The role of testicular biopsy in human assisted reproduction

U ovom diplomskom radu iznesene su spoznaje o epidemiologiji neplodnosti u ljudi, s posebnim osvrtom na situaciju u Republici Hrvatskoj. Rad pobliže opisuje ulogu ICSI metode u liječenju muške neplodnosti. Također se opisuju mikrokirurški postupci koji omogućuju izolaciju spermija iz muškog spolnog sustava kako bi se koristili za gore spomenutu ICSI metodu. Posebna pažnja posvećena je TESE postupku te njegovoj novijoj varijanti, metodi nazvanoj mTESE. Iznesena su i prva hrvatska iskustva s TESE. Rezultati upućuju na činjenicu da je biopsija sjemenika sa krioprezervacijom važna metoda u liječenju neplodnih muškaraca s azoospermijom.This graduation paper presented the findings on the epidemiology of infertility in humans with a special reference to the situation in the Republic of Croatia. The paper describes in detail the role of ICSI method in the treatment of male infertility. It also describes the microsurgical procedures that allow the isolation of spermatozoa from the male reproductive system to be used for the above-mentioned ICSI method. Special attention was paid to the TESE procedure and its newer variant, the method called mTESE. Herein, the first Croatian experience with TESE were presented. Results indicate that a testicular biopsy with cryopreservation important method in the treatment of infertile men with azoospermia

Ekstrakorporalno uklanjanje ugljičnog dioksida (ECCO2R) u liječenju puerpere sa sindromom akutnog respiracijskog distresa (ARDS) uzrokovanog bakterijskom upalom pluća

Extracorporeal carbon dioxide removal (ECCO2R) is a method of reducing surplus CO2 levels from patients who are adequately oxygenated via mechanical ventilation. Although the method is currently in an experimental stage, we present a case of acute respiratory distress syndrome (ARDS) caused by severe bacterial pneumonia in which before mentioned method was chosen and successfully utilized.Ekstrakorporalno uklanjanje ugljičnog dioksida (ECCO2R) je metoda smanjenja viška ugljičnog dioksida (CO2) u bolesnika koji su adekvatno oksigenirani putem mehaničke ventilacije. Iako je metoda trenutno u eksperimentalnoj fazi, prikazujemo bolesnicu sa sindromom akutnog respiracijskog distresa (ARDS) uzrokovanog teškom bakterijskom upalom pluća u liječenju koje je spomenuta metoda odabrana i uspješno primijenjena

Ekstrakorporalno uklanjanje ugljičnog dioksida (ECCO2R) u liječenju puerpere sa sindromom akutnog respiracijskog distresa (ARDS) uzrokovanog bakterijskom upalom pluća

Extracorporeal carbon dioxide removal (ECCO2R) is a method of reducing surplus CO2 levels from patients who are adequately oxygenated via mechanical ventilation. Although the method is currently in an experimental stage, we present a case of acute respiratory distress syndrome (ARDS) caused by severe bacterial pneumonia in which before mentioned method was chosen and successfully utilized.Ekstrakorporalno uklanjanje ugljičnog dioksida (ECCO2R) je metoda smanjenja viška ugljičnog dioksida (CO2) u bolesnika koji su adekvatno oksigenirani putem mehaničke ventilacije. Iako je metoda trenutno u eksperimentalnoj fazi, prikazujemo bolesnicu sa sindromom akutnog respiracijskog distresa (ARDS) uzrokovanog teškom bakterijskom upalom pluća u liječenju koje je spomenuta metoda odabrana i uspješno primijenjena

Successful treatment of genotype 3 hepatitis C infection in a noncirrhotic HIV infected patient on chronic dialysis with the combination of sofosbuvir and velpatasvir

