ARCHIVES OF THE BALKAN MEDICAL UNION

609-611

Authors: Is there an implication of intestinal microbiota in cardiovascular diseases?

Nowadays, more and more evidence points out to the interrelationship between intestinal microbiota and cardiovascular diseases. Gut microbiota is composed of a large number of microorganisms that live in the human gut and are involved in many physiological processes. Changes in the composition and activity of intestinal microbiota may lead or may accelerate the evolution of some cardiovascular diseases. Alterations in the composition of gut microbiota will induce dysbiosis, causing inflammation and initiating the development of cardiovascular diseases. These alterations may be secondary to intestinal infections, exposure to some environmental factors, changes in dietary habits, high stress, use of antibiotics. Studies have shown that gut microbiota is composed of six families, the Firmicutes, Bacteroidetes, Proteobacteria, Actino-bacteria, Fusobacteria, and Verrucomicrobia phyla1. These microorganisms are involved in the immune processes of the host, the fight against the pathogenic microorganisms and also in maintaining the integrity of intestinal barriers. Coronary heart disease and arterial hypertension are chronic diseases with a high prevalence. Some studies have demonstrated a link between the composition of gut microbiota and the increased risk of atherosclerosis, which is the main cause of coronary heart disease2,3. These studies have identified different species of bacteria, both in the gut and in the atheromatous plaques, suggesting that gut is a source of atherogenic bacteria2,3. The mechanisms by which these bacteria can initiate the atherosclerotic process (or in some cases protect against it) are still unknown. Trimethylamine N-oxide (TMAO) is a microbial metabolite that was studied for its effects on cardiovascular diseases after the discovery of a positive correlation between the serum level of TMAO and the atherosclerotic plaque area. This correlation was partially explained by the role that TMAO plays in the inhibition of reverse cholesterol transport and the accumulation of macrophage cholesterol4,5. One study has found that the TMAO level in patients with an acute coronary syndrome is an independent predictor of short-term and long-term major adverse cardiac events6. The implication of gut microbiota in arterial hypertension has been demonstrated by animal studies7,8. Adnan et al have shown that the blood pressure can be influenced by the exchange of gut microbiota between spontaneously hypertensive rats and Wistar-Kyoto rats7. The ratio of Firmicutes and Bacteroidetes is considered specific for intestinal dysbiosis9. In animal studies, the alteration of this ratio correlated with arterial hypertension, suggesting that gut microbiota could be a potential target of future antihypertensive therapies9. Heart failure is the final stage of evolution of the majority of cardiovascular diseases, with high mortality rates. One study has comparatively analyzed the bacteria and fungi in the feces of patients with heart failure with those of healthy controls and demonstrated that patients with chronic heart failure have more pathogenic bacteria10. Moreover, some species, like Candida, Shigella, and Campylobacter, were positively correlated with the severity of the heart failure10. Patients with heart failure, with decreased cardiac output, have gastrointestinal mucosa congestion and ischemia, with subsequent alterations in the composition of gut microflora and also intestinal functions. These alterations will lead to bacterial translocation, the release of endotoxins in the circulation, promoting a systemic inflammatory response. Some authors suggested that TMAO can be used as a biomarker for prognosis stratification in patients with heart failure11, although the exact mechanisms of increased levels of TMAO in patients with heart failure are still unknown. Other gut microbiota metabolites, p-cresyl sulfate and phenylacetylglutamine, have been suggested by some studies to be involved in the appearance of cardiovascular diseases12,13. Based on the above findings, the future cardiovascular therapies may include gut microbiota and their metabolites as potential targets. These therapies could be represented not only by drugs but also by diet changes and supplementation with prebiotics and/or probiotics.

621-629

Authors: Berik N. DZHUMABEKOV, Auyeskhan T. DZHUMABEKOV, Dzhumagaly K. ISMAILOV, Talgat A. BAITILEUOV, Ildar R. FAKHRADIYEV

