Automated Machine Learning to Develop Predictive Models of Metabolic Syndrome in Patients with Periodontal Disease.

Metabolic syndrome is experiencing a concerning and escalating rise in prevalence today. The link between metabolic syndrome and periodontal disease is a highly relevant area of research. Some studies have suggested a bidirectional relationship between metabolic syndrome and periodontal disease, where one condition may exacerbate the other. Furthermore, the existence of periodontal disease among these individuals significantly impacts overall health management. This research focuses on the relationship between periodontal disease and metabolic syndrome, while also incorporating data on general health status and overall well-being. We aimed to develop advanced machine learning models that efficiently identify key predictors of metabolic syndrome, a significant emphasis being placed on thoroughly explaining the predictions generated by the models. We studied a group of 296 patients, hospitalized in SCJU Sibiu, aged between 45-79 years, of which 57% had metabolic syndrome. The patients underwent dental consultations and subsequently responded to a dedicated questionnaire, along with a standard EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) questionnaire. The following data were recorded: DMFT (Decayed, Missing due to caries, and Filled Teeth), CPI (Community Periodontal Index), periodontal pockets depth, loss of epithelial insertion, bleeding after probing, frequency of tooth brushing, regular dental control, cardiovascular risk, carotid atherosclerosis, and EQ-5D-5L score. We used Automated Machine Learning (AutoML) frameworks to build predictive models in order to determine which of these risk factors exhibits the most robust association with metabolic syndrome. To gain confidence in the results provided by the machine learning models provided by the AutoML pipelines, we used SHapley Additive exPlanations (SHAP) values for the interpretability of these models, from a global and local perspective. The obtained results confirm that the severity of periodontal disease, high cardiovascular risk, and low EQ-5D-5L score have the greatest impact in the occurrence of metabolic syndrome.

IL-1 Beta-A Biomarker for Ischemic Stroke Prognosis and Atherosclerotic Lesions of the Internal Carotid Artery.

Background and Objectives: Stroke is a leading cause of mortality and morbidity worldwide. Treatment of this pathology is still under development and its risk factors remain to be determined. Therefore, we aim to determine the role of interleukin-1 beta in atherosclerotic lesions of the internal carotid artery as a risk factor for stroke and the role of this biomarker in stroke prognosis. Materials and Methods: This study enrolled 56 patients diagnosed with ischemic stroke in the anterior vascular territory (AVT) and posterior vascular territory (PVT). All the patients had venous blood collected at admission and 7 days after the onset of the cerebral ischemia in order to determine the plasma concentration of interleukin-1 beta. At the same time, an extracranial carotid ultrasound was performed. Results: The interleukin-1 beta collected at admission was positively correlated with the NIHSS at admission (Pearson index 0.424), and both measurements were correlated with carotid stenosis (Spearmen correlation index of 0.529 and 0.653, respectively). Conclusions: Interleukin-1 beta could be a reliable biomarker for stroke prognosis and the development of atherosclerotic lesions of the internal carotid.

Interactions between Metabolic Syndrome, MASLD, and Arterial Stiffening: A Single-Center Cross-Sectional Study.

Metabolic-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), has emerged as a prominent global cause of chronic liver disease and is increasingly recognized as associated with atherosclerotic vascular illness, consolidating its position along traditional cardiovascular risk factors. Individuals with MASLD exhibit a combination of metabolic syndrome risk factors, carotid atherosclerosis, and increased arterial stiffness, hinting at shared pathogenesis. In this study, we aim to explore liver involvement and arterial stiffness within metabolic syndrome. We enrolled 75 patients (30 male and 45 female) with either liver steatosis on conventional ultrasound, altered liver function tests, or the presence of cardiometabolic risk factors after excluding liver pathology other than MASLD. Clinical evaluation, laboratory measurements, abdominal and carotid ultrasounds, vibration-controlled transient elastography (VCTE, Fibroscan), and assessment with the Arteriograph (Tensiomed) were performed. The 26 patients diagnosed with MetS had significantly higher liver involvement as quantified via the hepatic steatosis index (HSI), Fibrosis-4 (FIB4), aspartate aminotransferase to platelet ratio index (APRI) category, and VCTE measurements, as well as Agile 3+ and Agile 4 scores which use a combination of clinical and laboratory parameters together with results obtained from VCTE to reflect the probability of advanced liver fibrosis or cirrhosis. Patients with MetS also exhibited more pronounced vascular involvement as quantified via arterial stiffness measurements and CIMT (carotid intima-media thickness). We applied a two-step clustering algorithm to enhance our analysis, which gave us pertinent insight into the interplay between metabolic syndrome elements and typologies of hepatic steatosis and arterial stiffness degrees. Notably, of the three obtained clusters, the cluster showing increased levels of hepatic steatosis and arterial stiffness also exhibited the highest prevalence of metabolic syndrome and its constituting components. The results have significant clinical implications, advocating for a comprehensive diagnostic approach when MetS or MASLD is suspected.

