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1.
Eur Heart J ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33596594

RESUMO

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

2.
Genome Med ; 13(1): 5, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430949

RESUMO

BACKGROUND: Ebola virus disease (EVD) is an often-fatal infection where the effectiveness of medical countermeasures is uncertain. During the West African outbreak (2013-2016), several patients were treated with different types of anti-viral therapies including monoclonal antibody-based cocktails that had the potential to neutralise Ebola virus (EBOV). However, at the time, the efficacy of these therapies was uncertain. Given the scale of the outbreak, several clinical phenotypes came to the forefront including the ability of the same virus to cause recrudescence in the same patient-perhaps through persisting in immune privileged sites. Several key questions remained including establishing if monoclonal antibody therapy was effective in humans with severe EVD, whether virus escape mutants were selected during treatment, and what is the potential mechanism(s) of persistence. This was made possible through longitudinal samples taken from a UK patient with EVD. METHODS: Several different sample types, plasma and cerebrospinal fluid, were collected and sequenced using Illumina-based RNAseq. Sequence reads were mapped both to EBOV and the human genome and differential gene expression analysis used to identify changes in the abundance of gene transcripts as infection progressed. Digital Cell Quantitation analysis was used to predict the immune phenotype in samples derived from blood. RESULTS: The findings were compared to equivalent data from West African patients. The study found that both virus and host markers were predictive of a fatal outcome. This suggested that the extensive supportive care, and most likely the application of the medical countermeasure ZMab (a monoclonal antibody cocktail), contributed to survival of the UK patient. The switch from progression to a 'fatal' outcome to a 'survival' outcome could be seen in both the viral and host markers. The UK patient also suffered a recrudescence infection 10 months after the initial infection. Analysis of the sequencing data indicated that the virus entered a period of reduced or minimal replication, rather than other potential mechanisms of persistence-such as defective interfering genomes. CONCLUSIONS: The data showed that comprehensive supportive care and the application of medical countermeasures are worth pursuing despite an initial unfavourable prognosis.

3.
J Clin Med ; 9(12)2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33256044

RESUMO

High-flow nasal therapy (HFNT) is a unique system that delivers humidified, heated oxygen-enriched air via nasal cannula at high flow rates. It is a promising therapy for chronic obstructive pulmonary disease (COPD) patients. Several studies have examined the physiologic effects of this therapy in the patient population and have revealed that it improves mucociliary clearance, reduces nasopharyngeal dead space, and subsequently increases CO2 washout. It also improves alveolar recruitment and gas exchange. These mechanisms may explain the promising results observed in recently published studies that examined the role of HFNT in stable COPD patients.