Introduction. Wound regeneration is an important process in surgical interventions. Failure of an intestinal anastomosis is an important intestinal surgery problem. The objective of the study. To evaluate the effect of platelet-rich plasma (PRP) and compare the effectiveness of various application methods in intestinal anastomosis regeneration in rabbits. Methods. Platelet-rich auto-plasma was obtained from 81 rabbits, which was used to study two methods of applying PRP (injection into the muscle layer / soaking in the intestinal wall) in comparison with the control group, on the end-to-end small-intestinal anastomosis. Results. The analysis of the histological and morphometric data showed that the regeneration between the samples of intestinal anastomosis treated with PRP soaking and injections into the intestinal wall is more favorable in comparison with the control group, which, in turn, was determined by the quantitative ratio of inflammatory infiltrate, fibroblast proliferation, neo-angiogenesis, and collagen deposition. PRP soaking in the intestinal wall significantly increased the number of adhesions battles. The analysis of the deformation and strength characteristics of the formed anastomoses also showed significantly high values ​​of the rupture strength of the anastomoses treated with PRP, in contrast with the control group. Conclusion. PRP injection into the muscular layer of the intestinal wall significantly reduces the development of adhesions in comparison with the PRP-saturated group of intestinal anastomoses. Further research is needed to clarify the optimal method of PRP application, which will improve the regeneration of the intestinal anastomosis.

639-646

Authors: Tatiana V. KHMARA , Pavlina V. HRYHORIEVA, Svitlana D. NOVYCHENKO, Olga P. KHAPITSKA

Introduction. A clear knowledge on the variations of blood supply and innervation of muscles in different areas of the body allows the surgeon to select the neurovascular pedicle, when performing muscle transposition operations using microsurgical techniques, to correctly choose the muscle flap, the method of replacing the defect and the localization of the donor area. The objective of the study: to clarify the information about the sources of innervation and blood supply to the gracilis muscle, adductor muscles and pectineus muscles, as well as to investigate the intramuscular distribution of nerves and arteries in the muscles of the medial group of the thigh in human fetuses aged 4-10 months. Materials and methods. The peculiarities of the fetal topography of the arteries and nerves of the medial femoral group muscles were studied in 42 human fetuses aged 4-10 months using the methods of macro microscopic preparation, vascular injection, surface staining of the prepared vessels and nerves, and morphometry. Results. It has been established that the distribution of nerves and arteries is uneven in the thickness of the muscles of the medial group of the thigh, at the same time the middle third of all adductor muscles is supplied with blood and innervated more intensively. The places where nerves penetrate into the thickness of the muscles of the medial femoral group, do not coincide with the places where the arteries enter, pectineus muscle is an exception. The nature of the intramuscular distribution of nerves and arteries depends on the structure and function of the muscle. The intramuscular nerve trunks are interconnected in the gracilis and adductor magnus muscles, forming loops and arcades. Nerve connections between the obturator and sciatic nerves are found in the thickness of the adductor magnus muscle. Conclusions. In the picture of the intramuscular distribution of nerves and arteries in the muscles of the medial group of the thigh in human fetuses, three forms can be distinguished: loose, trunk, and mixed. In the thickness of the muscles of the medial femoral group, the distribution of nerves and arteries is uneven. Segmentation is preserved in the intramuscular distribution of arteries in the muscle gracilis, adductor longus and magnus muscles, while in the distribution of nerves in these muscles segmentation is absent.

653-658

Authors: Milena D. KARCHEVA , Anton P. GEORGIEV, Alexander B. BLAZHEV

Introduction. Rubella is a worldwide contagious disease with self-limited symptoms and a generalized rash. Epidemiology of rubella changed after licensing the vaccine in 1969. Children’s rubella is a self-limited infection, but when it occurs during pregnancy, there is a risk of severe damage to the fetus. Objectives. The aim of this study was to determine the immunity against rubella virus in pregnant women in Pleven Region, Bulgaria. Methods. A cross-sectional study was carried out on pregnant women hospitalized in a Clinic of obstetrics and gynecology, University Hospital-Pleven, Bulgaria. Quantitative determination of specific Immunoglobulin G (IgG) antibodies against rubella virus was performed by Enzyme-Like Immunosorbent Assay (ELISA). Data were analyzed using the Microsoft Office Excel 2007 software. Results. Between January 2018 and December 2018 there were collected and tested to Rubella virus IgG antibody 242 serum samples. Two hundred and four (84.30%) of them were positive, 29 (11.98%) were negative and 9 (3.72%) – equivocal. The age of examined women was between 14 and 45 years, average 27, sd±6.429. We found high seropositivity within age group 21-30 years of age. The immunization status of the investigated women shows – unimmunized – 79, selectively immunized with one dose of monovaxin – 58, immunized with combined (measles, mumps, rubella) vaccine one dose – 82, with a double immunization schedule – 23. In each group there were seropositive women. Conclusions. Data analysis shows that pregnant women have high immunity and a tendency for lower morbidity rates of acute rubella infection.

659-671

Authors: Maria CHRISSINI, Dimitra SIFAKI-PISTOLLA, Nikolaos TZANAKIS, Ioanna TSILIGIANNI

Introduction. The identification of the type and site of origin in undifferentiated tumours of unknown primary site using immunohistochemistry is a frequent requirement in pathology practice. There are many histologic lesions that display similar morphologic aspects, with misdiagnosis potentially resulting in over- or undertreatment. This makes the diagnostic accuracy extremely important in the era of targeted therapies. The objective of the study was to evaluate the process of diagnosis in 50 melanoma cases presenting as poorly differentiated or undifferentiated tumours with unknown primary origin, with emphasis on the immunohistochemical algorithm. Methods. 50 cases were selected to analyse the utility of IHC testing in diagnosing poorly differentiated malignancies. The immunohistochemical evaluation was based on the staining percentage of cells: focal positive <50%, diffuse positive >50%, negative (-) 0%. Results. After applying the Fan Lin algorithm, for most of the cases (45), the cytokeratin and CD45 proved negative, while S100 and vimentin were positive in diffuse or zonal patterns. For the 3 cases analysed by applying the Turin algorithm, the first antibody panel consisted in testing CK7/CK20, that showed no expression for all 3 cases. Conclusions. In this study, we demonstrated that the immunohistochemical examination of poorly differentiated malignant tumours is a reliable and valuable test and is recommended as a standard method in diagnosis along with the correlations with clinical and histological data.

685-691

Authors: Aleksandra CATIC´-ÐORÐEVIC´ , Nikola STEFANOVIC´, Ivana STOŠIC´, Ivana DAMNJANOVIC´, Ivana MILANOVIC´, Novica BOJANIC´, Radmila VELICˇKOVIC´-RADOVANOVIC´

Introduction. The risk of inappropriate prescribing and inadequate drug use in the elderly population is growing with ageing associated physiological changes and polypharmacy due to increased number of chronic diseases. In order to optimize the therapy, numerous criteria have been developed which can help pharmacists and physicians to implement rational pharmacotherapy. The objectives of the study were to survey the practice of medication use in patients older than 65 years with different stages of renal failure and to identify potentially inappropriate prescribing, as well as to justify the role of pharmacists in pharmacotherapy optimization. Material and methods. This retrospective study included 100 patients with average age of 72.30±5.00 years. Demographic, clinical and pharmacotherapy data were collected from hospital discharge summary after one day hospital examination at the Clinic of Nephrology of Clinical Center Niš, Serbia. Potentially inadequate drugs were identified by STOPP criteria (Screening Tool of Older Persons’ Prescriptions), while START criteria (Screening Tool to Alert doctors to Right Treatment) pointed out the lack of potentially helpful drugs in therapy. Results. 63 STOPP and 60 START criteria were identified. The most common STOPP criteria were the use of benzodiazepines (14%) and duplication of therapy (11%). The greatest influence on the occurrence of STOPP criteria was the total number of medications in therapy. START criteria identified the lack of statins in therapy in 19% of patients with cardiovascular disease and in 13% with diabetes mellitus type 2. The occurrence of START criteria was mostly influenced by the number of comorbidities. Conclusions. The presence of potentially inadequate prescribed and the lack of potentially useful drugs in the complex pharmacotherapy of elderly patients is the reason for including pharmacists in a team which creates optimal pharmacotherapy for elderly.

699-704

Authors: Mihaela C. OLARIU, Elena L. STOICHITOIU, Adriana NURCIU, Gabriela ANDRIESCU, Mihai H. OLARIU , Camelia C. DIACONU

