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Epidemiological Analysis and Geographical Distribution of Patients Suffering from Rheumatoid Arthritis, Eligible for First-Line Therapy/Monotherapy Treatment with Subcutaneous Formulation of Tocilizumab in the Republic of Macedonia

Abstract

Rheumatoid arthritis is an inflammatory arthritis characterized by synovial tissue inflammation that leads to structural damage and disability. There are several treatment options available, which include glucocorticoids, DMARDs and biologics given alone as monotherapy or in a variety of combinations. Recent evidence has shown that early treatment is important in reducing the rate of progression of erosions and decreasing disability. The lack of adequate statistical data on number of patients that are eligible for first-line therapy/monotherapy of rheumatoid arthritis in Macedonia, triggered this epidemiological analyse describing eligible patients for first-line treatment/monotherapy distributed by gender, age and geographical allocation. The study was conducted by fulfilling a tailored questionnaire every two months in a period of six months (September 2017-February 2018) by including summarized data not related to personal data of patients nor specific drug information. The results have shown that a total of 115 patients in Macedonia are eligible for first-line therapy, whereby 54 (46%) patients were eligible for monotherapy of rheumatoid arthritis. Precise determination of these data provides patients’ determination by geographical allocation and proper selection of the best treatment option and optimized therapy for each patient, furthermore when subcutaneous formulation of tocilizumab is available as an effective clinically proven treatment option for RA

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Evaluation of Correlation Between the Pharmacogenetic Profiles of Risperidone Treated Psychiatry Patients with Plasma and Urine Concentration of Risperidone and its Active Moiety 9-OH Risperidone Determined with Optimized Bioanalytical LC Method

Abstract

Atypical antipsychotic risperidone is widely used first-line monotherapy in schizophrenia and combined therapy in bipolar disorders. Therapeutic plasma concentrations of risperidone and its active moiety are directly influenced by genetic variations in metabolic CYP450 enzymes (CYP2D6 and CYP3A4/5) and transporter (ABCB1) protein and additional environmental factors. Since active metabolite 9-OH risperidone has a greater percentage of the pharmacologically active fraction and is equipotent to the parent drug risperidone, it is assumed that it contributes significantly to therapeutic and adverse effects.

Unpredictable dose/concentration ratio, narrow therapeutic index, number of interactions, along with serious adverse reactions (ADR), raises the need for individualization of risperidone treatment and establishing of good therapeutic regime using TDM.

A simple and reliable validated bioanalytical liquide-liquide extraction HPLC/UV method was applied for the simultaneous determination of risperidone and its active metabolite, 9-OH risperidone, in human plasma and urine of 52 hospitalized schizophrenia/bipolar disorder patients treated with risperidone as monotherapy and in polytherapy. All the patients were previously genotyped for CYP2D6 (EM=30, EM/IM=14, IM=4 IM/PM=1 and PM=3) and ABCB1 using Real-Time PCR methods with TaqMan SNP genotyping suitable assays according to the guidelines of the manufacturer (Life Technologies, USA).The influence of CYP2D6 phenotype on metabolic ratio MR (Ris/9-OHRis) in plasma (p=0.012) and in urine (p=0.048) was confirmed. Statistically significant correlation (R2=55.53%, Rho=0.844, p<0,0001) for MR in both plasma and urine indicates that urine may be utilized as appropriate media for initial CYP2D6 phenotype identification and selection of patients on risperidone treatment with high risk for ADR.

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Evaluation of Pain Following the Use of Scalpel Versus Electrosurgery for Skin Incisions in the Facial Regions

Abstract

Introduction: Postoperative pain presents a significant medical problem. It can create a considerable discomfort in the immediate postoperative period and thus increase patient’s morbidity. Multiple mechanisms are involved in its’ etiology, one of them being the method of tissue incision. The aim of this study is to compare the early postoperative pain following incision with two different methods, scalpel and electrosurgery in the facial regions.

Material and methods: Eighty patients with both benign and malignant skin lesions in the facial regions undergoing surgery were enrolled in this study. Patients were randomized in two groups. In group A, comprising 40 patients, cold steel surgical scalpel №15 was used for the surgical procedure. Electrosurgical microneedle with 0.06mm tip radius and generator unit KLS Martin Electrosurgical Unit ME MB 2 set on cutting mode, power 12 W was used for performing the surgery in group B including the same number of patients. After the surgery patients were given analgesics on their demand. The total number of on demand analgesics requirements was calculated. The patients were also asked to note the oral analgesics they were taking after being released from the hospital.

Results: Results of this study showed a statistically significant difference between the groups in the analgesics demand on the day of the operation (p=0.041). On the day of the operation 52.5% patients in the scalpel group and only 30% of the patents of the electrosurgery group received analgesics on demand. In all other analysed time points, the patients in the scalpel group received analgesics more often than the patients in the microneedle group, but with no statistically confirmed difference between the groups (p>0.05). Even more significant is the fact that patients treated with electrosurgery that needed analgesics, had significantly bigger excision area median 471 (rank 283-589) compared to the patients treated with the conventional method 289 (rank 177-432) (p=0.016).