4.
Invest Radiol ; Publish Ahead of Print2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33350717

RESUMO

The aim of this study was to determine the feasibility and performance of a deep learning system used to create synthetic artificial intelligence-based fat-suppressed magnetic resonance imaging (AFSMRI) scans of the knee. MATERIALS AND METHODS: This single-center study was approved by the institutional review board. Artificial intelligence-based FS MRI scans were created from non-FS images using a deep learning system with a modified convolutional neural network-based U-Net that used a training set of 25,920 images and validation set of 16,416 images. Three musculoskeletal radiologists reviewed 88 knee MR studies in 2 sessions, the original (proton density [PD] + FSPD) and the synthetic (PD + AFSMRI). Readers recorded AFSMRI quality (diagnostic/nondiagnostic) and the presence or absence of meniscal, ligament, and tendon tears; cartilage defects; and bone marrow abnormalities. Contrast-to-noise rate measurements were made among subcutaneous fat, fluid, bone marrow, cartilage, and muscle. The original MRI sequences were used as the reference standard to determine the diagnostic performance of AFSMRI (combined with the original PD sequence). This is a fully balanced study design, where all readers read all images the same number of times, which allowed the determination of the interchangeability of the original and synthetic protocols. Descriptive statistics, intermethod agreement, interobserver concordance, and interchangeability tests were applied. A P value less than 0.01 was considered statistically significant for the likelihood ratio testing, and P value less than 0.05 for all other statistical analyses. RESULTS: Artificial intelligence-based FS MRI quality was rated as diagnostic (98.9% [87/88] to 100% [88/88], all readers). Diagnostic performance (sensitivity/specificity) of the synthetic protocol was high, for tears of the menisci (91% [71/78], 86% [84/98]), cruciate ligaments (92% [12/13], 98% [160/163]), collateral ligaments (80% [16/20], 100% [156/156]), and tendons (90% [9/10], 100% [166/166]). For cartilage defects and bone marrow abnormalities, the synthetic protocol offered an overall sensitivity/specificity of 77% (170/221)/93% (287/307) and 76% (95/125)/90% (443/491), respectively. Intermethod agreement ranged from moderate to substantial for almost all evaluated structures (menisci, cruciate ligaments, collateral ligaments, and bone marrow abnormalities). No significant difference was observed between methods for all structural abnormalities by all readers (P > 0.05), except for cartilage assessment. Interobserver agreement ranged from moderate to substantial for almost all evaluated structures. Original and synthetic protocols were interchangeable for the diagnosis of all evaluated structures. There was no significant difference for the common exact match proportions for all combinations (P > 0.01). The conspicuity of all tissues assessed through contrast-to-noise rate was higher on AFSMRI than on original FSPD images (P < 0.05). CONCLUSIONS: Artificial intelligence-based FS MRI (3D AFSMRI) is feasible and offers a method for fast imaging, with similar detection rates for structural abnormalities of the knee, compared with original 3D MR sequences.

6.
Clin Epidemiol ; 12: 1171-1181, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149694

RESUMO

Purpose: Medication patterns include all medications in an individual's clinical profile. We aimed to identify chronic co-morbidity treatment patterns through medication use among COPDGene participants and determine whether these patterns were associated with mortality, acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and quality of life. Materials and Methods: Participants analyzed here completed Phase 1 (P1) and/or Phase 2 (P2) of COPDGene. Latent class analysis (LCA) was used to identify medication patterns and assign individuals into unobserved LCA classes. Mortality, AECOPD, and the St. George's Respiratory Questionnaire (SGRQ) health status were compared in different LCA classes through survival analysis, logistic regression, and Kruskal-Wallis test, respectively. Results: LCA identified 8 medication patterns from 32 classes of chronic comorbid medications. A total of 8110 out of 10,127 participants with complete covariate information were included. Survival analysis adjusted for covariates showed, compared to a low medication use class, mortality was highest in participants with hypertension+diabetes+statin+antiplatelet medication group. Participants in hypertension+SSRI+statin medication group had the highest odds of AECOPD and the highest SGRQ score at both P1 and P2. Conclusion: Medication pattern can serve as a good indicator of an individual's comorbidities profile and improves models predicting clinical outcomes.