Introduction. In the last years, the non-invasive methods of evaluating liver fibrosis were imposed in the current medical practice. The objective of the study was to evaluate the role of 2D Shear Wave elastography in the dynamic monitoring of liver fibrosis compared to a validated method – Fibromax. Materials and methods. 37 patients with chronic hepatitis C infection and advanced fibrosis (F3/F4) who received treatment with Paritaprevir/Ritonavir + Ombitasvir + Dasabuvir were included. The evaluation was done at baseline, 12 weeks after the end of treatment and 48 weeks after therapy. Results. There was a significant and positive correlation of high degree, according to the Spearman’s rho correlation coefficient, between 2D Shear Wave elastography and Fibromax, showing very similar results both at the beginning of therapy (p<0.001, R=0.726) and one year after its completion (p<0.001, R=0.961). The correlation between platelet count and the non-invasively estimated liver fibrosis degree is statistically significant, being moderately negative (p=0.009, R=0.426) – patients with low platelet count at baseline did not present an improvement of fibrosis or it was not statistically significant one year after stopping the treatment. Direct antiviral therapy with Paritaprevir/Ritonavir + Ombitasvir + Dasabuvir, besides the chronic hepatitis C eradication rate of 99-100%, also determines a statistically significant improvement (p<0.001) of the degree of liver fibrosis. Conclusions. There is a strong correlation between the two non-invasive methods analyzed, which recommends routine use of 2D Shear Wave elastography alone or in combination with other tests. In addition to the remarkable effectiveness of the therapeutic regimen used (SVR rates >95%), there is also a significant improvement of fibrosis, which prevents progression to cirrhosis and hepatocellular carcinoma.

712-719

Authors: Andreea TOMA, Patricia FURDUI, Alexandra CHIRILA, Alina L.A. OANCEA, Raluca GRIGORE, Serban V.G. BERTESTEANU

Inflammation of the salivary glands manifest differently, depending on the etiologic agent and patient population. Inflammatory and infectious pathology of the salivary glands is multifactorial and has a multimodal therapy. Bacterial infections are the result of ductal blockage or decreased salivary production. On this background, retrograde contamination of glandular parenchyma occurs. Some systemic viral infections produce salivary pathology such as mumps or AIDS. Many granulomatous infections can affect salivary glands such as tuberculosis (TB), syphilis, tularemia, toxoplasmosis, actinomycosis, and bartonellosis. Salivary inflammation occurs either in the secretory canal or in the whole gland. Suppuration of the salivary glands in immunosuppressed individuals can extend to cervicofacial regions and the mediastinum and require immediate treatment. Interdisciplinary collaboration with the infectionist, parasitologist and radiologist is the golden standard towards the benefit of the patient. Authors describe the clinical features and treatment of inflammatory diseases of the salivary glands.

725-730

Authors: Lucian IORGA, Dragos MARCU, Ovidiu BRATU, Bogdan SOCEA, Tiberiu P. NEAGU2, Simona BUNGAU, Ana Maria A. STANESCU, Camelia C. DIACONU, Dan MISCHIANU

Primary extragonadal germ-cell tumors (EGCTs) are a rare group of neoplasms, that can exist anywere along the midline of the body, without the evidence of a primary gonadal tumor. Their morphology varies widely and includes teratoma, seminoma, yolk sac tumor, embryonal carcinoma, choriocarcinoma, and mixed GCTs. The ethiopathogenesis of EGCT is poorly understood, existing multiple theories. Diagnosis is often difficult, but an accurate one should be made in order to apply a correct management.

739-744

Authors: Ana-Maria CIOTI, Ana Maria A. STANESCU , Ioana V. GRAJDEANU, Daniela MIRICESCU, Bogdan SERBAN, Ovidiu G. BRATU, Camelia C. DIACONU

Human Papilloma Virus (HPV) is the virus responsible for the most common and widespread sexually-transmitted infection. Most sexually active people will acquire at least one type of HPV in their lifetime and some may be repeatedly infected. In most cases, HPV infection is transient and asymptomatic, but when the infection persists it can cause benign diseases, precancerous lesions and malignancies of various locations. Low risk HPV types can produce proliferative lesions either in the skin or mucosa, whereas high risk types possess carcinogenic potential. This paper is a review of the latest data in the literature regarding the clinical manifestations of HPV infections, current prevention and therapeutic possibilities.

749-752

Authors: Madalina A. MUNTEANU, Gina GHEORGHE, Ana Maria A. STANESCU, Ovidiu G. BRATU, Camelia C. DIACONU

Despite considerable improvements in medical care over the past 25 years, cardiovascular disease (CVD) remains a major public health challenge. Dyslipidemias are one of the topics of greatest interest in cardiology. Decreasing serum cholesterol level is a central objective for preventing cardiovascular events. The current European Society of Cardiology guidelines recommend evaluation of the cardiovascular risk, treatment decisions being based on this risk, and clinician–patient discussion about the risk (shared decision making).

