48 research outputs found
Neopstruktivna koronarna bolest - kliniÄka važnost, dijagnostika, lijeÄenje i prijedlog nove patofizioloÅ”ke klasifikacije
New data gathered from large clinical trials indicate that nonobstructive coronary artery disease (non-CAD) is a clinical entity that should not be ignored. It is estimated that 50% of female population undergoing coronarography are diagnosed with non-CAD. There is also an increase in the prevalence of non-CAD in both genders, which is probably due to gradual expanding of clinical indications for angiography in patients with angina. Furthermore, considering the increased mortality risk established recently, a prognosis of non-CAD is not benign as previously thought. However, the concept and definition of non-CAD remains elusive causing difficulties in diagnosis and treatment. One of the major shortcomings is the exclusion-based diagnosis of non-CAD. Furthermore, treatment of non-CAD still presents a great challenge and optimal therapy is yet to be determined. There are two major hypotheses explaining the pathophysiological mechanisms of non-CAD, i.e. ischemic hypothesis based on abnormal microvascular dysfunction and non-ischemic one based on altered pain perception. This review encompasses a broader spectrum of pathophysiological mechanisms of non-CAD, and proposes a new way of classification based on the major disorder involved: type I (ischemic mechanisms) and type II (non-ischemic mechanisms), depending on which mechanism predominates. Hopefully, this would provide new insights in the understanding of this disorder, thus leading to accurate and early diagnosis and successful treatment, especially considering the increased mortality risk in these patients.Novi podaci prikupljeni iz velikih kliniÄkih ispitivanja pokazuju da je neopstruktivna koronarna bolest (ne-OKB) kliniÄki entitet koji se ne smije zanemariti. Procjenjuje se da se u 50% ženske populacije koja se podvrgava koronarografiji dijagnosticira ne-OKB. TakoÄer postoji poveÄanje uÄestalosti ne-OKB u oba spola, Å”to je vjerojatno posljedica postupnog Å”irenja kliniÄkih indikacija za koronarografiju u bolesnika s anginom pektoris. Nadalje, s obzirom na poveÄani rizik od smrtnosti koji je nedavno ustanovljen, prognoza ne-OKB nije dobroÄudna kao Å”to se ranije mislilo. MeÄutim, koncept i definicija ne-OKB ostaju nedovoljno definirani, Å”to uzrokuje poteÅ”koÄe kako u dijagnozi tako i u lijeÄenju. Jedan od glavnih nedostataka je dijagnostika ne-OKB koja se temelji na dijagnozi iskljuÄivanja. Nadalje, lijeÄenje ne-OKB i dalje predstavlja velik izazov, a optimalnu terapiju tek treba odrediti. Postoje dvije glavne hipoteze koje objaÅ”njavaju patofizioloÅ”ke mehanizme ne-OKB. Ishemijska hipoteza temelji se na mikrovaskularnoj disfunkciji, a neishemijska hipoteza na promijenjenoj percepciji boli. Ovaj pregledni Älanak obuhvaÄa Å”irok spektar patofizioloÅ”kih mehanizama ne-OKB i predlaže novi naÄin klasifikacije temeljen na glavnom poremeÄaju koji je ukljuÄen u patofiziologiju: tip I. (ishemijski mehanizam) i tip II. (ne-ishemijski mehanizam), ovisno o tome koji mehanizam prevladava. Nadamo se da Äe to omoguÄiti nove spoznaje u razumijevanju ovoga poremeÄaja, Å”to dovodi do toÄne i rane dijagnoze i uspjeÅ”nog lijeÄenja, osobito s obzirom na poveÄani rizik smrtnosti kod ovih bolesnika
Povezanost koÅ”tane mineralne gustoÄe i sastavnica metaboliÄkog sindroma u postmenopauzalnih žena sa Å”eÄernom boleÅ”Äu tipa 2