7.
Crit Care Explor ; 2(10): e0214, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33134932

RESUMO

Objectives: To construct a highly detailed yet practical, attainable roadmap for enhancing the likelihood of neurologically intact survival following sudden cardiac arrest. Design Setting and Patients: Population-based outcomes following out-of-hospital cardiac arrest were collated for 10 U.S. counties in Alaska, California, Florida, Ohio, Minnesota, Utah, and Washington. The 10 identified emergency medical services systems were those that had recently reported significant improvements in neurologically intact survival after introducing a more comprehensive approach involving citizens, hospitals, and evolving strategies for incorporating technology-based, highly choreographed care and training. Detailed inventories of in-common elements were collated from the ten 9-1-1 agencies and assimilated. For reference, combined averaged outcomes for out-of-hospital cardiac arrest occurring January 1, 2017, to February 28, 2018, were compared with concurrent U.S. outcomes reported by the well-established Cardiac Arrest Registry to Enhance Survival. Interventions: Most commonly, interventions and components from the ten 9-1-1 systems consistently included extensive public cardiopulmonary resuscitation training, 9-1-1 system-connected smart phone applications, expedited dispatcher procedures, cardiopulmonary resuscitation quality monitoring, mechanical cardiopulmonary resuscitation, devices for enhancing negative intrathoracic pressure regulation, extracorporeal membrane oxygenation protocols, body temperature management procedures, rapid cardiac angiography, and intensive involvement of medical directors, operational and quality assurance officers, and training staff. Measurements and Main Results: Compared with Cardiac Arrest Registry to Enhance Survival (n = 78,704), the cohorts from the 10 emergency medical services agencies examined (n = 2,911) demonstrated significantly increased likelihoods of return of spontaneous circulation (mean 37.4% vs 31.5%; p < 0.001) and neurologically favorable hospital discharge, particularly after witnessed collapses involving bystander cardiopulmonary resuscitation and shockable cardiac rhythms (mean 10.7% vs 8.4%; p < 0.001; and 41.6% vs 29.2%; p < 0.001, respectively). Conclusions: The likelihood of neurologically favorable survival following out-of-hospital cardiac arrest can improve substantially in communities that conscientiously and meticulously introduce a well-sequenced, highly choreographed, system-wide portfolio of both traditional and nonconventional approaches to training, technologies, and physiologic management. The commonalities found in the analyzed systems create a compelling case that other communities can also improve out-of-hospital cardiac arrest outcomes significantly by conscientiously exploring and adopting similar bundles of system organization and care.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33236058

RESUMO

OBJECTIVES: Endovascular and open thoraco-abdominal aortic aneurysm (TAAA) repair is associated with specific complications. Circulating dipeptidyl peptidase 3 (cDPP3) is a novel biomarker that shows a strong association with organ failure which has not been assessed in surgical settings. Therefore, the objective of this study was to assess the prognostic capabilities of cDPP3 for predicting patient survival and organ failure following open and endovascular TAAA repair. METHODS: Thirty-three patients undergoing TAAA repair were assessed in this prospective observational single-centre study. cDPP3 levels were serially measured perioperatively until 72 h after admission to the intensive care unit (ICU). In-hospital mortality and any organ failure were the clinical end points. RESULTS: Postoperative organ failure was detected in 17 patients (51.5%), and 6 patients died after surgery (18.2%). At 12 h after admission to the ICU, cDPP3 levels were significantly increased in patients who died or developed organ failure (P < 0.001). cDPP3 levels after surgery demonstrated a remarkable predictive accuracy for in-hospital mortality [12 h area under the receiver operating characteristic curve (AUC): 0.907 (P < 0.001), 24 h AUC: 0.815 (P = 0.016), 48 h AUC: 0.914 (P = 0.003)] and the development of organ failure [12 h AUC: 0.882 (P < 0.001), 24 h AUC: 0.850 (P < 0.001), 48 h AUC: 0.846 (P < 0.001)]. Additionally, a significant correlation between cDPP3, the sequential organ failure assessment score and procalcitonin, C-reactive protein and interleukin-6 levels (P < 0.001, P < 0.001, P = 0.011, P = 0.007, respectively) based on all available measurements and time points was observed. CONCLUSIONS: The present findings highlight the role of cDPP3 as an early, highly specific postoperative biomarker for prediction of in-hospital mortality and organ failure after TAAA repair.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33006443

