Risk Factors of Thrombophilia-Related Mutations for Early and Late Pregnancy Loss.

Background and Objectives: This retrospective cohort study investigates the role of genetic thrombophilia in pregnant women experiencing early pregnancy loss compared to those with late pregnancy loss. Materials and Methods: Participants were categorized into early and late pregnancy loss groups based on gestational age. A total of 156 patients were included, out of which 103 had early-trimester pregnancy losses and 96 had multiple miscarriages. Results: The study revealed a synergistic effect of Factor V Leiden (FVL G1691A) and Methylenetetrahydrofolate Reductase (MTHFR C677T) mutations (coefficient 3.42). Prothrombin (PT) G20210A and ß-Fibrinogen 455 G>A mutations exhibited a significant interaction (coefficient 1.98). Additionally, MTHFR A1298C and Plasminogen Activator Inhibitor-1 (PAI-1 4G/5G) mutations showed a significant interaction (coefficient 1.65). FVL G1691A and Endothelial Protein C Receptor (EPCR) allele A1/A2 mutations also demonstrated a significant association (coefficient 2.10). Lastly, MTHFR C677T and Glycoprotein IIb/IIIa T1565C mutations interacted significantly (coefficient 1.77). Risk factor analysis identified several mutations associated with early pregnancy loss, including PAI-1 4G/5G homozygous (OR 3.01), FVL G1691A heterozygous (OR 1.85), and MTHFR A1298C heterozygous (OR 1.55). Both homozygous and heterozygous MTHFR C677T mutations were significant risk factors (OR 2.38; OR 2.06), as was PT G20210A homozygous mutation (OR 1.92). The PAI-1 4G/4G homozygous variant posed a risk (OR 1.36). Late pregnancy loss was associated with MTHFR A1298C homozygous mutation (OR 3.79), ß-Fibrinogen 455 G>A heterozygous mutation (OR 2.20), and MTHFR A1298C heterozygous mutation (OR 2.65). Factor XIII G1002T heterozygous mutation (OR 1.18) and PAI-1 4G/5G homozygous mutation (OR 2.85) were also significant risk factors. EPCR allele A1/A2 (OR 1.60) and A2/A3 (OR 1.73) mutations were identified as significant risk factors for late pregnancy loss. Furthermore, FVL G1691A homozygous mutation, PT G20210A homozygous mutation, MTHFR C677T heterozygous mutation, MTHFR A1298C heterozygous mutation, and EPCR allele A1/A2 were identified as significant risk factors for multiple miscarriage. Conclusions: This study highlights significant interactions and risk factors related to genetic thrombophilia mutations in different types of pregnancy loss, contributing valuable insights for miscarriage management guidelines.

Maternal and Newborn Characteristics-A Comparison between Healthy and Thrombophilic Pregnancy.

A thrombophilic woman is more likely to experience difficulties during pregnancy, difficulties that will also affect the development of the newborn. This study aims to compare maternal and newborn characteristics between healthy and thrombophilic pregnancy. The following characteristics were analysed: maternal characteristics (BMI- body mass index, haemostasis parameters, thrombophilia-specific treatment) and newborn characteristics (gestational period, birth weight, the Apgar score). This follow-up study spanning five years, from 2018 to 2022, focuses on a cohort of 500 women who underwent delivery hospitalization in the western region of Romania. The maternal characteristics influence the newborn: the greater the weight of the mother with thrombophilia, the more the chances that the fetus will have a lower birth weight; increasing the dose of LMWH (low molecular weight heparin), connected with the necessity to control the homeostasis parameters, the more likely the fetus will be born with a lower birth weight. A pregnant woman with thrombophilia, treated appropriately, having a normal weight, and not presenting other risk factors independent of thrombophilia, will have a newborn with characteristics similar to a healthy pregnant woman.

A Systematic Review Assessing the Impact of Vitamin D Levels on Adult Patients with Lymphoid Malignancies.

