Establishment and Validation of Prognostic Nomograms Based on Serum Copper Level for Patients With Early-Stage Triple-Negative Breast Cancer

Background: Altered copper levels have been observed in several cancers, but studies on the relationship between serum copper and early-stage triple-negative breast cancer (TNBC) remain scare. We sought to establish a predictive model incorporating serum copper levels for individualized survival predictions.Methods: We retrospectively analyzed clinicopathological information and baseline peripheric blood samples of patients diagnosed with early-stage TNBC between September 2005 and October 2016 at Sun Yat-sen University Cancer Center. The optimal cut-off point of serum copper level was determined using maximally selected log-rank statistics. Kaplan-Meier curves were used to estimate survival probabilities. Independent prognostic indicators associated with survival were identified using multivariate Cox regression analysis, and subsequently, prognostic nomograms were established to predict individualized disease-free survival (DFS) and overall survival (OS). The nomograms were validated in a separate cohort of 86 patients from the original randomized clinical trial SYSUCC-001 (SYSUCC-001 cohort).Results: 350 patients were eligible in this study, including 264 in the training cohort and 86 in the SYSUCC-001 cohort. An optimal cut-off value of 21.3 μmol/L of serum copper was determined to maximally divide patients into low- and high-copper groups. After a median follow-up of 87.1 months, patients with high copper levels had significantly worse DFS (p = 0.002) and OS (p < 0.001) than those with low copper levels in the training cohort. Multivariate Cox regression analysis revealed that serum copper level was an independent factor for DFS and OS. Further, prognostic models based on serum copper were established for individualized predictions. These models showed excellent discrimination [C-index for DFS: 0.689, 95% confidence interval (CI): 0.621–0.757; C-index for OS: 0.728, 95% CI: 0.654–0.802] and predictive calibration, and were validated in the SYSUCC-001 cohort.Conclusion: Serum copper level is a potential predictive biomarker for patients with early-stage TNBC. Predictive nomograms based on serum copper might be served as a practical tool for individualized prognostication.

Serum Copper Level and Polycystic Ovarian Syndrome: A Meta-Analysis

<b><i>Introduction:</i></b> The association of serum copper with polycystic ovarian syndrome (PCOS) has been studied for years, but no definite conclusion is drawn. Therefore, we conducted a meta-analysis to investigate serum copper concentrations in PCOS subjects compared with healthy controls. <b><i>Methods:</i></b> Electronic search was performed in PubMed, Google Scholar, and Scopus up to June 30, 2020, without any restriction. Standardized mean differences (SMDs) with corresponding 95% CIs in serum copper levels were employed with random-effects model. <i>I</i>² was applied to evaluate heterogeneity among studies. <b><i>Results:</i></b> Nine studies, measuring plasma copper levels in 1,168 PCOS patients and 1,106 controls, were included. Pooled effect size suggested serum copper level was significantly higher in women with PCOS (SMD = 0.51 μg/mL, 95% CI = [0.30, 0.72], <i>p</i> &#x3c; 0.0001). The overall heterogeneity was not connected with subgroups of the country, but derived from the opposite result of 1 study. <b><i>Conclusion:</i></b> Our research generally indicated circulating copper level in PCOS sufferers was significantly higher than normal controls. Large-scale studies are still needed to elucidate the clear relation between copper status and etiology of PCOS.

EFFECT OF DIETARY COPPER SUPPLEMENTATION ON SERUM COPPER LEVEL AND PERFORMANCE OF FEMALE WEST AFRICAN DWARF (Fouta djallon) GOATS

The effects of dietary copper supplementation on serum copper level and performance were studied in a 174-day feeding experiment involving 16 female West African dwarf goats level and using depletion - repletion approach, The results obtained showed a significantly lower (P<0.05) but traces of serum copper after depletion combined with pre depletion (1.70 to 1.90 Ug/dl serum) and after 42 days of dietary repletion (1.28 to 2.50 Ug/dl serum). The best responses in terms of growth rate (0.114 kg/day) highest dry matter intake (1.43 Ugg feed DM) were induced by 240.68 Ug Cug DM of feed. The goats managed maintenance requirement for copper was 5.033 UgCuw0.75. while the dietary copper supplementation requirement was 240.68 Ug They had free access to salt licks and water. Cu/g DM of feed for optimum weight gain, growth rate and dry matter intake.

