The role of fibrosis in cardiomyopathies: An opportunity to develop novel biomarkers of disease activity.

Cardiomyopathies encompass a spectrum of heart disorders with diverse causes and presentations. Fibrosis stands out as a shared hallmark among various cardiomyopathies, reflecting a common thread in their pathogenesis. This prevalent fibrotic response is intricately linked to the consequences of dysregulated extracellular matrix (ECM) remodeling, emphasizing its significance in the development and progression the disease. This review explores the ECM involvement in various cardiomyopathies and its impact on myocardial stiffness and fibrosis. Additionally, we discuss the potential of ECM fragments as early diagnosis, prognosis, and risk stratification. Biomarkers deriving from turnover of collagens and other ECM proteins hold promise in clinical applications. We outline current clinical management, future directions, and the potential for personalized ECM-targeted therapies with specific focus on microRNAs. In summary, this review examines the role of the fibrosis in cardiomyopathies, highlighting the potential of ECM-derived biomarkers in improving disease management with implications for precision medicine.

Deciphering Pro-angiogenic Transcription Factor Profiles in Hypoxic Human Endothelial Cells by Combined Bioinformatics and in vitro Modeling.

Background: Constant supply of oxygen is crucial for multicellular tissue homeostasis and energy metabolism in cardiac tissue. As a first response to acute hypoxia, endothelial cells (ECs) promote recruitment and adherence of immune cells to the dysbalanced EC barrier by releasing inflammatory mediators and growth factors, whereas chronic hypoxia leads to the activation of a transcription factor (TF) battery, that potently induces expression of growth factors and cytokines including platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). We report a hypoxia-minded, targeted bioinformatics approach aiming to identify and validate TFs that regulate angiogenic signaling. Results: A comprehensive RNA-Seq dataset derived from human ECs subjected to normoxic or hypoxic conditions was selected to identify significantly regulated genes based on (i) fold change (normoxia vs. hypoxia) and (ii) relative abundancy. Transcriptional regulation of this gene set was confirmed via qPCR in validation experiments where HUVECs were subjected to hypoxic conditions for 24 h. Screening the promoter and upstream regulatory elements of these genes identified two TFs, KLF5 and SP1, both with a potential binding site within these regions of selected target genes. In vitro, siRNA experiments confirmed SP1- and KLF5-mediated regulation of identified hypoxia-sensitive endothelial genes. Next to angiogenic signaling, we also validated the impact of TFs on inflammatory signaling, both key events in hypoxic sensing. Both TFs impacted on inflammatory signaling since endogenous repression led to increased NF-κB signaling. Additionally, SP1 silencing eventuated decreased angiogenic properties in terms of proliferation and tube formation. Conclusion: By detailed in silico analysis of promoter region and upstream regulatory elements for a list of hypoxia-sensitive genes, our bioinformatics approach identified putative binding sites for TFs of SP or KLF family in vitro. This strategy helped to identify TFs functionally involved in human angiogenic signaling and therefore serves as a base for identifying novel RNA-based drug entities in a therapeutic setting of vascularization.

Artificial Intelligence Identifies an Urgent Need for Peripheral Vascular Intervention by Multiplexing Standard Clinical Parameters.

BACKGROUND: Peripheral artery disease (PAD) is a significant burden, particularly among patients with severe disease requiring invasive treatment. We applied a general Machine Learning (ML) workflow and investigated if a multi-dimensional marker set of standard clinical parameters can identify patients in need of vascular intervention without specialized intra-hospital diagnostics. METHODS: This is a retrospective study involving patients with stable PAD (sPAD, Fontaine Class I and II, n = 38) and unstable PAD (unPAD, Fontaine Class III and IV, n = 18) in need of invasive therapeutic measures. ML algorithms such as Random Forest were utilized to evaluate a matrix consisting of multiple routinely clinically available parameters (age, complete blood count, inflammation, lipid, iron metabolism). RESULTS: ML has enabled a generation of an Artificial Intelligence (AI) PAD score (AI-PAD) that successfully divided sPAD from unPAD patients (high AI-PAD in sPAD, low AI-PAD in unPAD, cutoff at 50 AI-PAD units). Furthermore, the probability score positively coincided with gold-standard intra-hospital mean ankle-brachial index (ABI). CONCLUSION: AI-based tools may be promising to enable the correct identification of patients with unstable PAD by using existing clinical information, thus supplementing clinical decision making. Additional studies in larger prospective cohorts are necessary to determine the usefulness of this approach in comparison to standard diagnostic measures.

Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics.

The family of RNA-binding proteins (RBP) functions as a crucial regulator of multiple biological processes and diseases. However, RBP function in the clinical setting of idiopathic pulmonary fibrosis (IPF) is still unknown. We developed a practical in silico screening approach for the characterization of RBPs using multi-sources data information and comparative molecular network bioinformatics followed by wet-lab validation studies. Data mining of bulk RNA-Sequencing data of tissues of patients with IPF identified Quaking (QKI) as a significant downregulated RBP. Cell-type specific expression was confirmed by single-cell RNA-Sequencing analysis of IPF patient data. We systematically analyzed the molecular interaction network around QKI and its functional interplay with microRNAs (miRs) in human lung fibroblasts and discovered a novel regulatory miR-506-QKI axis contributing to the pathogenesis of IPF. The in silico results were validated by in-house experiments applying model systems of miR and lung biology. This study supports an understanding of the intrinsic molecular mechanisms of IPF regulated by the miR-506-QKI axis. Initially applied to human lung disease, the herein presented integrative in silico data mining approach can be adapted to other disease entities, underlining its practical relevance in RBP research.

Combined high-throughput library screening and next generation RNA sequencing uncover microRNAs controlling human cardiac fibroblast biology.

BACKGROUND: Myocardial fibrosis is a hallmark of the failing heart, contributing to the most common causes of deaths worldwide. Several microRNAs (miRNAs, miRs) controlling cardiac fibrosis were identified in recent years; however, a more global approach to identify miRNAs involved in fibrosis is missing. METHODS AND RESULTS: Functional miRNA mimic library screens were applied in human cardiac fibroblasts (HCFs) to identify annotated miRNAs inducing proliferation. In parallel, miRNA deep sequencing was performed after subjecting HCFs to proliferating and resting stimuli, additionally enabling discovery of novel miRNAs. In-depth in vitro analysis confirmed the pro-fibrotic nature of selected, highly conserved miRNAs miR-20a-5p and miR-132-3p. To determine downstream cellular pathways and their role in the fibrotic response, targets of the annotated miRNA candidates were modulated by synthetic siRNA. We here provide evidence that repression of autophagy and detoxification of reactive oxygen species by miR-20a-5p and miR-132-3p explain some of their pro-fibrotic nature on a mechanistic level. CONCLUSION: We here identified both miR-20a-5p and miR-132-3p as crucial regulators of fibrotic pathways in an in vitro model of human cardiac fibroblast biology.

Inflammatory Drivers of Cardiovascular Disease: Molecular Characterization of Senescent Coronary Vascular Smooth Muscle Cells.

The senescence of vascular smooth muscle cells (VSMCs) has been implicated as a causal pro-inflammatory mechanism for cardiovascular disease development and progression of atherosclerosis, the instigator of ischemic heart disease. Contemporary limitations related to studying this cellular population and senescence-related therapeutics are caused by a lack of specific markers enabling their detection. Therefore, we aimed to profile a phenotypical and molecular signature of senescent VSMCs to allow reliable identification. To achieve this goal, we have compared non-senescent and senescent VSMCs from two in vitro models of senescence, replicative senescence (RS) and DNA-damage induced senescence (DS), by analyzing the expressions of established senescence markers: cell cycle inhibitors- p16 INK4a, p14 ARF, p21 and p53; pro-inflammatory factors-Interleukin 1ß (IL-1ß), IL-6 and high mobility group box-1 (HMGB-1); contractile proteins-smooth muscle heavy chain- (MYH11), smoothelin and transgelin (TAGLN), as well as structural features (nuclear morphology and LMNB1 (Lamin B1) expression). The different senescence-inducing modalities resulted in a lack of the proliferative activity. Nucleomegaly was seen in senescent VSMC as compared to freshly isolated VSMC Phenotypically, senescent VSMC appeared with a significantly larger cell size and polygonal, non-spindle-shaped cell morphology. In line with the supposed switch to a pro-inflammatory phenotype known as the senescence associated secretory phenotype (SASP), we found that both RS and DS upregulated IL-1ß and released HMGB-1 from the nucleus, while RS also showed IL-6 upregulation. In regard to cell cycle-regulating molecules, we detected modestly increased p16 levels in both RS and DS, but largely inconsistent p21, p14ARF, and p53 expressions in senescent VSMCs. Since these classical markers of senescence showed insufficient deregulation to warrant senescent VSMC detection, we have conducted a non-biased proteomics and in silico analysis of RS VSMC demonstrating altered RNA biology as the central molecular feature of senescence in this cell type. Therefore, key proteins involved with RNA functionality, HMGB-1 release, LMNB-1 downregulation, in junction with nuclear enlargement, can be used as markers of VSMC senescence, enabling the detection of these pathogenic pro-inflammatory cells in future therapeutic studies in ischemic heart disease and atherosclerosis.