Hepatic Involvement across the Metabolic Syndrome Spectrum: Non-Invasive Assessment and Risk Prediction Using Machine Learning.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) and metabolic syndrome (MetS) are inextricably linked conditions, both of which are experiencing an upward trend in prevalence, thereby exerting a substantial clinical and economic burden. The presence of MetS should prompt the search for metabolic-associated liver disease. Liver fibrosis is the main predictor of liver-related morbidity and mortality. Non-invasive tests (NIT) such as the Fibrosis-4 index (FIB4), aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), hepatic steatosis index (HIS), transient elastography (TE), and combined scores (AGILE3+, AGILE4) facilitate the detection of liver fibrosis or steatosis. Our study enrolled 217 patients with suspected MASLD, 109 of whom were diagnosed with MetS. We implemented clinical and biological evaluations complemented by transient elastography (TE) to discern the most robust predictors for liver disease manifestation patterns. Patients with MetS had significantly higher values of FIB4, APRI, HSI, liver stiffness, and steatosis parameters measured by TE, as well as AGILE3+ and AGILE4 scores. Machine-learning algorithms enhanced our evaluation. A two-step cluster algorithm yielded three clusters with reliable model quality. Cluster 1 contained patients without significant fibrosis or steatosis, while clusters 2 and 3 showed a higher prevalence of significant liver fibrosis or at least moderate steatosis as measured by TE. A decision tree algorithm identified age, BMI, liver enzyme levels, and metabolic syndrome characteristics as significant factors in predicting cluster membership with an overall accuracy of 89.4%. Combining NITs improves the accuracy of detecting patterns of liver involvement in patients with suspected MASLD.

A Severity Score and Outcome Prediction in Patients that Suffered an Ischemic Stroke.

Background: Stroke is the main cause of disability and exitus worldwide. The prediction of mortality of this pathology represents a major challenge. More than that, the infection with the SARS-CoV-2 virus is a challenge for every clinician worldwide, and hypercoagulability is one of its biggest concerns that can lead to stroke. Objective: Our aim was to develop a severity stroke index for both SARS-CoV-2 stroke patients and noninfected stroke patients which we hope to be helpful in patient's management. Methods: We conducted a prospective study during January 2021-June 2021 which included 80 patients who suffered an ischemic stroke, 40 of which had both stroke and SARS-CoV-2 infection. We have established a panel of biomarkers including CRP, IL-6, fibrinogen, ESR, D-dimer, leucocytes, lymphocytes, and NLR and compared the results of our two cohorts. Results: SARS-CoV-2 stroke patients have experienced elevated levels of biomarkers that rise in inflammation such as hs-CRP, IL-6, and D-dimer, comparing to noninfected stroke patients. Also, the probability of exitus in SARS-CoV-2 patients is 4.2 times higher than in noninfected subjects. With regard to stroke severity, we have concluded that a NIHSS score higher than 15 points considerably influences the death rate, the probability of exitus being 9.16 times higher than in NIHSS score lower than 15. Conclusion: Based on our result, we have established a severity score index which includes NIHSS score, age, gender, the presence/absence of COVID-19 infection, and the following biomarkers: hs-PCR, IL-6, D-dimer, fibrinogen, and ESR, which can be used as a tool to guide patient's management.

Prognostic markers for ischemic stroke - are they truly reliable?

