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ABCG2 and SLCO1B1 gene polymorphisms in the Croatian population
No full textBackground: Organic anion-transporting polypeptide 1B1 (OATP1B1) and the ATP-binding cassette subfamily G member 2, ABCG2, are important transporters involved in the transport of endogenous substrates and xenobiotics, including drugs. Genetic polymorphisms of these transporters have effect on transporter activity. There is significant interethnic variability in the frequency of allele variants.
Aim: To determined allele and genotype frequencies of ABCG2 and SLCO1B1 genes in Croatian populations of European descent. Subjects and methods: A total of 905 subjects (482 women) were included. Genotyping for ABCG2 c.421C> A (rs2231142) and for SLCO1B1 c.521T> C (rs4149056), was performed by real-time polymerase chain reaction (PCR) using TaqManVR DME Genotyping Assays.
Results: For ABCG2 c.421C> A, the frequency of CC, CA and AA genotypes was 81.4%, 17.8% and 0.8% respectively. The frequency of variant ABCG2 421 A allele was 9.7%. For SLCO1B1 c.521T> C, the frequency of TT, TC and CC genotypes was 61.7%, 34.8% and 3.5% respectively. The frequency of variant SLCO1B1 521 C allele was 20.9%.
Conclusion: The frequency of the ABCG2 and SLCO1B1 allelic variants and genotypes in the Croatian population is in accordance with other European populations. Pharmacogenetic analysis can serve to individualise drug therapy and minimise the risk of developing adverse drug reactions
Long-Term Outcome of Differentiated Thyroid Cancer Patients—Fifty Years of Croatian Thyroid Disease Referral Centre Experience
No full textBackground: Indolent nature but a high incidence of differentiated thyroid cancer (DTC) remains a challenge for optimizing patient care. Therefore, prognostic factors present valuable information for determining an adequate clinical approach. Methods: This study assessed prognostic features of 1167 papillary (PTC) and 215 follicular (FTC) thyroid cancer patients that had undergone surgery between 1962 and 2012, and were followed-up up to 50 years in a single institution, till April 2020. Age, gender, tumor size, presence of local and distant metastases at presentation, extrathyroidal extension, disease recurrence, and cancer-specific survival were evaluated. Results: In multivariate analysis, factors affecting the worse outcome were age (p = 0.005), tumor size (p = 0.006), and distant metastases (p = 0.001) in PTC, while extrathyroidal extension (p < 0.001), neck recurrence (p = 0.002), and distant metastases (p < 0.001) in FTC patients. Loco-regional recurrence rate was 6% for PTC and 4.7% for FTC patients, while distant metastases were detected in 4.2% PTC and 14.4% of FTC patients. The 10-year cancer-specific survival rates for PTC and FTC were 98.6% and 89.8%, respectively (p < 0.001). Conclusions: Negative prognostic factors, besides distant metastases, were older age and greater tumor size in PTC, and extrathyroidal extension and neck recurrence in FTC patients. The recurrence and mortality rates were very low
Tarsal tunnel syndrome
No full textSindrom tarzalnog tunela (STT) relativno je rijetka kompresivna mononeuropatija donjih ekstremiteta uzrokovana kompresijom tibijalnog živca ili njegovih ogranaka (medijalnog ili lateralnog plantarnog živca) u području tarzalnog kanala. Pripada skupini kanalikularnih sindroma, a iako puno rjeđi, može se smatrati ekvivalentnim sindromu karpalnog tunela. Klinički se očituje pojavom boli, poglavito u medijalnom dijelu tabana te žarenjem i trncima u području prva tri prsta stopala. Uz kliničku procjenu, za dijagnosticiranje ove neuropatije najčešće se koriste elektrodijagnostičke pretrage – elektroneurografija (ENG) i elektromiografija (EMG), te ultrazvučna pretraga. Liječenje STT-a može biti konzervativno i kirurško. Konzervativno liječenje preporučuje se bolesnicima s lakšim do umjerenim tegobama, dok se kirurško liječenje provodi u bolesnika s težim oštećenjima. Cilj je ovog preglednog rada prikazati novije spoznaje vezane za STT s naglaskom na potvrdu kliničke dijagnoze najčešće korištenim dijagnostičkim pretragama kao što su elektroneurografija (ENG) i elektromiografija (EMG) te ultrazvučni pregled.Tarsal tunnel syndrome (TTS) is relatively rare compressive mononeuropathy of lower extremities caused by compression of tibial nerve and its associated branches (medial and lateral plantar nerve) in tarsal tunnel. It is one of canalicular sindromes, although much less common, and is equivalent of carpal tunnel syndrome. Clinically it is presented with pain in medial foot aspect, numbness and parestesia in the first three toes. Beside clinical assessement, diagnosis of this neuropathy is made by the use of electrodiagnostic procedures of neurography (ENG) and electromiography (EMG) and diagnostic ultrasound imaging. The management of tarsal tunnel syndrome can be conservative or operative. Patients with light to moderate simptoms are treated conservatively while those with severe damage undergo operative treatment. The aim of this systematic narrative review is to scrutinize the literature to date of TTS with emphasis on clinical diagnosis validation via neurography (ENG) and electromiography (EMG), and diagnostic ultrasound
