Comprehensive exploration of FCHO1 mutations: Clinical manifestations and implications across disorders.

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.

Monkeypox Diagnosis in Clinical Settings: A Comprehensive Review of Best Laboratory Practices.

An outbreak of monkeypox (Mpox) was reported in more than 40 countries in early 2022. Accurate diagnosis of Mpox can be challenging, but history, clinical findings, and laboratory diagnosis can establish the diagnosis. The pre-analytic phase of testing includes collecting, storing, and transporting specimens. It is advised to swab the lesion site with virus transport medium (VTM) containing Dacron or polyester flock swabs from two different sites. Blood, urine, and semen samples may also be used. Timely sampling is necessary to obtain a sufficient amount of virus or antibodies. The analytical phase of infectious disease control involves diagnostic tools to determine the presence of the virus. While polymerase chain reaction (PCR) is the gold standard for detecting Mpox, genome sequencing is for identifying new or modified viruses. As a complement to these methods, isothermal amplification methods have been designed. ELISA assays are also available for the determination of antibodies. Electron microscopy is another effective diagnostic method for tissue identification of the virus. Wastewater fingerprinting provides some of the most effective diagnostic methods for virus identification at the community level. The advantages and disadvantages of these methods are further discussed. Post-analytic phase requires proper interpretation of test results and the preparation of accurate patient reports that include relevant medical history, clinical guidelines, and recommendations for follow-up testing or treatment.

Safety and efficacy of tisotumab vedotin with cervical cancers: A systematic review and meta-analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

Transvaginal morcellation within an enclosed bag in gynecological surgeries: a comprehensive systematic review and analysis of safety, efficacy, and outcomes.

PURPOSE: This systematic review aims to comprehensively assess the safety and efficacy of transvaginal morcellation within an enclosed bag in gynecological surgeries, with a focus on its benefits, potential risks, and recommendations for its use. METHODS: We conducted a comprehensive search of Epistemonikos, Web of Science, Medline (PubMed), Scopus, and Cochrane databases for studies on transvaginal contained morcellation in adult patients undergoing gynecological surgeries. The review included 22 studies that met the inclusion criteria, encompassing diverse surgical procedures, patient profiles, and outcomes. These studies were thoroughly reviewed and analyzed to assess the safety and efficacy of the morcellation technique. RESULTS: Key findings from the selected studies indicate that transvaginal morcellation within an enclosed bag offers several advantages in gynecological surgeries, including reduced invasiveness, shorter operative times, and minimal blood loss when compared to conventional methods. The risk of tumor recurrence or dissemination appears to be low when appropriate precautions are taken, emphasizing the technique's safety, especially when performed by experienced surgical teams. While some studies reported complications, these were generally not directly associated with the morcellation technique. CONCLUSION: Transvaginal morcellation within an enclosed bag demonstrates potential as a safe and effective option for gynecological surgeries. The technique offers the benefits of minimally invasive procedures, including reduced bleeding, shorter recovery times, and improved cosmetic outcomes. This review also highlights the need for standardization in study methodologies and reporting, as the heterogeneity in outcomes across the selected studies poses challenges in drawing definitive conclusions.

Combined Stromal Vascular Fraction and Fractional CO2 Laser Therapy for Hypertrophic Scar Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: Hypertrophic scars (HTSs) result from aberrant wound healing processes, leading to raised, thickened tissue with functional discomfort and cosmetic concerns. Current treatments, including corticosteroid injections and laser therapy, have limitations. Stromal vascular fraction (SVF) therapy and CO2 laser treatment offer promising avenues, with SVF therapy showing regenerative potential and CO2 laser therapy promoting precise tissue removal and wound healing. This study aims to investigate the combined application of SVF therapy and CO2 laser treatment for HTS, aiming to enhance treatment efficacy, tissue remodeling, and aesthetic outcomes, ultimately improving patient satisfaction in HTS management. METHOD: PubMed, Scopus, Embase, and Web of Science databases have been searched for relevant studies. The "R" software (version 4.3.1) along with the "tidyverse" and "meta" statistical packages utilized to analyze data related to the efficiency of this combined method. A random-effects model was fitted to the data. For each study, continuous outcomes were pooled by calculating the standardized mean difference, along with their 95% confidence intervals. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model. RESULTS: Six articles fulfilled our inclusion criteria and were included in our review. Results from the pooled analysis of Vancouver Scar Scale (VSS) scores across three included studies indicated a significant impact of the SVF+CO2 method on VSS scores post-treatment (SMD=-3.0144; 95% CI:-4.3706 to -1.6583, p<0.0001). However, analysis of transepidermal water loss levels before and after treatment showed no significant difference (SMD=-2.7603; 95% CI: -6.8729 to 1.3522; p=0.1883). Comparatively, in a pooled analysis of two studies, the combined SVF+CO2 method demonstrated superior efficacy in VSS scores compared to other methods (SMD= -1.3573; 95% CI: -2.2475 to -0.4672, p = 0.0028), with moderate heterogeneity across studies (I^2=23.0%, p = 0.2545). CONCLUSION: The combined application of SVF and CO2 laser treatment shows significant promise in improving hypertrophic scars' appearance and texture. The SVF+CO2 method demonstrates superior efficacy compared to other modalities, suggesting its potential as a valuable therapeutic approach for hypertrophic scar management. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Knowledge, Attitudes, and Barriers Toward Research Among Medical Students: A Cross-sectional Study in Turkey.

