Is Circulating DNA and Tumor Cells in Myeloma the Way Forward?

Multiple myeloma (MM) is the second deadliest hematological cancer. Despite the enormous innovation on MM treatment in the last decades, still 48% of patients die within 5 years after diagnosis. MM diagnosis and therapeutic strategy mainly rely on direct bone marrow (BM) assessment. Given the MM heterogeneity, BM biopsies do not accurately reflect the whole disease status, hampering accurate disease prognosis. Moreover, biopsies are painful and invasive procedures, highlighting the need for non-invasive and more accurate source of biomarkers. Liquid biopsies are promising sources of biomarkers that may overcome these limitations. Peripheral blood carries circulating myeloma components that are being extensively explored since the last few years as an alternative to BM aspirates. These include circulating tumor cells (CTC), cell-free DNA (cfDNA), and extracellular vesicles containing miRNA and proteins. The current review summarizes scientific evidence establishing BM as a gold standard for the diagnosis, prognosis, and evaluation of minimal residual disease. We discuss the last advances regarding cfDNA and CTC biomarkers from peripheral blood in patients with MM as well as the statistical validations. This paper addresses the technological hurdles associated with liquid biopsies and examines the missing steps for their inclusion into the clinical practice.

In Vitro Ballooned Hepatocytes Can Be Produced By Primary Human Hepatocytes and Hepatic Stellate Cell Sheets

Background Despite the increasing prevalence of Nonalcoholic steatohepatitis (NASH) worldwide, there is no effective treatment available for this disease. “Ballooned hepatocyte” is a characteristic finding in NASH and is correlated with disease prognosis, but their mechanisms of action are poorly understood; furthermore, neither animal nor in vitro models of NASH have been able to adequately represent ballooned hepatocytes. Herein, we engineered cell sheets to develop a new in vitro model of ballooned hepatocytes. Methods Primary human hepatocytes (PHH) and Hepatic stellate cells (HSC) were co-cultured to produce cell sheets, which were cultured in glucose and lipid containing medium, following which histological and functional analyses were performed. Results Histological findings showed hepatocyte ballooning, accumulation of fat droplets, abnormal cytokeratin arrangement, and the presence of Mallory-Denk bodies and abnormal organelles. These findings are similar to those of ballooned hepatocytes in human NASH. Functional analysis showed elevated levels of TGFβ-1, SHH, and p62, but not TNF-α, IL-8. Conclusions Exposure of PHH/HSC sheets to a glucolipotoxicity environment induces ballooned hepatocyte without inflammation. Moreover, fibrosis is an important mechanism underlying ballooned hepatocytes and could be the basis for the development of a new in vitro NASH model with ballooned hepatocytes.

Getting Vaccinated Helps: Prospective Study Reveals Lower CT Severity Scores amongst COVID Vaccine Recipients

Context Computerized tomography (CT) is an invaluable imaging investigation for evaluating COVID-19 disease. CT detects early changes of COVID-19 pneumonia and predicts the disease prognosis based on a semiquantitative 25-point CT severity score (CT-SS). India launched its vaccination drive in January 2021 with two different vaccines being approved by the government. These vaccines are believed to prevent the disease itself, in majority of the cases and at least decrease disease severity, in the rest. Aim This study aims to evaluate the CT-SS in vaccinated and non-vaccinated subjects who have been diagnosed with COVID-pneumonia or are COVID suspects. Subjects and Methods A total of 3,235 patients with typical COVID-19 related imaging findings on HRCT thorax were included in the study. These subjects were divided into three age categories, 18–44, 45–59 and ≥60 years. The CT severity scores were allotted by experienced radiologists. Medians of the scores in different age groups were compared amongst vaccinated and non-vaccinated individuals using the Kruskal–Wallis H test. A p-value < 0.05 was considered significant. All results were shown with 95% confidence interval. Results The difference in the medians amongst the vaccinated and non-vaccinated groups was significant, p-values being < 0.001 in all age categories. Conclusion The mean CT-SS was less in vaccinated subjects and the difference in median CT-SS amongst vaccinated and non-vaccinated individuals was statistically significant, thus sending an important message that it is mandatory for the population at large to get vaccinated to reduce infection rate/disease severity.

