Implication of Tumor Necrosis Factor - Alpha in Preeclampsia

Introduction: Preeclampsia is an exacerbation of a generalized inflammatory response, physiologically present in the third trimester of pregnancy.Aim: The aim of the study consists in the evaluation of proinflammatory cytokine TNF-α in the context of preeclampsia. Material and Method: A transversal study was performed in three groups of patients: non-pregnant patients, patients with normal pregnancies in the third trimester, patients with preeclampsia. Serum TNF-α levels were determined using the immunometric sandwich EIA method.Results: The results obtained confirm a significant increase (p<0.01) in circulating TNF-α levels in the last trimester of pregnancy, compared to the non-pregnant status. Significantly increased serum TNF-α concentrations (p<0.001) were also found in pregnant patients with preeclampsia, compared to normotensive pregnant women. Conclusion: This proinflammatory cytokine can be a potential marker of the severity of the preeclamptic syndrome, without being an indicator of the fetal status at birth

Clozapine: An Updated Overview of Pharmacogenetic Biomarkers, Risks, and Safety—Particularities in the Context of COVID-19

Background: clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords “clozapine” and “schizophrenia”, “side effects”, “agranulocytosis”, “TRS”, or “bipolar affective disorder (BAF)” for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: we selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: we considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions’ severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) a CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with the proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together

Correlation of Caries Prevalence, Oral Health Behavior and Sweets Nutritional Habits among 10 to 19-Year-Old Cluj-Napoca Romanian Adolescents

Background and objectives: The primary oral disease during adolescence is dental caries. Less is known about the caries prevalence, oral health behavior, and sweets nutritional habits in Romanian adolescents. The objective of this study was to assess the actual caries prevalence among Romanian adolescents in a representative area of Romania, Cluj, and to correlate with oral hygiene behaviors and dietary sugary foods intake. Materials and methods: We have done a cross-sectional study of 650 adolescents aged 10 to 19-years-old (average age 15.3 &plusmn; 2.8). We performed the oral dental examination according to the WHO methodology, calculated the number of decayed, missing (due to caries), and filled teeth (DMFT index), assessed the oral hygiene and dietary behaviors using a two-section valid questionnaire and statistically analyzed the interrelation between DMFT, oral hygiene and eating behaviors by multivariate statistical analysis. Results: (a) The caries prevalence in the adolescent population enrolled in the study was 95.5%; (b) the mean DMFT was 3.13 &plusmn; 2.0, without significant differences between the urban and rural adolescents (p = 0.253); lower in females than males (p &lt; 0.050), (c) more than one third (33.7%, n = 219) of teenagers are seldom or never brush their teeth in the evening; (c) 40.6% of adolescents are missing the regular annual dental check-ups leading to an increased DMFT as shown in the multivariate analysis (p = 0.038); and (d) there is an increased prevalence of caries with age (p = 0.020), and with sugary sweetened beverages consumption (p = 0.028). Conclusions: Our study evidenced a persistent high caries prevalence in Romanian teenagers. Their dietary habits and irregular dental check-up were associated with the occurrence of dental conditions

State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer

Two-thirds of differentiated thyroid cancer (DTC) patients with distant metastases would be classified as radioactive iodine-refractory (RAIR-DTC), evolving into a poor outcome. Recent advances underlying DTC molecular mechanisms have shifted the therapy focus from the standard approach to targeting specific genetic dysregulations. Lenvatinib and sorafenib are first-line, multitargeted tyrosine kinase inhibitors (TKIs) approved to treat advanced, progressive RAIR-DTC. However, other anti-angiogenic drugs, including single targeted TKIs, are currently being evaluated as alternative or salvage therapy after the failure of first-line TKIs. Combinatorial therapy of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signalling cascade inhibitors has become a highly advocated strategy to improve the low efficiency of the single agent treatment. Recent studies pointed out targetable alternative pathways to overcome the resistance to MAPK and PI3K pathways’ inhibitors. Because radioiodine resistance originates in DTC loss of differentiation, redifferentiation therapies are currently being explored for efficacy. The present review will summarize the conventional management of DTC, the first-line and alternative TKIs in RAIR-DTC, and the approaches that seek to overcome the resistance to MAPK and PI3K pathways’ inhibitors. We also aim to emphasize the latest achievements in the research of redifferentiation therapy, immunotherapy, and agents targeting gene rearrangements in advanced DTC

State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer

Two-thirds of differentiated thyroid cancer (DTC) patients with distant metastases would be classified as radioactive iodine-refractory (RAIR-DTC), evolving into a poor outcome. Recent advances underlying DTC molecular mechanisms have shifted the therapy focus from the standard approach to targeting specific genetic dysregulations. Lenvatinib and sorafenib are first-line, multitargeted tyrosine kinase inhibitors (TKIs) approved to treat advanced, progressive RAIR-DTC. However, other anti-angiogenic drugs, including single targeted TKIs, are currently being evaluated as alternative or salvage therapy after the failure of first-line TKIs. Combinatorial therapy of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signalling cascade inhibitors has become a highly advocated strategy to improve the low efficiency of the single agent treatment. Recent studies pointed out targetable alternative pathways to overcome the resistance to MAPK and PI3K pathways&rsquo; inhibitors. Because radioiodine resistance originates in DTC loss of differentiation, redifferentiation therapies are currently being explored for efficacy. The present review will summarize the conventional management of DTC, the first-line and alternative TKIs in RAIR-DTC, and the approaches that seek to overcome the resistance to MAPK and PI3K pathways&rsquo; inhibitors. We also aim to emphasize the latest achievements in the research of redifferentiation therapy, immunotherapy, and agents targeting gene rearrangements in advanced DTC

Oncofertility and COVID-19: At the Crossroads between Two Time-Sensitive Fields

Background: COVID-19 infection has dominated our lives and left its mark on it. The impact on fertility is major, and the long-term consequences may be disastrous. When we talk about oncofertility, we are talking about those patients worried about the delay in receiving medical services (possible cancelation of surgery, decreased availability of medical services, reorientation of medical resources) due to COVID-19. Finally, patients&rsquo; worsening biological and reproductive statuses, associated with high levels of anxiety and depression, are closely related to social restrictions, economic impact, reorientation of medical resources, health policies, and fears of SARS-CoV-2 infection. Aim: We reviewed the current literature on fertility during the COVID-19 pandemic and its effect on cancer patients. Specifically, how cancer treatment can affect fertility, the options to maintain fertility potential, and the recovery options available after treatment are increasingly common concerns among cancer patients. Methods: A systematic literature search was conducted using two main central databases (PubMed&reg;/MEDLINE, and Web of Science) to identify relevant studies using keywords SARS-CoV-2, COVID-19, oncofertility, young cancer patient, cryopreservation, assisted reproductive techniques (ART), psychosocial, telemedicine. Results: In the present study, 45 papers were included, centered on the six main topics related to COVID-19. Conclusions: Fertility preservation (FP) should not be discontinued, but instead practiced with adjustments to prevent SARS-CoV-2 transmission. The increased risk of SARS-CoV-2 infection in cancer patients requires screening for COVID-19 before FP procedures, among both patients and medical staff in FP clinics, to prevent infection that would rapidly worsen the condition and lead to severe complications