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Acute Occlusion of the Infarct-Related Artery as a Predictor of Very Long-Term Mortality in Patients with Acute Myocardial Infarction
Aim. The survey’s aim was to examine the significance of infarct-related artery (IRA) occlusion (verified angiographically) on very long-term outcomes of patients with acute myocardial infarction, within the STEMI and NSTEMI diagnosis. Methods. A single-center, nonrandomized, registry-based study on patients treated for acute coronary syndrome with percutaneous coronary intervention between June 2011 and December 2016 was conducted. Patients with angiographically proven IRA occlusion (100% stenosis with TIMI flow 0 distal to occlusion) were categorized as occlusive myocardial infarction (OMI) and patients with patent IRA (50–99% stenosis with TIMI 1–3 flow) were categorized as nonocclusive myocardial infarction (NOMI) and very long-term outcomes were analyzed. Data were collected prospectively from the hospital’s PCI registry and the database of the Croatian Institute of Public Health. Results. A total of 2450 patients were included in the study. 796 (32.5%) patients had NOMI and 1654 patients (67.5%) had OMI. According to ECG changes, 1534 patients presented with STEMI (62,6%) and 916 with NSTEMI (37,8%). 88% of STEMI patients presented with OMI and 12% with NOMI, while patients with NSTEMI in 33,8% presented with OMI and in 66,81% with NOMI. A median follow-up was 4.7 years. There was no significant difference in cardiovascular mortality between the groups (14.8% vs 13.1%; OMI vs NOMI, respectively; p = 0.374) neither in all-cause mortality (19% vs 21.5%; OMI vs NOMI, respectively; p = 0.374). Patients with NSTEMI had a significantly higher very long-term mortality (21.6% vs 18.1%; NSTEMI vs STEMI, respectively; p = 0.029). Conclusion. )e main findings of the study are as follows: (1) total IRA occlusion was not associated with higher long-term mortality; (2) NSTEMI was associated with a higher mortality rate compared with STEMI, independent of angiographic presentation (OMI/NOMI); (3) IRA occlusion was not associated with significantly higher mortality rates in patients with STEMI and NSTEMI, respectively
Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience
Background: Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it’s use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed.
Methods: Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan–Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Results: Sixty-nine patients who had persistent PSA (≥0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58–106 months, range, 8–106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41–72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0–4.6, p=0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0–4.6, p=0.04), frst postoperative PSA (HR 1.02, 95% CI 1.0–1.04, p=0.03), and concomitant ADT (HR 3.3, 95% CI 1.2–8.6, p=0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37–6.74, p=0.006) and concomitant ADT (HR 4.41, 95% CI 1.6–12.12, p=0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03–1.12, p=0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26–9.6,p=0.02), extracapsular extension (HR 7.02, 95% CI 1.96–25.07, p=0.003), and surgical margin status (HR 2.86, 95% CI 1.03–7.97, p=0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00–1.08, p=0.02) and extracapsular extension (HR 4.24, 95% CI 1.08–16.55, p=0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity.
Conclusions: In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radio therapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations
Spondiloartritis kasnoga početka
Upalne reumatske bolesti u osoba starije životne dobi pokazuju određene specifičnosti u pogledu kliničke slike i pridruženih komorbiditeta, što može utjecati na njihovo dijagnosticiranje i terapijske odluke. Početak spondiloartritisa (SpA) u starijih osoba smatra se rijetkom pojavom, ali sve je više radova koji pokazuju njegovu veću pojavnost, što je povezano i s produljenjem životne dobi. Spektar je kliničkih manifestacija spondiloartritisa kasnoga početka (engl. late-onset SpA) raznolik, ali ipak postoje određena posebna obilježja u odnosu na bolest koja nastupa u mladoj dobi. Ta su obilježja najbolje proučena u aksijalnome spondiloartritisu/ankilozantnomu spondilitisu (AS), koji se uobičajeno pojavljuje u osoba mlađih od 40 do 45 godina, dok je nastup simptoma nakon 50. godine života rijetkost pa je dobna granica uvrštena i u novije klasifikacijske kriterije. Za ostale entitete SpA-a, uključivo psorijatični artritis (PsA), manje je podataka o kasnome početku, jer njihov nastup nije u toj mjeri povezan sa životnom dobi, iako i tu postoje određene spoznaje o obilježjima bolesti u tih bolesnika. Podatci o prevalenciji spondiloartritisa kasnoga početka nisu točno poznati, ali se pretpostavlja da bi ona mogla iznositi između 3 do 8% bolesnika
Global Impact of COVID-19 on Stroke Care and IV Thrombolysis
Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.
Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.
Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] −11.7 to −11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI −13.8 to −12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI −13.7 to −10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2–9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions.
Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months
Hibridni mikrokirurški i endovaskularni pristup u liječenju višestrukih moždanih aneurizmi: ilustrativni prikaz slučajeva i usporedba s podacima iz literature
Contemporary cerebral aneurysm treatment has advanced due to the expansion of microsurgical and endovascular techniques having different advantages and restraints. However, some aneurysms cannot be effectively treated by a single method alone due to their specific anatomy, location, complexity, and/or multiplicity. Subsequently, multiple aneurysms sometimes necessitate a hybrid strategy integrating both methods. The study aims were to discuss indications, possibilities, and challenges of a hybrid strategy in the decision making and treatment of multiple intracranial aneurysms. A single-institution illustrative case series of multiple intracranial aneurysm patients treated by a hybrid approach was analyzed and management outcome discussed and correlated with literature data. Following the treatment, both patients from our case series recovered well, having complete and stable aneurysmal occlusion with no relapse and no postoperative procedure-related complications or long-lasting neurological symptoms. In conclusion, a hybrid approach is advised as a treatment option for multiple cerebral aneurysms when a single modality is insufficient to bring satisfactory results. It may be a suitable and safe addition to an assortment of treatments pledging clinical improvement and enabling positive management outcome in patients with ruptured and non-ruptured multiple cerebralaneurysms.Suvremeno je liječenje cerebralnih aneurizmi uvelike napredovalo zahvaljujući ekspanziji mikrokirurških i endovaskularnih postupaka koji se odlikuju različitim podobnostima, ali i ograničenjima. Međutim, pojedine je aneurizme ponekad nemoguće uspješno liječiti samo jednom od metoda s obzirom na njihovu specifičnu anatomiju, lokalizaciju, složenost i/ili višestrukost. Upravo su višestruke aneurizme gdjekad podobne za hibridni pristup koji objedinjuje obje navedene metode. Namjera je ovoga rada raspraviti indikacije, mogućnosti i izazove hibridne strategije pri donošenju odluke o obliku liječenja višestrukih intrakranijskih aneurizmi. U radu prikazujemo analizu bolesnika s navedenim aneurizmama u kojih je primijenjen hibridni pristup i raspravljamo o rezultatima i ishodu liječenja uspoređujući ih s podacima iz literature. Oboje se je naših bolesnika uspješno oporavilo nakon provedenog liječenja, kad je nastupila potpuna i stabilna okluzija aneurizme bez znakova ponovne pojave aneurizme i bez komplikacija povezanih s provedenim postupkom, kao i bez trajnog neurološkog deficita. Zaključujemo kako je hibridni pristup preporučena opcija liječenja višestrukih moždanih aneurizmi u slučajevima kada je pojedinačna metoda liječenja nedostatna za osiguravanje zadovoljavajućih rezultata. Ovakav je pristup podoban i siguran kao alternativa rasponu drugih oblika liječenja usmjerenih ka kliničkom poboljšanju i pozitivnom ishodu u bolesnika s rupturiranim i nerupturiranim višestrukim moždanim aneurizmama
Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation: The GLORIA-AF registry
Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anti-coagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and 1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores 2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anti-coagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial
Povezanost polimorfizma apolipoproteina E i epilepsije u djece
Apolipoprotein E (APOE) plays an important role in lipid metabolism and is a proven risk factor for development of dementia and other neurodegenerative diseases. The aim of the study was to determine the possible connection between particular APOE alleles, blood lipid profile and different types of epilepsy in children. Alleles of the APOE gene, blood cholesterol (total, high density lipoprotein and low-density lipoprotein (LDL) cholesterol, and triglyceride levels were analyzed in blood samples of 111 children with epilepsy and 118 age- and sex-matched children without epilepsy. Distribution of APOE genotypes was the same in children of both groups. Significantly increased levels of total cholesterol and LDL cholesterol were found in control group (Z=3.49 and 3.52
respectively, p0.05). There were statistically significant differences in the levels of total cholesterol (Z=2.09; p<0.05) and LDL cholesterol (Z=2.05; p<0.05) according to the type of epilepsy in favor of symptomatic epilepsy. The study confirmed that there was no connection between APOE and type of epilepsy in children and showed the children with epilepsy to have lower total cholesterol and LDL cholesterol levels. Interestingly, this also held true for children with idiopathic epilepsy compared to those with symptomatic condition.Apolipoprotein E (APOE) ima veliku ulogu u metabolizmu lipida i dokazan je čimbenik rizika za razvoj demencije i drugih neurodegenerativnih bolesti. Cilj istraživanja bio je utvrditi moguću povezanost pojedinih alela APOE, profila lipida u krvi i različitih tipova epilepsije u djece. Aleli APOE, kolesterol u krvi (ukupni kolesterol, lipoproteini visoke gustoće i lipoproteini
