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Prevalence of occult hepatitis B virus infection and characterisation of hepatitis B surface antigen mutants among adults in western Croatia
Introduction and Objectives: Occult hepatitis B virus (HBV) infection (OBI) is characterised by low levels of hepatitis B virus (HBV) DNA in the blood/liver of patients with negative hepatitis B surface antigen (HBsAg). This study aimed to determine the OBI prevalence and virological characteristics (viral genotypes and HBsAg mutants) in patients with an "anti-HBc only" serological profile. Materials and Methods: A total of 24 900 serum samples were routinely screened for hepatitis B markers over a five-year period. All anti-HBc-positive/HBsAg-negative/anti-HBs-negative sera were selected and analysed for the presence of HBV DNA. Mutational analyses of the HBs gene and polymerase gene sequences were performed. Results: 1749 (7.02%) sera were anti-HBc positive, and 113 (0.45%) sera had an "anti-HBc only" serological profile (HBsAg/anti-HBs negative). HBV DNA was detected in 12/113 (10.61%) "anti-HBc only" positive sera, representing 0.048% of all routinely tested samples. Due to extremely low viremia, HBV genome was successfully sequenced in only two sera where subgenotype D3 was confirmed. Mutational analyses of the S gene revealed multiple missense mutations. In addition to the M133I, Y134F, and G145R mutations, already associated with diagnostic escape, we also found nine novel OBI-related S-gene mutations - S136Y, F158L, K160N, E164G, S167L, A168V, L175S, S210I and F212C. Conclusions: We detected multiple known and novel S gene mutations in 2/12 (16.6%) OBI cases, nevertheless, further studies are required to determine their role in the pathogenesis of OBI. Understanding the frequencies of clinically relevant HBV mutations may contribute to improvement of diagnostic protocols
Inverted Papilloma of the Septum: a Case Report and Our Experience in the Treatment of Patients with Sinonasal Inverted Papilloma
Cilj: prikaz slučaja bolesnice s dijagnozom invertnog papiloma septuma i retrospektivna analiza dosadašnjih iskustava u liječenju bolesnika sa sinonazalnim invertnim papilomom na Klinici za otorinolaringologiju i kirurgiju glave i vrata Kliničkog bolničkog centra Rijeka. Prikaz slučaja: 30-godišnja bolesnica s otežanim disanjem kroz nos i učestalim epistaksama javila se na otorinolaringološki pregled 2022. godine. Endoskopijom nosa utvrđena je perforacija u prednjim regijama septuma. Dijagnostička obrada uključivala je biopsiju sluznice, slikovnu obradu i krvne pretrage za probir na c-ANCA i p-ANCA autoantitijela, kao i test za angiotenzin-konvertirajući enzim (ACE). Nalaz patohistološke analize pokazao je kako se radi o invertnom papilomu te je provedeno kirurško liječenje. Potom je retrospektivnom analizom utvrđeno kako su u razdoblju od travnja 2014. do ožujka 2022. godine u Klinici za otorinolaringologiju i kirurgiju glave i vrata Kliničkog bolničkog centra Rijeka liječena 22 bolesnika s dijagnozom sinonazalnog invertnog papiloma. Iskustva s njihovim liječenjem također su prikazana u ovom radu. Zaključak: Bolesnici sa sinonazalnim invertnim papilomom uspješno se liječe u našoj ustanovi endoskopskom kirurgijom sinusa. Diferencijalno-dijagnostički o ovom je tumoru potrebno razmišljati i u mladih bolesnika i bolesnica s atipičnom prezentacijom bolesti. Potrebna su daljnja istraživanja u svrhu razjašnjenja etiologije bolesti i mogućnosti predikcije recidivizma i/ili maligne alteracije ovih tumora.Aim: We present a case of a female patient diagnosed with inverted papilloma of the nasal septum and retrospective analysis of previous experiences in the treatment of patients with sinonasal inverted papilloma. The patients were treated at the Clinic for Otolaryngology and Head and Neck Surgery in the Clinical Hospital Center Rijeka. Case report: A 30-year-old patient with difficulty in breathing through the nose and frequent epistaxis came for an otolaryngological examination in 2022. Nasal endoscopy revealed a perforation in the anterior regions of the septum. Diagnostic process included mucosal biopsy, imaging, and blood tests to screen for c-ANCA and p-ANCA autoantibodies, as well as an angiotensin-converting enzyme (ACE) test. Pathohistological analysis established the diagnosis of inverted papilloma and surgical treatment was performed. After this case we did a retrospective analysis and established that in the period from April 2014 to March 2022, 22 patients with sinonasal inverted papilloma were treated in the Clinic for Otorhinolaryngology and Head and Neck Surgery, Rijeka Clinical Hospital Center. Experiences with their treatment are also presented in this paper. Conclusion: Patients with sinonasal inverted papilloma are successfully treated in our institution. Differential diagnosis of this tumor should be considered in young patients with atypical disease presentation. Further research is needed in order to clarify etiology and predict the possibility of recurrence and / or malignant alteration of these tumors
