FTIR monitoring of the 13-valent pneumococcal conjugate vaccine for lung cancer patients: Changes in amides vibrations correlated with biochemical assays.

Lung cancer is one of the most lethal cancers. Unfortunately, respiratory tract infections are very common in lung cancer patients, delaying appropriate anticancer therapy. To increase therapy efficiency, in this study we examined the effect of 13-Valent Pneumococcal Conjugate Vaccine on the immune response in lung cancer patients, which indirectly affects the success of anticancer therapy. The study was done using biochemical tests and Fourier Transform InfraRed (FTIR) spectroscopy. For this purpose, serum from lung cancer patients aged 52 ± 9 years (III and IV clinical stage; 79 %; n = 103) before and seven as well as 30 days after vaccination was collected. Obtained results showed increasing concentrations of immunoglobulin IgG and IgG2 groups in patients after vaccination in comparison with group before vaccination. This result was confirmed by FTIR spectroscopy, where higher absorbances of amides vibrations were observed after vaccination. Interestingly, lack of differences in the amides absorbances between patients 7 and 30 days after vaccination were noticed. FTIR spectra also showed changes in the ratio between amide I and amide III as well as between amide II and amide III in the groups of patients after vaccination. From deconvolution of made I range (1600 cm-1-1700 cm-1) decrease of the ratio between α-helix and ß-sheet around 0.05 was noticed in serum collected from patients after vaccination in comparison with patients before vaccination. Using Principal Component Analysis (PCA) analysis of FTIR data it was observed that serum collected from all three analyzed groups of samples was possible to differentiate. The highest accuracy in differentiation group of samples before and 7 days after vaccination was visible in amide I, while before and 30 days after vaccination using amide II. Correlation between immunoglobulin IgG and IgG2 concentrations obtained by biochemical assays and FTIR were noticed only in the group of serum collected 30 days after vaccination, which suggested that FTIR spectroscopy reflects biochemical data.

Toll-like Receptors: Key Players in Squamous Cell Carcinoma Progression.

Background/Objectives Lung squamous cell carcinoma (SCC) is one of the major subtypes of lung cancer, characterized by diverse molecular pathways and variable clinical outcomes. This study focused on assessing the levels of TLR-2, TLR-3, TLR-4, TLR-7, TLR-8, and TLR-9 on peripheral blood lymphocytes in patients with newly diagnosed SCC compared to a group of healthy controls, in the context of disease development and patient survival, conducted over three years. The study aimed to investigate the differences in TLR expression between SCC patients and healthy people and to understand their role in the development of the disease and patient survival over three years. Methods: The study included the assessment of TLR-2, TLR-3, TLR-4, TLR-7, TLR-8, and TLR-9 levels on peripheral blood lymphocytes in patients with newly diagnosed SCC and in the control group. The expression of TLRs was measured using flow cytometry, and the soluble forms of the tested TLRs were measured using enzyme-linked immunosorbent assays. All the analyses were conducted over a three-year period from the time patients were recruited to the study. The obtained test results were statistically analyzed. Results: Results showed statistically significant differences in TLR expression between the groups, with higher TLR levels correlating with an advanced stage of disease and poorer survival rates. This suggests that the deregulation of TLR levels may be involved in promoting tumor development and influencing its microenvironment. Conclusions: The research, conducted over three years, indicates the need for further research on the role of TLRs in SCC, including their potential use as therapeutic targets and biomarkers. This may help to increase the effectiveness of standard treatments and improve clinical outcomes in patients with SCC.

Analysis of Selected Toll-like Receptors in the Pathogenesis and Advancement of Non-Small-Cell Lung Cancer.