niske gustoće (LDL)) te vrijednosti triglicerida analizirani su u uzorcima krvi kod 111 djece s epilepsijom i 118 djece podudarne dobi i spola bez epilepsije. Distribucija APOE genotipova bila je ista u djece obiju skupina. Značajno povišene razine ukupnog kolesterola i LDL kolesterola utvrđene su u kontrolnoj skupini (Z=3,49 odnosno 3,52, p0,05). Postojale su statistički značajne razlike u razinama ukupnog kolesterola (Z=2,09; p<0,05) i LDL kolesterola (Z=2,05; p<0,05) ovisno o vrsti epilepsije u korist simptomatske epilepsije. Studija je potvrdila da ne postoji povezanost između APOE i tipa epilepsije u djece te je pokazala da djeca s epilepsijom imaju niži ukupni kolesterol i LDL kolesterol, ali je nađeno da djeca koja imaju simptomatsku epilepsiju imaju veću koncentraciju ukupnog i LDL kolesterola u odnosu na one s idiopatskom epilepsijom
Mikrokirurško liječenje recidivirajućih intrakranijskih aneurizma nastalih nakon endovaskulanih postupaka: ilustrativni prikaz serije bolesnika i pregled literature
Microsurgical clipping and endovascular coiling are both effective management modalities for intracranial aneurysms, whereas recent procedures are mainly directed towards endovascular treatment because of its minimally invasive nature. However, such a treatment has been associated with a bigger risk of recurrent aneurysmal growth and re-bleeding urging a selection of optimal strategies to overcome these hazards. It seems that the most appropriate method of choice is microsurgical clipping, which is much more technically challenging due to recurrent aneurysm demanding configuration created by the initial coiling. Herein, we present an illustrative institutional case series of recurrent intracranial aneurysms following endovascular treatment, and discuss the controversies and benefits of their subsequent microsurgical management, based on our experience and on literature review. Considering the results reported in this paper, it seems that careful selective microsurgical neck clipping with/without aneurysmal sac resection and coil extraction remains the preferred management option for recurrent intracranial aneurysms, resulting in high obliteration rates, long-term occlusion stability, and low morbidity/mortality. In conclusion, to bring a satisfactory outcome, the multidisciplinary management of recurrent intracranial aneurysms after endovascular treatment should be adjusted to aneurysm morphology/size/location, and individualized according to patient needs.Mikrokirurški i endovaskularni postupci podjednako su uspješne metode liječenja intrakranijskih aneurizma. Ipak, u novije se vrijeme u njihovom liječenju sve više rabe različite endovaskularne metode zbog svoje minimalne invazivnosti. Međutim, ovi su terapijski postupci povezani s povećanim rizicima recidivirajućeg aneurizmatskog rasta i ponovne rupture, što pobuđuje potrebu odabira najpovoljnijih strategija za sprječavanje ovakvih rizika. Čini se kako je mikrokirurško selektivno postavljanje klipse na vrat recidivirajuće aneurizme najprikladnija metoda izbora, unatoč tomu što je tehnički izazovna zbog zahtjevnog oblika aneurizme nastalog uslijed prethodnog postavljanja zavojnica u aneurizmatsku vreću. Prikazujući ilustrativnu seriju bolesnika, u radu predstavljamo naša iskustva u liječenju recidivirajućih intrakranijskih aneurizma nastalih nakon endovaskularnog liječenja te raspravljamo prednosti i nedostatke naknadnog mikrokirurškog liječenja temeljem pregleda literature. U skladu s rezultatima ovoga rada, čini se kako je pažljivo mikrokirurško selektivno postavljanje klipse na vrat aneurizme s resekcijom aneurizmatske vreće i uklanjanjem zavojnica ili bez toga preporučena mogućnost liječenja recidivirajućih intrakranijskih aneurizma, koja osigurava visok stupanj obliteracije i dugoročnu stabilnost okluzije aneurizmatske vreće, kao i nisku razinu pobola i smrtnosti. Zaključujemo kako multidisciplinarno liječenje recidivirajućih intrakranijskih aneurizma nastalih nakon endovaskularnih postupaka treba biti prilagođeno obliku, veličini i smještaju aneurizme, kao i primjereno potrebama svakog pojedinog bolesnika
Human C2a and C6a iPSC lines and H9 ESC line have less efficient cardiomyogenesis than H1 ESC line: Beating enhances cardiac differentiation
Background: Human induced pluripotent stem cells (hiPSCs) need to be thoroughly characterized to exploit their potential advantages in various aspects of biomedicine. The aim of this study was to compare the efficiency of cardiomyogenesis of two hiPSCs and two human embryonic stem cell (hESC) lines by genetic living cardiomyocyte labeling. We also analyzed the influence of spontaneous beating on cardiac differentiation.
Methods: H1 and H9 hESC lines and C2a and C6a hiPSC lines were induced into in vitro directed cardiac differentiation. Cardiomyogenesis was evaluated by the analysis of cell cluster beating, cardiac protein expression by immunocytochemistry, ability of cells to generate calcium transients, and cardiomyocyte quantification by the myosin light chain 2v-enhanced green fluorescent protein gene construct delivered with a lentiviral vector.
Results: Differentiation of all cell lines yielded spontaneously beating cell clusters, indicating the presence of functional cardiomyocytes. After the cell dissociation, H1-hESC-derived cardiomyocytes exhibited spontaneous calcium transients, corresponding to autonomous electrical activity and displayed ability to transmit them between the cells. Differentiated hESC and hiPSC cells exhibited striated sarcomeres and expressed cardiac proteins sarcomeric a-actinin and cardiac troponin T. Cardiomyocytes were the most abundant in differentiated H1 hESC line (20% more than in other tested lines). In all stem cell lines, cardiomyocyte enrichment was greater in beating than in non-beating cell clusters, irrespective of cardiomyogenesis efficiency.
Conclusion: Although C2a and C6a hiPSC and H9 hESC lines exhibited efficient cardiomyogenesis, H1 hESC line yielded the greatest cardiomyocyte enrichment of all tested lines. Beating of cell clusters promotes cardiomyogenesis in tested hESCs and hiPSCs
Spontani nestanak nefunkcionalnog adenoma hipofize u mjesec dana: prikaz slučaja
Spontaneous resolution of nonfunctioning pituitary adenoma after hemorrhagic apoplexy is a rare clinical entity of unknown etiology and is defined as disappearance of a tumor with out any specific treatment. Here we present a 54-year-old male patient who presented with acute onset of severe headache, vomiting, photophobia, and sonophobia. He was referred to brain computed tomography, which showed a 16x12x16 mm tumor mass located in the sellar region with signs of hemorrhage. Endocrinologic evaluation was consistent with under-function of pituitary gonadotropic cells. Magnetic resonance imaging (MRI) performed ten days later was consistent with hemorrhagic apoplexy of the pituitary adenoma. The patient’s symptoms resolved after conservative treatment with dexamethasone, but he was scheduled for elective pituitary surgery. Preoperative MRI was performed one month after the first one and disclosed normal pituitary gland without any signs of adenoma. Our case is remarkable due to the fact that spontaneous remission of pituitary adenoma occurred within the first month, which is the shortest interval reported to date. Our case highlights the importance of conservative therapy as the first-line treatment for pituitary apoplexy in the absence of neurological impairment, since spontaneous remission may occur in a short time interval.Spontana regresija nefunkcionalnog adenoma hipofize nakon hemoragijske apopleksije je iznimno rijedak klinički entitet nepoznate etiologije, a definiran je kao nestanak tumora bez primijenjenog liječenja. Naš 54-godišnji bolesnik prezentirao se izrazito jakom, naglo nastalom glavoboljom, povraćanjem, fotofobijom i sonofobijom. Bolesnik je upućen na hitnu kompju toriziranu tomografiju mozga koja je pokazala selarnu tumorsku tvorbu 16x12x16 mm sa zonom krvarenja. Endokrinološki nalazi upućivali su na disfunkciju gonadotropnih stanica hipofize. Nakon deset dana učinjena je magnetska rezonanca (MR) kojom je potvrđena hemoragijska apopleksija adenoma hipofize. Simptomi su se povukli nakon primijenjene konzervativne terapije deksametazonom, ali je bolesnik zakazan za kiruršku resekciju adenoma. Prijeoperacijski MR učinjen mjesec dana nakon prvoga pokazao je normalnu hipofizu bez znakova adenoma. Posebnost našega slučaja je vrijeme manje od mjesec dana u kojem se dogodila spontana remisija, što je najkraće dosad opisano vrijeme u svjetskoj literaturi. Naš slučaj naglašava važnost konzervativne terapije kao prve terapijske linije kod apopleksije adenoma hipofize u bolesnika bez neuroloških deficita i to upravo zbog činjenice što je spontana remisija moguća u kratkom vremenskom intervalu nakon pojave samih simptoma