<p>Prema literaturnim podacima poslednjih godina velika pažnja je usmerena ka operativnom riziku i mortalitetu koji su postali najvažniji kriterijumi u ocenama rezultata rada hirur&scaron;kih ustanova, ali i svakog hirurga posebno. Zahvaljujući kompleksnom profilu pacijenata koji se podvrgavaju hirur&scaron;kim intervencijama, precizna procena operativnog rizika postaje sve teža. Predikcija ishoda intervencije u najvećoj meri zavisi od preoperativnih faktora rizika. Ipak, neminovno je da i faktori koji su vezani za samu operaciju u određenom stepenu utiču na ishod hirur&scaron;ke intervencije. Shodno tome, dobar model za procenu rizika treba da obuhvati faktore koji će imati najbolju prediktivnu vrednost. Thoracoscore je prvi bodovni sistem razvijen od strane Francuskog udruženja grudnih i vaskularinih hiruga. Zbog nedovoljne primene tokom poslednje decenije i nekonzistentnih rezultata nije do&scaron;lo do &scaron;irokog međunarodnog prihvatanja ovog modela i njegove rutinske upotrebe. Ova činjenica ukazuje na nedostake samog modela i potrebu za rekalibracijom u cilju postizanja bolje saglasnosti između predikcije operativnog rizika i kliničkog stanja bolesnika. Cilj rada je bio da se ustanovi realna vrednost Thoracoscore bodovnog sistema u proceni operativnog rizika i mortaliteta nakon anatomskih i neanatomskih resekcija pluća u na&scaron;im uslovima, i da se utvrdi prediktivna vrednost faktora rizika koji nisu obuhvaćeni Thoracoscore bodovnim sistemom na ishod grudno-hirur&scaron;kih operacija. Istraživanje je sprovedeno po tipu prospektivne kliničke studije i obuhvatilo je 957 bolesnika operisanih na Klinici za grudnu hirurgiju Instituta za plućne bolesti Vojvodine. Izvr&scaron;ene hirur&scaron;ke procedure bile su anatomske resekcije (lobektomija, bilobektomija, pneumonektomija, Sleeve resekcija, segmentektomija) i neanatomske resekcije pluća (Wedge resekcija i druge atipične resekcije). Thoracoscore je izračunat za svakog bolesnika na osnovu devet parametara: godine starosti, pol, ASA skor, dispnea skor, procena op&scaron;teg stanja bolesnika, dijagnostička grupa, hitnost operacije, vrsta operacije i broj komorbiditeta. S obzirom da prediktivna vrednost Thoracoscore bodovnog sistema u proceni operativnog rizika nije bila adekvatna realnom stanju, regresionom analizom je evaluiran značaj tri nova faktora: forsirani ekspiratorni volumen u prvoj sekundi (FEV1), reoperacija i hirur&scaron;ki pristup (torakotomija, video-asistirana torakoskopija &ndash; VATS). Nakon &scaron;to je univarijantnom analizom potvrđeno da su ovi faktori nezavisni prediktori operativnog ishoda, originalni Thoracoscore model je rekalibrisan. Multivarijantnom analizom putem logističke regresije izračunati su novi beta koeficijenti za originalnih devet faktora, kao i za tri nova, te je kreiran lokalni model za procenu operativnog rizika koji je prilagođen na&scaron;oj populaciji. Prosečna starosti bolesnika bila je 62 &plusmn; 7,52 godina. Većinu uzorka (60,7%) činili su pripadnici mu&scaron;kog pola. Najveći broj resekcija činile su lobektomije (61,4%). Malignitet je bio najučestalija indikacija za operaciju (90,3%). Najveći broj bolesnika imao je 1-2 komorbiditeta (64,3%). Prosečna stopa operativnog rizika na osnovu Thoracoscore-a (4,7% ) bila je veća je od stvarnog (2,9%) intrahospitalnog mortalita (p&lt;0,01). Ovaj model je pokazao zadovoljavajuće rezultate jedino u grupi niskog rizika. Predikcija mortaliteta lokalnim modelom za procenu operativnog rizika u grudnoj hirurgiji se, u statističkom smislu, ne razlikuje od stvarnog mortaliteta (p = NS). Thoracoscore ima dobru diskriminativnu moć, ali nezadovoljavajuću kalibrisanost. Shodno tome, Thoracoscore model se može koristiti za stratifikaciju rizika, ali ne i za predikciju mortaliteta. Za razliku, lokalni model je pokazao dobru diskriminaciju i kalibrisanost u na&scaron;im uslovima. Interni model za procenu rizika bi bio od velike koristi u svakodnevnom kliničkom radu, budući da bi oslikavao realno stanje populacije u kojoj je razvijen i vr&scaron;io preciznu predikciju operativnog rizika.</p> / <p>According to the literature data, over the past several years, great attention has been focused on operative risk and mortality which have become the most important criteria in evaluating the results from surgical departments and individual surgeons, as well. Because of complex profiles of patients undergoing surgical interventions, it is becoming more difficult to assess the risk precisely. Prediction of surgical outcomes mostly depends on the preoperative risk factors. However, factors related to the procedure itself effect the surgical outcome to a certain degree. Therefore, a good risk assessment model must contain factors which will have the best predictive value. Thoracoscore is the first scoring system developed by the French Association of Thoracic and Vascular Surgeons. Due to insufficient utilization over the past decade and inconsistent results, this model has not been widely accepted for routine use. This fact indicates that the model lacks certain aspects and needs to be recalibrated in order to achieve better concordance between the predicted operative risk and the clinical state of the patient. The aim of this study was to determine real value of Thoracoscore scoring system for estimation of operative risk and mortality following anatomic and non-anatomic lung resections in our settings, and to determine predictive value of factors not included in Thoracoscore on the outcome of thoracic surgeries. This prospective study included 957 patients who underwent lung resections at the Thoracic surgery clinic of Institute for Lung Diseases of Vojvodina. Performed surgical procedures were anatomic lung resections (lobectomy, bilobectomy, pneumonectomy, Sleeve resection, segmentectomy) and non-anatomic lung resections (Wedge resection and other atypical resections). Thoracoscore was calculated for each patient based on the following nine parameters: age, gender, ASA score, dyspnea score, performance status classification, diagnostic group, urgency of surgery, surgical procedure and number of comorbidities. Because predictive value of Thoracoscore did not correspond to the actual results, regression analysis was used to evaluate the significance of three new risk factors: forced expiratory volume in the first second (FEV1), reoperation, and surgical approach (thoracotomy, video-assisted thoracoscopy &ndash; VATS). After univariate analysis confirmed that these three factors are independent predictors of operative risk, the original Thoracoscore model was recalibrated. With the use of multivariate analysis by logistic regression, new beta coefficients were calculated for the original nine parameters, as well as for the new three, and consequently a local model for surgical risk assessment that is adapted to our population was created. Average age of patients was 62 &plusmn; 7.52 years. Most of the patients were males (60.7%). Lobectomies constituted the largest number (61.4%) of performed surgeries. The most common indications for surgery were malignant causes (90.3%). Most frequently, patients had 1-2 comorbidities (64.3%). Mean operative risk based on Thoracoscore (4.7%) was greater than the actual intrahospital mortality (2.9%) (p&lt;0.01). This model had adequate results only in the low risk group of patients. Predicted mortality by the local model was not statistically different from the actual mortality (p = NS). Thoracoscore had good discriminative ability, but inadequate calibration. Because of this, Thoracoscore model can be used for risk stratification, but not for mortality prediction. On the other hand, local model showed good discrimination and calibration in our population. Therefore, an internal model for risk assessment would be of great use in everyday clinical practice because it would reflect the real state of the population in which it was developed, predicting the risk more precisely.</p>