Comprehensive Bioinformatics Identifies Key microRNA Players in ATG7-Deficient Lung Fibroblasts.

BACKGROUND: Deficient autophagy has been recently implicated as a driver of pulmonary fibrosis, yet bioinformatics approaches to study this cellular process are lacking. Autophagy-related 5 and 7 (ATG5/ATG7) are critical elements of macro-autophagy. However, an alternative ATG5/ATG7-independent macro-autophagy pathway was recently discovered, its regulation being unknown. Using a bioinformatics proteome profiling analysis of ATG7-deficient human fibroblasts, we aimed to identify key microRNA (miR) regulators in autophagy. METHOD: We have generated ATG7-knockout MRC-5 fibroblasts and performed mass spectrometry to generate a large-scale proteomics dataset. We further quantified the interactions between various proteins combining bioinformatics molecular network reconstruction and functional enrichment analysis. The predicted key regulatory miRs were validated via quantitative polymerase chain reaction. RESULTS: The functional enrichment analysis of the 26 deregulated proteins showed decreased cellular trafficking, increased mitophagy and senescence as the major overarching processes in ATG7-deficient lung fibroblasts. The 26 proteins reconstitute a protein interactome of 46 nodes and miR-regulated interactome of 834 nodes. The miR network shows three functional cluster modules around miR-16-5p, miR-17-5p and let-7a related to multiple deregulated proteins. Confirming these results in a biological setting, serially passaged wild-type and autophagy-deficient fibroblasts displayed senescence-dependent expression profiles of miR-16-5p and miR-17-5p. CONCLUSIONS: We have developed a bioinformatics proteome profiling approach that successfully identifies biologically relevant miR regulators from a proteomics dataset of the ATG-7-deficient milieu in lung fibroblasts, and thus may be used to elucidate key molecular players in complex fibrotic pathological processes. The approach is not limited to a specific cell-type and disease, thus highlighting its high relevance in proteome and non-coding RNA research.

Cardiac endurance training alters plasma profiles of circular RNA MBOAT2.

Marathon running is an extreme physical activity, which determines cardiopulmonary adaption of athletes. Circular RNAs (circRNAs) as potential biomarkers in the blood stream have so far not been tested after such strenuous activities. In silico approaches were performed to identify the potential candidate circRNA MBOAT2. Next, we demonstrated high stability and conservation of circRNA MBOAT2 as well as its abundancy in human plasma. In addition to Sanger sequencing of the circRNA specific head-to-tail junction, or back-splice site, we established a synthetic plasmid standard which allowed exact copy number calculations of circRNA MBOAT2. We then analyzed plasmatic circRNA MBOAT2 and observed a significantly lower level 24 h after the marathon. Such alterations were correlated to physical exercise parameters confirming the role of circRNA MBOAT2 as a promising noncoding RNA biomarker detecting cardiopulmonary adaption.NEW & NOTEWORTHY In brief, we herein report a timeline of circulating circular RNA (circRNA) MBOAT2 in a cohort of marathon runners. Time-course analysis of plasmatic circRNA MBOAT2 demonstrated a significantly lowered level 24 h after the marathon. Abundancy of circRNA was correlated to physical exercise parameters highlighting the role of circRNA MBOAT2 as a valuable noncoding RNA biomarker detecting and following up cardiopulmonary adaption.

Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis.

Inflammation is a hallmark and potent driver of pathological vascular remodelling in atherosclerosis. However, current anti-inflammatory therapeutic strategies have shown mixed results. As an alternative perspective on the conundrum of chronic inflammation emerging evidence points towards a small subset of senescent cells as a critical player and central node driving atherosclerosis. Senescent cells belonging to various cell types are a dominant and chronic source of a large array of pro-inflammatory cytokines and various additional plaque destabilizing factors, being involved with various aspects of atherosclerosis pathogenesis. Antagonizing these key agitators of local chronic inflammation and plaque instability may provide a causative and multi-purpose therapeutic strategy to treat atherosclerosis. Anti-senescence treatment options with translational potential are currently in development. However, several questions and challenges remain to be addressed before these novel treatment approaches may enter the clinical setting.

