Veterinary medicine - Repository of PHD, master's thesis
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Association between ACE gene polymorphism and severity of clinical presentation in patients with systemic sclerosis
No full textUvod: Sistemsku sklerozu (SSc) obilježava autoimunost, upala, vaskulopatija i fibroza. U sličnim patofiziološkim mehanizmima sudjeluje sustav renin-angiotenzin (RAS) čija je središnja molekula enzim za pretvorbu angiotenzina (ACE). Njegova aktivnost ovisi o insercijskom (II), delecijskom (DD) i kodominantnom (ID) polimorfizmu u intronu 16 ACE-gena, pri čemu nosioci polimorfizma DD naspram II imaju dvostruko veću aktivnost ACE.
Hipoteza: Bolesnici s polimorfizmom DD ACE-genotipa imaju težu kliničku sliku SSc.
Cilj: Ispitati povezanost ACE-genotipa s fenotipskim obilježjima oboljelih od SSc.
Ispitanici i metode: Provedena je retrospektivna analiza povezanosti polimorfizma ACE-gena s težinom manifestacija SSc na više organskih sustava pri postavljanju dijagnoze u 135 bolesnika, nakon 5 godina u 105 i nakon 10 godina praćenja u 70 bolesnika.
Rezultati: Nije nađena statistički značajna povezanost polimorfizma ACE-gena s težinom kliničke slike SSc. Međutim, u vremenskoj točki nakon deset godina zabilježena je statistički značajna razlika između 3 genotipa u vrijednosti komponente komplementa C4 (najniža vrijednost u genotipu II, a najviša u genotipu DD) te istisne frakcije lijeve klijetke (LVEF; najniža vrijednost u genotipu ID, a najviša u DD). Tijekom desetogodišnjeg perioda došlo je do statistički značajnog pada vrijednosti sedimentacije eritrocita (SE) i forsiranog ekspiracijskog volumena tijekom prve sekunde (FEV1) u genotipu ID te do značajnog povećanja ukupnog zbroja bodova na Medsgerovoj ljestvici težine bolesti u genotipu II i ID.
Zaključak: Hipoteza da bolesnici s polimorfizmom DD ACE-gena imaju težu kliničku sliku SSc nije potvrđena. Međutim, genotipovi II i ID mogli bi biti prediktori progresije bolesti.Introduction: Systemic sclerosis (SSc) is characterized by autoimmunity, inflammation, vasculopathy and fibrosis. Renin-angiotensin system (RAS) is implicated in similar pathophysiological mechanisms. The central molecule of RAS is angiotensin converting enzyme (ACE) whose activity is regulated by the insertion (II), deletion (DD) or codominant (ID) polymorphism in introne 16 of the ACE gene. DD polymorphism carriers have twice the ACE activity of those with II polymorphism.
Hypothesis: ACE DD polymorphism carriers have more severe multiorgan manifestations of SSc.
Aim: Analysis of the association between ACE gene polymorphism and phenotypic features of SSc.
Patients and methods: Analysis of the association between severity of SSc multiorgan manifestations and ACE gene polymorphism was performed in 135, 105 and 70 patients at the time of diagnosis, after 5 and 10 years of follow-up, respectively.
Results: No statistically significant association between ACE gene polymorphism and the severity of multiorgan SSc manifestations was found. At a time point after 10 years of follow-up, statistically significant differences between the 3 genotypes were found in C4 complement levels (lowest values in II, highest in DD genotype) and left ventricular ejection fraction (LVEF; lowest values in ID, highest in DD genotype). During 10 years of follow-up, there was a statistically significant decrease in erythrocyte sedimentation rate (ESR) and forced expiratory volume during the first second (FEV1) in genotype ID and increase in total sum of Medsger severity index in genotypes II and ID.
Conclusion: Hypothesis that ACE DD polymorphism carriers have more severe multiorgan SSc manifestations has been rejected. II and ID genotype could be biomarkers of disease progression
Gene analysis of the complement system in adult patients with elements of thrombotic microangiopathy – case series
No full textTrombotična mikroangiopatija (TMA) je patohistološki entitet obilježen stvaranjem tromba u mikrocirkulaciji, a klinički se definira posljedičnom mikroangiopatskom hemolitičkom anemijom (MAHA) i trombocitopenijom uz oštećenje ciljnih organa, najčešće akutnim oštećenjem bubrega (ABO). Određivanje etiologije može biti složeno. Oblik bolesti trombotična trombocitopenična purpura (TTP) uzrokovan je smanjenom aktivnošću proteaze ADAMTS13. Većina drugih oblika tzv. sekundarne TMA, vezana je etiološki uz neki patogeni proces u organizmu, najčešće hipertenzivnu krizu. Međutim, i u tim stanjima moguć je poremećaj sustava komplementa, što je glavno etiološko obilježje primarnog atipičnog hemolitičko-uremijskog sindroma (aHUS). Zbog toga je važna serološka analiza sustava komplementa, a u nekim slučajevima i njegova genska analiza. Prikazujemo karakteristike deset pacijenata kod kojih su prisutni laboratorijski i/ili patohistološki elementi TMA i u kojih je učinjena i serološka i genska analiza sustava komplementa. U troje pacijenata nađene su patogene ili vjerojatno patogene genske varijante povezane s dijagnozom primarnog aHUS-a. Svi oni su imali MAHA i ABO te patohistološki dokazanu TMA. Kod druge skupine od troje pacijenata nađena je na biopsiji bubrega TMA, ali su svi ostali rezultati (uključujući gensku analizu sastavnica komplementa) bili neupadljivi. Radilo se o pacijentima koji su se prezentirali hipertenzivnom krizom, a testiranje je provedeno u svrhu predtransplantacijske obrade. Kod preostalih četvero pacijenata pronađene su rizične genetske varijante za razvoj aHUS-a. Svi ovi pacijenti (osim jednog) imali su MAHA + ABO. U dva pacijenta nije nađena TMA u tkivu bubrega, no biopsija je učinjena mjesec dana nakon akutne bolesti. Genetska analiza sustava komplementa preporučuje se učiniti ako nema jasnoga sekundarnog uzroka TMA ili ako je važna za određivanje terapije, odnosno za transplantaciju bubrega.Thrombotic microangiopathy (TMA) is a pathohistological entity characterized by the formation of thrombi in microcirculation, with clinically defined consequent microangiopathic hemolytic anemia (MAHA) and thrombocytopenia with damage to target organs, most often acute kidney injury (AKI). Determining the etiology can be complex. Thrombotic thrombocytopenic purpura (TTP) is caused by reduced activity of the protease ADAMTS13. Most other forms, so-called secondary TMA, are etiologically linked to some pathogenic process in the body, most often a hypertensive crisis. Even in these conditions, a disorder of the complement system is possible, which is the main etiological feature of primary atypical hemolytic uremic syndrome (aHUS). This is why serological analysis of the complement system, and in some cases its genetic analysis, is important. We present the characteristics of ten patients in whom laboratory and/or pathohistological elements of TMA were present, and in whom both serological and gene analysis of the complement system were performed. Genetic pathogenic or likely pathogenic variants associated with the diagnosis of primary aHUS were found in three patients. All of them had MAHA and AKI and pathohistologically proven TMA. In another group of three patients, TMA was found on kidney biopsy, but all other results (including gene analysis of complement components) were unremarkable. These were patients who presented with hypertensive crisis, and the testing was done for the purpose of pretransplant workup. In the remaining four patients, genetic risk variants for the development of aHUS were found. All these patients (except one) had MAHA + AKI. In two patients no TMA was found in the kidney tissue – but the biopsy was done one month after the acute illness. Gene analysis of the complement system is recommended if there is no clear secondary cause of TMA or if it is important for determining therapy, or for kidney transplantation
Comparison of Clinical, Pathological, and Procedural Characteristics of Adult and Pediatric Acute Appendicitis before and during the COVID-19 Pandemic
No full textBackground: This study aims to analyze the impact of the COVID-19 pandemic on the clinical, pathological, and surgical characteristics of acute appendicitis (AA) at the University Hospital Centre (UHC) Zagreb.
Methods: This retrospective study analyzed demographic, clinical, and surgical data from consecutive AA patients. Data were collected from an electronic database for two periods: 1 January to 31 December 2019 (pre-COVID-19), and 11 March 2020, to 11 March 2021 (COVID-19 pandemic).
Results: During the two study periods, 855 appendectomies were performed, 427 in the pre-pandemic, and 428 during the pandemic. Demographic data were comparable between groups. There was statistically no significant difference in the type of appendectomy (p = 0.33) and the median hospital length of stay (3; (2–5) days, p = 0.08). There was an increase in the conversion rate during the pandemic period (4.2% vs. 7.7%, p = 0.03). The negative appendectomy rate and the incidence of perforated AA did not differ significantly (p = 0.34 for both).
Conclusions: We did not observe a significant increase in the rate of AA complications during the COVID-19 pandemic at the UHC Zagreb. This may be attributed to two factors: (1) AA was diagnosed and treated as an emergency, which remained available during the pandemic, and (2) diagnostic and therapeutic protocols remained unaltered. We recommend a laparoscopic approach even during the COVID-19 pandemic
A Comparative Study of the Aggregate Index of Systemic Inflammation (AISI) and C-Reactive Protein (CRP) in Predicting Odontogenic Abscesses Severity: A Novel Approach to Assessing Immunoinflammatory Response
No full textBackground/Objectives: Odontogenic abscesses are a common cause of emergency visits to oral and maxillofacial surgery departments and can lead to life-threatening complications if they are not recognized and treated promptly. The aim of this study was to evaluate the prognostic value of the Aggregate Index of Systemic Inflammation (AISI) in comparison to other systemic inflammatory indices, including the Systemic Immune Inflammation Index (SII), the Neutrophil-to-Lymphocyte Ratio (NLR), the Platelet-to-Lymphocyte Ratio (PLR), and the Lymphocyte-to-Monocyte Ratio (LMR), in predicting the severity of odontogenic abscesses.
Methods: This retrospective study included 221 patients hospitalized for odontogenic abscesses at Dubrava University hospital between January 2019 and December 2023. Clinical and laboratory data, including AISI, SII, NLR, PLR, and LMR, were collected. The severity of the abscesses was assessed using the Symptom Severity (SS) Score and patients were categorized into less severe and severe groups based on their scores. An ROC curve analysis was used to assess the predictive accuracy of each inflammatory index.
Results: The AISI was identified as the most effective predictor of abscess severity and had the highest sensitivity (SE = 82.93) and specificity (SP = 81.63) among the indices analyzed. It outperformed C-reactive protein (CRP) in predicting severe abscesses with an AUC of 0.90 compared to 0.74 for CRP. In addition, AISI showed significant correlations with length of hospital stay and the occurrence of systemic inflammatory response syndrome (SIRS).
Conclusions: The AISI index is a better predictor of odontogenic abscess severity compared to other systemic inflammatory markers and CRP. Its integration into clinical practice could improve the early detection of high-risk patients, leading to better treatment outcomes and lower risks of complications
Outcome of pelvic ring injuries
No full textOutcome evaluation is of major importance to provide data to analyze the value of the chosen treatment concept. Despite an increasing effort of analyzing outcome after treatment of different pelvic ring injuries, a mixture of different outcome parameters is in use. The Majeed score is most frequently used for mid- to long-term evaluation and the quality of life is analyzed using the SF-36 score. The lack in nearly all studies is that different treatment concepts are used, and only selected evaluation parameters are reported. Until today, no well-accepted standardized measurement instruments are available to analyze the clinical and radiological results after pelvic ring injuries. Overall, stability-based long-term sequelae can be expected with increasing complaints from stable type A injuries to completely unstable type C injuries. Beside a fracture-type specific treatment, concomitant injuries of other injury regions and associated local pelvic injuries (complex pelvic trauma) seem to additionally influence the results. Results of treatment of specific fracture types are sparse as a wide range of different injury types and different treatment concepts are analyzed within these analyses. A sufficient pelvic outcome instrument which addresses relevant pelvic outcome parameters is still missing. Thus, future evaluation of long-term results after pelvic ring. injuries should include prospective, multicenter outcome studies with comparable parameters
Calcitonin-Gene-Related Peptide in Migraine and Tension-Type Headache in Children During Interictal Period
No full textBackground/Objectives: Research on calcitonin-gene-related peptide (CGRP) in adult migraine is extensive, but its role in childhood migraine remains unclear. This study aimed to evaluate serum CGRP levels in children experiencing migraine and tension-type headache (TTH) during interictal periods, comparing these levels to age-matched healthy controls.
Methods: A total of 66 migraine patients, 59 with TTH, and 53 controls were recruited and stratified by headache onset age: under 7, 7–12, and over 12 years. CGRP levels were quantified using enzyme-linked immunosorbent assay (ELISA).
Results: The migraine patients showed significantly higher serum CGRP levels than both the TTH patients and the controls (p < 0.001), with no significant difference between the latter two groups. Among the migraine patients, those without aura (MO) exhibited higher CGRP levels than those with aura (MA). The CGRP levels were lower in the. MA patients whose headaches began between ages 7 and 12 compared to the subjects with MO, while no significant differences were found in the patients whose headaches began after age 12.
