Substance P Concentration in Gestational Diabetes and Excessive Gestational Weight Gain and Its Impact on Neonatal Anthropometry.

Fetal programming is a process initiated by intrauterine conditions, leaving a lasting impact on the offspring's health, whether they manifest immediately or later in life. It is believed that children born to mothers with gestational diabetes mellitus (GDM) and excessive gestational weight gain (EGWG) may be at an increased risk of developing type 2 diabetes mellitus (T2DM) and obesity later in their adult lives. Substance P is a neurotransmitter associated with obesity development and impairment of insulin signaling. Dysregulation of substance P could lead to several pregnancy pathologies, such as preeclampsia and preterm birth. Our study aimed to compare substance P concentrations in serum and umbilical cord blood in patients with GDM, EGWG, and healthy women with a family history of gestational weight gain. Substance P levels in umbilical cord blood were significantly higher in the GDM group compared to the EGWG and control groups. Substance P levels in serum and umbilical cord blood were positively correlated in all groups and the GDM group. A very interesting direction for future research is the relationship between the concentration of substance P in newborns of diabetic mothers and the occurrence of respiratory distress syndrome as a complication of impaired surfactant synthesis. To our knowledge, it is the first study assessing substance P concentration in GDM and EGWG patients.

Influence of Breastfeeding on the State of Meta-Inflammation in Obesity-A Narrative Review.

Obesity has become an emerging health issue worldwide that continues to grow in females of reproductive age as well. Obesity, as a multisystem and chronic disease, is associated with metabolic inflammation, which is defined as chronic low-grade systemic inflammation mediated by, i.a., adipose tissue macrophages. Lactation has been proven to have a beneficial influence on maternal health and could help restore metabolic balance, especially in the state of maternal obesity. In this review, we aimed to analyze the influence of breastfeeding on chronic low-grade meta-inflammation caused by obesity. We performed a comprehensive literature review using the PubMed, Science Direct, and Google Scholar electronic databases. For this purpose, we searched for "metabolic inflammation"; "meta-inflammation"; "obesity"; "breastfeeding"; "fetal programming"; "energy metabolism"; "postpartum"; "immunity"; "immune system"; and "inflammation" keyword combinations. While the clinical impact of breastfeeding on maternal and offspring health is currently well known, we decided to gain insight into more specific metabolic effects of adiposity, lipid, and glucose homeostasis, and immunological effects caused by the activity of cytokines, macrophages, and other immune system cells. Further research on the immunological and metabolic effects of breastfeeding in obese patients is key to understanding and potentially developing obesity therapeutic strategies.

Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors.

The standard treatment of ovarian cancer (OC) patients, including debulking surgery and first-line chemotherapy, is unsatisfactory because of recurrent episodes in the majority (~70%) of patients with advanced OC. Clinical trials have shown only a modest (10-15%) response of OC individuals to treatment based on immune checkpoint inhibitors (ICIs). The resistance of OC to therapy is caused by various factors, including OC heterogeneity, low density of tumor-infiltrating lymphocytes (TILs), non-cellular and cellular interactions in the tumor microenvironment (TME), as well as a network of microRNA regulating immune checkpoint pathways. Moreover, ICIs are the most efficient in tumors that are marked by high microsatellite instability and high tumor mutation burden, which is rare among OC patients. The great challenge in ICI implementation is connected with distinguishing hyper-, pseudo-, and real progression of the disease. The understanding of the immunological, molecular, and genetic mechanisms of OC resistance is crucial to selecting the group of OC individuals in whom personalized treatment would be beneficial. In this review, we summarize current knowledge about the selected factors inducing OC resistance and discuss the future directions of ICI-based immunotherapy development for OC patients.

Abnormalities in the KRAS Gene and Treatment Options for NSCLC Patients with the G12C Mutation in This Gene-A Literature Review and Single-Center Experience.

Mutations in the KRAS gene are among the most common mutations observed in cancer cells, but they have only recently become an achievable goal for targeted therapies. Two KRAS inhibitors, sotorasib and adagrasib, have recently been approved for the treatment of patients with advanced non-small cell lung cancer with the KRAS G12C mutation, while studies on their efficacy are still ongoing. In this work, we comprehensively analyzed RAS gene mutations' molecular background, mutation testing, KRAS inhibitors' effectiveness with an emphasis on non-small cell lung cancer, the impact of KRAS mutations on immunotherapy outcomes, and drug resistance problems. We also summarized ongoing trials and analyzed emerging perspectives on targeting KRAS in cancer patients.

