Veterinary medicine - Repository of PHD, master's thesis
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Urine high–sensitive troponin I in children cannot offer an applicable alternative to serum
No full textIntroduction: In children, congenital heart defects represent the primary cause of increased serum troponin I. The elimination process of cardiac troponin I from the bloodstream and the factors influencing this process remain unknown. The objective of this study was to explore the role of troponin I as an indicator of cardiac damage in children both in serum and urine, a concept previously investigated in adults.
Methods: Our prospective study involved 70 children under 24 months of age. The first group underwent ventricular septal defect repair, while the second group involved children who had undergone partial cavopulmonary anastomosis. For these groups, urine and serum troponin I were assessed on four occasions. The third group, consisting of healthy children, underwent a single measurement of urine troponin I.
Results: Serum troponin I values exhibited an expected elevation in the early postoperative period, followed by a return to lower levels. Significantly higher concentrations of serum troponin I were observed in the first group of children (p < 0.05). A positive correlation was found between troponin I in the first three measurements and cardiopulmonary bypass and aortic cross-clamping time. There was no discernible increase in urine troponin I directly related to myocardial damage; troponin I couldn't be detected in most urine samples.
Discussion: The inability to detect troponin I in urine remains unexplained. Potential explanatory factors may include the isoelectric point of troponin I, elevated urinary concentrations of salts and urea, variations in urine acidity (different pH levels), and a relatively low protein concentration in urine
Metformin and pancreatic neuroendocrine tumors: A systematic review and meta-analysis
No full textBACKGROUND
Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant. In this perspective, metformin is emerging as a molecule of interest. Retrospective studies have described metformin, a widely used agent for the treatment of patients with type 2 diabetes mellitus (T2DM), to be effective in modulating different tumor-related events, including cancer incidence, recurrence and survival by inhibiting mTOR phosphorylation. This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET. AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and post-treatment outcomes of pNET.
METHODS
A systematic review of the published literature was undertaken, focusing on the role of T2DM and metformin in insurgence and prognosis of pNET, measured through outcomes of tumor-free survival (TFS), overall survival and progression-free survival. RESULTS A total of 13 studies (5674 patients) were included in this review. Analysis of 809 pNET cases from five retrospective studies (low study heterogeneity with I² = 0%) confirms the correlation between T2DM and insurgence of pNET (OR = 2.13, 95%CI = 1.56-4.55; P < 0.001). The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients (hazard ratio = 1.84, 95%CI = 0.78-2.90; P < 0.001). The study heterogeneity was intermediate, with I² = 51%. A few studies limited the possibility of performing pooled analysis in the setting of metformin; therefore, results were heterogeneous, with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.
CONCLUSION
T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients. Unfortunately, a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET
Equivalent: Combined use of videolaryngoscope and bonfils intubation endoscope as rescue option for difficult airway management: a case report
No full textOtežani dišni put predstavlja velik izazov za kliničare, pogotovo ako je neočekivan. Anesteziolozima su na raspolaganju brojne smjernice i široka paleta pomagala za zbrinjavanje dišnoga puta, a kad pojedinačne tehnike zakažu, savjetuje se primjena kombiniranih tehnika. Predstavljamo slučaj otežane intubacije kod pedesetogodišnjeg muškarca kod kojega je planirana zamjena aortnog zalistka. Anamnezom nisu utvrđene ranije otežane intubacije. Prijeoperacijska procjena dišnoga puta bila je bez osobitosti. Indeks tjelesne mase iznosio je 29 kg/m2. Nakon neuspješne pojedinačne primjene direktne laringoskopije, videolaringoskopije i intubacijskog endoskopa BONFILS (BIE) primijenili smo kombiniranu tehniku kombinirajući videolaringoskop i BIE. Dok smo videolaringoskopom osigurali potreban prostor za plasiranje BIE i poboljšali prikaz kroz obilan sekret, BIE nam je poslužio kao vodilica za endotrahealni tubus, što je dovelo do uspješne intubacije. Budući da tehnika zahtijeva skupu opremu, iskustvo u njenoj primjeni te barem dva anesteziologa, prikladnija je kao izvanredna mjera nego kao redovni postupak. S obzirom na potencijalno katastrofalne posljedice neuspješne intubacije ovladavanje naprednim tehnikama zbrinjavanja dišnoga puta ostaje od ključne važnosti, a kombinirana tehnika jedna je od njih.Difficult airway management poses a great challenge for clinicians, especially if it is unanticipated. Numerous guidelines and a wide array of devices constitute the anesthesiologist’s armamentarium for managing the airway. When the use of individual devices fails, the use of combination techniques is advised. We present a case of difficult intubation in a 50-year-old male patient scheduled for aortic valve replacement. He had no prior history of difficult airway management, and no abnormalities
were detected on preoperative airway assessment. Body mass index was 29 kg/m2. After the separate use of direct laryngoscopy, videolaryngoscopy and a BONFILS intubation endoscope (BIE) had failed, we resorted to a combination technique, combining videolaryngoscopy and BIE. While the videolaryngoscope provided the space needed for BIE and visual guidance through copious secretions, the BIE served as a stylet for endotracheal tube guidance, leading to successful intubation. Since the technique requires costly equipment, experience in handling it and at least two operators, it is more
appropriate as a rescue measure than an elective procedure. Given the potentially disastrous outcomes of failed intubation, mastering advanced airway management techniques remains of vital importance, and the combination technique is one of them
von Willebrand factor/factor VIII concentrate (Wilate) prophylaxis in children and adults with von Willebrand disease
No full textLong-term prophylaxis with a von Willebrand factor (VWF) concentrate is recommended in patients with von Willebrand disease (VWD) who have a history of severe and frequent bleeds. However, data from prospective studies are scarce. WIL-31, a prospective, noncontrolled, international phase 3 trial, investigated the efficacy and safety of Wilate prophylaxis in severe patients with VWD. Male and female patients 6 years or older with VWD types 1, 2 (except 2N), or 3 who had completed a prospective, 6-month, on-demand, run-in study (WIL-29) were eligible to receive Wilate prophylaxis for 12 months. At baseline, patients (n = 33) had a median age of 18 years. Six (18%) patients had severe type 1, 5 (15%) had type 2, and 22 (67%) had type 3 VWD. The primary end point of a >50% reduction in mean total annualized bleeding rate (TABR) with Wilate prophylaxis vs prior on-demand treatment was met; mean TABR during prophylaxis was 5.2, representing an 84.4% reduction. The bleeding reduction was consistent across age, sex, and VWD types. The mean spontaneous ABR was 3.2, representing an 86.9% reduction vs on-demand treatment. During prophylaxis, 10 (30.3%) patients had 0 bleeding events and 15 (45.5%) patients had 0 spontaneous bleeding events. Of 173 BEs, 84.4% were minor and 69.9% treated. No serious adverse events related to study treatment and no thrombotic events were recorded. Overall, WIL-31 showed that Wilate prophylaxis was efficacious and well-tolerated in pediatric and adult patients with VWD of all types. The WIL-29 and WIL-31 trials were registered at www.ClinicalTrials.gov as #NCT04053699 and #NCT04052698, respectively
Editors' role in shaping the publishing environment and guiding authors in the era of artificial intelligence
No full textCritically Ill Patients with Newly Diagnosed Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: Case Series and Literature Review
No full textANCA-associated vasculitides (AAVs) are rare diseases with a prevalence of less than 200 cases per million persons and an incidence of less than 25 cases per million person-years. Their presenting features can vary from prodromal and nonspecific symptoms to dramatic organ-specific symptoms such as respiratory failure due to diffuse alveolar hemorrhage (DAH) and acute kidney injury (AKI). The latter two are hallmark features of pulmonary-renal syndrome, a potentially fatal condition that necessitates early recognition and treatment in intensive care units (ICUs) and rapid induction of immunosuppressive therapy.
Background and case summaries: We described three patients with newly diagnosed AAV during the treatment of critical illness. All patients had DAH and two had AKI. The initial disease severity was extremely high in patients with myeloperoxidase (MPO)-AAV, reaching Sequential Organ Failure Assessment (SOFA) scores of 15 and 14 with predicted mortality ≥ 95.2%. Both patients needed mechanical ventilation, one additional venovenous extracorporeal membrane oxygenation (VV-ECMO), and renal replacement therapy. The patient with proteinase 3 (PR3)-AAV had a less severe disease, SOFA 3, requiring only modest oxygen supplementation and exhibiting only hematuria with normal renal function parameters. Immunosuppressive therapy was initiated during the ICU stay. The patient with the most severe clinical presentation died during the ICU stay because of sepsis, and the other two patients were discharged home.
Conclusions: Patients with AAV presenting with pulmonary-renal syndrome necessitate various degrees of organ support. Nevertheless, these patients can be successfully treated in the early, critical stages of the disease and achieve remission
Radiographic predictors of peritumoral brain edema in intracranial meningiomas: a review of current controversies and illustrative cases
No full textMeningiomas are among the most common primary tumors of the central nervous system. In the past several decades, many researchers have emphasized the importance of radiographic findings and their possible role in predicting the various aspects of the meningioma biology. One of the factors most commonly analyzed with respect to the lesions’ clinical behavior is peritumoral brain edema (PTBE), not only one of the most common signs associated with meningiomas, but also a significant clinical problem. Radiographic predictors of PTBE are usually noted as being the size of the tumor, its location, irregular margins, heterogeneity, and the peritumoral arachnoid plane with its pial vascular recruitment. Here, we review the available literature on the topic of these radiographic predictors of PTBE formation, we analyze the methodology of the research conducted, and we highlight the many controversies still present. Indeed, the evidence about PTBE pathogenesis, predictive factors, and clinical significance still seems to be mostly inconclusive, despite intense research in the area. We believe that by highlighting the many inconsistencies in the methodology used, we can showcase how little is actually known about the pathogenesis of PTBE, which in turn has important clinical implications. Additionally, we provide several MR images of intracranial meningiomas from our own practice which, we believe, showcase the unpredictable nature of PTBE, and demonstrate vividly the topics we discuss
The impact of COVID-19 infection on multiple sclerosis disease course across 12 countries: a propensity-score-matched cohort study
No full textBackground: The relationship between coronavirus disease 2019 (COVID-19) infection and multiple sclerosis (MS) relapse and disease progression remains unclear. Previous studies are limited by small sample sizes and most lack a propensity-matched control cohort.
Objective: To evaluate the effect of COVID-19 infection on MS disease course with a large propensity-matched cohort.
Design: This multi-centre cohort study analysed relapse and disability outcomes post-COVID-19 infection after balancing covariates using a propensity score matching method. The study period was from the 11th of September 2019 to the 16th of February 2023. The mean follow-up period was 1.7 years.
Methods: Data were retrieved from the MSBase Registry. Propensity scores were obtained based on age, sex, disease duration, baseline Expanded Disability Status Scale (EDSS), MS course, relapses pre-baseline, disease-modifying therapy (DMT) class and country. Primary outcomes were time to first relapse, annualised relapse rate (ARR) and time to confirm EDSS progression. Secondary outcomes were time to EDSS of 3, 4 or 6. Sensitivity analyses with baseline DMT classes were performed.
Results: The study included 2253 cases and 6441 controls. After matching, there were 2161 cases and an equal number of matched controls. Cases had a significantly higher ARR (ARR = 0.10 [95% CI 0.09-0.11]) compared to controls (ARR = 0.07 [95% CI 0.06-0.08]). Cases had a significantly greater hazard of time to first relapse compared to controls (hazard ratio (HR) = 1.54 [95% CI 1.29-1.84]). There was no association between COVID-19 infection and 24-week EDSS progression (HR = 1.18 [95% CI 0.92-1.52]), or time to EDSS of 3, 4 or 6. For patients on interferons and glatiramer acetate (BRACE), COVID-19 infection was associated with a greater hazard of time to first relapse (HR = 1.83 [95% CI 1.25-2.68]) and greater hazard of time to EDSS of 3 (HR = 2.04 [95% CI 1.06-3.90]) compared to patients on BRACE therapy without COVID-19 infection.
Conclusion: COVID-19 infection was associated with a significantly increased MS relapse rate and a shorter time to first relapse. There was no effect on confirmed EDSS progression over the short term. These results support ongoing COVID-19 risk minimisation strategies to protect patients with MS
Invasive pneumococcal disease in adults after the introduction of pneumococcal vaccination: a retrospective study in the metropolitan area of Zagreb, Croatia (2010–2022)
No full textIntroduction: Invasive pneumococcal disease (IPD) is a severe form of illness caused by Streptococcus pneumoniae with high morbidity and mortality rate in the general population, particularly in children <5 years of age, adults ≥65 years of age and the immunocompromised. As known, pneumococcal vaccination lowers the risk of IPD so the aim of this study was to investigate whether the introduction of pneumococcal vaccination has influenced the incidence and mortality of IPD in adults in Croatia.
Materials and methods: A retrospective study was conducted among adult patients (aged ≥18 years) hospitalized due to IPD in the metropolitan area of Zagreb from 1st January 2010 to 31st December 2022. Number of vaccine doses distributed were obtained from the healthcare system.
Results: During the study period, 389 patients were hospitalized, of whom 214 (55.5%) were male. The annual incidence of IPD ranged from 0.6 to 4.1/100,000 population. A total of 185 (47.6%) patients were ≥ 65 years of age and 309 (79.4%) were ≥ 50 years of age. In 331 (85.1%) of the patients, at least one risk factor was identified, with age ≥ 65 years being the most common. Bacteremic pneumonia was the most frequent clinical presentation of IPD (66.3%). Indication for vaccination had 249 patients (64%) but only 11 patients (4.4%) were vaccinated. Also, 64 patients (16.5%) died. Serotype was determined in 233 (59.9%) of the isolates, with serotype 3 being the most frequent (49, 21%), followed by serotype 14 (38, 16.3%) and 19A (15, 6.4%). A total of 180 isolates (77.3%) were included in the 13-valent conjugate vaccine, 208 (89.3%) in the 20-valent conjugate vaccine and 212 (91%) in the 23-valent pneumococcal polysaccharide vaccine.
Discussion: The introduction of pneumococcal vaccination has led to a significant decrease in the incidence and mortality of IPD in adults. To further reduce morbidity and mortality from IPD, it is necessary to increase vaccine coverage in adults, particularly in individuals with risk factors. It may be beneficial to lower the recommended vaccination age from ≥65 to ≥50 years as the substantial difference in the incidence rates of IPD between these age groups was noticed
Further validation of the association between MAPT haplotype-tagging polymorphisms and Alzheimer’s disease: neuropsychological tests, cerebrospinal fluid biomarkers, and APOE genotype
No full textIntroduction: Genetic studies have shown that variants in the microtubule-associated protein tau (MAPT) gene, which encodes tau protein, can increase the risk for Alzheimer's disease (AD). Additionally, two haplotypes of the MAPT gene (H1 and H2) are associated with various neurodegenerative disorders, including AD. This study aimed to test the association of MAPT haplotypes (H1 and H2) and MAPT haplotype-tagging polymorphisms (rs1467967, rs242557, rs3785883, rs2471738, del-In9, rs7521) with AD.
Methods: The study included 964 individuals: 113 with AD, 53 with mild cognitive impairment (MCI), 54 with other dementias, and 744 healthy controls.
Results: The results showed that individuals carrying the A allele in the MAPT rs1467967 polymorphism, the GG genotype in the MAPT rs7521 polymorphism, and the G allele in the MAPT rs242557 polymorphism had worse performance on various neuropsychological tests. Carriers of the C allele in MAPT rs2471738 polymorphism and CC homozygotes also showed worse performance on neuropsychological tests and pathological levels of several cerebrospinal fluid (CSF) biomarkers. However, T allele carriers in the MAPT rs2471738 polymorphism were more represented among patients with dementia and apolipoprotein E (APOE) ɛ4 carriers. Carriers of the H2 MAPT haplotype had worse performance on various neuropsychological tests, consistent with our previous study, which associated the H2 MAPT haplotype with pathological levels of CSF AD biomarkers. Regarding the MAPT rs3785883 polymorphism, further research is needed since both the AA and GG genotypes were associated with pathological levels of CSF and plasma AD biomarkers.
Discussion: In conclusion, further genetic studies are needed to elucidate the role of MAPT haplotypes and MAPT haplotype-tagging polymorphisms in the development of AD