Tracking Radiolabeled Endothelial Microvesicles Predicts Their Therapeutic Efficacy: A Proof-of-Concept Study in Peripheral Ischemia Mouse Model Using SPECT/CT Imaging

Microvesicles, so-called endothelial large extracellular vesicles (LEVs), are of great interest as biological markers and cell-free biotherapies in cardiovascular and oncologic diseases. However, their therapeutic perspectives remain limited due to the lack of reliable data regarding their systemic biodistribution after intravenous administration. Methods: Applied to a mouse model of peripheral ischemia, radiolabeled endothelial LEVs were tracked and their in vivo whole-body distribution was quantified by microSPECT/CT imaging. Hindlimb perfusion was followed by LASER Doppler and motility impairment function was evaluated up to day 28 post-ischemia. Results: Early and specific homing of LEVs to ischemic hind limbs was quantified on the day of ischemia and positively correlated with reperfusion intensity at a later stage on day 28 after ischemia, associated with an improved motility function. Conclusions: This concept is a major asset for investigating the biodistribution of LEVs issued from other cell types, including cancer, thus partly contributing to better knowledge and understanding of their fate after injection.

Impact of the absence of dental support on cancer patients during the COVID-19 pandemic

Purpose With the suspension of routine services due to the coronavirus disease-2019 (COVID-19) pandemic, a significant number of the population has been presenting acute oral alterations without proper treatment. Through telecontact, this study aimed to identify individuals in treatment and had been treated for cancer who had their clinical dental care interrupted by the COVID-19 pandemic. Methods Individuals with oncologic diseases were selected from a telephone list of a clinical research center specializing in the care of cancer patients. We included those who answered an online questionnaire about their general health status and oral problems when they were unable to access dental care during the pandemic. Statistical analysis was performed using Fisher and Chi-square tests. The significance level was set at 5% (p<0.05). Results Of the 280 patients recruited, 104 answered the questionnaire. There were 75 (72.1%) were women, of which 22 (36.7%) were under antineoplastic treatment, and 30 (68.2%) had already been treated; 29 (27.9%) were men, of which 15 (25.0%) were under antineoplastic treatment and 14 (31.8%) had already been treated. Of the universal sample, 64 (61.5%) had no complaints regarding their general health, and 74 (71.1%) had no difficulties in their daily activities due to teeth/mouth problems. However, the rates of oral problems were not statistically significant (p=NS). Conclusion In dentistry, telephone support and digital tools are useful and necessary instruments for the follow-up of cancer patients during the pandemic.

A Systematic Review on the Role of the Perfusion Computed Tomography in Abdominal Cancer

Background and purpose Perfusion Computed Tomography (CTp) is an imaging technique which allows quantitative and qualitative evaluation of tissue perfusion through dynamic CT acquisitions. Since CTp is still considered a research tool in the field of abdominal imaging, the aim of this work is to provide a systematic summary of the current literature on CTp in the abdominal region to clarify the role of this technique for abdominal cancer applications. Materials and Methods A systematic literature search of PubMed, Web of Science, and Scopus was performed to identify original articles involving the use of CTp for clinical applications in abdominal cancer since 2011. Studies were included if they reported original data on CTp and investigated the clinical applications of CTp in abdominal cancer. Results Fifty-seven studies were finally included in the study. Most of the included articles (33/57) dealt with CTp at the level of the liver, while a low number of studies investigated CTp for oncologic diseases involving UGI tract (8/57), pancreas (8/57), kidneys (3/57), and colon–rectum (5/57). Conclusions Our study revealed that CTp could be a valuable functional imaging tool in the field of abdominal oncology, particularly as a biomarker for monitoring the response to anti-tumoral treatment.

Bringing Macrophages to the Frontline against Cancer: Current Immunotherapies Targeting Macrophages

Macrophages are found in all tissues and display outstanding functional diversity. From embryo to birth and throughout adult life, they play critical roles in development, homeostasis, tissue repair, immunity, and, importantly, in the control of cancer growth. In this review, we will briefly detail the multi-functional, protumoral, and antitumoral roles of macrophages in the tumor microenvironment. Our objective is to focus on the ever-growing therapeutic opportunities, with promising preclinical and clinical results developed in recent years, to modulate the contribution of macrophages in oncologic diseases. While the majority of cancer immunotherapies target T cells, we believe that macrophages have a promising therapeutic potential as tumoricidal effectors and in mobilizing their surroundings towards antitumor immunity to efficiently limit cancer progression.

