University of Zagreb Medical School Repository
University of Zagreb Medical School RepositoryNot a member yet
2851 research outputs found
Sort by
A single-arm, open-label study to assess the immunogenicity, safety, and efficacy of etanercept manufactured using the serum-free, high-capacity manufacturing process administered to patients with rheumatoid arthritis
Get PDFObjective: To evaluate the immunogenicity, safety, and efficacy of etanercept (ETN) manufactured
using the serum-free, high-capacity manufacturing (SFHCM) process in patients with rheumatoid
arthritis (RA).
----- Methods: In this global, multicenter, open-label, single-arm study (NCT02378506), 187 adult patients
with moderate to severe RA received ETN 50 mg once weekly for 24 weeks manufactured using the
SFHCM process. Immunogenicity (presence of antidrug antibodies (ADAs) and neutralizing antibodies
(NAbs)) was assessed at 12 and 24 weeks. Safety and efficacy were evaluated at 4, 12, and 24 weeks.
----- Results: Eight (4.5%) patients tested positive for ADA, and there were no NAbs detected at any time
throughout the study. Ninety (48.1%) patients reported treatment-emergent adverse events (AEs), of
which 27 (14.4%) reported injection-site reactions, and 43 (23.0%) reported infections. The majority of
AEs were mild or moderate in severity, and the drug was well tolerated. Throughout the duration of
the study (week 4 to week 24), there was a progressive increase in the American College of Rheumatology
(ACR)-defined responses (ACR20: 55.9%–82.0%, ACR50: 16.1%–57.8%, and ACR70: 3.2%–26.7%)
from baseline and the proportion of patients achieving low disease activity and remission, with a
corresponding decrease in measures of disease activity.
----- Conclusion: The immunogenicity, safety, and efficacy of ETN manufactured using the SFHCM process
were similar to the current approved ETN formulation. ClinicalTrials.gov registration: NCT02378506
Association analyses identify 31 new risk loci for colorectal cancer susceptibility
Get PDFColorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention
Dementia care in the Danube Region. A multi-national expert survey
Get PDFBackground: Dementia is a particularly severe societal challenge in several countries of the
Danube Region due to higher-than-average increment in population longevity, disproportionate
increase of the old-age dependency ratio, and selective outward migration of health care
professionals. A survey was conducted among dementia experts to obtain a deeper understanding
of the dementia care structures and services in this geographical area, and to identify
the educational needs of health care professionals, and the availability of assistive technology. ------
Subjects and methods: A standardized questionnaire was sent out to 15 leading dementia
experts/clinicians in 10 Danube Region countries inquiring about professional groups
involved in dementia care, availability and reimbursement of services, inclusion of dementia
in professional education and training, acceptability of Internet-based education, and availability
of assistive technology. The authors are the survey respondents. -----
Results: The majority of individuals with dementia receive care in the community rather
than in institutions. The roles of medical specialties are disparate. General practitioners
usually identify dementia symptoms while specialists contribute most to clinical diagnosis
and treatment. Health care professionals, particularly those who work closely with patients
and carers, have limited access to dementia-specific education and training. The greatest need
for dementia-specific education is seen for general practitioners and nurses. An Internetbased
education and skill-building program is considered to be equivalent to traditional faceto-
face but offer advantages in terms of convenience of access. Assistive technology is
available in countries of the Danube Region but is significantly underused. -----
Conclusion: Dementia care in the Danube Region can be improved by an educational and
skill-building program for health care professionals who work in the frontline of dementia
care. Such a program should also attempt to enhance interdisciplinary and intersectorial
collaboration, to intensify the interaction between primary care and specialists, and to
promote the implementation of assistive technology
Recovery from sudden sensorineural hearing loss may be linked to chronic stress levels and steroid treatment resistance