Background: Scientific research is essential in medicine to practice evidence-based medicine and improve healthcare quality. Research experience enables students to hone their skills in thinking critically, understanding data, and evaluating the strengths and weaknesses of scientific articles. Objective: This study aims to determine knowledge, attitudes, and barriers toward research and assess research participation experience among medical students in Turkey. Methods: We conducted a cross-sectional study among medical students in Turkey. Data was collected using an online self-administered questionnaire. Results: A total of 487 students, 65.1% female, completed the questionnaire. The majority of students (78.9%) showed a poor level of knowledge regarding research, although 23.2% had previously participated in a research project. Females reported significantly higher positive attitude scores (32.2 versus 31.3, p = 0.034) than males. Graduates of high schools based abroad had substantially lower knowledge scores than Anatolian, Science, and Private High School graduates (1.4 versus 2.7, 2.6, 2.4; p < 0.001). Students with experience in a research project had significantly higher knowledge scores (2.7 versus 2.3, p = 0.045). Students who wish to participate in a scientific research project in their future career had both substantially higher positive attitude scores (32.4 versus 29.6, p < 0.001) and knowledge scores (2.5 versus 1.8, p < 0.001) than those with no interest. Conclusion: Most participants had a positive attitude but lacked research knowledge. Some perceived barriers were lack of funding, time, proper mentoring, laboratories, and facilities. Developing better training systems may help to convert students' positive attitudes toward research into improved knowledge, practices, and overcoming research barriers. Supplementary information: The online version contains supplementary material available at 10.1007/s40670-024-01987-0.

Safety and efficacy of danicopan in patients with paroxysmal nocturnal hemoglobinuria: a systematic review and meta-analysis.

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).

Factors Influencing Anxiety Levels in Oncology Patients: A Study on the Impact of Earthquakes.

OBJECTIVE: This study aims to explore the multifaceted factors influencing anxiety levels in oncology patients, with a specific focus on the impact of earthquakes in the context of Turkey. Our objective is to identify and understand sociodemographic, clinical, and lifestyle determinants associated with anxiety in cancer patients, examining how traumatic events, such as earthquakes, contribute to heightened anxiety levels. MATERIALS AND METHODS: A cross-sectional study was conducted, involving 149 oncology patients undergoing treatment at two prominent oncology centers in Turkey. The study collected comprehensive sociodemographic information and assessed anxiety levels using the Beck Anxiety Scale. The dataset was analyzed using SPSS 20.0 (IBM Corp., Armonk, NY), employing a range of statistical methods including descriptive statistics, independent t-tests, Mann-Whitney U tests, and Chi-square tests. RESULTS: The findings underscore several factors significantly linked to anxiety levels in oncology patients. Notably, women, younger patients (age <65), and individuals with specific cancer types exhibited higher anxiety levels. Elevated anxiety was also associated with compromised physical functioning, experiences of earthquakes, irregular sleep patterns, dietary habits, fatigue, and the use of antidepressants. CONCLUSION: This study provides insights into the intricate interplay of factors influencing anxiety levels in oncology patients. Understanding these determinants is paramount for tailoring effective psychosocial support and interventions. The results underscore the need for holistic approaches to enhance the overall quality of life for cancer patients. Gender, age, cancer type, physical well-being, lifestyle choices, and exposure to trauma all play pivotal roles in influencing anxiety levels. These findings hold practical implications for the development and implementation of targeted psychosocial interventions aimed at improving anxiety management and overall well-being for oncology patients.

Investigating the blood rheology in the first trimester pregnancies with high risk for preeclampsia.

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.

Exploring the Clinical Impact of RANK Pathway Inhibition in Advanced Breast Cancer: Insights From a Retrospective Study on CDK4/6 Inhibitors and Antiresorptive Therapy.

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.