Total Artificial Heart Salvage of a Heterotopic Heart Transplant Patient.

Rescuing heterotopic heart transplantation (HHT) patients remains a challenge in the field. When a 41-year-old patient was transferred to our service, we chose a novel approach that is reported herein. The HHT had been performed over 20 years ago, and in 2016, because of complications, the patient was listed for transplant with a 1A status. For the first time, the SynCardia 50cc total artificial heart (TAH) (SynCardia Systems, LLC, Tucson, AZ) was used in an HHT patient. Investigators attained approval to use the SynCardia 50cc investigational device, as this was an emergent case with few options. The donor heart from the HHT was left in place, alongside the TAH. By leaving the donor heart from the HHT, the need for long and tedious extensive dissection around the right lung was eliminated; thereby reducing the potential risk of lung parenchymal injury, massive bleeding, and complex air leaks. The procedure was successful, and the patient underwent a successful orthotopic heart transplantation six months after being placed on TAH.

Long Noncoding RNA-Enriched Vesicles Secreted by Hypoxic Cardiomyocytes Drive Cardiac Fibrosis.

Long non-coding RNAs (lncRNAs) have potential as novel therapeutic targets in cardiovascular diseases, but detailed information about the intercellular lncRNA shuttling mechanisms in the heart is lacking. Here, we report an important novel crosstalk between cardiomyocytes and fibroblasts mediated by the transfer of lncRNA-enriched extracellular vesicles (EVs) in the context of cardiac ischemia. lncRNA profiling identified two hypoxia-sensitive lncRNAs: ENSMUST00000122745 was predominantly found in small EVs, whereas lncRNA Neat1 was enriched in large EVs in vitro and in vivo. Vesicles were taken up by fibroblasts, triggering expression of profibrotic genes. In addition, lncRNA Neat1 was transcriptionally regulated by P53 under basal conditions and by HIF2A during hypoxia. The function of Neat1 was further elucidated in vitro and in vivo. Silencing of Neat1 in vitro revealed that Neat1 was indispensable for fibroblast and cardiomyocyte survival and affected fibroblast functions (reduced migration capacity, stalled cell cycle, and decreased expression of fibrotic genes). Of translational importance, genetic loss of Neat1 in vivo resulted in an impaired heart function after myocardial infarction highlighting its translational relevance.

Leber's Hereditary Optic Neuropathy: Novel Views and Persisting Challenges.

BACKGROUND & OBJECTIVE: Leber's hereditary optic neuropathy is an inherited form of optic neuropathy, genetically and pathophysiologically based on mitochondrial insufficiency causing bilateral loss of central vision mostly amongst young adults. Despite being one of the most common mitochondrial diseases, the explanation for its pathophysiological background and effective clinical solutions remain elusive. Widening the scope in the search for pathological findings beyond the optic system has yielded several non-ophthalmologic findings, which might imply that Leber's hereditary optic neuropathy is in fact a multi-systemic disease. CONCLUSION: The aim of this review is to provide an overview of literature regarding the epidemiology, etiology, pathogenesis, clinical features, diagnostics and possible treatment options and drug targets, as well as presenting challenges related to the disease and proposing a diagnostic algorithm based on current clinical experience.

Clinical significance of Cyclin D1, FGF3 and p21 protein expression in laryngeal squamous cell carcinoma.

PURPOSE: Laryngeal squamous cell carcinoma (LSCC) represents one of the most common cancers of the head and neck and the search for molecular markers is required for early diagnosis, prognosis and optimal therapy. The purpose of this study was to investigate the clinical significance of Cyclin D1, FGF3, p16 and p21 protein expression in LSCC and laryngeal dysplasia (LD) and to evaluate the associations between their expression levels and clinicopathological parameters of patients with LSCC. METHODS: Immunohistochemistry was employed to detect and quantify the expression levels of Cyclin D1, FGF3, p16 and p21 in the laryngeal tissues of 48 LSCC patients, 32 patients with LD and 28 subjects with healthy laryngeal mucosa (HLM). RESULTS: Significantly higher percentage of LSCC patients had positive Cyclin D1 expression compared with LD patients and HLM subjects (both p<0.01) and positive FGF3 expression than HLM subjects (p<0.05), while no differences in p16 and p21 positive expression were found among studied groups. The levels of Cyclin D1, FGF3 and p16 expression, as evaluated by immunostaining score, were significantly higher in patients with LSCC compared with LD and HLM groups (all p<0.05). Cyclin D1 proved to be highly sensitive and specific marker in differentiating LSCC from LD (sensitivity 81.2%, specificity 83.9%), while high sensitivity (81.2%) and lower specificity (41.4%) was observed in differentiating from HLM. Cyclin D1 and p21 expression levels were associated with regional lymph node metastases (both p<0.05) and Cyclin D1 expression levels significantly correlated with LSCC lymphatic invasion (x(2)=8.862; df=3; ?=0.031). CONCLUSIONS: Cyclin D1, FGF3 and p16 are overexpressed in patients with LSCC. Cyclin D1 is a highly sensitive marker in differentiating LSCC from LD or HLM. Cyclin D1 and p21 expression levels may be useful as predictive markers of metastases in LSCC.

Primary nasal tuberculosis: a case report.

INTRODUCTION: During the past two decades, tuberculosis (TBC) both pulmonary and extrapulmonary, has emerged to be a major health problem. Nasal tuberculosis is a specific inflammatory process which is, in most cases, joined by the inflammation of neck lymph nodes. CASE REPORT: Thirty-year-old man presented with shortness of breath through the nose and periodical headaches. Clinical examination showed signs of chronic rhinitis, with slight granular changes of nasal septal mucosa. Laboratory analyses were within the reference ranges. Nasal and throat swabs for bacteria and fungi were normal. Skin allergy testing to standard inhalatory allergens was positive. Computer rhinomanometry showed increased nasal resistance at medium difficulty level, on the right. Radiography of paranasal sinuses indicated chronic polysinusitis on the right. Anti-allergy therapy was prescribed. The patient came for checkup after a month with subjective deterioration and a neck tumefact on the right. Nasal endoscopy revealed the presence of dark red infiltrates with the 3 mm diameter on nasal septal mucosa, dominantly on the right, with small greyish nodules. This findings indicated a potential specific nasal inflammatory process. In the upper jugulodigastric area, on the left, painless tumefact 3 x 5 cm in size was palpated, it was mobile comparing to supra- and infrastructure, with unaltered skin above. The definite diagnosis was established on the basis of the results of nasal mucosa biopsy. After histopathological diagnosis was obtained, we started with antituberculosis therapy at once. CONCLUSION: Due to actual trends of TBC incidences, otolaryngologist should have in mind nasal TBC, when granulomatose lesions are found in nose.

Nasal septum extramedullary plasmacytoma.

INTRODUCTION: Plasmacytomas are malignant tumors characterized by abnormal monoclonal proliferation of plasma cells. They originate in either bone--solitary osseous plasmacytoma, or in soft tissue--extramedullary plasmacytoma (EMP). EMP represents less than 1% of all head and neck malignancies. CASE REPORT: We presented a case of EMP of the nasal septum in a 44-year-old male who had progressive difficulty in breathing through the nose and frequent heavy epistaxis on the right side. Nasal endoscopy showed dark red, soft, polypoid tumor in the last third of the right nasal cavity arising from the nasal septum. The biopsy showed that it was plasmacytoma. Bence Jones protein in the urine, serum electrophoresis, bone marrow biopsy, skeletal survey and other screening tests failed to detect multiple myeloma. This confirmed the diagnosis of EMP. The mass was completely removed via an endoscopic approach, and then, 4 week later, radiotherapy was conducted with a radiation dose of 50 Gray. No recurrence was noted in a 3-year follow-up period. CONCLUSION: EMP of the nasal cavity, being rare and having long natural history, represents a diagnostic and therapeutic challenge for any ear, nose and throat surgeon. Depending on the resectability of the lesion, a combined therapy is the accepted treatment.

Antrochoanal polyp of unusual size.

This paper presents antrochoanal polyp of unusually large size (8x5 cm), which we removed in a 34-year old patient by the antral portion by the Caldwell-Luc approach and the portion form the epipharynx through the oral cavity with skew pliers for the pharynx biopsy.

Neonatal screening of hearing function by otoacustic emissions--a single center experience.

BACKGROUND/AIM: Nowadays development of techniques enables detection of hearing impairment in a very short time, immediately after birth by using otoacoustic emissions. They are low-pitched sounds produced in physiologically clear cochlea and can be recorded in cochlear outer meatus. By this method, complete data are found on a whole presynaptic auditory nervous system functioning that has mostly been affected by pathological changes making it a perfect screening test. Reliability and sensibility of this method is up to 98%. The aim of this study was to present the first results of systematic neonatal screening of hearing function by otoacoustic emissions in the Clinical Center Kragujevac (Kragujevac, Serbia). METHODS: This prospective study of neonatal hearing screening function, initiated systematically by the 2008 at the Clinical Center Kragujevac, included full-term newborns and premature born ones, within the first 24 h after birth, using a DPOAEs interacoustics otoread-screener. Retesting was done after a month. RESULTS: From January 1st, 2009 to December 1st, 2010, a total number of examined infants by this method was 1,994 out of which 1,778 were full-term and 216 were premature born. The test passing was higher in the group of full-term babies (92.5%) than in the preterm ones (55.1%). No bilateral answers were recorded in premature born children compared to the full-term ones, of whom a larger number was with missing lateral responses. The results of re-examination test in the group of full-term born and premature newborns were 83.7%, and 61%, respectively. CONCLUSION: Deliberately provoked transient otoacoustic emission is an efficient method in testing hearing function in newborns, since it is non-invasive, rapid and objective. Its correlation with audibly evoked potentials is very high, which confirms its reliability.

Total fixation of cricoarytenoid joint of a patient with rheumatoid arthritis and Hashimoto thyroiditis.

INTRODUCTION: The incidence of cricoarytenoid joint fixation in case of rheumatoid arthritis is 17 to 33%. In later stages of rheumatoid arthritis, a gradual fixation of cricoarytenoid joint develops and both halves of the larynx become less movable which calls for endotracheal intubation; while total fixation of this joint demands surgical tracheotomy. Hashimoto thyroiditis can display symptoms which are difficult to distinguish from the ones present in total fixation of cricoarytenoid joint caused by rheumatoid arthritis. CASE OUTLINE: A 60-year-old woman in terminal stage of rheumatoid arthritis and Hashimoto thyroiditis, diagnosed after clinical and other examinations. She was treated for strident breathing with surgical tracheotomy. The microscopic examination of the larynx with the use of laryngoscopic pincers suggested the immovability of the right and very limited movability of the left arytenoid cartilage. A computerized endovideostroboscopy showed only passive vertical vibrating movements of the right vocal cord and irregular vibrations of the left vocal cord. CONCLUSION: Total fixation of the cricoarytenoid joint can be caused by many pathological processes, but so far references have shown no case of rheumatoid arthritis and Hashimoto thyroiditis. In differential diagnostics, one of many examinations is the microscopic examination of the larynx, but it is very important to determine the movability of the arytenoid cartilage with the use of appropriate instruments in total endotracheal anaesthesia while the patient is fully relaxed. Movements in cricoarytenoid joints in patients with Hashimoto thyroiditis and the same conditions are preserved.

[Sudden hearing loss--our experience in treatment with vasoactive therapy].

INTRODUCTION: A specific title "sudden hearing loss" refers to illness which is characterized by a sudden, rapid sensoneural hearing loss mostly in one ear without obvious causes, accompanied with dizziness, and without vestibular symptomatology. It is defined as a hearing loss for more than 30 dB on 3 or more successive frequencies which appear in 72 hours. OBJECTIVE: The main goal of our paper was to estimate success of implementation of vasoactive method in patients with sudden hearing loss of senso-neural type in different ranges in hospital conditions. METHOD: Our research covered 37 patients hospitalized because of a sudden hearing loss of sensoneural type in different ranges. Diagnosis, in all patients, was established by clinical ORL examination, audiology and vestibular examination. R including CT and MR, neurological, internist and laboratory examinations were used in order to exclude other aetiology. In monitored patients, we started treatment with vasoactive therapy, ampules of xanthinol nicotinate (one ampule of 2 ml, 300 mg) or ampules of pentoxiphylline (one ampule of 5 ml, 100 mg) in form of infusions with addition of vitamins with an everyday gradual increase of dosage up to 12 ampules of xanthinol nicotinate and up to 5 ampules of pentoxiphylline. Then we started with an everyday decrease of dosage down to the first one. RESULTS: After the complete curing protocol, we found out that in patients with light and medium senso-neural damages of hearing sense (23 or 62%), hearing recovery was complete. In patients with heavy damage of hearing (9 or 24%), partial success was evidenced. The most difficult cases, with complete hearing loss, heavy buzzing and vertiginous problem (5 or 14%) responded to therapy, so buzzing and vertiginous problems disappeared but hearing was not improved. CONCLUSION: Usage of vasoactive medicaments in hospital conditions in treatment of sudden hearing loss gives good results and it is the closest to aetiological therapy.