Differences in Outcomes Between Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer Patients in Upper Middle-Income versus High-Income Countries: A Retrospective Study from 4 Oncology Centers.

BACKGROUND Therapeutic options for human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (mBC) are developing rapidly. This study aimed to determine the differences in the survival outcomes of patients with HER2-positive mBC in relation to access to anti-HER therapy at 3 oncology centers in upper-middle-income countries (UMICs) and 1 oncology center in a high-income country (HIC). MATERIAL AND METHODS We retrospectively identified 42 patients from Croatia (HIC), 71 patients from Serbia (UMIC), and 57 from Bosnia and Herzegovina (UMIC) diagnosed with HER2-positive mBC who were treated between January 2015 and December 2020. The pathohistological features of the tumors were obtained from the pathological findings, which were made according to standard procedures for each center. Patients were treated depending on the availability of therapy, which differed for centers in different countries. We evaluated disease-free survival, progression-free survival, and overall survival (OS) based on the availability of first- and second-line anti-HER2 therapy in UMICs vs HIC. RESULTS OS in first-line therapy was better in patients treated with dual HER2 blockade than in patients treated without dual HER2 blockade, P<0.001. OS in second-line therapy was significantly better in patients treated with trastuzumab emtansine than in patients treated with other reported regimens, P=0.004. CONCLUSIONS Results of our study showed superior survival among patients who were treated with dual first-line HER2 therapy as well as second-line trastuzumab emtansine therapy than in those patients in other centers where these drugs were not available. Raising awareness about this could help improve the situation.

The GSTO2 (rs156697) Polymorphism Modifies Diabetic Nephropathy Risk.

Background and Objectives: In the development of type 2 diabetes mellitus (T2DM) and its complications, genetic and environmental factors play important roles. Diabetic nephropathy (DN), one of the major microangiopathic chronic diabetic complications, is associated with an increased risk of major cardiovascular events and all-cause mortality. The present study was designed to investigate the possible modifying effect of glutathione transferase polymorphisms (GSTM1, GSTT1, GSTP1 rs1138272/rs1695, GSTO1 rs4925 and GSTO2 rs156697) in the susceptibility to T2DM and diabetic nephropathy. Materials and Methods: GSTM1 and GSTT1 deletion polymorphisms were determined by multiplex PCR, whereas GSTO1, GSTO2, and GSTP1 polymorphisms were determined by the real-time PCR in 160 T2DM patients and 248 age- and gender-matched controls. Advanced glycation end products (AGEs) were measured by ELISA. Results: Among six investigated GST polymorphisms, a significant association between the GST genotypes and susceptibility for development of diabetes mellitus was found for the GSTM1, GSTT1, GSTP1 (rs1138272) and GSTO1 polymorphisms. When the GST genotypes' distribution in diabetes patients was assessed in the subgroups with and without diabetic nephropathy, a significant association was found only for the GSTO2 rs156697 polymorphism. Diabetic patients, carriers of the GSTM1 null, GSTT1 null and variant GSTO1*AA genotypes, had significantly increased levels of AGEs in comparison with carriers of the GSTM1 active, GSTT1 active and referent GSTO1*CC genotypes (p < 0.001, p < 0.001, p = 0.004, respectively). Conclusions: The present study supports the hypothesis that GST polymorphisms modulate the risk of diabetes and diabetic nephropathy and influence the AGEs concentration, suggesting the potential regulatory role of these enzymes in redox homeostasis disturbances.

Child Neurology: Bartonella henselae Neuroretinitis in 2 Patients.

Neuroretinitis due to Bartonella henselae infection is a rare cause of vision loss in children. Two pediatric cases of acute unilateral vision loss accompanied by edema of the optic nerve on fundoscopic examination are presented. Severe causes of vision loss were excluded. During the course of the disease, macular stellate exudates emerged on control fundoscopic examinations, and diagnosis of neuroretinitis was made. A causative agent was confirmed by serologic examination, as high titers of IgM and IgG antibodies to Bartonella henselae were detected. Both patients significantly recovered after oral antibiotic treatment.

Availability of technology for managing cancer patients in the Southeast European (SEE) region.

Background: The Southeast European (SEE) region of 10 countries and about 43 million people differs from Western Europe in that most SEE countries lack active cancer registries and have fewer diagnostic imaging devices and radiotherapy (RT) units. The main objective of this research is to initiate a common platform for gathering SEE regional cancer data from the ground up to help these countries develop common cancer management strategies. Methods: To obtain detailed on-the-ground information, we developed separate questionnaires for two SEE groups: a) ONCO - oncologists regarding cancer treatment modalities and the availability of diagnostic imaging and radiotherapy equipment; and b) REG - national radiation protection and safety regulatory bodies regarding diagnostic imaging and radiotherapy equipment in SEE facilities. Results: Based on responses from 13/17 ONCO participants (at least one from each country) and from 9/10 REG participants (all countries but Albania), cancer incidence rates are higher in those SEE countries that have greater access to diagnostic imaging equipment while cancer mortality-to-incidence (MIR) ratios are higher in countries that lack radiotherapy equipment. Conclusion: By combining unique SEE region information with data available from major global databases, we demonstrated that the availability of diagnostic imaging and radiotherapy equipment in the SEE countries is related to their economic development. While immediate diagnostic imaging and radiation therapy capacity building is necessary, it is also essential to develop both national and SEE-regional cancer registries in order to understand the heterogeneity of each country's needs and to establish regional collaborative strategies for combating cancer.