<p>Veno-arterijski gradijent ugljen-dioksida (Pv-aCO2) se smatra pokazateljem adekvatnosti microcirculatornog venskog protoka. U stanjima usporenog protoka dolazi do povećavanja Pv-aCO2 zbog fenomena zadržavanja CO2. Vrednost Pv-aCO2 predložena je kao dodatni cilj rane usmerene terapije kod pacijenata sa septičnim &scaron;okom. Cilj rada bilo je utvrditi postojanje korelacije promene Pv-aCO2 s promenom SOFA (&ldquo;Sequential Organ Failure Assessment&rdquo;) skora (delta SOFA) nakon primene rane ciljane terapije, kao i korelacije vrednosti različitih pokazatelja krvnog protoka unutar prvih 12 sati od početka lečenja pacijenata sa sepsom. Sekundarni cilj bilo je utvrditi postojanje korelacije Pv-aCO2 6 sati nakon početka rane ciljane terapije (T6) s dužinom boravka u intenzivnoj jedinici i ishodom lečenja. Prospektivnim, neintervencijskim ispitivanjem obuhvaćeno je 150 pacijenata sa sepsom ili septičnim &scaron;okom. Merenja serumskog laktata, saturacije kiseonikom me&scaron;ane venske krvi (ScvO2) i Pv-aCO2 vr&scaron;ena su na početku rane ciljane terapije (T0), posle 6 i 12 sati (T6, T12). Pv-aCO2 se računao kao razlika između parcijalnog pritiska ugljen dioksida arterijske i me&scaron;ane venske krvi. Vrednost SOFA skora određivana je u vremenu T0 i nakon 48 časova (T48). Pacijenti su za potrebe analize podeljeni u dve grupe na osnovu promene SOFA skora [(1) pacijenti kod kojih je do&scaron;lo do smanjenja SOFA skora (delta SOFA &lt; 0); (2) pacijenti kod kojih je smanjenje SOFA skora izostalo (delta SOFA &ge; 0)] i na osnovu vrednosti Pv-aCO2 u vremenu T6 [(1) pacijenti sa visokim Pv-aCO2 (&ge; 0.8 kPa); (2) pacijenti sa normalnim Pv-aCO2 (&lt; 0.8 kPa)]. Između dve grupe pacijenata, sa normalnim i visokim Pv-aCO2, statistički značajne razlike uočene su samo u odnosu na najvi&scaron;u vrednost respiratorne komponente SOFA skora (p=0.01). Uočena je statistički značajna korelacija između vrednosti Pv-aCO2 i laktata u vremenu T6 (r=0.2), Pv-aCO2 i ScvO2 u vremenu T0 (r=-0.4) i T12 (r=-0.24) kao i laktata i ScvO2 u vremenu T0 (r=-0.26) i T12 (r=-0.18). Analizom ponavljanih merenja nije utvrđena statistički značajna korelacija između promene vrednosti Pv-aCO2 unutar prvih 6 sati s promenom SOFA skora unutar prvih 48 sati nakon početka rane ciljane terapije (p=0.12). Utvrđeno je da su vrednosti Pv-aCO2 u vremenu T6 bile lo&scaron; prediktor smrtnog ishoda. Nisu utvrđene statistički značajne razlike u dužini boravka u intenzivnoj jedinici i ishodu lečenja u zavisnosti od vrednosti Pv-aCO2.</p> / <p>Central venous-arterial CO2 difference (Pv-aCO2) reflects adequacy of microcirculatory venous flow. Widening of Pv-aCO2 due to CO2-stagnant phenomenon is described in the low flow states. Pv-aCO2 was proposed as an additional resuscitation target for patients with septic shock.The aim of this study was to examine correlation between changes in Pv-aCO2 and SOFA score as well as different blood flow indices (lactate, mixed venous oxygen saturation) 12 hours after onset of resuscitation in patients with sepsis or septic shock. Secondary aim was to evaluate association of delta CO2 6 hours after onset of resuscitation and patient outcomes (length of stay in the ICU, mortality). Prospective observational study included 150 patients with sepsis. Simultaneous measurements of lactate, mixed venous oxygen saturation (ScvO2) and delta PCO2 were performed at onset of resuscitation (T0) and after 6 hours (T6). Delta PCO2 was calculated as a difference between arterial PCO2 and PCO2 from mixed venous blood. Organ dysfunction was evaluated with the Sequential Organ Failure Assessment (SOFA) score at T0 and after 48 hours (T48). Mortality was assessed after 28 days. For data analysis purposes two groups were created based on delta SOFA [(1) patients with SOFA score decrease (delta SOFA &lt;0); (2) patients without SOFA score decrease (delta SOFA &ge; 0)] and based on Pv-aCO2 [(1) patients with high Pv-aCO2 (&ge;0.8 kPa); (2) patients with normal Pv-aCO2 (&lt;0.8 kPa). Patients with high and normal Pv-aCO2 differed only with respect to highest respiratory SOFA score (p=0.01) Change in Pv-aCO2 between T0 and T6 was not in correlation with change in SOFA score between T0 and T48 (p=0.12). Moderate statistically significant correlation was found between Pv-aCO2 and lactate at T6 (r=0.2), and moderate inverse correlation between Pv-aCO2 and ScvO2 at T0 (r=-0.4) and T12 (r=-0.25) and ScvO2 and lactate at T0 (r=-0.27) and T12 (r=-0.18). Pv-aCO2 at T6 was not associated with 28-day mortality and length of stay in the ICU.</p>

<p>Brahiterapija visokim brzinama doze (HDR&ndash;BT) predstavlja efikasan modalitet zračenja kod pacijenata sa lokalizovanim karcinomom prostate (CaP) svih rizika. Za razliku od transkutane radioterapije i brahiterapije niskim brzinama doze (LDR&ndash;BT), kod ove grupe pacijenata u intersticijalnoj HDR&ndash;BT jo&scaron; uvek nisu jednoznačno definisane ukupne doze zračenja, način frakcionisanja kod pacijenata sa lokalizovanim CaP različitih rizika. U periodu od 2009&ndash;2018.god. HDR&ndash;BT kao jedinim načinom lečenja (monoterapija) u Op&scaron;toj bolnici Medicinski sistem Beograd, lečeno je 35 pacijenata (6 (17,1%) pacijenata niskog rizika, 21 (60%) pacijent srednjeg rizika i 8 (22,9%) pacijenata visokog rizika) sa lokalizovanim CaP različitih rizika od relapsa i progresije bolesti. Grupe pacijenata sa srednjim i visokim rizikom spojene su u jednu grupu (grupa sa vi&scaron;im rizikom). Tehnika sprovođenja HDR&ndash;BT, osim u pojedinačnim specifičnim detaljima, bila je slična kao i kod LDR&ndash;BT. Aplikacija igala, segmentacija, delineacija i planiranje HDR&ndash;BT vr&scaron;eno je kori&scaron;će&scaron;em transrektalnog ultrazvuka (TRUS) i izocetričnog radioskopskog C&ndash;luka, a zračenje je sprovedeno na uređaju Microselectron HDR sa zatvorenim radioaktivnim izvorom 192Ir početne aktivnosti 370 GBq. Aplikovane terapijske doze (TD), u opsegu od 30&ndash;57 Gy frakcionisane su u 3&ndash;4 nezavisne frakcije sa razmakom od 2&ndash;3 nedelje između frakcija, a individualizovane su prema nivou rizika, stanju organa u riziku (OAR) i kvalitetu aplikacije (indeksu prekrivanja CTV sa planiranom terapijskom dozom (CI100%) i mogućno&scaron;ću za&scaron;tite OAR). Uspe&scaron;nost terapije ocenjivana je postignutom biohemijskom kontrolom (BFS &ndash; biochemical&ndash;free&ndash;survival), prema ASTRO i Phoenix kriterijumima, kao i ukupnim preživljavanjem u periodu od 5 godina (2&ndash;9 godina) posle sprovedene terapije. U niskorizičnoj grupi pacijenata lečenih HDR&ndash;BT, BFS je postignuta kod svih pacijenata kao i ukupno preživljavanje. U grupi pacijenata sa vi&scaron;im rizikom BFS je postignuta kod 95,8% lečenih pacijenata, a ukupno 5&ndash;to godi&scaron;nje preživljavanje je 96,4%. BFS u ovom istraživanju se pokazala statistički značajnije bolja nego ona koju su prikazali drugi autori. Na osnovu rizika, nivoa PSA, TD i indeksa pokrivenosti CTV sa TD, izvr&scaron;eno je modelovanje terapijskih parametara kori&scaron;ćenjem MANN (multilauyer artificial neural network). Određena optimalna doza zračenja (TD) u HDR&ndash;BT lokalizovanog CaP niskog rizika je 40,7 Gy za CI100% = 1,01. Kod vi&scaron;ih rizika TD = 50,9 Gy za CI100% = 1,6. TD se frakcioni&scaron;e u 4 nezavisne frakcije sa razmakom od 2&ndash;3 nedelje. Ovakav izbor parametara HDR&ndash;BT (TD, CI100%, i način frakcionisanja), uz individualizaciju i kontrolu u toku svake aplikacije, obezbedio bi prihvatljiv nivo kasnih postiradijacionih komplikacija gradusa G1&ndash;G3 na uretri (&lt; 17% ukupnog broja lečenih pacijenata), uz minimimalne komplikacije na rektumu (pretežno G1&ndash;G2) i zanemarljive komplikacije na mokraćnoj be&scaron;ici.</p> / <p>High&ndash;dose rate brachytherapy (HDR&ndash;BT) is an effective therapy modality for patients with localized prostate cancer (CaP) of all risks. In contrast to an external beam radiotherapy and low&ndash;dose rate brachytherapy (LDR&ndash;BT), in these patients, the interstitial HDR&ndash;BT, the total radiation dose and fractionation is not unambiguously defined. Between 2009&ndash;2018 35 patients with localized CaP (6 (17.1%) low&ndash;risk patients, 21 (60%) patients medium&ndash;risk and 8 (22.9%) high&ndash;risk) were treated with HDR&ndash;BT, as the only treatment (monotherapy) in the General Hospital Medical System Belgrade. The group of patients with medium&ndash;risk and high&ndash;risk were merged into a single group (group with a higher&ndash;risk). Technique implementation of HDR&ndash;BT was similar as in the LDR&ndash;BT. Application of needles, segmentation, delineation, and planning of HDR&ndash;BT was performed with transrectal ultrasound (TRUS) and izocentrically mounted radioscopic C&ndash;arm. Irradiation was done on the Microselectron&ndash;HDR brachytherapy unit with a sealed radioactive source 192Ir (370 GBq). The dose (TD), in the range of 30&ndash;57 Gy was given fractionated in independent fractions (3&ndash;4) with a pause of 2&ndash;3 weeks between fractions. TD was individualized according to the risk, the conditions of organs at risk (OAR) and quality of the application (coverage index CI100%), as well as, the ability to protect OAR. Treatment result was evaluated by the achieved biochemical control (BFS &ndash; biochemical&ndash;free&ndash;survival) according to ASTRO and/or Phoenix criteria, as well as an overall survival in the period of 5 years (2&ndash;9 years) after the completion of the treatment. In the low&ndash;risk group, BFS has been achieved in all patients and overall survival rate is 100%. In the group of patients with higher risk BFS was achieved in 95.8% of treated patients, and 5&ndash;year survival rate was 96.4%. BFS in this study was proved to be statistically significantly better than showed by other authors. On the basis of the risk, the level of PSA, TD and CI100%, modeling was performed using the MANN (multilayer artificial neural network). The determined optimal dose TD for localized CaP of low risk is 40.7 Gy for CI100% = 1.0. At higher risk TD = 50.9 Gy for CI100% = 1.6. TD was given in 4 independent fractions with the interval of 2&ndash;3 weeks between each fraction. These HDR&ndash;BT parameters (TD, CI100%, and the fractionation scheme) with the individualization and control during each application would provide an acceptable level of late complications grade G1&ndash;G3 to the urethra (in less than 17% of treated patients), with minimum complications on the rectum (predominantly grade G1&ndash;G2) and insignificant complications rate on the urinary bladder.</p>

<p>Degenerativne bolesti kičme nastaju kao posledica promena na dinamičkim segmentima kičmenog stuba. Klinički ove promene se mogu manifestovati u vidu radikulopatije, mijelopatije i radikulomijelopatije. Najče&scaron;će primenjivana metoda operativnog lečenja kod ovih pacijenata je prednja cervikalna diskektomija sa fuzijom koja omogućava adekvatnu anatomsku i funkcionalnu restituciju degenerativno promenjene cervikalne kičme. Imajući u vidu da su već kompromitovane nervne strukture u riziku od dodatnih o&scaron;tećenja u različitim fazama operativnog zahvata primena intraoperativnog neurofiziolo&scaron;kog monitoringa je dobila svoje mesto i u hirur&scaron;kim tretmanima degenerativnih oboljenja kičme. Svrha primene neuromonitoringa je da obezbedi povratnu informaciju hirurgu o promenama u funkciji nervnih struktura pre nego &scaron;to dođe do ireverzibilnih o&scaron;tećenja. Na ovaj način moguće je prevenirati nastanak novog ili pogor&scaron;anje postojećeg deficita. Takođe intraoperativni nalazi neurofiziolo&scaron;kih parametara mogu da ukažu na težinu postojećeg oboljenja i da budu prediktori ishoda lečenja. Ciljevi ove doktorske disertacije bili su utvrđivanje faza operativnog zahvata u kojima najče&scaron;će dolazi do promena u neurofiziolo&scaron;kim parametrima, kao i postojanje korelacije nalaza intraoperativnog neurofiziolo&scaron;kog monitoringa sa preoperativnim kliničkim nalazom pacijenta kao i rezultatima procene ishoda nakon prednje cervikalne diskektomije se fuzijom. Ova studija je obuhvatila 30 pacijenata kod kojih je indikovano operativno lečenje degenerativnih promena u vratnom segmentu kičmenog stuba prednjom mikrodiskektomijom sa fuzijom. Preoperativno je izvođen klinički pregled pacijenata i kori&scaron;teni su Numerička skala bola i Upitnik za pacijente sa bolom u vratnoj kičmi, koji su takođe popunjavani na otpustu i mesec dana nakon operacije. U toku hirur&scaron;ke procedure upotrebom intraoperativnog neurofiziolo&scaron;kog monitoringa registrovani su somatosenzorni (SSEP) i motorni evocirani potencijali (MEP), kao i spontana elektromiografija. Kod svih SSEP do&scaron;lo je do statistički značajnog povećanja amplitude (p&lt;0,05), dok je kod desnog n. medianusa zabeleženo i statistički značajno skraćenje latence (p&lt;0,05). Značajne promene se beleže između početka i kraja operativnog zahvata, kao i u fazi uklanjanja intervertebralnog diska kada dolazi do dekompresije. U vrednostima pražne struje potrebne za dobijanje MEP nije bilo statistički značajnih promena izuzev kod m. triceps brachii obostrano. Kod pacijenata sa radikulopatijom vrednost pražne struje za dobijanje mi&scaron;ićnog odgovora je statistčki značajno niža u odnosu na pacijente sa mijelopatijom (p&lt;0,05). SSEP koreliraju sa poremećajem senzibiliteta, refleksnim odgovorom i bolom. MEP koreliraju takođe sa refleksnim odgovorom, dok negativna korelacija sa manuelnim mi&scaron;ićnim testom pokazuje da klinički očuvana gruba mi&scaron;ićna snaga ne mora biti pokazatelj pravog stanja motornog sistema. Preoperativne vrednosti NDI su se statistički značajno smanjile mesec dana nakon operacije (p&lt;0,05). U vrednostima bola postoji statistčki značajna razlika između svih merenje (p&lt;0,008), izuzev između bola na otpustu i mesec dana nakon operacije (p&gt;0,008). Latenca desnog n.medianusa pokazuje negativnu, a amplituda pozitivnu korelaciju sa vrednostima bola mesec dana postoperativno (p&lt;0,05). Povećanje amplitude i skraćenje latence SSEP ukazuje na značajan stepen dekompresije. Stabilnost MEP ukazuje na intraoperativnu očuvanost motornih puteva i da nije do&scaron;lo do novog motornog deficita niti produbljivanja postojećeg. SSEP i MEP koreliraju sa kliničkim nalazom, dok su vrednosti bola i NDI statistički značajno manje nakon operacije. Ovi rezultati ukazuju da klinički nalaz pacijenta korelira sa neurofiziolo&scaron;kim nalazom, kao i da introperativne promene neurofiziolo&scaron;kih parametara mogu biti prediktivni faktor ishoda operativnog lečenja.</p> / <p>Degenerative spinal diseases are consequence of spondylotic changes on dynamic segments of spinal column. These changes can result in different clinical appearances such as radiculopathy, myelopathy and radiculomyelopathy. The most common surgical procedure used in treatment of this group of patients is anterior cervical discectomy and fusion (ACDF) which can provide adequate anatomical and functional restitution of degenerative cervical spine. Considering the fact that already compromised neural structure can be additionally damaged in different stages of surgical procedure, use of intraoperative neurophysiological monitoring (IONM) has role in surgical treatment of degenerative spinal diseases. The aim of use of IONM is to provide real time feedback for surgeon regarding changes in function of neural structures before irreversible damage occurs. This is the way to prevent new neurological deficit from occurring or to prevent worsening of preexisting deficit. Results of intraoperative monitoring can additionally emphasize severity of disease and help in outcome assessment. The aim of this doctoral thesis was to determine phases of surgical procedure in which changes in neurophysiological parameters occurs most commonly. Another aim was to determine correlation between findings of intraoperative neurophysiological monitoring and clinical assessment and outcome prediction in patients treated with anterior cervical discectomy with fusion. Thirty patients who met inclusion criteria were enrolled in this study. All of them were treated surgically due to degenerative changes of cervical spine and ACDF were performed in all cases. Patients were thoroughly examined before surgery. Detailed neurological examination were performed together with Numeric pain rating scale (NPRS) and Neck Disability index (NDI) questionnaire. NPRS and NDI were applied on discharge from the hospital and one month after surgery. During surgery we registered somatosensory evoked potentials (SSEP), motor evoked potentials (MEP) and spontaneous elektromiography. In all SSEP there were statistically significant increase in amplitude (p&lt;0.05), while in the case of right n. medianus statistically significant shortening of the latency (p&lt;0.05) was recorded. Significant changes are recorded between beginning and the end of the surgical procedure, as well as in the phase of removing of the intervertebral disc when decompression occurs. In the threshold intensity needed to elicit the MEP there were no statistically significant changes except for m. triceps brachii bilaterally. In patients with radiculopathy, the value of the stimulus intensity needed for obtaining muscular response was statistically significantly lower in comparison with patients with myelopathy (p&lt;0.05). SSEP showed the best correlation with sensory disorder, tendon reflexes and pain. MEPs also correlate with tendon reflexes, while a negative correlation with a manual muscle strength testing results shows that clinically preserved muscle strength does not have to be reliable indicator of the motor system condition. Preoperative NDI values were statistically significantly reduced a month after surgery (p&lt;0.05). In pain values there is a statistically significant difference between all measurements (p&lt;0.008), except between pain on release and a month after surgery (p&gt;0.008). The right n.medianus latency shows a negative, and the amplitude shows positive correlation with pain values one month postoperatively (p&lt;0.05). Increasing amplitude and shortening latency of the SSEP indicates a significant degree of decompression. The stability of the MEP indicates the intraoperative preservation of motor pathways and absence of both new motor deficiency or worsening of the existing one. SSEP and MEP correlate with clinical findings, while pain and NDI values are statistically significantly less after surgery. These results indicate that clinical findings in the patients correlate with the neurophysiological findings. Results also points out that the intraoperative changes in neurophysiological parameters can be a predictive factor for the outcome of surgical treatment.</p>

<p>U savremenoj hirurgiji imperativ je da hirur&scaron;ka procedura bude efikasna, ali i da obezbedi kvalitetan i brz oporavak. Najbitniji segment operativnog lečenja je obezbediti maksimalan učinak kako bi se osobi omogućio brz i potpun povratak aktivnostima dnevnog života. Posebno je pojačano&nbsp;&nbsp; interesovanje za rekonstrukciju prednjeg ukr&scaron;tenog ligamenta kod mlađe i sporsko aktivne populacije. Trendovi u medicini kao i u ortopedskoj hirurgiji idu u pravcu smanjenja postoperativnog krvarenja, bola i skraćenja postoperativnog oporavka. Supstancija sa antifibrinolitičkim delovanjem, kao &scaron;to je traneksamična kiselina, svakako je na&scaron;la svoje mesto u smanjenju postoperativnog krvarenja. Ciljevi istraživanja su se odnosili na utvrđivanje uticaja lokalno aplikovane traneksamične kiseline tokom rekonstrukcije prednjeg ukr&scaron;tenog ligamenta kolena na postoperativno krvarenje, posmatrane laboratorijske parametre, mere obima kolena, učestalosti postoperativnih komplikacija i kvaliteta postoperativnog oporavka između dve grupe ispitanika (ispitivana i kontrolna grupa). Studija je bila eksprimentalnog karaktera i sprovedena je u Kliničkom centru Vojvodine u Novom Sadu uz odobrenje etičke komisije. U istraživanje, metodom slučajnog izbora, bila su uključena 124 ispitanika oba pola raspoređena u dve grupe (ispitivana i kontrolna), a kod kojih je indikovana operativno zbrinjavanje prekida prednjeg ukr&scaron;tenog ligamenta kolena i koji su dali pristanak da budu uključeni u studiju. Svi prikupljeni podaci su beleženi u protokol, koji je za ovo istraživanje posebno dizajniran. Ispitanici su bili podvrgnuti operativnom zahvatu, uz primenu op&scaron;te ili spinalne anestezije, sa postavljenom pneumatskom poveskom na operisanom ekstremitetu. Ispitivanoj grupi bilo je lokalno aplikovano 20 ml traneksamične kiseline, dok je u kontolnoj grupi na isti način aplikovano 20 ml NaCl 0,9 % rastvora. Postoperativni gubici krvi su praćeni i beleženi tokom 24 h od operacije, dok su laboratorijki nalazi uzorkovani preoperativno i sedmog postoperativnog dana. U posmatranom periodu (preoperativno, sedmog postoperativnog dana, treće i &scaron;este postoperativne nedelje) kod ispitanika je praćen obim kolena i pojava komplikacija (hematom, hemartroza). Nakon sprovedenog istraživanje, prikupljeni podaci su dokumentovani i statistički obrađeni. Rezultati istraživanja jasno ukazuju da postoji statistički značajna razlika (t=7.181, p&lt;0.001) u količni postoperativnog krvarenja između grupa. Prosečno postoperativno krvarenje u ispitivanoj grupi je bilo 71.29&plusmn;40.76 ml, u odnosu na kontrolnu grupu gde je postoperativno krvarenje iznosilo 154.35&plusmn;81.45 ml. U kontrolnoj grupi, postoperativno se beleže niže vrednosti hemoglobina (t=9.608, p&lt;0.001) i hematokrita (t=8.325, p&lt;0.001), i vi&scaron;e vrednosti trombocita (t=2.201, p=0.032) nego u ispitivanoj grupi. Podaci o postoperativnom bolu ispitanika govore u prilog statistički značajnoj razlici u jačini bola prve nedelje nakon operacije između ispitivane i kontrolne grupe (t=2.405, p=0.018) i treće nedelje nakon operacije (t=3.700, p&lt;0.001). U ispitivanoj grupi zabeležena je ređa pojava hematoma 6.45% (n=4), dok je u kontrolnoj grupi 19.35% (n=12). Svi pacijenti u uzorku su popunili upitnik o postoperativnom kvalitetu oporavka. Nije zabeležena statistički značajna razlika u kvalitetu postoperativnog oporavka nakon operacije između dve analizirane grupe ispitanika. Dobijeni rezultati o postoperativnom krvarenju, nakon aplikovane traneksamične kiseline, ukazuju na efikasnost leka i pri lokalnoj primeni tokom rekonstrukcije prednjeg ukr&scaron;tenog ligamenta kolena. S obzirom na insuficijentnost podataka, ovo ispitivanje stvara &scaron;iru osnovu za dalja istraživanja.</p> / <p>In modern surgery, we need an effective surgical procedure, which provides quality and rapid recovery. The most important segment of surgical treatment is to provide maximum impact to allow a person to return quickly and fully to the activities of daily living. There has been particular interest in the reconstruction of the anterior cruciate ligament in the younger and sport active population. Trends in medicine, as well as in orthopedic surgery, are heading towards reducing postoperative bleeding, pain, and postoperative recovery. A substance with antifibrinolytic activity, such as tranexamic acid, has certainly found its place in reducing postoperative bleeding. The objectives of the study were to determine the effect of locally applied tranexamic acid during the reconstruction of the anterior cruciate knee ligament on postoperative bleeding, observed laboratory parameters, measures of knee circumference, frequency of postoperative complications, and quality of postoperative recovery between the two groups of subjects (study and control group). The study was prospective, conducted at the Clinical Center of Vojvodina in Novi Sad with the approval of the ethics committee. The study, by random selection method, included 124 subjects of both sexes, divided into two groups (tested and control), which indicated operative management of the anterior cruciate ligament rupture and gave informed consent for inclusion in the study. All data collected were recorded in a protocol, which was specifically designed for this research. Subjects underwent surgery, with general or spinal anesthesia, with pneumatic attachment placed on the extremity undergoing surgery. The test group was given topically 20 ml of tranexamic acid, while the control group was administered 20 ml in the same way. NaCl 0.9% solution. Postoperative blood losses were monitored and recorded within 24 h of surgery, while laboratory findings were sampled preoperatively and on the seventh postoperative day. During the observed period (preoperatively, on the seventh postoperative day, on the third and sixth postoperative weeks), the knee volume and the occurrence of complications (hematoma, hemarthrosis) were monitored in the subjects. Following the survey, the data collected were documented and statistically processed. The study results indicate that there was a statistically significant difference (t = 7.181, p &lt;0.001) in the amount of postoperative bleeding between groups. The mean postoperative bleeding in the study group was 71.29 &plusmn; 40.76 ml, compared to the control group where postoperative bleeding was 154.35 &plusmn; 81.45ml. In the control group, lower hemoglobin values (t = 9.608, p &lt;0.001) and hematocrit (t = 8.325, p &lt;0.001) were observed postoperatively, and higher platelet counts (t = 2.201, p = 0.032) than in the study group. The data on the postoperative pain of the respondents support a statistically significant difference in the severity of pain on the first week after surgery between the study and the control group (t = 2.405, p = 0.018) and the third week after surgery (t = 3.700, p &lt;0.001). In the study group, the incidence of hematoma was less than 6.45% (n = 4), while in the control group it was 19.35% (n = 12). All patients in the sample completed a questionnaire on postoperative quality of recovery. There was no statistically significant difference in the quality of postoperative recovery after surgery between the two analyzed groups of subjects. The results of post-operative bleeding, after administrated tranexamic acid, indicate the efficacy of the drug and at a local application during the reconstruction of the anterior cruciate ligament. Due to the insufficiency of data, this study creates a broad basis for further research.</p>