Diabetes mellitus type 2 is associated with greater bone mineral density (BMD) due to obesity, although rapid bone loss observed over time could be explained by elevated chronic inflammation. The objective of this study was to investigate the relationship between central adiposity and hyperinsulinemia, as well as inflammation markers with vertebral and femoral BMD and bone turnover markers in postmenopausal women with type 2 diabetes. Femoral and vertebral BMD, osteocalcin, pyrilinks D, beta-CrossLaps (B-CTx), insulin, C-reactive protein (CRP), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) were measured in 114 postmenopausal female patients with diabetes type 2. The patients of similar age, HbA1c levels and diabetes duration were divided into 2 groups based on their body mass index (BMI) values: lower or equal to 27 kg/m2(31 patients) and higher than 27 kg/m2(83 patients). Lower levels of osteocalcin (p=0.001), B-CTx (p=0.000007) and pyrilinks D (p=0.0365), and higher femoral BMD (p=0.00006), insulin level (p=0.0002), PAI-1 (p=0.00000) and CRP (p=0.002) were found in the overweight group. There were no significant differences in vertebral BMD and fibrinogen. Osteocalcin and B-CTx showed inverse correlation, and femoral BMD positive correlation with waist circumference, insulin level and PAI-1. This suggests that abdominal obesity and hyperinsulinemia as components of the metabolic syndrome could increase femoral BMD by lowering bone rate. In addition, the only inflammation marker linked with femoral BMD was PAI-1, which is associated with increased mineralization of cortical bone in mouse models.Å eÄerna bolest tipa 2 povezana je s veÄom koÅ”tanom mineralnom gustoÄom (bone mineral density, BMD) zbog debljine, iako se zamijeÄeni ubrzani gubitak koÅ”tane mase tijekom vremena može objasniti prisustvom kroniÄne upale. Cilj ovoga istraživanja bio je utvrditi povezanost biljega koÅ”tane pregradnje i koÅ”tane gustoÄe s centralnom debljinom, hiperinzulinemijom kao i upalnim biljezima u postmenopauzalnih žena sa Å”eÄernom boleÅ”Äu tipa 2. U 114 ispitanica izmjerena je koÅ”tana gustoÄa kralježnice i kuka, odreÄeni su osteokalcin, pirilinks D, beta-CrossLaps (B-CTx), inzulin, C-reaktivni protein (CRP), fibrinogen i inhibitor aktivatora plazminogena-1 (PAI-1). Ispitanice sliÄne dobi, podjednakog trajanja dijabetesa te HbA1c bile su podijeljene u dvije skupine prema indeksu tjelesne mase (ITM): niži ili jednaki 27 kg/m2(31 ispitanica) te veÄi od 27 kg/m2 (83 ispitanice). Niže vrijednosti osteokalcina (p=0,001), B-CTx (p=0,000007) i pirilinksa D (p=0,0365) te viÅ”e vrijednosti koÅ”ane gustoÄe kuka (p=0,00006), inzulina (p=0,0002), PAI-1 (p=0,0000) i CRP (p=0,002) utvrÄene su u skupini s prekomjernom tjelesnom težinom. Nije bilo statistiÄki znaÄajne razlike u koÅ”tanoj gustoÄi kralježnice i vrijednosti fibrinogena. Osteokalcin i B-CTx su negativno korelirali, dok je BMD kuka bio u pozitivnoj korealciji s opsegom struka, inzulinom i PAI-1. Ovi rezultati upuÄuju na to da sastavnice metaboliÄkog sindroma, centralna debljina i hiperinzulinemija utjeÄu na poveÄanje koÅ”tane gustoÄe kuka inhibirajuÄi koÅ”tanu pregradnju. Jedini upalni biljeg povezan s BMD kuka bio je PAI-1 koji poveÄava mineralizaciju kortikalne kosti na miÅ”jem modelu
Association of galectin-3 and significant atherosclerotic epicardial artery disease in patients with chronic coronary syndrome
Hepatitis CāAssociated Diabetes Mellitus
Diabetes type 2 mellitus (T2DM) is the most common extrahepatic association of hepatitis C virus (HCV) infection. Substantial research has suggested that insulin resistance (IR) has crucial importance in development of type 2 diabetes in HCV-infected patients. Several pathophysiological mechanisms are proposed, such as direct effect of HCV proteins on inhibition of the insulin-signaling pathway inducing central insulin resistance (IR), while overproduction of inflammatory cytokines and increased lipolysis promote peripheral IR.Ā IR in HCV-infected patients is associated with impaired sustained virologic response (SVR) and higher incidence of hepatocellular carcinoma (HCC). Some, but not all, studies have shown improvements in achieving SVR in patients with interferon/ribavirin (RBV) therapy co-treated with metformin or pioglitazone as well as beneficiary effect on the incidence of hepatocellular carcinoma. Recent studies indicate that response to the new direct-acting antiviral (DAA) treatments is unaffected by insulin resistance thus diminishing importance of IR in the new era of DAA.Ā Additionally, viral eradication by DAAs has been shown to ameliorate insulin resistance, attenuating the risk of new-onset diabetes type 2. However, those metabolic improvements are sustainable long after the treatment remains unclear
Pharmacogenomic Testing in the Era of Patient-Tailored HCV Treatment
Hepatitis C affects approximately 180 million people worldwide, with 3ā4 million newly infected each year. Hepatitis C virus (HCV) has been classified into seven different genotype categories, wherein HCV genotype 1 (HCV-1) is the most prevalent. To date, there is still no vaccine available against HCV infection. Until recently, combination therapy of pegylated interferon-a (PegIFN) and ribavirin (RBV) has been the standard of care. Nevertheless, for many patients, particularly those infected with HCV genotype 1 (HCV-1), this treatment has resulted with unsatisfactory treatment response rates and high adverse drug reaction (ADR) rates. Many clinical factors, including pharmacogenetics, influence the treatment response rate. This review focuses on the association between pharmacogenetics and HCV antiviral therapy in patients infected with HCV genotype 1 and other genotypes (GT); patients reinfected with HCV after liver transplantation; and patients coinfected with HCV and human immunodeficiency virus. Data considering triple therapy in HCV-infected patients are also reviewed. Additionally, various genetic polymorphisms, with an emphasis to IL-28B, and their association with pharmacogenetic testing in HCV are discussed
Urolithiasis and Osteoporosis: Clinical Relevance and Therapeutic Implications
Several clinical and epidemiological studies revealed increased bone turnover and lower bone mass in patients with urolithiasis. Bone mass loss is particularly evident in idiopathic calcium stone formers. However, pathogenetic mechanisms and factors implicated in bone loss in these patients are still unknown. Dietary calcium restriction, increased intake of salt and animal proteins, vitamin D receptor polymorphisms are likely risk factors, while role of inflammatory cytokines, osteopontin and prostaglandin mediated bone resorption is yet to be determined. Regarding treatment and prevention, it has been proven that calcium supplements and high calcium diet with the addition of potassium alkali have an important role in prevention and treatment of both, urolithiasis and osteoporosis. Thiazide diuretics reduce hypercalciuria in renal tubules, and in addition promote osteoblast differentiation. Finally, bisphosphonates, a commonly used drugs in treatement of osteoporosis, show the potential to inhibit calcium stone formation, whereas a possible protective effect of antioxidants in bone loss and renal injurie needs to be investigated further
Changing the Landscape of Hypertension Management With SGLT2i
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a newer class of drugs that have primarily been used in the treatment of type 2 diabetes. However, as new findings from clinical trials have become available, their indication has been expanded to include treatment of heart failure and chronic kidney disease without the presence of diabetes. The pathophysiological mechanisms of extraglycemic effects of SGLT2i are still being unraveled, but one of the most prominent consequences is a decrease in blood pressure, which has implications for hemodynamics and arterial stiffness. Recent findings indicate that this class of drugs has a beneficial effect on lowering nocturnal blood pressure (BP), with special importance in type 2 diabetes (DMT2), since unregulated nocturnal hypertension is associated with an increased incidence of cardiovascular (CV) events. In this mini-review, we have summarized current knowledge about the effects of SGLT2i on blood pressure, including office, home, and ambulatory BP, and potential implications for treatment of hypertension in diabetic and non-diabetic individuals, with positive effects on cardiorenal outcomes
Serumska vrijednost osteoprotegerina u bolesnika s kalcificirajuÄom aortnom stenozom u ovisnosti o zatajenju srca
The aim of the study was to assess the role of serum osteoprotegerin (OPG) as a biomarker in patients with aortic valve stenosis (AS) in relation to heart failure and symptomatic status. This was a case control study, which included 51 patients with AS and 39 control subjects. At the time of study enrolment, detailed medical history was obtained and all subjects underwent physical examination, chest x-ray and echocardiography. OPG levels were measured in all subjects, and serum N-terminal of the pro b-type natriuretic peptide (NT pro BNP) levels were determined in patients with AS. Serum OPG levels were elevated in patients with AS compared to control subjects (p=0.001). Pa-tients with heart failure due to AS had elevated serum OPG levels in comparison to patients without heart failure (p=0.001). A significant correlation between OPG and symptomatic status was observed in all patients with AS (p<0.001), however, it was not the case in patients without heart failure (p=0.425). There was a positive correlation between OPG and NT pro BNP concentrations with objective signs of heart failure on chest x-ray (p<0.001). Negative correlation of OPG concentrations with aortic valve area was present (p<0.040), as well as with left ventricular ejection fraction (p<0.001). Serum OPG could be a valuable biomarker in the evaluation of severity of calcified AS and serve as an additional indicator besides clinical presentation and echocardiography in the assessment of surgical treatment or aortic valve replacement.Cilj ove studije bio je ocijeniti ulogu osteoprotegerina (OPG) kao biljega u bolesnika sa stenozom aortnog srÄanog za-liska u odnosu na prisutne simptome kao i stupanj srÄanog zatajenja. U studiju je bio ukljuÄen 51 bolesnik s aortnom steno-zom (AS) i 39 kontrolnih ispitanika. Prije ukljuÄenja u studiju uzeta je detaljna anamneza, uÄinjen je fizikalni pregled, ren-tgenska snimka srca i pluÄa te ehokardiografija. OPG je odreÄen u svih ispitanika, a N-terminalni nastavak pro b-tipa natriu-retskog peptida (NT pro BNP) bio je odreÄen u bolesnika s AS. OPG je bio poviÅ”en u bolesnika s AS u odnosu na kontrolne ispitanike (p=0,001). Bolesnici sa srÄanim zatajenjem zbog AS imali su poviÅ”ene razine OPG-a u odnosu na bolesnike bez srÄanog zatajenja (p=0,001). ZnaÄajna korelacija izmeÄu OPG-a i simptomatskog statusa bila je zapažena u svih bolesnika s AS (p<0,001), ali to nije bio sluÄaj u bolesnika bez srÄanog zatajenja (p=0.425). Zabilježena je i pozitivna korelacija izmeÄu koncentracije OPG-a i NT pro BNP-a s objektivnim znakovima srÄanog zatajenja na rentgenskoj snimci srca i pluÄa (p<0,001). TakoÄer je opažena negativna korelacija OPG-a i areje aortnog zaliska (p<0,040) te istisne frakcije lijeve klijetke (p<0,001). OPG bi mogao predstavljati vrijedan biljeg u procjeni težine kalcificirane AS te bi mogao poslužiti kao dodatni indikator prilikom odluÄivanja o kirurÅ”kom lijeÄenju ili zamjeni aortnog zaliska, naravno, uz kliniÄku prezentaciju i ehokardiografiju
UÄinak hipertireoze i antitiroidne terapije na koÅ”tanu gustoÄu - patofizioloÅ”ki mehanizmi te kliniÄko znaÄenje
Gravesā disease is an autoimmune disease characterized by excessive thyroid hormone
production. One of the consequences of that state can be a decrease in bone mineral density (BMD).
Gravesā disease is often treated with antithyroid drugs (ATD) as first line therapy, which can lead to disease
remission. Moreover, recent data show that improvement in BMD can be expected. However, vitamin D
deficiency can coexist along with Gravesā disease, which is also involved in the process of bone remodeling.
It is still not known whether lower values of vitamin D can contribute to onset of Gravesā disease and if its
supplementation might be helpful in therapy for hyperthyroidism. In the past couple of decades, osteopenia
and osteoporosis have become a major health burden not only in post-menopausal women but also as a result
of other diseases, leading to extensive research into various pathophysiological mechanisms responsible
for bone remodeling. The Wnt (wingless integrated) signaling pathway is a very important factor in bone
homeostasis, especially the canonical pathway. Present data indicate that stimulation of the Wnt pathway
leads to bone mass increase and, in contrast, its inhibition leads to bone mass decrease. Hence, inhibitors of
the canonical Wnt pathway became the focus of interest, in particular sclerostin and dickkopf 1 (DKK1).
Hyperthyroidism and osteopenia/osteoporosis are quite common today and can coexist together or as separate
entities. In this article, we aimed to give an overview of possible associations and potential mutual
pathophysiological mechanisms.Gravesova bolest je autoimuna bolest karakterizirana prevelikom proizvodnjom hormona Å”titnjaÄe. Jedna od posljedica
toga stanja može biti sniženje mineralne gustoÄe kosti. LijeÄi se antitireoidnim lijekovima kao prvim izborom Äime se može
postiÄi remisija bolesti. Postizanjem remisije, može se oÄekivati i poboljÅ”anje mineralne gustoÄe kosti. No, uz Gravesovu
bolest, može postojati i snižena vrijednost vitamina D koji je takoÄer važana za procese pregradnje kosti. JoÅ” je uvijek
otvoreno pitanje mou li snižene vrijednosti vitamina D pridonijeti nastanku Gravesove bolesti i da li bi njegova supstitucija
mogla pomoÄi u lijeÄenju hipertireoze. Kako je smanjena mineralna gustoÄa kosti danas rasprostranjena Å”irom svijeta, u
proÅ”lim desetljeÄima poÄeo se istraživati Wnt put. Ovaj put vrlo je važan za homeostazu kosti, osobito njegov dio koji se
naziva kanoniÄki put u kojem sudjeluju i sklerostin i dickkopf 1 kao inhibitori. Svi spomenuti Äimbenici, odnosno stanja,
danas su uÄestala i mogu postojati zajedno i odvojeno. Ovim Älankom pokuÅ”ali smo dati pregled moguÄe veze izmeÄu njih
Impact of pharmacotherapeutic education on medication adherence and adverse outcomes in patients with type 2 diabetes mellitus: a prospective, randomized study
Aim To evaluate the impact of pharmacotherapeutic education
on 30-day post-discharge medication adherence
and adverse outcomes in patients with type 2 diabetes
mellitus (T2DM).
Methods The prospective, randomized, single-center
study was conducted at the Medical Department of University
Hospital Dubrava, Zagreb, between April and June
2018. One hundred and thirty adult patients with T2DM
who were discharged to the community were randomly
assigned to either the intervention or the control group.
Both groups during the hospital stay received the usual
diabetes education. The intervention group received additional
individual pre-discharge pharmacotherapeutic
education about the discharge prescriptions. Medication
adherence and occurrence of adverse outcomes (adverse
drug reactions, readmission, emergency department visits,
and death) were assessed at the follow-up visit, 30 days after
discharge.Results The number of adherent patients was significantly
higher in the intervention group (57/64 [89.9%] vs 41/61
[67.2%]; Ļ2 test, P = 0.003]. There was no significant difference
between the groups in the number of patients who
experienced adverse outcomes (31/64 [48.4%] vs 36/61
[59.0%]; Ļ2 test, P = 0.236). However, higher frequencies of
all adverse outcomes were consistently observed in the
control group.
Conclusion Pharmacotherapeutic education of patients
with T2DM can significantly improve 30-day post-discharge
medication adherence, without a significant reduction
in adverse clinical outcomes