Background: Stroke is one of the leading causes of mortality and morbidity worldwide. Despite extensive research, to this date there is no panel of biomarkers for the prevention and prognosis of ischemic stroke and there is still much incomplete and insufficiently researched information. Aim: We conducted a prospective, observational study between January and June 2020. The main objective of this study was to clarify the role of inflammation markers, i.e. neutrophil/ lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), high-sensitivity C - reactive protein (hsCRP) in ischemic stroke and whether there is or not a correlation between these markers and carotid stenosis. Study design: In the study we included 150 subjects divided in two groups: study group - 100 subjects and control group - 50 subjects. Methods: Data collected during the research (at the time of patient admission): 1) biological sample: 5 ml of peripheral blood were collected in a vial with clot activator and separating gel, from which the following laboratory tests were performed: hsCRP, neutrophils, lymphocytes, platelets. NLR and PLR were subsequently calculated as the ratio of neutrophils to lymphocytes, respectively platelets and lymphocytes), 2) paraclinical examinations: extracranial carotid Doppler ultrasound examination. Results: The results were impressive: high-sensitivity C reactive protein (hsCRP), neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were strongly, respectively moderately correlated with the severity of stroke (the severity being established with the NIHS (National Institute of Health Stroke) score. None of the inflammation markers included in the present study was correlated with carotid stenosis. Conclusion: hsCRP, NLR and PLR may potentially be prognostic markers for ischemic stroke, being of major help in preventing its possible complications.

From a bispecific monoclonal antibody to gene therapy: A new era in the treatment of hemophilia A.

The treatment of hemophilia A has progressed amazingly in recent years. Emicizumab, a bispecific-humanized monoclonal antibody, is able to improve coagulation by bridging activated factor IX and factor X. Emicizumab is administered subcutaneously and much less often compared to factor VIII products. It has low immunogenicity, does not require dose adjustment, and can be administered regardless of the presence of factor VIII inhibitors. Thrombin generation assays but not factor VIII activity are indicated to guide and monitor the treatment. Emicizumab has enabled the conversion of patients with severe forms into patients with milder forms of hemophilia A. It has reduced the number of bleeding episodes compared to both on-demand and prophylactic substitution therapy and has an excellent safety profile. Gene therapy can elevate factor VIII plasma levels for many years after a single treatment course, could offer long-term protection from bleeding episodes, and minimize or eliminate the need for substitutive treatment with factor VIII concentrates. Gene therapy can provoke an immune response, manifested by an increase in common liver enzymes, that require immunotherapy. Long term monitoring is necessary to identify possible adverse effects. Future objectives are: the development of an ideal viral vector, the possibility of its re-administration, the use of gene therapy in hemophiliac children, and determining whether it can be successfully used to induce immune tolerance to factor VIII ceteri paribus. The future will determine the place of each type of treatment and group of patients for which it is indicated.

Venetoclax in Acute Myeloid Leukemia.

BACKGROUND: Substantial progress in the therapeutic arsenal used to treat acute myeloid leukemia became possible in the last decade, as a result of advances in gene editing and descriptive and functional genomics. OBJECTIVE: The aim of this study is to analyze the efficacy and safety of venetoclax in the treatment of acute myeloid leukemia. METHODS: A mini-review was achieved using the articles published in PubMed and Web of Science in the last year, prior to 05.05.2021, which were searched using the terms "acute myeloid leukemia" and "venetoclax" and the new patents published in this field. RESULTS: BCL-2 inhibitors administered in monotherapy are active against acute myeloid leukemia cells, but their efficacy is partially limited because they do not target other antiapoptotic proteins and venetoclax induced overexpression of the other antiapoptotic molecules. Venetoclax-based combinations (including those with hypomethylating agents) were able to improve outcomes for older patients with acute myeloid leukemia, including both remission rates and overall survival. Other drugs used in combination with venetoclax include: FLT3 inhibitors, IDH2 inhibitors, chidamide, ibrutinib, lapatinib, mivebresib, triptolide, metabolic inhibitors, nucleoside analogs, and classical chemotherapeutics. Both the mechanisms of venetoclax resistance and the ways to overcome it, as well as the adverse effects of venetoclax are analyzed. CONCLUSION: The management of unfit and older patients with acute myeloid leukemia should be personalized and be the result of evaluating patient- and disease-specific factors that are essential to their care. Combinations that include venetoclax are an increasingly well-documented option for many of them.

Role of biological markers and CT severity score in predicting mortality in patients with COVID­19: An observational retrospective study.

COVID-19 pandemic is a continuing ongoing emergency of public concern. Early identification of markers associated with disease severity and mortality can lead to a prompter therapeutic approach. The present study conducted a multivariate analysis of different markers associated with mortality in order to establish their predictive role. Confirmed cases of 697 patients were examined. Demographic data, clinical symptoms and comorbidities were evaluated. Laboratory and imaging severity scores were reviewed. A total of 133 (19.1%) out of 697 patients succumbed during hospitalization. Obesity was the most common comorbidity, followed by hypertension, diabetes, coronary heart disease and chronic kidney disease. Compared with the survivor patients, non-survivors had a higher prevalence of diabetes, chronic kidney disease and coronary heart disease, as well as higher values of laboratory markers such as neutrophil-lymphocyte ratio (NLR), D-dimer, procalcitonin, IL-6 and C Reactive protein (CRP) and respectively high values of imaging severity scores. Multivariate regression analysis showed that high values of the proposed markers and chest computerized tomography (CT) severity imaging score were predictive for in hospital death: NLR [hazard ratio (HR): 3.127 confidence interval (CI) 95: 2.137-4.576]; D-dimer [HR: 6.223 (CI 95:3.809-10.167)]; procalcitonin [HR: 4.414 (CI 95:2.804-6.948)]; IL-6 [HR: 3.344 (CI 95:1.423-7.855)]; CRP [HR:2.997 (CI 95:1.940-4.630)]; and CT severity score [HR: 3.068 (CI 95:1.777-5.299)]. Laboratory markers and imaging severity scores could be used to stratify mortality risk in COVID-19 patients.

The Influence of Periodontal Disease on Oral Health Quality of Life in Patients with Cardiovascular Disease: A Cross-Sectional Observational Single-Center Study.

Background and Objectives: Cardiovascular disease is a leading cause of global death with a rising prevalence and a heavy economic burden. Periodontal disease has been associated with cardiovascular diseases­including incident coronary heart disease, peripheral artery disease and ischemic stroke. The study evaluates the quality of life of patients with cardiovascular and periodontal disease from the point of view of oral health by using the short version of the Oral Health Impact Profile (OHIP-14) questionnaire. Materials and Methods: This study included a total of 221 patients (61.86 ± 15.03 years old) selected from the Emergency Hospital of Sibiu, Romania. The participants self-completed the OHIP-14 questionnaire and they benefited from an oral health examination conducted to assess the presence and the severity of periodontal disease. Results: Out of the 147 patients with cardiovascular disease, 77.5% had periodontal disease (32.6% stage I, 29.2% stage II, and 15.6% stage III and IV). The presence of periodontal disease was associated with a lower oral-health-related quality of life (p < 0.001, ANOVA) and with a higher OHIP-14 score in patients with cardiovascular disease (18.67 ± 8.17, p < 0.001 ANOVA). No significant difference was observed concerning patient sex and background; however, age, body mass index and the lack of an appropriate oral hygiene routine had a strong association with the individual quality of life. The general OHIP-14 score was higher in patients with periodontal disease and associated cardiovascular disease, the presence of both cardiovascular and periodontal disease being associated with a lower quality of life. Conclusions: By increasing the patients' awareness to oral healthcare measures, better outcomes and improved oral-health-related quality of life could be observed.

Warfarin involvement, in comparison to NOACs, in the development of systemic atherosclerosis.

Adverse effects of drugs are one of the objective criteria used for choosing the most appropriate anticoagulant. It is worrying that warfarin may be involved in the progression of systemic atherosclerosis, as more and more articles suggest. Warfarin has been widely used in the past and has greater efficacy compared to dabigatran in patients with mechanical heart valves; there is an antidote to it and it is cheap. Unfortunately, warfarin inhibits the synthesis and activity of Matrix-Gla-Protein, which is the major vitamin K-dependent inhibitor of arterial calcification - an active process associated with atherosclerosis, stimulated by inflammatory mechanisms. Vitamin K antagonizes the NF-κB signaling mechanism and contributes to the prevention of arterial calcifications. Warfarin given in experimental animal models of atherosclerosis contributed to the occurrence of an increased number of aortic calcifications. Warfarin treatment used in clinical trials was associated with the progressive increase of coronary atheroma calcification. Younger patients are more sensitive to warfarin-related arterial calcifications compared to older patients, due to warfarin-induced cellular senescence changes. Non-vitamin K antagonist direct oral anticoagulants do not interact with vitamin K. Edoxaban reduces the inflammatory process in the vascular walls and the proliferation of smooth vascular muscle cells, so it is involved in the prevention of vascular maladaptive remodeling process. Apixaban is able to stabilize the coronary atherosclerotic process. Randomized clinical trials are needed to evaluate the impact of warfarin on plaque stability and cardiovascular evolution of patients.