RESUMO

BACKGROUND: Cachexia is a major cause of morbidity in pancreatic ductal adenocarcinoma (PDAC) patients. Our purpose was to understand the impact of PDAC-induced cachexia on brain metabolism in PDAC xenograft studies, to gain new insights into the causes of cachexia-induced morbidity. Changes in mouse and human plasma metabolites were characterized to identify underlying causes of brain metabolic changes. METHODS: We quantified metabolites, detected with high-resolution 1 H magnetic resonance spectroscopy, in the brain and plasma of normal mice (n = 10) and mice bearing cachexia (n = 10) or non-cachexia (n = 9) inducing PDAC xenografts as well as in human plasma obtained from normal individuals (n = 24) and from individuals with benign pancreatic disease (n = 20) and PDAC (n = 20). Statistical significance was defined as a P value ≤0.05. RESULTS: The brain metabolic signature of cachexia-inducing PDAC was characterized by a significant depletion of choline of -27% and -21% as well as increases of glutamine of 13% and 9% and formate of 21% and 14%, relative to normal controls and non-cachectic tumour-bearing mice, respectively. Good to moderate correlations with percent weight change were found for choline (r = 0.70), glutamine (r = -0.58), and formate (r = -0.43). Significant choline depletion of -38% and -30%, relative to normal controls and non-cachectic tumour-bearing mice, respectively, detected in the plasma of cachectic mice likely contributed to decreased brain choline in cachectic mice. Similarly, relative to normal controls and patients with benign disease, choline levels in human plasma samples of PDAC patients were significantly lower by -12% and -20% respectively. A comparison of plasma metabolites from PDAC patients with and without weight loss identified significant changes in glutamine metabolism. CONCLUSIONS: Disturbances in metabolites of the choline/cholinergic and glutamine/glutamate/glutamatergic neurotransmitter pathways may contribute to morbidity. Metabolic normalization may provide strategies to reduce morbidity. The human plasma metabolite changes observed may lead to the development of companion diagnostic markers to detect PDAC and PDAC-induced cachexia.

10.
J Card Surg ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032387

RESUMO

BACKGROUND: To share the results of a web-based expert panel discussion focusing on the management of acute and chronic aortic disease during the coronavirus (COVID-19) pandemic. METHODS: A web-based expert panel discussion on April 18, 2020, where eight experts were invited to share their experience with COVID-19 disease touching several aspects of aortic medicine. After each talk, specific questions were asked by the online audience, and results were immediately evaluated and shared with faculty and participants. RESULTS: As of April 18, 73.3% answered that more than 200 patients have been treated at their respective settings. Sixty-four percent were reported that their hospital was well prepared for the pandemic. In 57.7%, the percentage of infected healthcare professionals was below 5% whereas 19.2% reported the percentage to be between 10% and 20%. Sixty-seven percent reported the application of extracorporeal membrane oxygenation in less than 2% of COVID-19 patients whereas 11.8% reported application in 5%-10% of COVID-19 patients. Thirty percent of participants reported the occurrence of pulmonary embolism in COVID-19 patients. Three percent reported to have seen aortic ruptures in primarily elective patients having been postponed because of the anticipated need to provide sufficient ICU capacity because of the pandemic. Nearly 70% reported a decrease in acute aortic syndrome referrals since the start of the pandemic. CONCLUSION: The current COVID-19 pandemic has-besides the stoppage of elective referrals-also led to a decrease of referrals of acute aortic syndromes in many settings. The reluctance of patients seeking medical help seems to be a major driver. The number of patients, who have been postponed due to the provisioning of ICU resources but having experienced aortic rupture in the waiting period, is still low. Further, studies are needed to learn more about the influence that the COVID-19 pandemic has on the treatment of patients with acute and chronic aortic disease.

11.
J Clin Med ; 9(10)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066382

RESUMO

Acute kidney injury (AKI) is one of the most common post-operative complications and is closely associated with increased mortality after open and endovascular thoracoabdominal aortic aneurysm (TAAA) repair. Ribonuclease (RNase) 1 belongs to the group of antimicrobial peptides elevated in septic patients and indicates the prediction of two or more organ failures. The role of RNase 1 and its antagonist RNase inhibitor 1 (RNH1) after TAAA repair is unknown. In this study, we analyzed RNase 1 and RNH1 serum levels in patients undergoing open (n = 14) or endovascular (n = 19) TAAA repair to determine their association with post-operative AKI and in-hospital mortality. Increased RNH1 serum levels after open TAAA repair as compared with endovascular TAAA repair immediately after surgery and 12, 48, and 72 h after surgery (all p < 0.05) were observed. Additionally, elevated RNase 1 and RNH1 serum levels 12, 24, and 48 h after surgery were shown to be significantly associated with AKI (all p < 0.05). RNH1 serum levels before and RNase 1 serum levels 12 h after TAAA repair were significantly correlated with in-hospital mortality (both p < 0.05). On the basis of these findings, RNase 1 and RNH1 may be therapeutically relevant and may represent biomarkers for post-operative AKI and in-hospital mortality.

13.
J Vasc Surg ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33002587

RESUMO

OBJECTIVE: The present study evaluated the psoas muscle area and attenuation (radiodensity), quantified by computed tomography, together with clinical risk assessment, as predictors of outcomes after fenestrated and branched endovascular aortic repair (FBEVAR). METHODS: The present single-center study included 504 patients who had undergone elective FBEVAR for pararenal or thoracoabdominal aortic aneurysms. The clinical risk assessment included age, sex, comorbidities, body mass index, glomerular filtration rate, aneurysm size and extent, cardiac stress test results, ejection fraction, and American Society of Anesthesiologists (ASA) score. Preoperative computed tomography was used to measure the psoas muscle area and attenuation at the L3 level. The lean psoas muscle area (LPMA; area in cm2 multiplied by attenuation in Hounsfield units [HU]) was calculated by multiplying the area by the attenuation. The risk factors for 90-day mortality, major adverse events (MAEs), and long-term mortality were determined using multivariable analysis. MAEs included 30-day or in-hospital death, acute kidney injury, myocardial infarction, respiratory failure, paraplegia, stroke, and bowel ischemia. A novel risk stratification method was proposed according to the strongest predictors of mortality and MAEs on multivariable analysis. RESULTS: The 30-day mortality, 90-day mortality, and MAE rates were 2.0%, 5.6%, and 20%, respectively. The independent predictors of 90-day mortality were chronic obstructive pulmonary disease, chronic kidney disease, ASA score, and LPMA. The independent predictors of MAEs were aneurysm diameter, glomerular filtration rate, and LPMA. For long-term mortality, the independent predictors were chronic kidney disease, congestive heart failure, extent I-III thoracoabdominal aortic aneurysms, ASA score, and LPMA. The patients were stratified into three groups according to the ASA score and LPMA: low risk, ASA score II or LPMA >350 cm2HU (n = 290); medium risk, ASA score III and LPMA ≤350 cm2HU (n = 181); and high risk, ASA score IV and LPMA ≤350 cm2HU (n = 33). The 90-day mortality and MAE rates were 1.7% and 16% in the low-, 7.2% and 24% in the medium-, and 30% and 33% in the high-risk patients, respectively (P < .001 and P = .02, respectively). Patients with ASA score IV and LPMA <200 cm2HU, indicating sarcopenia (n = 14) had a 43% risk of death within 90 days. The 3-year survival estimates were 80% ± 3% for the low-, 70% ± 4% for the medium-, and 35% ± 9% for the high-risk patients (P < .001). The mean follow-up time was 3.1 ± 2.3 years. CONCLUSIONS: LPMA was a strong predictor of outcomes and the only independent predictor of both mortality and MAEs after FBEVAR. A high muscle mass was protective against complications, regardless of the ASA score. Risk stratification based on the ASA score and LPMA can be used to identify patients at excessively high operative risk.

14.
Infect Dis Clin North Am ; 34(4): 659-676, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33011047

RESUMO

The evolution of resistance to antimicrobial agents in gram-negatives has challenged the role of the clinical microbiology laboratory to implement new methods for their timely detection. Recent development has enabled the use of novel methods for more rapid pathogen identification, antimicrobial susceptibility testing, and detection of resistance markers. Commonly used methods improve the rapidity of resistance detection from both cultured bacteria and specimens. This review focuses on the commercially available systems available together with their technical performance and possible clinical impact.

15.
ERJ Open Res ; 6(3)2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32964006

RESUMO

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS.

16.
Cancers (Basel) ; 12(10)2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32992569

RESUMO

Optimal use of multiparametric magnetic resonance imaging (mpMRI) can identify key MRI parameters and provide unique tissue signatures defining phenotypes of breast cancer. We have developed and implemented a new machine-learning informatic system, termed Informatics Radiomics Integration System (IRIS) that integrates clinical variables, derived from imaging and electronic medical health records (EHR) with multiparametric radiomics (mpRad) for identifying potential risk of local or systemic recurrence in breast cancer patients. We tested the model in patients (n = 80) who had Estrogen Receptor positive disease and underwent OncotypeDX gene testing, radiomic analysis, and breast mpMRI. The IRIS method was trained using the mpMRI, clinical, pathologic, and radiomic descriptors for prediction of the OncotypeDX risk score. The trained mpRad IRIS model had a 95% and specificity was 83% with an Area Under the Curve (AUC) of 0.89 for classifying low risk patients from the intermediate and high-risk groups. The lesion size was larger for the high-risk group (2.9 ± 1.7 mm) and lower for both low risk (1.9 ± 1.3 mm) and intermediate risk (1.7 ± 1.4 mm) groups. The lesion apparent diffusion coefficient (ADC) map values for high- and intermediate-risk groups were significantly (p < 0.05) lower than the low-risk group (1.14 vs. 1.49 × 10-3 mm2/s). These initial studies provide deeper insight into the clinical, pathological, quantitative imaging, and radiomic features, and provide the foundation to relate these features to the assessment of treatment response for improved personalized medicine.

17.
Curr Hematol Malig Rep ; 15(6): 424-435, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32920736

RESUMO

PURPOSE OF REVIEW: The treatment of acute lymphoblastic leukemia (ALL) in adolescent and young adult (AYA) patients has markedly improved with the adoption of pediatric-inspired protocols. However, there remain several subtypes of ALL that represent significant therapeutic challenges. Here, we review the current evidence guiding treatment of Philadelphia chromosome-positive (Ph+), Philadelphia chromosome-like (Ph-L), and early T-precursor (ETP) ALL in the AYA population. RECENT FINDINGS: Clinical trials in Ph + ALL have demonstrated the superior efficacy of second- and third-generation tyrosine kinase inhibitors (TKIs) to induce and maintain remission. Current efforts now focus on determining the durability of these remissions and which patients will benefit from transplant. For Ph-like and ETP ALL, recent studies are investigating the addition of novel agents to standard treatment. The treatment of Ph + ALL has significantly improved with the addition of potent TKIs. However, the treatment of Ph-like and ETP ALL remains a challenge. At this time, the judicious use of allogenic transplant is the only current approach to modify this increased risk.

18.
Chronic Obstr Pulm Dis ; 7(4): 362-369, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32926607

RESUMO

Background: The effect of high-flow nasal therapy (HFNT) in individuals with an exacerbation of chronic obstructive pulmonary disease (COPD) and hypercapnia is not well studied. We assessed patient tolerance and impact of air-gas therapy delivered by humidified HFNT (20-35 L/min) on gas exchange in hypercapnic COPD patients during hospitalization for COPD exacerbation. We hypothesized that HFNT use would be safe and well tolerated in individuals hospitalized for COPD exacerbation regardless of the degree of hypercapnia. Methods: Patients hospitalized for a COPD exacerbation were included if they were hypercapnic (arterial partial pressure of carbon dioxide [PaCO2] > 45 mmHg), ≥ 10 pack-year history, and agreed to treatment with HFNT, along with daily arterial blood gas (ABG) samples and bedside spirometry. They were placed on a HFNT system following admission for at least 3 days with an air-gas blend to maintain a flow rate between 20-35 L/min and fraction of inspired oxygen (FiO2) titrated to keep oxygen saturation (SaO2) values > 90%. Patient tolerance of HFNT and evidence of clinical deterioration as defined by worsening hypoxia or hypercapnia was the primary endpoint. Results: Ten consecutive patients participated in the study. The patients had frequent prior exacerbations, were hypercapnic, dyspneic, and gas trapped. Participants received an air-gas flow rate (median [interquartile range (IQR)] 25 (IQR 20-30) L/min and FiO2 of 30 (IQR 30-30) %. There was no increase in PaCO2- levels (p = 0.26) or dyspnea (Borg scale, p= 0.52) while using HFNT. No patient discontinued HFNT, had further decompensation, required non-invasive ventilation or intubation during the study period. Conclusion: In a pilot study, patients experiencing a severe COPD exacerbation were able to tolerate continuous HFNT safely regardless of degree of hypercapnia.

19.
BMJ ; 370: [1-14], Sept. 04, 2020.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1129878

RESUMO

What is the role of drug interventions in the treatment of patients with covid-19? The latest version of this WHO living guidance focuses on remdesivir, following the 15 October 2020 preprint publication of results from the WHO SOLIDARITY trial. It contains a weak or conditional recommendation against the use of remdesivir in hospitalised patients with covid-19 The first version on this living guidance focused on corticosteroids. The strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic corticosteroids in patients with non-severe covid-19 are unchanged.


Assuntos
Pneumonia Viral/tratamento farmacológico , Corticosteroides/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Antirretrovirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Metanálise , Pandemias/prevenção & controle
20.
Vasa ; : 1-9, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32815460

RESUMO

Background: Acute kidney injury (AKI) as complication after open and endovascular repair of thoracoabdominal aortic aneurysm (TAAA) is one major predictor of mortality and postoperative complications. We evaluated tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as combined early biomarker for AKI detection and predictor of patients' outcome. Patients and methods: Between 2014 and 2015, 52 patients have been enrolled in this observational study, of whom 29 (55.8%) underwent elective open repair and 23 (44.2%) endovascular repair. TIMP2 × IGFBP7 were measured until 48 hours after admission on intensive-care unit (ICU) and were analyzed regarding their predictive ability for AKI (defined according to the KDIGO criteria) requiring temporary renal replacement therapy (RRT) and 90-day mortality using ROC curves. Results: Mean patient age was 64.5 years (Min: 43, Max: 85), endovascular treated patients were older (p <0.0001). 40.4% (n = 21) developed AKI, and 21.2% (n = 11) required renal replacement therapy. In-hospital and total mortality rates were 7.7% (n = 4) and 9.6% (n = 5), respectively. At no time a significant difference in TIMP2 × IGFB7 levels between patients undergoing open or endovascular surgery was observed. The predictive quality of the TIMP2 × IGFBP7 value on ICU admission was sound regarding AKI requiring temporary renal replacement therapy (sensitivity: 55.56% [38.1-72.1%], specificity: 90.91% [58.7-99.8%] with an area under the curve [AUC]: 0.694 [0.543-0.820]). Mean follow-up was 13.2 months (Min: 2, Max: 20), regarding the 90-day mortality, the predictive property of the TIMP2 × IGFBP7 value was not sufficient (sensitivity: 80% [28.4-99.5%], specificity: 52.38% [36.4-68%], and AUC: 0.607 [0.454-0.746]). Conclusions: TIMP2 × IGFBP7 level measured 6-12 hrs postoperatively may be useful as an early detectable biomarker for AKI requiring temporary renal replacement therapy. It seems not suited to predict patients' outcome following complex thoracoabdominal aortic surgery, regardless if performed by open or endovascular repair.

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