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Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1529
Catarina Lourenço ◽  
Vera Constâncio ◽  
Rui Henrique ◽  
Ângela Carvalho ◽  
Carmen Jerónimo

Urologic cancers are a heterogeneous group of tumors, some of which have poor prognosis. This is partly due to the unavailability of specific and sensitive diagnostic techniques and monitoring tests, ideally non- or minimally invasive. Hence, liquid biopsies are promising tools that have been gaining significant attention over the last decade. Among the different classes of biomarkers that can be isolated from biofluids, urinary extracellular vesicles (uEVs) are a promising low-invasive source of biomarkers, with the potential to improve cancer diagnosis and disease management. Different techniques have been developed to isolate and characterize the cargo of these vesicles; however, no consensus has been reached, challenging the comparison among studies. This results in a vast number of studies portraying an extensive list of uEV-derived candidate biomarkers for urologic cancers, with the potential to improve clinical outcome; however, without significant validation. Herein, we review the current published research on miRNA and protein-derived uEV for prostate, bladder and kidney cancers, focusing on different uEV isolation methods, and its implications for biomarker studies.

2021 ◽  
Vol 12 ◽  
Fernanda O. Novais ◽  
Camila Farias Amorim ◽  
Phillip Scott

Cutaneous leishmaniasis exhibits a wide spectrum of clinical presentations from self-resolving infections to severe chronic disease. Anti-parasitic drugs are often ineffective in the most severe forms of the disease, and in some cases the magnitude of the disease can result from an uncontrolled inflammatory response rather than unrestrained parasite replication. In these patients, host-directed therapies offer a novel approach to improve clinical outcome. Importantly, there are many anti-inflammatory drugs with known safety and efficacy profiles that are currently used for other inflammatory diseases and are readily available to be used for leishmaniasis. However, since leishmaniasis consists of a wide range of clinical entities, mediated by a diverse group of leishmanial species, host-directed therapies will need to be tailored for specific types of leishmaniasis. There is now substantial evidence that host-directed therapies are likely to be beneficial beyond autoimmune diseases and cancer and thus should be an important component in the armamentarium to modulate the severity of cutaneous leishmaniasis.

2021 ◽  
Vol 11 (1) ◽  
Howon Lee ◽  
Silvia Park ◽  
Jae-Ho Yoon ◽  
Byung-Sik Cho ◽  
Hee-Je Kim ◽  

AbstractLeukapheresis is used for the mechanical removal of leukaemic cells in hyperleukocytosis. However, the effectiveness of leukapheresis remains unclear due to selection and confounding factors in the cohorts. We compared the effectiveness of leukapheresis among the subgroups according to either the 2016 World Health Organization classification or the number of cytogenetic abnormalities with a retrospective, single-centre study from January 2009 to December 2018. Acute myeloid leukaemia (AML, n = 212) and acute lymphoblastic leukaemia (ALL, n = 97) were included. The 30-day survival rates (95% confidence interval, 95% CI) for AML and ALL were 86.3% (81.6–90.9%) and 94.8% (90.3–99.2%), respectively. For AML, ‘primary AML with myelodysplasia-related changes’ and ‘AML with biallelic mutation of CEBPA’ showed better 30-day survival outcomes (P = 0.026) than the other subgroups. A higher platelet count after leukapheresis was associated with better 30-day survival in AML patients (P = 0.029). A decrease in blast percentage count after leukapheresis was associated with better 30-day survival in ALL patients (P = 0.034). Our study suggested that prophylactic platelet transfusion to raise the platelet count to 50 × 109/L or greater might improve clinical outcome in AML patients undergoing leukapheresis.

2021 ◽  
Jesús Troya García ◽  
Paul Bastard ◽  
Laura Planas-Serra ◽  
Pablo Ryan ◽  
Montse Ruíz ◽  

Abstract Background: In a recent study, autoantibodies neutralizing type I interferons (IFNs) were present in at least 10% of cases of critical COVID-19 pneumonia. These autoantibodies neutralized most type I IFNs but rarely IFN-beta.Objectives: We aimed to define the prevalence of autoantibodies neutralizing type I IFN in a cohort of patients with severe COVID-19 pneumonia treated with IFN-beta-1b during hospitalization and to analyze their impact on various clinical variables and outcomes.Methods: We analyzed stored serum/plasma samples and clinical data of COVID-19 patients treated subcutaneously with IFN-beta-1b from March to May 2020, at the Infanta Leonor University Hospital in Madrid, Spain. Results: The cohort comprised 47 COVID-19 patients with severe pneumonia, 16 of whom (34%) had a critical progression requiring ICU admission. The median age was 71 years, with 28 men (58.6%). Type I IFN-alpha- and omega-neutralizing autoantibodies were found in 5 of 47 patients with severe pneumonia or critical disease (10.6%). The autoantibodies did not neutralize IFN-beta. No demographic, comorbidity, or clinical differences were seen between individuals with or without autoantibodies. We found a significant correlation between the presence of neutralizing autoantibodies and higher C-reactive protein levels (p=5.10e-03) and lower lymphocyte counts (p=1.80e-02). Survival analysis suggested that neutralizing autoantibodies may increase the risk of death (4/5, 80% vs 12/42, 28.5%).Conclusion: Autoantibodies neutralizing type I IFN underlie severe/critical COVID-19 stages in at least 10% of cases, correlate with increased C-RP and lower lymphocyte counts, and confer a trend towards increased risk of death. Subcutaneous IFN-beta treatment of hospitalized patients did not seem to improve clinical outcome. Studies of earlier, ambulatory IFN-beta treatment are warranted.