Plasma activity of the antioxidant enzymes in predicting diabetic nephropathy progression.

INTRODUCTION: The aim of the study was to examine whether biomarkers of oxidative stress are predictors of diabetic nephropathy (DN) progression. METHODS: The study involved 45 patients with type 2 diabetes and DN and 15 healthy controls. Patients were followed for 3 years and the annual percentage change in eGFR was used to estimate the progression of DN. Patients with an annual percentage change in eGFR above the cutoff value of - 5.48%/year were classified in group 1, those with an annual percentage change in eGFR ≤ - 5.48%/year in group 2. RESULTS: The 28 patients in group 1 had the annual percentage change in eGFR of - 4.78 and 39.12%/year, and for the 17 patients in group 2 it ranged from - 24.86 to - 6.18%/year. At the onset of the study no significant differences were found between the groups in demographic, clinical or laboratory parameters. Plasma activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were significantly lower in patients than in the controls. During 3-year study kidney function and size changed insignificantly in group 1, while eGFR and kidney size decreased and proteinuria increased significantly in group 2. Multivariate linear regression analysis selected male gender, duration of diabetes, systolic blood pressure, fasting serum glucose, urine protein/creatinine ratio as factors associated with DN progression. Plasma activity of GPX and SOD were selected as positive predictors of annual percentage change in eGFR. CONCLUSION: Besides already known factors, plasma activity of GPX and SOD were found to be significant independent predictors of DN progression.

Evaluation of Cyclin D1 expression by western blotting methods and immunohistochemistry in breast cancer patients.

PURPOSE: Considering that cyclin D1 had a prognostic and clinical value for breast cancer patients, adequate measurement of cyclin D1 is necessary. METHODS: In this investigation, we detect cyclin D1 expression in tumour and peritumoral tissue of breast cancer patients by Western blotting method and by immunohistochemistry. RESULTS: Cyclin D1 expression decreased significantly with each advanced clinical stage of disease and tumour size. Also, patients without lymph node involvement, with positive hormone receptors and Luminal A type of tumours had significantly increased the expression of cyclin D1. We show that cyclin D1 expression correlates with longer RFS in the entire group of patients, in the group of ER-positive and in the group of HER2-negative patients. Patients who were both ER and cyclin D1 positive had a better prognosis. CONCLUSION: Taken together, our results, showing correlation of cyclin D1 with clinical stage, tumour size and lymph nodes, suggest that cyclin D1 expression, detected by Western blotting, could be considered as an additional marker for the staging of breast cancer, as well as a marker for longer RFS and survival in ER-positive breast cancer patients.

Differences in Risk Factors and Prevalence of Vascular Calcification between Pre-Dialysis and Hemodialysis Balkan Nephropathy Patients.

Aims: The aim of this study was to compare the risk factors and prevalence of vascular calcification (VC) in pre-dialysis and hemodialysis (HD) patients with Balkan endemic nephropathy (BEN) or other kidney diseases (non-BEN). Materials and Methods: The study involved 115 patients, 32 pre-dialysis and 83 HD patients, separated into groups of BEN and non-BEN patients. In addition to interviews, objective examinations and laboratory analyses, VC was assessed using Adragao score. Results: Patients with BEN were significantly older in both groups, while pre-dialysis BEN patients had significantly lower systolic blood pressure, serum cholesterol and phosphorus levels, but higher urinary excretion of phosphorus than non-BEN patients. These differences were lost in HD groups. In pre-dialysis patients, prevalence of VC was lower in BEN than in non-BEN group and mean VC score differed significantly between them (2.8 (1.7) vs. 4.6 (1.8); p = 0.009). No significant difference in VC score was found between BEN and non-BEN patients on HD. Multivariate analysis showed that in pre-dialysis patients VC score >4 was associated with lower iPTH and higher serum cholesterol level, but in the HD group with higher serum triglyceride level and longer HD vintage. Conclusions: Lower prevalence of risk factors for VC in the BEN than non-BEN patients was found in pre-dialysis but not in HD group and this was reflected in the prevalence and severity of VC in the groups. Prevalence of VC and mean VC score were significantly lower in pre-dialysis BEN than in non-BEN patients but not for those on HD.

Duration of valproic acid monotherapy correlates with subclinical thyroid dysfunction in children with epilepsy.

