221 research outputs found
Solution structure of beta(2)-microglobulin and insights into fibrillogenesis
No full textThe solution structure of human b2-microglobulin (b2-m) was determined by 1H NMR spectroscopy and restrained modeling calculations.
Compared to the crystal structure of type I major histocompatibility complex (MHC-I), where the protein is associated to the heavy-chain
component, several differences are observed, i.e., increased separation between strands A and B, displacements of strand CV and loop DE,
shortening of strands D and E. These modifications can be considered as the prodromes of the amyloid transition. Even minor charge changes
in response to pH, as is the case with H31 imidazole protonation, trigger the transition that starts with unpairing of strand A. The same
mechanism accounts for the partial unfolding and fiber formation subsequent to Cu2+ binding which is shown to occur primarily at H31.
Solvation of the protected regions in MHC-I decreases the tertiary packing by breaking the contiguity of the surface hydrophobic patches via
surface charge cluster. Mutants or truncated forms of h2-m can be designed to remove the instability from H31 titration or to enhance the
instability through surface charge suppression. By monitoring the conformational evolution of wild-type protein and variants thereof, either
in response or absence of external perturbation, valuable insights into intermediate structure and fibrillogenesis mechanisms are gained
Clinical importance of nontuberculous mycobacteria isolates from the respiratory specimens
No full textNetuberkulozne mikobakterije (NTM) sveprisutni su mikrooganizmi koje nalazimo primarno u tlu i vodi. One su oportunistički patogeni, a najvažniji oblik bolesti koje uzrokuju je plućni oblik (NTM-PB). Stoga se ove mikobakterije primarno promatraju kroz respiratorne izolate, bili to sputumi, lavati ili bioptati plućnog tkiva. Ovaj rad se upravo zato bavi proučavanjem kliničke važnosti netuberkuloznih mikobakterija izoliranih iz respiratornih uzoraka.
Globalno se prati porast izolacije i incidencije te shodno tome, prevalencije plućne bolesti uzrokovane netuberkuloznim mikobakterijama. Jedan od mogućih razloga je i starenje populacije, porast pridruženih komorbiditeta i pad imuniteta, trend koji pratimo u svim zemljama, najviše onim razvijenim.
Prema novim smjernica ATS/ERS/ESCMID/IDSA društava, vrste NTM na koje globalno treba obratiti pozornost su Mycobacterium avium complex (MAC), Mycobacterium kansasii, M. xenopi od spororastućih te M. abscessus od brzorastućih. Lokalna istraživanja pokazuju rezultate koji su različiti ovisno o dijelu svijeta u kojemu su rađena, a spoznalo se i da frekvencija izolacije NTM te prevalencija NTM-PB ovisi i o zemljopisnom položaju.
U Republici Hrvatskoj rađeno je nekoliko istraživanja na temu netuberkuloznih mikobakterija. Neke od spoznaja proizašlih iz tih istraživanja su porast frekvencije izolacije NTM iz respiratornih izolata, klinički najznačajnije vrste (M. xenopi, M. kansasii, M. abscessus i MAC) te različita zemljopisna (priobalni u odnosu na kontinentalni dio) rasprostranjenost NTM i opterećenost NTM-PB. Zaključno tome, poznavanje kliničke važnosti NTM vrste je važno pri postavljanju definitivne dijagnoze NTM-PB i adekvatnom liječenju bolesti.Nontuberculous mycobacteria (NTM) are ubiquitous, opportunistic microorganisms found primarily in soil and water. The most common form of disease they cause is the pulmonary form (nontuberculous mycobacterial pulmonary disease, NTM-PD), and most important specimens for evaluation are respiratory specimens (sputum, lavages, or lung tissue biopsies). Thus, this paper examines the clinical importance of nontuberculous mycobacteria isolated from respiratory samples. Globally, there is an increase in isolation and incidence of NTM and, consequently, the prevalence of NTM-PD. One of the possible reasons is the aging of the population with increasing number of comorbidities and a decline in immunity, a trend that is present in all countries, especially developed ones.
