ARCHIVES OF THE BALKAN MEDICAL UNION

203-205

Authors: Hongyun WANG, Xinyue ZHU, Junjie XIAO

Living forever is a beautiful vision that human being has been pursuing. With the development of science and technology, an increasing number of approaches have been emerging for repairing and regenerating the damaged organs, such as cell therapy, gene therapy and transplant etc. However, the side effects of these methods limit their clinical use. For example, myoblast transplantation leads to an increase in number of early postoperative arrhythmic events(1). Therefore, it has a long way to use these approaches for clinical therapy in a short-term and it is urgent to look for secure effective strategies. Recently, extracellular vesicles (EVs) have attracted extensive interests as a potential therapeutic strategy of diseases such as cancer, cardiovascular diseases etc. A growing number of investigations demonstrate that various engineered EVs can repair the damaged tissue in vivo(2). This editorial highlights 6 selected papers dedicated to the engineered extracellular vesicles as well as nanoparticles, including: 1) classical strategies for modifying EVs; 2) the roles of engineered EVs in treatment. Besides, the outlook for engineered EVs has been briefly discussed. To improve the efficiency of EVs as well as targeted tissue retention, several investigations were performed. Kyle et al firstly used a cardiomyocytes specific peptide (CMP) to make the cardiac-targeted EVs(3). It was then verified that the modified EVS (CMP- EVs) can be specifically taken up by cardio-myocytes both in vitro and in vivo. This approach laid the foundation for cell and cardiac-specific EVs delivery, which gives a reference for studying targeted-EV. Interestingly, Tang et al came up with a novel idea based on the recruitment of platelets by injured endothelial cells(4). These authors decorated platelet-microvesicles (inside of platelet, similar with EVs) on the surface of cardiosphere-derived cardiac stem cells (CSCs), which significantly increased the retention in the heart. This manipulation approach is safe and straightforward, which opens novel insights into targeted-EVs for therapy. Recently, Liming et al used an adhesive hydrogel to enhance the retention of EVs(5). The EVs were immobilized in an adhesive hydrogel (Exo-pGel) and the encapsulated-EVs can stay at the injured area. The Exo-pGel presents a promising strategy for preclinical treatment. It has been well established that the engineered EVs have great potential for disease treatment in animal models. Vandergriff et al systemically investigated the role of CMP- EVs in cardiac dysfunction treatment. The authors found that EVs conjugated with cardiac homing peptide (CHP, similar with CMP) can protect heart from ischemia/reperfusion injury owing to their increased retention(6). This work demonstrates a novel approach for increasing delivery of myocardial infarction treatment. Liu et al reported that EVs loading with novel complex hydrogels can promote wounds healing, which provides another effective hydrogel strategy for engineering EVs(7). Li et al investigated the roles of Exo-pGel in treatment of spinal cord injury. The Exo-pGel significantly promoted nerve recovery via inhibiting oxidative stress and inflammation5. Besides, Chuanjiang He et al give an insight into how EVs engineered as powerful tools in translational medicine(8). In conclusion, there are strategies for engineering EVs/nanoparticles, with potential roles in disease treatment. Notably, more preclinical investigations and clinical trials are still needed to elucidate the possibility of engineered EVs and nanoparticles in human diseases treatment.

215-223

Authors: Krystallenia I. ALEXANDRAKI , Georgios BOUTZIOS, Ioanna ANTONOPOULOU, Theodoros G. PAPAIOANNOU, Lamprini Iro BARTSIOKA, Panagiotis MOSCHOURIS, Angeliki KARAPANAGIOTI, Vasiliki MAVROEIDI, Konstantinos MAKRILAKIS, Leonidas DUNTAS, Gregory A. KALTSAS, Stavros LIATIS

Introduction. The association of autoimmune thyroid disease (AITD) with diabetes mellitus type-1 (DM1) has been previously documented. However, limited data exist regarding the association of AITD and diabetes mellitus type-2 (DM2). The objective of the study was to expose the role of AITD on DM2 and the impact of AITD in euthyroid patients with pre-diabetes. Euthyroid prediabetic patients were defined by impaired fasting glucose and/or glucose intolerance. Material and methods. We assessed static and dynamic insulin resistance (IRI) and insulin secretion indices (ISI), and the disposition index (DI). Results. Out of 166 patients studied, 31.9% had AITD; impaired fasting glucose (IFG) prevalence was the same with non-AITD patients. In contrast, impaired glucose tolerance (IGT) was less prevalent in AITD compared to non-AITD patients (9.4% versus 28.3%, p=0.008). IRI did not differ between the two groups. The dynamic ISI, 1st phase and 2nd phase insulin release, and the DI showed a worse insulin secretion in non-AITD compared to AITD patients (0.54 versus 0.45, p=0.029; 1029.3 versus 864.3, p=0.033; 354.8 versus 286.5, p=0.035; 0.09 versus 0.07, p=0.02, respectively). On the other hand, hsCRP was higher in AITD versus non-AITD individuals (p=0.008). Conclusions. Although individuals with pre-diabetes and AITD presented with higher levels of low-grade inflammation, their dynamic ISI and the DI, were less impaired.

233-242

Authors: Asparuh G. NIKOLOV , Maria L. TZEKOVA, Konstantin M. KOSTOV, Alexander B. BLAZHEV

Introduction. Matrix metalloproteinases (MMPs) are important target genes for angiotensin II (AII), which subsequently alters MMP expression in extracellular matrix (ECM) and lead to remodeling process. Objective. To investigate whether an association between serum levels of MMP-12, AII and left ventricular hypertrophy exists in patients with heart failure with mid-range ejection fraction (HFmrEF) and arterial hypertension (AH). Material and methods. 56 patients with HFmrEF and AH were examined, mean age 65.62±9.69 years, and 22 age and sex-matched healthy subjects, mean age 56.4±5.53 years. 41 patients had hypertension-mediated organ damage and 15 did not. Patients were divided in two subgroups: subjects with left ventricular hypertrophy (n=32), (HFmrEF+LVH), and subjects without left ventricular hypertrophy (n=24), (HFmrEF-LVH). ELISA was used for measuring AII and MMP-12. Results: Serum MMP-12 levels were statistically significant lower in patients, than in controls: 0.0033 ng/mL (0.0022 ÷ 0.0071) vs. 0.0075 ng/mL (0.0068 ÷ 0.016) (KW=7.37; p=0.006). MMP-12 showed correlation with grade of AH (r=0.28; p=0.03). Patients with HFmrEF+LVH showed statistically significant higher levels of AII: 8.533 pg/mL (1.477÷13.009) than HFmrEF-LVH 1.333 pg/mL (0.477÷6.932) and healthy controls 1.539 pg/mL (0.274÷5.218); (KW=3.48; p=0.04). AII correlated with stage of AH (r=0.47; p=0.001). MMP-12/AII ratio was significantly higher in patients with HFmrEF+LVH than in HFmrEF-LVH 3.867 vs. 0.0025 (p<0.001). Conclusions. Our data suggest an association between serum MMP-12 levels, AII and grade and stage of AH. Determination of serum MMP-12/Angiotensin II profile may be a useful method for monitoring of development and progression of left ventricular hypertrophy.

250-256

Authors: Andrei BRADU , Pavel BANOV, Emil CEBAN

Introduction. Urinary lithiasis is an important health issue, with an estimated prevalence of 2-3% in the general population and about 70% of recurrence rate. The objective of the study. To evaluate the efficacy of combined medication (potassium and magnesium tribasic citrate and pyridoxine) versus traditional general recommendations, in removing the remaining stone fragments after extracorporeal shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy. Material and methods. The study enrolled 60 patients after kidney or ureteral stones treatment performed by extracorporeal shock wave lithotripsy (ESWL), with signs of calculus disintegration, ureteroscopy (URS) with contact lithotripsy, and after percutaneous nephrolithotomy (PNL). The patients were randomly divided into 2 groups. Patients from Group I (n=30) were administered potassium citrate tribasic 2.7 gr, magnesium citrate tribasic 376 mg, pyridoxine 25 mg in sachet, twice daily for two months. The control group (Group II), initially consisting of 30 patients, was prescribed only general recommendations. Results. The increase in daily diuresis was statistically significant compared to the control group (2275±257 mL vs 1580 ± 321 mL, p <0.05). The urine pH in the study group was statistically significant higher (7.1±0.3) compared to the control group (6.2±0.9), p <0.01. The renal colic during the expulsion period of disintegrated calculus fragments was present in 1.8±0.3 cases (study group) compared with 6.7±0.8 (control group), p> 0.001. The „stone-free“ rate was the basic index of the study. The rate of spontaneous removal of disintegrated stone fragments was 90.0% in the study group compared with 71.4% in the control group (p <0.05). The visual analogue scale (VAS) score was 4 points in the study group and 7 points in the control group. Conclusions. The addition of combined therapy in the postoperative treatment of urinary calculi reduces the expulsion time of disintegrated calculus fragments, the number of attacks of renal colic and possibly the need for analgesic administration.