Vitamin D deficiency has been correlated with various conditions, including the risk of developing lymphoid malignancies. This systematic review aimed to assess the association between vitamin D levels at diagnosis of lymphoid malignancies, patient outcomes, and survival. A systematic review was conducted, encompassing 15 studies published until January 2023, involving 4503 patients, examining the relationship between vitamin D and lymphoid cancers. The median age of the patients was 56.5 years, with a median follow-up duration of approximately 36 months across studies. The overall median vitamin D level at initial measurement was 20.4 ng/mL, while a <20 ng/mL threshold was used to define vitamin D insufficiency. The results demonstrated significant associations between vitamin D levels and patient outcomes in several lymphoid malignancies, with a pooled risk in disease progression of 1.93 and a pooled hazard ratio of 2.06 for overall survival in patients with 25-(OH)D levels below the normal threshold of 20 ng/mL. Among findings, it was demonstrated that supplemental vitamin D improves the chemosensitivity of tumors by reducing the rate of tumor growth compared with vitamin D or chemotherapy alone. Vitamin D had a protective effect for patients with DLBCL under R-CHOP treatment, while vitamin D insufficiency was associated with the impairment of rituximab treatment and showed worse clinical outcomes in chimeric antigen receptor T-cell (CAR-T) recipients. Although one study found no association between vitamin D deficiency and the cause of death, most associated vitamin D insufficiency with early clinical failure and lower survival probability. In conclusion, his systematic review highlights the importance of vitamin D levels in the prognosis and survival of patients with lymphoid malignancies. Further research is needed to better understand the underlying mechanisms and explore the potential benefits of vitamin D supplementation in managing these cancers.

Assessment of the Particularities of Thrombophilia in the Management of Pregnant Women in the Western Part of Romania.

Background and objectives: Thrombophilia in pregnant women is a condition whose incidence is constantly increasing worldwide, and, under these conditions, the development of preventive procedures is becoming essential. In this study, we aimed to evaluate thrombophilia in pregnant women in the western part of Romania and to establish anthropometric characteristics, socioeconomic features, and genetic and risk factors. Material and Methods: 178 pregnant women were divided into three study groups, according to the type of thrombophilia, aiming to carry out the genetic profile and the acquired one. Anthropometric measures and biological tests were performed. Results: The mixed type of thrombophilia predominates. The particularities of pregnant women diagnosed with thrombophilia are higher age, living in an urban environment, with normal BMI, approximately 36 weeks of gestational period, and having at least one miscarriage. Regarding the most frequent thrombophilic genetic markers, we obtained the MTFHR gene mutation C677T and A1298C, followed by the PAI-1 4G/5G gene mutation. Smoking represents an aggravating factor in the evolution of this pathology, manifested through the increase of D-dimers and the decrease in antithrombin values, simultaneously with the increase in therapeutic need. Conclusions: The predominance of MTHFR and PAI-1 4G/5G gene polymorphism is a particularity of pregnant women with thrombophilia from the western part of Romania. Smoking is confirmed as an important risk factor in spontaneous abortion.

Assessing Pretransplant and Posttransplant Therapy Response in Multiple Myeloma Patients.

Multiple myeloma (MM) is a hematologic cancer defined by an abnormal development of clonal plasma cells in the bone marrow, releasing vast quantities of immunoglobulins and different proteins. In the majority of patients, MM remains incurable despite decades of medical improvement and a number of treatment breakthroughs. Frontline standard-of-care has little long-term success, with the majority of patients eventually relapsing, although the overall progression-free survival (PFS) has improved significantly in the last ten years. Patients who are eligible for a transplant have the highest PFS rate at 5 years, depending on medication response and other various factors that are yet to be discovered. Therefore, the current study aimed to evaluate the response to VCD (bortezomib, cyclophosphamide, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) used as pretransplant regimens, as well as to compare responses between thalidomide and lenalidomide used as maintenance therapy posttransplant. This retrospective study was performed on a group of 105 hospitalized patients in the Hematology Department of the Timisoara Municipal Emergency Clinical Hospital between January 2016 and December 2021. Data was collected from the paper records of patients with MM who were under-followed. The treatment regimens used as induction therapy were either VCD or VTD if cyclophosphamide was contraindicated. Of the 105 patients, 27 became eligible for bone marrow transplantation. Furthermore, they received maintenance therapy which was based on either lenalidomide with dexamethasone or thalidomide with dexamethasone. Of the 62 patients treated with VTD, 17.7% were in complete remission before stem cell transplantation. Of the 43 patients treated with VCD, 37.2% were in complete remission. The 5-year mean progression-free survival (PFS) in the entire cohort was better in the group treated with the VTD regimen (31.6 vs. 27.2 months). However, in the 27 patients undergoing maintenance after ASCT, the PFS with thalidomide was 35.5 months (95% CI = 27-42), while the PFS rate in those receiving maintenance treatment with lenalidomide was 46.1 months (95% CI = 20-73). VCD proved to be superior to VTD in inducing complete pretransplant responses. Regarding maintenance therapy, patients from the lenalidomide group had superior responses compared with those under thalidomide.

Approach to Thrombophilia in Pregnancy-A Narrative Review.

Thrombophilia is a genetic predisposition to hypercoagulable states caused by acquired haemostasis conditions; pregnancy causes the haemostatic system to become hypercoagulable, which grows throughout the pregnancy and peaks around delivery. Genetic testing for thrombophilic gene mutations is evaluated using different methodologies of real-time polymerase chain reaction and DNA microarrays of specific genes. Adapting the general care of the pregnant woman to the particularities caused by thrombophilia is an important component, so screening is preferred to assess the degree of genetic damage that manifests itself as a risk of thrombosis. The major goal of this narrative review was to quantitatively evaluate the literature data on the specific care of pregnant women with thrombophilia that are at risk of developing unplanned miscarriages.

Evaluation of the Relapse Risk and Survival Rate in Patients with Hodgkin Lymphoma: A Monocentric Experience.

Background and objectives: Hodgkin lymphoma (HL) is characterized by the presence of malignant Reed Sternberg cells. Although the current curability rate in patients with HL has increased, up to 30% of those in the advanced stages and 5% to 10% of those in limited stages of the disease, relapse. According to the studies, the relapse risk in HL decreases after 2 years. The purpose of this study is to evaluate the relapse risk and event free survival (EFS) in patients with HL treated with Doxorubicin, Bleomycin, Vinblastine and Dacarbazine (ABVD), or treated with Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone (BEACOPP) regimens. Material and methods: In an observational, consecutive-case scenario, 71 patients (median age 32 years; range 16 to 80 years) diagnosed within a 4-year timeframe were enrolled; all patients were treated according to standards of care. The average follow-up duration was 26 months. Results: The risk of relapse, in patients older than 40 years, decreased after 1 year, OR = 0.707 (95% CI 0.506 to 0.988), and 2 years, OR = 0.771 (95% CI 0.459 to 1.295), respectively. Patients in the advanced stages had a higher International Prognostic Score (IPS) (score ≥ 4). The overall survival at 2 years was 57.74% and the disease-specific survival at 2 years was 71.83%. Regardless, the chemotherapy regimen and the EFS time, advanced stage, high IPS and bulky disease were still associated with an increased relapse risk in patients with HL. Conclusions: The use of ABVD chemotherapy regimen followed by 2 years EFS was associated with a reduced relapse risk.

High Carbohydrate Diet Is Associated with Severe Clinical Indicators, but Not with Nutrition Knowledge Score in Patients with Multiple Myeloma.

Although the survival rate of patients diagnosed with multiple myeloma has doubled over the last few decades, due to the introduction of new therapeutic lines and improvement of care, other potential contributors to the therapeutic response/relapse of disease, such as nutrient intake, along with nutrition knowledge, have not been assessed during the course of the disease. The purpose of this research was to assess nutrition knowledge and diet quality in a group of patients with a diagnosis of multiple myeloma. Anthropometric, clinical and biological assessments and skeletal survey evaluations, along with the assessment of nutritional intake and general nutrition knowledge, were performed on 61 patients with a current diagnosis of multiple myeloma. A low carbohydrate diet score was computed, classified in tertiles, and used as a factor in the analysis. Patients in tertiles indicative of high carbohydrate or low carbohydrate intake showed significant alteration of clinical parameters, such as hemoglobin, uric acid, albumin, total proteins, beta-2 microglobulin, percentage of plasmacytes in the bone marrow and D-dimers, compared to patients in the medium carbohydrate intake tertile. Nutrition knowledge was not associated with clinical indicators of disease status, nor with patterns of nutrient intake. Better knowledge of food types and nutritional value of foods, along with personalized nutritional advice, could encourage patients with MM to make healthier decisions that might extend survival.