Conclusion: In accordance with previous studies our results suggested a significantly reduced postoperative pain in the electrosurgery group.

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Giant Fibroepithelial Polyp of Vulva: A Case Report and Review of Literature

Abstract

Fibroepithelial stromal polyps of vulva are the type of mesenchymal lesion that typically occurs in women of reproductive period. They are common, usually small and hystologically benign. Larger lesions are rare and likely arise from proliferation of mesenchymal cells within the hormonally sensitive subepithelial stromal layer of the lower genital tract. We present a case of 16 year old female with a giant polypoid lesion of the vulva localized on the right labium. The mass measure was 18×12×3 cm. Total surgical resection of the lesion was performed. Histopathological examination reported a fibroepithelial stromal polyp of the vulva. The patient showed no evidence of recurrence four years after the resection. Fibroepithelial polyps of the vulvar region are benign lesions that have a wide range of morphologic appearances and may be misinterpreted as malignant. Total excision is the best treatment options and histopathological examination is strongly recommended to rule out a malignant neoplasm.

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Hyperfibrinogenemia in Peripheral Arterial Disease: Coexistent and Independent Risk Factor (A Report of Two Cases and Review of Literature)

Abstract

These case reports aim to show that hyperfibrinogenemia is a risk factor for the progression and prognosis of peripheral arterial disease (PAD), in patients with and without diabetes mellitus type 2.

We present a patient with PAD who has type 2 diabetes mellitus, who has previously been repeatedly treated for lower limb ischemia with multiple vascular surgeries performed. A few weeks before admission the patient developed critical lower limb ischemia, which was treated with an iliaco-popliteal and femorofemoral bypass. The patient had elevated serum fibrinogen values. In the current admission, renewed left limb ischemia was diagnosed, and surgically evaluated with a recommendation for amputation of the left limb as a surgical recommendation. Our second patient had a stable intermittent claudication, dyslipidemia and hyperfibrinogenemia. He was successfully treated for those risk factors. Regular monitoring of the patient showed improved claudication distance and quality of life

Our case reports, supported by a literature review, demonstrate that hyperfibrinogenemia is a possible risk factor for progression and the prognosis of PAD.

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ICGEB Workshop on Next Generation Diagnostics, 22/03/2018-24/03/2018, Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia

Abstract

More than 200 participants from Europe, Asia, Africa and South America attended the two days ICGEB Workshop on Next Generation Diagnostics, 22/03/2018-24/03/2018, at the Macedonian Academy of Sciences and Arts (MASA) in Skopje, Republic of Macedonia. The meeting provided an overview of the current and future use of next generation sequencing (NGS), proteomics and other high-throughput technologies in the diagnostic setup of malignant, inherited and communicable diseases. In addition, considerable emphasis was placed on the potential use of these techniques for disease prognostication, patient stratification and monitoring responses to therapy. Specific topics included NGS-based diagnostics of solid tumors, hematological malignancies, inherited and infectious diseases, proteomic-based approaches for biomarker discovery, predictive biomarkers for personalized treatment strategies, and bioinformatic analysis of NGS data. The meeting also provided a unique platform for fruitful discussions between internationally recognized experts and young researchers from developing countries, providing new perspectives and ideas on broader implementation of these techniques for personalized management and care.

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Immunohistochemical Expression of Epidermal Growth Factor Receptor in Hepatocellular Carcinoma

Abstract

Introduction: Epidermal growth factor receptor (EGFR) signaling plays an important role in various cancers, including hepatocellular carcinoma (HCC). We aimed to evaluate immunoexpression of EGFR in HCC and surrounding non-tumor liver tissue and to correlate it to multiple clinicopathologic data.

Material and Methods: We analyzed 60 patients with HCC for multiple clinicopathologic characteristics and survival.

Presence of the immunosignal and the percentage of positive tumor cells at the whole tumor tissue sample and adjacent cirrhotic liver tissue were semi-quantitatively determined.

Results: Nineteen patients (31.67%) were female and 41 (68.33%) were male ranging in age from 31 to 85 years, median 61.88±10.51.

Mean survival time for female patients was 8.86±1.76 months, for male 13.03±1.50 months and overall survival was 11.6051±1.19 months.

The most patients had: T2 status (41.67%), no enlarged lymph nodes (90%), vascular invasion (63.33%) and well differentiated (43.33%) tumors.

EGFR immunoexpression was determined in range from 0% to 100% in both tumor and non-tumor tissue with mean value of 39.58% in tumor and 86.86% in cirrhotic tissue (p<0.00).

Higher percent of tumor EGFR positive cells were found in cases with higher T status, higher levels of AFP and poorly differentiated carcinoma, but not significantly.

Lower percent of tumor EGFR positive cells were found in patients with vascular invasion and enlarged lymph nodes, but also not significantly.

EGFR expression in tumor tissue significantly influenced survival of the patients (p<0.05).

Conclusion: The study showed that expression of EGFR in lower percentage of tumor cells was associated to favorable prognosis, making it a potential prognostic marker and therapeutic target.

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Inter- and Intra-Hemispheric EEG Coherence Study in Adults with Neuropsychiatric Disorders

Abstract

Functional connectivity between different regions of the brain in the resting state has been a recent topic of interest in neurophysiological research. EEG coherence happened to be an useful tool for measuring changes in neuro-psycho-physiological functioning which are not detectable by simply measuring amplitude or power spectra.

The aim of our study was to investigate the changes in the EEG coherence in groups of different mental disorders such as: depression, general anxiety disorder, ADHD, Asperger syndrome and headaches, compared to control group. All measures were made in two conditions: eye opened (EO) and eyes closed (EC).

The obtained results show that in EO condition there is a significantly lower coherence for delta waves between analyzed groups. For theta coherence only for Asperger syndrome we found lower coherence compared to control group, ADHD and headaches in parietal region (P3-P4). Obtained results for intrahemispheric coherence have shown that there was significantly lower coherence in both conditions for delta and theta bands in almost all sites for Asperger’s syndrome, and opposite increased intrahemispheric coherence for patients with headaches (for delta band in the anterior regions and for theta band in the posterior regions). ADHD patients expressed lower delta inter-hemispheric coherence in frontal regions, and increased coherence of theta in central regions but increased delta coherence in posterior regions only in EO condition. For depressive and anxiety patients we found decreased intrahemispheric coherence for EO condition for delta brain waves all over the cortex. Concerning the coherence in anxiety patients in our current study we have obtained hypo coherence in centro-parieto-occipital region only for delta in inter-hemispheric coherence and also lower delta coherence through the cortex for intrahemispheric coherence.

Our findings for interhemispheric hyper coherence in subjects with depression specifically for alpha and beta bands were confirmed in other studies.

We suggest that EEG coherence analysis could be a sensitive parameter in the detection of electrophysiological abnormalities in patients with anxiety, depression, ADHD, Asperger syndrome and headaches. These results can confirm the development of QEEG state and trait biomarkers for psychiatric disorders.

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Intrapartum Procedures for Prevention of Infections and Complications in Mothers During Childbirth

Abstract

Introduction: Multiple factors can cause infection and other pathological conditions in mothers during childbirth. These risk factors and diseases/complications can be prevented or timely detected through the implementation of special protocols/procedures. The aim of this paper is to identify the implementation of procedures/measures for the prevention and detection of infections and risk factors for morbidity and mortality in four hospitals in the Republic of Macedonia, before and during childbirth.

Material and Methods: A retrospective study was conducted in four hospitals in R. Macedonia, in December 2016, on certain days according to the same principle of selection in all institutions. The questionnaire used contained relevant and specific questions related to the application of procedures and protocols at the maternity clinic at the time of admission to the birthplace and immediately prior to delivery.

Results: The study analyzes the performed procedures from 137 obstetric histories. Cardiotocograph was taken after the admission in a hospital in 86% of the mothers; a temperature was measured at only 47.5%, and arterial tension at 89.8%. Immediately before delivery, the color and odor of the vaginal discharge in 98.5% of the mothers was checked, urine was analyzed only in 8% of the mothers, and the analysis of the time of rupture of the mammalian sheaths in 98.6% of the mothers.

Conclusion: The study showed that part of the analyzed procedures was not sufficiently implemented, and the percentage distribution varied between hospitals. There is a need for introduction of organized programs with standard procedures in maternity wards in order to protect against infections and other pathological conditions during childbirth.

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Jakub Chlebowski, Rector Magnificus Exultus – A Distinguished Professor of Internal Medicine in Postwar North-East Poland

Abstract

Jakub Chlebowski (Jakub Frydman) (1905-1969) was a distinguished professor of internal medicine and skillful organizer of health care system in Bialystok region in the North east Poland. He graduated medicine in 1929 and worked at local university in prewar Vilnius. During World War Two, arrested by the Soviets and exiled to Siberian work camps he managed to return to Poland with Kosciuszko Division of Polish Army. Then, he continued to serve as a military and university medical doctor in Cracow and Lodz, finally to take over position of director of Internal Diseases Department in 1951 in Bialystok, holding an office of rector magnificus of Medical University of Bialystok from 1959 to 1962. Chlebowski trained generations of internal medicine specialists, who later became eminent representatives of emerging branches of internal medicine as distinct subspecialties in the field of cardiology, endocrinology and gastroenterology in Bialystok. In course of anti-Semitic campaign during March Events in 1968, he was disposed from the post of director of the university hospital department. Constantly harassed, he immigrated with the family to Israel to die in public traffic accident in 1969. Jakub Frydman, who survived not only hunger of food, but also metaphorical “hunger of humanity” during World War Two, turned out to be as good and useful as daily bread for Polish community after wartime. He was so devoted in this action, that he even changed his surname into Chlebowski (Polish: Chleb=English: Bread). In this way, due to similar experience and experience-shaped mentality, Chlebowski could be counted among medical authorities of the time, the individuals with such a high moral standard as Janusz Korczak (1878 or 1879-1942) or Julian Kramsztyk (1851-1926).

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