Nasal polyposis in cystic fibrosis: experience from CF Center, UHC Zagreb

Cystic fibrosis (CF) is a lethal autosomal recessive disease, caused by mutations in the CF transmembrane conductance regulator gene (CFTR). CFTR mutations affect epithelial cells in the lungs, sinuses, pancreas, liver, kidneys, intestine and sweat glands, causing abnormally viscous mucus production, thickening of digestive fluids and salty sweat. The consequences for the respiratory system are mucus buildup, decreased mucociliary clearance and tissue inflammation. A change in microbioma follows, with S. aureus and P. aeruginosa being prevalent in most patients, as they have the capacity of biofilm formation causing chronic colonization. This represents the basis for recurrent infection. At the same time, pancreatic insufficiency leads to malabsorption of fat-soluble vitamins, i.g. vitamin D3, a powerful immunomodulator implicated in both pulmonary and sinus pathophysiology. CF is marked by a high incidence of nasal polyposis, even in the pediatric population and ENT follow-up is mandatory. CF nasal polyposis is a distinctive form of nasal polyposis and its treatment and follow up present many challenges. CF affects one out of every 3000 newborns. The total number of patients with CF in Croatia is 175, and the majority of them now refer to our CF Center of Zagreb University Center where they are approached by a multidisciplinary team: both pediatric and adult pulmologists, gastroenterologists, endocrinologists, rhinologists, microbiologists and nutritionists. We aimed to review our experience with CF patients from a rhinologist point of view and present the prevalence and specifics of nasal polyposis in cystic fibrosis patients from our CF Center

Nasal polyposis in cystic fibrosis: experience from CF Center, UHC Zagreb

Cystic fibrosis (CF) is a lethal autosomal recessive disease, caused by mutations in the CF transmembrane conductance regulator gene (CFTR). CFTR mutations affect epithelial cells in the lungs, sinuses, pancreas, liver, kidneys, intestine and sweat glands, causing abnormally viscous mucus production, thickening of digestive fluids and salty sweat. The consequences for the respiratory system are mucus buildup, decreased mucociliary clearance and tissue inflammation. A change in microbioma follows, with S. aureus and P. aeruginosa being prevalent in most patients, as they have the capacity of biofilm formation causing chronic colonization. This represents the basis for recurrent infection. At the same time, pancreatic insufficiency leads to malabsorption of fat-soluble vitamins, i.g. vitamin D3, a powerful immunomodulator implicated in both pulmonary and sinus pathophysiology. CF is marked by a high incidence of nasal polyposis, even in the pediatric population and ENT follow-up is mandatory. CF nasal polyposis is a distinctive form of nasal polyposis and its treatment and follow up present many challenges. CF affects one out of every 3000 newborns. The total number of patients with CF in Croatia is 175, and the majority of them now refer to our CF Center of Zagreb University Center where they are approached by a multidisciplinary team: both pediatric and adult pulmologists, gastroenterologists, endocrinologists, rhinologists, microbiologists and nutritionists. We aimed to review our experience with CF patients from a rhinologist point of view and present the prevalence and specifics of nasal polyposis in cystic fibrosis patients from our CF Center

Inhalatory therapy of children

Inhalacijska terapija jedan je od stupova liječenja plućnih bolesti. Na dostavu lijeka u pluća utječu anatomija dišnog sustava, fizikalno-kemijska svojstva samog lijeka te čimbenici prijenosa lijeka (sredstva za dostavljanje lijeka, tehnika disanja i njihova interakcija). Tijekom vremena osmišljeni su razni načini provođenja inhalacijske terapije, kao na primjer: inhalatori, tlačno-dozni inhaleri (engl. pressurised metered-dose inhalers – pMDI) i inhaleri suhih prašaka (dry-powder inhalers – DPI). Svaki od navedenih načina provođenja inhalacijske terapije ima svoje prednosti i mane, koje je potrebno poznavati kako bi se mogle zadovoljiti potrebe pacijenta.Inhalation therapy is one of pillars of respiratory disease therapy. Main factors that influence drug delivery to lungs are respiratory system anatomy, physical and chemical characteristics of drug and drug transfer factors (inhalation therapy modalities, breathing techniques and its’ interactions). Various inhalation therapy modalities were invented: nebulizers, pressurised metered-dose inhalers – pMDI and dry-powder inhalers – DPI. Each one of them has its’ advantages and flaws, which one has to be acquinted with in order to be able to choose the optimal modality for patient