Abdul Rashid Abdul Rahman

The year 2020 has been dominated by a communicable disease which most did not see coming and are ill- prepared to handle. While daily headlines the world over are dominated by new cases and death from COVID-19, other major health issues must not take a back seat. As of 30thNovember this year, 357 people have died of COVID-19 in Malaysia,while close to 15,000 Malaysians died of Ischemic Heart Disease (IHD) alone. With IHD and cerebrovascular accident (CVA) being the number 1 and number 3 causes of death (15% and 8% of all death, respectively) our focus on COVID-19 must not distract us from the ‘elephant in the room’. Evidence from UK showed that while hospitalization due to acute myocardial infarction (AMI) has significantly decreased by 50%, out of hospital cardiac arrest has significantly increased by 56%; and in hospital mortality from AMI has increased by at least 35% during the pandemic. Patients are shying away from coming for scheduled follow ups, and there has been a reduction in guideline recommended care for NCD. This is confounded by early scare which suggested that treatment of risk factors for NCDs, especially for hypertension, dyslipidemia, and diabetes, may increase susceptibility to and worsen prognosis for patients with COVID-19. Since COVID-19 is a new entity, latest evidence generated are mainly from observational studies with few clinical trials with the exception of vaccine trials. What do we know about management of NCD in the COVID-era?Since the discovery that SARS-COV-2 virus attached itself to the ACE2 receptors before entering cells, alarm bells were sounded that patients treated with RAAS inhibitors may be susceptible to and have worse prognosis. Withup to 60% of hypertensiveworldwide taking this class of drugs, the concern is understandable. Reassuringly, 6 observational studies from 4 countries and 1 RCT from a 5th country showed this not to be true. Studies from China and Italy showed that those on RAAS inhibitors have better prognosis and this has triggered an RCT which hypothesized that pre-treatment with angiotensin receptor blockers may be beneficial in preventing pulmonary damage in these patients. Another RCT is looking at recombinant human ACE2 as treatment for patients with COVID-19. In diabetic patients, an observational study from New York showed those on statin has reduced mortality compared to non-user and in a large UK based primary care setting there was no increased risk of COVID-19 among patients prescribed SGLT2 inhibitors. The SGLT2 inhibitors have been proven to improve clinical outcome including mortality in diabetics and could be safely used to treat patients during the pandemic. Based on a nationwide retrospective cohort in the UK, overall mortality was higher for diabetics admitted to ICU or HDU and with greatest mortality impact in younger patients.The next few months will see more prospective intervention studies publishedaddressing the various unanswered questions. It is worth remembering that substandard care is responsible for upto 84% of CV death. Hence, we shouldnot let our guards down with NCDs even when the world’s attention is focused on COVID-19.International Journal of Human and Health Sciences Supplementary Issue: 2021 Page: S10

2021 ◽  
pp. 000313482199867
Keiichi Okano ◽  
Hironobu Suto ◽  
Minoru Oshima ◽  
Yasuhisa Ando ◽  
Hiroyuki Matsukawa ◽  

Although the efficacy of neoadjuvant therapies for pancreatic cancer (PDAC) is reported in recent years, ideal neoadjuvant treatment for patients with potentially resectable (R) PDAC remains uncertain. We conducted the retrospective study about the effect of short-term neoadjuvant chemoradiotherapy (sNACRT) on R PDAC. The 94 patients received curative intent pancreatectomy for R PDAC between 2000 and 2016. Among them, 31 patients received sNACRT (S1 60 mg/m2/day for 2w and RTx 30 Gy/2w). Clinical outcomes of the 31 patients with sNACRT were analyzed in comparison with 63 patients without sNACRT. The 1-, 3-, and 5-year overall survival (OS) rates were 93, 71, and 62% in the patients with sNACRT and 78, 35, and 26% in the patients without sNACRT ( P = .0007), respectively. Lymph node metastasis was found in 41.9% of patients with sNACRT and 56.5% of patients without sNACRT ( P = .09). Microscopic tumor infiltration at resection margins (R1) was found in no patient with sNACRT and 5 patients (7.9%) without sNACRT ( P=.042). Retropancreatic infiltration ( P = .04), lymphatic invasion ( P = .002), plexus invasion ( P = .042), and main pancreatic duct extension ( P = .004) were significantly fewer in patients with sNACRT than the patients without sNACRT. The recurrences were found in 64% of patients with sNACRT (39% distant, 16% local, and 10% mix pattern) and 68% in patients without sNACRT (28% distant, 21% local, and 19% mix pattern). The recurrence patterns were significantly different ( P = .008) between the groups. Short-term neoadjuvant chemoradiotherapy decreased R1 resection rate and improved OS. Short-term neoadjuvant chemoradiotherapy may provide ideal local control during the short term and improve clinical outcome of R PDAC.

2021 ◽  
Vol 8 ◽  
Mark J. Schuuring ◽  
Ivana Išgum ◽  
Bernard Cosyns ◽  
Steven A. J. Chamuleau ◽  
Berto J. Bouma

Introduction: Echocardiography is widely used because of its portability, high temporal resolution, absence of radiation, and due to the low-costs. Over the past years, echocardiography has been recommended by the European Society of Cardiology in most cardiac diseases for both diagnostic and prognostic purposes. These recommendations have led to an increase in number of performed studies each requiring diligent processing and reviewing. The standard work pattern of image analysis including quantification and reporting has become highly resource intensive and time consuming. Existence of a large number of datasets with digital echocardiography images and recent advent of AI technology have created an environment in which artificial intelligence (AI) solutions can be developed successfully to automate current manual workflow.Methods and Results: We report on published AI solutions for echocardiography analysis on methods' performance, characteristics of the used data and imaged population. Contemporary AI applications are available for automation and advent in the image acquisition, analysis, reporting and education. AI solutions have been developed for both diagnostic and predictive tasks in echocardiography. Left ventricular function assessment and quantification have been most often performed. Performance of automated image view classification, image quality enhancement, cardiac function assessment, disease classification, and cardiac event prediction was overall good but most studies lack external evaluation.Conclusion: Contemporary AI solutions for image acquisition, analysis, reporting and education are developed for relevant tasks with promising performance. In the future major benefit of AI in echocardiography is expected from improvements in automated analysis and interpretation to reduce workload and improve clinical outcome. Some of the challenges have yet to be overcome, however, none of them are insurmountable.

2021 ◽  
Yidong Zhou ◽  
Yaping Xu ◽  
Changjun Wang ◽  
Yuhua Gong ◽  
Yanyan Zhang ◽  

Abstract Background: Circulating tumor DNA (ctDNA) provides a promising noninvasive alternative to evaluate the efficacy of neoadjuvant chemotherapy (NCT) in breast cancer. Methods: Herein, we collected 63 tissue (aspiration biopsies and resected tissues) and 206 blood samples (baseline, during chemotherapy (Chemo), after chemotherapy (Post-Chemo), after operation (Post-Op), during follow-up) from 32 patients, and preformed targeted deep sequencing with a customed 1,021-gene panel. Results: As the results, TP53 (43.8%) and PIK3CA (40.6%) were the most common mutant genes in the primary tumors. At least one tumor-derived mutation was detected in the following number of blood samples: 21, baseline; 3, Chemo; 9, Post-Chemo; and 5, Post-Op. Four patients with pathologic complete response had no tissue mutation in Chemo and Post-Chemo blood. Compared to patients with mutation-positive Chemo or Post-Chemo blood, the counterparts showed a superior primary tumor decrease (median, 86.5% versus 54.6%) and lymph involvement (median, one versus 3.5). All five patients with mutation-positive Post-Op developed distant metastases during follow-up, and the sensitivity of detecting clinically relapsed patients was 71.4% (5/7). The median DFS was 9.8 months for patients with mutation-positive Post-Op but not reached for the others (HR 23.53; 95% CI, 1.904–290.9; p < 0.0001). Conclusions: Our study shows that sequential monitoring of blood ctDNA was an effective method for evaluating NCT efficacy and patient survival. Integrating ctDNA profiling into the management of LABC patients might improve clinical outcome.Trial registration: This prospective study recruited LABC patients at Peking Union Medical College Hospital ( Identifier: NCT02797652).

Natalie Duric ◽  
Tamas Szakmany

In critically ill patients with COVID-19, concomitant abnormalities of coagulation have been seen with an unusually high incidence. Standard coagulation tests are limited in their ability accurately to reflect the severity of the pro-thrombotic phenotype observed in severe COVID-19 infections. In this narrative review we consider the role of rotational thromboelastometry (ROTEM) as a near bedside test allowing a more comprehensive assessment of haemostatic function in the context of COVID-19 infection. Comprehensive literature search was conducted on PubMed, revealing 13 publications on the subject. The coagulopathy of this disease process appears to be insufficiently represented with often normal conventional coagulation test parameters. Whilst not the perfect substitute for in vivo coagulation, studies utilising rotational thromboelastometry assays in COVID-19 patients have demonstrated increased maximum clot firmness (consistent with hyper-coagulability) and reduced maximum lysis (consistent with &ldquo;fibrinolytic shutdown&rdquo;). ROTEM appears to be a possible tool for risk stratification and to monitor the potential modulation of fibrinogen-dependent coagulation processes with enhanced anti-coagulation strategies. Precisely how these coagulation abnormalities can be modified by optimum, individualised medical interventions to improve clinical outcome, however, remains unclear.

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