From the latest guidelines of ATS/ERS/ESCMID/IDSA societies, the species that globally present a threat are Mycobacterium avium complex (MAC), M. kansasii, M. xenopi from slow-growing and M. abscessus from rapid-growing NTMs. Also, many local researches show results that are different depending on the part of the world in which they were conducted. Furthermore, it was found that the frequency of NTM isolation and NTM-PD depends on the geographical location. In Croatia, several studies have been conducted in this area. From them, we know that the isolation frequency of NTM and NTM-PD is rising, and that most clinically significant species are M. xenopi, M. kansasii, M. abscessus and MAC. Also, it was shown that the burden of NTM isolation and NTM-PD differs in the continental part of the country, compared to the coastal part. Finally, awareness and knowledge of clinical importance is important when making a definitive diagnosis of NTM-PD and deciding on optimal treatment regimen
Simulation of a detector system for positron emission tomography
No full textPozitronska emisijska tomografija (PET) je moćna neinvazivna dijagnostička metoda nuklearne medicine koja se bazira na koincidentnoj detekciji dvaju kolinearnih γ fotona čiji izvor je u anihilaciji pozitrona i elektrona. Temeljno svojstvo PET sustava je osjetljivost, koja se definira kao omjer opaženih koincidentnih događaja i ukupnog broja anihilacijskih događaja koje proizvodi izvor, a ovisi o efikasnosti detektora i prostornoj akceptanciji. Razvoj geometrije realnih PET sustava temeljen je na simulacijama provedenim na 8 jednostavnih modela u programskom paketu GATE. Jednostavni modeli poslužili su za precizne interpretacije prostornih raspodjela i udjela različitih mehanizama interakcije γ zračenja i scintilacijskih materijala. Za odabrane LSO i LFS materijale pokazalo se da prostorni raspored interakcija γ fotona u kristalu ima maksimum na prednjoj strani što je u skladu sa atenuacijskim ponašanjem γ zračenja. Od interakcija dominiraju one u kojima je deponirana ukupna energija anihilacijskog gama zračenja od 511 keV sa 48 % udjela, dok je 46 % događaja u kojima je depozicija energije gama čestica u intervalu od 50–400 keV, što odgovara Comptonovim raspršenjima, dok se Rayleighovo raspršenje dograda u 6 % događaja. U simulacijskom sučelju GATE konstruirane su dvije realne PET geometrije: jedna manja sa 4 prstena radijusa 0.135 m sa po 48 detektorskih modula unutar prstena, a druga veća sa 16 prstenova radijusa 0.630 m sa po 200 detektorskih modula unutar prstena. Detektorski moduli su dimenzija 20x16x16 mm3 za malu odnosno 20x20x25 mm3 za veliku geometriju i sastoje se od 4x4 scintilacijska kristala dimenzija 20x3x3 mm3. Simulacija sa točkastim izvorom u središtu geometrije pokazala je da je osjetljivost 5.55 % za manju geometriju odnosno 2.48 % za veću geometriju, uz uvjet da se opažaju samo anihilacijski fotoni koji u detektorima deponiraju svu energiju u prozoru 0.4–0.6 MeV, što je usporedivo sa standardnim PET sustavima. Ispitan je utjecaj atenuirajućeg materijala (fantoma), kao i utjecaj konačne veličine pozitronskog izvora na osjetljivost PET sustava. Konačno određena je gornja granica osjetljivosti konstruiranih PET sustava, kao ona u kojoj bi se uzimali u obzir svi koincidentni događaji u kojima je depozicija energije gama čestica u puno širem energijskom prozoru 0.05–0.65 MeV. Dobiveni rezultati pokazuju da su gornje granice osjetljivosti PET sustava 55.75 % za manju odnosno 23.51 % za veću geometriju.Positron emission tomography (PET) is powerful non-invasive diagnostic technique of nuclear medicine based on detecting coincidence events of two colinear γ photons emerging from positron-electron annihilation events. Basic property which characterizes PET system is sensitivity for coincidences which is defined as a ratio of detected coincidence events and all annihilation events which emerge from the source. Sensitivity depends on detection efficiency and solid angle of PET system. Development of geometries for modern PET systems made in software package GATE was based on tests conducted on 8 simple models. Models were used in order to understand mechanism of γ radiation interaction with scintillation