Serum Copper Level in Patients with Heart Failure and its Related Factors

Background: Congestive Heart Failure (CHF) is a debilitating disorder that affects 1-2% of the general population. Despite recent advances in the management of heart failure, symptomatic heart failure still has a poor prognosis, so the importance of evaluating these patients is emphasized. The micronutrients are not produced in the body, but they should be taken in the required amount of diet, and their required amount is generally less than 100 mg per day. Copper deficiency leads to hypertrophic cardiomyopathies in several experimental models, which ultimately leads to systolic and diastolic cardiac function impairment. Copper deficiency is the only nutritional factor that increases cholesterol, blood pressure, homocysteine, and uric acid, leads to glucose intolerance, and increases thrombotic and oxidative damage. Objectives: The aim of this assessment is to examine the serum copper level in patients with Heart failure hospitalized in Rajaie Cardiovascular, Medical and Research Center and its related factors in the period of 2017-18. Methods: This as a prospective descriptive study conducted on patients with heart failure hospitalized in Rajaee Cardiovascular, Medical and Research Center. Research variables included serum copper level, Pro-BNP serum level, heart failure etiology, Seattle Heart Failure Model (SHFM), age, gender, BMI, history of diabetes, history of airway disease, duration of heart failure diagnosis, smoking, presence of shortness of breath, the amount of ejection fraction (EF), initial blood pressure, serum hemoglobin levels, white blood cell count, creatinine, cholesterol, sodium and uric acid. Accordingly, 80 patients with heart failure have been evaluated and the results of the evaluation of patients have been put together based on the aims of the study. Results: Of the evaluated cases, there were 52 (65%) male and 35 (28%) female. The mean and standard deviation of the patients' age was 49.9 ± 16.2 years, also the mean and standard deviation of serum copper was 189.28 ± 58.3 (range:80-150). The evaluated indices in this study included severe NYHA (P = 0.90), ejection fraction (EF) in echocardiography (P = 0.40), serum Pro BNP (P = 0.45) and prognosis of disease according to Seattle Heart Failure Model (P = 0.63), because non of the patients copper serum level were under the baseline we could not found statistically significant relationship between serum copper level and EF, pro BNP, NYHA function class and prognosis of the disease according to Seattle Heart failure model, while there was a significant statistical relationship between serum copper levels and etiology of heart failure (P = 0.02). Conclusions: Copper does not have a significant effect on the status of patients with heart failure, and only some differences were observed in the etiology of heart failure.

Assessment of Serum Copper Level among Sudanese Patients with vitiligo

Background: Vitiligo is a common skin disease of unknown etiology characterized clinically by depigmented patches, which can be localized or generalized; it usually runs a chronic course with an un predictable outcome and failure of complete cure in many affected individuals. Many communities consider it a contagious disease which leads to a great psychological and social stigma for patients; previous studies showed that copper might be associated with the pathogenesis of vitiligo. The aim of this study was to assess copper level in Sudanese vitiligo patients. Methods: This is a case-control study conducted in dermatology clinics in Khartoum state during the period from November 2018 to February 2019. Blood samples were obtained from 100 participants, 50 from vitiligo patients and 50 from non-vitiligo subjects representing a control group. Serum copper was measured by mind-ray (automation). Results: A highly significant increase (P-value = 0.000) in the copper level was seen in vitiligo patients compared with the control group. Of the total number of patients, 17 (34%) were females and 33 (66%) were males. According to the duration of the disease, the copper level was significantly increased in patient group with a disease duration of > one year compared to the patient group six months–one year and patient group < 6 months; we found no significance of the family history, 18% of the case group had a family history while 42 (82%) had no family history. Discussion: The relationship between the serum level of copper and vitiligo has been assessed by many studies. Copper is one of the trace elements that was found to be important for tyrosinase enzyme that catalyzes the first steps in melanin synthesis in the skin. Some studies showed that the disease was associated with low serum levels of copper and since vitiligo is a disease that is characterized clinically by white areas of skin with no melanin, these studies seem to be logical. However, in this study, the serum level of copper was found to be high in vitiligo patients which might be justified by the release of copper from the destroyed melanocytes. Another justification might be a defect in the carrier protein for copper. Conclusion: The study found that the serum copper was significantly increased in vitiligo patients compared to the control and it is recommended that serum copper level and copper profile should be assessed routinely in vitiligo patients. Keywords: vitiligo, depigmentation, copper, Sudanese

The Effects of Antiepileptic Drugs (AED) on Serum Copper Level in Children with Epilepsy

Background: Epilepsy is a central nervous system disorder in which brain activity becomes irregular, causing seizures or periods of unusual behavior, sensations, and sometimes loss of awareness. Serum copper level may change due to long term use of antiepileptic drugs. Objective: The purpose of the present study was to assess the serum copper level in childhood epilepsy treated with long-term Anti-Epileptic Drug (AED). Methodology: This cross-sectional study was carried out in the Department of Paediatric Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU) during March to August’ 2013. Sample size was one hundred, among these fifty were case (epileptic child who had received anti-epileptic drugs (Carbamazepine and/or Valproic acid) for more than three months) and rest fifty were control (newly diagnosed epileptic child, who yet not received antiepileptic drug). Result: The mean copper level was 1.11±0.32 µg/ml in case group and 0.96±0.20 µg/ml in control group, which was statistically significant (p<0.05). Conclusion: The use of one drug or multiple drugs in the treatment of epileptic patients may play significant role in increasing copper serum level.