Iatrogenic Hyperkalemia Caused by Incorrect Medication Intake – a Case Report
Cilj: Hiperkalijemija je zbog svojih posljedica i pratećeg mortaliteta hitno stanje koje treba što ranije prepoznati i započeti s liječenjem. Ovaj rad ima za cilj prikazati dio dostupne dijagnostike i metode liječenja hiperkalijemije, ali i ukazati na nelogičnosti osiguravajućeg društva koje indirektno mogu dovesti do fatalnih posljedica za bolesnike. Prikaz slučaja: Bolesnik prikazan ovim radom pravovremeno je stigao u Objedinjeni hitni bolnički prijam gdje mu je zbog prisutne simptomatologije i nalaza elektrokardiograma postavljena sumnja na hiperkalijemiju. Navedeno je u kratkom vremenu potvrđeno uređajem point of care te je započeto liječenje. Incijalno se liječenje sastojalo od odgovarajuće medikamentozne terapije i transkutane elektrostimulacije, a zatim je postavljen privremeni elektrostimulator srca i provedena hitna dijaliza. Kasnije se heteroanamnestički doznalo da je bolesnik zabunom uzimao dvije vrećice kalijeva citrata ujutro i navečer, što je posljedično dovelo do jatrogene hiperkalijemije. Na otpusnom pismu, samo četiri dana pred navedeni događaj, uz preostalu terapiju naveden je nezaštićeni naziv lijeka Kalinora: kalijev citrat / kalijev hidrogenkarbonat 2/2 g 2 eff. i 1 eff. naizmjenično dnevno. Bolesnik je masu efervete protumačio kao propisanu jutarnju i večernju dozu, a liječnik obiteljske medicine prethodno je zamijenio propisanu formulaciju kalijevim citratom koji proizvodi JGL. Zaključak: Jatrogena hiperkalijemija jest rijetko stanje, ali kao i brojne druge komplikacije može nastati zbog pogrešnog uzimanja propisane terapije. Kako bi adherentnost bolesnika bila bolja, treba razmotriti uporabu zaštićenih naziva lijekova koji su bolesnicima razumljiviji. Liječnik obiteljske medicine ili ljekarnik svakako moraju propisati i izdati neki od zaštićenih oblika lijeka, stoga se nameće pitanje zašto to nije dopušteno bolničkom liječniku.Aim: Hyperkalemia, due to its consequences and accompanying mortality, is an emergency condition that should be recognized and treated as soon as possible. This paper aims to present some of the available diagnostics and treatment methods for hyperkalemia, but also to point out the illogicalities of the insurance fund, which can indirectly lead to fatal consequences for patients. Case report: The patient presented in this paper arrived in time at the Integrated Emergency Hospital Admission where, due to the present symptoms and electrocardiogram findings, hyperkalemia was suspected. The above was confirmed in a short time with the "point of care" device and the treatment was started. The initial treatment consisted of appropriate drug therapy and transcutaneous electrostimulation, then a temporary cardiac electrostimulator was placed and emergency dialysis was performed. Later, heteroanamnesis revealed that the patient mistakenly took two bags of potassium citrate in the morning and in the evening, which consequently led to iatrogenic hyperkalemia. On the discharge letter, just four days before the mentioned event, along with the remaining therapy, the generic name of the drug Kalinor was stated: potassium citrate / potassium hydrogen carbonate 2/2 g 2 eff. and 1 eff. alternately daily. The patient interpreted the effervescent mass as the prescribed morning and evening dose, and the general practitioner had previously replaced the prescribed formulation with potassium citrate produced by JGL. Conclusion: Iatrogenic hyperkalemia is a rare condition, but like many other complications, it can occur due to the incorrect use of the prescribed therapy. In order to improve patient adherence, the use of brand names of drugs that are more understandable to patients should be considered. A general practitioner or a pharmacist must certainly choose a brand medicine when prescribing and dispensing, and the question arises as to why this is not allowed for a hospital doctor