materials precisely and for understanding of spatial distribution of interactions. For LSO and LFS scintillation crystals it was shown that spatial distribution of interactions has maximum in front part of the crystal which is consistent with attenuation of γ radiation. Considering types of interactions of γ photons with crystals, the biggest energy deposition of 511 keV γ photons comes above 400 keV in 48 % of events while interactions due to Compton scattering in energy interval 50–400 keV contribute in 46 % of events and finally Rayleigh scattering in 6 % of events. Two real PET geometries were constructed using simulation interface GATE: one smaller consisting of 4 detection rings with radius 0.135 m with 48 detector modules per ring and second bigger with 16 detection rings with radius 0.630 m with 200 detector modules per ring. Dimensions of detector modules were 20x16x16 mm3 for small geometry and 20x20x25 mm3 for big geometry and they consisted of 4x4 scintillation crystals sized 20x3x3 mm3. Simulation with pointlike source in the center of geometry gave sensitivity of 5.55 % for smaller and 2.48 % for bigger geometry with condition that detected photons had deposited energy in interval 0.4–0.6 MeV similar to standard PET systems. Furthermore, attenuation material (phantom) was introduced as well as volume distribution of positron source in order to investigate their influence on PET sensitivity. Eventually, the upper limit of sensitivity of developed PET system was determined by using all coincidence events in which deposited energy of γ photons was in wider window 0.05–0.65 MeV. Results showed that upper limits for sensitivity were 55.75 % for smaller and 23.51 % for bigger geometry
Epidemiology and clinical relevance of nontuberculous mycobacteria isolated from pulmonary samples in Croatia
No full textUvod: klinička važnost netuberkuloznih mikobakterija (NTM) izoliranih iz uzoraka plućnog porijekla u Hrvatskoj nije u potpunosti poznata. ----- Cilj: izračunati incidenciju izolacije NTM-a i plućne mikobakterioze, zabilježiti regionalne razlike i ocijeniti valjanost
mikrobioloških kriterija pri postavljanju dijagnoze i praćenju pojavnosti bolesti. ----- Materijali i metode: u istraživanje su uključeni svi državljani Hrvatske kod kojih je izolirana NTM u razdoblju između 2006. i 2012. godine. Za definiciju plućne mikobakterioze korišteni su mikrobiološki te cjeloviti kriteriji Američkog torakalnog društva iz 2007. godine. ----- Rezultati: najčešće izolirane vrste NTM-a su Mycobacterium gordonae i M. xenopi, a klinički su najznačajnije M. avium complex, M. kansasii i
M. xenopi. Prosječna godišnja incidencija izolacije NTM-a iznosi 3,9 na 100 000 stanovnika, no unutar Hrvatske zabilježene su značajne
zemljopisne razlike u samoj distribuciji NTM vrsta. Također, prosječna godišnja incidencija plućne mikobakterioze dvostruko je veća u
obalnom u odnosu na kontinentalni dio Hrvatske (0,32 naprema 0,16), dok ukupna incidencija u Hrvatskoj iznosi 0,22 slučaja na 100 000 stanovnika. Uvidom u medicinsku dokumentaciju i usporedbom valjanosti, nađena je dobra korelacija mikrobioloških i cjelovitih kriterija. ----- Zaključak: raste incidencija plućne mikobakterioze u Hrvatskoj. Postoje značajne zemljopisne razlike u distribuciji vrsta NTM-a i incidenciji bolesti između obalnog i kontinentalnog dijela Hrvatske. Mikrobiološki kriterij ima značajnu ulogu u procjeni godišnje incidencije plućne mikobakterioze i praćenju pojavnosti bolesti.Background: clinical relevance of nontuberculous mycobacteria (NTM) isolated from pulmonary samples in Croatia is
largely unknown. ----- Objective: estimate the isolation rate of the NTM, record geographical differences, assess the clinical relevance
of different NTM species and the burden of pulmonary NTM disease (PNTM). ----- Design: study included all Croatian residents with NTM isolated from pulmonary samples in the period from 2006
through 2012. Microbiological and full criteria of the American Thoracic Society (ATS) were used to establish a case definition of the PNTM. ----- Results: the most frequently isolated NTM species were Mycobacterium gordonae and M. xenopi. The average annual
incidence of pulmonary NTM isolation was 3.9/100 000. Species distribution differed between coastal and continental
Croatia. Clinically most relevant NTM species in Croatia were M. avium complex, M. kansasii and M. xenopi. We estimated annual
incidence of the PNTM at 0.22/100 000. This estimated annual incidence was 0.32/100 000 in the coastal and 0.16/100 000 in the
continental region. Good correlation between the microbiological and the full ATS criteria in the estimation of the disease burden was found. ----- Conclusion: Geography plays a role in the NTM species distribution, as well as the distribution of the PNTM. The
incidence of the PNTM in Croatia is rising, but the overall burden of the disease is still low compared to tuberculosis
Epidemiologija i klinička važnost plućnih infekcija uzrokovanih netuberkuloznim mikobakterijama [Epidemiology and clinical relevance of nontuberculous mycobacteria isolated from pulmonary samples in Croatia]
No full textBackground: clinical relevance of nontuberculous mycobacteria (NTM) isolated from pulmonary samples in Croatia is
largely unknown. ----- Objective: estimate the isolation rate of the NTM, record geographical differences, assess the clinical relevance
of different NTM species and the burden of pulmonary NTM disease (PNTM). ----- Design: study included all Croatian residents with NTM isolated from pulmonary samples in the period from 2006
through 2012. Microbiological and full criteria of the American Thoracic Society (ATS) were used to establish a case definition of the PNTM. ----- Results: the most frequently isolated NTM species were Mycobacterium gordonae and M. xenopi. The average annual
incidence of pulmonary NTM isolation was 3.9/100 000. Species distribution differed between coastal and continental
Croatia. Clinically most relevant NTM species in Croatia were M. avium complex, M. kansasii and M. xenopi. We estimated annual
incidence of the PNTM at 0.22/100 000. This estimated annual incidence was 0.32/100 000 in the coastal and 0.16/100 000 in the
continental region. Good correlation between the microbiological and the full ATS criteria in the estimation of the disease burden was found. ----- Conclusion: Geography plays a role in the NTM species distribution, as well as the distribution of the PNTM. The
incidence of the PNTM in Croatia is rising, but the overall burden of the disease is still low compared to tuberculosis
Epidemiology and clinical relevance of nontuberculous mycobacteria isolated from pulmonary samples in Croatia
No full textUvod: klinička važnost netuberkuloznih mikobakterija (NTM) izoliranih iz uzoraka plućnog porijekla u Hrvatskoj nije u potpunosti poznata. ----- Cilj: izračunati incidenciju izolacije NTM-a i plućne mikobakterioze, zabilježiti regionalne razlike i ocijeniti valjanost
mikrobioloških kriterija pri postavljanju dijagnoze i praćenju pojavnosti bolesti. ----- Materijali i metode: u istraživanje su uključeni svi državljani Hrvatske kod kojih je izolirana NTM u razdoblju između 2006. i 2012. godine. Za definiciju plućne mikobakterioze korišteni su mikrobiološki te cjeloviti kriteriji Američkog torakalnog društva iz 2007. godine. ----- Rezultati: najčešće izolirane vrste NTM-a su Mycobacterium gordonae i M. xenopi, a klinički su najznačajnije M. avium complex, M. kansasii i
M. xenopi. Prosječna godišnja incidencija izolacije NTM-a iznosi 3,9 na 100 000 stanovnika, no unutar Hrvatske zabilježene su značajne
zemljopisne razlike u samoj distribuciji NTM vrsta. Također, prosječna godišnja incidencija plućne mikobakterioze dvostruko je veća u
obalnom u odnosu na kontinentalni dio Hrvatske (0,32 naprema 0,16), dok ukupna incidencija u Hrvatskoj iznosi 0,22 slučaja na 100 000 stanovnika. Uvidom u medicinsku dokumentaciju i usporedbom valjanosti, nađena je dobra korelacija mikrobioloških i cjelovitih kriterija. ----- Zaključak: raste incidencija plućne mikobakterioze u Hrvatskoj. Postoje značajne zemljopisne razlike u distribuciji vrsta NTM-a i incidenciji bolesti između obalnog i kontinentalnog dijela Hrvatske. Mikrobiološki kriterij ima značajnu ulogu u procjeni godišnje incidencije plućne mikobakterioze i praćenju pojavnosti bolesti.Background: clinical relevance of nontuberculous mycobacteria (NTM) isolated from pulmonary samples in Croatia is
largely unknown. ----- Objective: estimate the isolation rate of the NTM, record geographical differences, assess the clinical relevance
of different NTM species and the burden of pulmonary NTM disease (PNTM). ----- Design: study included all Croatian residents with NTM isolated from pulmonary samples in the period from 2006
through 2012. Microbiological and full criteria of the American Thoracic Society (ATS) were used to establish a case definition of the PNTM. ----- Results: the most frequently isolated NTM species were Mycobacterium gordonae and M. xenopi. The average annual
incidence of pulmonary NTM isolation was 3.9/100 000. Species distribution differed between coastal and continental
Croatia. Clinically most relevant NTM species in Croatia were M. avium complex, M. kansasii and M. xenopi. We estimated annual
incidence of the PNTM at 0.22/100 000. This estimated annual incidence was 0.32/100 000 in the coastal and 0.16/100 000 in the
continental region. Good correlation between the microbiological and the full ATS criteria in the estimation of the disease burden was found. ----- Conclusion: Geography plays a role in the NTM species distribution, as well as the distribution of the PNTM. The
incidence of the PNTM in Croatia is rising, but the overall burden of the disease is still low compared to tuberculosis
Epidemiology and clinical relevance of nontuberculous mycobacteria isolated from pulmonary samples in Croatia
No full textUvod: klinička važnost netuberkuloznih mikobakterija (NTM) izoliranih iz uzoraka plućnog porijekla u Hrvatskoj nije u potpunosti poznata. ----- Cilj: izračunati incidenciju izolacije NTM-a i plućne mikobakterioze, zabilježiti regionalne razlike i ocijeniti valjanost
mikrobioloških kriterija pri postavljanju dijagnoze i praćenju pojavnosti bolesti. ----- Materijali i metode: u istraživanje su uključeni svi državljani Hrvatske kod kojih je izolirana NTM u razdoblju između 2006. i 2012. godine. Za definiciju plućne mikobakterioze korišteni su mikrobiološki te cjeloviti kriteriji Američkog torakalnog društva iz 2007. godine. ----- Rezultati: najčešće izolirane vrste NTM-a su Mycobacterium gordonae i M. xenopi, a klinički su najznačajnije M. avium complex, M. kansasii i
M. xenopi. Prosječna godišnja incidencija izolacije NTM-a iznosi 3,9 na 100 000 stanovnika, no unutar Hrvatske zabilježene su značajne
zemljopisne razlike u samoj distribuciji NTM vrsta. Također, prosječna godišnja incidencija plućne mikobakterioze dvostruko je veća u
obalnom u odnosu na kontinentalni dio Hrvatske (0,32 naprema 0,16), dok ukupna incidencija u Hrvatskoj iznosi 0,22 slučaja na 100 000 stanovnika. Uvidom u medicinsku dokumentaciju i usporedbom valjanosti, nađena je dobra korelacija mikrobioloških i cjelovitih kriterija. ----- Zaključak: raste incidencija plućne mikobakterioze u Hrvatskoj. Postoje značajne zemljopisne razlike u distribuciji vrsta NTM-a i incidenciji bolesti između obalnog i kontinentalnog dijela Hrvatske. Mikrobiološki kriterij ima značajnu ulogu u procjeni godišnje incidencije plućne mikobakterioze i praćenju pojavnosti bolesti.Background: clinical relevance of nontuberculous mycobacteria (NTM) isolated from pulmonary samples in Croatia is
largely unknown. ----- Objective: estimate the isolation rate of the NTM, record geographical differences, assess the clinical relevance
of different NTM species and the burden of pulmonary NTM disease (PNTM). ----- Design: study included all Croatian residents with NTM isolated from pulmonary samples in the period from 2006
through 2012. Microbiological and full criteria of the American Thoracic Society (ATS) were used to establish a case definition of the PNTM. ----- Results: the most frequently isolated NTM species were Mycobacterium gordonae and M. xenopi. The average annual
incidence of pulmonary NTM isolation was 3.9/100 000. Species distribution differed between coastal and continental
Croatia. Clinically most relevant NTM species in Croatia were M. avium complex, M. kansasii and M. xenopi. We estimated annual
incidence of the PNTM at 0.22/100 000. This estimated annual incidence was 0.32/100 000 in the coastal and 0.16/100 000 in the
continental region. Good correlation between the microbiological and the full ATS criteria in the estimation of the disease burden was found. ----- Conclusion: Geography plays a role in the NTM species distribution, as well as the distribution of the PNTM. The
incidence of the PNTM in Croatia is rising, but the overall burden of the disease is still low compared to tuberculosis
New therapeutic approaches for treatment of drug-sensitive and drug-resistant pulmonary tuberculosis
No full textPrema podacima SZO za 2019., procijenjeni broj novooboljelih od tuberkuloze u svijetu je oko 10 milijuna, a preminulih 1.4 milijuna. Tuberkuloza i u današnje vrijeme predstavlja vrlo značajan javnozdravstveni i stručni problem, pogotovo zbog porasta broja bolesnika koji imaju višestruko rezistentnu tuberkulozu (MDR-TB) i prošireno rezistentnu tuberkulozu (XDR-TB). Osjetljiva tuberkuloza se prema važećim smjernicama liječi terapijskim režimom koji se sastoji od intenzivne faze u trajanju od 2 mjeseca te faze održavanja koja najčešće traje 4 mjeseca. Novi terapijski pristupi u liječenju osjetljive tuberkuloze pluća su većinom dizajnirani kako bi se skratilo vrijeme terapije sa 6 mjeseci na 4 mjeseca uvođenjem fluorokinolona ili viših doza standardnih antituberkulotika, no za sada su se pokazali inferiornima u odnosu na standarni režim lijčenja. Ono što obećava jesu studije o primjeni linezolida, klofazimina, bedakvilina i pretomanida u liječenju osjetljive tuberkuloze koje su u tijeku. Višestruko rezistentna i prošireno rezistentna tuberkuloza se prema smjernicama liječi primjenom duljih ili kraćih režima liječenja u trajanju od 9-12 odnosno 18-20 mjeseci primjenom najmanje 5 antituberkuloznih lijekova. Novi terapijski pristupi u liječenju rezistentne tuberkuloze također idu za skraćenjem duljine liječenja kao što je to u slučaju istraživanja osjetljive tuberkuloze. Korištenje modernih molekularnih metoda poput sekvenciranja nove generacije u testiranju rezistencije sojeva M. tuberculosis na antituberkulozne lijekove važno je jer će u skoroj budućnosti omogućiti stvaranje individualiziranih režima liječenja temeljenih na genetskom profilu bakterija.According to WHO data for 2019, the estimated number of new cases of tuberculosis and deaths attributted to tuberculosis are 10 million, and 1.4 million, respectively. Tuberculosis is still a very significant public health and professional problem, especially due to the increase in the number of patients with multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). According to the current guidelines, sensitive tuberculosis is treated with a therapeutic regimen consisting of an intensive phase lasting 2 months and a maintenance phase that usually lasts 4 months. New therapeutic approaches in the treatment of drug-sensitive pulmonary tuberculosis have mostly been designed to shorten therapy time from 6 months to 4 months by introducing fluoroquinolones or higher doses of standard antituberculotics, but so far without much success. What is promising are ongoing clinical studies on the use of linezolid, clofazimine, bedaquiline and pretomanide in the treatment of susceptible tuberculosis. MDR-TB and XDR-TB is treated according to the guidelines by applying longer or shorter treatment regimens lasting 9-12 or 18-20 months using at least 5 drugs. New therapeutic approaches in the treatment of drug-resistant tuberculosis also aimed to shorten the duration of treatment as well as the studies of drug-sensitive tuberculosis. The use of modern molecular methods such as next generation sequencing (NGS) in testing the resistance of M. tuberculosis strains to drugs will in the near future allow the creation of individualized treatment regimens based on the genetic profile of bacteria
Treatment outcomes and five-year survival of patients with nontuberculous mycobacterial pulmonary disease in Croatia
No full textPlućne manifestacije netuberkuloznih mikobakterijskih infekcija (NTM-PD) najčešći su oblik bolesti i sve se više prepoznaju kao važan klinički entitet u ljudi. Najčešće zahvaćaju stariju populaciju s predležećim kroničnim plućnim bolestima. Cilj ove studije bio je utvrditi karakteristike bolesnika s NTM-PD u Hrvatskoj te zabilježiti kliničke ishode i dugoročno preživljavanje nakon završetka terapije. Ovaj stručni rad predstavlja retrospektivnu kohortnu studiju na svim hrvatskim stanovnicima s NTM izoliranim iz respiratornih uzoraka u razdoblju od 1. siječnja 2006. do 31. prosinca 2015. i praćenjem do 31. prosinca 2018. Podaci analizirani u ovoj studiji predstavljaju centralizirane podatke Nacionalnoga registra bolesnika s izoliranim NTM koji se od 2008. godine vodi u Nacionalnome referentnome laboratoriju za mikobakterije (NRML) pri Hrvatskom zavodu za javno zdravstvo (HZJZ), a sadrži kliničke, radiološke te podatke o ishodu liječenja i datum smrti. Tijekom promatranoga razdoblja, u registru je identificirano ukupno 2109 epizoda plućnih NTM izolata kod 2050 bolesnika. Kriteriji za definitivnu bolest zadovoljilo je 137 (29,3%), a bez bolesti 302 (64,3%) od ukupno 468 epizoda s potpunom medicinskom dokumentacijom. Preostalih je 29 (6,2%) epizoda klasificirano kao vjerojatna bolest. Medijan dobi bolesnika s definitivnom NTM plućnom bolesti iznosio je 66,5 (16-90) godina. Od ukupnoga broja bolesnika u ovoj skupini, 62 (45,3%) bolesnika su bile žene. Najčešći komorbiditet u 44,5% bolesnika bila je kronična opstruktivna plućna bolest. Mikrobiološko izlječenje postignuto je u 82,8% bolesnika nakon adekvatnoga NTM liječenja, u 64,7% bolesnika liječenih TB protokolom, te u 64,3% bolesnika liječenih kratkim NTM protokolom, a spontana konverzija
kulture u 41,2% neliječenih bolesnika. U Hrvatskoj NTM plućnu bolest najčešće uzrokuje M. xenopi i MAC s ukupnim 5- godišnjom smrtnošću od 36.5%. Terapija prema smjernicama rezultirala je četiri puta većom vjerojatnošću izlječenja u usporedbi s neadekvatno liječenima ili neliječenim bolesnicima. Ishodi liječenja razlikuju se prema terapijskom režimu i uzročnoj vrsti mikobakterije. Rano započinjanje terapije moglo bi unaprijediti kratkoročne ishode. Potrebna su daljnja istraživanja kako bi se utvrdio utjecaj na dugoročno preživljenje.Pulmonary manifestations of non-tuberculous mycobacterial infections (NTM-PD) are the most common form of the disease and are increasingly recognized as an important clinical entity in humans, most commonly affecting the elderly population with pre-existing chronic lung disease. The aim of this study was to determine characteristics of NTM-PD patients in Croatia, and record clinical outcomes and long-term survival after therapy completion. This study represents a retrospective cohort study on all Croatian residents with NTM isolates from respiratory samples in the period from 1 January 2006 to 31 December 2015 and a follow-up until 31 December 2018. The data analyzed in this study represent centralized data from the National registry of patients with NTM isolate founded in 2008 and managed at the National Reference Mycobacteria Laboratory (NRML) at the Croatian Institute of Public Health (CIPH), containing clinical, radiological and data on treatment outcomes and date of death. During the observed period, in the NRML a total of 2109 episodes of pulmonary NTM isolates were identified in 2050 patients. Criteria for definite disease were met by 137 (29.3%) while for no disease by 302 (64.3%) from total of 468 episodes with full medical records. Remaining 29 (6.2%) episodes were classified as probable disease. The median age of patients with definitive NTM lung disease was 66.5 (16-90) years. Of the total number of patients in
this group, 62 (45.3%) patients were women. The most common comorbidity was chronic obstructive pulmonary disease, in 44.5% of patients. Microbiological cure was observed in 82.8% of patients after adequate NTM treatment, in 64.7% of patients treated with TB protocol, and in 64.3% of patients treated with short NTM protocol while spontaneous culture conversion was observed in 41.2% of untreated patients. In Croatia, NTM-PD was most commonly caused by M. xenopi and MAC with 36.5% 5-year mortality. Guideline-compliant treatment resulted in a four times higher chance of being
cured. Treatment outcomes differed with respect to different treatment regimens and causal species. Early treatment initiation may improve short term outcomes while further investigations are needed to determine impact on the long-term survival
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