To identify potential risk factors for the development of subclinical hypothyroidism following long-term valproic acid monotherapy in children with epilepsy. Serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine, thyreoglobulin antibodies, and thyroid peroxidase antibodies were determined in 41 patients and in 41 sex- and age-matched healthy children. Mean valproic acid treatment duration was 2.80±1.96 years. The valproic acid group had higher serum thyroid-stimulating hormone (p<0.001) and free triiodothyronine (p<0.05) levels compared to the control group. Serum thyroid-stimulating hormone and free triiodothyronine were above the upper limit for healthy controls in 34% and 32% of patients, respectively, and no clinical features of thyroid dysfunction were observed. Duration of valproic acid monotherapy for less than four years was a risk factor for elevated thyroid-stimulating hormone levels. One third of children with normal range serum valproic acid levels may have elevated serum thyroid-stimulating hormone and free triiodothyronine levels, especially in the first four years of treatment.

Comprehensive geriatric assessment: comparison of elderly hemodialysis patients and primary care patients.

BACKGROUNDS: The quality of life and survival of elderly depend not only on their age but on many social and health factors. In the present study, comprehensive geriatric assessment (CGA) was made in elderly patients on regular hemodialysis (HD) and those without chronic kidney disease recruited in primary health care in order to compare their sociodemographic characteristics, physical health, functional ability and social support. METHOD: The 106 HD patients and 300 primary care patients aged 70 years and more were studied. Data on sociodemographic characteristics, neurosensory deficits, pain, falls, polypharmacy, basic activities of daily living (ADL) questionnaire, instrumental activities of daily living (IADL) questionnaire were obtained during interview. The Timed Up and Go, Nutritional Health Checklist, Two Question Instrument for depression and Charlson comorbidity index (CCI) were applied. RESULTS: No significant differences were found for age, gender, education level and dwelling between the two groups. A lower percentage of HD patients lived alone when compared with controls. BMI >25 kg/m(2) had 43.4% of HD patients and 49.3% of controls. CCI differed significantly between HD and primary care patients (median: 6 vs. 4) and significantly more HD patients reported depression. No significant difference was found between groups for cognitive dysfunction and ADL, but HD patients had significantly lower IADL scores than controls. The mobility of HD patients was worse; 45.7% of them reported falls in the previous year but only 9.7% from the controls. CONCLUSIONS: CGA revealed that HD patients had significantly higher CCI, worse IADL score, mobility and reported more frequent falls, depression and impaired vision than primary care patients.

High prevalence of risk factors for chronic kidney disease in Balkan endemic nephropathy foci.

BACKGROUND/AIMS: The aim of this study was to find out the prevalence of the most frequent risk factors for chronic kidney disease (CKD) and the prevalence of urinary abnormalities in adult inhabitants of three Balkan endemic nephropathy (BEN) villages near Bijeljina, Bosnia and Herzegovina. METHODS: The survey consisted of an interview, blood pressure measurement, and urine dipstick test for proteinuria, hematuria, and glycosuria. RESULTS: The study involved 1625 (739 males, aged 51 ± 16 years) subjects: 319 (19.6%) with positive family history for BEN, 585 (36%) with hypertension, 604 (37.2%) above 60 years, 146 (9%) with diabetes, and 566 (34.8%) with none of these risk factors. Proteinuria was present in 6.2-7.1% of the subjects with risk factors for CKD but in 3.4% of those without risk factors. Systolic blood pressure and BEN in brother/sister were found to be significant variables associated with proteinuria, but female gender and history of kidney disease with hematuria. CONCLUSION: In addition to a family burden for BEN, other risk factors for CKD were highly prevalent in BEN villages of the Bijeljina municipality. The frequency of proteinuria was higher in the at-risk group than in the group without risk factors and increased with the number of risk factors.

Platinum - sensitive relapsed epithelial ovarian cancer: not all the patients benefit from reinduction with carboplatin and paclitaxel.

BACKGROUND: It is widely accepted that patients with ovarian cancer relapsing 6 to 12 months after completion of a platinum-based regimen are considered to be partially platinum-sensitive. The aim of this study was to evaluate and correlate the efficacy and toxicity of reinduction with paclitaxel-carboplatin in a platinum-sensitive epithelial ovarian cancer patient cohort with previous platinum-free interval (PFI). MATERIAL/METHODS: We studied retrospectively 39 patients with platinum-sensitive epithelial ovarian cancer, who received primary chemotherapy at the Institute for Oncology and Radiology of Serbia, between January 2002 and May 2008. All patients were treated with paclitaxel and carboplatin for metastatic disease. Subsequent to progression, patients were re-treated with the same chemotherapy in group A (PFI 6-12 months) or group B (PFI ≥12 months). RESULTS: The number of patients in group A was 14, and in group B it was 25. Response rate to reinduction in group A was 36% (partial response, 36%; stable disease, 0%; progressive disease, 64%) and in group B was 68% (complete response, 60%; partial response, 8%; stable disease, 4%; progressive disease, 28%; P=.05). The median response duration of the patients in group A arm was 20 months, whereas it was 17 months for those in group B (P=.721). There were no significant differences in the toxicity profile between the 2 groups. CONCLUSIONS: In terms of objective response rate this study supports the reinduction of carboplatin and paclitaxel in patients with a prior PFI of at least 12 months only. To define the best approach and the optimal treatment of patients with partially platinum-sensitive disease more precisely, future studies should apply treatment-free interval as a stratification criterion.