Corneal Biomechanics and Other Factors Associated with Postoperative Astigmatism after Cataract Surgery
This study aimed to investigate the impact of the cornea’s biomechanical properties, corneal hysteresis (CH), and corneal resistance factor (CRF) on postoperative astigmatism after cataract surgery and determine the other factors that influence it. Forty eyes of 40 patients (13M/27F; the median age of 74) were included in this prospective study, underwent 2.75 mm incision cataract surgery, and were followed for 30 days. Visits were scheduled at baseline before surgery (V0), the 1st (V1), the 7th (V2), and the 30th (V3) postoperative days. The main parameters estimated and analyzed with Statistica® 14.0.1 were CH, CRF, astigmatism diopter, and axis. Following the cataract surgery, the CH did not significantly change during the study visits (p = 0.109). However, there was a significant change in the CRF from baseline during the study visits (per protocol set) (p = 0.002). After a slight but insignificant increase from V0 to V1, post hoc analysis found a significant decrease in the mean CRF from V1 to V2 (p = 0.049) with no substantial change from V2 to V3. According to the post hoc analysis, the median astigmatism diopter increased significantly only from V0 to V1 (p = 0.001) and slightly but not significantly decreased to the end of the study with the achievement of a near-baseline value. The main predictors for the final astigmatism diopter (R2 = 0.898) obtained by stepwise regression analysis were its values at V0, V1, and V2 (p < 0.001). The CRF at V1 was marginally significant, with a negative parameter estimate of −0.098303 (p = 0.0623). In conclusion, there was no correlation between preoperative CH and CRF and postoperative astigmatism using 2.75 mm incision cataract surgery. However, the final astigmatism diopter’s main predictors were its baseline values before cataract surgery, the first, and the seventh postoperative days
DIABETIC KETOACIDOSIS VS. HYPEROSMOLAR HYPERGLICEMIC STATE IN CHILDREN
DM 1 je o inzulinu ovisan dijabetes koji se najčešće dijagnosticira u dječjoj ili adolescentnoj dobi i najčešće je autoimune prirode. On zahtjeva pomno praćenje i primjena inzulina uz režim prehrane i fizičke aktivnosti. DM 2 je dijabetes uzrokovan inzulinskom rezistencijom koja može biti potpuna ili djelomična. Najčešće se nalazi u pretile djece, a genetska predispozocija također ima ulogu u nastanku. Zahtjeva modifikacije životnih navika uz oralne lijekove i ponekad inzulinsku terapiju. Bitna je psihološka potpora obitelji, edukacija djeteta i obitelji, praćenje pacijenata i prevencija nastanka komplikacija. DKA je akutna komplikacija dijabetesa koja je karakterizirana hiperglikemijom (> 11,1 mmol/L) , ketozom (> 3,0 mmol/L BHOB u krvi) i metaboličkom acidozom (pH 33,3 mmol/L), hiperosmolarnosti seruma (> 320 mOsm/kg), ketoacidoza uglavnom nije prisutna no može biti (pH>7.3, bikarbonati >15,0 mmol/L) te promjene mentalnog statusa. Ekstremna dehidracija je prisutna radi osmotske diureze. Simptomi HHS-a su velika žeđ, često uriniranje, suha koža i usta, slabost i brzo zamaranje, zamućenje vida, tahikardija, hipotenzija i promjene mentalnog statusa. Najčešće komplikacije HHS-a su moždani edem, tromboembolija i renalna ozljeda. Laboratorijski nalazi za dijagnosticiranje DKA-e i HHS-a uključuju mjerenje GUK-a, određivanje acidobaznog statusa, BUN-a, određivanje serumskih i urinskih ketona te određivanje elektrolita. Terapija za DKA-u i HHS-e uključuje agresivnu korekciju tekućine te monitoriranje i ispravljanje disbalansa elektrolita (pogotovo kalija), niske doze brzodjelujućeg inzulina uz pomno praćenje vitalnih znakova te praćenje nastanka mogućih komplikacija (ponajviše moždani edem).DM 1 is an insulin-dependent diabetes that is most often diagnosed in childhood or adolescence and is most often autoimmune in nature. It requires careful monitoring and administration of insulin along with diet and physical activity. DM 2 is diabetes caused by insulin resistance, which can be complete or partial. It is most often found in obese children, and genetic predisposition also plays a role in its occurrence. It requires lifestyle modifications along with oral medications and sometimes insulin therapy. Psychological support of the family, education of the child and family, monitoring of patients and prevention of complications are essential. DKA is an acute complication of diabetes characterized by hyperglycemia (> 