759-763

Authors: Mihail TUSALIU , Iulia TITA, Lavinia G. ILINCA, Cristina M. GOANTA, Florentin A. VREJU, Octavian D. PALADE

Introduction. Sialolithiasis is one of the most common pathologies of the salivary glands. When calculi are present in the distal excretory duct, in the hilum or in the parenchyma, complete removal of the submandibular gland is recommended. Case report. We present the case of a 43-year-old male patient, suffering from left chronic submandibular sialadenitis. The patient accused recurring colic and intermittent swelling of the left submandibular gland experienced for about 10 years, with a progressive evolution. CT scan revealed a lower volume of the left submandibular gland compared to the right submandibular gland, the presence of a microcalcification in the parenchyma and an oval calcification corresponding to the projection area of the left submandibular gland’s duct. A left sub mandibulectomy was performed. Conclusion. Complete removal of the submandibular gland is the most effective therapy for sialolithiasis, being associated with better long-term outcomes and low operative morbidity.

771-775

Authors: Alexandra BOLOCAN, Bogdan SOCEA, Dan N. PADURARU, Oana BOTEZAN, Octavian ANDRONIC, Andra MORAR, Cristina MOLDOVAN, Alexandra ENE, Roxana TURTUREA, Mara CARSOTE , Ana VALEA

Introduction. Pineal tumors are an inhomogeneous group of lesions with pineal origin, characterized by various degrees of hypothalamic-pituitary dysfunction. Case presentation. We present the case of a patient with pineal germinoma and hypogonadotropic hypogonadism who was evaluated in several medical centers. A 31-year-old male patient with a history of primary hypothyroidism and pineal germinoma, for which he underwent surgery, radiation and chemotherapy, was admitted for frontal-temporal headache, nausea and moderate intensity asthenia. Clinical examination revealed normal weight, normal blood pressure, left eye strabismus, pale skin, diminished facial and body hair, bilateral gynecomastia. The endocrine profile showed adequate thyroid hormone replacement, low normal basal cortisol levels (5.88 µg/dL, normal 5-25 µg/dL), low IGF-1 (Insulin-like Growth Factor) (93.2 pg/mL, normal 115-307 pg/mL), low gonadotrophins, testosterone (0.57 ng/mL, normal 1.3-8.53 ng/mL) and estradiol (<10 pg/mL, normal 15-60 pg/mL). Breast ultrasound showed bilateral asymmetric gynecomastia, BIRADS-2. No tumors or surgery complications were found on MRI (Magnetic Resonance Imaging) exam. A diagnosis of hypogonadotropic hypogonadism was established and surgical cure of gynecomastias, as well as testosterone replacement therapy were recommended. Conclusions. Pineal germinomas are rare tumors associated with increased risk of endocrine dysfunctions, including hypogonadotropic hypogonadism, as a consequence of germinoma-specific therapy. Frequent biochemical assessment as well as follow-up imaging are needed, in order to prevent tumor recurrence and long-term complications related to the germinoma itself or the chosen therapy.

781-786

Authors: Leonid I. DVORETSKY , Mariya A. KARNAUSHKINA, Roza M. VAKOLYUK, Nelly V. DUBROVSKAYA

Introduction. Evans’ syndrome (autoimmune hemolytic anemia combined with thrombocytopenia) is a rare hematological syndrome in the elderly. Case report. A 94-year-old patient was diagnosed with Evans’ syndrome with the secretion of monoclonal protein. The disease manifested initially by a periodic decrease in hemoglobin and platelet counts, accompanied by a deterioration of the clinical condition, and the development of a hemorrhagic syndrome. Long-term glucocorticoid therapy led to the development of osteoporosis, complicated by compression fracture of the lumbar vertebra. The main clinical manifestations of the disease (pain, limited mobility) were associated with the development of this complication. Conclusions. Diagnosis of Evans’ syndrome in elderly patients requires the exclusion of other similar diseases. Long-term glucocorticoid treatment can cause complications, such as osteoporosis with a risk of vertebral fracture. The resulting complications can disrupt the quality of life to a much greater extent than the underlying disease. When choosing a treatment for elderly patients with Evans’ syndrome, it is necessary to consider the possible benefits and the risk of complications.