(1) Background: Non-small-cell lung cancer (NSCLC) represents a significant global health challenge, contributing to numerous cancer deaths. Despite advances in diagnostics and therapy, identifying reliable biomarkers for prognosis and therapeutic stratification remains difficult. Toll-like receptors (TLRs), crucial for innate immunity, now show potential as contributors to cancer development and progression. This study aims to investigate the role of TLR expression as potential biomarkers in the development and progression of NSCLC. (2) Materials and Methods: The study was conducted on 89 patients diagnosed with NSCLC and 40 healthy volunteers, for whom the prevalence of TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 was assessed on selected subpopulations of T and B lymphocytes in the peripheral blood of recruited patients along with the assessment of their serum concentration. (3) Result: Our study showed several significant changes in NSCLC patients at the beginning of the study. This resulted in a 5-year follow-up of changes in selected TLRs in recruited patients. Due to the high mortality rate of NSCLC patients, only 16 patients survived the 5 years. (4) Conclusions: The results suggest that TLRs may constitute real biomarker molecules that may be used for future prognostic purposes in NSCLC. However, further validation through prospective clinical and functional studies is necessary to confirm their clinical utility. These conclusions may lead to better risk stratification and tailored interventions, benefiting NSCLC patients and bringing medicine closer to precision.

Enhancing Immune Response in Non-Small-Cell Lung Cancer Patients: Impact of the 13-Valent Pneumococcal Conjugate Vaccine.

Background: Non-small-cell lung cancer (NSCLC) is one of the most frequently diagnosed diseases among all types of lung cancer. Infectious diseases contribute to morbidity and mortality by delaying appropriate anti-cancer therapy in patients with NSCLC. Methods: The study aimed to evaluate the effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) in 288 newly diagnosed NSCLC patients. The analysis of the post-vaccination response was performed after vaccination by assessing the frequency of plasmablasts via flow cytometry and by assessing the concentration of specific anti-pneumococcal antibodies using enzyme-linked immunosorbent assays. Results: The results of the study showed that NSCLC patients responded to the vaccine with an increase in the frequencies of plasmablasts and antibodies but to a lesser extent than healthy controls. The immune system response to PCV13 vaccination was better in patients with lower-stage NSCLC. We found higher antibody levels after vaccination in NSCLC patients who survived 5 years of follow-up. Conclusions: We hope that our research will contribute to increasing patients' and physicians' awareness of the importance of including PCV13 vaccinations in the standard of oncological care, which will extend the survival time of patients and improve their quality of life.

Pembrolizumab-combination therapy for NSCLC- effectiveness and predictive factors in real-world practice.

Introduction: Pembrolizumab combined with chemotherapy has become the standard of care for patients with non-small-cell lung cancer (NSCLC) and the expression of programmed death ligand 1 (PD-L1) in <50% of tumour cells (TC). Methods: We evaluated the efficacy of the treatment in real-world practice, paying attention to the predictive factors, with a special focus on low level of PD-L1 expression. This study is a multicenter retrospective analysis of patients with stage IV NSCLC. Results: A group of 339 consecutive patients was analysed, among them 51% patients with low PD-L1 expression. In the overall population, the ORR was 40.6%, median PFS and OS were 13 months (95% CI 11.4-15) and 16.8 months (95% CI 13.3-20.3), respectively. In multivariate analysis for the entire study population, performance status - ECOG 1 vs. 0 (HR 2.2, 95%CI 1.1-4.6; p=0.02), neutrophil to lymphocyte ratio (NLR)>3 (HR 2.3, 95%CI 1.3-4.2; p=0.04), presence of liver (HR 2.0, 95%CI 1-3.7; p=0. 03) and bone metastases (HR 1.3, 95%CI 1-3; p=0.04), weight loss (HR 1.8, 95%CI 1.1-2.8; p=0.01) and sum of measurable lesions diameters >110 mm (HR 1.7, 95%CI 1-2.9, p=0.049) had a negative impact on OS. Conclusions: In the real world, patients can clinically benefit from immunochemotherapy, regardless of the expression of PD-L1 and the histological type. Other clinicopathological factors such as performance status, extent, and location of secondary lesions have prognostic significance.

Estrogen Receptor Signaling in Breast Cancer.