11.1 mmol/L), ketosis (> 3.0 mmol/L BHOB in the blood) and metabolic acidosis (pH 33.3 mmol/L), serum hyperosmolarity (> 320 mOsm/kg), ketoacidosis is mostly not present but can be (pH > 7.3, bicarbonates > 15.0 mmol/L ) and changes in mental status. Extreme dehydration is present due to osmotic diuresis. Symptoms of HHS include excessive thirst, frequent urination, dry skin and mouth, weakness and fatigue, blurred vision, tachycardia, hypotension, and changes in mental status. The most common complications of HHS are cerebral edema, thromboembolism and renal injury. Laboratory findings for diagnosing DKA and HHS include measurement of GUC, determination of acid-base status, BUN, determination of serum and urine ketones, and determination of electrolytes. Therapy for DKA and HHS includes aggressive fluid correction and monitoring and correction of electrolyte imbalances (especially potassium), low doses of fast-acting insulin with close monitoring of vital signs and monitoring of possible complications (mainly cerebral edema)
TESTOSTERONE REPLACEMENT THERAPY IN LATE ONSET HYPOGONADISM
This paper aims to find out the utility of testosterone replacement therapy (TRT) in managing LOH, focusing on its implications for muscle mass, strength, bone density, sexual function, mood, cognitive abilities, cardiovascular health, and prostate well-being. Gonads, including testes in males, are essential for producing reproductive cells and hormones like T, which is crucial for male physical characteristics, sexual function, and overall health. T production is regulated by the HPG axis and affects various bodily functions, from muscle and bone health to mood and cognitive abilities. Hypogonadism, characterized by reduced T production, can arise from issues within the testes themselves (primary) or from problems in the hypothalamus or pituitary gland (secondary). Diagnosing this condition involves measuring serum T levels. Testosterone replacement therapy is explored as a treatment for LOH in older men, offering potential benefits for muscle mass, strength, bone density, sexual function, and mood. But TRT's impact on cardiovascular and prostate health remains controversial. Various TRT delivery methods exist, including injections, patches, gels, oral applications, and nasal gels, each with specific advantages, potential side effects, and monitoring requirements to manage risks effectively. Despite advances, no TRT method fully meets all criteria for optimal treatment as defined by the WHO, with ongoing research and individualized patient considerations guiding therapy choices
NEUROENDOCRINOLOGY OF ROMANTIC LOVE
This review paper explores the neurobiological mechanisms underlying romantic and maternal love, focusing on specific brain regions and the role of the neuropeptide oxytocin. Using functional magnetic resonance imaging (fMRI), the studies examined brain activity in individuals experiencing love, revealing that romantic love activates areas such as the middle insula, anterior cingulate cortex, caudate nucleus, and putamen, which are associated with emotional processing and reward. Deactivations in regions linked to negative emotions, such as the amygdala, were also observed, suggesting that love enhances positive feelings while suppressing negative ones. Comparing romantic and maternal love, the studies found overlapping activation in brain regions abundant in oxytocin and vasopressin receptors, highlighting their importance in bonding and attachment. Oxytocin was shown to play a crucial role in enhancing social bonding, trust, and positive behaviors. It increases the recognition of emotional expressions and promotes in-group trust. Genetic variations in the oxytocin receptor gene (OXTR) were found to influence social behaviors and attachment. Behavioral interventions increasing gratitude expressions, facilitated by oxytocin, improved relationship quality and time spent together. These findings suggest that oxytocin enhances partner touch responses and visual attention to familiar faces, supporting its role in social bonding
Alopecia Areata - Current and Emerging Therapies
Alopecia Areata (AA) is an autoimmune disorder characterized by non-scarring hair loss. Its pathogenesis is not clear, but may include various factors like a genetic predisposition, immune system dysfunction, oxidative stress, allergies and the skin and gut microbiome. AA can affect individuals of all ages and has its peak incidence in the second and third decades of life.