<p>Ciljevi: Cilj ove studije je da ispita bezbednost rane karotidne endarterektomije (CEA) u odnosu na odložene CEA nakon akutnog ishemijskog neurolo&scaron;kog deficita (TIA/CVI). Drugi cilj je da istražimo da li postoji razlika u brzini neurolo&scaron;kog oporavka između navedenih grupa. Metode: Ukupno 157 ispitanika u prospektivnoj studiji je praćeno 30 dana postoperativno. Grupa I ili rana CEA, je imala 50 ispitanika operisanih od 3. do 14. dana po TIA/CVI događaju. Grupa II ili odložena CEA, je imala 107 ispitanika operisanih od 15. do 180. dana nakon TIA/CVI. Praćen je proceduralni op&scaron;ti i specifični morbiditet i mortalitet u 30-dnevnom postoperativnom periodu. Rankin skor (mRS) smo koristili za procenu neurolo&scaron;kog invaliditeta. U odnosu na vrednost mRS skora smo formirali dve podgrupe mRS&lt;3 i mRS3. U statističkoj analizi koristili smo Pirsonov hi test, Studentov test, ANOVU analizu varijanse, Boniferonijev test i multiplu analizu varijanse za ponovljena merenja (GLM- general line model), kao i parametarsku i neparametarsku korelaciju i regresiju. Nivo značajnosti je bio 0,05. Rezultati: Prosečna starost ispitanika je bila 66,72 godine uz 66,2% osoba mu&scaron;kog pola. U grupi I je prosečno vreme do intervencije bilo 9,5 dana, a u grupi II 72,22 dana. Grupe su homogene u odnosu na faktore rizika i komorbiditet. Grupa I je imala 54% nestabilnih aterosklerotskih plakova u poređenju sa grupom II gde ih je bilo 31,8% (&chi;2 = 7.084; p &lt; 0.01). U grupi I TIA je imalo 50% ispitanika, a u grupi II CVI nalaza je bilo 68,2% (&chi;2 =4.825; p &lt;0.05). CVI do 1 cm veličine je statistički značajno vi&scaron;e zastupljen u grupi I , a CVI do 2 cm u grupi II (&chi;2 = 6.913; p &lt;0.05). Stopa CVI je u grupi I bila 2.0% a u grupi II je 2.8% (F = 0.083; p &gt; 0.05). Stopa postoperativnog infarkta miokarda (IM) je u grupi I je 2.0% a u grupi II je 1.9%. Stopa specifičnog hirur&scaron;kog morbiditeta je u grupi I 4.0% a u grupi II 3.7%. U grupi I ukupni morbiditet bio 6.0% a u grupi II 7.5%, razlika nije bila statistički značajna (F =0.921; p &gt; 0.05). Mortaliteta u obe grupe nije bilo. CVI/IM/smrt stopa je u grupi I bio 4.0% a u grupi II je bio 4.7% (F = 0.122; p &gt;0.05). Hiperlipidemija je signifikantan faktor rizika za CVI/IM/smrt (&chi;2 = 4.083; p &lt; 0.05). Pobolj&scaron;anje mRS je u grupi I imalo 52%, a u grupi II 31,8% pacijenata (&chi;2 = 5.903; p &lt;0.01). Relativni rizik je 2,4 odnosno toliko puta je veća &scaron;ansa da kod bolesnika dođe do promene mRS ako je bolesnik u grupi I. Pad mRS koji nastupa između trećeg i desetog dana nakon CEA je statistički visoko značajno izraženiji u grupi ranih CEA ( F 3,701 df 1 p=0,029). Kod bolesnika sa TIA u preko 60% slučajeva do&scaron;lo je do pada mRS, a kod onih koji su imali CVI u oko 25.5% (&chi;2 = 18.050; p &lt; 0.01). Kod Rankin skora podgrupe mRS&lt;3 i mRS3 je pad bio značajan i po vremenu (F 18,774; df 6; p=0,000) i po podgrupi ali je daleko brži pad zapažen u podgrupi mRS&lt;3(F 6,010; df 1; p=0,003). Zaključak: Rana CEA je jednako bezbedna kao i odložena CEA u pogledu incidence perioperativnog morbiditeta i mortaliteta. Ranom CEA se postiže znatno brži neurolo&scaron;ki oporavak pacijenata, naročito onih sa TIA i mRS&lt;3 skorom.</p> / <p>Objectives: The aim of this study was to investigate the safety of early carotid endarterectomy (CEA) in relation to the delayed CEA after acute ischemic neurological events (TIA / CVI). The second objective was to investigate whether there is a difference in speed of neurological recovery between these groups. Methods: A total of 157 patients in the prospective study followed 30 days postoperatively. Group I or early CEA, had 50 patients operated from 3 to 14 days after TIA / CVI event. Group II or delayed CEA, had 107 patients operated from 15 to 180 days after the TIA / CVI. Accompanied by the general and specific procedural morbidity and mortality in 30-day postoperative folow up. Rankin score (mRS) were used for evaluation of neurologic disability. In relation to the value of mRS score we formed two subgroups mRS &lt;3 i mRS3. In the statistical analysis we used the Pearson chi test, Student&#39;s test, ANOVA analysis of variance, Boniferony test and multiple analysis of variance for repeated measures (GLM- general line model), as well parametric and nonparametric correlation and regression. The significance level was 0.05. Results: The mean age was 66.72 years with 66.2% of males. In Group I is the average time to intervention was 9.5 days, and in group II 72.22 days. The groups were homogeneous in relation to risk factors and comorbidities. Group I had 54% of unstable atherosclerotic plaques compared with group II, where it was 31.8% (&chi;2 = 7.084; p &lt;0.01). In the group I TIA had 50% of respondents, while in group II CVI was 68.2% (&chi;2 = 4.825; p &lt;0.05). CVI to 1 cm in size were significantly more frequent in the group I, a CVI to 2 cm in group II (&chi;2 = 6.913; p &lt;0.05). CVI rate in the group I was 2.0%, and in group II was 2.8% (F = 0.083, p&gt; 0.05). Postoperative myocardial infarction (MI) in the group I is 2.0%, and in group II was 1.9%. Specific surgical morbidity rate in the group I and 4.0% in the group II 3.7%. In group I total morbidity was 6.0% in group II 7.5%, the difference was not statistically significant (F = 0.921; p&gt; 0.05). Mortality in both groups was not. CVI/IM/death rate in group I was 4.0% in group II was 4.7% (F = 0.122; p&gt; 0.05). Hyperlipidemia is a significant risk factor for CVI/IM/death (&chi;2 = 4.083; p&lt;0.05). Improving mRS in the group I had 52% and in group II 31.8% of patients (&chi;2 = 5.903; p &lt;0.01). The relative risk was 2.4 times as much and is more likely to occur in patients mRS changes if the patient in group I. Improving mRS that occurs between the third and tenth days after CEA was highly statistically significantly greater in the group of early CEA (F 3,701 df 1 p = 0.029). In patients with TIA in 60% of cases there was a decline mRS, and those had CVI in about 25.5% (&chi;2 = 18.050; p &lt;0.01). In Rankin score subgroups mRS &lt;3 i mRS 3 the decline was significant and time (F 18,774; df 6; p =0.000) and in the subgroup but it is far more rapid decline observed in the subgroup mRS &lt;3 (F 6.010; df 1; p = 0.003). Conclusions: Early CEA is as safe as the delayed CEA in respect incidence of perioperative morbidity and mortality. Early CEA is achieved significantly faster recovery of neurological patients, especially those with TIA and mRS &lt;3 compared with delayed CEA.</p>

<p>Uvod: Stratifikacija rizika je postala integralna komponenta savremenog pristupa tretmanu u kliničkoj praksi. Danas se u dijagnostici i lečenju akutnog infarkta miokarda (AIM) koriste različiti skorovi rizika kao prognostički instrumenti za kratkoročan i dugoročan ishod bolesti. Nužni proceduralni procesi, u toku primarne perkutane koronarne intervencije (pPKI), kao i saznanja o distribuciji i vrstama lezija koronarnih arterija su od velikog značaja, te se preporučuje finalna evaluacija rizika neposredno nakon izvr&scaron;ene pPKI. Metode istraživanja podataka omogućavaju pronalaženje skrivenih obrazaca u podacima, otkrivanje njihovih uzročno-posledičnih veza I odnosa, te razvoj savremenih prediktivnih modela. Cilj: Kreiranje i testiranje jednostavnog, praktičnog i u svakodnevnoj praksi upotrebljivog prediktivnog modela za procenu intra-hospitalnog ishoda lečenja pacijenata obolelih od AIM sa ST-elevacijom (STEMI) lečenih pPKI. Metode: Istraživanje je unicentrična, retrospektivna, ali I prospektivna studija. U retrospektivnu studiju je uključeno 1495 pacijenta sa STEMI koji su lečeni na Klinici za kardiologiju Instituta za kardiovaskularne bolesti Vojvodine (IKVBV) kod kojih je u cilju rekanalizacije infarktne arterije izvr&scaron;ena pPKI, u periodu od decembra 2008. godine do decembra 2011. godine. Svaki pacijent je inicijalno predstavljen sa 629 obeležja sadržanih u postojećem IKVBV informacionom sistemu, koja