Analysis of Turkish Breast Cancer Patients With ATM-Heterozygous Germline Mutation According to Clinicopathological Features.

OBJECTIVE: The ATM gene is one of the most common breast cancer (BC) susceptibility genes after BRCA1/2 and has been shown to be a moderate BC susceptibility gene. The association between ATM germline mutation and clinical features of BC is now unknown. In this article, clinicopathological features of BC patients with ATM germline heterozygous mutation were investigated. MATERIALS AND METHODS: Patients admitted to the Medical Genetics department of a tertiary hospital between January 2020 and December 2022 were examined. Only invasive BC patients with pathogenic mutation, likely pathogenic mutation, or variants of uncertain significance (VUS) were included in the study. RESULTS: In all, 121 patients were included in the study. The median age at the first cancer diagnosis of the patients was 44 years. Of the total number of patients, 75.2% (91) had the histological subtype of infiltrating ductal carcinoma, and 43% (52) had Luminal B molecular subtype features. At a median follow-up of 16 months, 5.8% (7) of patients developed cancer in the contralateral breast. In addition, 7.4% (9) of the patients developed a second primary cancer during follow-up. When the patients were compared according to ATM variant classification, the localization, histologic types, and molecular subtypes of the BC were not different between all groups (respectively; p=0.68, p=0.65, p=0.32). CONCLUSIONS: To the best of our knowledge, this is the first publication that evaluates the clinical and pathological characteristics of BC patients with germline heterozygous ATM mutations in the Turkish population. When patients were compared according to variant classifications of ATM mutation, patients' histological and molecular subtypes were similar.

Ribociclib-induced pulmonary infiltrates in a patient with breast cancer.

INTRODUCTION: Breast cancer is the most common cancer in women worldwide. One of the treatment choices used in hormone receptor positive and HER2 expression negative metastatic breast cancer is cyclin dependent kinase 4/6 (CDK) inhibitors. There are differences between the effects and adverse events of all CDK4/6 inhibitors. In this report, we describe a 48-year-old female patient with breast cancer who developed pulmonary infiltrates secondary to drug in the second year of follow-up with Ribociclib therapy. CASE REPORT: The patient who used ribociclib for metastatic breast cancer was admitted to hospital for routine controls. The patient, in the eighth month of ribociclib treatment, had no active complaints. In the patient's imaging, pulmonary infiltrates were detected in the lower lobe of the right lung. MANAGEMENT AND OUTCOME: The drug was continued in the patient who was asymptomatic and had no infectious signs. Pneumonitis, interstitial lung disease, tuberculosis, COVID-19 and other viral agents were excluded in the patient. A minimal increase in pulmonary infiltrates was observed in the follow-up. However, the patient who does not have any complaints is currently continuing ribociclib at 600 mg/day. DISCUSSION: The pulmonary infiltrates that developed in the patient increased with continued use of ribociclib, suggesting that this was due to ribociclib. The Naranjo Adverse Drug Reaction Probability Scale also indicates probable relationship.

Major and minor salivary gland cancers: A multicenter retrospective study.

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.

Demographic, clinical and laboratory characteristics of adult-onset minimal change disease in Turkey: Turkish Society of Nephrology-Glomerular Diseases (TSN-GOLD) Working Group.

PURPOSE: In our study, diagnostic and demographic characteristics of patients diagnosed with minimal change disease (MCD) by biopsy, clinical and laboratory findings in our country were investigated. METHODS: Data were obtained from the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group database. Demographic characteristics, indications for biopsy, diagnosis of the glomerular diseases, comorbidities, laboratory and biopsy findings of all patients were recorded. The data presented are cross-sectional and includes application data for the biopsy period. RESULTS: Of 3875 patients, 233 patients with MCD (median age 35.0 years) were included in the study, which constitutes 6.0% of the total glomerulonephritis database. Renal biopsy was performed in 196 (84.1%) patients due to nephrotic syndrome. Median serum creatinine was 0.7 (0.6-1.0) mg/dl, mean eGFR was 104 ± 33 ml/min/1.73 m2 and median proteinuria 6000 mg/day. The number of patients under the age of 40 years was 139 (59.7%) (Group A), and the number of patients aged 40 years and over was 94 (40.3%) (Group B). Compared to Group A, global sclerotic glomeruli (24 vs. 43, p < 0.001) interstitial inflammation (15 vs. 34, p < 0.001), interstitial fibrosis (20 vs. 31, p = 0.001, vascular changes (10 vs. 25, p < 0.001) and tubular atrophy (18 vs. 30, p < 0.001) were found to be significantly higher in Group B. There was no difference in immunofluorescent staining properties between the two groups. CONCLUSION: Our data are generally compatible with the literature. Chronic histopathological changes were more common in patients aged 40 years and older than younger patients. Studies investigating the effects of these different features on renal survival are needed.

A possible interaction between favipiravir and methotrexate: Drug-induced hepatotoxicity in a patient with osteosarcoma.

INTRODUCTION: Favipiravir is an antiviral agent that is recently used for SARS-CoV2 infection. The drug-drug interactions of favipiravir especially with chemotherapeutic agents in a patient with malignancy are not well known. CASE REPORT: The patient diagnosed with metastatic osteosarcoma was given high dose methotrexate treatment, and favipiravir was started on the third day of the treatment with suspicion of SARS-CoV2 infection. Grade 3 hepatotoxicity developed after favipiravir.Management & outcome: The acute viral hepatitis panel and autoimmune liver disease panel were negative. The ultrasound of the abdomen was unremarkable for any hepatobiliary pathology. The all viral and hepatobiliary possible etiological factors were ruled out. The patient's liver enzymes increased just after (12 hours later) the initiation of favipiravir, and we diagnosed toxic hepatitis caused by favipiravir-methotrexate interaction. Therefore, methylprednisolone 1 mg/kg dose was started for a presumed diagnosis of toxic hepatitis. Hepatotoxicity completely regressed after favipiravir was discontinued. DISCUSSION: Favipiravir may inhibit methotrexate elimination by inhibiting aldehyde oxidase and its sequential use may cause hepatotoxicity in this case. The clinicians should keep in mind possible drug interactions while using new antiviral agents against SARS-CoV2 like favipiravir.

Dangerous interaction of bitter melon (Momordica charantia) with pazopanib: A case of acute pancreatitis.

INTRODUCTION: Acute pancreatitis associated with Pazopanib has been reported in the literature. Bitter Melon (Momordica Charantia) is traditionally used as a folk medicine in many regions. In this report, we describe a 65-year-old patient with a diagnosis of renal cell carcinoma, admitted to the hospital with symptoms of acute pancreatitis at the 8th year of pazopanib treatment. CASE REPORT: The patient diagnosed with renal cell carcinoma was admitted to the hospital with the complaint of abdominal pain, nausea, and vomiting in the 8th year of Pazopanib treatment. It was noticed from the patient's history that he had received Bitter Melon extract for 4 days prior to the beginning of his complaints (100-150 ml/day). Levels of serum amylase and lipase were measured as 9163 U/L and 14,206 U/L, respectively. MANAGEMENT & OUTCOME: Pazopanib drug was held. The patient was treated for acute pancreatitis. Pazopanib treatment was started again after the clinical condition of the patient had improved and levels of serum amylase and lipase had returned to normal levels. Levels of serum amylase and lipase did not increase again after re-administration of pazopanib treatment. DISCUSSION: It is thought that Bitter Melon extract and pazopanib interaction might have led to acute pancreatitis. To the best of our knowledge, this case is the first to highlight the interaction of Bitter Melon extract with pazopanib. The Drug Interaction Probability Scale indicates that there is a probable association between bitter melon and acute pancreatitis.

Current status of biosimilars in Turkey: A survey among medical oncologists.

INTRODUCTION: To evaluate biosimilar understanding and preference trends of medical oncologists in Turkey. METHODS: A survey consisting of 24 multiple-choice questions with checkbox answers was conducted among medical oncologists. The questionnaire was divided into five parts to some intentions: demographic characteristics, general knowledge about biosimilars, knowledge about local approval and reimbursement issues, individual preference trends, and ranking the knowledge of their own. All answers were analyzed as whole cohort, specialists and fellows. RESULTS: Fellows (n = 47) consisted 42%, and academic clinicians (n = 37) consisted 35% of the participants. In the whole cohort, the overall rate of correct answers was 55.1% in the general knowledge about the biosimilars part, and 26.7% in the local approval and reimbursement issues part. At all, 57.7% of the participants declared that they object to switch from a reference product to a biosimilar product. The rate of those who defined themselves as extremely knowledgeable decreased from 8.1% to 2.7% in the whole cohort at the end of the survey. CONCLUSION: The need for more accurate and clarified local regulations and education emerging in the biotechnology era must be met.