Association of Underlying Comorbidities and progression of COVID-19 Infection Among 2586 Patients Hospitalized in the National Capital Region of India: A Retrospective Cohort Study

Objectives This study is conducted to observe the association of diabetes (DM), hypertension (HTN), and chronic kidney disease on the prognosis and mortality of COVID-19 infection in hospital admitted patients.Methods This is a single centre, observational, retrospective study carried out at Sir Ganga Ram Hospital, Delhi, India. the burden of comorbidities on the prognosis and clinical outcome of COVID-19 patients admitted patients from April 8, 2020, to October 4, 2020. Chi-square and relative risk test were used to observe the association of comorbidities and disease prognosis.Results A total of 2586 patients were included in the study consisting of 69.6% of male patients. All the comorbidities were significantly associated with ICU admission and mortality. The relative risk showed that CKD is most prone to severity as well as mortality of the COVID-19 infection followed by HTN and DM. Further with the increase in comorbidity, the risk of ICU admission and mortality increases.Conclusion Diabetes, hypertension and CKD, all are associated with progression of COVID-19 disease to severity and higher mortality risk. The number of underlying comorbid condition is directly proportional to the progression of disease severity and mortality.

Oral Cancer Theranostic Application of FeAu Bimetallic Nanoparticles Conjugated with MMP-1 Antibody

Metastatic oral squamous cell carcinoma (SCC) displays a poor disease prognosis with a 5-year survival rate of 39%. Chemotherapy has emerged as the mainstream treatment against small clusters of cancer cells but poses more risks than benefits for metastatic cells due to the non-specificity and cytotoxicity. To overcome these obstacles, we conjugated antibodies specific for matrix metalloproteinase-1 (MMP-1), a prognostic biomarker of SCC, to iron–gold bimetallic nanoparticles (FeAu NPs) and explored the capability of this complex to target and limit SSC cell growth via magnetic field-induced hyperthermia. Our results showed that 4.32 ± 0.79 nm sized FeAu NPs were superparamagnetic in nature with a saturation magnetization (Ms) of 5.8 emu/g and elevated the media temperature to 45 °C, confirming the prospect to deliver hyperthermia. Furthermore, conjugation with MMP-1 antibodies resulted in a 3.07-fold higher uptake in HSC-3 (human tongue squamous cell carcinoma) cells as compared to L929 (fibroblast) cells, which translated to a 5-fold decrease in cell viability, confirming SCC targeting. Finally, upon magnetic stimulation, MMP-1-FeAu NPs conjugate triggered 89% HSC-3 cellular death, confirming the efficacy of antibody-conjugated nanoparticles in limiting SCC growth. The synergistic effect of biomarker-specific antibodies and magnetic nanoparticle-induced hyperthermia may open new doors towards SCC targeting for improved disease prognosis.

Erectile dysfunction and testosterone levels prior to COVID-19 disease: What is the relationship?

Objective: We aimed to investigate the relationship between COVID-19 and Erectile Dysfunction (ED) and the effect of serum testosterone level on the disease prognosis. Methods: Between April-December 2020, 70 patients who were admitted with a complaint of ED after having COVID-19 and whose serum testosterone level was checked for varicocele, premature ejaculation, and infertility reasons before COVID-19. The patients filled the International Index of Erectile Function (IIEF-5) and their testosterone level was checked. The questionnaire was arranged to assess the first month before COVID-19 and after COVID-19. Testosterone levels of the patients before and after COVID-19 were compared. The relationship between testosterone levels and hospitalization in the intensive care was evaluated.Results: It was revealed that testosterone levels and IIEF-5 scores after COVID-19 in all patients were statisticaly and significantly different compared to the period before COVID-19 (p < 0.05). Testosterone levels of patients in need of intensive care were significantly higher than those without any need of intensive care (p < 0.05).Conclusions: Our study has presented that COVID-19 may cause ED and high testosterone levels increase the rate of hospitalization in the intensive care by intensifying the disease.

