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Analysis of Reporting Trends of Serious Adverse Events Associated With Anti‐Obesity Drugs
No full textABSTRACT
Concern over the side effects of anti‐obesity medications, particularly if severe, has grown as their use has increased. Thus, the objective was to use trends in the reporting of suspected adverse events associated with anti‐obesity medications that have been approved for sale in the European Union to attempt to uncover discrepancies in the safety of these medications. The study was designed as secondary research, based on data about the number of adverse drug reactions (both serious and non‐serious) reported to the EudraVigilance database. Trends of the annual reporting rates for the six anti‐obesity drugs were analyzed by the Joinpoint Trend Analysis Software that divides the trendline into an optimum number of segments connected by “joinpoints” and tests the significance of the trend within each segment. The trends of serious adverse drug events showed clear differences among the anti‐obesity drugs: while all drugs had significant increasing trends during a few initial years after their appearance on the market, only the annual number of reports for semaglutide continued to grow ever since (annual change + 67.1%,
= 0.000). On the contrary, a continuous increase in the reporting rate of non‐serious adverse drug events was observed only for liraglutide (annual change + 33.8%,
= 0.000) while for the other anti‐obesity drugs, including semaglutide, the trends after the initial period were either negative or did not increase significantly. In conclusion, among the anti‐obesity drugs currently approved, only semaglutide shows a continuously increasing trend in the annual reporting of serious adverse events, suggesting a need for further investigation of safety signals
Metabolic Dysfunction-Associated Steatotic Liver Disease Induced by Microplastics: An Endpoint in the Liver–Eye Axis
No full textThere is a significant, rather than just anecdotal, connection between the liver and the eyes. This connection is evident in noticeable cases such as jaundice, where the sclera has a yellow tint. But this can be seen through even more subtle indicators, such as molecules known as hepatokines. This relationship is not merely anecdotal; in some studies, it is referred to as the “liver–eye axis”. Ubiquitous environmental contaminants, such as microplastics (MPs), can enter the bloodstream and human body through the conjunctival sac, nasolacrimal duct, and upper respiratory tract mucosa. Once absorbed, these substances can accumulate in various organs and cause harm. Toxic substances from the surface of the eye can lead to local oxidative damage by inducing apoptosis in corneal and conjunctival cells, and irregularly shaped microparticles can exacerbate this effect. Even other toxicants from the ocular surface may be absorbed into the bloodstream and distributed throughout the body. Environmental toxicology presents a challenge because many pollutants can enter the body through the same ocular route as that used by certain medications. Previous research has indicated that the accumulation of MPs may play a major role in the development of chronic liver disease in humans. It is crucial to investigate whether the buildup of MPs in the liver is a potential cause of fibrosis, or simply a consequence of conditions such as cirrhosis and portal hypertension
Intrakapsularni temporomandibularni poremećaji označavaju aktivnost aksijalnog spondiloartritisa
No full textObjectives: The group of spondyloarthritis (SpA) disorders shares common clinical manifestations,
including internal derangement (ID) of temporomandibular joint (TMJ). This study aimed to investigate SpA activity in patients with ID of TMJ. Materials and Methods: We assessed 200 patients with neck pain using the Assessment of Spondyloarthritis International Society (ASAS) criteria. TMJ was examined using Diagnostic Criteria for Temporomandibular Disorders (DC/TMD protocol). Patients with SpA were divided into three groups: symptomatic ID of TMJ, asymptomatic ID of TMJ, or healthy TMJ (controls). Activity of SpA was evaluated using the Ankylosing Spondylitis Disease Activity Score
(ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Disease Activity Index in Psoriatic Arthritis (DAPSA), patients’ self-estimated SpA activity, difficulties in performing daily activities, pain intensity (visual analogue scale) and laboratory parameters. Results: Patients with symptomatic and asymptomatic ID showed statistically significantly increased ASDAS, anti-streptolysin titer, patients’ self-estimated axial pain and activity of SpA, and decreased hematocrit than the control. Patients with symptomatic ID also had statistically significant earlier onset of SpA, along with increased BASDAI and DAPSA, total body pain, difficulties in performing daily activities, platelet count, and serum alpha-amylase but lower hemoglobin concentration than controls. Patients with asymptomatic ID had higher frequencies of exacerbated axial SpA and sacroiliac joint ankylosis compared to the control. Conclusion: All patients with SpA and ID showed increased axial disease activity.Cilj rada: Skupina bolesti spondiloartritisa (SpA) ima zajedničke kliničke pojavnosti, uključujući intrakapsularni temporomandibularni poremećaj (IK TMP). Ovo istraživanje imalo je za cilj istražiti aktivnost SpA-e kod bolesnika s IK TMP-om. Materijali i metode: Dijagnosticirali smo SpA kod 200 bolesnika s bolovima u vratu koristeći se međunarodnom razradbom ASAS (engl. The Assessment of SpondyloArthritis International Society). Temporomandibularni zglob (TMZ) pregledan je s pomoću protokola Dijagnostički kriteriji za temporomandibularne poremećaje (DK/TMP). Bolesnici sa SpA-om podijeljeni su u tri
skupine: simptomatski IK TMP, asimptomatski IK TMP ili zdravi TMZ (kontrola). Aktivnost SpA-e procijenjena je korištenjem ASDAS-a (engl. Ankylosing Spondylitis Disease Activity Score), BASDAI-ija (engl. Bath Ankylosing Spondylitis Disease Activity Index), DAPSA-e (engl. Disease Activity Index in Psoriatic Arthritis), aktivnosti SpA-e koju su bolesnici sami procijenili, poteškoća u obavljanju dnevnih aktivnosti, jakosti bolova (vizualna analogna ljestvica) i laboratorijskim parametrima. Rezultati: Bolesnici sa simptomatskim i asimptomatskim IK TMP-om imali su statistički značajno veći ASDAS, titar antistreptolizina,
samoprocjenu aksijalne boli i aktivnost SpA-e te smanjeni hematokrit u odnosu prema kontroli. Bolesnici sa simptomatskim IKTMP-om dodatno su imali statistički značajno raniji početak SpA-e, zajedno s povećanim BASDAI-jem i DAPSA-om, bolovima u cijelom tijelu, poteškoćama u obavljanju dnevnih aktivnosti, broju trombocita i koncentracijom α-amilaze u serumu, ali manju koncentraciju hemoglobina od kontrole. Bolesnici s asimptomatskim IK TMP-om imali su veću učestalost pogoršanja aksijalnoga spondiloartritisa (SpA) i ankiloze sakroilijačnoga zgloba u usporedbi s kontrolom. Zaključak: Kod svih bolesnila sa SpA-om i IK TMP-om zabilježena je povećana aksijalna aktivnost bolesti
Effect of Dexmedetomidine on Cardiopulmonary Bypass Induced Inflammatory Response in Patients Undergoing Aortic Valve Replacement
No full textSurgical aortic valve replacement (SAVR) remains an essential treatment option for patients with aortic stenosis (AS). Open-heart surgery requires the use of cardiopulmonary bypass (CPB), which triggers an inflammatory response that can lead to end-organ dysfunction and severe complications. Dexmedetomidine, a highly selective α2-adrenergic agonist, is widely used in anesthesia and intensive care medicine for its sedative, analgesic, and sympatholytic properties. This study aimed to investigate whether dexmedetomidine exerts a clinically relevant anti-inflammatory effect in patients undergoing open-heart surgery and to determine the optimal dose. A prospective, double-blind, placebo-controlled study was conducted, including 60 patients randomized into three groups according to dexmedetomidine dose. Inflammatory markers (IL-6, TNF-α), renal function, and other clinical parameters were analyzed at multiple time points. Statistical analyses were performed to assess differences between the groups. Dexmedetomidine administration significantly affected TNF-α levels 12 h after CPB (p = 0.033), while previously reported suppression of IL-6 was not observed. Dexmedetomidine was associated with lower opioid consumption before extubation and showed a tendency to reduce postoperative delirium. Diuresis was significantly increased on the first postoperative day in dexmedetomidine-treated patients (p = 0.003), with no significant changes in other renal parameters. The incidence of atrial fibrillation was highest in the control group and lowest in the high-dose dexmedetomidine group, though this difference was not statistically significant. These results suggest that dexmedetomidine influences inflammatory and clinical outcomes; however, further research is needed to confirm its long-term benefits and optimal dosing strategies
Prognostic Value of Biomarkers in COVID-19: Associations with Disease Severity, Viral Variants, and Comorbidities—A Retrospective Observational Single-Center Cohort Study
No full textCoronavirus disease (COVID-19) exhibits a wide spectrum of clinical severity and has been associated with specific biomarkers linked to disease progression and outcomes. This retrospective study analyzed sera from 1222 adult COVID-19 patients hospitalized at the University Hospital for Infectious Diseases in Croatia. We examined the association between several laboratory biomarker levels measured at patient admission and disease severity, fatal outcomes, viral variants and clinical parameters. Deceased patients and surviving patients with severe COVID-19 exhibited significantly elevated levels of several biomarkers on admission, including hs-troponin T, N-terminal pro-brain natriuretic peptide, creatine kinase, C-reactive protein, procalcitonin, interleukin-6, lactate dehydrogenase, lactate, urea and creatinine. Random forest models identified lymphocyte percentage, D-dimers, and hs-troponin T as the most important biomarkers for fatal outcome prediction, achieving 84.1% accuracy. Patients infected with the Delta SARS-CoV-2 variant exhibited significantly higher levels of proinflammatory, cardiac and renal biomarkers. Vaccination correlated with reduced proinflammatory parameters and higher lymphocyte proportions. Hypertension, chronic renal disease and diabetes were associated with increased cardiac, renal and metabolic biomarker levels, respectively. These findings highlight the association of several laboratory biomarkers with COVID-19 severity, viral variants, vaccination status and comorbidities, potentially offering prognostic insights into COVID-19 outcomes
Eurovision Song Contest: Can juries assess the quality of songs objectively?
No full textThis paper analyses the role of jury votes in the Eurovision Song Contest (ESC). We analysed the results of the six ESCs (from 2017 to 2023) in terms of the differences (1) between public and jury votes, (2) among jury votes, and (3) among public votes at the national and ESC levels. We applied 15,251 Spearman rank correlations. The role (mission) of the jury return in the competition, as explained by the organiser, is to ensure objectivity since it was concluded that the public is not entirely capable of objectively evaluating songs. Considering the mission of the jury return and the assumption that juries can fulfil it, we expected that the correlations between each national jury and ESC jury and among national juries would be high. Furthermore, it was expected that the correlations between each national public and ESC public and among the national public would be low or at least lower than those in the jury cases. However, the results are different and are the opposite of expectations. Additionally, the influence of juries on the results is equal to that of the public (without the rest of the world). Consequently, with the current voting system, the jury mission is only partly achieved, and the inclusion of juries highly influences the winner such that the winner is different from what the public thinks it should be. The situation becomes even more severe when the public has to accept a winner that was their only fifth choice (as in ESC 2024). The final conclusion is that the (jury) voting system still needs to be upgraded in the future, and our research proposals include establishing two awards, a jury award and a public award, among others
NK cell-derived IFNγ mobilizes free fatty acids from adipose tissue to promote early B cell activation during viral infection
No full textThe immune system plays a major role in the regulation of adipose tissue homeostasis. Viral infection often drives fat loss, but how and why this happens is unclear. Here, we show that visceral adipose tissue transiently decreases adiposity following viral infection. Upon pathogen encounter, adipose tissue upregulates surface expression of ligands for activating receptors on natural killer cells, which drives IFN gamma secretion. This cytokine directly stimulates adipocytes to shift their balance from lipogenesis to lipolysis, which leads to release of lipids in circulation, most notably of free fatty acids. The free fatty acid oleic acid stimulates early-activated B cells by promoting oxidative phosphorylation. Oleic acid promoted expression of co-stimulatory B7 molecules on B cells and promoted their ability to prime CD8+ T cells. Inhibiting lipid uptake by activated B cells impaired CD8+ T cell responses, causing an increase of viral replication in vivo. Our findings uncover a previously unappreciated mechanism of metabolic adaptation to infection and provide a better understanding of the interactions between immune cells and adipose tissue in response to inflammation
Polycyclic aromatic hydrocarbon (PAH) exposure among European adults: Evidence from the HBM4EU aligned studies
No full textPolycyclic aromatic hydrocarbons (PAHs) are persistent environmental pollutants with well-documented associations to adverse health effects, posing significant public health challenges across Europe. Human exposure to 13 urinary PAH metabolites was assessed in a harmonized cohort of European adults aged 20-39, representing diverse geographic regions across Europe: North (Iceland and Denmark), East (Poland and the Czech Republic), South (Croatia and Portugal), and West (France, Germany, Switzerland, and Luxembourg). This study aimed to achieve a unified understanding of PAH exposure by employing stringent participant selection criteria and harmonizing biomarker analyses by utilizing high-quality analytical protocols across multiple laboratories in Europe. Key findings revealed consistently elevated metabolite levels in smokers compared to non-smokers, with naphthalene metabolites dominating the profiles over phenanthrene and fluorene derivatives. Country-specific analyses highlighted Poland as having the highest naphthalene metabolite concentrations, while Luxembourg exhibited elevated pyrene metabolite levels. Urbanization influenced exposure, with slightly higher metabolite concentrations in town populations compared to rural areas. While sex-based stratification revealed no marked differences, gender emerged as a significant covariate in regression models, with women generally displaying higher exposure to naphthalene metabolites. Educational level further stratified exposure, with lower education correlating with increased PAH levels. Multivariate linear regression identified key exposure factors, including sampling season (i.e., summer, winter, autumn, and spring), dietary habits e.g., smoked foods, and proximity to smoke-prone environments. This dataset provides a significant baseline for evaluating the European Commission's Chemicals Strategy for Sustainability (CSS) and underscores the utility of harmonized human biomonitoring studies in informing targeted public health interventions
Differential Effects of Rutin and Its Aglycone Quercetin on Cytotoxicity and Chemosensitization of HCT 116 Colon Cancer Cells to Anticancer Drugs 5-Fluorouracil and Doxorubicin
No full textBackground: Rutin and quercetin are natural flavonoids with a variety of beneficial health effects, including anticancer activity. In the present study, we compared cytotoxicity and chemosensitization of human colon cancer HCT116 cells to anticancer drugs 5-fluorouracil (5-FU) and doxorubicin (DOX) by both compounds. Methods: The 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) test was used to determine cell viability. Western blot and immunofluorescence techniques were employed in the detection of expression of proteins involved in oxidative stress, apoptosis, and autophagy. Results: Quercetin treatment resulted in reduced cell viability compared to rutin at the same dose, suggesting greater cytotoxicity than rutin against HCT116 cells. Quercetin was also a better chemosensitizer of DOX than rutin, further reducing cell viability. However, rutin was a better chemosensitizer of 5-FU than quercetin. All treatments induced apoptosis, with rutin and DOX inducing intrinsic and 5-FU inducing extrinsic apoptotic cell death. Autophagy was induced in all treatments and played a pro-survival role, with the exception of DOX treatment. Different treatment regimens specifically modulated cancer cell signaling pathways involved in the regulation of oxidative stress, apoptosis, and autophagy. Conclusions: The results of the current study suggest that rutin and quercetin, although structural analogs, act as specific modulators of signaling pathways in cancer cells, differentially affecting cancer cell cytotoxicity and chemosensitization to anticancer drugs, based on the presence of a free hydroxyl group at the C-3 position of the flavonoid backbone at quercetin or rutinose in rutin
Falls in the Third Age of Life – Public Health Perspective and Challenges for the Future
No full textPadovi i ozljede u populaciji treće životne dobi predstavljaju veliki javnozdravstveni izazov kako u Hrvatskoj tako i u svijetu. Uzrokuju najveći broj hospitalizacija, dugotrajno bolničko liječenje i invalidnost te mogu voditi u smrtni ishod. Čak 30 % osoba starijih od 65 i 50 % osoba starijih od 80 godina iskuse barem jedan pad godišnje. U Hrvatskoj, u starijih od 65 godina 64,1 % hospitalizacija čine ozljede nastale kao posljedica pada, što ujedno predstavlja i vodeći uzrok smrti. Fizioterapijska prevencija padova i njihovih posljedica nezaobilazan je primjer integriranog procesa skrbi usmjerenog na osobu i zahtijeva brojniju radnu snagu i restrukturiranje usluga.Falls and fall-related injuries in the elderly population represent a major public health challenge both in Croatia and in the world. They cause the greatest number of hospitalizations, long-term hospital treatment, disability and can lead to death. As many as 30% of people over 65 and 50% of people over 80 experience at least one fall a year. In Croatia, in people over 65 years, 64.1% of hospitalizations are caused by injuries resulting from falls, which is also the leading cause of death. Physiotherapy prevention of falls and consequences is an unavoidable example of an integrated person-centred care process and requires a larger workforce and restructuring of services