Oncologic Disorders Research Articles

Evaluation of the Efficacy of Flow-Cytometry in the Work-up of Leukopenia: An Institutional Retrospective Analysis

Flow-cytometry is an advantageous test which was first used in the 1950s and has now expanded to include the various fields of Immunology, Hematology, Oncology, Blood-banking and Genetic disorders. However, it is a relatively expensive and time-consuming test. We noticed that in our institution, many of the referrals for leukopenia were being evaluated by the flow-cytometry test. Hence, we aimed to review the utility and efficacy of this test with a focus on highlighting the areas where it can be avoided. We designed a retrospective study to examine data from all leukopenia/neutropenia referrals made to our center in the timespan of 1993-2018. The study included all patients aged >18 years; excluded any patients who were not directly seen in the hematology clinic by the time of data collection. The study protocol was approved by our Institutional review board (IRB). We received de-identified data, reviewed those charts, categorized them based on their reason for referral; presence of underlying cardiovascular disease, liver disease, rheumatological disease, hepatomegaly, splenomegaly. We then looked at what percentage of these patients received flow-cytometry analysis and how many of them turned out to be positive for hematologic malignancies.We further conducted statistical analysis using SAS to examine these trends. After filtering out patients based on exclusion criteria we ended up with 152 patients in our study. The reason for referral was varied and included bi-cytopenias (6.5%), concern for malignancy(1.31%), aplastic anemia (2.63%), pancytopenia (3.2%) with the majority being for neutropenia (44.7%). We found co-existing cardiovascular disease in 4.6% of patients which included congenital heart disease (28.5%), atrial fibrillation (42%), coronary artery disease (28.5%), congestive heart failure (14.2%) and supraventricular tachycardia (14.2%). Co-existing liver disease was seen in 15% of the patients and was categorized as Hepatitis C infection (47.3%), cirrhosis of the liver (36.8%) and metastatic neoplasm to the liver (5.26%). Rheumatological disease was seen in 13% of patients with the causes being rheumatoid arthritis (47%), Systemic lupus erythematosus (30%), Myasthenia gravis (5.8%), Felty's syndrome (5.8%), and Sarcoidosis (5.8%).Hepatomegaly was seen in 3% of patients and splenomegaly was seen in 7.8% of patients. Flow-cytometry analysis was done in 36% of patients and not done in 64% of patients. It was positive in only 3.9% of patients which resulted in diagnosis of Acute myeloid leukemia (0.65%), Large granular leukemia(0.65%), Myelodysplastic syndrome(0.65%) and Natural-Killer cell lymphoproliferative disorder (0.65%). Further work up revealed elevated IgG, monoclonal gammopathy, aplastic anemia in 1.97% of patients. The overall predominant causes of leukopenia were benign ethnic neutropenia (17%), medication related (12.5%), autoimmune (5.2%), malignancy (3.9%), viral (4.6%), toxic (2.6%) causes. The medications which caused neutropenia were antibiotic and antifungal (1.31%), anti-seizure (3.2%), immunosuppressant and immunomodulatory (3.2%), psychiatric (2.6%).During evaluation of leukopenia, a thorough history can rule out toxic and medication-related causes. The review of old medical records and laboratory results can lead to the diagnosis of chronic benign and congenital leukopenia which can avert unwarranted testing. Abstinence from alcohol may lead to reversal of the neutropenia if alcohol is the toxin responsible. Viral testing for HIV and hepatitis should be performed. Evaluation for autoimmune causes is much needed. Since the overall positivity of flow-cytometry was very low in our analysis (3.9%), we propose that such thorough preliminary evaluation can avoid the need for many of these tests. The data showed that leukopenia referrals come with a wide range of underlying causes including congenital disorders (benign ethnic, familial, congenital neutropenia) and acquired disorders (infection, toxins, medications, nutritional, rheumatological, autoimmune, idiopathic, hematologic malignancies). Peripheral blood flow-cytometry although sensitive for detecting some hematologic malignancies, is unnecessary in the majority of cases. Hence, we highlight here the varied benign causes of neutropenia and quantify them as seen in a tertiary referral center to enable decisions on the judicious use of this test. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Survey of Acceptance of Human Papillomavirus Vaccine Among Parents of Children Followed in Hematology/Oncology Clinic at a Single Institution in Louisiana

