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Background Methods Results Conclusion Tisotumab vedotin (TV) holds promise for treating recurrence or metastatic cervical cancer (r/mCC), with recent FDA approval for second‐line use in recurrent or metastatic cases. Our research aims to evaluate TV's efficacy and safety in these patients, focusing on overall survival (OS) and progression‐free survival (PFS) outcomes.We searched five electronic databases in February 2024, retrieved articles, screened them based on inclusion and exclusion criteria, and assessed their quality. A meta‐analysis of the extracted data was performed and applied a random‐effects model for our analysis.The search identified 86 articles, with six meeting the inclusion criteria. Meta‐analysis revealed 80.8% and 48.0% OS at 6 and 12 months, and a 29.9% PFS at 6 months. Combined treatment with carboplatin or pembrolizumab showed 33.0% PFS at 1 year and 15.1% at 2 years. The objective response rate (ORR) was 21.0%, reaching 43.3% with combined treatment. Confirmed disease control rate (CDCR) was 70.0% overall and in combination. The median duration of response (DOR) was 6.1 months, increasing to 9.5 months in combined treatment, with a consistent time to response (TTR) of 1.4 months. Adverse events included ocular issues (conjunctivitis 30.3%, dry eye 18.7%) and common side effects (nausea 38.4%, epistaxis 35.7%).This systematic review and meta‐analysis highlights the potential of TV as a treatment option for r/mCC patients. However, healthcare providers must communicate safety profiles and recommend prophylactic measures for optimal patient outcomes. Further studies, particularly assessing combination treatments, are needed to clarify TV's role in treatment algorithms and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pregnancy is a dynamic process associated with changes in vascular and rheological resistance. Maternal maladaptation to these changes is the leading cause of pregnancy complications such as preeclampsia. OBJECTIVE: This study aimed to assess the hemorheological alterations in pregnancies with a high risk for preeclampsia in the first trimester. METHODS: Ninety-two pregnant women were allocated into the high preeclampsia risk group (37 cases) and control groups (55 cases). Plasma and whole blood viscosity and red blood cell morphodynamic properties, including deformability and aggregation were assessed by Brookfield viscometer and laser-assisted optical rotational cell analyzer (LORRCA) at 11–14 gestational weeks. RESULTS: Whole blood viscosity was significantly higher in the high-risk group at all shear rates. Plasma viscosity and hematologic factors showed no differences between the groups. Hematocrit levels positively correlated with high blood viscosity only in the high-risk group. There were no significant changes in the other deformability and aggregation parameters. CONCLUSIONS: Changes in the whole blood viscosity of pregnant women with high preeclampsia risk refer to impaired microcirculation beginning from the early weeks of gestation. We suggest that the whole blood viscosity is consistent with the preeclampsia risk assessment in the first trimester, and its measurement might be promising for identifying high-preeclampsia-risk pregnancies. [ABSTRACT FROM AUTHOR]

Background: Ehlers-Danlos Syndrome (EDS) is a serious chronic condition that leads to diminished quality of life and psychological problems. The current study aimed to systematically reviewed the existing literature on EDS patients' health-related quality of life (HRQoL), calculate mean HRQoL value, and determine the association between demographical and publication-related characteristics with HRQoL. Methods: Four electronic databases were used to identify papers on HRQOL in adults with EDS (Scopus, Medline (by Pubmed), Epistemonikos, and Web of Science). A random-effects meta-analysis was also performed on the 36-item Short Form Survey (SF-36) measure. Results: We contained 37 studies that fulfilled the inclusion criteria. According to the SF-36 metaanalysis, EDS patients and the general population had significant differences in all HRQoL components (p<0.01). In EDS patients, the Physical Component Summary (35.34/100) was more seriously impacted than the Mental Component Summary (45.21/100) in these patients. Conclusion: Individuals with EDS have significantly lower HRQoL in all aspects compared to the general population, with the physical component of wellbeing being the most pronounced disparity. Future research should look into the impact of different patient characteristics, evaluate the complications of EDS and their effects on wellbeing, and develop multiple intervention strategies to improve HRQoL. [ABSTRACT FROM AUTHOR]

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated intravascular hemolysis (IVH). Current treatments like Eculizumab and Ravulizumab have limitations, with many patients still requiring transfusions. This study aimed to investigate the safety and efficacy of the new emergent treatment called Danicopan., Methods: We systematically searched five electronic databases - Epistemonikos, Web of Science, Medline, Scopus, and ClinicalTrials - to ensure comprehensive coverage. The systematic review was conducted following the PRISMA guidelines, ensuring methodological rigor., Results: Four studies were eligible for inclusion, all of them were multicenter trials with 79 patients studied. Treatment with Danicopan led to a notable improvement in hemoglobin levels and a decrease in reticulocyte counts. However, LDH levels did not significantly change after treatment. Additionally, there was a significant increase in GPI-deficient erythrocytes but not in GPI-deficient granulocytes. Total and direct bilirubin levels showed significant differences between treatment groups, and there was an improvement in FACIT scores from baseline., Conclusions: Our systematic review and meta-analysis support the potential of Danicopan as a viable therapeutic option for PNH patients. The targeted inhibition of factor D within the complement system by Danicopan demonstrates both safety and efficacy in managing PNH, as evidenced by our findings., Registration: This paper was registered with the PROSPERO database (CRD42024499375).

FCH domain only 1 (FCHO1) is a key player in clathrin-mediated endocytosis, vital for various cellular processes, including immune regulation and cancer progression. However, the clinical implications of FCHO1 mutations, particularly in combined immunodeficiency, remain unclear. This systematic review aims to provide an objective analysis of the molecular genetics, clinical manifestations, and potential therapeutic targets associated with FCHO1 mutations. A systematic search following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted across electronic databases up to March 25, 2024, to identify studies investigating the relationship between FCHO1 and different clinical manifestations. Eligibility criteria were applied to screen studies, and data extraction included study characteristics, reported symptoms, genetic variants, and primary outcomes. In silico analyses were performed to assess protein-protein interactions and gene expression patterns. Five studies were included, offering insights into the molecular genetics, T-cell deficiency mechanisms, clinical manifestations, and potential therapeutic targets associated with FCHO1 mutations. Molecular analyses identified specific mutations disrupting FCHO1 function, leading to impaired T-cell proliferation, cytokine production, and susceptibility to infections. Clinically, patients exhibited recurrent infections, lymphopenia, and malignancies, with allogeneic hematopoietic stem cell transplantation emerging as a therapeutic option. In silico analyses revealed potential interactions and co-expression between FCHO1 and genes involved in cancer progression and immune signaling pathways. This systematic review objectively elucidates the multifaceted role of FCHO1 in immune regulation and disease pathogenesis. Understanding the molecular mechanisms underlying FCHO1 mutations and their impact on disease manifestations is crucial for guiding clinical management and developing targeted therapeutic strategies., (© 2024 Wiley Periodicals LLC.)

Background and Objective: Breast cancer (BC) remains a significant health concern, particularly in advanced stages where the prognosis is poor. The combination of endocrine therapy (ET) with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) has improved outcomes for advanced BC (aBC) patients. However, resistance to CDK4/6i remains a challenge, with no validated biomarkers to predict response. The receptor activator of the nuclear factor-kB (RANK) pathway has emerged as a key player in aBC, particularly in luminal BC. RANK overexpression has been associated with aggressive phenotypes and resistance to therapy. In view of these findings, we proceeded to investigate the potential involvement of the RANK pathway in luminal BC resistance to CDK4/6i. The objective was to evaluate the effectiveness of denosumab in increasing overall survival (OS) and progression-free survival (PFS)., Methods: In this retrospective analysis, 158 BC patients with bone metastases were included. Patients with human epidermal growth factor receptor-2 (HER2)-negative and hormone receptor-positive BC who received palbociclib or ribociclib in addition to antiresorptive medication were included. Patients received either denosumab or zoledronic acid (ZA) therapy. The primary endpoint was OS, with PFS as a secondary endpoint., Results: Although the PFS and OS of denosumab were better than ZA in this study, it did not show a significant difference between the two drugs. Meanwhile, mOS was not achievable in patients in the denosumab group, while it was 34.1 months in patients in the ZA group. The hazard ratio (HR) showed a significant improvement for the denosumab group in patients under 60 of age (HR: 0.33, p<0.01), patients with a score of 1 HER2 overexpression (HR: 0.09, p=0.01), and patients with resistant endocrine (HR: 0.42, p=0.02) compared to ZA., Conclusion: This study highlights the potential clinical relevance of the RANK pathway in BC treatment, and our findings suggest that denosumab may offer significant benefits in terms of PFS and OS for certain subgroups, particularly those with HER2 scores of 1, patients under 60, and those with endocrine-resistant BC. In conclusion, considering that RANK pathway status may be a predictive biomarker for CDK4/6i treatment and may cause treatment resistance, our results demonstrate the clinical relevance of the combination of CDK4/6i + ET with RANKL inhibition., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of Kartal Dr. Lütfi Kirdar City Hospital issued approval 2023/514/250/2. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Akdag et al.)