Evaluation Serum Copper Levels in Preeclampsia and Healthy Pregnant Women

Background: Preeclampsia is a fatal medical disorder of pregnancy. It has been associated with adverse course and outcome of the pregnancy resulting in increased maternal and infant mortality and morbidity. As the pathogenesis of preeclampsia is not completely understood, prevention remains a complex issue. In recent times, there has been an increasing prevalence in the incidence of preeclampsia globally. The aim of this study is to determine the states of the copper in pregnant women with preeclampsia. Methods: This case-control study was carried out in the Department of Biochemistry, Mymensingh Medical College, Mymensingh, from July 2013 to June 2014. The subjects were selected on the basis of inclusion and exclusion criteria by purposive method. This study included 73 patients with preeclampsia as case (Gr.I) classified into two subgroups according to the gestational age: Gr.I(a); preeclampsia in the second trimester (n = 35), and Gr.I(b); preeclampsia in the third trimester (n = 38). Copper levels were analyzed and results were compared with 73 apparently healthy pregnant control (Gr.II), and the corresponding gestational age subgroups [Gr.II(a); normal pregnancy of second trimester (n = 35) and Gr.II(b), normal pregnancy of third trimester (n = 38)]. Results: The mean serum copper level was significantly (p<0.001) lower in case group than that of control group. Similar extent of reduction was observed in serum copper level at different gestational age groups of preeclamptic women when compared with corresponding control groups. Conclusion: Estimation of serum copper level should be incorporated in pre eclamptic patients for prevention of complications. Birdem Med J 2019; 9(1): 18-22

Effect of Management System on Serum Copper Level and Haematology of Jabal Akhdar Breed Goats in two Sites in Al Jabal Al Akhdar Region of Oman

ABSTRACT: Blood samples were collected from randomly selected healthy Jabal Akhdar breed goats reared in two sites in the Jabal Akhdar region of Oman. Seven males and 65 female goats, age range 2 months to 4 years, raised in Shnoot Al-Dar village were kept under a semi-intensive system (SIS) and 2 males and 18 females, age range 4 months to 5 years, raised in Al-Ala'lana village and kept the under free range system (FRS) were studied. Serum Cu and haematological values were measured. There were no significant (p>0.05) effects of age, sex or serum copper levels on the haematology of goats, so data was pooled and only the effects of the management system on serum Cu and haematology were analysed. There were highly significant (p<0.001) differences between the two systems in all parameters studied. FRS goats were higher than SIS goats in mean values (± SE) of serum Cu (mg/l) 0.60 ± 0.07 vs 0.48 ± 0.33, red blood cells (RBC) (X1012/L) value 15.03 ± 0.42 vs 14.97 ± 0.25, mean cell volume (MCV) (fl) 21 ± 21 vs 19.57 ± 0.19, and haematocrit (HCT) (%) value 31.84 ± 0.59 vs 29.6 ± 0.35. SIS values were higher than FRS in haemoglobin (Hb) (g/dl) 9.34 ± 0.16 vs 9.26 ± 0.27, mean cell haemoglobin (MCH) (pg) 6.21 ± 0.05 vs 6.16 ± 0.08 and mean cell haemoglobin concentration (MCHC) (g/dl) 31.96 ± 0.38 vs 29.05 ± 0.64. Therefore, it is evident that the management system can affect the serum copper levels and haematology of the Jabal Akhdar breed of goats in the Jabal Akhdar region of Oman.

Utility of Serum Copper Level Estimation in Patients Suffering from Alzheimer’s Disease

Background: Alzheimer’s disease is the most common cause of dementia. Metals such as zinc , copper, iron are likely involved in the neurodegeneration of Alzheimer’s disease . Copper can catalyze a flux of reactive oxygen species that can damage functional and structural macromolecules in brain. Most studies found association of high serum copper level with Alzheimer’s disease but also some studies did not. Methods: Total 48 patients of Alzheimer’s disease who were diagnosed according to NIA-AA ( National institute of Aging – Alzheimer’s Association) recommendation ( revised NINCDS-ADRDA) criteria were taken as study population purposively and 42 age and sex matched control were selected. Fasting serum copper level were done for both groups. Comparison of serum copper level of Alzheimer’s patients with that of the control group were done to see association. Results : A total of 28 male and 20 female with mean age of 66.20 ± 9.42 (mean±SD) years, 22 male and 20 female with mean age of 63.54 ± 9.74 (mean±SD) years constituted as case and control groups, respectively. The mean of serum copper in case and control groups were 0.95 ± 0.37 versus 0.92 ± 0.25 mg/L (P > 0.05). The present study found that serum copper levels are non-significantly higher in patients with AD than control group, however it did not show a significant relationship with severity of dementia. Conclusion: So our suggestion was to perform a study work including total serum copper level , serum ceruloplasmin level and free serum copper level comparing between a large Alzheimer’s Disease patients group and age , sex matched apparently healthy control group to understand the copper dyshomeostasis in Alzheimer’ Disease. Bangladesh Journal of Neuroscience 2017; Vol. 33 (2): 96-102