Human Papillomavirus infection (HPV) is the most common sexually transmitted disease, with about 14 million cases diagnosed annually, and causing cancers of the anogenital tract. Vaccination against HPV was first introduced in the United States in 2006 and the vaccine is now recommended as a preventive therapy for children, adolescents, and young adults from 9 years to 26 years. Despite this recommendation, a small number of parents still refuse to immunize their children with this vaccine. We performed a survey of 41 parents whose children had been followed at Children's Hospital of New Orleans for oncologic and hematologic disorders, and queried them on their knowledge af HPV and acceptance of the vaccine. We assumed that individuals whose children had been diagnosed with cancer diagnoses would be more knowledgeable about and receptive to the vaccine. IRB approval had been obtained and parents properly consented. Children were ages 10-21 years (mean 14.8+/-.43 years). Sixteen were African-American, 17 white, 5 of mixed ethnicity, and 3 self-identified as Asian or Native American. Fifty-four percent said that they had knowledge (even if superficial) of the vaccine, while 20% said they had not. Seventy-three percent said that they were aware of how to obtain it. Only 7 (17%) were not aware of what problems could be caused by the virus. Fifty-eight percent felt that the vaccine was important while 56% indicated that it should be incorporated into the vaccine schedule. Fifty-nine percent indicated an intent to have their son or daughter vaccinated. The vast majority (71%) knew how to obtain the vaccine through their PCP with just over half of the parents having already discussed the issue with the PCP. We examined the effect of ethnic or racial grouping and found that the only significant difference between racial or ethnic groups was in awareness of how to obtain the vaccine, with more African-American parents noting that they did not know where to get the vaccine for their children. As noted, we had thought that individuals whose children may have been diagnosed with cancer would have a greater sense of urgency about vaccinating their children. Parents of children with cancer diagnoses were more knowledgeable about HPV in general, had more likely heard or read about the vaccine, were more aware of how to obtain it (p<0.05 for all survey questions) but paradoxically they did not think of the vaccine as any more important than did those parents of children with non-oncologic disorders (p=0.5). However they were more likely to want the vaccine incorporated into the vaccine schedule and would want their children to be vaccinated (p<0.001). We acknowledge that the number of individuals surveyed is relatively small. However, the number of parents willing to have their child vaccinated is still far short of the goal of an 80% annual rate that has been set for the United States to reach by 2026. As noted, seventy-one of our parents indicated knowledge of how to obtain the vaccine, the main sources of information being their physician, TV or newspaper but those still having reservations felt they did not have sufficient information or that there possibly could be side-effects, while a minority did not agree with compulsory vaccines or felt that the vaccine would encourage inappropriate behavior in their children. All of this means that there is still considerable work to do in persuading individuals of the worthwhileness of vaccinating children in the appropriate age groups.

Meyerozyma guilliermondii species complex: review of current epidemiology, antifungal resistance, and mechanisms.

Meyerozyma guilliermondii has been accepted as a complex composed of Meyerozyma guilliermondii, Meyerozyma carpophila, and Meyerozyma caribbica. M. guilliermondii is a saprophyte detected on human mucosa and skin. It can lead to serious infections in patients with risk factors like chemotherapy, immunodeficiency, gastrointestinal or cardiovascular surgery, and oncology disorders. Most deaths related to M. guilliermondii infections occur in individuals with malignancy. In recent decades, incidence of M. guilliermondii infections is increased. Sensitivity of this microorganism to conventional antifungals (e.g., amphotericin B, fluconazole, micafungin and anidulafungin) was reduced. Prophylactic and empirical uses of these drugs are linked to elevated minimal inhibitory concentrations (MICs) of M. guilliermondii. Drug resistance has concerned many researchers across the world. They are attempting to discover appropriate solution to combat this challenge. This study reviews the most important mechanisms of resistance to antifungals developed by in M. guilliermondii species complex.

The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases.

The endocannabinoid system (ECS) dynamically regulates many aspects of mammalian physiology. ECS has gained substantial interest since growing evidence suggests that it also plays a major role in several pathophysiological conditions due to its ability to modulate various underlying mechanisms. Furthermore, cannabinoids, as components of the cannabinoid system (CS), have proven beneficial effects such as anti-inflammatory, immunomodulatory, neuromodulatory, antioxidative, and cardioprotective effects. In this comprehensive review, we aimed to describe the complex interaction between CS and most common age-related diseases such as neuro-degenerative, oncological, skeletal, and cardiovascular disorders, together with the potential of various cannabinoids to ameliorate the progression of these disorders. Since chronic inflammation is postulated as the pillar of all the above-mentioned medical conditions, we also discuss in this paper the potential of CS to ameliorate aging-associated immune system dysregulation.