Get PDFPurpose This article investigates the possible connections between the level of chronic stress and success of steroid therapy in patients with sudden sensorineural hearing loss (SSNHL). Method A single-center, retrospective, longitudinal cohort study on 55 patients in a tertiary referral otology center was examined. Patients diagnosed with SSNHL between 2014 and 2017 were asked to complete a Measure of Perceived Stress (Brajac, Tkalcic, Dragojević, & Gruber, 2003 ) questionnaire. Inclusion criteria were patients > 18 years of age, SSNHL diagnosed within 4 previous weeks, completed steroid treatment, and complete documentation. Results There were 30 patients (55%) that showed significant improvement in their pure-tone audiogram (PTA) hearing threshold average (≥ 15 dB) after steroid treatment. Two-step cluster analysis identified 3 clusters based on average PTA hearing threshold recovery and average Measure of Perceived Stress scores. The difference between pretreatment and posttreatment hearing levels was significantly higher in the cluster with moderate stress compared to clusters with mild and high stress levels (Kruskal-Wallis test, Friedman test, p < .001). There were no significant differences in average PTA hearing threshold recovery after steroid therapy between groups of patients with mild and severe stress. Conclusion Patients with moderate stress levels show significantly better results after steroid treatment for SSNHL than patients with low or high stress levels
Arterijska krutost kao pokazatelj vaskularnoga starenja u bolesnika s upalnim bolestima crijeva [Arterial stiffness as a marker of vascular aging in IBD patients]
Get PDFChronic inflammatory bowel diseases (IBD) are associated with premature atherosclerosis caused
by endothelial dysfunction and increased arterial intima-media. In conditions characterized by
chronic systemic inflammation, like IBD, chronic inflammatory process through dyslipidemia and
accelerated atherosclerosis leads to increase in arterial stiffness of the large arteries. The crucial
role of arterial stiffness in the development of cardiovascular disease is well known and arterial
stiffness measurement is increasingly being used for cardiovascular risk assessment and it is an
indicator of vascular aging. Non-invasive measurement of pulse wave velocity (PWV) and
augmentation index (Aix) has predictive value for future fatal cardiovascular events and overall
cardiovascular risk. In our research, nearly half of the examinees had increased PWV (45%) and
subclinical target organ damage. There were no differences in arterial stiffness markers in Crohn's
disease (CD) and ulcerative colitis (UC) patients. Also, patients divided according to disease
phenotype, localization and applied therapy showed no differences in PWV and Aix markers.
Increased PWV (>8m/s) is the most prevalent marker of subclinical target organ damage in our
IBD patient cohort. We also showed that PWV increases with age and becomes higher than PWV
in the control group of examinees with well-controlled arterial hypertension. Accelerated vascular
aging is the result of prolonged duration of IBD as the most plausible cause of increased PWV.
Patients also had increased Aix as a marker of increased arterial stiffness of medium and small
arteries. Age and duration of IBD were strong and independent predictors of increased PWV in all
groups of IBD patients. These results show that IBD with chronic, systemic inflammation plays a
role in the development of accelerated atherosclerosis, increased arterial stiffness and subclinical
target organ damage similar to arterial hypertension, an established risk factor for arterial stiffness.
Also, we can conclude that increased arterial stiffness and accelerated vascular aging are more
pronounced in those patients with a more prolonged duration of IBD. Our results of increased PWV
and Aix in IBD patients with longer disease duration are contributing to the fact that chronic
inflammation is responsible for alterations of both large and smaller arteries and leads to target
organ damage in these patients, regardless of current disease activity. Premature atherosclerosis
and dyslipidemia should be closely monitored and treated, especially in IBD patients with longer
disease duration
Razvoj topline u zoni bušenja kosti - usporedba utjecaja svrdla vođenoga rukom ili strojno [Heat Buildup In The Bone Drilling Zone: Machine Vs. Hand Guided Drill]
Get PDFThe principal operative fracture treatment is open reduction and internal fixation during
which the plate is fixed to the bone by screws placed into predrilled holes.
Previous research has been based on the linear motion of the drill exclusively. In the
clinical environment the direction of the drilling depends on the surgeon so it is not always
possible to maintain a constant direction.
