17 research outputs found
Thrombophilia and other conditions associated with acute forms of cardiovascular disease
Svjedoci smo sve cĢesĢcĢih slucĢajeva akutnih koronarnih sindroma u mlaÄih bolesnika, odnosno u bolesnika u kojih ne nalazimo prisutne tipicĢne preinacĢive ili nepreinacĢive cĢimbenike rizika. VecĢina studija definira mlaÄe pacijente kao osobe dobi do 45 godina. U takvih se bolesnika obicĢno dijagnosticira akutni infarkt miokarda (AIM) s normalnim koronarnim arterijama, odnosno koronarne arterije ne pokazuju intraluminalne nepravilnosti (stroga definicija) ili arterije s manjim stupnjem stenoze, ali hemodinamski bez znacĢenja (u vecĢini slucĢajeva < 30% stenoza). Nedavno objavljena studija (APPROACH) utvrdila je ucĢestalost akutnog infarkta miokarda s normalnim koronarnim arterijama u iznosu od 2,8% u bolesnika podvrgnutih koronarnoj angiografiji kod AIM-a. Diferencijalna dijagnoza takvih akutnih koronarnih zbivanja ukljucĢuje miokarditis, stres miokardiopatije i sindrom baloniranja vrsĢka lijeve klijetke. Ne postoji jedinstveno objasĢnjenje nastanka AIM-a s normalnim koronarnim arterijama, ali predlozĢeno je nekoliko mogucĢih mehanizama: latentna ateroskleroza, vazospazam, tromboza i hiperkoagulabilno stanje, embolizacija i upala. Postoje stecĢeni i nasljedni sindrom trombofilije.
U ovom cĢemo prikazu opisati povezanost izmeÄu nasljednih oblika tromboflije u koje ubrajamo mutaciju faktora V Leiden, mutacija gena za protrombin, manjak proteina C i proteina S, manjak antitrombina i mutacija gena za glikoprotein inhibitor plazminogen aktivatora-1 s akutnim oblicima srcĢanozĢilnih bolesti.We are witnessing increasingly frequent cases of acute coronary syndrome in younger patients, or in patients who did not present the typical risk factors. Most studies define younger patients as persons under 45 years of age. Such patients are typically diagnosed with acute myocardial infarction (AMI) with normal coronary arteries, i.e. the coronary artery does not show intraluminal anomalies (strict definition) or with a smaller artery stenosis but hemodynamically insignificant (in most cases <30% stenosis). A recently published study (APPROACH) determined the prevalence of AMI with normal coronary arteries was 2.8% in patients who underwent coronary angiography for AMI. Differential diagnosis of such acute coronary events includes myocarditis, stress cardiomyopathy, and Takotsubo syndrome. There is no single explanation for the origin of AMI with normal coronary arteries, but a few possible mechanisms have been suggested: latent atherosclerosis, vasospasm, thrombosis and hypercoagulability, embolization, and inflammation. We differentiate between acquired and inherited thrombophilia syndrome.
In this report, we will describe a link between hereditary forms of trombophilia (a mutation of factor V Leiden, prothrombin gene mutation, deficiency of protein C and protein S, antithrombin deficiency, and mutations in the gene for glycoprotein plasminogen activator inhibitor-1) and acute forms of cardiovascular disease
Bendamustin: stari lijek u novoj eri za bolesnike s ne-Hodgkinovim limfomima i kroniÄnom limfocitnom leukemijom
The aim of this review is to present data on bendamustine, a non-cross resistant alkylating agent, alone or in combination for treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Bendamustine is currently approved for rituximab-resistant indolent NHL and CLL in patients not fit for conventional chemotherapy. Recent studies have shown superiority of bendamustine combination with rituximab (B-R) in first line treatment of indolent NHLs and mantle cell lymphoma, suggesting a shift of the standard of care in this setting. B-R regimen has also shown efficacy in relapsed setting suggesting the possible treatment option for patients failing conventional chemotherapy. In rituximab-resistant NHL, the recent GADOLIN study exploring the addition of obinutuzumab to bendamustine has yielded impressive result changing the standard of care in this hard-to-treat population. Concerning CLL, despite inferiority to the standard of care in young fit patients, as defined in CLL10 study, B-R has yielded a more beneficial toxicity profile and its use in first line treatment should be decided individually. In relapsed setting, the addition of ibrutinib to B-R has shown superior results compared to B-R alone, possibly changing the paradigm of treatment of relapsed CLL. In conclusion, bendamustine as a single agent or in combinations has shown activity with acceptable toxic profile in the treatment of patients with indolent NHLs or CLL without del(17p) mutation.Cilj ovoga preglednog rada je procijeniti aktivnost bendamustina te njegovih kombinacija u ne-Hodgkinovim limfomima (NHL) i kroniÄnoj limfocitnoj leukemiji (KLL). Bendamustin je sada indiciran u Republici Hrvatskoj za lijeÄenje rituksimab-rezistentnog NHL-a i u bolesnika s KLL-om koji nisu kandidati za konvencionalnu terapiju. No, kombinacija bendamustina s rituksimabom (B-R) u prvoj liniji terapije indolentnog NHL-a i limfoma plaÅ”tene zone pokazala se boljom od konvencionalne kemoterapije pa bi B-R trebao postati zlatni standard u prvoj liniji lijeÄenja ovih limfoma. Protokol B-R ĀtakoÄer ima aktivnost u relapsnom indolentnom NHL-u te predstavlja opciju za bolesnike koji su progredirali nakon konvencionalne kemoterapije. U rituksimab-rezistentnom NHL-u nedavna studija GADOLIN koja je prouÄavala dodatak Āobinutuzumaba bendamustinu pokazala je jasnu superiornost prema bendamustinu i promijenila zlatni standard u ovoj Āpopulaciji zahtjevnoj za lijeÄenje. U KLL-u usprkos inferiornosti B-R prema FCR-u u studiji CLL10 B-R je bio obilježen boljim profilom toksiÄnosti te se može ponuditi pojedinim bolesnicima na temelju individualizirane odluke. U relapsnom okružju KLL-a dodatak ibrutiniba protokolu B-R pokazao je superiornost prema B-R s moguÄom promjenom paradigme lijeÄenja ovih bolesnika. ZakljuÄno, bendamustin sam ili u kombinacijama pokazao je visoku aktivnost s povoljnim toksiÄnim profilom u lijeÄenju indolentnih NHL-a i KLL bez mutacije del(17p)
Myelodysplastic syndrome in a patient with untreated chronic lymphoproliferative neoplasm
U bolesnika s kroniÄnom limfoproliferativnom bolesti (LPB) veÄa je uÄestalost nastanka sekundarnih neoplazma. Istodobna pojava limfoproliferativne neoplazme (LPN) i mijelodisplastiÄnog sindroma (MDS) vrlo je rijetka. Druga hematoloÅ”ka neoplazma dijagnosticira se sluÄajno tijekom kontrola ili pri dodatnim analizama zbog
nesukladnih kliniÄkih ili laboratorijskih nalaza. Prikazujemo dijagnostiÄki postupak, tijek bolesti i lijeÄenje 65-godiÅ”nje bolesnice s kroniÄnom limfoproliferativnom neoplazmom i MDS-om sa suviÅ”kom blasta tipa 2
(MDS-EB2). VodeÄi nalaz bila je neutropenija, a tek su citoloÅ”kim analizama koÅ”tane srži i periferne krvi dijagnosticirane navedene neoplazme. LijeÄenje jedne i druge hematoloÅ”ke neoplazme nije dalo zadovoljavajuÄe rezultate i MDS je progredirao u akutnu mijeloiÄnu leukemiju. U bolesnika s limfoproliferativnom neoplazmom i citopenijom
valja tragati za moguÄim drugim uzrocima takvih aberantnih nalaza. Pri lijeÄenju tih bolesnika razumno je lijeÄiti dominantnu bolest.High frequency of second malignancies is observed in chronic lymphoproliferative disease (LPD) patients. The simultaneous occurrence of myelodysplastic syndrome (MDS) with untreated LPD is extremely rare. Second haematological neoplasms are usually diagnosed incidentally during a routine clinical check-up, or due to
discordant clinical or laboratory findings. We are reporting diagnostic procedures, clinical course, and treatment of a 65-year-old woman with chronic lymphoproliferative neoplasm and MDS with excess of blasts type 2 (MDSEB2). Neutropenia was the most aberrant finding. A diagnosis of two malignant haematological neoplasms was done by cytological analysis and immunophenotyping of bone marrow and peripheral blood cells. In spite of treating both neoplasms no satisfactory results were achieved and MDS progressed to acute myeloid leukaemia. In patients with lymphoproliferative neoplasms and cytopenias it is important to find out other causes of these laboratory findings. In such patients the dominant disease should be treated. A concomitant MDS should be suspected and examined
Bendamustine: an Old Drug in the New Era for Patients with Non-Hodgkin Lymphomas and Chronic Lymphocytic Leukemia
The aim of this review is to present data on bendamustine, a non-cross resistant alkylating agent, alone or in combination for treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Bendamustine is currently approved for rituximab-resistant indolent NHL and CLL in patients not fit for conventional chemotherapy. Recent studies have shown superiority of bendamustine combination with rituximab (B-R) in first line treatment of indolent NHLs and mantle cell lymphoma, suggesting a shift of the standard of care in this setting. B-R regimen has also shown efficacy in relapsed setting suggesting the possible treatment option for patients failing conventional chemotherapy. In rituximab-resistant NHL, the recent GADOLIN study exploring the addition of obinutuzumab to bendamustine has yielded impressive result changing the standard of care in this hard-to-treat population. Concerning CLL, despite inferiority to the standard of care in young fit patients, as defined in CLL10 study, B-R has yielded a more beneficial toxicity profile and its use in first line treatment should be decided individually. In relapsed setting, the addition of ibrutinib to B-R has shown superior results compared to B-R alone, possibly changing the paradigm of treatment of relapsed CLL. In conclusion, bendamustine as a single agent or in combinations has shown activity with acceptable toxic profile in the treatment of patients with indolent NHLs or CLL without del(17p) mutation
Heart Failure with Mid-Range or Mildly Reduced Ejection Fraction in the Era of SodiumāGlucose Co-Transporter 2 Inhibitors: Do We Now Provide Better Care for the āMiddle Child of HFā? Real-World Experience from a Single Clinical Centre
Heart failure (HF) with mid-range or mildly reduced ejection fraction (HFmrEF) is a separate clinical entity in the HF spectrum, with a left ventricular ejection fraction ranging from 40 to 49%. While sodium glucose co-transporter 2 inhibitors have become the cornerstone therapy for the entire HF spectrum, there are a few clinical trials of HFmrEF. This prospective observational study was conducted at Dubrava University Hospital, Zagreb, Croatia, from May 2021 to October 2023. We recruited 137 participants diagnosed with HFmrEF at admission. The majority were male, with a median age of 72 and overweight. A total of 110 participants were followed for 6 months and LVEF remained the same in the majority of patients (n = 62, 56.4%), improved in 32 patients (29.1%), and decreased in 3 patients (2.73%). A total of 64 participants were followed for 12 months: 39 remained the same (60.94%) and 25 improved. There were 13 deaths in (9.5%). While the empagliflozin group had a lower BMI at 6-month- and lower HbA1c at 12-month follow-up, there were no differences in death, HF hospitalizations, ER visits, or urinary tract infections in between groups. Despite recent and daily advances in the treatment of all HF phenotypes, HFmrEF still represents a challenge in everyday clinical practice
Systemic mastocytosis in Croatia
Cilj: Ciljevi ove studije bili su identificirati bolesnike sa sistemskom mastocitozom (SM) u Republici Hrvatskoj (RH) i analizirati njihove kliniÄke karakteristike. Ispitanici i metode: Retrospektivno su iz osam hematoloÅ”kih centara u RH identificirani bolesnici sa SM. Analizirane su kliniÄke karakteristike, te naÄini i ishodi lijeÄenja ovih bolesnika. Rezultati: UkljuÄeno je 20 bolesnika, medijan dobi bio je 40,5 godina (raspon 24ā77), a veÄinu su Äinile žene (n=12). Dominirali su bolesnici s indolentnom SM (ISM, n=11), dok je uÄestalost agresivne SM (ASM, n=4), āÅ”uljajuÄeā sistemske mastocitoze (SSM, n=3) i SM s pridruženom zloÄudnom hematoloÅ”kom boleÅ”Äu (SM-AHND, n=2) bila manja. Gotovo su svi bolesnici imali kožni osip, a znaÄajan broj njih i dispeptiÄne smetnje, alergijsku dijatezu, bolove u kostima i osteoporozu. Antihistaminike je primala veÄina bolesnika, a citoredukciju 10 bolesnika (ISM=3, SSM=2, ASM=4, SM-AHND=1). VeÄina bolesnika koja je zahtijevala citoreduktivno lijeÄenje primala je interferon alfa-2a (2
ISM, 1 SSM i 3 ASM), dva steroida (1 ISM i 1 SM-AHND), te po jedan imatinib (SSM) i kladribin (ASM). Svi su bolesnici lijeÄeni u prvoj liniji interferonom alfa-2a i kladribinom postigli parcijalnu remisiju, a dva bolesnika lijeÄena imatinibom i steroidom bila su refraktorna na lijeÄenje. Nije bilo prekida lijeÄenja interferonom zbog nuspojava. Nakon medijana praÄenja od 33 mjeseca preminulo je troje bolesnika, jedan s ASM i oba s SM-AHND. Medijan preživljenja bolesnika s ISM/SSM nije dostignut naspram bolesnika s ASM/SM-AHND, gdje je iznosio 105 mjeseci (p=0,009). ZakljuÄak: KliniÄke karakteristike i ishodi lijeÄenja bolesnika sa SM u RH sliÄni su onima iz velikih svjetskih centara. NajÄeÅ”Äe koriÅ”ten citoreduktivni lijek u RH bio je interferon alfa-2a koji se pokazao sigurnim i uÄinkovitim.Aim: The aims of this study were to identify patients with systemic mastocytosis (SM) in Croatia and to analyze their clinical characteristics. Patients and methods: Patients with SM treated at eight hospitals in Croatia were retrospectively identified and their clinical characteristics, treatment patterns and outcomes were analyzed. Results:Twenty patients were included, median age was 40.5years (range 24-77), and most were females (n=12) . Patients with indolent SM (ISM, n=11) predominated, followed by aggressive SM (ASM, n=4), smoldering SM (SSM, n=3) and SM with an associated hematological neoplastic disorder (SM-AHND, n=2). Only one patient (with ASM) did not have cutaneous involvement, and a significant proportion of SM patients had dyspepsia, allergic diathesis, bone pains and osteoporosis. Antihistamines were administered in the majority of the patients, whereas ten patients needed cytoreductive treatment (ISM, n=3, SSM n=2, ASM, n=4, SM-AHND, n=1). Most SM patients in need for cytoreduction received interferon alpha-2a (two ISM, one SSM and three ASM), two received steroids (one ISM and one SM-AHND), one received imatinib (SSM) and the last patient was treated with cladribine (ASM). All patients treated first-line with interferons and cladribine achieved partial remission, whereas two patients treated with imatinib and steroid were refractory. None of the patients discontinued interferon due to drug-related side-effects. After a median follow-up of 33 months, three patients died, one with ASM and two with SM-AHND.The median survival of ISM/SSM patients was higher than in ASM/SM-AHND patients in whom it was 105 months (p=0.009). Conclusion: Clinical characteristics and treatment outcomes of SM patients in Croatia are comparable to those from large international centers. The most commonly administered cytoreductive drug in Croatia was interferon alpha-2a which was shown to be safe and effective