Remdesivir Decreases Mortality in COVID-19 Patients with Active Malignancy.

Simple SummaryPatients with active malignancies have an increased risk for severe SARS-CoV-2 infection and high mortality from COVID-19. Additionally, due to the underlying immune deficiency, prolonged replication and a higher rate of escape mutations are seen. Thus, it is crucial to introduce direct antiviral agents, whereas there is only limited knowledge of their efficacy and optimal regimens mainly from small series in oncologic patients. In this real-world experience study, 252 patients with active malignancy were found among 4890 hospitalized patients for COVID-19. We have shown that patients with malignancy benefit from early remdesivir therapy, resulting in a decrease in 28-day in-hospital mortality by 80%. Factors independently associated with a worse prognosis include low glomerular filtration rate and low peripheral oxygen saturation at baseline. The results not only confirm the lifesaving effect of remdesivir in oncologic patients, but also underline the need to optimize therapy, including kidney protection and early oxygen therapy.Data on the use of remdesivir, the first antiviral agent against SARS-CoV-2, are limited in oncologic patients. We aimed to analyze contributing factors for mortality in patients with malignancies in the real-world CSOVID-19 study. In total, 222 patients with active oncological disorders were selected from a nationwide COVID-19 study of 4890 subjects. The main endpoint of the current study was the 28-day in-hospital mortality. Approximately half of the patients were male, and the majority had multimorbidity (69.8%), with a median age of 70 years. Baseline SpO2 < 85% was observed in 25%. Overall, 59 (26.6%) patients died before day 28 of hospitalization: 29% due to hematological, and 20% due to other forms of cancers. The only factor increasing the odds of death in the multivariable model was eGFR < 60 mL/min/m2 (4.621, p = 0.02), whereas SpO2 decreased the odds of death at baseline (0.479 per 5%, p = 0.002) and the use of remdesivir (0.425, p = 0.03). This study shows that patients with COVID-19 and malignancy benefit from early remdesivir therapy, resulting in a decrease in early mortality by 80%. The prognosis was worsened by low glomerular filtration rate and low peripheral oxygen saturation at baseline underlying the role of kidney protection and early hospitalization.

Pediatric reference interval verification for 17 specialized immunoassays and cancer markers on the Abbott Alinity i system in the CALIPER cohort of healthy children and adolescents.

Clinical laboratory investigation of autoimmune, metabolic, and oncologic disorders in children and adolescents relies on appropriateness of reference intervals (RIs). The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) previously established comprehensive pediatric RIs for specialized immunoassays on the Abbott ARCHITECT system. Herein, we aim to verify performance on new Alinity i assays by evaluating sera collected from healthy children as per Clinical andLaboratory Standards Institute (CLSI) EP-28A3C guidelines. Precision, linearity, and method comparison experiments were completed for 17 specialized Alinity immunoassays, including cancer antigens, autoimmune peptides, and hormones. Sera collected from healthy children and adolescents (birth-18 years, n=100) were evaluated. CLSI-based verification was completed using previously established CALIPER RIs for ARCHITECT assays as the reference. Of 17 specialized immunoassays assays, only anti-cyclic citrullinated peptides (anti-CCP) did not meet acceptable verification criterion (i.e.,≥90% of results within ARCHITECT reference CI). Anti-thyroglobulin, anti-thyroid peroxidase, and carcinoembryonic antigen did notrequire age-specific consideration beyond one year of age, with 63, 91, and 80% of samples equalling the limit ofdetection, respectively. Estimates were separated by sex for relevant assays (e.g., sex hormone binding globulin, total and free prostate specific antigen). Findings support transferability of pediatric RIs on ARCHITECT system to the Alinity system for 16 specialized immunoassays in the CALIPER cohort and willbe a useful resource for pediatric clinical laboratories using Alinity assays. Further work is needed to establish evidence-based interpretative recommendations for anti-CCP and continue to evaluate pediatric RI acceptability for newly available assay technologies.

Targeting of the Mitochondrial TET1 Protein by Pyrrolo[3,2-b]pyrrole Chelators.