The influence of the hand controlled drilling on the heat buildup in the drilling zone was
analyzed systematically and it has been found that hand guided drill produces more heat
compared to the machine controlled drilling. That justifies the introduction of automatic bone
drilling systems into operative fracture treatment
Imunohistokemijska analiza izraženosti antigena skupine rak-testis u neinvazivnim duktalnim karcinomima dojke [Immunohistochemical analysis of cancer/testis antigens in noninvasive ductal breast cancer]
Get PDFCancer/testis antigens (CTAs) are a large family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues, with the exception of the testes and placenta. Numerous immunohistochemical studies have reported associations between CTA expression and a negative estrogen receptor (ER) status in breast tumors and demonstrated that CTAs are frequently expressed in tumors with higher nuclear grade. The expression of CTAs has not been studied as extensively in ductal carcinoma in situ (DCIS) as it has been in invasive breast cancer. The present retrospective study included archived paraffin-embedded specimens from 83 patients diagnosed with DCIS in the period between January 2007 and December 2014. The follow-up time for local recurrence ranged between 1 and 8 years (mean, 5.02 years). Antigens from the melanoma-associated antigen gene (MAGE) family, namely multi-MAGE-A, MAGE-A1, MAGE-A10 and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen, were evaluated by immunostaining and their subcellular location was investigated. Presence of tumor-infiltrating lymphocytes (TILs) was evaluated on all sections, together with the histopathological variables of DCIS. Specific tested antigens exhibited associations with histopathological parameters for DCIS and all demonstrated statistically significant associations with nuclear staining, simultaneous cytoplasmic and nuclear staining, and local recurrence. Additional analysis of TILs indicated that they were significantly associated with tumor grade (P=0.023), central necrosis (P<0.001), ER (r=-0.322, p=0.003) and PR (r=-0.285, p=0.009). Overall, CTAs from the MAGE family (MAGE-A1, multi-MAGE-A and MAGE-A10) and NY-ESO-1 associate with histopathological predictive variables of DCIS. The expression of antigens NY-ESO-1 and MAGE-A10 could serve an important role in the treatment of patients with negative histopathological predictive variables, but further analysis is required. Simultaneous cytoplasmic and nuclear protein expression of MAGE-A family and NY-ESO-1 CTAs may represent an independent marker for local recurrence. Taken together, the present data suggest that CTAs are not perfect indicators of invasiveness for DCIS but could inform treatment strategies for patients when taken in combination with other histopathological predictive variables. However, this was a small study and further larger studies will be necessary to confirm the current findings
Silicon foil patching for blast tympanic membrane perforation: a retrospective study
Get PDFAim: To establish whether covering the tympanic membrane perforation after war blast injury with silicon foil can enhance the ear drum healing rate and to determine the appropriate timing of silicon patching.
----- Methods: We retrospectively analyzed the charts of 210 patients wounded during the Homeland War in Croatia 1991-1995, with 315 blast tympanic membrane perforations. In 44 patients (61 perforations), the eardrum perforation was covered by silicon foil, whereas in 166 patients (254 perforations) it was left to heal spontaneously. The patients who underwent the patching procedure were divided in two groups according to the time period between the blast injury and the procedure: 38 perforations were treated within 3 days and 23 perforations were treated 4 to 6 days after the blast injury.
------ Results: The rate of tympanic membrane healing in the silicon foil patching group was significantly higher (91.8%) than that in the group of perforations left to heal spontaneously (79.9%, P = 0.029). The healing rate was significantly higher in the group treated within 3 days after the blast injury (97.4%) than in the group treated 4 to 6 days after the injury (82.6%, P = 0.042).
----- Conclusion: Covering the perforation after the war blast injury with silicon foil significantly improves the rate of tympanic membrane healing. To obtain the best healing outcome, the procedure should be performed within the first 72 hours after the trauma
Utilization of somatic healthcare in Croatian patients with schizophrenia spectrum disorder, major depression, PTSD and the general population
Get PDFBackground: Utilization of somatic healthcare services is highly predictive of the development of chronic physical
illnesses and increased mortality risks. The objective of this study was to assess the differences in healthcare utilization
among patients with schizophrenia spectrum disorders (SSD), major depressive disorder (MDD) and posttraumatic
stress disorder (PTSD) and the general population in Croatia.
----- Methods: We enrolled 566 Croatian participants from the general population, 282 with SSD, 178 with MDD, and 86
with PTSD. The primary outcome was a self-reported specialist consultation for non-psychiatric (e.g., somatic) causes
within the previous 12 months.
----- Results: Although SSD patients with chronic physical illnesses were significantly more often hospitalized for physical
illness than the general population, the proportion of patients who had a specialist consultation were equal in SSD and
the general population. MDD and PTSD patients had significantly higher adjusted odds for specialist consultation than
the general population and SSD patients (MDD compared to SSD: OR = 2.14; 95% CI 1.27–3.59; PTSD compared to SSD:
OR = 2.03; 95% CI 1.00–4.10).
----- Conclusions: SSD patients’ utilization of somatic healthcare is equal to the general population, despite their increased
healthcare needs. However, their utilization is lower than in MDD and PTSD patients and, therefore, probably not
adequate
Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus
Get PDFSystemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk