30 diverse, three-dimensional scaffolds. The unified approach significantly expanded the range of bridged ring systems that contain both a nitrogen atom and an aromatic ring.

14.
Am J Cardiol ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33279483

RESUMO

We sought to determine if the absence of hypertension in older adults can be used to identify those at lower risk of atherosclerotic cardiovascular disease (ASCVD). We identified participants ≥75 years old free of cardiovascular disease (CVD) in the National Institutes of Health Pooled Cohorts with and without hypertension. We assessed the association between systolic blood pressure (BP), diastolic BP, and cardiovascular events using multivariable modeling. The association between predicted ASCVD risk and observed events was compared. Of 2667 adults aged ≥75 years, 67.9% had hypertension. Lower systolic BP correlated with lower CVD event rates. ASCVD predicted risk score and systolic BP were both independently associated with ASCVD event rates. Among adults with similar ASCVD predicted risk estimates, those without (vs. with) hypertension had lower observed event rates across the predicted risk spectrum. The absence of hypertension may help refine the risk stratification of older adults, particularly those with intermediate predicted risk.

15.
J Knee Surg ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33231282

RESUMO

Patella alta is a common and significant abnormality responsible for many patellofemoral joint-related conditions. Many methods of patella height measurements are described; however, patellotrochear index (PTI) is the most logical method as it measures the direct relation between patella and trochlea. The aim of this study is to investigate PTI in normal healthy asymptomatic volunteers to understand the patellofemoral relation in normal knees. Twenty-five healthy volunteers underwent magnetic resonance imaging (MRI) scans of both knees. Two observers independently measured PTI on two different occasions at 6-week interval. Statistical analysis was performed to identify intra- and interobserver correlation between two observers and the mean value of PTI. Agreement analysis was performed according to Bland and Altman. Comparisons of means were made using paired t-tests. The mean age of 25 healthy volunteers was 21.28 years (19-23) with a male:female ratio of 14:11. The overall mean PTI value of all observations was 36.8% and pooled standard deviation (SD) 11.5%. Intraclass correlation (ICC) testing showed "good" interobserver ICC between two observers for PTI for both first (0.80) and second (0.84) set of measurements. There was "excellent" intraobserver correlation for two sets of measurements of PTI made by each first (0.96) and second (0.91) observer. Intraobserver repeatability for PTI was ± 0.07 and ± 0.1, respectively, for the first and second observer. Interobserver repeatability for PTI was ± 0.159 and ± 0.133, respectively, for the first and second set of measurements. Analysis of individual measurements of patella and trochlear articular cartilage revealed that the largest repeatability values were for trochlea measurements. The study reports that the average PTI in asymptomatic healthy knee utilizing current clinical MRI scanning conditions is 36.8%. This provides surgeons with a gold standard normal PTI value, which can serve as a target value in clinical diagnosis as well as surgical correction of patella height. There is good to excellent intra- and interobserver correlation with limited variability in assessing patella height using PTI on MRI scan.

16.
Cell Stem Cell ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33232662

RESUMO

Squamous cell carcinoma (SCC) is a global public health burden originating in epidermal stem and progenitor cells (ESPCs) of the skin and mucosa. To understand how genetic risk factors contribute to SCC, studies of ESPC biology are imperative. Children with Fanconi anemia (FA) are a paradigm for extreme SCC susceptibility caused by germline loss-of-function mutations in FA DNA repair pathway genes. To discover epidermal vulnerabilities, patient-derived pluripotent stem cells (PSCs) conditional for the FA pathway were differentiated into ESPCs and PSC-derived epidermal organotypic rafts (PSC-EORs). FA PSC-EORs harbored diminished cell-cell junctions and increased proliferation in the basal cell compartment. Furthermore, desmosome and hemidesmosome defects were identified in the skin of FA patients, and these translated into accelerated blistering following mechanically induced stress. Together, we demonstrate that a critical DNA repair pathway maintains the structure and function of human skin and provide 3D epidermal models wherein SCC prevention can now be explored.

17.
Blood Adv ; 4(22): 5745-5754, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33216887

RESUMO

BK polyomavirus (BKPyV) infection is a major complication of hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT). Treatment options are limited, poorly effective, and have significant toxicities. Cellular therapy using T cells directed against BKPyV is an emerging therapy, and we report efficacy in controlling BKPyV-associated disease in highly immunocompromised patients. Virus-specific T cells (VSTs) against BKPyV were manufactured using either blood from the patient's stem cell donor (donor-derived VSTs) or from unrelated donors (third-party VSTs). VSTs were used to treat BKPyV in 38 HSCT recipients and 3 SOT recipients between June 2017 and December 2019. Overall response rate was 86% in patients treated for BK viremia, 100% in patients treated for hemorrhagic cystitis, and 87% in patients treated for both BK viremia and hemorrhagic cystitis. No infusional toxicity, de novo graft-versus-host disease, or rejection of the organ occurred attributable to the VST infusion. BKPyV-specific immune responses were demonstrated by interferon-γ production by peripheral blood mononuclear cells postinfusion in response to BKPyV antigens. VSTs are a safe and potentially effective strategy to treat BKPyV and associated symptoms in recipients of HSCT and SOT. Cellular therapy should be considered for all patients with BKPyV and underlying immune suppression at risk of complications. This trial was registered at www.clinicaltrials.gov as #NCT02532452.