Health risks analysis and complex procedure for estimating the efficiency of targeted activities performed within regional public healthcare systems and aimed at reducing mortality among the population caused by cardiovascular diseases and oncologic diseases

Introduction. Preservation and growth of the country population is the top national priority in the Russian Federation. A contemporary approach focuses on several especially urgent demographic issues that can be resolved, among other things, due to public healthcare systems becoming more efficient. The present research work is vital due to the necessity to achieve target medical and demographic parameters fixed in the national and federal projects and regional programs. These parameters include life expectancy and mortality caused by cardiovascular and oncologic diseases. The goal of this work is a development of new approaches for the complex evaluation of potential management reserves of health population indicators and the prognosis of efficiency of targeted activities performed within public healthcare systems and aimed at increasing life expectancy through reducing mortality among the population caused by cardiovascular diseases and oncologic diseases. Material and methods. The work dwells on solving a “direct” task in the “medical activities - morbidity - mortality” triple analysis system; the solution involves predicting changes in morbidity and mortality under preset, planned, or scenario changes in parameters related to the public healthcare system. We modelled cause-and-effect relations in the above system, applying mathematical statistics techniques (correlation-regression analysis and factor analysis) with the consequent medical expertise of obtained results. Results. These procedures allow assessing health losses and spot out priorities in activities performed within the public healthcare system as well as ranking managerial decisions, already taken or only planned, as per their efficiency, taking into account territories; sex and age structure of the population; diseases, their subclasses and gravity; specific activities performed within the public healthcare system (prevention, diagnostics, or treatment). We should stress that the most significant potential management reserves of reducing mortality are achieved on territories with maximum mortality levels due to reserves for the reduction in it; these reserves are manageable due to prevention and early diagnostics. Conclusion. Research techniques and results described in the present work can be used in practice to achieve target parameters fixed by national and regional priorities and to select an optimal set of activities aimed at reducing mortality among the population.

Case Report: Management of Malignancy-Exacerbated Pemphigus Vulgaris During COVID-19 Pandemic

Pemphigus vulgaris is an intraepidermal autoimmune mucocutaneous blistering disease whose etiopathogenesis includes various trigger factors, i.e., drugs and malignancies. We present a case of malignancy-exacerbated pemphigus vulgaris which required a careful diagnostic process in order to rule out paraneoplastic pemphigus, along with the challenges posed by the need of treating both cutaneous and oncologic diseases. Possible post-operative complications post-poned the start of first-line immunosuppressive treatment of pemphigus. Moreover, the infective risks had to be minimized during the peak of the COVID-19 pandemic in Italy. Intravenous immunoglobulins were chosen as “bridge” therapy before the tumor surgical excision, followed by rituximab in post-operative phase.

Management and Clinical Outcome of Posterior Reversible Encephalopathy Syndrome in Pediatric Oncologic/Hematologic Diseases: A PRES Subgroup Analysis With a Large Sample Size