RATIONALE: Data on anti-HCV therapy in patients on dialysis is still evolving. Sofosbuvir is mainly eliminated through the renal route and there is controversy about its use in these patients. ----- PATIENT CONCERNS: We describe a 53-year-old male patient with HCV genotype 3 and human immunodeficiency type 1 (HIV) infection on chronic dialysis. HIV infection was diagnosed in 1987 and since July 2007 the patient was compliant with his antiretroviral therapy (ART) and had an undetectable plasma HIV viral load on all follow-up measurements. The patient was known to have HCV infection since 1997 but has never been treated for chronic hepatitis C. Because of progressive renal impairment dialysis started in 2005. ----- DIAGNOSIS: Before anti-HCV treatment commenced the patient liver transient elastography (FibroScan) indicated F3 fibrosis (stiffness, 11.6 kPa) and his HCV RNA viral load was 320,798 IU/mL (Abbott RealTime HCV assay). ----- INTERVENTION: Fixed dose combination of sofosbuvir/velpatasvir (400 mg/100 mg) for 11 weeks. ----- OUTCOMES: Twelve weeks after treatment cessation HCV RNA was undetectable, hence the patient achieved a sustained virologic response. The drugs were well tolerated and the patient did not report any side effects. ----- LESSONS: Sofosbuvir/velpatasvir may be an option for HCV genotype 3 infection in patients coinfected with HIV on long-term dialysis

Etiology and outcome of bacterial infections in patients with liver cirrhosis - a retrospective cohort study

Uvod: Bakterijske infekcije čest su uzrok komplikacija i dekompenzacije kod bolesnika s cirozom jetre. Cilj je ove studije proučiti etiologiju, kliničke manifestacije, tijek i ishod bakterijskih infekcija te identificirati prediktore mortaliteta kod bolesnika s cirozom jetre i sepsom. Materijali/metode: Proveli smo retrospektivnu kohortnu studiju u koju je uključeno 257 bolesnika s cirozom jetre koji su bili hospitalizirani u Klinici za infektivne bolesti „Dr. Fran Mihaljević“ (KZIB) u petogodišnjem razdoblju (2011. - 2015.). Analizirali smo demografske, kliničke te mikrobiološke podatke s ciljem identifikacije prediktora mortaliteta. Rezultati: Najčešći klinički sindrom kod prijema bolesnika bila je primarna bakterijemija nepoznatog ishodišta (40,8 %). Prethodno dijagnosticiranu kroničnu bolest jetre imalo je 39,2 % bolesnika. Kod 50 % bolesnika najčešći uzrok ciroze jetre bio je alkoholne geneze. Uzročnik je izoliran kod 71,4 % bolesnika, najčešće iz hemokultura (59,1 %). Korekcija empirijske terapije učinjena je u 11,2 % slučajeva, uzevši u obzir mikrobiološke izolate. Medijan do početka adekvatne antimikrobne terapije bio je 3 dana. Do komplikacija je došlo kod 62,2 % bolesnika. Ukupni mortalitet za vrijeme hospitalizacije iznosio je 28,5 %. Odgođena adekvatna antimikrobna terapija u razdoblju ≥ 72 sata, invazivna mehanička ventilacija i akutno bubrežno zatajenje pokazale su se neovisno povezanima sa smrtnim ishodom. Zaključak: Ovom smo studijom opisali epidemiologiju i etiologiju bakterijemija kod bolesnika s cirozom jetre u Hrvatskoj. S obzirom na to da je infekcija prvi prezentirajući znak ciroze u našoj kohorti, naglašava se potreba za sustavnijim probirom u svrhu ranog otkrivanja kronične bolesti jetre i sprječavanja komplikacija. Visoka stopa multiplo-rezistentnih infekcija iz opće populacije naglašava potrebu za izradom nacionalnih smjernica za empirijsko liječenje bakterijskih infekcija kod bolesnika s cirozom jetre.Introduction: Bacterial infections are a common cause of complications and decompensation in patients with liver cirrhosis. The objective of this study is to evaluate the etiology, clinical manifestations, course and outcome of bacterial infections and identify mortality predictors in patients with liver cirrhosis and sepsis. Materials/Methods: We conducted a retrospective cohort study involving 257 patients hospitalized at the University Hospital for Infectious Diseases, Zagreb over a five-year period (2011 - 2015). We analysed demographical, clinical, and microbiological data in order to identify the mortality predictors. Results: The most common clinical syndrome on admission was bacteremia of unknown origin. Chronic liver disease (CLD) was previously diagnosed in 39,2 % of patients. In 50,0 % of the cases, CLD was alcohol induced. The causative agent was isolated in 71,4 % of patients, mostly from blood cultures. Empirical therapy was corrected in 11,2 % of cases (according to microbiological findings). Median time of adequate antimicrobial therapy onset was 3 days. Complications occurred in 62,2 % of patients. Hospital stay mortality rate was 28,5 %. Delayed adequate antimicrobial therapy for a period ≥ 72 hours, invasive mechanical ventilation and acute renal failure were independently associated with fatal outcomes. Conclusion: This study describes the epidemiology and etiology of bacteriemia in liver cirrhosis patients in Croatia. Since infection is the initial sign of cirrhosis presence in our cohort, systematic screening for timely detection of CLD and prevention of complications is crucial. High rate of multiple drug resistant infections from the general population underscores the need to develop national guidelines for empirical treatment of bacterial infections in patients with liver cirrhosis