Clinical and laboratory outcomes of the solid cancer patients reinfected with SARS-CoV-2.

Introduction: The objective of this study was to evaluate the clinical and laboratory outcomes of solid cancer patients who were reinfected with COVID-19. Methods: Patients who were tested negative on the COVID-19 PCR test and those with improved clinical conditions after infection with COVID-19 were enrolled in this study. Patients who received a positive COVID-19 PCR test 28 days after the initial positive PCR test were considered as reinfected. Results: A total of 1024 patients with the diagnosis of solid malignancy and COVID-19 PCR positivity were examined. The reinfection rate was 3.1%. Mortality rate of reinfection was 34.3%. The serum ferritin and creatinine values in reinfection were found to be significantly higher than the first infection (respectively; p = 0.015, p = 0.014). Conclusion: This study has demonstrated one of the first preliminary clinical results of COVID-19 reinfection in solid cancer patients.

Plain language summary Solid cancer patients are at a higher risk than general population in terms of COVID-19 infectivity and COVID-19-associated death and disease. It is also known that COVID-19 infection has a more severe course in immunocompromised patients. Solid cancer patients may be a vulnerable subgroup of patients to reinfection with COVID-19. The rate of reinfection was 3.1% (n = 32) in our study population of 1024 solid cancer patients who were tested positive on a COVID-19 PCR test. The death rate of the patients with solid cancer was 34.3% (n = 11). In addition, we demonstrated that intensive care follow-up is significantly longer during the reinfection period. It was demonstrated that the time between the last dose of chemotherapy for the patients and the reinfection COVID PCR positivity did not affect the death rate. The COVID-19 pandemic has affected people's daily lives and treatments in many aspects. Owing to the high death rate of reinfection, even if cancer patients have reinfection, our approach is to continue cancer treatment as soon as the patient is cured. Finally, we support the priority vaccination of cancer patients.

The neutrophil-lymphocyte ratio and its relationship with insulin resistance in obesity

Background/aim: In this study, our aim was to investigate the neutrophil/lymphocyte (N/L) ratio, variations in leukocytes and leukocyte subtypes, and the relationship between N/L ratio and insulin resistance (IR) in obesity. Materials and methods: Ninety-six patients and 40 healthy controls were included in this study. Patients' blood glucose levels, insulin levels, and hemogram parameters upon 8 h of fasting were determined. Body mass index (BMI) and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) values were calculated. Results: Neutrophil numbers were found to be higher among obese patients with IR than among non-IR obese patients. The N/L ratio was, moreover, found to be higher among obese patients with IR when compared to non-IR obese patients. A positive correlation was found between insulin resistance and both neutrophil and WBC counts. Positive correlations were also found between insulin levels and the N/L ratio, WBC counts, and neutrophil counts Conclusion: In our study, leukocyte numbers and subtypes were determined to be higher among obese individuals than among healthy individuals. The N/L ratio was increased significantly only among obese patients with IR. Further studies are needed in order to better demonstrate the relationship between the N/L ratio and IR/inflammation.

An assessment of the relationship between thyroid nodule characteristics, insulin resistance and arterial stiffness in euthyroid nodular goiter.

OBJECTIVES: Publications suggesting that thyroid nodule might be associated with insulin resistance and metabolic syndrome are quite interesting. There is a need for studies assessing the relationship between nodule presence and cardiovascular risk in individuals with non-functioning nodular goiter. The purpose of the present study is to reveal whether or not insulin resistance, nodule presence, and nodule stiffness affect arterial stiffness, which is a reliable and valid cardiovascular risk indicator, in individuals with euthyroid nodular goiter using the pulse wave analysis (PWA). MATERIALS AND METHODS: 50 patients with euthyroid nodular goiter and 50 healthy volunteers were included in the study. All participants were examined by B-mode thyroid ultrasound, and the participants in the nodular goiter group were also examined by strain elastography (SE). The strain index of nodules was calculated according to the Rago scoring. Also, fasting plasma glucose (FPG) and insulin levels were measured, and HOMA-IR. Arterial stiffness measurements of the participants were performed using a PWA device which employs a cuff-based oscillometric method from the brachial artery. RESULTS: PWV was found to be significantly higher in the euthyroid nodular goiter group (p < 0.001). PWV was found to be positively correlated with FPG and waist circumference. Fasting plasma glucose was found to be higher in the group with nodular goiter (p = 0.03). However, no difference was found between the groups in terms of HOMA-IR and insulin level. HOMA-IR was not correlated with thyroid volume, nodule volume, and nodule count. Also, HOMA-IR was not correlated with strain index value and PWA data. CONCLUSION: We found that PWV was significantly higher in patients with euthyroid nodular goiter. This result suggests that these patients may be at risk for cardiovascular disease.

Association of neutrophil-to-lymphocyte ratio and microalbuminuria in patients with normal eGFR.

AIMS: The aim of this study was to evaluate the association between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and microalbuminuria in patients with normal estimated glomerular filtration rate (eGFR). METHODS: 174 patients who had eGFR ≥ 60 mL/min/1.73 m2 were studied. Patients were divided into two groups according to the urinary albumin excretion as microalbuminuric group (n = 105) and normoalbuminuric group (n = 69). NLR and PLR levels were calculated. RESULTS: NLR was significantly higher (p < 0.05) in microalbuminuric patients (1.91 ± 0.70) compared with normoalbuminuric patients (1.63 ± 0.53). A positive correlation was found between urine albumin excretion and NLR in the whole study group (r = 0.214, p < 0.005). CONCLUSIONS: Higher NLR levels were found in microalbuminuric patients with normal eGFR. Also a significant positive correlation was observed between albuminuria and NLR.

Relationship between Helicobacter pylori infection and celiac disease: a cross-sectional study and a brief review of the literature.

INTRODUCTION: Whether Helicobacter pylori triggers celiac disease (CD) or protects against CD is currently the subject of research. In the literature, there are epidemiologic studies that have reported conflicting results regarding the association between H. pylori and CD. AIM: To compare the prevalence of CD autoantibody positivity and the levels of CD autoantibodies between H. pylori-positive and H. pylori-negative subjects. MATERIAL AND METHODS: This study was prospectively designed and included 240 dyspeptic patients who underwent upper gastrointestinal endoscopy with gastric and duodenal biopsies. The patients were divided into two groups according to presence of H. pylori infection. The serum levels of immunoglobulin (Ig) A, tissue transglutaminase antibodies (tTGA; IgA and IgG classes), and anti-endomysial antibodies (EMA; IgA and IgG classes) were measured for all participants by a blinded biochemistry expert. RESULTS: There were no significant differences in the serum levels of CD autoantibodies or IgA between the two groups. There were also no significant differences in the percentages of subjects with positive CD serologies or subjects with IgA deficiencies between the groups. CONCLUSIONS: Helicobacter pylori remains one of the bacterial species that is most likely to trigger autoimmunity. However, studies have failed to reveal a relationship between H. pylori and CD; thus, additional basic work on the immunological aspects of the microbial-host interactions and longitudinal studies enrolling patients at very early stages of the disease may help us to address this issue.

The effect of glycemic control on CEA, CA 19-9, amylase and lipase levels.

BACKGROUND: Diabetes mellitus is closely related to pancreas cancer. In this study we aimed to investigate the effect of hyperglycemia on tumor and inflammation markers, as well as pancreatic exocrine functions. METHODS: A total of 98 consecutive diabetic patients with poor glycemic control, and 50 healthy controls were included in the study. We measured hsCRP, erythrocyte sedimentation rate (ESR), CA19-9, CEA, amylase and lipase in addition to routine biochemistry tests, before and after euglycemia was achieved. RESULTS: Fasting blood glucose, HbA1c, CA19-9, CEA, hsCRP, ESR, triglycerides, AST, ALT, GGT, ALP, total cholesterol and LDL-C levels decreased significantly with the regulation of glycemic control. Amylase and lipase levels increased with the regulation of glycemic control. After glycemic control, CA19-9 and CEA levels were still higher, whereas amylase and lipase levels were still lower in the diabetic group compared with the control group. Basal HbA1c showed significant correlation with CA19-9, CEA, amylase and lipase. CONCLUSIONS: We propose to repeat observations of tumor markers after hyperglycemia is resolved, in order to avoid unnecessary invasive tests. Our data also suggest that pancreatic exocrine function was improved with lowering blood glucose in a short period of time.