Acinetobacter Baumannii Pneumonia Associated with Mechanical Ventilation in COVID-19 Pandemic

Infekcije uzrokovane bakterijom Acinetobacter baumannii predstavljaju veliki javnozdravstveni problem. Acinetobacter baumannii kontaminira bolničko okruženje, kožu i sluznice pacijenata te se prenosi rukama osoblja uzrokujući oportunističke infekcije kao što su upale pluća povezane s mehaničkom ventilacijom, bakterijemije, infekcije rana te urinarne infekcije. Ventilatorom uzrokovana upala pluća druga je po učestalosti nozokomijalna infekcija u jedinicama intenzivnog liječenja. Vodeći čimbenik rizika za razvoj ventilatorom uzrokovane upale pluća jest invazivna mehanička ventilacija. U pacijenata s bolešću COVID-19, liječenje u jedinicama intenzivnog liječenja često je zahtijevalo intubaciju i uporabu mehaničke ventilacije izlažući ih riziku od razvoja ventilatorom uzrokovane upale pluća. S obzirom na brojna preklapanja u kliničkoj slici COVID upale pluća i upale pluća povezane s ventilatorom, teško je sa sigurnošću odrediti njezinu prevalenciju. Oštećenja pluća uzrokovana bolešću COVID-19, imunosupresivna terapija, često profilaktičko korištenje antibiotika i organizacijske teškoće – prenapučenost u jedinicama intenzivnog liječenja, manjak osoblja, potreba za zaštitom osoblja od virusa SARS-CoV-2 (engl. Severe acute respiratory syndrome coronavirus 2) infekcije i dr., pridonijeli su povećanoj pojavnosti ventilatorom izazvane upale pluća uzrokovane Acinetobacter baumannii u pacijenata oboljelih od COVID-a. Brojni mehanizmi otpornosti na antibiotike, uz posljedično sve veću prevalenciju višestruko otpornih sojeva Acinetobacter baumannii predstavljaju izazov u liječenju. U osjetljivih sojeva, monoterapija karbapenemima dovodi do pozitivnog ishoda. Liječenje karbapenem-otpornih Acinetobacter baumannii sojeva u kompliciranim infekcijama provodi se uglavnom kolistinom. Kolistin se može primjenjivati intravenski i inhalacijski te ga se preporučuje koristiti u kombinaciji s drugim djelotvornim antibioticima.Infections caused by Acinetobacter baumannii are a major public health issue. Acinetobacter baumannii contaminates the hospital environment, skin, and mucous membranes of patients and is transmitted by the hands of staff, causing opportunistic infections such as pneumonia associated with mechanical ventilation, bacteremia, wound infections, and urinary tract infections. Ventilator-associated pneumonia is the second most common nosocomial infection in the intensive care units. The leading risk factor for the development of ventilator-associated pneumonia is invasive mechanical ventilation. In the patients with COVID-19 disease, the treatment in intensive care units often required intubation and the use of mechanical ventilation, exposing them to the risk of developing ventilator-associated pneumonia. Given the numerous overlaps in the clinical picture of COVID-19 pneumonia and ventilator-associated pneumonia, it is difficult to determine its prevalence with certainty. Lung damage caused by COVID-19, immunosuppressive therapy, frequent prophylactic use of antibiotics, and organizational difficulties (overcrowding in intensive care units, staff shortages, the need to protect staff from severe acute respiratory syndrome coronavirus 2 infection, etc.) have contributed to the increased incidence of ventilator-associated pneumonia in COVID-19 patients. Numerous mechanisms of antibiotic resistance and the increasing prevalence of multidrug-resistant strains such as carbapenem-resistant Acinetobacter baumannii present a challenge in treatment. In susceptible strains, monotherapy with carbapenems leads to a positive outcome. The treatment of carbapenem-resistant Acinetobacter baumannii strains in complicated infections is carried out mainly with colistin. Colistin can be administered intravenously or by inhalation, and it’s use in combination with other effective antibiotics is recommended

Six minute walk test in children with cystic fibrosis before and during treatment with cystic fibrosis transmembrane conductance regulator modulators

Uvod. Narušena tjelesna spremnost bitno negativno utječe na kvalitetu života oboljelih od cistične fibroze (CF). Može se procijeniti šest-minutnim testom hoda (6MWT). Cilj istraživanja. Istražiti povezanost primjene modulatora transmembranskog regulatora provodljivosti za CF (CFTR) s poboljšanjem tjelesne spremnosti. Metode. Ovo retrospektivno istraživanje provedeno je s podatcima prikupljenim od maloljetnih bolesnika ≥ 5 god. koji su u razdoblju od 15. 10. 2021. do 30. 10. 2022. započeli liječenje eleksakaftorom/tezakaftorom/ivakaftorom (ELX/TEZ/IVA) ili lumakaftorom/ivakaftorom (LUM/IVA) u Centru za cističnu fibrozu djece i odraslih Kliničkog bolničkog centra Zagreb. Ispitanici su praćeni prvih 12 mjeseci liječenja te im je svaka tri mjeseca određen indeks tjelesne mase (BMI), učinjena spirometrija i 6MWT. Praćena je promjena navedenih parametara u tom razdoblju te međuodnos rezultata 6MWT-a i BMI-ja, odnosno plućne funkcije. Nedostajali podatci nadomješteni su primjenom imputacije. Rezultati. 36 bolesnika (medijan dobi 14 god.) uključeno je u istraživanje; njih 27 liječeno s ELX/TEZ/IVA, a 9 s LUM/IVA. Prosječna duljina hodne pruge na početku liječenja iznosila je 522,1 ± 99,9 m, a nakon 12 mjeseci 592,0 ± 106,3 m (p < 0,001). Pritom je najveće povećanje duljine hodne pruge bilo zabilježeno u prvih šest mjeseci liječenja (p = 0,023). Promjena z-vrijednosti BMI-ja (p = 0,006) i postotka prediktivne vrijednosti FEV1 (ppFEV1) (p < 0,001) tijekom 12 mjeseci praćenja također je bila značajna. Duljina hodne pruge nakon 12 mjeseci liječenja pozitivno je korelirala sa z-vrijednošću BMI-ja (p = 0,002) i ppFEV1 (p < 0,001). Zaključak. Liječenje CFTR modulatorima praćeno je i klinički i statistički značajnim poboljšanjem tjelesne spremnosti uz pozitivnu korelaciju s poboljšanjem uhranjenosti i plućne funkcije.Background. Exercise tolerance is compromised in many patients with cystic fibrosis (CF) and negatively affects their quality of life. The six-minute walk test (6MWT) can be used to assess exercise tolerance. Aim. To investigate whether cystic fibrosis transmembrane conductance regulator (CFTR) modulators are associated with an improvement in exercise tolerance. Methods. This is a retrospective study including children aged ≥ 5 years who began treatment with lumacaftor/ivacaftor (LUM/IVA) or elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) at the Cystic Fibrosis Centre for Children and Adults at the University Hospital Centre Zagreb in the period between 15. 10. 2021. and 30. 10. 2022. Patients were monitored during the first 12 months of treatment; every 3 months body mass index (BMI) was calculated and spirometry and 6MWT were performed. Collected data were analysed for a change in 6MWT results, BMI and percent-predicted FEV1 (ppFEV1) as well as correlation between these parameters. Missing values were replaced using imputation methods. Results. 36 patients (median age 14 years) were included; 27 received ELX/TEZ/IVA and 9 received LUM/IVA. Average 6MWT walking distance (6MWD) prior to treatment and after 12 months were 522.1 ± 99.9 and 592.0 ± 106.3 m respectively (p < 0.001). Average increase in 6MWD in the first half-year was significantly higher than in the following 6 months (p = 0.023). Changes in BMI z-score (p = 0.006) and ppFEV1 (p < 0.001) during treatment were also significant. 6MWD at 12 months positively correlated with BMI z-score (p = 0.002) and ppFEV1 (p < 0.001). Conclusions. Both clinically and statistically significant improvement in 6MWT results was visible following initiation of CFTR modulator treatment. A positive correlation with lung function improvement and improvement in BMI was observed

Six minute walk test in children with cystic fibrosis before and during treatment with cystic fibrosis transmembrane conductance regulator modulators

Uvod. Narušena tjelesna spremnost bitno negativno utječe na kvalitetu života oboljelih od cistične fibroze (CF). Može se procijeniti šest-minutnim testom hoda (6MWT). Cilj istraživanja. Istražiti povezanost primjene modulatora transmembranskog regulatora provodljivosti za CF (CFTR) s poboljšanjem tjelesne spremnosti. Metode. Ovo retrospektivno istraživanje provedeno je s podatcima prikupljenim od maloljetnih bolesnika ≥ 5 god. koji su u razdoblju od 15. 10. 2021. do 30. 10. 2022. započeli liječenje eleksakaftorom/tezakaftorom/ivakaftorom (ELX/TEZ/IVA) ili lumakaftorom/ivakaftorom (LUM/IVA) u Centru za cističnu fibrozu djece i odraslih Kliničkog bolničkog centra Zagreb. Ispitanici su praćeni prvih 12 mjeseci liječenja te im je svaka tri mjeseca određen indeks tjelesne mase (BMI), učinjena spirometrija i 6MWT. Praćena je promjena navedenih parametara u tom razdoblju te međuodnos rezultata 6MWT-a i BMI-ja, odnosno plućne funkcije. Nedostajali podatci nadomješteni su primjenom imputacije. Rezultati. 36 bolesnika (medijan dobi 14 god.) uključeno je u istraživanje; njih 27 liječeno s ELX/TEZ/IVA, a 9 s LUM/IVA. Prosječna duljina hodne pruge na početku liječenja iznosila je 522,1 ± 99,9 m, a nakon 12 mjeseci 592,0 ± 106,3 m (p < 0,001). Pritom je najveće povećanje duljine hodne pruge bilo zabilježeno u prvih šest mjeseci liječenja (p = 0,023). Promjena z-vrijednosti BMI-ja (p = 0,006) i postotka prediktivne vrijednosti FEV1 (ppFEV1) (p < 0,001) tijekom 12 mjeseci praćenja također je bila značajna. Duljina hodne pruge nakon 12 mjeseci liječenja pozitivno je korelirala sa z-vrijednošću BMI-ja (p = 0,002) i ppFEV1 (p < 0,001). Zaključak. Liječenje CFTR modulatorima praćeno je i klinički i statistički značajnim poboljšanjem tjelesne spremnosti uz pozitivnu korelaciju s poboljšanjem uhranjenosti i plućne funkcije.Background. Exercise tolerance is compromised in many patients with cystic fibrosis (CF) and negatively affects their quality of life. The six-minute walk test (6MWT) can be used to assess exercise tolerance. Aim. To investigate whether cystic fibrosis transmembrane conductance regulator (CFTR) modulators are associated with an improvement in exercise tolerance. Methods. This is a retrospective study including children aged ≥ 5 years who began treatment with lumacaftor/ivacaftor (LUM/IVA) or elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) at the Cystic Fibrosis Centre for Children and Adults at the University Hospital Centre Zagreb in the period between 15. 10. 2021. and 30. 10. 2022. Patients were monitored during the first 12 months of treatment; every 3 months body mass index (BMI) was calculated and spirometry and 6MWT were performed. Collected data were analysed for a change in 6MWT results, BMI and percent-predicted FEV1 (ppFEV1) as well as correlation between these parameters. Missing values were replaced using imputation methods. Results. 36 patients (median age 14 years) were included; 27 received ELX/TEZ/IVA and 9 received LUM/IVA. Average 6MWT walking distance (6MWD) prior to treatment and after 12 months were 522.1 ± 99.9 and 592.0 ± 106.3 m respectively (p < 0.001). Average increase in 6MWD in the first half-year was significantly higher than in the following 6 months (p = 0.023). Changes in BMI z-score (p = 0.006) and ppFEV1 (p < 0.001) during treatment were also significant. 6MWD at 12 months positively correlated with BMI z-score (p = 0.002) and ppFEV1 (p < 0.001). Conclusions. Both clinically and statistically significant improvement in 6MWT results was visible following initiation of CFTR modulator treatment. A positive correlation with lung function improvement and improvement in BMI was observed

Six minute walk test in children with cystic fibrosis before and during treatment with cystic fibrosis transmembrane conductance regulator modulators

Uvod. Narušena tjelesna spremnost bitno negativno utječe na kvalitetu života oboljelih od cistične fibroze (CF). Može se procijeniti šest-minutnim testom hoda (6MWT). Cilj istraživanja. Istražiti povezanost primjene modulatora transmembranskog regulatora provodljivosti za CF (CFTR) s poboljšanjem tjelesne spremnosti. Metode. Ovo retrospektivno istraživanje provedeno je s podatcima prikupljenim od maloljetnih bolesnika ≥ 5 god. koji su u razdoblju od 15. 10. 2021. do 30. 10. 2022. započeli liječenje eleksakaftorom/tezakaftorom/ivakaftorom (ELX/TEZ/IVA) ili lumakaftorom/ivakaftorom (LUM/IVA) u Centru za cističnu fibrozu djece i odraslih Kliničkog bolničkog centra Zagreb. Ispitanici su praćeni prvih 12 mjeseci liječenja te im je svaka tri mjeseca određen indeks tjelesne mase (BMI), učinjena spirometrija i 6MWT. Praćena je promjena navedenih parametara u tom razdoblju te međuodnos rezultata 6MWT-a i BMI-ja, odnosno plućne funkcije. Nedostajali podatci nadomješteni su primjenom imputacije. Rezultati. 36 bolesnika (medijan dobi 14 god.) uključeno je u istraživanje; njih 27 liječeno s ELX/TEZ/IVA, a 9 s LUM/IVA. Prosječna duljina hodne pruge na početku liječenja iznosila je 522,1 ± 99,9 m, a nakon 12 mjeseci 592,0 ± 106,3 m (p < 0,001). Pritom je najveće povećanje duljine hodne pruge bilo zabilježeno u prvih šest mjeseci liječenja (p = 0,023). Promjena z-vrijednosti BMI-ja (p = 0,006) i postotka prediktivne vrijednosti FEV1 (ppFEV1) (p < 0,001) tijekom 12 mjeseci praćenja također je bila značajna. Duljina hodne pruge nakon 12 mjeseci liječenja pozitivno je korelirala sa z-vrijednošću BMI-ja (p = 0,002) i ppFEV1 (p < 0,001). Zaključak. Liječenje CFTR modulatorima praćeno je i klinički i statistički značajnim poboljšanjem tjelesne spremnosti uz pozitivnu korelaciju s poboljšanjem uhranjenosti i plućne funkcije.Background. Exercise tolerance is compromised in many patients with cystic fibrosis (CF) and negatively affects their quality of life. The six-minute walk test (6MWT) can be used to assess exercise tolerance. Aim. To investigate whether cystic fibrosis transmembrane conductance regulator (CFTR) modulators are associated with an improvement in exercise tolerance. Methods. This is a retrospective study including children aged ≥ 5 years who began treatment with lumacaftor/ivacaftor (LUM/IVA) or elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) at the Cystic Fibrosis Centre for Children and Adults at the University Hospital Centre Zagreb in the period between 15. 10. 2021. and 30. 10. 2022. Patients were monitored during the first 12 months of treatment; every 3 months body mass index (BMI) was calculated and spirometry and 6MWT were performed. Collected data were analysed for a change in 6MWT results, BMI and percent-predicted FEV1 (ppFEV1) as well as correlation between these parameters. Missing values were replaced using imputation methods. Results. 36 patients (median age 14 years) were included; 27 received ELX/TEZ/IVA and 9 received LUM/IVA. Average 6MWT walking distance (6MWD) prior to treatment and after 12 months were 522.1 ± 99.9 and 592.0 ± 106.3 m respectively (p < 0.001). Average increase in 6MWD in the first half-year was significantly higher than in the following 6 months (p = 0.023). Changes in BMI z-score (p = 0.006) and ppFEV1 (p < 0.001) during treatment were also significant. 6MWD at 12 months positively correlated with BMI z-score (p = 0.002) and ppFEV1 (p < 0.001). Conclusions. Both clinically and statistically significant improvement in 6MWT results was visible following initiation of CFTR modulator treatment. A positive correlation with lung function improvement and improvement in BMI was observed

Novel Therapeutic Agents in Treatment of Alzheimer’s Disease

Razvoj medicine produžio je ljudski životni vijek, ali povećanjem udjela starog stanovništva raste i incidencija neurodegenerativnih bolesti kao što je Alzheimerova bolest. Donedavno je jedina opcija za liječenje Alzheimerove bolesti bila simptomatska terapija u obliku inhibitora kolinesteraze (rivastigmin, donepezil, galantamin) ili antagonista NMDA receptora (memantin). Pokušaji pronalaska potencijalne terapije koja ne ublažava samo kliničku sliku, već može i usporiti ili potpuno zaustaviti progresiju neurološkog i kognitivnog propadanja, usmjereni su na dvije osnovne morfološke karakteristike bolesti – amiloidne plakove i hiperfosforilirane tau neurofibrilarne snopiće, zbog čega se naziva antiamiloidnom i antitau terapijom. Taj se terapijski pristup temelji na inhibiciji sinteze beta-amiloida ili proteina tau, sprječavanju njihova taloženja u agregate ili uklanjanju nastalih patoloških oblika primjenom specifičnih protutijela. Jedan takav lijek, aducunumab (originalno ime Aduhelm), nedavno je odobrio FDA za liječenje blage Alzheimerove bolesti.The developments in the field of medicine have led to an increase in human lifespan, but with it comes the growth of older population which is followed by an increase in incidence of neurodegenerative diseases such as Alzheimer’s disease. Until recently, the only available therapy for Alzheimer’s disease was symptomatic in nature, such as the cholinesteraze inhibitors (rivastigmine, donepezil, galantamine) and the NMDA receptor antagonist memantine. Current attempts to find the potential disease-modifying therapy are targeting two typical morphological features of the disease, amyloid plaques and tau protein neurofibrillary tangles, which is why they are classified as anti-amyloid and anti-tau therapy. This approach is based on inhibition of beta-amyloid or tau protein synthesis, prevention of their aggregation or promotion of their clearence through use of specific antibodies. One such drug, aducunumab (brand name Aduhelm), has recently been approved by the FDA for treatment of mild Alzheimer’s disease