Recent Insights and Recommendations for Preventing Excessive Gestational Weight Gain.

Recommendations for weight gain during pregnancy are based on pre-pregnancy body mass index (BMI). Pregnancy is a risk factor for excessive weight gain and many endocrine problems, making it difficult to return to pre-pregnancy weight and increasing the risk of postpartum obesity and, consequently, type 2 diabetes and metabolic syndrome. Both excessive gestational weight gain (EGWG) and obesity are associated with an increased risk of gestational hypertension, pre-eclampsia, gestational diabetes, cesarean section, shoulder dystocia, and neonatal macrosomia. In the long term, EGWG is associated with increased morbidity and mortality, particularly from diabetes, cardiovascular disorders, and some cancers. This study aims to present recommendations from various societies regarding weight gain during pregnancy, dietary guidance, and physical activity. In addition, we discuss the pathophysiology of this complication and the differential diagnosis in pregnant women with EGWG. According to our research, inadequate nutrition might contribute more significantly to the development of EGWG than insufficient physical activity levels in pregnant women. Telehealth systems seem to be a promising direction for future EGWG prevention by motivating women to exercise. Although the importance of adequate pre-pregnancy weight and weight gain during pregnancy is well known, an increasing number of women gain excessive weight during pregnancy.

Premature rupture of membranes and changes in the vaginal microbiome - Probiotics.

Preterm birth affects approximately 15 million women worldwide, of which 30 % is due to preterm premature rupture of membranes (PPROM). The reasons for shortening the duration of pregnancy are seen in genetic, hormonal, immunological and socio-economic conditions. Recent years have provided a lot of evidence on the impact of the microbiota and whole microbiome on pregnant women, suggesting that the microorganisms inhabiting the vagina significantly affect the risk of preterm delivery. The aim of the study was to review studies evaluating the composition of the vaginal microflora and its role in the occurrence of preterm labor caused by PPROM, and to evaluate the potential beneficial effect of probiotics on preventing the development of preterm labor. Vaginal microbial dysbiosis is observed in PPROM, which, due to its association with a high risk of prematurity and infection, increases neonatal morbidity and mortality. Further research on biomarkers for screening, early prognosis and diagnosis of PPROM seems advisable. Probiotics as a potential intervention can prevent the development of pathological vaginal flora, reducing the risk of infection in women planning pregnancy and pregnant women.

Prognostic Value of Inflammatory Burden Index in Advanced Gastric Cancer Patients Undergoing Multimodal Treatment.

Since increasing evidence underlines the prominent role of systemic inflammation in carcinogenesis, the inflammation burden index (IBI) has emerged as a promising biomarker to estimate survival outcomes among cancer patients. The IBI has only been validated in Eastern gastric cancer (GC) patients; therefore, the aim of this study was to evaluate the IBI as a prognostic biomarker in Central European GC patients undergoing multimodal treatment. Ninety-three patients with histologically confirmed GC who underwent multimodal treatment between 2013 and 2021 were included. Patient recruitment started with the standardization of neoadjuvant chemotherapy (NAC). Blood samples were obtained one day prior to surgical treatment. The textbook outcome (TO) served as the measure of surgical quality, and tumor responses to NAC were evaluated according to Becker's system tumor regression grade (TRG). A high IBI was associated with an increased risk of postoperative complications (OR 2.95, 95% CI 1.13-7.72). In multivariate analysis, a high IBI (HR = 2.56, 95% CI 1.28-5.13) and a high neutrophil-to-lymphocyte ratio (NLR, HR = 2.55, 95% CI 1.32-4.94) were associated with an increased risk of death, while NAC administration (HR = 0.40, 95% CI 0.18-0.90) and TO achievement (HR = 0.42, 95% CI 0.22-0.81) were associated with a lower risk of death. The IBI was associated with postoperative complications and mortality among GC patients undergoing multimodal treatment.

Impact of Obesity and Diabetes in Pregnant Women on Their Immunity and Vaccination.

Pregnant women with obesity and diabetes are at increased risk of developing infections and other complications during pregnancy. Several mechanisms are involved in the immunological mechanisms that contribute to reduced immunity in these populations. Both obesity and diabetes are associated with chronic low-grade inflammation that can lead to an overactive immune response. Pregnant women with obesity and diabetes often have an increase in pro-inflammatory cytokines and adipokines, such as TNF-α, IL-6, IL-1ß, leptin, and resistin, which are involved in the inflammatory response. Insulin resistance can also affect the functioning of immune cells. Furthermore, both conditions alter the composition of the gut microbiome, which produces a variety of biomolecules, including short-chain fatty acids, lipopolysaccharides, and other metabolites. These substances may contribute to immune dysfunction. In addition to increasing the risk of infections, obesity and diabetes can also affect the efficacy of vaccinations in pregnant women. Pregnant women with obesity and diabetes are at increased risk of developing severe illness and complications from COVID-19, but COVID-19 vaccination may help protect them and their fetuses from infection and its associated risks. Since both obesity and diabetes classify a pregnancy as high risk, it is important to elucidate the impact of these diseases on immunity and vaccination during pregnancy. Research examining the efficacy of the COVID-19 vaccine in a high-risk pregnant population should be of particular value to obstetricians whose patients are hesitant to vaccinate during pregnancy. Further research is needed to better understand these mechanisms and to develop effective interventions to improve immune function in these populations.

Biomolecules Involved in Both Metastasis and Placenta Accreta Spectrum-Does the Common Pathophysiological Pathway Exist?

The process of epithelial-to-mesenchymal transition (EMT) is crucial in the implantation of the blastocyst and subsequent placental development. The trophoblast, consisting of villous and extravillous zones, plays different roles in these processes. Pathological states, such as placenta accreta spectrum (PAS), can arise due to dysfunction of the trophoblast or defective decidualization, leading to maternal and fetal morbidity and mortality. Studies have drawn parallels between placentation and carcinogenesis, with both processes involving EMT and the establishment of a microenvironment that facilitates invasion and infiltration. This article presents a review of molecular biomarkers involved in both the microenvironment of tumors and placental cells, including placental growth factor (PlGF), vascular endothelial growth factor (VEGF), E-cadherin (CDH1), laminin γ2 (LAMC2), the zinc finger E-box-binding homeobox (ZEB) proteins, αVß3 integrin, transforming growth factor ß (TGF-ß), ß-catenin, cofilin-1 (CFL-1), and interleukin-35 (IL-35). Understanding the similarities and differences in these processes may provide insights into the development of therapeutic options for both PAS and metastatic cancer.

Efficacy of Osimertinib in Lung Squamous Cell Carcinoma Patients with EGFR Gene Mutation-Case Report and a Literature Review.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the leading cause of cancer-related mortality worldwide. It is responsible for 80-85% of lung cancer cases. NSCLC can be divided into several groups, led by adenocarcinoma (ADC)-40-50% and squamous cell carcinoma (SCC)-20-30%. The development of new molecular therapies targeting particular abnormalities such as mutations in the EGFR (Epidermal Growth Factor Receptor) gene or ROS1 or ALK genes rearrangements resolved in novel strategies in advanced NSCLC management. EGFR mutation occurs mostly in patients with ADC and those patients are mostly females with no or light smoking history. The hereby presented patient fitted the ADC characteristics, while they were diagnosed with SCC. The unusual diagnosis implied further genetic testing, which established the occurrence of L858R substitution in exon 21 in the EGFR gene. A 63-year-old female was admitted to the unit due to a dry cough, pain in the right chest area and dyspnoea. When diagnosed, the patient had a peripheral mass in the right lung superior lobe (55 × 40 mm), satellite nodules in the apex of the same lung and packets of disintegrating lymph nodes. Positron Emission Tomography (PET-CT) confirmed a diffuse neoplastic process qualified as stage IV on the TNM scale. Due to EGFR gene mutation, the woman was administered osimertinib, however, the treatment did not succeed, and other therapeutic solutions were undertaken. The patient died 10 months after diagnosis. Patients with advanced ADC harboring EGFR mutation can receive osimertinib, a third-generation tyrosine kinase inhibitor (TKI), however, the use of TKIs in SCC remains controversial. In some published cases, osimertinib treatment led to success, in others, the therapy did not result in the expected final effect. Small sample groups and diverse molecular backgrounds indicate the need for further research in this field. Thus, the treatment decision-making process in those patients overall remains extremely demanding and ambiguous.