Estrogen receptor (ER) signaling is a critical regulator of cell proliferation, differentiation, and survival in breast cancer (BC) and other hormone-sensitive cancers. In this review, we explore the mechanism of ER-dependent downstream signaling in BC and the role of estrogens as growth factors necessary for cancer invasion and dissemination. The significance of the clinical implications of ER signaling in BC, including the potential of endocrine therapies that target estrogens' synthesis and ER-dependent signal transmission, such as aromatase inhibitors or selective estrogen receptor modulators, is discussed. As a consequence, the challenges associated with the resistance to these therapies resulting from acquired ER mutations and potential strategies to overcome them are the critical point for the new treatment strategies' development.

Could Immune Checkpoint Disorders and EBV Reactivation Be Connected in the Development of Hematological Malignancies in Immunodeficient Patients?

Primary immunodeficiencies (PIDs) and secondary immunodeficiencies (SIDs) are characterized by compromised immune function, rendering individuals susceptible to infections and potentially influencing cancer development. Epstein-Barr virus (EBV), a widespread herpesvirus, has been linked to cancer, particularly in those with weakened immune systems. This study aims to compare selected immune parameters, focusing on immune checkpoint molecules (PD-1/PD-L1, CTLA-4/CD86, CD200R/CD200), and EBV reactivation in patients with chronic lymphocytic leukemia (CLL, a representative of SIDs) and common variable immunodeficiency (CVID, a representative of PIDs). We performed a correlation analysis involving patients diagnosed with CLL, CVID, and a healthy control group. EBV reactivation was assessed using specific antibody serology and viral load quantification. Peripheral blood morphology, biochemistry, and immunophenotyping were performed, with emphasis on T and B lymphocytes expressing immune checkpoints and their serum concentrations. Our findings revealed elevated EBV reactivation markers in both CLL and CVID patients compared with healthy controls, indicating increased viral activity in immunodeficient individuals. Furthermore, immune checkpoint expression analysis demonstrated significantly altered percentages of T and B lymphocytes expressing PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200 in CLL and CVID patients. This suggests a potential interplay between immune checkpoint dysregulation and EBV reactivation in the context of immunodeficiency. In conclusion, our study underscores the intricate relationship between immune dysfunction, EBV reactivation, and immune checkpoint modulation in the context of immunodeficiency-associated cancers. The altered expression of immune checkpoints, along with heightened EBV reactivation, suggests a potential mechanism for immune evasion and tumor progression. These findings provide insights into the complex interactions that contribute to cancer development in immunocompromised individuals, shedding light on potential therapeutic targets for improved management and treatment outcomes. Further investigations are warranted to elucidate the underlying mechanisms and to explore potential interventions to mitigate cancer risk in these patient populations.

Exploring the Significance of Immune Checkpoints and EBV Reactivation in Antibody Deficiencies with Near-Normal Immunoglobulin Levels or Hyperimmunoglobulinemia.

This study delves into the intricate landscape of primary immunodeficiencies, with a particular focus on antibody deficiencies characterized by near-normal immunoglobulin levels or hyperimmunoglobulinemia. Contrary to the conventional focus on genetic dysregulation, these studies investigate the key roles of immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, on selected subpopulations of T and B lymphocytes and their serum concentrations of soluble forms in patients recruited for the studies in healthy volunteers. In addition, the studies also show the role of Epstein-Barr virus (EBV) reactivation and interactions with tested pathways of immune checkpoints involved in the immunopathogenesis of this disease. By examining the context of antibody deficiencies, this study sheds light on the nuanced interplay of factors beyond genetics, particularly the immune dysregulations that occur in the course of this type of disease and the potential role of EBV reactivation, which affects the clinical presentation of patients and may contribute to the development of cancer in the future, especially related to hematological malignancies.

Next-Generation Sequencing-Based Analysis of Clinical and Pathological Features of PIK3CA-Mutated Breast Cancer.