This study investigated the management and clinical outcomes along with associated factors of posterior reversible encephalopathy syndrome (PRES) in childhood hematologic/oncologic diseases. We present data from children with hematologic/oncologic diseases who developed PRES after treatment of the primary disease with chemotherapy and hematopoietic stem cell transplantation (HSCT) at 3 medical centers in Changsha, China from 2015 to 2020, and review all previously reported cases with the aim of determining whether this neurologic manifestation affects the disease prognosis. In the clinical cohort of 58 PRES patients, hypertension [pooled odds ratio (OR) = 4.941, 95% confidence interval (CI): 1.390, 17.570; P = 0.001] and blood transfusion (OR = 14.259, 95% CI: 3.273, 62.131; P = 0.001) were significantly associated with PRES. Elevated platelet (OR = 0.988, 95% CI: 0.982, 0.995; P &lt; 0.001), hemoglobin (OR = 0.924, 95% CI: 0.890, 0.995; P &lt; 0.001), and blood sodium (OR = 0.905, 95% CI: 0.860, 0.953; P &lt; 0.001), potassium (OR = 0.599, 95% CI: 0.360, 0.995; P = 0.048), and magnesium (OR = 0.093, 95% CI: 0.016, 0.539; P = 0.008) were protective factors against PRES. Data for 440 pediatric PRES patients with hematologic/oncologic diseases in 21 articles retrieved from PubMed, Web of Science, and Embase databases and the 20 PRES patients from our study were analyzed. The median age at presentation was 7.9 years. The most common primary diagnosis was leukemia (62.3%), followed by solid tumor (7.7%) and lymphoma (7.5%). Most patients (65.0%) received chemotherapy, including non-induction (55.2%) and induction (44.8%) regimens; and 86.5% used corticosteroids before the onset of PRES. Although 21.0% of patients died during follow-up, in most cases (93.2%) this was not attributable to PRES but to severe infection (27.3%), underlying disease (26.1%), graft-vs.-host disease (14.8%), multiple organ dysfunction syndrome (8.0%), and respiratory failure (3.4%). PRES was more common with HSCT compared to chemotherapy and had a nearly 2 times higher mortality rate in patients with oncologic/hematologic diseases than in those with other types of disease. Monitoring neurologic signs and symptoms in the former group is therefore critical for ensuring good clinical outcomes following treatment of the primary malignancy.

IL-31, itch and hematological malignancies

Pruritus is one of the most common symptoms experienced by neoplastic patients. The pathogenesis of neoplastic itch is complex and multifactorial and could be due to an unbalanced production of humoral mediators by altered immune effector cells. IL-31 is a pro-inflammatory cytokine produced by CD4 + T helper cells. The aim of this review was to evaluate the role of this Th2 cytokine and its receptor IL-31RA, in the onset of neoplastic pruritus. We analysed scientific literature looking for the most relevant original articles linking IL-31to itch in oncologic diseases. Interleukin-31 seems to be a main itch mediator in several hematologic disease such as Cutaneous T cells lymphomas. In these patients IL-31 was positively linked to itch level, and IL-31 matched with disease stage. IL-31 seems to play an important role in the signalling pathway involved in pruritus, but it is also suggested to play a proinflammatory and immunomodulatory role which could play a part in the progression of the neoplastic disease. Further studies will be fundamental in facing pruritus in oncologic patients, since this problem compromise their quality of life worsening an already critic picture.

Evaluation of Hypersensitivity Reactions in Pediatric Patients Using Biological Drugs

<b><i>Introduction:</i></b> Biological drugs are currently used for the treatment of chronic inflammatory, autoimmune, and neoplastic diseases. With their expanding indication spectrum and increasing use, hypersensitivity reactions to these drugs are also becoming more frequent. The present study aimed to report the incidence and the features of such reactions in pediatric patients using biologicals for the treatment of various diseases. <b><i>Methods:</i></b> The medical records of pediatric patients treated with biological agents between October 1, 2011 and August 31, 2019 were reviewed and adverse reactions were evaluated retrospectively. <b><i>Results:</i></b> During the study period, 211 patients (116 boys, 55%) used 21 different biological drugs for the treatment of various diseases. Their median age at the time of the first treatment was 139.9 (IQR: 92.2–187.8) months. Hematologic-oncologic diseases were the most common indication for biological therapy (97/211; 46.0%), followed by rheumatologic diseases (82/211; 38.9%). Of the 211 patients, 14 (6.64%) experienced reactions to biological drugs. The most common culprit agent was rituximab (57.1%). Most of the patients (85.7%) had a history of reactions either during the infusion or within 1 h after taking the drug. Five patients underwent desensitization to the culprit drug, while 7 other patients continued treatment with a reduced dose/infusion rate or premedication. Also 1 patient continued to take the drug without any additional treatment. <b><i>Conclusion:</i></b> It was reported that 6.64% of the patients who received biologic drug therapy for various reasons in our hospital had hypersensitivity. The most common culprit agent was rituximab, and most of the reactions were immediate reactions.