The high-performance technology CRISPR/Cas9 improves knowledge and management of acute myeloid leukemia.

Knowledge on acute myeloid leukemia pathogenesis and treatment has progressed recently, but not enough to provide ideal management. Improving the prognosis of acute myeloid leukemia patients depends on advances in molecular biology for the detection of new therapeutic targets and the production of effective drugs. The CRISPR/Cas9 technology allows gene insertions and deletions and it is the first step in investigating the function of their encoded proteins. Thus, new experimental models have been developed and progress has been made in understanding protein metabolism, antitumor activity, leukemic cell maintenance, differentiation, growth, apoptosis, and self-renewal, the combined pathogenetic mechanisms involved in leukemogenesis. The CRISPR/Cas9 system is used to understand drug resistance and find solutions to overcome it. The therapeutic progress achieved using the CRISPR/Cas9 system is remarkable. FST gene removal inhibited acute myeloid leukemia cell growth. Lysine acetyltransferase gene deletion contributed to decreased proliferation rate, increased apoptosis, and favored differentiation of acute myelid leukemia cells carrying MLL-X gene fusions. The removal of CD38 gene from NK cells decreased NK fratricidal cells contributing to increased efficacy of new CD38 CAR-NK cells to target leukemic blasts. BCL2 knockout has synergistic effects with FLT3 inhibitors. Exportin 1 knockout is synergistic with midostaurin treatment in acute myeloid leukemia with FLT3-ITD mutation. Using the results of CRISPR/Cas9 libraries and technology application will allow us to get closer to achieving the goal of curing acute myeloid leukemia in the coming decades.

Saliva pH and Flow Rate in Patients with Periodontal Disease and Associated Cardiovascular Disease.

BACKGROUND Periodontal disease, a frequent oral health problem, is connected with cardiovascular morbidity and mortality. This study aimed to assess the unstimulated saliva flow rate and saliva pH as markers of the severity of periodontal disease in patients with cardiovascular disease. MATERIAL AND METHODS A cohort of 155 patients (78 men and 77 women, aged 30-92 years) was included, and a structured questionnaire obtained information about their health status, oral healthcare behaviors, and eating habits. An oral examination was performed to assess periodontal status and presence of dental calculus. The unstimulated whole salivary flow rate and salivary pH were measured. An oral hygienization was performed, and 3 months later, salivary flow rate and pH were reevaluated. RESULTS A severe form of periodontal disease was found in 22.4% of patients. Disease severity was strongly correlated with low pH values (6.25 in stage IV periodontal disease), lower salivary flow rate (0.28 mL/min), smoking, poor oral hygiene habits and obesity, with no significant differences by sex. We observed a significant increase of pH (up to 6.30±0.17) in patients with severe periodontal disease (P=0.001) and salivary flow rate values (0.29±0.07 mL/min; P=0.014) 3 months after oral hygienization. There was a strong association between the severity of periodontal disease and presence of cardiovascular disease (P=0.001). CONCLUSIONS Our study suggests that the decrease of salivary flow rate and pH level might be associated with the severity of periodontal disease.

Management of patients with chronic lymphocytic leukemia during the SARS-CoV-2 pandemic.

Oncohematological patients are prone to develop infections due to immunosuppression caused by the disease and chemo-immunotherapy. The aim of this review was to outline the details of the management of patients with chronic lymphocytic leukemia (CLL) during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Patients with CLL often exhibit inadequate humoral and cellular immune responses to various infections and vaccinations. Patients under the 'watch and wait' strategy have a lower risk of infections, including with SARS-CoV-2, compared with those undergoing therapeutic interventions, but they still have a higher risk than age-matched controls. Patients with CLL have a high risk of developing severe forms of coronavirus disease-2019 (COVID-19), particularly if they are undergoing chemo-immunotherapy. The total anti-SARS-CoV-2 antibody titer demonstrates a slower increase in patients with CLL infected with the virus, and the antibody levels tend to decrease after reaching a maximum level sooner than in healthy individuals. This leads to a late negativation of the PCR tests and a longer duration of hospitalization. In total, ~1/3 of patients with CLL do not develop a persistent titer of antiviral antibodies, and this is associated with the presence of hypogammaglobulinemia. It appears that patients with CLL have the worst outcomes amongst patients with malignant hemopathies and SARS-CoV-2 infection. Bruton tyrosine kinase inhibitors reduce the hyperinflammatory status of patients with CLL with COVID-19, which is accompanied by decreased levels of serum inflammatory markers, ferritin and D-dimer, and serum levels of pro-inflammatory cytokines, but they increase the risk of infections and impaired humoral immunity. An abrupt discontinuation of these may promote the rapid decompensation of CLL, which may even mimic the clinical manifestations of COVID-I9, including a significant increase in cytokine release. In conclusion, therapeutic decisions must be personalized to each patient with CLL and each at risk patient must be quarantined during the SARS-CoV-2 pandemic to reduce their risk of contraction.

Thrombin Generation in Chronic Liver Diseases-A Pilot Study.

The knowledge about coagulation disorders in patients with chronic liver disease changed in the last decade. The aim of this study was to analyze the parameters of thrombin generation in patients with chronic liver disease, as they are the most appropriate biomarkers to explore coagulation. (1) Background: The knowledge about coagulation disorders in patients with chronic liver disease changed in the last decade. The study of thrombin generation in patients with chronic liver disease provides a much more accurate assessment of the coagulation cascade; (2) Methods: This study is a prospective observational pilot study on hospitalized patients with chronic liver diseases that analyzed thrombin generation performed from their platelet-poor plasma versus that of control subjects. We analyzed a group of 59 patients with chronic liver disease and 62 control subjects; (3) Results: Thrombin generation was lower in hepatitis and cirrhosis patients compared to controls and decreases as the disease progressed. Lag time was higher in ethanolic etiology compared to the control group. Peak thrombin and endogenous thrombin potential were shorter in all etiologies when compared to the control group. The velocity index was significantly lower in HCV hepatopathies, ethanolic, and mixed etiology when compared with normal individuals; (4) Conclusions: Given the variability of thrombin generation in patients with chronic liver disease, its assay could serve to identify patients with high thrombotic and hemorrhagic risk and establish personalized conduct toward them.

Coagulation disorders in SARS-CoV-2 infection.

A better understanding of the pathogenetic mechanisms triggered by SARS-CoV-2 infection may contribute to a more effective management of patients with COVID-19. Coagulation dysfunction is a key pathogenetic element of this disease as well as a challenge for practitioners. Marked inflammatory process found in severe forms of COVID-19, the complement activation, the cytokine storm, and disruption of the renin-angiotensin-aldosterone system are involved in the onset of thrombotic microangiopathy and large vessel coagulopathy. Virus-induced procoagulant activity occurs at the systemic level. Intravascular microthrombi disrupt vascularization in various tissues and organs, contributing to the occurrence of multiorgan failure and explain the higher morbidity and all-cause mortality of patients. It is estimated that almost 20% of patients with COVID-19 have significant coagulation disorders, and about a quarter of those hospitalized in intensive care units are prone to develop thrombosis events under prophylactic anticoagulant treatment. Some of patients who have been immunized after healing from the SARS-CoV-2 infection have a hypercoagulable state and are prone to develop thrombosis. Hypercoagulability is supported by thrombelastographic analysis: patients have an acceleration of the propagation phase of blood clot formation and higher clot strength. Markers of coagulation dysfunction in SARS-CoV2 are: decreased platelet count, increased INR, presence of fibrin degradation products, and especially higher plasma levels of D-dimers, which predict unfavorable outcome in these patients. Age, pre-existing diseases and associated risk factors, together with careful monitoring of clinical evolution and laboratory parameters allow the choice of the best personalized prophylactic or curative anticoagulant treatment.

Monoclonal Antibodies, Bispecific Antibodies and Antibody-Drug Conjugates in Oncohematology.

BACKGROUND: The therapeutic outcomes and the prognosis of patients with various hematologic malignancies are not always ideal with the current standard of care. OBJECTIVE: The aim of this study is to analyze the results of the use of monoclonal antibodies, bispecific antibodies and antibody-drug conjugates for the therapy of malignant hemopathies. METHODS: A mini-review was achieved using the articles published in Web of Science and PubMed between January 2017 and January 2020 and the new patents were made in this field. RESULTS: Naked monoclonal antibodies have improved the therapeutic results obtained with standard of care, but they also have side effects and the use of some of them can lead to the loss of the target antigen through trogocytosis, which explains the resistance that occurs during therapy. The results obtained with naked monoclonal antibodies have been improved by a better monoclonal antibody preparation, the use of bispecific antibodies (against two antigens on the target cell surface or by binding both surface antigen on target cells and T-cell receptor complex, followed by cytotoxic T-lymphocytes activation and subsequent cytolysis of the target cell), the use of monoclonal or bispecific constructs in frontline regimens, combining immunotherapy with chemotherapy, including through the use of antibody-drug conjugates (which provides a targeted release of a chemotherapeutic agent). CONCLUSION: Immunotherapy and immuno-chemotherapy have improved the outcome of the patients with malignant hemopathies through a targeted, personalized therapy, with reduced systemic toxicity, which in some cases can even induce deep complete remissions, including minimal residual disease negativity.

Pragmatic Analysis of Dyslipidemia Involvement in Coronary Artery Disease: A Narrative Review.

BACKGROUND: Dyslipidemia is the main factor involved in the occurrence and progression of coronary artery disease. OBJECTIVE: The research strategy is aimed at analyzing new data on the pathophysiology of dyslipidemia involvement in coronary artery disease, the modalities of atherogenic risk estimation and therapeutic advances. METHODS: Scientific articles published in PubMed from January 2017 to February 2018 were searched using the terms "dyslipidemia" and "ischemic heart disease". RESULTS: PCSK9 contributes to the increase in serum levels of low-density lipoprotein-cholesterol and lipoprotein (a). The inflammation is involved in the progression of hyperlipidemia and atherosclerosis. Hypercholesterolemia changes the global cardiac gene expression profile and is thus involved in the increase of oxidative stress, mitochondrial dysfunction, and apoptosis initiated by inflammation. Coronary artery calcifications may estimate the risk of coronary events. The cardioankle vascular index evaluates the arterial stiffness and correlates with subclinical coronary atherosclerosis. The carotid plaque score is superior to carotid intima-media thickness for risk stratification in patients with familial hypercholesterolemia and both can independently predict coronary artery disease. The lipoprotein (a) and familial hypercholesterolemia have a synergistic role in predicting the risk of early onset and severity of coronary atherosclerosis. A decrease in atherosclerotic coronary plaque progression can be achieved in patients with plasma LDL-cholesterol levels below 70 mg/dL. A highly durable RNA interference therapeutic inhibitor of PCSK9 synthesis could be a future solution. CONCLUSION: The prophylaxis and treatment of coronary artery disease in a dyslipidemic patient should be based on a careful assessment of cardio-vascular risk factors and individual metabolic particularities, so it may be personalized.

Chimeric Antigen Receptor-Engineered T-Cells - A New Way and Era for Lymphoma Treatment.

BACKGROUND: Patients with refractory or relapsed diffuse large B-cell lymphoma have a poor prognosis with the current standard of care. OBJECTIVE: Chimeric Antigen Receptor T-cells (CAR T-cells) are functionally reprogrammed lymphocytes, which are able to recognize and kill tumor cells. The aim of this study is to make progress in this area. METHODS: A mini-review was achieved using the articles published in Web of Science and PubMed in the last year and the new patents were made in this field. RESULTS: The responses to CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel are promising; the objective response rate can reach up to 83%, and the complete response rate ranges between 40 and 58%. About half of the patients may have serious side effects, such as cytokine release syndrome and neurotoxicity. Current and future developments include the improvement of CAR T-cell expansion and polyfunctionality, the combined use of CAR T-cells with a fusion protein between interferon and an anti-CD20 monoclonal antibody, with checkpoint inhibitors or small molecule sensitizers that have apoptotic-regulatory effects. Furthermore, the use of IL-12-expressing CAR T-cells, an improved technology for the production of CAR T-cells based on targeted nucleases, the widespread use of allogeneic CAR T-cells or universal CAR T-cells obtained from genetically engineered healthy donor T-cells are future developments actively considered. CONCLUSION: CAR T-cell therapy significantly improved the outcome of patients with relapsed or refractory diffuse large B-cell lymphoma. The advances in CAR T-cells production technology will improve the results and enable the expansion of this new immunotherapy.

Liver infarction in a patient with Clostridium Difficile colitis. A possible connection?

.