Clinically, it presents with patchy hair loss which can advance to total scalp hair loss (AA totalis) or complete loss of body hair (AA universalis). Nail involvement is also commonly associated. The course of the disease is unpredictable, and early disease onset and severe initial presentation are negative prognostic factors.
The diagnosis is mainly clinical and based on the pattern of hair loss. Additionally, trichoscopy or in some cases a scalp biopsy can be performed.
The treatment is adjusted to the severity of AA. Mild and unifocal cases can be treated with topical therapies, preferably with intralesional corticosteroids. In more severe cases, systemic therapies are indicated, including immunosuppressants such as methotrexate or cyclosporine. Recently, JAKi like baricitinib and ritlecitinib have emerged as promising new treatments for severe cases of AA.
To conclude, AA is challenging due to its unpredictable course and the potential psychological impact on the patients. The emerging therapies offer new hope for patients with severe AA to achieve hair regrowth and improvement of the quality of life
Congenital diaphragmatic hernia: clinical and surgical aspects
Kongenitalna dijafragmalna hernija je prirođeni defekt dijafragme koji nastaje zbog
poremećaja embrionalnog razvoja same dijafragme. Etiologija nastanka CDH je još uvijek
nepoznata, ali pretpostavlja se da u nastanku sudjeluju multifaktorijalni čimbenici. Zbog
poremećaja u razvoju dijafragme zaostaje komunikacija između prsne i abdominalne šupljine
te dolazi do protruzije abdominalnih organa u toraks. Protrudirani organi interferiraju sa
razvojem organa torakalne šupljine, prvenstveno sa razvojem pluća. Patofiziološki, najbitnije
promjene koje nastaju zbog CDH su promjene dišnog i kardiovaskularnog sustava:
hipoplazija pluća, plućna hipertenzija i disfunkcija ventrikula. Dijagnoza CDH se najčešće
postavlja u trudnoći, na rutinskom ultrazvučnom pregledu trudnice. Klinička slika izravno
korelira sa stupnjem hipoplazije pluća i plućne hipertenzije. Ovisno o tome, u prva 24-48 h
po porodu, novorođenče može razviti akutni respiratorni distres. Osim respiratornih
simptoma, CDH može uzrokovati i poremećaje gastrointestinalnog i mišićno-koštanog
sustava, poremećaje u razvoju te gubitak sluha. Liječenje CDH se temelji na uspostavi uredne
saturacije i ventilacije nakon poroda te elektivnog kirurškog zahvata nakon uspostave
hemodinamske stabilnosti novorođenčeta.Congenital diaphragmatic hernia is a congenital defect of the diaphragm resulting
from a disruption of the embryonic development of the diaphragm. The etiology of CDH is
still unknown, but it is assumed that multiple factors are involved. Due to disorders in the
development of the diaphragm, there is abnormal communication between the thoracic and
abdominal cavity, which causes the protrusion of abdominal organs into the thorax.
Protruding organs interfere with the development of the organs in the thoracic cavity,
primarily with the development of the lungs. Pathophysiologically, the most important
changes that occur due to CDH are changes in the respiratory and cardiovascular systems:
pulmonary hypoplasia, pulmonary hypertension and ventricular dysfunction. The diagnosis of
CDH is most often made during pregnancy, on a routine ultrasound examination of the
pregnant woman. The clinical signs directly correlate with the degree of hypoplasia of the
lungs and pulmonary hypertension. Depending on this, in the first 24-48 hours after delivery,
the newborn may develop acute respiratory distress. In addition to respiratory symptoms,
CDH may also cause gastrointestinal and musculoskeletal disorders, development disorders
and hearing loss. Treatment of CDH is based on the establishment of regular saturation and
ventilation after delivery and elective surgical repair after the establishment of hemodynamic
stability of the newborn
Kidney transplantation and Fabry disease
Fabryeva bolest je označena kao rijetka X-vezana bolest koja proizlazi iz potpunog ili djelomičnog nedostatka enzima alfa-galaktozidaze A zbog mutacija gena GLA. Ovaj genetski poremećaj uzrokuje nakupljanje globotriaosilceramida (Gb3) unutar stanica, što rezultira povećanim razinama Gb3 u plazmi. Incidencija bolesti procjenjuje se na 1:50,000 do 1:117,000 kod muškaraca. Simptomi bolesti su akroparestezije (bolovi u ekstremitetima ili cijelom tijelu), hipohidroza, gastrointestinalni problemi poput bolova u trbuhu. Na koži se mogu pojaviti različite manifestacije, uključujući male crvene mrlje oko pupka, razvoj angiokeratoma te očne manifestacije poput zamagljenja leće i oštećenja rožnice. Fabryeva nefropatija obično započinje s mikroalbuminurijom i/ili proteinurijom, često već u djetinjstvu. Kada se pacijenti predstavljaju s takvim simptomima, liječnici bi trebali razmotriti mogućnost Fabryeve bolesti kroz detaljnu anamnezu i fizikalni pregled. Također je važno provjeriti elektrolite, bubrežnu funkciju, sediment urina te napraviti EKG i ehokardiogram radi otkrivanja srčanih problema. Dijagnoza se obično potvrđuje testiranjem razine enzima alfa-galaktozidaze A, a biopsija kože ili bubrega može pomoći ako su testovi nedostupni. Kronična bolest bubrega predstavlja jedan od najznačajnijih izazova kod osoba s Fabryjevom bolešću, što povećava rizik od završne faze bolesti bubrega u toj populaciji. Transplantacija bubrega je optimalna terapija za pacijente s Fabryjevom bolešću jer se pokazalo da je recidiv bolesti u presatku rijedak.Fabry disease is classified as a rare X-linked disorder resulting from complete or partial deficiency of the enzyme alpha-galactosidase A due to mutations in the GLA gene. This genetic disorder leads to the accumulation of globotriaosylceramide (Gb3) within cells, resulting in increased levels of Gb3 in the plasma. The incidence of the disease is estimated at 1:50,000 to 1:117,000 in males. Symptoms of the disease include acroparesthesia (pain in the limbs or throughout the body), hypohidrosis, gastrointestinal problems such as abdominal pain. Various manifestations can appear on the skin, including small red spots around the navel, development of angiokeratomas, and ocular manifestations such as lens opacity and corneal damage. Fabry nephropathy typically begins with microalbuminuria and/or proteinuria, often already in childhood. When patients present with such symptoms, doctors should consider the possibility of Fabry disease through detailed history-taking and physical examination. It is also important to check electrolytes, kidney function, urinary sediment, and perform an EKG and echocardiogram to detect heart problems. Diagnosis is usually confirmed by testing the level of alpha-galactosidase A enzyme, and a skin or kidney biopsy may help if tests are unavailable. Chronic kidney disease is one of the most significant challenges in individuals with Fabry disease, increasing the risk of end-stage kidney disease in this population. Kidney transplantation is the optimal therapy for patients with Fabry disease as recurrence of the disease in the graft is rarely reported and usually occurs many years after transplantation