Povezanost kliničkih karakteristika i morfoloških parametara s rupturom aneurizme prednje komunikacijske arterije
No full textWe analyzed aneurysm morphology, demographic and clinical characteristics in patients with anterior communicating artery (ACoA) aneurysms to investigate the risk factors contributing to aneurysm rupture. A total of 219 patients with ACoA aneurysms were admitted to our hospital between January 2016 and December 2020, and morphological and clinical characteristics were analysed retrospectively in 153 patients (112 ruptured and 41 unruptured). Medical records were reviewed to obtain demographic and clinical data on age, gender, presence of hemorrhage, history of hypertension, diabetes, heart disease, and kidney disease. Morphological parameters examined on 3-dimensional digital subtraction angiography included aneurysm size, neck diameter, aspect ratio, size ratio, bottleneck ratio, height/width ratio, aneurysm angle, (in)flow angle, branching angle, number of aneurysms per patient, shape of the aneurysm, aneurysm wall morphology, variation of the A1 segment, and direction of the aneurysm. Male gender, aspect ratio, height/width ratio, non-spherical and irregular shape were associated with higher odds of rupture, whilst controlled hypertension was associated with lower odds of rupture, when tested using univariate logistic regression model. In multivariate model, controlled hypertension, presence of multiple aneurysms, and larger neck diameter reduced the odds of rupture, while irregular wall morphology increased the risk of rupture. Regulated hypertension represented a significant protective factor from ACoA aneurysm rupture. We found that ACoA aneurysms in male patients and those with greater aspect ratios and height/width ratios, larger aneurysm angles, presence of daughter sacs and irregular and non-spherical shapes were at a higher risk of rupture.Analizirali smo morfologiju aneurizme, demografske i kliničke karakteristike u bolesnika s aneurizmom prednje komunikacijske arterije (ACoA) kako bismo istražili čimbenike rizika koji doprinose rupturi aneurizme. Ukupno je 219 bolesnika s aneurizmom ACoA primljeno u našu bolnicu u razdoblju od siječnja 2016. do prosinca 2020. godine, a morfološke i kliničke karakteristike analizirane su retrospektivno u 153 bolesnika (112 puknutih i 41 neprekinuta). Pregledani su medicinski zapisi kako bi se dobili demografski i klinički podaci za dob, spol, prisutnost krvarenja, povijest hipertenzije, dijabetes, srčane bolesti i bolesti bubrega. Morfološki parametri ispitani na trodimenzionalnoj digitalnoj subtrakcijskoj angiografiji uključivali su veličinu aneurizme, promjer vrata, odnos između normalne visine aneurizme i širine vrata aneurizme (aspect ratio), odnos između visine aneurizme i prosječnog promjera svih krvnih žila povezanih s aneurizmom (size ratio), odnos između širine fundusa aneurizme i širine vrata aneurizme (bottleneck ratio), odnos između najveće normalne visine aneurizme i širine aneurizme (height/width ratio), kut aneurizme, ugao ulaska tijeka krvne struje u fundus aneurizme (inflow angle), kut grananja, broj aneurizma po bolesniku, oblik aneurizme, morfologiju stijenke aneurizme, varijaciju segmenta A1 i smjer aneurizme. Muški spol, odnos između normalne visine aneurizme i širine vrata aneurizme, odnos između najveće normalne visine aneurizme i širine aneurizme, nesferičan i nepravilan oblik bili su povezani s većim izgledima za puknuće, dok je kontrolirana hipertenzija bila povezana s manjom vjerojatnosti puknuća kada je testirano primjenom modela s univarijatnom logističkom regresijom. U multivarijatnom modelu su kontrolirana hipertenzija, prisutnost više aneurizma i veći promjer vrata smanjili izglede za puknuće, dok je nepravilna morfologija stijenke povećala rizik od puknuća. Regulirana hipertenzija predstavlja značajan zaštitni čimbenik od pucanja aneurizme ACoA. Utvrdili smo da su aneurizme ACoA u muških bolesnika i one s većim odnosom između normalne visine aneurizme i širine vrata aneurizme te one s većim odnosom između najveće normalne visine aneurizme i širine aneurizme, većim kutovima aneurizme, prisutnošću kćeri vrećica te nepravilnim i nesferičnim oblicima u većem riziku od puknuća
Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality
No full textBackground and Purpose: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year.
Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020).
Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths.
Conclusions: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT
Rinogeni meningitis uzrokovan kongenitalnim kolesteatomom apeksa piramide: simultano kirurško liječenje transotičkim i transsfenoidnim pristupom
No full textA 66-year-old male patient was admitted due to high fever, severe headaches and disturbance of consciousness. Meningitis was confirmed by lumbar puncture and intravenous antimicrobial therapy was started. Since he had undergone radical tympanomastoidectomy 15 years before, otogenic meningitis was suspected, so the patient was referred to our department. Clinically, the patient manifested watery discharge from the right nostril. Microbiological analysis verified Staphylococcus aureus in a cerebrospinal fluid (CSF) sample acquired by lumbar puncture. Radiological work-up, including computed tomography and magnetic resonance imaging scans, showed an expanding lesion of the petrous apex of the right temporal bone disrupting the posterior bony wall of the right sphenoid sinus with radiological characteristics indicating cholesteatoma. Those findings confirmed rhinogenic meningitis caused by expansion of the petrous apex congenital cholesteatoma into the sphenoid sinus, allowing nasal bacteria to enter the cranial cavity. The cholesteatoma was removed completely by the simultaneous transotic and transsphenoidal approach. Since the right labyrinth was already non-functional, there was no surgical morbidity after labyrinthectomy. The facial nerve remained preserved and intact. The transsphenoidal approach enabled removal of the sphenoid portion of the cholesteatoma and two surgeons met together at the level of the retrocarotid segment of the cholesteatoma, completely removing the lesion. This case represents an extremely rare condition in which a petrous apex congenital cholesteatoma expanded through the petrous apex to the sphenoid sinus, causing CSF rhinorrhea and rhinogenic meningitis. According to available literature, this is the first case of petrous apex congenital cholesteatoma causing rhinogenic meningitis successfully treated with the simultaneous transotic and transsphenoidal approach.Bolesnik u dobi od 66 godina primljen je zbog visoke temperature, jake glavobolje i poremećaja svijesti. Lumbalna punkcija potvrdila je meningitis i započeta je intravenska antibiotska terapija. Budući da je 15 godina ranije kod bolesnika rađena radikalna timpanomastoidektomija, postavljena je sumnja na otogeni meningitis te je upućen na našu Kliniku. Nakon primitka je uočena desnostrana rinolikvoreja, a ponovljenom lumbalnom punkcijom u likvoru je izoliran Staphylococcus aureus. Radiološka obrada uključujući kompjutoriziranu tomografiju i magnetsku rezonancu pokazala je ekspanzivnu leziju vrha piramide desne temporalne kosti s destrukcijom stražnje stijenke sfenoidnog sinusa i radiomorfološkim osobinama kolesteatoma. Ovi nalazi potvrdili su da se radi o rinogenom meningitisu koji je uzrokovan širenjem kongenitalnog kolesteatoma vrha piramide u sfenoidni sinus, što je omogućilo prodor bakterija iz nosa u endokranij. Kolesteatom je u cijelosti odstranjen simultanim kombiniranim transotičkim i transsfenoidnim pristupom. Budući da je desni labirint od ranije bio nefunkcionalan, nije bilo kirurškog morbiditeta nakon labirintektomije. Očuvani su integritet i funkcija ličnog živca. Transsfenoidni pristup omogućio je odstranjenje sfenoidnog dijela kolesteatoma, a oba operatera susrela su se na razini retrokarotidnog segmenta kolesteatoma koji je tako odstranjen u cijelosti. Ovaj bolesnik predstavlja iznimno rijedak slučaj kod kojega se kongenitalni kolesteatom vrha piramide proširio u sfenoidni sinus uzrokujući rinolikvoreju i rinogeni meningitis. Prema dostupnoj literaturi, ovo je prvi takav slučaj koji je ujedno uspješno liječen simultanim transotičkim i transsfenoidnim pristupom
Prediktori seksualnog zadovoljstva: internacionalna studija
No full textThe aim of this cross-cultural study was to examine predictors of sexual satisfaction. For the present analysis, we used a large-scale sample database that included 8821 individuals from 4 countries. All participants completed the same questionnaires, which were designed to capture numerous important variables that have been shown to correlate with sexual satisfaction. According to our results, predictors of sexual satisfaction were classified into four general categories (demographic factors, psychological factors, sociocultural factors, and pathophysiological factors). Our international study found statistically significantly higher satisfaction among homosexual participants, participants aged 18 to 23 years, those with a higher level of education, in a relationship, with a current sexual partner, in a current partnered (unmarried) relationship, and without a diagnosed sexual or mental disorder. At the same time, we found that the correlation between sexual satisfaction and the different predictors varied considerably across countries, which calls for further research.Cilj ove međukulturalne studije bio je ispitati prediktore seksualnog zadovoljstva općenito. Za ovu analizu koristili smo opsežnu bazu podataka uzorka koja uključuje 8821 pojedinca iz 4 zemlje. Svi su sudionici ispunili iste upitnike koji su bili osmišljeni kako bi obuhvatili brojne važne varijable za koje se pokazalo da koreliraju sa seksualnim zadovoljstvom. Prema našim rezultatima, prediktori seksualnog zadovoljstva klasificirani su u četiri opće kategorije (demografski čimbenici, psihološki čimbenici, sociokulturni čimbenici i patofiziološki čimbenici). Naše međunarodno istraživanje pokazalo je statistički značajno veće zadovoljstvo homoseksualnih sudionika, sudionika u dobi od 18 do 23 godine, s višom razinom obrazovanja, u vezi, sa sadašnjim seksualnim partnerom, u trenutnoj partnerskoj (nevjenčanoj) vezi i bez dijagnosticirane seksualne ili mentalni poremećaj. U isto vrijeme, otkrili smo da korelacija između seksualnog zadovoljstva i različitih prediktora znatno varira među zemljama, što zahtijeva daljnje istraživanje
Plućno krvarenje i glomerulonefritis s polumjesecima u pacijentu sa seropozitivnom antiglomerularnom bolesti bazne membrane i anti-neutrofilnim citoplazmičnim antitijelima
No full textAnti-glomerular basement membrane (anti-GBM) disease is an acute and life-threatening systemic autoimmune disorder. The coexistence of circulating anti-neutrophil cytoplasmic antibodies (ANCA) and anti-GBM disease, the so-called double-positive disease (DPD), is exceptionally rare. We report a unique case of DPD manifesting as pulmonary-renal syndrome (PRS) in a 46-year-old woman who first presented with clinical and radiological suspicion of pneumonia. Chest computed tomography scan later revealed bilateral alveolar hemorrhage. Kidney biopsy showed necrotizing crescentic (100% glomeruli) glomerulonephritis. On immunofluorescence microscopy, glomeruli were global linear positive for IgG, confirming anti-GBM disease. Double positivity was detected for circulating anti-myeloperoxidase ANCA (p-ANCA) and anti-GBM antibodies. Acute renal failure evolved rapidly. Therapeutic plasma exchange (TPE) and hemodialysis (HD) were initiated early in combination with intravenous pulse corticosteroid therapy followed by oral methylprednisolone and cyclophosphamide. Pulmonary hemorrhage resolved, but renal function could not be preserved. The patient remains HD dependent. This case report highlights that pulmonary symptomatology
may be the leading clinical presentation of PRS, with initially normal renal function at DPD onset. Early recognition and diagnosis are therefore crucial to timely clinical intervention. The role of prompt kidney biopsy and initiation of TPE and HD in PRS must not be underestimated.Bolest protiv glomerularne bazalne membrane (anti-GBM) je akutna i po život opasna sistemska autoimuna bolest. Pojava cirkulirajućih antitijela na citoplazmu granulocita (engl. anti-neutrophil cytoplasmic antibody, ANCA) u bolesnika sa anti-GBM glomerulonefritisom, tako zvana dvostruko pozitivna bolest (engl. double-positive disease, DPD), je vrlo rijetka. Prikazujemo 46 godišnju bolesnicu u koje je prvo klinički i radiološki postavljena sumnja na upalu pluća, a koja se kasnije manifestirala sa pulmo-renalnim sindromom (PRS) odnosno DPD. Kompjutorskom tomografijom pluća dokazano je alveolarno krvarenje. Biopsijom bubrega dokazan je nekrotizirajući glomerulonefritis (100 % glomerula). Imunoflorescencija je pokazala pozitivne linearne IgG depozite, što odgovara anti-GBM glomerulonefritisu. U bolesnice su dokazana antitijela na mijeloperoksidazu p-ANCA i antitijela na glomerularnu bazalnu membranu. Liječena je terapijskom izmjenom plazme (engl. therapeutic plasma exchange, TPE), hemodijalizom te kombinacijom parenteralne pulsne terapije kortikosteroidima, kasnije oralnom primjenom metilprednisolona i ciklofosfamida. Došlo je do regresije krvarenja u plućima ali se bubrežna funkcija nije oporavila, zbog čega smo nastavili s redovitim hemodijalizama. Ovaj prikaz bolesnice pokazuje kako u DPD, plućna simptomatologija može biti vodeći simptom PRS sa urednom bubrežnom funkcijom u početku. Rano prepoznavanja i dijagnoza su značajni za pravovremeni početak liječenja. Potrebno je naglasiti značaj rane biopsije bubrega, ranog početka TPE te po potrebi i nadomještanje bubrežne funkcije hemodijalizom
Operacijsko liječenje penetrirajuće rane mozga i pridružene perforirajuće ozljede oka uzrokovane metalnim objektom male brzine kretanja: prikaz slučaja i uvid u literaturu
No full textPenetrating traumatic brain injury accompanied by perforating ocular injury caused by low-velocity foreign bodies is a life-threatening condition, a surgical emergency and a major challenge in surgical practice, representing a severe subtype of non-missile traumatic brain injury, which is a relatively rare pathology among civilians. Optimal management of such an injury remains controversial, requiring full understanding of its pathophysiology and a multidisciplinary expert approach. Herein, we report a case of penetrating brain and associated perforating eye injury and discuss relevant literature providing further insight into this demanding complex multi-organ injury. We present a case of 39-year-old male patient with transorbital penetrating brain and perforating ocular injury undergoing emergency surgery to remove a retained sharp metallic object from the left parietal lobe. Following appropriate and urgent diagnostics, a decompressive left-sided fronto-temporo-parietal craniectomy was immediately performed. A retained sharp metallic object (a slice of a round saw) was successfully removed, while primary left globe repair and palpebral and fornix reconstruction were performed afterwards by an ophthalmologist. A prophylactic administration of broad-spectrum antibiotics was applied to prevent infectious complications. Early postoperative recovery was uneventful. The patient was discharged on day 45 post-injury having moderate right-sided motor weakness, ipsilateral facial nerve central palsy, and light motoric dysphasia. The vision to his left eye was completely and permanently lost. In conclusion, management of non-missile transorbital penetrating brain injury can be satisfactory when proper clinical and radiologic evaluation, and amply, less radical surgical approach is performed early. A multidisciplinary routine is a prerequisite in achieving a favorable management outcome.Penetrirajuća ozljeda mozga i pridružena perforirajuća ozljeda oka uzrokovana stranim tijelima male brzine kretanja po život je opasno, hitno kirurško stanje koje predstavlja veliki izazov u kirurškoj opskrbi, kao i tešku podvrstu mirnodopske ozljede mozga, koja je relativno rijetka u civilnoj populaciji. Optimalno liječenje ovakve ozljede i nadalje je dvojbeno te zahtijeva potpuno razumijevanje patofiziologije njezinog razvoja, kao i multidisciplinarni ekspertni pristup. U ovom radu donosimo prikaz slučaja penetrirajuće ozljede mozga i pridružene perforirajuće ozljede oka te uvid u recentnu literaturu, kako bi podrobno raspravili o ovoj zahtjevnoj i složenoj višeorganskoj ozljedi. Muškarac u dobi od 39 godina zadobio je transorbitalnu penetrirajuću ozljedu mozga i perforirajuću okularnu ozljedu zbog čega je podvrgnut hitnom kirurškom liječenju kako bi se uklonilo oštar metalni objekt zaostalo u području lijevog tjemenog režnja. Nakon provedene žurne dijagnostike, odmah je učinjena dekompresijska ljevostrana fronto-temporo-parijetalna karniektomija te je uspješno uklonjeno zaostalo metalno strano tijelo (odsječak cirkularne pile), nakon čega je po oftalmologu učinjena primarna opskrba ozljede lijeve očne jabučice i rekonstrukcija vjeđa i forniksa kroz slojeve lijevo. Profilaktička primjena antibiotika širokoga spektra provedena je kako bi se spriječio nastanak infekcijskih komplikacija. Rani poslijeoperacijski oporavak bio je zadovoljavajući. Bolesnik je otpušten iz bolnice 45. dan nakon ozljede s umjerenom motoričkom slabošću desnih udova, istostranom centralnom facioparezom i blagom motoričkom disfazijom. Vid na lijevome oku trajno je i potpuno izgubljen. Zaključujemo kako liječenje mirnodopske transorbitalne penetrirajuće ozljede mozga može biti uspješno ako je provedena pravodobna primjerena klinička i radiološka provjera i ako je primijenjen ogovarajući manje radikalan rani kirurški pristup. Multidisciplinarna opskrba preduvjet je postizanju povoljnog učinka liječenja