264-268

Authors: Andrei BRADU, Emil CEBAN

Introduction. Due to the increase in the incidence of reno-ureteral lithiasis worldwide from 1% to 15%, varying according to age, sex, race, and geographical location, extracorporeal shock wave lithotripsy remains the method of choice in the treatment of reno-ureteral lithiasis. The need for antibacterial prophylaxis is required only in well-defined cases, uroculture with antibacterial sensitivity being crucial in order to reduce the infectious complications. The objective of the study was to evaluate the need for antibiotic administration and to detect risk factors for the development of post-ESWL bacteriuria. Material and methods. Between 05 Nov 2018 – 10 Dec 2019, a group of 120 patients with the diagnosis of reno-ureteral lithiasis was selected, who underwent ESWL treatment in Department of Urology and Surgical Nephrology from Republican Clinical Hospital „Timofei Mosneaga“. In all 120 patients, urine sample was taken before and after ESWL. In all patients included in the study, uroculture with antibiogram was performed. Results. The uroculture results obtained before ESWL were positive in 25 (20.84%) patients without any clinical symptoms and absence of leukocytes in the general urine analysis more than 10 per high power field. At the same time, the number of positive urine culture after ESWL increased significantly in 47 patients. Conclusions. Antibiotic prophylaxis is not justified in the absence of definite risk factors such as positive urine culture before ESWL, JJ stent or nephrostome and a history of infectious reno-ureteral lithiasis or recurrent urinary tract infections.

278-283

Authors: Iryna I. KARPENKO , Elina Yu. FROLOVA-ROMANIUK, Natalia M. ZHELEZNIAKOVA

Introduction. The high medical and social significance of type 2 diabetes mellitus (T2DM) is not only due to its prevalence, but also to serious complications that lead to a decrease in the quality of patients’ life, early disability, and high mortality. The objective of the study was to evaluate the histological and morphometric features of the oesophagus mucous membrane in patients with gastroesophageal reflux disease (GERD) and T2DM compared to patients with GERD without T2DM. Material and methods. 67 patients with GERD and T2DM and 50 patients with GERD without T2DM, matched for age and sex, were examined. Comparative morphometry of histological changes of the oesophageal mucosa was performed. Results. The histological investigation showed that in patients of the main study group (with GERD and T2DM), almost all the studied parameters had a significantly more severe course and exceeded similar indicators of the group with isolated GERD: the thickness of the basal layer (1.86±0.04 points against 0.97±0.02 points), papillae height (1.71±0.06 points versus 0.72±0.07 points), inflammatory epithelial infiltration (1.88±0.03 points against 1.27±0.07 points), width of intercellular spaces (2.04±0.08 against 1.10±0.07 points) (p<0.01 in all cases). Conclusions. The inflammatory process in the oesophageal mucosae in patients with GERD without T2DM has a more superficial character and is limited mainly to the epithelial layer, whereas hyperplastic changes in the mucous membrane of the oesophagus are more pronounced in patients with GERD and T2DM.

290-297

Authors: Leila ALI, Reza ALAGHEHBANDAN, Valentin T. MOLDOVAN, Diana DEREWICZ, Anca M. CORICOVAC, Octav GINGHINA, Maria SAJIN, Mariana COSTACHE

Introduction. The most important histologic prognostic factors for melanoma remain depth of invasion and mitotic rate. In a digital era, precision (in terms of reproducibility and inter laboratories repeatability), as well as image evidence, are new qualitative parameters. The objective of the study was to evaluate in a retrospective analysis any significant difference among the Breslow digital assessments performed using two different immunohistochemical stains and the gold standard, hematoxylin eosin stain. Material and methods. We evaluated 130 primary cutaneous melanomas diagnosed in a two-year period (2016-2017) with known Breslow scale. Immunohistochemistry staining (SOX10 and Melan A) was perform followed by slide scanning. Aperio Imagescope and StataCorp software were used for data acquisition and statics. Results. No significantly statistic differences were recorded between groups in terms of Breslow values (p=0.98, Kruskal-Wallis test). Conclusions. All three stains perform similar in evaluating depth of invasion regardless of the method used to quantify it. The pathologist should consider using an accurate and precise method like a digital measurement technique for daily reports.

304-311

Authors: Mihail BANACU, Bogdan SOCEA, Adrian PELINARU, Ioan LASCAR

Introduction. Ovarian cancer is characterized by a high capacity of relapse, even in cases in whom cytoreductive surgery with curative intent followed by platinum and taxanes-based chemotherapy were performed. In such cases, attention was focused on determining if iterative cytoreduction might improve the long-term outcomes and how far these boundaries can be pushed. While for secondary cytoreduction multiple studies have been conducted, for tertiary and quaternary cytoreduction data are significantly scarcer. The objective of the study. This paper aims to realize a systematic review of the studies published so far on the theme of quaternary cytoreduction. Methodology. We searched medical journals in English language published from January 2010 to December 2019. Results. Six studies involving 110 patients submitted to quaternary cytoreduction met the inclusion criteria. Data reported in the above mentioned studies demonstrate that quaternary cytoreduction can be safely performed both at the level of the lower and the upper abdomen, in order to maximize the debulking effort. However, a significantly lower number of cases will be considered candidates for this type of procedure, when compared to secondary or even tertiary cytoreduction, an adequate selection process being mandatory in order to minimize the postoperative risks. Conclusions. Although it is less frequently feasible when compared to secondary or tertiary cytoreduction, quaternary cytoreduction might be beneficial in selected cases.

320-323

Authors: Nicolae BACALBASA, Irina BALESCU, Mihaela VILCU, Ioana HALMACIU , Camelia C. DIACONU, Simona DIMA, Iulian BREZEAN

Krukenberg tumors are ovarian metastases from different malignancies, most often originating from the gastrointestinal tract. However, in rare cases, other primary tumors, even with extra-abdominal location, might lead to the development of such lesions. Neither the mechanism of development, prognostic significance or therapeutic strategy are not clearly defined so far. It seems that these lesions are more frequently encountered in patients with BRCA1/2 mutations. Most often, Krukenberg tumors are bilateral lesions associated with ascites and with firm areas at the level of the ovarian surface. This paper aims to review existing data regarding Krukenberg tumors from breast cancer.

329-332

Authors: Catalin G. BEJINARIU, Romana MANESCU, Laura M. BOGHIAN, Matei GHEORGHIU – BRANARU, Siramona POPESCU, Silviu A. MARINESCU

Introduction. Scalp tumours raise multiple problems regarding the radical excision of the neoplasm followed by reconstructive surgery. Prolonged sun exposure and administration of immunosuppressive medication are the main risk factors for the onset of this neoplasm. The paper presents the advantages and disadvantages of scalp reconstruction using rhomboid flaps, after surgical excision of the skin cancer. Case presentation. The paper presents the case of a 83-year-old patient admitted for the treatment of squamous cell carcinoma located on the scalp. The pathological history of the patient showed that there were multiple hospitalizations for the treatment of chronic heart failure and hypertension. The therapeutic protocol included excision of a squamous cell carcinoma located in the scalp, followed by immediate reconstruction with three rhomboid flaps advanced towards the midline. The local evolution of the patient was favorable, the flaps integrating without complications, obtaining in this context a very good result from an aesthetic point of view. Conclusions. The use of the reconstructive technique involving the transposition of three rhomboid flaps to cover the soft tissue defects located in the scalp region is a feasible solution that offers very good aesthetic results.

339-344

Authors: Raluca GRIGORE, Anca I. CIRSTEA, Paula BEJENARU, Catrinel B. SIMION-ANTONIE, Gloria S. MUNTEANU, Alexandru NICOLAESCU, Mihnea CONDEESCU-COJOCARITA, Serban V.G. BERTESTEANU

Introduction. Paragangliomas are benign tumours that arise from the paraganglionic system. The most frequently encountered symptoms of tympanojugular paragangliomas are pulsatile tinnitus and conductive hearing loss. High resolution computed tomography, with reconstruction in axial and coronal planes, is mandatory in every suspected case of tympanojugular paraganglioma. The treatment is guided by the classification of Fish. Cases presentation. We present two cases in whom the clinical manifestations and paraclinical investigations established the diagnosis of tympanojugular paraganglioma. Both surgery and postoperative evolution are described for each case. In most of these tumours, surgery remains the mainstay treatment. According to the preoperative plan of the first case, it was decided that the tumour can be resected safely, without compromising the cranial nerves. In the second case, the entire tumour was removed, but with the sacrifice of the inferior cranial nerve, caught in the tumour mass. Conclusions. These tumours have the tendency to involve multiple vital structures of the skull base. A detailed preoperative plan of treatment is required to maximize tumour resection, while minimizing morbidity of the great vessels and lower cranial nerves.

350-357

Authors: Iryna CHORNOMYDZ, Oksana BOYARCHUK, Andrii CHORNOMYDZ , Natalia YAREMA, Uliana MUDRYK

Introduction. Stevens-Johnson syndrome is a rare, severe and life-threatening condition that develops mostly in response to drug use. Case presentation. We present a case of Stevens-Johnson syndrome in a boy of 11 years old, most probably developed in response to a combination of etiologic factors, such as virus infection, use of ibuprofen, and topical use of sulfanilamide agents. The clinical picture of the child was suggestive, involving tunica mucosa of mouth, genitals, conjunctiva, and skin. Parenteral administration of glucocorticoids, detoxification, antibiotic prophylaxis, and topical treatment led to rapid regression of clinical symptoms and prevented the development of complications. Conclusions. The treatment of Stevens-Johnson syndrome involves systemic glucocorticoids in combination with topical therapy. In our patient, the treatment avoided serious complications and led to rapid regression of cutaneous manifestations. The etiology of Stevens-Johnson syndrome is sometimes difficult to establish. Physicians should avoid polypragmasia and unreasonable prescription of drugs and be aware of the risk of Stevens-Johnson syndrome, especially in pediatric patients.

361-362

Authors: Petru E. MUNTEAN, Cristina G. NECULCEA

On 18th of April 2020, a 49-year-old woman developed a fever of 38.40C, with no other symptoms. After taking oral nonsteroidal anti-inflammatory agents for 2 days, the temperature returned to normal. On 20th of April 2020, she complained of persistent dry cough, sore throat, ageusia, anosmia and chest distress. The next day, she presented to the Emergency Department of Arges County Hospital, Pitesti, Romania. She divulged that she had been in close contact with a friend, who had been recently confirmed with the diagnosis of COVID-19. A high-resolution computed tomography (CT) of the chest was performed, that revealed multiple images of patchy ground-glass opacities in bilateral lower lobes (Figure 1). Given the close contact history and imaging findings, she was admitted as a suspected case of SARS-CoV-2 infection. On admission, physical examination unveiled normal vital signs, with oxygen saturation of 96% while breathing ambient air, lung auscultation normal. The antigen test for influenza was negative. Arterial blood gas analysis pointed out a pO2 of 103 mmHg, potassium 3.3 mEq/L, calcium 1.09 mmol/L and glucose 113 mg/dL. The blood routine tests revealed: white blood cell count 3.99 10^9/Liter, red blood cell count 6.41 10^12/Liter, hemoglobin 13.4 g/dL, hematocrit 40.1%, neutrophils 1.99 10^9/Liter, lymphocytes 39.9%, D-dimers 0.526 ug/mL, troponin T 7.22 ng/L, ferritin 192 ng/mL, procalcitonin 15 ug/L, creatine kinase-MB 27 U/L, lactic acid dehydrogenase (LDH) 481 U/L, fibrinogen 455 mg/dL, normal liver and renal function, normal prothrombin time. The electrocardiogram was normal. On 22th of April, the lab confirmed that the oropharyngeal swab test of SARS-CoV-2 by qualitative real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay was positive. After seven days of symptomatic treatment and hydroxychloroquine therapy, the patient’s respiratory symptoms significantly improved. The dynamics of high-resolution CT of the chest revealed systematic absorption of lung lesions (Figure 2). After two consecutive (24 hours apart) oropharyngeal swab tests of SARS-CoV-2 RNA negative, the patient was discharged on 30th of April, with the indication for home quarantine for at least 14 days. SARS-CoV-2 RNA by oropharyngeal swab remained negative in the follow-up visit on 13th of May 2020. Take home messages: The accuracy of chest CT in symptomatic patients with COVID-19 is high, but used as a single diagnostic test, CT can not accurately diagnose or exclude coronavirus infection and should not be relied upon as a screening or diagnostic tool for COVID-19 pneumonia. Chest CT is rather helpful in evaluating the complications of COVID-19 and is indicated in patients with COVID-19 and worsening respiratory symptoms. The most common imaging findings are of an atypical or organising pneumonia, with bilateral involvement, especially of the lower lobes. Point of care lung ultrasound may be useful for the diagnosis and can detect abnormalities even in asymptomatic patients. The definitive diagnostic test for SARS-CoV-2 infection is the RT-PCR test.