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is a well-known oncogene with a high prevalence of mutation in breast cancer patients. The effect of the mutation is a deregulation in phosphatidylinositol 3-kinase-related pathways, and, consequently, in unrestricted cell growth and differentiation. With the advent of precision oncology, PIK3CA has emerged as a pivotal treatment target, culminating in the recent approval of alpelisib. Despite years of research on this genetic alteration, certain aspects of its influence on the prognosis of breast cancer remain ambiguous. The purpose of this analysis is to characterize the clinical picture of breast cancer patients with PIK3CA mutation in comparison to the PIK3CA-wild-type group. We examined 103 tumor samples from 100 breast cancer patients using a next-generation sequencing panel. Presence of the mutation was linked to an older age at diagnosis, a lower expression of Ki67 protein, a greater percentage of tumors expressing progesterone receptors, and a notably higher incidence of metastatic disease at presentation. No significant differences were identified in overall and progression-free survival between the two groups. Our findings enhance the understanding of how PIK3CA mutations shape the clinical and prognostic landscape for breast cancer patients.

The Importance of the Immune System and Molecular Cell Signaling Pathways in the Pathogenesis and Progression of Lung Cancer.

Lung cancer is a disease that in recent years has become one of the greatest threats to modern society. Every year there are more and more new cases and the percentage of deaths caused by this type of cancer increases. Despite many studies, scientists are still looking for answers regarding the mechanisms of lung cancer development and progression, with particular emphasis on the role of the immune system. The aim of this literature review was to present the importance of disorders of the immune system and the accompanying changes at the level of cell signaling in the pathogenesis of lung cancer. The collected results showed that in the process of immunopathogenesis of almost all subtypes of lung cancer, changes in the tumor microenvironment, deregulation of immune checkpoints and abnormalities in cell signaling pathways are involved, which contribute to the multistage and multifaceted carcinogenesis of this type of cancer. We, therefore, suggest that in future studies, researchers should focus on a detailed analysis of tumor microenvironmental immune checkpoints, and to validate their validity, perform genetic polymorphism analyses in a wide range of patients and healthy individuals to determine the genetic susceptibility to lung cancer development. In addition, further research related to the analysis of the tumor microenvironment; immune system disorders, with a particular emphasis on immunological checkpoints and genetic differences may contribute to the development of new personalized therapies that improve the prognosis of patients.

Expression of CTLA-4 and CD86 Antigens and Epstein-Barr Virus Reactivation in Chronic Lymphocytic Leukemia-Any Link with Known Prognostic Factors?

Infection with Epstein-Barr virus (EBV) worsens the prognosis in chronic lymphocytic leukemia (CLL), but the underlying mechanisms are not yet established. We intended to assess whether EBV affects the course of CLL by the deregulation of the CTLA-4/CD86 signaling pathway. We used polymerase chain reaction to measure the load of EBV DNA in the blood of 110 newly diagnosed patients with CLL. The expression of CTLA-4 and CD86 antigen on lymphocytes was assessed with flow cytometry. Additionally, CTLA-4 and CD86 serum concentrations were measured through enzyme-linked immunosorbent assays. Fifty-four percent of the patients had detectable EBV DNA [EBV(+)]. In EBV(+) patients the CTLA-4 and CD86 serum concentrations and their expressions on investigated cell populations were significantly higher than in EBV(-) patients. EBV load correlated positively with unfavorable prognostic markers of CLL and the expression of CTLA-4 on CD3+ lymphocytes (r = 0.5339; p = 0.027) and CD86 on CD19+ cells (r = 0.6950; p < 0.001). During a median follow-up period of 32 months EBV(+) patients were more likely to require treatment or have lymphocyte doubling (p < 0.001). Among EBV(+) but not EBV(-) patients, increased expressions of CTLA-4 lymphocytes were associated with elevated risks of progression. We propose that EBV coinfection may worsen prognosis in CLL patients, partly due to EBV-induced up-regulation of CTLA-4 expression.

Toll-like Receptor 2 as a Marker Molecule of Advanced Ovarian Cancer.