Ultrasound Distinction between Simple Recurrent Urinary Tract Infections and a Specific Bladder Wall Inflammatory Entity called Cystitis Cystica

A specific representative of recurrent urinary tract infections (UTI) called cystitis cystica (CC) was assessed by ultrasound. The aim of the study was to delineate, by means of ultrasound measurement (US) of bladder wall thickness (BWT), the children with mere repeated UTI from those prone to frequent UTI due to CC. Two groups were compared, the control group of 30 with recurrent UTI without US CC BWT changes, and the group of 30 children with characteristic CC bladder wall thickening in whom cystoscopy was performed for verification the diagnosis of CC. BWT of >3 mm (>2.8 mm and >3.3 mm) was found as cut-of value for distinction of CC versus simple recurrent UTI. US BWT measurement is useful in diagnosing CC and therefore valuable in decision about need of UTI prophylaxis

Pozitivna povratna sprega cističnog cistitisa: uloga povratnih infekcija mokraćnog sustava u broju nodoznih čvorića u sluznici mokraćnog mjehura

The main purpose of this study was to demonstrate positive feedback loop between bladder wall nodules (nodules being one of the key diagnostic factors), bladder wall thickness, and recurrent urinary tract infections. Cystitis cystica was diagnosed in 115 prepubertal girls (mean age 7.79}3.05 years) by optic examination of bladder mucosal nodules and by ultrasonographic measurement of bladder wall thickness. Bladder wall thickness increased with the frequency of recurrent urinary tract infections as well as with the number of nodules on bladder wall mucosa (3.52}0.522 mm ≤5 nodules vs. 4.42}0.429 mm 6-10 nodules vs. 5.20}0.610 mm >10 nodules, respectively). Study results suggested that early control of urinary tract infections by chemoprophylaxis could prevent higher grades of bladder wall mucosal changes and consequently shorten the length of chemoprophylaxis.Osnovni cilj ove studije bio je prikazati pozitivnu povratnu spregu između broja nodula na sluznici mokraćnog mjehura (ključni čimbenik u dijagnozi), debljine sluznice mokraćnog mjehura i broja ponavljanih infekcija mokraćnog sustava. U 115 djevojčica srednje predpubertetske dobi od 7,79}3,05 godina dijagnoza cističnog cistitisa je postavljena cistoskopskim pregledom sluznice mokraćnog mjehura i ultrazvučnim mjerenjem njezine debljine. Debljina sluznice se progresivno povećavala s brojem nodula (3,52}0,522 mm ≤5 nodula prema 4.42}0.429 mm 6-10 nodula prema 5,20}0,610 mm >10 nodula) usporedno s povećenjem broja uroinfekcija. Smatramo da se ranom profilaksom uroinfekcija može spriječiti razvoj opsežnih promjena na sluznici mokraćnog mjehura s posljedičnim skraćenjem profilaktične primjene antibiotika/uroantiseptika

Antibiotic-associated diarrhea and Clostridium difficile-associated disease: an observational retrospective study at the University Hospital for Infectious Diseases "Dr. Fran Mihaljević" in Zagreb

Postantimikrobni proljev (PAP) je komplikacija povezana s primjenom antimikrobnih lijekova. Incidencija PAP je različita s obzirom na vrstu antimikrobnog lijeka i čimbenike rizika, a varira između 5–25%. Clostridium difficile (C. difficile) je najčešći uzročnik PAP. Cilj ovog istraživanja bio je istražiti epidemiološke i kliničke osobitosti postantimikrobnog proljeva i bolesti povezane s C. difficile u odraslih bolesnika liječenih u Klinici za infektivne bolesti "Dr. Fran Mihaljević" u Zagrebu. Retrospektivno su analizirane povijesti bolesti bolesnika hospitaliziranih od 1. siječnja 2012. do 31. lipnja 2013. godine. Od 217 bolesnika s PAP, C. difficile je dokazan u 161 (74%) bolesnika. Medijan dobi bolesnika iznosio je 72 godine (raspon 23–93 godine); 105 (48%) ih je bilo muškog spola. Barem jedan od čimbenika rizika imalo je 212 (98%) bolesnika od kojih su najčešći bili: starija životna dob (≥60 godina) u 164 (76%), hospitalizacija ≤30 dana prije pojave PAP u 153 (71%), prethodno imunosupresivno liječenje u 28 (13%). Antimikrobni lijekovi koji su najčešće bili povezani s nastankom PAP bili su: penicilini u 63 (29%), cefalosporini u 56 (26%), metronidazol u 40 (18%) te kinoloni u 38 (17%) bolesnika. Najčešći razlozi uzimanja antimikrobnog lijeka bili su: infekcija mokraćnog sustava u 65 (30%), infekcija dišnog sustava u 48 (22%) te gastrointestinalna infekcija u 25 (12%). Leukocitoza je pri prijmu zabilježena u 128 (80%) bolesnika; medijan broja leukocita iznosio je 13,3×109/L (raspon 4–71×109/L); medijan vrijednosti CRP iznosio je 66,9 mg/L (raspon 0,4–391 mg/L). Bolest je prosječno trajala 11 (raspon 1–67) dana. Većina naših ispitanika uspješno je izliječena uz stopu smrtnosti od 4%, a stopu recidiva od 7% tijekom 6-mjesečnog praćenja. U multiplom regresijskom modelu, trajanje bolesti do hospitalizacije te vrijednost CRP-a pokazali su se značajnim neovisnim prediktorima ukupnog trajanja i težine bolesti. Nije bilo statistički značajne razlike u najvažnijim demografskim, kliničkim i laboratorijskim značajkama bolesnika s etiološki dokazanim i nedokazanim PAP. Za sveobuhvatniji uvid u epidemiološke i kliničke osobitosti postantimikrobnog proljeva i bolesti povezane s C. difficile potrebno je u buduća istraživanja uključiti i ambulantno liječene bolesnike s blažim kliničkim oblicima bolesti.Antibiotic-associated diarrhea (AAD) is a complication related to the use of antibiotics. The incidence of AAD varies, depending on the type of antibiotic and risk factors, between 5–25%. Clostridium difficile (C. difficile) is the most common cause of AAD. The aim of the study was to determine epidemiological and clinical characteristics of AAD and Clostridium difficile-associated disease among adult patients hospitalized at the University Hospital for Infectious Diseases in Zagreb. Medical charts of patients hospitalized between January 1, 2012 and June 31, 2013 were retrospectively analyzed. Out of 217 patients with AAD, C. difficile was confirmed in 161 (74%) cases. Median age of patients was 72 years (range 23–93 years); 105 (48%) were male. At least one of the risk factors for development of AAD was present in 212 (98%) patients, with the most frequent being: older age (≥60 years) in 164 (76%), hospitalization in the past 30 days before onset of AAD in 153 (71%), previous immunosuppressive treatment in 28 (13%) patients. The most frequent antibiotics associated with AAD were: penicillins in 63 (29%), cephalosporins in 56 (26%), metronidazole in 40 (18%), and quinolones in 38 (17%) patients. The most frequent reasons for antibiotic treatment were: urinary tract infection in 65 (30%), respiratory tract infection in 48 (22%), and gastrointestinal infection in 25 (12%) cases. At admission, leukocytosis was registered in 128 (80%) patients; median WBC count was 13,3×109/L (range 4–71×109/L); median CRP was 66,9 mg/L (range 0,4–391 mg/L). Median disease duration was 11 (range 1–67) days. Most of our patients were successfully cured with mortality rate of 4%, and recurrence rate of 7% during the 6-month follow-up period. Multiple regression model showed that both, duration of symptoms prior to hospitalization and CRP level at admission, were significant independent predictors of duration and outcome of the disease. There were no statistically significant differences in most relevant demographic, clinical and laboratory parameters among patients with and without confirmation of C. difficile. For the overall epidemiological and clinical conclusions related to antibiotic-associated diarrhea and Clostridium difficile-associated disease, patients with less severe diseases and ambulatory treatment should be included in future studies, too

Ultrasound Distinction between Simple Recurrent Urinary Tract Infections and a Specific Bladder Wall Inflammatory Entity called Cystitis Cystica

A specific representative of recurrent urinary tract infections (UTI) called cystitis cystica (CC) was assessed by ultrasound. The aim of the study was to delineate, by means of ultrasound measurement (US) of bladder wall thickness (BWT), the children with mere repeated UTI from those prone to frequent UTI due to CC. Two groups were compared, the control group of 30 with recurrent UTI without US CC BWT changes, and the group of 30 children with characteristic CC bladder wall thickening in whom cystoscopy was performed for verification the diagnosis of CC. BWT of >3 mm (>2.8 mm and >3.3 mm) was found as cut-of value for distinction of CC versus simple recurrent UTI. US BWT measurement is useful in diagnosing CC and therefore valuable in decision about need of UTI prophylaxis

Increasing the Focus on Children's Complex and Integrated Care Needs: A Position Paper of the European Academy of Pediatrics

There is wide variation in terminology used to refer to children living with complex needs, across clinical, research and policy settings. It is important to seek to reconcile this variation to support the effective development of programmes of care for this group of children and their families. The European Academy of Pediatrics (EAP) established a multidisciplinary Working Group on Complex Care and the initial work of this group examined how complex care is defined in the literature. A scoping review was conducted which yielded 87 papers with multiple terms found that refer to children living with complex needs. We found that elements of integrated care, an essential component of care delivery to these children, were repeatedly referred to, though it was never specifically incorporated into a term to describe complex care needs. This is essential for practice and policy, to continuously assert the need for integrated care where a complex care need exists. We propose the use of the term Complex and Integrated Care Needs as a suitable term to refer to children with varying levels of complexity who require continuity of care across a variety of health and social care settings

Cystic Fibrosis – results of CFTR modulators in Croatia

Cistična fibroza najčešća je nasljedna bolest, koja skraćuje životni vijek, a uzrokuje je defekt u genu za transmembranski regulator provodljivosti cistične fibroze (eng. cystic fibrosis transmembrane regulator – CFTR). Poremećena je homeostaza elektrolita, što se očituje simptomima u više organskih sustava. Plućne manifestacije, s kroničnim infekcijama, upalom i, na kraju, respiratornim zatajenjem, ostaju i dalje najvažnija prijetnja životnom vijeku bolesnika. Do prije jednog desetljeća bilo je dostupno samo simptomatsko liječenje. Od 2012. g. dostupno je liječenje tzv. modulatorima CFTR-proteina i njihovim kombinacijama za osobe s cističnom fibrozom koje nose različite varijante CFTR-gena. Pojavom tih lijekova uvelike se promijenila perspektiva i kvaliteta života ljudi s cističnom fibrozom, ali postavljeni i novi izazovi u vezi s dugoročnim komplikacijama, pitanje eventualnog smanjenja konvencionalnog liječenja, ali i financiranja terapije, koja je mnogim bolesnicima nedostupna. Iznesene su bazične spoznaje o cističnoj fibrozi i funkciji CFTR-proteina, klasifikaciji varijanata CFTR-gena, mogućnostima liječenja CFTR-modulatorima te osnovni ishodi liječenja bolesnika s cističnom fibrozom u Hrvatskoj, gdje se ta terapija primjenjuje od jeseni 2021. godine.Cystic fibrosis, the most frequent lifespan shortening hereditary disease in Caucasians, is caused by a defect in the CFTR (cystic fibrosis transmembrane regulator) gene. Disturbed electrolyte homeostasis leads to the development of different symptoms in multiple organs. Pulmonary manifestations with chronic infections and inflammation result in respiratory failure and remain the most important life-shortening factor. Until recently only symptomatic treatment was available. In year 2012. a new treatment approach with small molecules that modulate the CFTR protein was introduced. Different combinations of CFTR modulators are applicable to certain patients carrying different variants of the CFTR gene. CFTR modulators made a huge difference in the quality of life and perspectives of people with cystic fibrosis. At the same time, new challenges emerged regarding long term complications and possible reduction of conventional treatment options, as well as financial issues that are an obstacle to the use of these drugs for many patients. This paper brings basic insight into cystic fibrosis, the function of CFTR protein, the classification of CFTR gene variants and possibilities of treatment with CFTR modulators as well as basic outcomes of CFTR modulators treatment in Croatia, where this therapy was introduced in autumn 2021

Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020

Background Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). Methods We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. Results Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133). Conclusions SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination