scholarly journals Severity scoring of lung oedema on the chest radiograph is associated with clinical outcomes in ARDS

Thorax ◽  
2018 ◽  
Vol 73 (9) ◽  
pp. 840-846 ◽  
Author(s):  
Melissa A Warren ◽  
Zhiguou Zhao ◽  
Tatsuki Koyama ◽  
Julie A Bastarache ◽  
Ciara M Shaver ◽  
...  
Keyword(s):  
Pulmonary Oedema ◽  
Clinical Outcomes ◽  
Fluid Management ◽  
Intraclass Correlation ◽  
Response To Therapy ◽  
Organ Donors ◽  
Lung Weight ◽  
Lung Oedema ◽  
Derivation Cohort ◽  
Non Invasive

BackgroundThere is no accurate, non-invasive measurement to estimate the degree of pulmonary oedema in acute respiratory distress syndrome (ARDS). We developed the Radiographic Assessment of Lung Oedema (RALE) score to evaluate the extent and density of alveolar opacities on chest radiographs. After first comparing the RALE score to gravimetric assessment of pulmonary oedema in organ donors, we then evaluated the RALE score in patients with ARDS for its relationship to oxygenation and clinical outcomes.MethodsWe compared radiographs with excised lung weights from 72 organ donors (derivation cohort) and radiographs with clinical data from 174 patients with ARDS in the ARDSNet Fluid and Catheter Treatment Trial (validation cohort). To calculate RALE, each radiographic quadrant was scored for extent of consolidation (0–4) and density of opacification (1–3). The product of the consolidation and density scores for each of the four quadrants was summed (maximum score=48).ResultsAgreement between two independent reviewers for RALE score was excellent (intraclass correlation coefficient=0.93, 95% CI 0.91 to 0.95). In donors, pre-procurement RALE score correlated with height-adjusted total lung weight (ρ=0.59, p<0.001). In patients with ARDS, higher RALE scores were independently associated with lower PaO2/fractional inspired oxygen and worse survival. Conservative fluid management significantly decreased RALE score over 3 days compared with liberal fluid management.ConclusionsThe RALE score can be used to assess both the extent of pulmonary oedema and the severity of ARDS, by utilising information that is already obtained routinely, safely and inexpensively in every patient with ARDS. This novel non-invasive measure should be useful for assessing ARDS severity and monitoring response to therapy.

scholarly journals Measurements Methods for the Development of MicroRNA-Based Tests for Cancer Diagnosis

2021 ◽  
Vol 22 (3) ◽  
pp. 1176
Author(s):  
Francesca Precazzini ◽  
Simone Detassis ◽  
Andrea Selenito Imperatori ◽  
Michela Alessandra Denti ◽  
Paola Campomenosi
Keyword(s):  
Expression Profiling ◽  
Clinical Stage ◽  
Response To Therapy ◽  
Clinical Settings ◽  
Molecular Tools ◽  
Altered Expression ◽  
Circulating Micrornas ◽  
Non Invasive ◽  
Mirna Expression Profiling ◽  
Technological Limitations

Studies investigating microRNAs as potential biomarkers for cancer, immune-related diseases, or cardiac pathogenic diseases, among others, have exponentially increased in the last years. In particular, altered expression of specific miRNAs correlates with the occurrence of several diseases, making these molecules potential molecular tools for non-invasive diagnosis, prognosis, and response to therapy. Nonetheless, microRNAs are not in clinical use yet, due to inconsistencies in the literature regarding the specific miRNAs identified as biomarkers for a specific disease, which in turn can be attributed to several reasons, including lack of assay standardization and reproducibility. Technological limitations in circulating microRNAs measurement have been, to date, the biggest challenge for using these molecules in clinical settings. In this review we will discuss pre-analytical, analytical, and post-analytical challenges to address the potential technical biases and patient-related parameters that can have an influence and should be improved to translate miRNA biomarkers to the clinical stage. Moreover, we will describe the currently available methods for circulating miRNA expression profiling and measurement, underlining their advantages and potential pitfalls.

scholarly journals Mortality and clinical outcomes in patients with COVID-19 pneumonia treated with non-invasive respiratory support: A rapid review

2021 ◽  
Author(s):  
Dejan Radovanovic ◽  
Silvia Coppola ◽  
Elisa Franceschi ◽  
Fabrizio Gervasoni ◽  
Eleonora Duscio ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Respiratory Support ◽  
Rapid Review ◽  
Non Invasive

Non-contrast head CT alone for thrombectomy in acute ischemic stroke: analysis of the ANGEL-ACT registry

2021 ◽  
pp. neurintsurg-2021-017940
Author(s):  
Zeguang Ren ◽  
Gaoting Ma ◽  
Maxim Mokin ◽  
Ashutosh P Jadhav ◽  
Baixue Jia ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Clinical Outcomes ◽  
Primary Outcome ◽  
Ct Perfusion ◽  
Non Invasive ◽  
Vessel Imaging ◽  
Baseline Characteristics ◽  
Procedural Outcomes ◽  
Head Computed Tomography

BackgroudThe goal of this study was to determine if the choice of imaging paradigm performed in the emergency department influences the procedural or clinical outcomes after mechanical thrombectomy (MT).MethodsThis is a retrospective comparative outcome study which was conducted from the ANGEL-ACT registry. Comparisons were made between baseline characteristics and clinical outcomes of patients with acute ischemic stroke undergoing MT with non-contrast head computed tomography (NCHCT) alone versus patients undergoing NCHCT plus non-invasive vessel imaging (NVI) (including CT angiography (with or without CT perfusion) and magnetic resonance angiography). The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included change in mRS score from baseline to 90 days, the proportions of mRS 0–1, 0–2, and 0–3, and dramatic clinical improvement at 24 hours. The safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH, and mortality within 90 days.ResultsA total of 894 patients met the inclusion criteria; 476 (53%) underwent NCHCT alone and 418 (47%) underwent NCHCT + NVI. In the NCHCT alone group, the door-to-reperfusion time was shorter by 47 min compared with the NCHCT + NVI group (219 vs 266 min, P<0.001). Patients in the NCHCT alone group showed a smaller increase in baseline mRS score at 90 days (median 3 vs 2 points; P=0.004) after adjustment. There were no significant differences between groups in the remaining clinical outcomes.ConclusionsIn patients selected for MT using NCHCT alone versus NCHCT + NVI, there were improved procedural outcomes and smaller increases in baseline mRS scores at 90 days.

scholarly journals NPM1 mutations define a specific subgroup of MDS and MDS/MPN patients with favorable outcomes with intensive chemotherapy

2019 ◽  
Vol 3 (6) ◽  
pp. 922-933 ◽  
Author(s):  
Guillermo Montalban-Bravo ◽  
Rashmi Kanagal-Shamanna ◽  
Koji Sasaki ◽  
Keyur Patel ◽  
Irene Ganan-Gomez ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Myeloproliferative Neoplasm ◽  
Normal Karyotype ◽  
Progression Free Survival ◽  
Disease Status ◽  
Response To Therapy ◽  
Intensive Chemotherapy ◽  
Clinicopathologic Characteristics ◽  
Mutation Burden ◽  
The Impact

Abstract Nucleophosmin (NPM1) mutations are common in acute myeloid leukemia and are associated with high remission rates and prolonged survival with intensive chemotherapy. NPM1 mutations are rare in myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN), and the clinical outcomes of these patients, when treated with intensive chemotherapy, are unknown. We retrospectively evaluated the clinicopathologic characteristics and the impact of therapy in 31 patients with MDS or MDS/MPN and NPM1 mutations. Next-generation sequencing was performed at diagnosis in 22 patients. Median age was 62 years (range, 19-86). Twenty-four patients (77%) had normal karyotype, and all had multilineage dysplasia. Most patients could be classified as MDS with excess blasts (19/31, 61%). NPM1 mutations were detected at a median allele frequency of 0.38 (range, 0.09-0.49). Mutation burden did not correlate with bone marrow blast frequency, and its clearance seemed to be associated with decreased morphologic dysplasia. Ten of the 31 patients (32%) received cytotoxic chemotherapy, 20 (65%) hypomethylating agents, and 1 (4%) lenalidomide. Sequential sequencing was available in 16 (52%) patients, and mutation burden correlated with disease status and response to therapy. Patients treated with chemotherapy had higher complete response rates (90% vs 28%, P = .004), longer median progression-free survival (not reached vs 7.5 months, P = .023), and overall survival (not reached vs 16 months, P = .047). Intensive chemotherapy and allogeneic stem cell transplantation (SCT) may be associated with improved clinical outcomes in patients with NPM1-mutated MDS or MDS/MPN who are candidates for this form of therapy.

scholarly journals Multimodality imaging can shift the clinical approach and prognosis of a patient: from heart failure and angina to cardiac amyloidosis

2021 ◽  
Vol 31 (1) ◽  
pp. 103-110
Author(s):  
Alexandra Maria Chitroceanu ◽  
Alina Ioana Nicula ◽  
Roxana Cristina Rimbas ◽  
Mihaela Andreescu ◽  
Cristina Popp ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Amyloidosis ◽  
Multimodality Imaging ◽  
Clinical Status ◽  
Decompensated Heart Failure ◽  
Response To Therapy ◽  
Al Amyloidosis ◽  
Clinical Approach ◽  
Non Invasive ◽  
Life Threatening

AL (light chain) amyloidosis is a life threatening disease. Untreated patients with involvement of the heart, a condition known as cardiac amyloidosis (CA), tend to have the most rapid disease progression and worst prognosis. Therefore, it is essential to early recognize the signs of symptoms of CA, and to identify the affected individuals with readily available non-invasive tests, as timely therapy can prolong life. Different imaging tests are used to diagnose and stratify the risk of the disease noninvasively, and to follow-up of the disease course and response to therapy. In this light, we present a case of a woman with cardiovascular risk factors, initially admitted for typical angina and decompensated heart failure (HF), who was later diagnosed with AL amyloidosis with cardiac involvement, by using multimodality imaging assessment in a step-by-step fashion. This changed completely the prognosis of the patient. Timely chemotherapy and stem cell transplantation led to an improvement in clinical status, biomarkers, and in a regression of amyloid myocardial infi ltration showed by imaging.

scholarly journals The Effects of Low Pressure Domiciliary Non-Invasive Ventilation on Clinical Outcomes in Patients with Severe COPD Regardless Having Hypercapnia

2021 ◽  
Vol Volume 16 ◽  
pp. 817-824
Author(s):  
Christiaan Theunisse ◽  
Huibert H Ponssen ◽  
Netty T C de Graaf ◽  
Maaike Scholten-Bakker ◽  
Sten P Willemsen ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Low Pressure ◽  
Invasive Ventilation ◽  
Non Invasive ◽  
Non Invasive Ventilation ◽  
Severe Copd

scholarly journals Safety and efficacy of a prehospital initiated protocol of nitrates plus non-invasive ventilation on prehospital and Emergency Department outcomes for acute cardiogenic pulmonary oedema

2021 ◽  
Author(s):  
Ian Howard ◽  
Nicholas Castle ◽  
Loua Al Shaikh ◽  
Robert Owen
Keyword(s):  
Pulmonary Oedema ◽  
Treatment Protocol ◽  
Total Mortality ◽  
Signs And Symptoms ◽  
Acute Pulmonary Oedema ◽  
Emergency Setting ◽  
Invasive Ventilation ◽  
Historical Cohort ◽  
Non Invasive ◽  
Non Invasive Ventilation

Background Acute heart failure is a common presentation to Emergency Departments (ED) the world over. Amongst the most common presenting signs and symptoms is dyspnoea due to acute pulmonary oedema, a life threatening emergency that if left untreated or poorly managed. There is increasing evidence demonstrating improved outcomes following the use of vasodilators or non invasive ventilation for these patients in the emergency setting. Consequently, the potential exists that initiating these therapies in the prehospital setting will similarly improve outcomes. Methods A historical cohort study was conducted to assess the effect of a prehospital initiated treatment protocol of nitrates plus non invasive ventilation (NIV) versus regular therapy for severe cardiogenic APO on all-cause in-hospital mortality at 7 days, 30 days, and in total. Secondary outcomes included changes in EMS respiratory and haemodynamic parameters; admission status; length of stay; and emergency endotracheal intubation. Results The intervention led to an approximate 85% reduction in adjusted odds of mortality at 7 days compared to the regular therapy (AOR 0.15, 95% CI: 0.05 to 0.46, p = 0.001); approximate 80% reduction in odds of mortality at 30 days (AOR 0.19, 95% CI: 0.07 to 48, p < 0.0001); and Approximate 60% reduction in odds of total mortality (AOR 0.25, 95% CI: 0.12 to 0.56, p = 0.001). Conclusion The results of this analysis provide strong evidence of the potential synergistic benefits that can be achieved with the early implementation of a simple treatment protocol of prehospital administered nitrates and initiation of NIV for cardiogenic APO.

Treatment practices, response to therapy and adverse events in ANCA-associated vasculitis patients in Europe: top-line findings from a retrospective observational study

2019 ◽  
Author(s):  
Peter Rutherford ◽  
Dieter Goette
Keyword(s):  
Adverse Events ◽  
Clinical Outcomes ◽  
Real World ◽  
Response To Therapy ◽  
Remission Induction ◽  
Induction Treatment ◽  
Symptom Duration ◽  
Similar Distribution ◽  
Presenting Symptoms ◽  
Anca Associated Vasculitis

Abstract Background ANCA-associated vasculitis patient outcome data in the real world setting is scarce. This study measures key clinical outcomes and adverse effects over the first 12 months of remission induction therapy.Methods This was a retrospective study of 929 newly diagnosed [ND] and 268 relapsing patients [RP] conducted online by 399 clinicians. Each clinician completed a survey for 3 patients meeting the following criteria: initiated remission induction treatment for new or relapsing disease between Nov 2014 and Feb 2017, ≥ 6 months of therapy including ≥ 1 course of induction therapy, under continuous care for ≥12 months. Data were collected relating to baseline presentation and at 1, 3, 6, and 12 months.Results 58% were >55 years old with more granulomatosis with polyangiitis (GPA, 54%) versus microscopic polyangiitis (MPA, 46%), and <20% of patients had Birmingham Vasculitis Activity Scoring (BVAS) performed. Median symptom duration prior to diagnosis was 6 to 7 weeks. Presenting symptoms were similar between ND and RP, noted differences (≥ 5%) were more fever, rash, and neuropathy, and less renal disease in RP. The majority (68% ND and 84% RP) had at least one comorbidity at diagnosis, with a similar distribution. Glucocorticoids (GC) were used by 83% ND and 76% RP; >50% were still receiving GC at 12 months. Most common treatments were cyclophosphamide+GC for ND (59%) and rituximab+GC for RP (44%). Many patients had slow and/or partial response to therapy, by 12 months >60% had a full response. 81% of patients with response by month 1 maintained full response through month 12. Adverse events and infections were common, especially during the first 3 months when GC use is highest.Conclusions Real world data show that both ND and RP ANCA-associated vasculitis patients respond variably to induction remission treatment and many experience adverse events and infections over the first 12 months of treatment. The presence of comorbidities at treatment initiation in most patients compounded the adverse impacts of disease and treatment. This study improves our understanding of the reality of clinical outcomes in ANCA-associated vasculitis and the need for targeted therapeutic approaches.

scholarly journals P1062EXPANDED DIALYSIS (HDX): IS THERE AN IMPACT ON PATIENT REPORTED SYMPTOM?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jarrin Penny ◽  
Fabio R Salerno ◽  
Lisa Hur ◽  
Christopher McIntyre
Keyword(s):  
Quality Of Life ◽  
Clinical Outcomes ◽  
Symptom Burden ◽  
Well Being ◽  
Response To Therapy ◽  
High Flux ◽  
Patient Reported ◽  
Dialysis Membranes ◽  
The Impact

Abstract Background and Aims High flux dialysis membranes sufficiently remove smaller sized uremic toxins however, the accumulation and retention of larger middle molecular weight toxins, which are associated with chronic inflammation, cardiovascular disease and suboptimal outcomes are poorly cleared. The recent advent of medium-cut-off dialysis membranes, labelled “expanded dialysis” (HDx) are permeable to molecules of larger size responsible for poor clinical outcomes. However, it remains unclear if HDx can directly impact the symptoms associated with hemodialysis (HD). Symptom burden plays a significant role in quality of life (QOL) and mortality rates in the HD population. The London Evaluation of Illness (LEVIL), an application-based platform has been developed to measure patient reported outcomes (PROM). In comparison to cross-sectional PROM’s, LEVIL more accurately represents the fluctuations in daily symptoms and the impact of intervention. LEVIL evaluates general well-being, energy, sleep, appetite, pain and breathing, all of which are outcomes of interest on symptom burden in chronic kidney disease. Our aim was to determine if HDx therapy had any effect on symtoms/QOL domains using LEVIL. Method 28 patients from two dialysis centers in London Ontario were consented to participate. Patients were required to be over 18 years of age and on conventional thrice weekly maintenance HD for at least three months. 23 participants completed study and analyzed (five lost for various reasons). Baseline (BL) symptom characteristics were obtained while using high flux membrane for two weeks. Symptoms continued to be measured throughout the 12 weeks of HDx therapy two-three times weekly using LEVIL. Laboratory biomarkers including beta-2 microglobulin and free-light chains were collected at baseline and after 12 weeks of HDx therapy. Results Patients were stratified into tertiles (high/middle/low) using mean values of BL symptoms scores in each domain (wellbeing, energy, sleep, appetite, pain, breathing). Those in the high BL group were labeled as “control”. Low and middle BL measures were further stratified into responders vs. non-responders (responders were considered to have a 50% increase in any symptom domain by ≥50%). Of those domains which responded to HDx, 76% also had low BL scores with 27% having middle BL scores. General wellbeing, energy and sleep were domains with the greatest response reaching statistical significance after eight weeks of therapy. HDx had limited effect on appetite, pain and breathing. Although stratification was per domain, overall, 74% of the population studied did respond in at least one domain, with some responding in as many as five. Conclusion HDx using Theranova (Baxter) shows the most benefit in domains with low BL measures. Additionally, not everyone who had low BL scores responded after 12 weeks of therapy, leaving us to question whether HDx may have a latent effect in some individuals/populations. Those who had no response to therapy in certain domains also had greater baseline quality of life respectively. This information may assist in decision making/rationale for the utilization and implementation of such therapy. Although more work is required to further stratify symptoms in relation to demographic/biochemical finding and clinical outcomes. It is evident that HDx improves patient reported symptoms and QOL.

scholarly journals Quantitative PET imaging of PD-L1 expression in xenograft and syngeneic tumour models using a site-specifically labelled PD-L1 antibody

2019 ◽  
Vol 47 (5) ◽  
pp. 1302-1313 ◽  
Author(s):  
Camilla Christensen ◽  
Lotte K. Kristensen ◽  
Maria Z. Alfsen ◽  
Carsten H. Nielsen ◽  
Andreas Kjaer
Keyword(s):  
Pet Imaging ◽  
Predictive Value ◽  
Ex Vivo ◽  
Response To Therapy ◽  
Whole Body ◽  
Therapeutic Monitoring ◽  
Non Invasive ◽  
Tumour Bearing ◽  
Quantitative Pet

Abstract Purpose Despite remarkable clinical responses and prolonged survival across several cancers, not all patients benefit from PD-1/PD-L1 immune checkpoint blockade. Accordingly, assessment of tumour PD-L1 expression by immunohistochemistry (IHC) is increasingly applied to guide patient selection, therapeutic monitoring, and improve overall response rates. However, tissue-based methods are invasive and prone to sampling error. We therefore developed a PET radiotracer to specifically detect PD-L1 expression in a non-invasive manner, which could be of diagnostic and predictive value. Methods Anti-PD-L1 (clone 6E11, Genentech) was site-specifically conjugated with DIBO-DFO and radiolabelled with 89Zr (89Zr-DFO-6E11). 89Zr-DFO-6E11 was optimized in vivo by longitudinal PET imaging and dose escalation with excess unlabelled 6E11 in HCC827 tumour-bearing mice. Specificity of 89Zr-DFO-6E11 was evaluated in NSCLC xenografts and syngeneic tumour models with different levels of PD-L1 expression. In vivo imaging data was supported by ex vivo biodistribution, flow cytometry, and IHC. To evaluate the predictive value of 89Zr-DFO-6E11 PET imaging, CT26 tumour-bearing mice were subjected to external radiation therapy (XRT) in combination with PD-L1 blockade. Results 89Zr-DFO-6E11 was successfully labelled with a high radiochemical purity. The HCC827 tumours and lymphoid tissue were identified by 89Zr-DFO-6E11 PET imaging, and co-injection with 6E11 increased the relative tumour uptake and decreased the splenic uptake. 89Zr-DFO-6E11 detected the differences in PD-L1 expression among tumour models as evaluated by ex vivo methods. 89Zr-DFO-6E11 quantified the increase in PD-L1 expression in tumours and spleens of irradiated mice. XRT and anti-PD-L1 therapy effectively inhibited tumour growth in CT26 tumour-bearing mice (p < 0.01), and the maximum 89Zr-DFO-6E11 tumour-to-muscle ratio correlated with response to therapy (p = 0.0252). Conclusion PET imaging with 89Zr-DFO-6E11 is an attractive approach for specific, non-invasive, whole-body visualization of PD-L1 expression. PD-L1 expression can be modulated by radiotherapy regimens and 89Zr-DFO-6E11 PET is able to monitor these changes and predict the response to therapy in an immunocompetent tumour model.

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