Targeting of epigenetic mechanisms, such as the hydroxymethylation of DNA, has been intensively studied, with respect to the treatment of many serious pathologies, including oncological disorders. Recent studies demonstrated that promising therapeutic strategies could potentially be based on the inhibition of the TET1 protein (ten-eleven translocation methylcytosine dioxygenase 1) by specific iron chelators. Therefore, in the present work, we prepared a series of pyrrolopyrrole derivatives with hydrazide (1) or hydrazone (2–6) iron-binding groups. As a result, we determined that the basic pyrrolo[3,2-b]pyrrole derivative 1 was a strong inhibitor of the TET1 protein (IC50 = 1.33 μM), supported by microscale thermophoresis and molecular docking. Pyrrolo[3,2-b]pyrroles 2–6, bearing substituted 2-hydroxybenzylidene moieties, displayed no significant inhibitory activity. In addition, in vitro studies demonstrated that derivative 1 exhibits potent anticancer activity and an exclusive mitochondrial localization, confirmed by Pearson’s correlation coefficient of 0.92.

Nordic walking, a novel regime’s impact on functional capacity, quality of life and depression and anxiety in Post Covid-19 patients

In COVID-19, the respiratory system is most affected by cough, fever, and dyspnea. It has shown its impact on lung function and exercise is proven to aid in the restoration of the normal functioning of the lung. There have not been studies on Nordic walking in Covid-19 patients after discharge yet. The need for the research is aimed at documenting the efficacy of the Nordic walking program in Covid-19 patients after discharge. 70 patients with Post Covid-19 symptoms with age 20-50 years affected mildly to moderately will be included. Exclusion criteria will include Post Covid19 patients not willing to participate, those who required invasive ventilator support during their hospitalization period, and Post Covid-19 patients with pre-diagnosed cardiovascular, pulmonary, nephrological, neurological, metabolic, oncological, or musculoskeletal disorders that can limit physical functioning. After randomly assigning the patients into two groups, a baseline assessment will be taken; the interventions will be for 4 weeks in which Group A will undergo walking as a training program and Group B will perform Nordic walking. Functional capacity, HRQoL (Health-related quality of life), depression, and anxiety will be checked. The result of this study will focus on examining the efficacy of Nordic walking on functional capacity, HRQoL, and depression and anxiety in Post Covid-19 patients. To present a novel and intriguing approach to rehabilitation and to achieve effective results in Post Covid-19 patients.

Evaluating Translational Methods for Personalized Medicine-A Scoping Review.

The introduction of personalized medicine, through the increasing multi-omics characterization of disease, brings new challenges to disease modeling. The scope of this review was a broad evaluation of the relevance, validity, and predictive value of the current preclinical methodologies applied in stratified medicine approaches. Two case models were chosen: oncology and brain disorders. We conducted a scoping review, following the Joanna Briggs Institute guidelines, and searched PubMed, EMBASE, and relevant databases for reports describing preclinical models applied in personalized medicine approaches. A total of 1292 and 1516 records were identified from the oncology and brain disorders search, respectively. Quantitative and qualitative synthesis was performed on a final total of 63 oncology and 94 brain disorder studies. The complexity of personalized approaches highlights the need for more sophisticated biological systems to assess the integrated mechanisms of response. Despite the progress in developing innovative and complex preclinical model systems, the currently available methods need to be further developed and validated before their potential in personalized medicine endeavors can be realized. More importantly, we identified underlying gaps in preclinical research relating to the relevance of experimental models, quality assessment practices, reporting, regulation, and a gap between preclinical and clinical research. To achieve a broad implementation of predictive translational models in personalized medicine, these fundamental deficits must be addressed.

Fundamental concepts of lumbar fusion and single-position circumferential lumbar interbody fusion

Lumbar interbody fusion has revolutionized the treatment of lumbar spinal disorders. Through restoration of disc height and interbody fusion, a surgeon has more options, particularly less invasive options, for surgical techniques. Single-position circumferential lumbar interbody fusion is becoming more common in the treatment of degenerative, oncologic, traumatic, and deformity disorders of the adult spine. The concept of circumferential interbody fusion has established itself in recent years, but has been afflicted by the impracicality of repositioning intraoperatively as well as only being able to address one aspect of the spine at a time. With single-position techniques, the surgeon is able to save operative time, reduce logistical problems of multi-position techniques, and operate on the spine from more than one approach simultaneously. As technology and surgeon familiarly increases, single-position interbody surgery is expected to gain even wider adoption in the adult spine field.

Antiproliferative Ruthenium Complexes Containing Curcuminoid Ligands Tested In Vitro on Human Ovarian Tumor Cell Line A2780, towards Their Capability to Modulate the NF-κBTranscription Factor, FGF-2 Growth Factor, and MMP-9 Pathway.

So far, the polyphenolic components of turmeric have shown a significant pharmacological preventative activity for a wide spectrum of diseases, including oncological disorders. This type of natural product could be of great interest for the inhibition of cancer cell proliferation, displaying less side effects in comparison to classical chemotherapeutics. The poor bioavailability and quick metabolism of such natural compounds require new investigative methods to improve their stability in the organisms. A synthetic approach to increase the efficiency of curcuminoids is to coordinate them to metals through the beta-dicarbonyl moiety. We report the synthesis and the biological attempts on human ovarian carcinoma A2780 of ruthenium(II) complexes 1–4, containing curcuminoid ligands. The cytotoxicity of complexes 1–4 proves their antiproliferative capability, and a correlation between the IC50 values and NF-κB transcription factor, FGF-2, and MMP-9 levels was figured out through the principal component analysis (PCA).

Secretory phospholipase A2: a biomarker of inflammation in autoimmune, bacterial and viral diseases

Secretory phospholipases A2 (sPLA2) represent a large superfamily of enzymes with a molecular weight of 14-19 kDa, including 15 groups and more than 30 isoforms belonging to four types: secretory (sPLA2), cytosolic (cPLA2), calcium-independent (iPLA2) and lipoprotein-associated phospholipase A2 (LP-PLA2, PAF-AH). Eleven species of secretory sPLA2s (IB, IIA, IIC, IID, IIE, IIF, III, V, X, XIIA, and XIIB) have been found in mammals, performing versatile functions and participating in the pathogenesis of a wide range of diseases. On the one hand, sPLA2 may promote elimination of damaged, apoptotic cells by hydrolyzing membrane phospholipids, and exerts a strong bactericidal and antiviral properties, including pronounced effects against antibiotic-resistant strains of microorganisms. In this regard, the use of sPLA2 may represent a new strategy for the treatment of bacterial and viral infections. Moreover, due to the action of sPLA2 on its substrates, a number of biologically active molecules (arachidonic, lysophosphatidic acids, lysophospholipids, fatty acids, prostaglandins, leukotrienes, thromboxanes) are formed, which provide strong inflammatory, detergent, coagulating effects and increase vascular permeability. This pro-inflammatory role of sPLA2 may explain its increase levels and activity in cardiovascular, respiratory, autoimmune, metabolic, oncological, bacterial and viral disorders. The review article presents a classification of sPLA2 isoforms, their substrates, regulatory factors, biological significance, and mechanisms of their strong bactericidal, virucidal, and pro-inflammatory activity in the heart and lung disorders, autoimmune, metabolic, bacterial, and viral diseases. In particular, the mechanisms of the selective action of sPLA2 against Gram-positive and Gram-negative microorganisms are discussed. We consider diagnostic and prognostic significance, correlations between elevated levels and activity of sPLA2 and distinct clinical symptoms, severity and outcome in the patients with coronary heart disease (CAD), acute myocardial infarction (AMI), atherosclerosis, acute inflammatory lung injury (ALI), respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, bronchial asthma, bacterial infections, septicemia and viral (COVID-19) infections. The opportunity of using sPLA2 as a biomarker of the severity and outcome of patients with chronic obstructive pulmonary disease, bacterial infections, sepsis and viral infections, including COVID-19, is also considered.

Update on the Use of PET/MRI Contrast Agents and Tracers in Brain Oncology: A Systematic Review.

The recent advancements in hybrid positron emission tomography–magnetic resonance imaging systems (PET/MRI) have brought massive value in the investigation of disease processes, in the development of novel treatments, in the monitoring of both therapy response and disease progression, and, not least, in the introduction of new multidisciplinary molecular imaging approaches. While offering potential advantages over PET/CT, the hybrid PET/MRI proved to improve both the image quality and lesion detectability. In particular, it showed to be an effective tool for the study of metabolic information about lesions and pathological conditions affecting the brain, from a better tumor characterization to the analysis of metabolic brain networks. Based on the PRISMA guidelines, this work presents a systematic review on PET/MRI in basic research and clinical differential diagnosis on brain oncology and neurodegenerative disorders. The analysis includes literature works and clinical case studies, with a specific focus on the use of PET tracers and MRI contrast agents, which are usually employed to perform hybrid PET/MRI studies of brain tumors. A systematic literature search for original diagnostic studies is performed using PubMed/MEDLINE, Scopus and Web of Science. Patients, study, and imaging characteristics were extracted from the selected articles. The analysis included acquired data pooling, heterogeneity testing, sensitivity analyses, used tracers, and reported patient outcomes. Our analysis shows that, while PET/MRI for the brain is a promising diagnostic method for early diagnosis, staging and recurrence in patients with brain diseases, a better definition of the role of tracers and imaging agents in both clinical and preclinical hybrid PET/MRI applications is needed and further efforts should be devoted to the standardization of the contrast imaging protocols, also considering the emerging agents and multimodal probes.

Therapeutic Drug Monitoring as a Tool for Therapy Optimization.

The use of pharmacotherapy for improving healthcare in society is increasing. A vast majority of patients have either received subtherapeutic treatment (which could result from low pharmacokinetic) or experienced adverse effects due to the toxic levels of the drug. The medicines used to treat chronic conditions, such as epilepsy; cardiovascular diseases; and oncological, neurological, and psychiatric disorders, require routine monitoring. New targeted therapies suggest an individualized treatment that can slowly move practitioners away from the concept of a one-size-fits-all-fixed-dosing approach. Therapeutic drug use can be monitored based on pharmacokinetic, pharmacodynamic, and pharmacometric methods. Based on the experiences of therapeutic drug monitoring of various agents across the globe, we can look ahead to the possible developments of therapeutic drug monitoring in India.

Unveiling Leukocyte Extracellular Traps in Inflammatory Responses of the Central Nervous System.

Over the past nearly two decades, increasing evidence has uncovered how immune cells can actively extrude genetic material to entrap invading pathogens or convey sterile inflammatory signals that contribute to shaping immune responses. Originally identified in neutrophils, the release of decondensed chromatin fibers decorated with antimicrobial proteins, called extracellular traps (ETs), has been recognized as a specific form of programmed inflammatory cell death, which is now known to occur in several other leukocytes. Subsequent reports have shown that self-DNA can be extruded from immune cells even in the absence of cell death phenomena. More recent data suggest that ETs formation could exacerbate neuroinflammation in several disorders of the central nervous system (CNS). This review article provides an overview of the varied types, sources, and potential functions of extracellular DNA released by immune cells. Key evidence suggesting the involvement of ETs in neurodegenerative, traumatic, autoimmune, and oncological disorders of the CNS will be discussed, outlining ongoing challenges and drawing potentially novel lines of investigation.

Risk factors for unplanned removal of central venous catheters in hospitalized children with hematological and oncological disorders.

Central venous catheters (CVCs) are essential devices in the treatment of pediatric patients with hematological and oncological disorders; however, the most suitable type of CVC for these patients remains unclear. We retrospectively compared risk factors for unplanned removal of two commonly used CVCs, peripherally inserted central catheters (PICCs) and tunneled CVCs, to propose which is the better device. We followed 89 patients fitted with a tunneled CVC (total 21,395 catheter-days) and 84 fitted with a PICC (total 9177 catheter-days) between January 1, 2013 and December 31, 2015, until catheter removal. Patients with a PICC had a significantly higher 3-month cumulative incidence of catheter occlusion (5.2% vs. 0%, p = 4.08 × 10-3) and total unplanned removals (29.0% vs. 6.9%, p = 0.0316) than those with tunneled CVCs. However, the cumulative incidence of central line-associated bloodstream infection did not differ significantly by CVC type. Multivariable analysis identified younger age (< 2years) [sub-distribution hazard ratio (SHR) 2.29; 95% confidence interval (CI) 1.27-4.14] and PICC (SHR 2.73; 95% CI 1.48-5.02) as independent risk factors for unplanned removal. Thus, our results suggest that tunneled CVCs are preferable in pediatric patients with hematological and oncological disorders requiring long-term, intensive treatment.

The Destiny of a Gynecology Clinic from Bucharest and its’ patients during COVID-19 Pandemic – A sad Romanian story

Background/Aim: Since March 2020 when the number of COVID-19 positive patients reported a fulminant increase in Romania, reorganisation of the medical services took place in order to provide the possibility of treating increasing number of cases with this pathology and to diminish as much as possible the number of COVID-19 related deaths. The aim of the current paper is to analyse the outcomes of 273 patients with gynaecological cancers who could not be treated in the service were they were initially addressed. Material and Method: a total number of 343 patients with gynecologic oncology disorders were addressed to “Dr. Ion Cantacuzino” hospital in Bucharest Romania and could not be treated in this unit due to the fact that it became an auxiliary service for obstetrical COVID positive patients. Results: complete follow up was possible in 273 cases 87 patients were redistributed to other services of gynecologic oncology and received their surgical treatment as planned, 141 patients received their surgical treatment in other clinics after a mean delay of six months while 45 cases were further submitted to oncological treatment, four of them being dead at the end of the study. Conclusions: modification of hospital structure and diminishing the oncological patients’ access to oncologic surgery during COVID pandemic significantly impacted on gynecologic cancer care.

Pervasive role of the long noncoding RNA DNM3OS in development and diseases.

Thousands of unique noncoding RNAs (ncRNAs) are expressed in human cells, some are tissue or cell type specific whereas others are considered as house-keeping molecules. Studies over the last decade have modified our perception of ncRNAs from transcriptional noise to functional regulatory transcripts that influence a variety of molecular processes such as chromatin remodeling, transcription, post-transcriptional modifications, or signal transduction. Consequently, aberrant expression of many ncRNAs plays a causative role in the initiation and progression of various diseases. Since the identification of its developmental role, the long ncRNA DNM3OS (Dynamin 3 Opposite Strand) has attracted attention of researchers in distinct fields including oncology, fibroproliferative diseases, or bone disorders. Mechanistic studies have in particular revealed the multifaceted nature of DNM3OS and its important pathogenic role in several human disorders. In this review, we summarize the current knowledge of DNM3OS functions in diseases, with an emphasis on its potential as a novel therapeutic target. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.

Development of a serum-free, chemically-defined workflow solution for T cell culture

Abstract Cancer immunotherapy has become one of the most promising fields in the treatment of oncologic related disorders, by harnessing the power of T-cells. Expansion and/or differentiation of cells with the right therapeutic profiles, in a consistent and safe manner, requires the use of defined cell culture reagents. One major cause of variability is serum, with its undefined composition. The presence of undefined reagents can lead to the inability to reproduce results between labs, and stop the progression from discoveries to clinical applications. Here we introduce a chemically-defined serum substitute and a low DMSO cryopreservation solution specially designed for T cells. After identifying the essential cell property parameters, and establishing appropriate cell culture assays, we initiated formulation optimization. We were able to identify the critical components required for appropriate cell expansion and cryopreservation. We were able to develop a chemically-defined solution, comparable in performance to serum, while bringing the benefits of being fully defined. We were also able to develop a low DMSO cryopreservation solution, tailored for T cell applications, comparable in performance to home brew or other commercially available solutions containing 10% DMSO. Our development work was allowed to gain in depth knowledge of the impact of each component in T cell biology, allowing us at BioLegend to provide custom tailored solutions. The development of defined reagents provides a smooth transition and reproducibility between research and clinical development.

SCIENTIFIC STUDIES ON THE EFFECTS OF THE CHANGES IN TREATMENT PROCESSES DURING THE COVID-19 PANDEMIC ON INFERTILE COUPLES: LITERATURE REVIEW

Abstract: The COVID-19 pandemic has been rapidly raging. Suspending the services related to infertility and assisted reproductive techniques are among the measures taken to prevent the spread of the epidemic. Various guides and recommendations have been published by many national and international associations for this purpose. Recommendations foresee the completion of cycles that have already been initiated and require no new reproductive therapies to be initiated except for patients with low ovarian reserve and those with a background of oncological disorders. The majority of couples whose treatment is suspended/postponed throughout this process have experienced intense stress, sadness and anxiety. In addition, some of the patients do not have adequate coping skills. This article is designated as a literature review in order to provide information about the current emotional states of infertile couples throughout the COVID-19 pandemic and to guide the studies planned for their needs. Due to the fact that the subject is related to the pandemic, the years covered by the literature review were limited to 2019 and later. As a result of the literature review; 2 studies conducted in Turkey and 5 studies conducted abroad, examining the effects of COVID-19 on infertile couples, were included. Majority of studies revealed that suspending fertility treatments caused high levels of anxiety and stress in infertile couples. Providing psychological counseling services to couples through online platforms by health professionals is thought to enable couples to cope better with the situation.