18.
Cardiovasc Diagn Ther ; 10(5): 1480-1507, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33224769

RESUMO

Atherosclerotic cardiovascular disease is a key public health concern worldwide and leading cause of morbidity, mortality and health economic costs. Understanding atherosclerotic plaque microstructure in relation to molecular mechanisms that underpin its initiation and progression is needed to provide the best chance of combating this disease. Evolving vessel wall-based, endovascular coronary imaging modalities, including intravascular ultrasound (IVUS), optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS), used in isolation or as hybrid modalities, have been advanced to allow comprehensive visualization of the pathological substrate of coronary atherosclerosis and accurately measure temporal changes in both the vessel wall and plaque characteristics. This has helped further our appreciation of the natural history of coronary artery disease (CAD) and the risk for major adverse cardiovascular events (MACE), evaluate the responsiveness to conventional and experimental therapeutic interventions, and assist in guiding percutaneous coronary intervention (PCI). Here we review the use of different imaging modalities for these purposes and the lessons they have provided thus far.

19.
Curr Opin Lipidol ; 31(6): 356-361, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33027227

RESUMO

PURPOSE OF REVIEW: Increasing interest has focused on the potential cardioprotective effects of the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the basis of findings from epidemiology and cohort studies. This review will summarize the findings of contemporary clinical trials of omega-3 fatty acids. RECENT FINDINGS: Although a large clinical trial performed prior to the widespread use of statins demonstrated cardiovascular benefit with fish oils, subsequent studies have failed to reproduce this result. More recent studies have demonstrated a reduction in cardiovascular risk with administration of high-dose EPA, but not a carboxylic acid formulation containing both EPA and DHA or with lower doses of omega-3 fatty acids. SUMMARY: Administration of omega-3 fatty acids differing in either composition or dose produce variable effects on cardiovascular outcomes. This has implications for both the public health and pharmacological approach to cardiovascular prevention.

20.
Injury ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33051076

RESUMO

INTRODUCTION: Rib fractures are one of the most frequent causes of morbidity following blunt injury to the chest. Many of these patients require ICU care and often develop pulmonary complications. Prior studies have attempted to identify changes in predicted lung volumes or utilized the number of rib fractures to guide clinical decisions. A rib fracture triage pathway was developed to identify which patients will benefit from ICU level of care and shorten hospital length of stay for patients that do not require ICU care. METHODS: The triage pathway utilized patient's age, number of rib fractures, significant cardiopulmonary co-morbidities, and incentive spirometry volumes to determine admission disposition. The triage pathway was implemented on November 2016. All patients with rib fractures from November 2015 to 2017 were identified in the trauma registry. Data was collected on patients age, gender, Glasgow Coma Scale on arrival (GCS), injury severity score (ISS), number of rib fractures, incentive spirometry volumes, days in intensive care (ICU), ventilator days, length of stay (LOS), complications, and mortality. Patients with severe TBI, those arriving intubated, or died within 48 h were excluded. The patients remaining were 278 patients in the pre triage pathway group and 370 in the post triage pathway. RESULTS: There was no difference in age, gender, GCS, ISS, predicted incentive spirometry or number of rib fractures. The post treatment patients required significantly lower ICU admissions (64% vs 75%, p = 0.003), significantly lower pulmonary complication (5.1% vs 10.4%, p = 0.01), and significantly shorter hospital length of stay (6.8 d vs 7.5, p = 0.001) with no difference in mortality (1.6% vs 2.5%, p = 0.42) or readmission (0.3% vs. 0.7%, p = 0.4). Patient post triage protocol were also more likely to be discharge home (81% vs 70%, p = 0.0009) with less patients going to a skilled nursing facility (13% vs 21%, p = 0.01). CONCLUSIONS: Developing a rib fracture treatment and triage pathway can decrease ICU and hospital resource utilization and decrease pulmonary complications without increase in readmissions or mortality. Patients are more likely to be discharge home over a skilled nursing facility further decreasing health care cost. Level of Evidence IV Retrospective Study, Prognostic.

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