Conclusions: These findings suggest that elevated serum CGRP is indicative of pediatric migraine, with variations based on migraine type and age of onset. The difference in CGRP in preadolescent migraineurs with and without aura suggest that CGRP levels may vary depending on age and on migraine type
Molecular Mechanisms Affecting Statin Pharmacokinetics after Bariatric Surgery
No full textAccording to recent data, one in eight people in the world struggle with obesity. Obesity management is increasingly dependent on bariatric surgical interventions, as the combination of lifestyle modifications and pharmacotherapy could have a modest long-term effect. Surgery is recommended only for individuals whose body mass index (BMI) ≥ 40 kg/m2 and ≥ 35 kg/m2 in the presence of weight-related comorbidities. The most commonly performed procedures are sleeve gastrectomy and roux-en-Y gastric bypass. Pharmacokinetic and pharmacodynamic alterations occur as a result of the anatomical and physiological changes caused by surgery, which further differ depending on physicochemical drug factors and factors related to the dosage form. The following modifications are distinguished based on the type of bariatric surgery performed. Most bariatric patients have accompanying comorbidities, including dyslipidemia treated with hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins. Significant improvements in the lipid profile are observed early in the postoperative period. The data reported in this review on statin pharmacokinetic alterations have demonstrated substantial inter- and intravariability, making it difficult to adopt clear guidelines. Based on the current literature review, reducing the statin dose to the lowest effective with continuous monitoring is considered an optimal approach in clinical practice
Serum Hepatocyte Growth Factor Concentration Correlates with Albuminuria in Individuals with Optimal Blood Pressure and Untreated Arterial Hypertension
No full textBackground/Objectives: Hepatocyte growth factor (HGF) is a protective factor against acute renal injury and chronic renal fibrosis. A positive correlation between HGF and blood pressure (BP) has been established. This study aimed to determine the association between serum HGF concentration and albuminuria in subjects with optimal blood pressure (OBP) and untreated arterial hypertension (UAH), as well as its association with BP levels, serum glucose levels, and inflammatory markers.
Methods: Data from 563 subjects were analyzed. Albuminuria was normalized to urine creatinine and expressed as the albumin/creatinine ratio (ACR). HGF, serum glucose, C-reactive protein, and blood leucocyte counts were measured. BP was measured and subjects were divided into optimal blood pressure (BP 140/90 mmHg, N = 268) groups.
Results: The subjects with UAH were significantly older and had higher values of body mass index, waist circumference, serum total and LDL cholesterol levels, triglyceride levels, fasting glucose levels, and ACR (all p < 0.001). A significant positive correlation was found between serum HGF concentration and ACR in both groups. There was no difference or correlation between HGF and BP or inflammatory markers in either group. The multivariate regression analysis identified serum HGF concentration as a strong predictor of ACR increase (Beta = 0.376, p < 0.001).
Conclusion: This study found that serum HGF concentration is associated with albuminuria not only in individuals with untreated arterial hypertension, but also in those with optimal blood pressure. The results suggest that serum HGF is an independent predictor of ACR increase in both groups
The effectiveness of 4500 Joule therapeutic ultrasound in the treatment of calcific tendinitis of the shoulder
No full textKalcificirajući tendinitis ramena (KT) karakteriziran je odlaganjem kalcijevih depozita u tetive rotatorne manžete. Individualna medicinska gimnastika smatra se osnovnom u liječenju, dok su dokazi o učinkovitosti terapijskog ultrazvuka (T-UZV) nedostatni. Ovo dvostruko slijepo randomizirano (placebom kontrolirano) istraživanje imalo je cilj dokazati utječe li dodatak T-UZV-a jačine 4500 J individualnoj medicinskoj gimnastici u liječenju simptomatskog KT-a ramena na ishod rehabilitacije (smanjenje veličine kalcifikata, bol, pokretljivost, funkcionalna sposobnost i zadovoljstvo ispitanika ishodom) u odnosu na liječenje samo individualnom medicinskom gimnastikom. Ukupno 46 ispitanika s ultrazvučno dokazanim KT-om ramena podijeljeno je u dvije skupine (52 ispitivana ramena, 26 po skupini). Individualna medicinska gimnastika u obje skupine provodila se pola sata po pojedinačnoj terapijskoj intervenciji. U ispitivanoj skupini T-UZV (intenziteta 1,5 W/cm2, frekvencije 1 MHz, trajanja 10 min) se aplicirao 4 tjedna,
dok je kontrolna skupina dobivala tzv. ''sham'' T-UZV. Svi parametri ishoda rehabilitacije poboljšali su se nakon terapijske intervencije u obje skupine. Nakon terapijske intervencije zabilježeno je značajno smanjenje veličine kalcifikata u ispitivanoj skupini u odnosu na kontrolu: -10,92% (IQR 4,61% to 19,38%) vs. -5,04% (2,30% to 7,22%), P=0,008, kao i poboljšanje snage stiska šake. U drugim mjerenim pokazateljima ishoda rehabilitacije nisu zabilježene značajne razlike između skupina.Calcific shoulder tendinitis (CST) is characterized by carbonate apatite crystal deposition in the rotator cuff tendons. Therapeutic exercises have been the mainstay of CST treatment, and evidence for therapeutic ultrasound (T-US) utilization and efficacy is lacking. This double-blind, placebo-controlled study aimed to determine whether 4500 J T-US combined with therapeutic exercises is superior to therapeutic exercises alone regarding calcification size reduction, pain, shoulder mobility, handgrip strength, functional status (SPADI), and overall rehabilitation satisfaction in chronic symptomatic CST. 46 patients with sonographically confirmed CST were divided into two groups (52 shoulders, 26 per group) and performed the same therapeutic exercises for half an hour. In the treatment group T-US (an intensity of 1,5 W/cm2, 1 MHz frequency, 10 minutes per session), and in the control group, sham T-US was applied for 4 weeks. All assessed variables improved in both groups after the treatment. A significantly greater reduction in calcification size was recorded in the treatment group compared to control: -10,92% (IQR 4,61% to 19,38%) versus -5,04% (2,30% to 7,22%), P=0.008. An increase in hand grip strength was also observed in the treatment group compared to control while no significant differences were observed for other evaluated parameters
The importance of photoprotection in the treatment of acne
No full textAcne vulgaris je kronična upalna bolest pilosebacealne jedinice. Jedna je od najčešćih dermatoza i zahvaća oko 85% adolescenata, a najčešće se pojavljuje na licu, leđima i prsima u obliku neupalnih lezija (otvorenih i zatvorenih komedona) i upalnih promjena (papula, pustula i nodusa). Akne je polietiološka bolest za čiji nastanak je potrebna interakcija četiri osnovna etiopatogenetska čimbenika: folikularne hiperkeratinizacije, povećane kolonizacije pilocebacealnog folikula komenzalnom bakterijom Cutibacterium acnes, povećanog stvaranja sebuma te upalnog odgovora. U nastanku i tijeku akne treba istaknuti važnost utjecaja okolišnih čimbenika. Među njima izuzetno važnu ulogu ima ultraljubičasto (UV) zračenje koje putem različitih mehanizama dodatno pridonosi pogoršanju učinka gore navedenih čimbenika i pospješuje upalni odgovor. Na temelju brojnih istraživanja koja su pokazala kako UV zračenje ima negativan utjecaj na akne, fotoprotekcija se smatra važnim i neizostavnim postupkom u terapiji akne. Osim što sprječava pogoršanje akne, fotoprotekcija smanjuje rizik za nastanak dugotrajnih posljedica akne poput postupalnih hiperpigmentacija. Onemogućavajući prodiranje UV zraka u kožu, fotoprotekcija sprječava i interakciju UV zraka s aktivnim sastojcima farmakoterapije za akne koja inače uzrokuju veću fotoosjetljivost kože. Važno je educirati pacijente o svim korisnim učincima fotoprotekcije kako bi se postigao što bolji učinak propisane terapije za akne.Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. It is one of the most common dermatoses, affecting about 85% of adolescents, and typically appears on the face, back, and chest in a form of non-inflammatory lesions (open and closed comedones) and inflammatory lesions (papules, pustules, and nodules). Acne is a polyetiological disease, requiring the interaction of four main etiopathogenetic factors for its development: follicular hyperkeratinization, increased colonization of the pilosebaceous follicle by the commensal bacteria Cutibacterium acnes, increased sebum production and inflammatory response. The role of environmental factors greatly contributes to the development and course of acne. Ultraviolet (UV) radiation is one of the most important since it significantly exacerbates the effects of the main etiopathogenetic factors and intensifies the inflammatory response through various mechanisms. Based on numerous studies that have proved that UV radiation has a negative impact on acne, photoprotection is considered an important and essential procedure in acne therapy. Not only does photoprotection reduce the risk of long-term acne consequences, such as post-inflammatory hyperpigmentation, but it also prevents acne from worsening. By preventing UV rays from penetrating the skin, photoprotection also prevents their interaction with the active ingredients of acne pharmacotherapy, which would otherwise consequently cause increased photosensitivity of the skin. It is important to educate patients about all the beneficial effects of photoprotection in order to achieve the best possible effect of prescribed acne therapy