čine demografske karakteristike, podaci iz anamneze i kliničkog nalaza, parametri biohemijskih analiza krvi priprijemu, parametri ehokardiografskog pregleda, angiografski i proceduralni detalji i &scaron;ifre prijemnih dijagnoza. U svrhu istraživanja podataka kori&scaron;ćeno je programsko re&scaron;enje otvorenog koda Weka. Tokom evaluacije različitih algoritama izabran je algoritam koji daje najbolje rezultate po tačnosti predikcije i ROC parametru. U sklopu retrospektivnog dela izvr&scaron;ena je validacija prediktivnog modela&nbsp; desetostrukom unakrsnom validacijom na celom skupu podataka. Prospektivnom studijom je na uzorku od 400 pacijenata sa STEMI lečenih pPKI u toku 2015. godine izvr&scaron;ena dodatna validacija razvijenog prediktivnog modela. Za iste pacijente je izračunavat i GRACE skor rizika, te je upoređena njegova, i prediktivna moć razvijenog modela. Rezultati: Alternativno stablo odluke (ADTree) izdvojen je kao algoritam sa najboljim performansama u odnosu na ostale evaluirane algoritme. Cost sensitive klasifikacija je kori&scaron;ćena kao dodatna metodologija da bi se pojačala tačnost. ADTree stablo odluke izdvojilo je osam ključnih parametara koji najvi&scaron;e utiču na ishod intra-hospitalnog lečenja: sistolni krvni pritisak pri prijemu, ejekciona frakcija leve komore, udarni volumen leve komore, troponin, kreatinin fosfokinaza, ukupni bilirubin, T talas i<br />rezultat intervencije. Performanse razvijenog modela su: tačnost predikcije je 93.17%, ROC 0.94. Razvijeni model je na prospektivnoj validaciji zadržao performanse: tačnost predikcije 90.75%, ROC 0.93. &Scaron;iroko kori&scaron;ćeni GRACE skor je na prospektivnom skupu postigao ROC=0.86, &scaron;to pokazuje da je razvijeni prediktivni model superiorniji u odnosu na njega. Zaključak: Razvijeni prediktivni model je jednostavan i pouzdan. Njegova implementacija u svakodnevnu kliničku praksu, omogućila bi kliničarima da izdvoje visokorizične pacijente, nakon reperfuzionog tretmana, a potom kod njih intenziviraju tretman i kliničko praćenje, a sa ciljem smanjenja incidence intra-hospitalnih komplikacija i povećanja njihovog preživljavanja.</p> / <p>Introduction: Risk stratification has become an integral component of modern treatment in clinical practice. Today, the diagnosis and treatment of acute myocardial infarction (AMI) use different risk scores as a prognostic instruments for short-term and long-term outcome of the disease. The necessary procedural processes during primary percutaneous coronary intervention (pPCI) as well as knowledge about the distribution and types of lesions in coronary arteries are of great importance, and a final risk evaluation is recommended directly after the pPCI. Methods of data mining allow finding hidden patterns in data, disclosure of their causal connections and relationships, and the development of modern predictive models. Aim: To create and test a simple, practical and usable predictive model in daily practice for the&nbsp; assessment of intrahospital treatment outcome of patients with AMI with STsegment elevation (STEMI) treated with pPCI. Methods: Presented research is unicentric, retrospective but also prospective study. Retrospective study included 1495 patients with STEMI who were admitted to the Clinics of cardiology of the Institute of Cardiovascular Diseases Vojvodina (IKVBV). For the purpose of recanalization of the infarct artery, pPCI has been performed to these patients during the period from December 2008 to December 2011. Each patient was initially described with 629 attributes from the existing information system of IKVBV. Those attributes consist of demographic characteristics, data from history and clinical findings, biochemical parameters of blood tests on admission, the echocardiographic parameters, angiographic and procedural details and admission diagnosis codes. For model development, an open source software solution Weka was used. During the evaluation of different algorithms, algorithm that gives the best results in terms of accuracy and ROC parameter was chosen. As part of the retrospective study, in order to assess the models performance, ten-fold cross-validation on the entire data set was used. A prospective study, on a sample of 400 patients with STEMI, treated with pPCI in 2015, performed additional validation of the developed predictive model. GRACE risk score was calculated for the prospective study patients and comparison with the developed model has been performed. Results: Alternative decision tree (ADTree) was isolated as an algorithm with the best performance in relation to other algorithms evaluated. Cost sensitive classification was used as an additional methodology to enhance accuracy. ADTree selected eight key parameters that most influence the outcome of intra-hospital treatment: systolic blood pressure on admission, left ventricular ejection fraction, stroke volume of the left ventricle, troponin, creatine phosphokinase, total bilirubin, T wave and the result of the intervention. The performance of the developed model are: the accuracy of the prediction is 93.17%, ROC 0.94. The developed model kept its performance in prospective validation: accuracy of prediction 90.75%, ROC 0.93. Widely used GRACE score achieved ROC = 0.86 in the prospective study patients, indicating that developed predictive model is superior to him. Conclusion: Developed predictive model is simple and reliable. Its implementation in everyday clinical practice, would allow clinicians to distinguish high-risk patients after reperfusion treatment, and then for them to intensify treatment and clinical follow-up, with an aim of reducing the incidence of intra-hospital complications and increase their survival.</p>

<p>Uvod: Infertilitet pogađa 10-15% parova reproduktivnog doba. Vanetesna oplodnja (VTO) je najefikasniji vid tret-mana infertiliteta, ali uprkos značajnom napretku stopa uspeha VTO u proseku iznosi oko 30% po ciklusu. Glavnim razlogom neuspeha smatra se neadekvatan kvalitet embriona, dok se pretpostavlja da u 10-20% slučajeva razlog neuspeha leži u neadekvatnoj receptivnosti uterusa. Na osnovu inicijalnih istraživanja histeroskopija, koja predstvalja zlatni standard u dijagnostici i tretmanu patologije kavuma uterusa, se često izvodi u svakodnevnoj kliničkoj praksi kako bi se povećala uspe&scaron;nost VTO. Uprkos &scaron;irokoj primeni i dalje ne postoji dovoljno kvalitetnih dokaza o realnoj ulozi histeroskopije na ishod VTO kako kod patolo&scaron;kih stanja kavuma tako i rutinski, pre prvog ili rekurentnog poku&scaron;aja VTO. Cilj disertacije bio je da se utvrdi uticaj sprovođenja histeroskopije na ishod VTO, ustanovi učestalost prethodno neprepoznate patologije kavuma uterusa, kao i da se ispitaju stavovi pacijenata o primeni rutinske histeroskopije pred VTO. Materijal i metode: Istraživanje je sprovedeno u Kliničkom centru Vojvodine, u formi prospektivne studije u dve sukcesivne etape od 01.01.2015. do 01.04.2017. U prvoj etapi poređen je ishod VTO kod pacijentkinja kojima pred postupak VTO nije sprovedena histeroskopija (Grupa A), pacijentkinja kod kojih je dobijen uredan nalaz histeroskopije pred postupak VTO (Grupa B) i pacijentkinja gde je pred postupak VTO dobijen patolo&scaron;ki nalaz kavuma na histeroskopiji koji je u istom aktu tertian (Grupa C). Druga etapa istraživanja predstavljala je randomiziranu kontrolisanu studiju (RCT &ndash; randomised controlled trial). Nakon verifikacije urednog ultrazvučnog nalaza pred prvi postupak VTO, pacijentkinje su randomizirane u Grupu A2 kojima pred postupak VTO nije sprovedena histeroskopija i Grupu B2 kojima je pred postupak VTO sprovedena rutinska histeroskopija. Statistička analiza sprovedena je upotrebom odgovarajućeg softvera (JMP Ver. 9). Poređeni su podaci o osnovnim karakteristikama pacijenata, toka i ishoda ciklusa VTO. Primarni parametar ishoda bila je stopa kliničke trudnoće po embriotransferu. Pored analize ishoda primarno konstruisanih grupa, urađena je analiza i naknadno konstruisanih subgrupa, kao i predikcioni model uspeha VTO baziran na logističkoj regresiji. Rezultati: Studija je uključila 253 pacijentkinje (52 pacijentkinja iz Grupe A, 50 iz Grupe B, 50 iz Grupe C, 51 iz Grupe A2 i 50 iz Grupe B2). Nije postojala statistički značajna razlika u karakteristikama pacijentkinja, parametrima ovarijalne rezerve, broju dobijenih jajnih ćelija ni drugim parametrima toka postupka VTO među posmatranim grupama. U prvoj etapi istraživanja dobijena je statistički značajno (p=0,013) veća stopa kliničkih trudnoća kod pacijentkinja kojima je pred postupak VTO sprovedena histeroskopija - 50 % za Grupu B i 42% za grupu C u odnosu na 30,77% kod pacijentkinja bez histeroskopije (Grupa A), bez statistički značajne razlike među histeroskopskim grupama. U drugoj etapi istraživanja stopa kliničkih trudnoća prilikom upotrebe rutinske histeroskopije pred prvu VTO (Grupa B2) iznosila je 46% naspram 31,37% kod pacijentkinja bez histeroskopije pred prvu VTO (Grupa A2), iako uočena razlika nije dostigla statističku značajnost (p =0,089), uz relativan rizik (RR) za ostvarivanje kliničke trudnoće nakon primene histeoskopije uiznosio od 1,47 (95% CI 0,88-2,43) (p=0,13). Analizon subgrupa kod 100 pacijentkinja sa rutinski sprovedenom histeroskopijom pred VTO i 103 pacijentkinje bez histeroskopije pred VTO, dobijena je statistički značajnao veća stopa kliničkih trudnoća (48% naspram 31,07%, istim redom), uz RR od 1,54 (95% CI 1,08-2,20) (p=0,013), kao i stopa tekućih trudnoća od RR 1,49 (CI 1,01-2,19) (p= 0,039). Analiza ukupnog uticaja izvođenja histeroskopije pred VTO dobila je statistički značanjno veću stopu kliničkih trudnoća po ET za grupu histeroskopije uz RR 1,48 (CI 1,06-2,07) (p=0,017). Histeroskopijom je nakon urednog ultrazvučnog nalaza ustanovljeno postojanje patolo&scaron;kog nalaza kod 34,65% pacijenata i to 22,7% major patologije i 11,88% minor patologije kavuma. Nije postojala statistički značajna razlika u uspehu VTO u odnosu na sam nalaz histeroskopije. 98,67% pacijenata podržalo je rutinsku upotrebu histeroskopije pred prvi postupak VTO, dok je 83% pacijenata podržavlo rutinsku upotrebu histeroskopije pred svaki postupak VTO. U finalnom predikcionom modelu se uz AUC od 0,748 jedino postojanje visokokvalitetnog embriona uz odnos &scaron;ansi (OR) 7,91 (95% CI 1,80-56,06; p=0,0047), transfer blastociste uz OR 3,80 (95% CI 1,90-7,98; p=0,0001) i izvođenje histeroskopije pred VTO uz OR 2,13 (95% CI 1,14-4,08, p=0,0169) pokazalo statistički značajnim prediktorima trudnoće. Diskusija: Studija je dobila pozitivan uticaj histeroskopije na ishod postupka VTO, iskazan pre svega povećanjem stope kliničkih trudnoća nakon sprovođenja histeroskopije (bilo da je na histeroskopiji nađen uredan ili patolo&scaron;ki nalaz). Dodatna prednost histeroskopije predstavljala je i i detekcija prethodno nepropoznate patologije kavuma. Umeren efekat na ukupno pobolj&scaron;anje stope kliničkih trudnoća prilikom rutinskog sprovođenja histeroskopije pred prvu VTO, koji je statističku značajnost dostigao tek analizom subgrupa u skladu je sa nalazima novijih dobro dizajniranih studija koji donekle limitiraju nekritičku upotrebu histeroskopije. Biolo&scaron;ko obja&scaron;njenje potencijalnog pozitivnog uticaja histeroskopije najverovatnije leži u detekciji i tretmanu prethodno nepropoznate patologije kavuma, olak&scaron;avanju procedure embriotransfera, kao i humoralnim i molekularnim promenama koje nastaju u endometrijumu kao posledica odgovarajuće histeroskopske traume a koji su u dosa&scaron;anjim istraživanjima apostrofirani kao faktori koji mogu povećati receptivnost uterusa. Zaključak: Histeroskopija je efikasna, bezbedna i visoko prihvatljiva procedura koja dovodi do povećanja uspeha VTO u standardnim kliničkim indikacijama (prethodnog neuspelog postupka VTO i sumnje na patolo&scaron;ki nalaz kavuma uterusa) bilo da se na samoj histeroskopiji nađe uredan ili patolo&scaron;ki nalaz. Rutinska primena histeroskopije pred prvi postupak VTO se na osnovu rezultata studije ne može smatrati apsolutno opravdanom usled statistički nedovoljno značajnog povećanja stope kliničke trudnoće. Uzev&scaron;i u obzir visoku prihvatljivost od strane pacijenata i najverovatniji pozitivan efekat na stopu trudnoće primena rutinske histeroskopije pred prvu VTO bila bi opravdana ukoliko se implementira koncept ambulantne histeroskopije.</p> / <p>Introduction: Infertility affects 10-15% of all couples. In vitro fertilisation (IVF) is the most effective method of infertility treatment, but despite a significant improvement, success rate of IVF is still around 30% per cycle. The main reason for the IVF failure is inadequate embryo quality, but in 10-20% of cases the cause of IVF failure lies in impaired uterine receptivity. Based on earlier studies hysteroscopy, gold standard in the diagnosis and treatment of uterine cavity pathology, is often performed to increase IVF success. Despite its wide use, there is lack of high quality evidence regarding real contribution of hysteroscopy on IVF outcome in situations of uterine cavity pathology or routinely prior to first IVF or after recurrent implantation failure. The aim of this dissertation was to determine the influence of performing hysteroscopy on IVF outcome, as well as the incidence of previously unrecognized uterine pathology, and to examine patient&#39;s attitudes about performing routine hysteroscopy prior to IVF. Material and methods: The research was conducted in a prospective manner in two successive stages at Clinical Center of Vojvodina from 01.01.2015. until 01.04.2017. During first stage of the study IVF outcome was compared between patients who did not have a hysteroscopy prior to IVF (group A), patients with normal hysteroscopic finding prior to the IVF (Group B) and patients with abnormal hysteroscopic findings prior to IVF which was treated at the same time (Group C). The second stage of the study was a randomized controlled trial (RCT). After verification of normal ultrasound findings prior to the first IVF, patients were randomized to group A2 in who me hysteroscopy was not performed and group B2 who had routine hysteroscopy prior to first IVF. Statistical analysis was carried out using the appropriate statistical software (JMP Ver. 9). Patient characteristics, course and outcome of IVF cycle were compared between groups. The primary outcome was clinical pregnancy rate (CPR) per embryotransfer. In addition to analyzing the IVF outcomes in primarily defined groups, subgroup analysis was also performed, as well as IVF success pre-diction model based on logistic regression. Results: The study included 253 patients (52 patients in Group A, 50 in Group B, 50 in Group C, 51 in Group A2 and 50 in Group B2). There was no statistically significant difference in patient characteristics, ovarian reserve parameters, number of retrieved oocytes, or other relevant parameters of IVF course between the observed groups. In the first stage of the study there was statistically significant (p = 0.013) higher clinical pregnancy rate in patients who had a hysteroscopy before IVF - 50% for Group B and 42% for group C versus 30,77 % in patients without hysteroscopy before IVF (Group A), without statistically significant difference between hysteroscopic groups. In the second stage of the study, routine hysteroscopy prior to first IVF (Group B2) led to clinical pregnancy rate 46% versus 31.37% in patients without hysteroscopy prior to first IVF (Group A2), although without statistical significance (p = 0.089. Relative risk (RR) for achieving clinical pregnancy after performing hysteroscopy was 1.47 (95% CI 0.88-2.43) (p = 0.13). Subgroup analysis of 100 patients with routinely performed hysteroscopy before IVF and 103 patients without hysteroscopy prior to the IVF showed statistically significant higher rates of clinical pregnancies (48% versus 31.07%, in the same order), with RR of 1.54 (95% CI 1.08-2.20), (p = 0.013), and for ongoing pregnancies RR was 1.49 (95% CI 1.01-2.19) (p = 0.039). Overall effect of performing hysteroscopy prior to IVF resulted in a statistically significant increase in the clinical pregnancy with RR 1.48 (95% CI 1.06-2.07) (p = 0.017). After normal ultrasound finding hysteroscopy revealed 34.65% of pathological finding, 22.7% of major and 11.88% of minor pathology of the cavity). There was no statistically significant difference in IVF outcome based on hysteroscopy findings. 98.67% of patients supported the routine use of hysteroscopy before the first IVF procedure, while 83% of patients supported the routine use of the hysteroscopy before every IVF procedure. In the final prediction model, with the AUC of 0.748, only the presence of high quality embryos with odds ratio (OR) 7,91 (95% CI 1,80-56,06; p=0,0047), blastocyst transfer with OR 3,80 (95% CI 1,90-7,98; p=0,0001) and performing hysteroscopy prior to IVF with OR 2,13 (95% CI 1,14-4,08, p=0,0169) proved to be statistically significant predictors of pregnancy. Discussion: The study shoved a positive influence of hysteroscopy on the IVF outcome by increasing clinical pregnancy rate after performing hysteroscopy (whether hysteroscopy revealed normal or pathological finding). Additional benefit of hysteroscopy was detection of previously unrecognized uterine pathology. A moderate effect on the overall improvement in clinical pregnancy rate with use of routine hysteroscopy, which reached statistical significance only by subgroup analysis, is in line with findings of recent well designed studies that somewhat limit the noncritical use of hysteroscopy. A biological explanation of the potential positive effect of hysteroscopy is most likely due to detection and treatment of the previously unrecognized uterine pathology, facilitating embryotransfer procedure, as well as the humoral and molecular changes that occur in the endometrium as a consequence of the hysteroscopic trauma. Those changes were hypothesized as factors that can increase uterine receptivity by numerous research. Conclusion: Hysteroscopy is an effective, safe and highly acceptable procedure that increases IVF success when performed for accepted clinical indications (previous IVF failures, pathological findings of uterine cavity), whether hysteroscopy reveals normal or pathological finding. The routine use of hysteroscopy prior to first IVF based on this study can not be considered justified since increase in clinical pregnancy rate did not reach statistical significance. Given the high acceptance of this concept by the patients and moderate but probable positive effect on IVF outcome, implementation of routine hysteroscopy prior to first VTO would be justified only in office hysteroscopy setting.</p>

<p>Moždani udar predstavlja drugi uzrok smrti u celom svetu i neurolo&scaron;ku bolest sa najvećim stepenom invaliditeta. Za povoljan ishod moždanog udara veoma je važno sprečavanje i lečenje somatskih kompikacija (SK), pri čemu je njihova učestalost i značaj za oporavak pacijenata potcenjena, a uticaj na ishod moždanog udara zanemaren. Ciljevi istraživanja su bili da se utvrdi učestalost pacijenata sa somatskim komplikacijama u akutnoj fazi moždanog udara; zatim da se utvrdi učestalost svake pojedinačne somatske komplikacije: pneumonije, urinarnih infekcija, duboke venske tromboze, tromboembolije pluća, dijarealnog sindroma i akutnog koronarnog sindroma; zatim da se utvrde faktori rizika za nastanak svake pojedinačne SK, kao i da se utvrdi uticaj SK na ishod bolesti - iskazan kroz njihovu povezanost sa funkcionalnim statusom, dužinom hospitalizacije i mortalitetom pacijenata. Istraživanje je sprovedeno kao prospektivno i obuhvatilo je 403 pacijenta hospitalizovanih zbog akutnog moždanog udara na Klinici za neurologiju Kliničkog centra Vojvodine u periodu od godinu dana. Pacijenti su podeljeni u dve grupe, gde su prvu grupu sačinjavali pacijenti sa registrovanom jednom ili vi&scaron;e somatskih komplikacija (n = 162), a drugu su činili pacijenti koji nisu imali somatske komplikacije (n = 241). Evaluacija pacijenata obuhvatila je registrovanje sociodemografskih karakteristika, ličnu i porodičnu anamnezu, karakteristike moždanog udara, neurolo&scaron;ki status na prijemu i otpustu, funkcionalni status na prijemu i otpustu, laboratorijske analize krvi i urina na prijemu, vrstu i vreme nastanka pojedinačne somatske komplikacije, sve relevantne dijagnostičke metode za postavljenje dijagnoze i definisanje potencijalnih faktora rizika. Somatske komplikacije se če&scaron;će javljaju kod starijih osoba, prosečne starosti 72,9 godina, kod osoba ženskog pola i kod pacijenata sa hemoragijskim moždanim udarom. Somatske komplikacije registrovane su kod 40,2% pacijenata, pri tome urinarnu infekciju imalo je 20,3% pacijenata, pneumoniju 16,3%, infarkt miokarda 4,7%, plućnu tromboemboliju 3,4%, duboku vensku trombozu 2,4% i dijarealni sindrom 2,9% pacijenata. Nezavisni prediktori pneumonije su disfagija, naru&scaron;eno stanje svesti, hronična opstruktivna bolest pluća, mRS veći od 3. Prediktori urinarnih infekcija su: podatak o rekurentnim urinarnim infekcijama, ženski pol, starost preko 70 godina, mRS veći od 3 i NIHSS skor veći od 16. Kao nezavisni prediktori plućnog tromboembolizma dobijeni su duboka venska tromboza, naru&scaron;eno stanje svesti i gojaznost, dok se jedinim nezavisnim prediktorom dijarealnog sindroma pokazala starost pacijenta preko 70 godina. Prediktori akutnog koronarnog sindroma su: starost veća od 70 godina i hemoragijski moždani udar. Pacijenti sa SK, na kraju hospitalnog lečenja imaju značajno lo&scaron;iji funkcionalni status u odnosu na pacijente bez somatskih komplikacija. Somatske komplikacije statistički značajno produžavaju hospitalizaciju. Kod četvrtine pacijenata (25,9%) sa somatskim komplikacijama u akutnoj fazi moždanog udara registrovan je letalni ishod. Najveći procenat smrtnih ishoda kod pacijenata sa somatskim komplikacijama registrovan je kod pacijenata sa infarktom miokarda (63,2%), a najmanji kod pacijenata sa urinarnom infekcijom (18,3%).</p> / <p>Stroke is the second cause of death worldwide and neurological disease with the highest level of disability. For a favorable outcome of stroke, the prevention and treatment of somatic complications are of great importance, while their frequency and the importance of the recovery of patients are underestimated, and the influence on the outcome of stroke is neglected. The aims of the study were: to determine the frequency of patients with somatic complications in the acute phase of stroke; to determine the frequency of each somatic complication: pneumonia, urinary infections, deep venous thrombosis, lung thromboembolism, diarrheal syndrome, and acute coronary syndrome; to identify risk factors for the emergence of each somatic complication, as well as to determine the effect of those complications on the outcome of the disease - expressed through their association with the functional status, length of hospitalization and mortality of patients. The study was conducted as a prospective and included 403 patients hospitalized due to acute stroke at the Clinic for Neurology of the Clinical Center of Vojvodina for a period of one year. Patients were divided into two groups; the first group included patients with one or more somatic complications registered (n = 162), and the second group consisted of patients without any somatic complication (n = 241). Patient evaluation included registration of socio-demographic characteristics, personal and family history, stroke characteristics, neurological and functional status at the time of admission and discharge, laboratory analysis of blood and urine at admission, type and time of emergence of each somatic complication, all relevant diagnostic methods for setting diagnosis and defining potential risk factors. Somatic complications are more common in older people (the average age of 72.9 years) in females and in patients with hemorrhagic stroke. Somatic complications were reported in 40.2% of patients, 20.3% of patients had urinary infection, 16.3% pneumonia, 4.7% myocardial infarction, 3.4% pulmonary thromboembolism, deep venous thrombosis 2.4% and diarrheal syndrome 2.9% of patients. Independent predictors of pneumonia were dysphagia, impaired state of consciousness, chronic obstructive pulmonary disease, mRS higher than 3. Predictors of urinary infections were: data on recurrent urinary tract infections, female sex, age over 70 years, mRS higher than 3 and NIHSS score higher than 16. As independent predictors of pulmonary thromboembolism, deep venous thrombosis, impaired state of consciousness and obesity were obtained, while the only independent predictor of diarrheal syndrome proved to be the age of the patient over 70 years. Predictors of acute coronary syndrome were: age over 70 years and haemorrhagic stroke. Patients with somatic complications at the end of hospital treatment had significantly worse functional status compared to patients without somatic complications. Somatic complications statistically significantly prolong hospitalization. A quarter of patients (25.9%) with somatic complications in the acute phase of the stroke had a lethal outcome. The highest percentage of deaths in patients with somatic complications was registered in patients with myocardial infarction (63.2%) and the lowest was registered in patients with urinary tract infections (18.3%).</p>