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.

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.

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.

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.