Methodological approach to risk prediction noncompliance in patients with myocardial infarction

Aim. To develop a methodological approach in order to predict the risk of noncompliance in patients with myocardial infarction.Methods. 416 patients were questioned in the single-centered, prospective, non-randomized study using the original author's method. The patients were treated in specialized cardiological departments of the city of Kemerovo with the diagnosed myocardial infarction. The methodological approach to predicting the risk of non-compliance in patients with myocardial infarction covered 29 factors in 6 main blocks: sociodemographic and socio-economic characteristics, health status, medical and pharmaceutical culture of the patient, awareness of medical and pharmaceutical services, patient adherence to medical recommendations.Results. Patients with myocardial infarction were characterized by insufficient adherence to the therapy, low awareness of the disease, which can negatively affect the longterm disease prognosis. The identification of a large number of subjective factors limiting adherence to the therapy is the reason for the widespread use of noncompliance risk measurement among patients with myocardial infarction, which will allow determining the range of the risk group for each individual patient.Conclusion. The adherence to the treatment of patients with myocardial infarction is revealed as 80% which is indicated as low and requires the prophylactic use of educational and psychological programs that increase medical and social awareness and readiness to comply with the doctor's recommendations, and also justifies the need for complex risk measurement of non-compliance patients for personalized identification and addressing risk factors for poor adherence to therapy.

Platelet Index in Patients with Confirmed Coronavirus Disease 2019 Cases

BACKGROUND: Changes found on hematological examination are a helpful modality for assessing coronavirus disease 2019 (COVID-19). In addition, platelet index is a parameter that can help in assessing the COVID-19 disease prognosis. AIM: Objective of the study is to determine the difference in platelet index in nucleid acid amplification test (NAAT) confirmed COVID-19 patients, suspected COVID-19 with negative NAAT results, and non-COVID-19 controls. METHODS: This is an analytical observational study with 96 subjects; 48 subjects with confirmed COVID-19, 23 subjects suspected COVID-19 with negative NAAT results, and 24 non-COVID-19 control subjects. First, NAAT examination was carried out using the GeneXpert tool with the target genes of the E and N2 genes. Then, the platelet index was compared between the three groups by the Kruskal-Wallis test. RESULTS: There was no significant difference in the number of platelet (PLT), mean PLT volume (MPV), and PLT crit (PCT) between the three groups with p = 0.732, 0.741 and 0.483, respectively. In general, the number of PLT, MPV, and PCT in the three groups was within the normal reference value. CONCLUSIONS: There were no significant differences observed in the number of PLT, MPV, and PCT between COVID-19 patients with positive NAAT, COVID-19 suspects with negative NAAT, and non-COVID-19 controls. Therefore, detecting the severe acute respiratory syndrome coronavirus 2 virus by NAAT examination in COVID-19 patients has not altered the PLT index changes.

An Anomaly with Potential as a New Prognostic Marker in CLL with del(13q): Gain of 16p13.3

Deletion 13q [del(13q)] is a favorable prognostic marker if it is detected as a sole abnormality in chronic lymphocytic leukemia (CLL). However the clinical courses of cases with isolated del(13q) are quite heterogeneous. In our study, we investigated copy number variations (CNVs), loss of heterozygosity (LOH), and the size of del(13q) in 30 CLL patients with isolated del(13q). We used CGH+SNP microarrays in order to understand the cause of this clinical heterogeneity. We detected del(13q) in 28/30 CLL cases. The size of the deletion varied from 0.34 to 28.81 Mb, and there was no clinical effect of the deletion size. We found new prognostic markers, especially the gain of 16p13.3. These markers have statistically significant associations with short time to first treatment and advanced disease stage. Detecting both CNVs and LOH at the same time is an advantageous feature of aCGH+SNP. However, it is very challenging for the array analysis to detect mosaic anomalies. Therefore, it is very important to confirm the results by FISH. In our study, we detected approximately 9% mosaic del(13q) by microarray. In addition, the gain of 16p13.3 may affect the disease prognosis in CLL. However, additional studies with more patients are needed to confirm these results.