Veterinary medicine - Repository of PHD, master's thesis
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The COVID-19 pandemic impact on continuity of care provision on rare brain diseases and on ataxias, dystonia and PKU. A scoping review
No full textOne of the most relevant challenges for healthcare providers during the COVID- 19 pandemic has been assuring the continuity of care to patients with complex health needs such as people living with rare diseases (RDs). The COVID-19 pandemic accelerated the healthcare sector's digital transformation agenda. The delivery of telemedicine services instead of many face-to-face procedures has been expanded and, many healthcare services not directly related to COVID-19 treatments shifted online remotely. Many hospitals, specialist centres, patients and families started to use telemedicine because they were forced to. This trend could directly represent a good practice on how care services could be organized and continuity of care could be ensured for patients. If done properly, it could boast improved patient outcomes and become a post COVID-19 major shift in the care paradigm. There is a fragmented stakeholders spectrum, as many questions arise on: how is e-health interacting with 'traditional' healthcare providers; about the role of the European Reference Networks (ERNs); if remote care can retain a human touch and stay patient centric. The manuscript is one of the results of the European Brain Council (EBC) Value of Treatment research project on rare brain disorders focusing on progressive ataxias, dystonia and phenylketonuria with the support of Academic Partners and in collaboration with European Reference Networks (ERNs) experts, applying empirical evidence from different European countries. The main purpose of this work is to investigate the impact of the COVID-19 pandemic on the continuity of care for ataxias, dystonia and phenylketonuria (PKU) in Europe. The analysis carried out makes it possible to highlight the critical points encountered and to learn from the best experiences. Here, we propose a scoping review that investigates this topic, focusing on continuity of care and novel methods (e.g., digital approaches) used to reduce the care disruption. This scoping review was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) standards. This work showed that the implementation of telemedicine services was the main measure that healthcare providers (HCPs) put in place and adopted for mitigating the effects of disruption or discontinuity of the healthcare services of people with rare neurological diseases and with neurometabolic disorders in Europe
Serum Levels of S100A8/A9 as a Biomarker of Disease Activity in Patients with IgA Vasculitis
No full textS100A8/A9 protein is a well-known marker of disease activity or severity in many autoimmune and autoinflammatory diseases, but there have not been many studies about the role of S100A8/A9 in IgA vasculitis (IgAV). The aim of our study was to evaluate S100A8/A9 as a possible biomarker of activity in IgAV. We measured the serum levels of S100A8/A9 in pediatric patients with IgA vasculitis at the onset of the disease, after three months, and after six months. We compared these levels between patients with active disease, remission, and a control group, and assessed their correlation with disease activity and other markers of inflammation. Patients with active disease had significantly higher levels of serum S100A8/A9 (median ± SD) than those in the control group at the beginning of the disease (5740 ± 3157 ng/mL vs. 1447 ± 858.3 ng/mL; p < 0.0001), but also three months and six months after disease onset (p < 0.001). There was a positive correlation between S100A8/A9 serum levels and disease activity (p = 0.0003). Patients with active disease had significantly higher levels of S100A8/A9 than those in remission three months after disease onset (p = 0.0260). There was a correlation between S100A8/A9 and C-reactive protein, the C3 component of complement, ferritin, and fibrinogen. Serum levels of S100A8/A9 were also higher in patients with greater skin areas covered with rash. We demonstrated that serum levels of S100A8/A9 correlated well with disease activity and other biomarkers of inflammation in children with IgAV. According to our results, serum S100A8/A9 may be a good indicator of active disease in IgAV
The endocannabinoid system in appetite regulation and treatment of obesity
No full textThe endocannabinoid system (ECS) is a complex cell‐signaling system that is responsible for maintaining homeostasis by modulating various regulatory reactions in response to internal and environmental changes. The influence of ECS on appetite regulation has been a subject of much recent research, however, the full extent of its impact remains unknown. Current evidence links human obesity to ECS activation, increased endocannabinoid levels in both central and peripheral tissues, along with cannabinoid receptor type 1 (CBR1) up‐regulation. These findings imply the potential pharmacological use of the ECS in the treatment of obesity. Here, we present various pathophysiological processes in obesity involving the ECS, highlighting different pharmacological options for modulating endocannabinoid activity to treat obesity. However, the potential of those pharmacological possibilities remains under investigation and requires further research
Knowledge, attitudes and beliefs regarding HIV among medical students in Zagreb, Croatia
No full textBackground: Medical students, as future health-care providers (HCPs) play a significant role in shaping attitudes towards people living with HIV/AIDS (PLWHA) and should possess adequate knowledge of this infection. The study aim was to assess knowledge about HIV among medical students of the University of Zagreb School of Medicine, and to determine the level of discriminatory attitudes towards PLWHA.
Methods: We assessed knowledge about epidemiology, treatment, and prevention of HIV by using closed-ended and multiple-choice questions. Likert-scale questions were employed to determine attitudes towards PLWHA. Bivariate and multivariate ordinal logistic regression was used to assess correlates of certain discriminatory attitudes.
Results: 561 medical students participated, with 46.7% attending preclinical courses. Overall, 42.1% of students think they received sufficient information on HIV/AIDS during elementary and high school education. Among clinical students, 42.6%, 20.8% and 11.8% estimated accurately transmission risk after a needle injury, unprotected vaginal, and anal intercourse, respectively. 66.8% of clinical students were aware that treatment can prevent AIDS, while 58.7% and 69.8% were familiar with the rationale of using pre-exposure (PrEP) and post-exposure prophylaxis (PEP). In the multivariate analysis, individuals lacking infectology course attendance (aOR = 1.45; CI: 1.00-2.09) and those unaware of transmission routes (aOR = 1.49; CI: 1.06-2.09) showed higher odds of advocating HIV status disclosure compared to those who did not yet attend an infectology course. Students supporting extra protection for handling PLWHA bodily fluids were more likely to support refusal to treat PLWHA (aOR = 1.80; CI: 1.22-2.69) compared to those who did not support that opinion. Males were more inclined to state that they would refuse to treat PLWHA (aOR = 1.66; CI: 1.11-2.50) and disclose their HIV status (aOR = 1.62; CI: 1.17-2.27) than females. Overestimating needle injury transmission risk raised treatment refusal likelihood (aOR = 2.22; CI = 1.29-3.92) compared to those accurately informed of this risk.
Conclusion: Results indicate lack of knowledge of HIV transmission risks after specific exposures and about PrEP, PEP and treatment effectiveness. Gender and knowledge about HIV transmission risks influence students' attitudes towards PLWHA. Medical education should be focused on fostering correct attitudes and addressing stigma, which undermines prevention and treatment outcomes of PLWHA
No Difference between the Efficacy of High-Nitrate and Low-Nitrate Vegetable Supplementation on Blood Pressure after 16 Weeks in Individuals with Early-Stage Hypertension: An Exploratory, Double-Blinded, Randomized, Controlled Trial
No full textDietary inorganic nitrate lowers blood pressure (BP) in healthy individuals through improved nitric oxide (NO) bioavailability. However, there is limited evidence examining the long-term effects of dietary nitrate for managing hypertension. We aimed to determine whether the sustained intake of dietary nitrate improved BP and cardiovascular disease (CVD) risk factors in individuals with early-stage hypertension. The Dietary Nitrate (NO3) on BP and CVD Risk Factors (DINO3) Trial was a multi-center, double-blinded, parallel, randomized, controlled trial in participants with elevated BP. Participants were supplemented with high-nitrate (HN) (~400 mg nitrate) or low-nitrate (LN) vegetable powder (~50 mg nitrate) on top of their usual diets for 16 weeks. The primary outcome was office systolic BP at 16 weeks. The secondary outcomes were 24 h ambulatory BP, central BP, heart-rate-corrected augmentation index (AIx75), carotid–femoral pulse wave velocity (cf-PWV), lipids, and high-sensitivity C-reactive protein (hs-CRP). Sixty-six participants were randomized at baseline (39M:27F, age: 51.5 ± 10.8 years, BMI:27.9 ± 3.2 kg/m2). In an intention-to-treat analysis, no differences were observed between HN and LN groups in terms of office systolic BP at 16 weeks (3.91 ± 3.52 mmHg, p = 0.27) or secondary outcomes. In this exploratory study, sustained HN vegetable supplementation did not exhibit more favorable vascular effects than LN vegetable supplementation in individuals with elevated BP
Are important predictors of adverse outcome in children with symptomatic congenital cytomegalovirus infection overlooked in clinical settings?
No full textObjective: Congenital cytomegalovirus infection (cCMV) is a common, frequently unrecognized cause of childhood disability. The aim of the present study was to determine the symptoms that raise the suspicion of cCMV, define the neurodevelopmental outcomes, and assess their correlations.
Methods: This longitudinal observational study comprised 78 children with symptomatic cCMV who underwent neuropediatric follow-up for 4 to 17.9 years.
Results: Symptoms of central nervous system involvement, hearing/visual impairments, and hepatic involvement were mostly recognized. The average age of disease suspicion was 3.3 months. In terms of outcomes, 10.53% of the children developed complex minor neurological dysfunction and 23.68% developed cerebral palsy. Visual and hearing impairments occurred in 38.16% and 14.47% of patients, respectively. Intellectual disability was present in 30.26% of patients, and epilepsy in 21.05%. Microcephaly and hearing impairment was significantly associated with overall neurodevelopmental outcome. Microcephaly was also associated with poor motor outcomes, hearing impairment, and severe visual impairment. Furthermore, microcephaly and intrauterine growth restriction were significantly associated with poor cognitive outcomes.
Conclusion: Symptoms that raised the suspicion of cCMV-especially microcephaly, hearing impairment, and intrauterine growth restriction-were important parameters that were associated with outcomes; however, their recognition was often insufficient and/or late
Regional cerebral oxygen saturation variability and brain injury in preterm infants
No full textObjective: To examine whether variation of regional cerebral oxygen saturation (rScO2) within three days after delivery predicts development of brain injury (intraventricular/cerebellar hemorrhage or white matter injury) in preterm infants.
Study design: A prospective study of neonates <32 weeks gestational age with normal cranial ultrasound admitted between 2018 and 2022. All received rScO2 monitoring with near-infrared spectroscopy at admission up to 72 h of life. To assess brain injury a magnetic resonance imaging was performed at term-equivalent age. We assessed the association between rScO2 variability (short-term average real variability, rScO2ARV, and standard deviation, rScO2SD), mean rScO2 (rScO2MEAN), and percentage of time rScO2 spent below 60% (rScO2TIME<60%) during the first 72 h of life and brain injury.
Results: The median [IQR] time from birth to brain imaging was 68 [59-79] days. Of 81 neonates, 49 had some form of brain injury. Compared to neonates without injury, in those with injury rScO2ARV was higher during the first 24 h (P = 0.026); rScO2SD was higher at 24 and 72 h (P = 0.029 and P = 0.030, respectively), rScO2MEAN was lower at 48 h (P = 0.042), and rScO2TIME<60% was longer at 24, 48, and 72 h (P = 0.050, P = 0.041, and P = 0.009, respectively). Similar results were observed in multivariable logistic regression. Although not all results were statistically significant, increased rScO2 variability (rScO2ARV and rScO2SD) and lower mean values of rScO2 were associated with increased likelihood of brain injury.
Conclusions: In preterm infants increased aberration of rScO2 in early postdelivery period was associated with an increased likelihood of brain injury diagnosis at term-equivalent age
Prenatal assessment of brain malformations on neuroimaging: an expert panel review
No full textBrain malformations represent a heterogeneous group of abnormalities of neural morphogenesis, often associated with aberrations of neuronal connectivity and brain volume. Prenatal detection of brain malformations requires a clear understanding of embryology and developmental morphology through the various stages of gestation. This expert panel review is written with the central aim of providing an easy-to-understand road map to improve prenatal detection and characterization of structural malformations based on the current understanding of normal and aberrant brain development. For every developmental stage, the utility of each available neuroimaging modality, including prenatal multiplanar neuro sonography, anatomical MRI and advanced MRI techniques, as well as further insights from post-mortem imaging, has been highlighted
Impact of Human Papillomavirus on microRNA-21 Expression in Oral and Oropharyngeal Cancer—A Systematic Review
No full textRecently, microRNAs (miR) were identified to have potential links with oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) oncogenesis, specifically miR-21. Since HPV is a major risk factor for the development of these diseases, we aimed to search the literature regarding miR-21 expression in both HPV-positive and HPV-negative OSCC/OPSCC. The search was performed in the PubMed (MEDLINE), Scopus, Web of Science, and Cochrane electronic databases. The research question was as follows: Is there a difference in the tissue expression of miR-21 between patients with HPV-positive and those with HPV-negative OSCC/OPSCC? After conducting a meticulous search strategy, four studies were included, and they had a pooled sample size of 621 subjects with OSCC and/or OPSCC. Three studies did not find any significant difference in miR-21 expression between HPV-positive and HPV-negative OSCC/OPSCC. The findings of this systematic review showed that there are no differences in miR-21 expression between HPV-positive and HPV-negative OSCC/OPSCC. Nevertheless, it is worth noting that there are still insufficient studies regarding this important subject, because understanding how HPV influences miR-21 expression and its downstream effects can provide insights into the molecular mechanisms underlying OSCC/OPSCC development and progression
Systemic Inflammatory Index in Polycythemia Vera and Its Prognostic Implications
No full textBackground: This study aimed to evaluate the clinical and prognostic associations of the systemic inflammatory index (SII) in polycythemia vera (PV) patients. SII integrates information on absolute neutrophil (ANC), lymphocyte (ALC), and platelet counts into one index (calculated as ANCxALC/platelet count) and was previously shown to predict thrombotic and mortality risks in the general population.
Methods: A total of 279 PV patients treated in several hematologic centers in Croatia and Serbia was retrospectively evaluated.
Results: The median SII for the overall cohort was 1960. Higher SII stratified at the specific cut-off points was significantly associated with shorter time to thrombosis (TTT; p = 0.004) driven by arterial thrombotic events, and shorter overall survival (OS; p < 0.001). Higher SII was able to refine the European Leukemia Net-defined high-risk patient subgroup for both thrombotic and survival risks, especially in individuals over 60 years of age. SII and all other evaluated CBC components and indices (leukocytes, ANC, ALC, platelets, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR)) demonstrated low-to-modest prognostic properties, whereas SII outperformed other parameters with respect to TTT and OS prognostications.
Discussion: The presented results complement prior studies evaluating the prognostic performance of different CBC components for thrombotic and survival risk predictions and offer more options to personalize PV treatments