Ovarian cancer is a global problem that affects women of all ages. Due to the lack of effective screening tests and the usually asymptomatic course of the disease in the early stages, the diagnosis is too late, with the result that less than half of the patients diagnosed with ovarian cancer (OC) survive more than five years after their diagnosis. In this study, we examined the expression of TLR2 in the peripheral blood of 50 previously untreated patients with newly diagnosed OC at various stages of the disease using flow cytometry. The studies aimed at demonstrating the usefulness of TLR2 as a biomarker in the advanced stage of ovarian cancer. In this study, we showed that TLR2 expression levels were significantly higher in women with more advanced OC than in women in the control group. Our research sheds light on the prognostic potential of TLR2 in developing new diagnostic approaches and thus in increasing survival in patients with confirmed ovarian cancer.

Differential molecular response of larynx cancer cell lines to combined VPA/CDDP treatment.

Successful treatment of advanced larynx squamous cell carcinoma (LSCC) remains a challenge, mainly due to limited response to chemotherapy and the phenomenon of the drug resistance. Therefore, new chemotherapeutic solutions are needed. The aim of this study was to explore benefit of combined cisplatin (CDDP) and valproic acid (VPA) therapy in patients' derived LSCC cell lines. Cell viability assay was used to establish cellular response to the drug by isobolography followed by RNA sequencing (RNAseq) analysis. Danio rerio were used for in vivo studies. Depending on the cell line, we found that the combinations of drugs resulted in synergistic or antagonistic pharmacological interaction, which was accompanied by significant changes in genes expression profiles. The presented therapeutic scheme efficiently blocked tumor growth in an in vivo model, corresponding to the in vitro performed studies. Interestingly the RK5 cell line, upon the combined treatment acquired a molecular profile typically associated with epithelial to mesenchymal transition (EMT). Hence, our studies demonstrates that patient-specific personalized therapy of larynx cancer should be considered and the combination of cisplatin and valproic acid should be explored as a potential therapeutic strategy in the treatment of larynx cancer.

Epidermal Growth Factor Receptor and its Oncogenic EGFRvIII Variant in Benign and Malignant Brain Tumors.

BACKGROUND/AIM: Tumorigenesis and cancer progression might be driven by abnormal activation of growth factor receptors. Importantly, molecular changes in EGFR-dependent signaling is one of the most common characteristics of brain tumors. PATIENTS AND METHODS: HER1 and EGFRvIII variants in meningiomas and glioblastomas were evaluated at the RNA level. RESULTS: EGFRvIII was found in 18.6% of glioblastomas (GBM), whereas 25% of EGFRvIII positive tumors express wild-type EGFR as well. HER1 was over-expressed in benign meningiomas compared to glioblastomas, whereas HER1 expression in meningiomas differed significantly between sub-types of meningiomas. EGFRvIII and HER1 where positively correlated in glioblastomas. Yet, the patient overall survival did not differ between high- and low-HER1 expressing glioblastomas or between EGFRvIII positive and negative GBMs. CONCLUSION: HER1 may be considered as an independent factor for classification of benign meningiomas. The mRNA levels of HER1 or EGFRvIII should not be used as independent prognostic factors for patients with gliomas.

Competing Risks of Cancer and Non-Cancer Mortality When Accompanied by Lifestyle-Related Factors-A Prospective Cohort Study in Middle-Aged and Older Adults.

BACKGROUND: The study aimed to identify the association between the lifestyle-related factors and the cancer-specific, or non-cancer-specific mortality, when accompanied by a competing risk. Two statistical methods were applied, i.e., cause-specific hazard (CSH), and sub-distribution hazard ratio (SHR). Their respective key advantages, relative to the actual study design, were addressed, as was overall application potential. METHODS: Source data from 4,584 residents (34.2% men), aged 45-64 years, were processed using two different families of regression models, i.e., CSH and SHR; principal focus upon the impact of lifestyle-related factors on the competing risk of cancer and non-cancer mortality. The results were presented as hazard ratios (HR) with 95% confidence intervals (95% CI). RESULTS: Age, smoking status, and family history of cancer were found the leading risk factors for cancer death; the risk of non-cancer death higher in the elderly, and smoking individuals. Non-cancer mortality was strongly associated with obesity and hypertension. Moderate to vigorous physical activity decreased the risk of death caused by cancer and non-cancer causes. CONCLUSIONS: Specific, lifestyle-related factors, instrumental in increasing overall, and cancer-specific mortality, are modifiable through health-promoting, individually pursued physical activities. Regular monitoring of such health-awareness boosting pursuits seems viable in terms of public health policy making.

Assessment of Age-Induced Changes in Body Fat Percentage and BMI Aided by Bayesian Modelling: A Cross-Sectional Cohort Study in Middle-Aged and Older Adults.

BACKGROUND: Loss of fat-free mass (FFM) and gain in body fat (BF) are the key disability risk factors, also instrumental in perpetuating already existing functional disorders. Obesity construed in terms of body mass index (BMI) values, in view of undesirable gain in BF, is a risk factor for cardio-metabolic disorders. Both detrimental processes clearly evidence a scope of involutionary changes characteristic of an aging population, also standing for one of its greatest burdens. PURPOSE: The present study aimed to assess the changes in body composition (BC), in conjunction with the relationship between BF% and BMI, for defining overweight and obesity status in middle-aged and older adults, against the select indicator variables under study. MATERIALS AND METHODS: The study involved 4799 individuals (33.7% men), PONS Project participants, aged 43-64 years. BF% was measured with the aid of bioelectrical impedance analysis (BIA) method. Age-induced changes in BC were determined against BF%, fat mass (FM), FFM, BMI, fat mass index (FMI), and fat-free mass index (FFMI). The relationship between BF% and BMI was established with the aid of Bayesian regression models, adjusted for gender and age. RESULTS: In both genders, BF% increased with age at a similar annual rate. The reduction of FFM was noted mainly in men, which in conjunction with BF% gain ensured BMI stability. The increase in BF% in women with stable FFM affected an increase in BMI. Regardless of the BMI threshold, the anticipated (predicted) BF% increased with age in both genders. CONCLUSION: Monitoring of BC is of particular importance in older adults, in view of appreciably better characteristics of both the short- and long-term health predictors, as well as overall potential for developing specifically targeted, effective health interventions.

Chronic Lymphocytic Leukemia-Induced Humoral Immunosuppression: A Systematic Review.

Secondary immunodeficiency is observed in all patients with chronic lymphocytic leukemia (CLL) in varying degrees. The aim of the study was to review the available literature data on patients with CLL, with particular regard to the pathogenesis of the disease and the impact of humoral immunity deficiency on the clinical and therapeutic approach. A systematic literature review was carried out by two independent authors who searched PubMed databases for studies published up to January 2020. Additionally, Google Scholar was used to evaluate search results and support manual research. The search resulted in 240 articles eligible for analysis. After all criteria and filters were applied, 22 studies were finally applied to the analysis. The data analysis showed that the clinical heterogeneity of CLL patients correlates with the diversity of molecular abnormalities determining the clinical picture of the disease, the analysis of which enables setting therapeutic targets. Additionally, in improving the therapeutic method, it is worth introducing supportive therapies with the use of vaccines, antibiotics and/or immunoglobins. Moreover, humoral immunodeficiency in CLL has a strong influence on the risk of infection in patients for whom infections are a major cause of morbidity and mortality.

Predictors of new-onset heart failure and overall survival in metastatic breast cancer patients treated with liposomal doxorubicin.

Cardiovascular diseases (CVDs) are the major cause of morbidity/mortality among breast cancer (BC) patients. Observation of the daily practice in eight experienced Polish oncology centers was conducted to find all possible predictors of new cases of heart failure (HF) and overall survival (OS) of metastatic BC patients treated with liposomal doxorubicin, taking into account the impact of pre-existing CVDs. HF was the cause of premature discontinuation of liposomal doxorubicin therapy in 13 (3.2%) of 402 patients. The probability of developing HF was higher in women with pre-existing CVDs (HR 4.61; 95%CI 1.38-15.38). Independent of CVDs history, a lower risk of HF was observed in those treated with a cumulative dose of liposomal doxorubicin > 300 mg/m2 (HR 0.14; 95% CI 0.04-0.54) and taxane-naive (HR 0.26; 95% CI 0.07-0.96). Multivariate analysis including the presence of pre-existing CVDs and occurrence of new HF, revealed a liposomal doxorubicin in cumulative doses of > 300 mg/m2 as a beneficial predictor for OS (HR 0.61; 95% CI 0.47-0.78) independently of subsequent chemotherapy (HR 0.72; 95% CI 0.57-0.92) or endocrine therapy (HR 0.65; 95% CI 0.49-0.87). Higher doses of liposomal doxorubicin can decrease mortality in metastatic BC without increasing the risk of HF. The clinical benefit is achieved regardless of pre-existing CVDs and subsequent anticancer therapy.

A Two-Year Follow-Up Cohort Study-Improved Clinical Control over CVD Risk Factors through Weight Loss in Middle-Aged and Older Adults.

Modest weight loss enhances clinical control over cardiovascular disease (CVD) risk factors in overweight and obese individuals. This study aimed to assess the associations between individual weight loss and predefined criteria for clinical improvement in blood pressure, lipid levels, and glycemia. A two-year follow-up study involved 3388 (37.9% men) aged 45-64 years, BMI ≥ 25 kg/m2. Changes in body weight were calculated as a percentage of baseline weight; outcome variables: systolic (SBP), diastolic (DBP) blood pressure, high-density (HDL-C) and low-density (LDL-C) lipoproteins, fasting blood glucose (FBG), and triglycerides (TG) were construed as the differences between baseline and outcome values. Clinically significant improvement was defined as SBP/DBP reduction by 5 mm/Hg, FBG-20 mg/dL, LDL-C-10 mg/dL, TG-40 mg/dL, and HDL-C increase by 5 mg/dL. Apart from LDL-C, a modest 5%-10% weight loss was associated with clinically significantly improved outcomes. The incident rate ratios and 95% confidence intervals for clinical improvement of SBP were: 1.27 (1.14-1.40), DBP/1.30 (1.12-1.50), HDL/1.54 (1.18-2.02), and TG/1.69 (1.32-2.17). In the higher category of weight loss, associations were still manifest, although the results proved diagnostically challenging (low number of cases). Even though modest weight loss does enhance clinical control over CVD risk factors, offering regular medical guidance to patients is postulated to further boos the anticipated outcomes.

Optimal cut-off values for anthropometric measures of obesity in screening for cardiometabolic disorders in adults.

Excessive accumulation of body fat (BF) promotes obesity, whilst posing a significant health hazard. There being no agreed, optimal quantifying methods, application of BF variable in clinical practice is not deemed an effective assessment option. The study, involving 4,735 patients (33.6% men), aged 45-64, aimed to identify optimal cut-off values for anthropometric indicators of obesity to evaluate cardiometabolic risk. A minimum P-value approach was applied to calculate the cut-offs for BF%. Threshold values for body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height (WHTR) ratio, facilitating optimal differentiation of cardiometabolic risk, were based on BF%, expressed as a binary classifier. The newly estimated cut-off values for predicting cardiometabolic risk, based on BMI, were lower than the referential obesity thresholds, whereas the threshold values of WC, WHR, and WHTR were higher. Apart from dyslipidemia, the odds of cardiometabolic disorders were higher, when the anthropometric indicators under study exceeded the cut-off points in both sexes. The proposed cut-offs proved instrumental in predicting cardiometabolic risk, whilst highlighting diagnostic and clinical potential of BF%, whereas BMI boasted the highest predictive potential. Cardiometabolic risk also proved significantly higher even in the overweight patients.