Critically ill patients with COVID-19 treated in the Intensive Care Unit atthe University Hospital for Infectious Diseases „Dr. Fran Mihaljević“ in Zagreb

Cilj: Opisati karakteristike bolesnika, tijek bolesti, terapiju te ishod i komplikacije kod kritično oboljelih s COVID-19 liječenih u jedinici intenzivnog liječenja (JIL) Klinike za infektivne bolesti „Dr. Fran Mihaljević“ (KZIB) u Zagrebu. Materijali i metode: Opservacijska retrospektivna studija 38 odraslih bolesnika liječenih u JIL KZIB s dokazanim COVID-19 u razdoblju od 11. ožujka do 6. lipnja 2020. godine. Rezultati: Od ukupno 167 bolesnika s COVID-19 liječenih u KZIB, u JIL-u je liječeno 38 bolesnika (22,8%). Medijan dobi JIL bolesnika bio je 69.5 godina (33-85), umrlih 70 (43-85), a preživjelih 66 godina (33-80). Većina je bolesnika bila muškog spola (26 bolesnika ili 68%). Od komorbiditeta najčešći su bili arterijska hipertenzija (20- 53%), šećerna bolest (9-24%) te ishemijska bolest srca (8-21%). Svi su bolesnici primljeni zbog hipoksemijskog respiratornog zatajenja. Osim respiratornog zatajenja s primjenom mehaničke ventilacije u 30 (79%) bolesnika, česti su bili šok (25- 66%) te akutno bubrežno zatajenje (21- 55% bolesnika). Metode kontinuiranog nadomještanja bubrežne funkcije primjenjene su kod 13 (34%) bolesnika. Medijan trajanja hospitalizacije u JIL-u bio je 18 (3-68) dana, a mehaničke ventilacije 17 (5-43) dana. Ukupni je mortalitet bio 50%, a kod bolesnika koji su zahtijevali mehaničku ventilaciju 63%. Smrtnost je bila najveća u dobnoj skupini iznad 65. godine. Zaključak: Bolesnici s COVID-19, liječeni u JIL-u, često su i dugotrajno mehanički ventilirani, a tijekom boravka imaju brojne komplikacije bolesti i intenzivnog liječenja te visoku smrtnost. Najveća je smrtnost kod muškaraca starijih od 65 godina s arterijskom hipertenzijom, šećernom bolesti i ishemijskom bolesti srca.Objective: To describe the characteristics, clinical course, treatment, outcomes and complications in critically ill patients with COVID-19 treated in the intensive care unit (ICU) at the University Hospital for Infectious Diseases „Dr. Fran Mihaljević“ (UHID) in Zagreb. Materials and methods: A retrospective observational study of 38 adult patients with COVID-19 treated in the ICU at UHID between March 11 and June 6, 2020. Results: Among the 167 patients with COVID-19 treated at the UHID, 38 (22,8%) were admitted to the ICU. The mean age of these patients was 69.5 (33-85) years, 70 (43-85) years in deceased patients and 66 (33-80) in survivors. The majority of patients were male (26 patients- 68%). The mMost common comorbidities were arterial hypertension (20- 53%), diabetes mellitus (9- 24%) and ischaemic heart disease (8- 21%). All patients were admitted for hypoxaemic respiratory failure. In addition to acute respiratory failure with the need for mechanical ventilation (30- 79%), shock (25- 66%) and acute renal insufficiency (21- 55%) were common. Continuous renal replacement therapy was used in 13 (34%) patients. The median duration of ICU stay was 18 (3-68) days and of mechanical ventilation 19 (5-43) days. Overall mortality was 50%, 63% in patients who received mechanical ventilation and it was the highest in patients over 65 years of age. Conclusions: Patients with COVID-19, treated in the ICU, often require prolonged mechanical ventilation, have numerous complications of critical illness and ICU treatment, and high mortality rates. Mortality rate is highest in men over 65 years with comorbiditeies – arterial hypertension, diabetes mellitus and ischaemic heart disease

The treatment of chronic hepatitis B virus infection at the University Hospital for Infectious Diseases "Dr. Fran Mihaljević" in Zagreb in the period from 2008 to 2017

U razdoblju od 2008. do 2017. u Klinici za infektivne bolesti "Dr. Fran Mihaljević" u Zagrebu liječeno je 210 bolesnika s kroničnom HBV infekcijom koji su imali histološku i biokemijsku aktivnost bolesti. Stadij fibroze određivan je patohistološki i elastografski. Cirozu je već u početku imalo 14,5 % bolesnika. Iako je funkcionalno izlječenje bilo rijetko (5,5 % slučajeva) kod većine bolesnika postignuta je supresija virusne replikacije, usporavanje ili prekid razvoja fibroze, pa čak i regresija stadija fibroze za jedan stupanj po Metaviru u 16 % bolesnika. Zapaženo je smanjenje frekvencije pojave dekompenzirane ciroze i hepatocelularnog karcinoma za 2 do 3 puta u usporedbi s podacima kod neliječenih bolesnika. Bolesnici liječeni lamivudinom imali su visoku incidenciju razvoja rezistencije (32 % nakon 5 godina liječenja), te je terapija nastavljena tenofovirom uz većinom dobru podnošljivost i bez razvoja rezistencije. HBeAg nije se pokazao kao značajan prediktor težine i toka bolesti. Značajan je broj hematoloških i drugih imunosuprimiranih bolesnika (n = 24), koji terapiju primaju radi prevencije reaktivacije latentne HBV infekcije.A total of 210 patients with chronic HBV infection and histological and biochemical activity of disease were treated at the University Hospital for Infectious Diseases "Dr. Fran Mihaljević" in Zagreb in the period from 2008 to 2017. The fibrosis stage was determined histologically and by transient elastography, and cirrhosis was found initially in 14,5 % of the patients. Although functional recovery was rare (5.5 % of cases), the suppression of viral replication, slowing down or discontinuation of fibrosis progression was achieved in most of the treated. Even fibrosis regression by one stage in Metavir scale was achieved in 16 % of patients. There was also a decrease in the frequency of development of decompensated cirrhosis (2 patients) and hepatocellular carcinoma (2 patients) by 2 to 3 times in comparison to historical controls in nontreated patients. Patients treated with lamivudine had a high incidence of resistance development (32 % after 5 years). They continued therapy with tenofovir with good tolerability and no resistance development. HBeAg did not seem to be a significant predictor for the severity and the course of the disease. There is also a significant number of hematologic and other immunosuppressed patients (n = 24) receiving treatment to prevent the reactivation of latent HBV infection

The Role of Non-Alcoholic Fatty Liver Disease in Infections

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, affecting one third of the Western population. The hallmark of the disease is excessive storage of fat in the liver. Most commonly, it is caused by metabolic syndrome (or one of its components). Even though the development of NAFLD has multiple effects on the human organism resulting in systemic chronic low-grade inflammation, this review is focused on NAFLD as a risk factor for the onset, progression, and outcomes of infectious diseases. The correlation between NAFLD and infections is still unclear. Multiple factors (obesity, chronic inflammation, altered immune system function, insulin resistance, altered intestinal microbiota, etc.) have been proposed to play a role in the development and progression of infections in people with NAFLD, although the exact mechanism and the interplay of mentioned factors is still mostly hypothesized. In this article we review only the selection of well-researched topics on NAFLD and infectious diseases (bacterial pneumonia, COVID, H. pylori, urinary tract infections, C. difficile, bacteremia, hepatitis B, hepatitis C, HIV, and periodontitis)

Rezultati liječenja 3D-terapijom i model eliminacije infekcije HCV-om u Republici Hrvatskoj [Results of the 3D treatment and model of elimination of HCV infection in Croatia]

Chronic hepatitis C (CHC) has been recognized as a global health problem. World health organization (WHO) has set a goal to reduce new viral hepatitis infections by 90% and reducing deaths due to viral hepatitis by 65% by 2030. Achievement of this goal became possible by the discovery of direct acting antiviral agents (DAA). The aim of this paper is to describe the first Croatian experience in the treatment of CHC with the ombitasvir/paritaprevir/ritonavir + dasabuvir (PrOD) ± ribavirin (RBV) combined therapy. Mathematical model was used to estimate the prevalence and number of complications depending on the number of treated patients annually. Overall, 117 patients with HCV genotype 1 and 4 infection were treated with PrOD±RBV. Sustained virological response was achieved in 97% of treated patients without significant side effects and therapy discontinuation. The goal of reducing deaths by 65% can be achieved if 450 patients are treated annually. With epidemiological effort in early diagnosis combined with timely treatment, Croatia can be among first countries that would achieve WHO goals in the control of chronic viral hepatitis

Extracorporeal membrane oxygenation in COVID-19: Results of the Croatian Extracorporeal Membrane Oxygenation Referral Center

At the beginning of the COVID-19 pandemic, the role of extracorporeal membrane oxygenation (ECMO) was uncertain and the outcomes of ECMO-treated patients were unfavorable. During the pandemic, medical community realized that carefully selected patients may benefit from ECMO support. The goal of the study was to present the outcomes of ECMO-treated patients with severe COVID-19 ARDS referred to the respiratory ECMO hub in Croatia and to determine variables that influenced the outcome. Our study included all adult patients with confirmed COVID-19 ARDS that required ECMO treatment, in the period between February 2020 and April 2022. All ECMO circuits were veno-venous with femoro-jugular configuration, with drainage at the femoral site. A total of 112 adult patients with COVID-19 induced ARDS were included in the study. All patients had veno-venous ECMO treatment and 34 survived. Surviving patients were discharged home either from the hospital or from a designated rehabilitation facility. The mortality was associated with the incidence of nosocomial bacteremia, occurrence of heparin induced thrombocytopenia and acute renal failure. In order to reduce the mortality in COVID-19 ECMO patients, the treatment should be started as soon as criteria for ECMO are met. Furthermore, complications of the procedure should be detected as soon as possible. However, despite even the optimal approach, the mortality in COVID-19 ECMO patients will surpass that of non-COVID-19 ARDS ECMO patients, mostly due to poor resolving and long lasting ARDS with longer ECMO runs and ensuing infectious complications