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Mehmet Emin Buyukbayram,1 Zekeriya Hannarici,1 Yakup Duzkopru,2 Aykut Turhan,1 Alperen Akansel Caglar,1 P&inodot;nar Coban Esdur,1 Mehmet Bilici,1 Salim Basol Tekin,1 Do&gbreve;an Yaz&inodot;l&inodot;ta&scedil;2 1Department of Medical Oncology, Atatürk University Faculty of Medicine, Erzurum, Turkey; 2Department of Medical Oncology, Ankara Etlik City Hospital, Ankara, TurkeyCorrespondence: Mehmet Emin Buyukbayram, Department of Medical Oncology, Atatürk University Faculty of Medicine, Erzurum, 25100, Turkey, Tel +905392449362, Email m.eminbuyukbayram@hotmail.comObjective: Hormone positive breast cancer is a tumor with high mortality. Combining antihormonal therapy with cyclin dependent kinase 4/6 inhibitors (CDK4/6i) has resulted in longer survival. The effect of inflammatory parameters such as c-reactive protein and c-reactive protein/lymphocyte ratio (CLR) on efficacy and survival in CDK4/6i treatment is unknown. In our study, we aimed to investigate the role of CLR and some parameters in predicting progression-free survival (PFS) with CDK4/6i.Methods: This retrospective cohort study included 78 patients with denovo and recurrent metastatic breast cancer treated with CDK4/6i. Cut off values for the prediction of mortality by various numerical parameter scores were performed by ROC Curve analysis. The effect of clinical variables, inflammatory and histopathological parameters on survival was analyzed by Kaplan–Meier method.Results: Neutrophil/lymphocyte ratio (NLR) and CLR were statistically significant in predicting mortality (p < 0.05). Ki67 and CLR were correlated with PFS. Age and CLR were correlated with OS (p < 0.05). CLR was statistically significant for both PFS (p = 0.022) and OS (p = 0.006).Conclusion: In patients with metastatic hormone-positive breast cancer using CDK4/6i, low CLR and low Ki67 were correlated with longer PFS duration.Keywords: C-reactivated protein/lymphocyte ratio, hormone-positive breast cancer, progression-free survival

BACKGROUND AND AIM:: Orlistat and metformin are the currently used drugs for weight loss. We aimed to compare the effect of orlistat and orlistat plus metformin combination therapy on weight loss and insulin resistance in obese women. PATIENTS AND METHODS:: In all, 57 obese women (body mass index =30?kg/m2 and normal glucose tolerance) were included. All subjects took the same content and caloric diet therapy during the study. After a month of diet period, each individual was randomly assigned to receive 360?mg orlistat per day (group 1; n=30) or 360?mg orlistat plus 1700?mg metformin per day (group 2; n=27) during the next 3 months. Body weight and insulin resistance by the homeostasis model assessment model (HOMA-IR) was measured at baseline, first month and fourth month. RESULTS:: The mean weight loss in groups 1 and 2 was 1.36±0.8?kg (1.4±0.7%) and 1.11±0.7?kg (1.1±0.7%) from baseline to first month; 4.8±2.9?kg (5.28±3.0%) and 5.77±2.5?kg (6.17±2.9%) from first month to fourth month. Body weight was decreased in groups 1 (P< 0.001) and 2 (P< 0.001), but there was no statistically significant difference between groups. Change of HOMA-IR in groups 1 and 2 was 0.41±0.4 (14.9±10.1%) and 0.23±0.7 (8.16±12.3%) from baseline to first month; 0.49±0.77 (22.0±26%) and 0.95±0.88 (34.8±29.1%) from first month to fourth month. HOMA-IR value was decreased in groups 1 (P< 0.001) and 2 (P< 0.001) but was not different between groups during the study period. CONCLUSIONS:: Combination of orlistat with metformin did not result in an additional effect on weight loss and insulin resistance when compared to orlistat alone in our study. However, new studies which have more sample sizes and the longer study period are necessary for this purpose.International Journal of Obesity (2004) 28, 1059-1063. doi:10.1038/sj.ijo.0802707 Published online 22 June 2004 [ABSTRACT FROM AUTHOR]

Lithium is frequently used as a mood stabilizer in patients with mood disorders. Lithium has a narrow therapeutic index and high toxicity. Predisposing factors for intoxication are advanced age, diet disturbances, comorbid medical conditions affecting heart, kidneys or central nervous system and polypharmacy. CASE REPORT: Here we present a case of a 74-year-old woman with a history of Parkinson’s disease, hypertension and bipolar disorder. She was using quetiapine, valsartan with hydrochlorothiazide and levodopa with carbidopa. She presented with altered mental status and muscle rigidity. The patient was admitted with acute lithium intoxication after her second dose of treatment. Blood lithium level increased to 3.58 mEq/L. The woman was hospitalized in the Internal Medicine Intensive Care Unit. With hydration, her symptoms resolved and her lithium level returned to normal after 118 hours. CONCLUSIONS: Prescribing physicians and emergency room physicians should be aware of conditions which may cause a decreased threshold for intoxication.

Presents a letter to the editor about the effects of plasma fibrinogen levels and D-dimer on hypertensive patients.

Background: Immune checkpoint inhibitors (ICI) are generally associated with rare cardiac side effects, yet instances like myocarditis can be fatal. Therefore, detecting and managing left ventricular dysfunction early in ICI therapy is vital., Objectives: This study aims to evaluate whether left ventricular global longitudinal strain (LV GLS) is a predictor for early detection of cardiac dysfunction in patients receving ICI., Methods: This retrospective cohort study included 44 cancer patients who received ICI therapy and underwent pre- and post- treatment assessments of left ventricular ejection fraction (LVEF) and LV GLS between May 2022 and November 2023. Retrospective comparisons and evaluations were conducted on pre-treatment and 3-month interval LVEF and LV GLS measurements during the first year of treatment., Results: The median follow-up duration was 5.3 months (0.5-18.9). No statistically significant difference between baseline and subsequent time points was observed in LVEF and LV GLS values (p>0.05). At the 3-month evaluation, a notable decrease in LVEF and LV GLS was observed in two patients. One patient with reduced LVEF and LV GLS succumbed to myocarditis, and another experienced sudden death of unknown etiology. The other two patients had decreased LV GLS with normal LVEF. Subsequent follow-ups of the patients exhibiting decreased LV GLS alone revealed no further decline in LVEF or LV GLS., Conclusion: In our study, a reduction in LV GLS did not demonstrate a significant role in the early prediction of ICI-related myocarditis or cardiac dysfunction. Further validation through multicenter, large-scale, prospective studies with extended follow-up periods is needed to confirm these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Celebi Coskun, Coskun, Sahin, Levent, Coban, Koca, Sali, Demir, Deligonul, Tenekecioglu, Cubukcu, Evrensel and Vatansever Agca.)

Although there has been a reduction in head and neck squamous cell carcinoma occurrence, it continues to be a serious global health concern. The lack of precise early diagnostic biomarkers and postponed diagnosis in the later stages are notable constraints that contribute to poor survival rates and emphasize the need for innovative diagnostic methods. In this study, we employed machine learning alongside weighted gene co-expression network analysis (WGCNA) and network biology to investigate the gene expression patterns of blood platelets, identifying transcriptomic markers for HNSCC diagnosis. Our comprehensive examination of publicly available gene expression datasets revealed nine genes with significantly elevated expression in samples from individuals diagnosed with HNSCC. These potential diagnostic markers were further assessed using TCGA and GTEx datasets, demonstrating high accuracy in distinguishing between HNSCC and non-cancerous samples. The findings indicate that these gene signatures could revolutionize early HNSCC identification. Additionally, the study highlights the significance of tumor-educated platelets (TEPs), which carry RNA signatures indicative of tumor-derived material, offering a non-invasive source for early-detection biomarkers. Despite using platelet and tumor samples from different individuals, our results suggest that TEPs reflect the transcriptomic and epigenetic landscape of tumors. Future research should aim to directly correlate tumor and platelet samples from the same patients to further elucidate this relationship. This study underscores the potential of these biomarkers in transforming early diagnosis and personalized treatment strategies for HNSCC, advocating for further research to validate their predictive and therapeutic potential.

Introduction: Acute coronary syndromes and ischemic stroke have similar risk factors. Risk scores help to identify disease severity in both diseases. We aimed to evaluate if HEART (History, ECG, Age, Risk factors, and Troponin) score could predict re-hospitalization, recurrent cardiac/cerebrovascular events risk, and mortality within 1-year follow-up in patients presenting with acute ischemic stroke., Methods: Patients hospitalized with a diagnosis of acute ischemic stroke in our tertiary center between 2019 and 2021 were included in this retrospective study. CHA 2 DS 2 -VASc and HEART scores on admission were calculated. In-hospital, 1-month, and 1-year mortalities, as well as re-hospitalization due to recurrent ischemic (cardiac/cerebral), were defined as major adverse cardiac and cerebrovascular events (MACCE), and occurrence of MACCE was accepted as the primary endpoint of the study. Comparative statistical and regression analyses were obtained., Results: A total of 297 patients were included. The mortality rate for 30 days was 7.4% and 1 year was 20.5%. HEART and CHA 2 DS 2 -VASc scores were found independent risk factors associated with the occurrence of MACCE. Patients who experienced MACCE had higher HEART and CHA 2 DS 2 -VASc scores. Meanwhile, HEART score had better prognostic accuracy than CHA 2 DS 2 -VASc score when a cutoff value of 3.5 was set, which is associated with 84.7% sensitivity and 75.2% specificity in the prediction of MACCE., Conclusion: HEART score is effective in determining re-hospitalization and recurrent cerebral ischemic event risk as well as mortality within 30 days and 1 year in patients presenting with acute ischemic stroke. Thus, concomitant use of HEART and CHA 2 DS 2 -VASc scores may provide better characterization of worse prognosis in ischemic stroke patients with high sensitivity and specificity., Competing Interests: None

Background: CDK4/6 inhibitors combined with endocrine therapy have significantly improved treatment outcomes for metastatic hormone receptor-positive (HR+) breast cancer patients. However, the impact of low HER2 expression on treatment response and progression-free survival (PFS) remains unclear., Methods: This multicenter retrospective study included 204 HR+ breast cancer patients treated with a combination of CDK4/6 inhibitor and endocrine therapy. HER2-zero disease was detected in 138 (68%) and HER2-low disease in 66 (32%) patients. Treatment-related characteristics and clinical outcomes were analyzed, with a median follow-up of 22 months., Results: The objective response rate (ORR) was 72.7% in the HER2 low group and 66.6% in the HER2 zero group (p = 0.54). Median PFS was not significantly different between the HER2-low and HER2 zero groups (19 months vs.18 months, p = 0.89), although there was a trend toward longer PFS in the HER2-low group for first-line treatment (24 months progression-free survival rate 63% vs 49%). In recurrent disease, the median PFS was 25 months in the HER2-low group and 12 months in the HER2-zero group (p = 0.08), while in de novo metastatic disease, the median PFS was 18 months in the HER2-low group and 27 months in the HER2-zero group (p = 0.16). The order of CDK4/6 inhibitor use and the presence of visceral metastasis were identified as independent variables affecting PFS., Conclusion: Low HER2 expression did not significantly impact treatment response or PFS in HR+ breast cancer patients treated with a CDK4/6 inhibitor and endocrine therapy. Because of the conflicting results in the literature, further prospective studies are needed to evaluate the clinical significance of HER2 expression in HR+ breast cancer., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The author reports no conflict of interest.

Objective: To evaluate the effect of FDG-PET/CT in the radiological imaging of breast cancer (BC) patients planned for neoadjuvant treatment (NAT), on the clinical prognostic stage (CPS)., Study Design: A descriptive study., Place and Duration of Study: Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey, between June 2014 and September 2020., Methodology: Consecutive patients with stage I-III breast cancer (BC) who were planned for neoadjuvant treatment (NAT). The distribution of CPS detected by both conventional radiological methods (c-CPS) and FDG-PET/CT (PET-CPS) were compared., Results: Significant upstaging on CPS was detected with the addition of FDG-PET/CT to conventional imaging methods in 25/121 (20.7%) patients (p <0.001). In the c-CPS stage, IB, IIA, IIB, IIIA, IIIB patients, the stage change rate was 22.7%, 28.6%, 37.5%, 50%, and 9.1%, respectively. There was no change in patients with c-CPS stage IA and IIIC. There was a significant change in the cN stages (p <0.001), while no significant change was detected in the cT stages of the patients (p = 0.180). Upstaging was detected in 5/16 (6.3%, p=0.034), 14/71 (19.7%, p <0.01), 15 / 30 (50%, p <0.01) of initially cN 0, 1, 2 patients, respectively (p<0.001)., Conclusion: The change in CPS was due to nodal upstaging. The effectiveness of including FDG-PET/CT in the initial radiological imaging in patients planned for NAT should be evaluated with prospective studies evaluating treatment choices to be used in NAT. Key Words: PET scan, Breast cancer, Positron emission tomography, Neoadjuvant treatment, Cancer staging, Staging system, TNM.

Objective: To investigate the relationship between colon cancer (CC) subtypes defined by the status of tumor-infiltrating lymphocytes (TIL) and mismatch repair (MMR) combination with clinicopathological features and survival., Study Design: Observational study., Place and Duration of Study: Department of Medical Oncology, Haydarpaşa Numune Research and Training Hospital, Istanbul, Turkey, from July 2010 to March 2020., Methodology: Eighty-three patients with operated stage II colon cancer were included in the study. Pathology, surgery and oncological treatment and follow-up information were obtained from patient files; and statistical analyses were performed on overall survival (OS). Tumor-infiltrating lymphocytes and mismatch repair status was determined with the help of immunohistochemistry., Results: TIL-high and deficient MMR (dMMR) status were detected in 26 patients (31.3%) and 21 patients (25.3%), respectively. Tumors were divided into four subgroups according to TIL and MMR status. TIL-high/dMMR tumors had the most favourable prognosis, while TIL-low/proficient MMR tumors exhibited poor OS., Conclusion: The combination of TIL and MMR could enable us to differentiate patients' survival outcomes in more details. Therefore, considering that the TIL and MMR status, evaluated by IHC, may be a cost-effective and effective option for risk classification in patients with stage II colon cancer. Key Word: Lymphocytic response, Mismatch repair, Prognosis, Tumor-infiltrating lymphocytes, Stage II cancer, Colon cancer.

Predicting treatment failure and switching effective treatment immediately in patients with multiple sclerosis (MS) is important. We aimed to evaluate the usefulness of Modified Rio score (MRS) in predicting treatment failure in MS patients. This is a retrospective study, which was conducted in two University Hospital. 129 MS patients treated with İnterferon or glatiramer-acetate from 2 clinical sites, were retrospectively selected. MRS was calculated after the first year of therapy. Treatment failure was defined as the presence of a 1 point increase in EDSS, 2 clinical attacks, 1 clinical attack and progression, 1 clinical attack and new lesion on MRI except associated with an attack, or new lesion in 2 different MRI taken at least 3 months apart. The sensitivity, specificity, positive and negative predictive values of the MRS in predicting treatment failure were determined. 71 (55%) patients with score '0', 41 (31.8%) patients with score '1', 11 (8.5%) patients with score '2', 6 (4.7%) patients with score '3' were detected. 14 patients needed treatment switching during the first three years of the treatment. Sensitivity was 57%, specificity was 92%, positive predictive value was 95%, negative predictive value was 47% and accuracy was 89%. Modified Rio score (MRS) was found to be effective in determining the treatment failure as mentioned before. This study will be useful for clinicians who evaluate the treatment failure like us, and this study revealed that the MRS may also help predict treatment failure., (© 2020. Belgian Neurological Society.)

Objective: To determine the diagnostic value of breast and axillary maximum standard uptake (SUVmax) values for predicting ypT0 and ypN0 separately., Study Design: A descriptive study., Place and Duration of Study: Department of Medical Oncology, Haydarpasa Numune Training and Research Hospital, between May 2017 and September 2020.  Methodology: Consecutive patients with operated breast cancer (BC) after neoadjuvant chemotherapy (NAC) were evaluated. SUVmax on FDG-PET/CT after NAC at both primary tumour (postSUVmax-T) and axillary lymph nodes (postSUVmax-N) were assessed to predict the ypT0 and the ypN0, respectively.  Results: Clinically meaningful correlation was detected between postSUVmax-N with ypN0 in patients with human epidermal receptor-positive (Her2+) and triple-negative (TN) BC (in Her2+ BC: r=0.596, p <0.001, in TN BC: r=0.782, p = 0.001). The postSUVmax-N predicted ypN0 with 90.5% positive predictive value (PPV) and 85.7% negative predictive value (NPV) in patients with Her2+ and TN BC. The postSUVmax-T predicted ypT0 with 87.5% PPV and 100% NPV in patients with TN BC (AUC: 0.938, P <0.01) Conclusion: According to this study's findings, the FDG-PET/CT may be an alternative to sentinel lymph node biopsy (SNB) to protect patients from axillary lymph node dissection when the expected FNR of the SNB is high in patients with Her+ and TN BC. Key Words: Breast cancer, FDG PET/CT, Neoadjuvant therapy.

Background: Since March 2020, during the Coronavirus disease 2019 (COVID-19) pandemic, it has been observed that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has neurological involvement with various clinical tables., Methods: We present 3 new cases admitted to our clinic with various neurological findings which were affected by SARS-CoV-2., Results: Imaging studies have shown that inflammatory/demyelinizing lesions appeared in different areas of the central nervous system which were accepted as an atypical demyelinating spectrum associated with Covid 19., Conclusions: With increasing experience, it has been suggested that SARS-CoV-2 may also have a neurotrophic effect. The spectrum of neurological involvement is also expanding as the pandemic continues. These 3 cases suggest that the virus plays a role in the clinical onset of the inflammatory/demyelinating disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Irisin is a novel myokine/adipokine that is released into the circulation in response to types of exercise and increases energy expenditure. Disorders in the endocrine system related to reproduction, which occur due to the chronic or excessive exercise, cause a decrease in women's sexual desire. However, the role of irisin hormone on sexual desire in women has not been elucidated. We hypothesized that chronic irisin exposure would decrease sexual incentive motivation for male partners by affecting the endocrine system in female rats. We tested this by quantifying and comparing of both sexual incentive motivation and active investigation for sexual partner, and also changes in the serum hormone levels in chronically irisin-treated female rats. As a result, chronic irisin exposure decreased the time spent near the male rat, male preference ratio, and male investigation preference ratio. Furthermore, serum testosterone and progesterone levels significantly decreased and estradiol levels increased while kisspeptin-1 levels were not changed by chronic irisin exposure in female rats. These data indicate that chronic irisin exposure may cause low sexual incentive motivation for opposite-sex partners in female rats via changes in reproductive hormones. The results suggest that irisin hormone may play a role in decreased sexual desire due to long-term exercise in women., (Copyright © 2021. Published by Elsevier Inc.)