Pneumonia in Immunosuppressed Patients

Plućne infekcije važan su uzrok morbiditeta i mortaliteta u imunosuprimiranih bolesnika. U posljednje se vrijeme spektar imunokompromitiranih bolesnika znatno proširio zbog povećanja broja bolesnika koji primaju imunosupresivnu terapiju nakon transplantacije organa ili u sklopu liječenja autoimunosnih upalnih bolesti, bolesnika s malignim i hematološkim bolestima te onih s infekcijom virusom humane imunodeficijencije. Imunosupresija može nastati kao posljedica neutropenije, oštećenja humoralne ili stanične imunosti ili primjene kortikosteroida. Rizik od infekcije pojedinim patogenima ovisi o vrsti imunosnog deficita te stupnju i trajanju imunosupresije. Uz uobičajene patogene oportunistički patogeni mogu uzrokovati teške infekcije u imunosuprimiranog bolesnika. Također, u tih su bolesnika česte istodobne multiple infekcije. Rano postavljanje specifične mikrobiološke dijagnoze i započinjanje ciljanoga mikrobiološkog liječenja mogu smanjiti morbiditet i mortalitet.Pulmonary infections are a significant cause of morbidity and mortality in immunocompromised hosts. In recent years, the spectrum of immunocompromised patients has significantly increased as a result of a growing number of patients receiving immunosuppressive drug regimens for the management of organ transplantation or autoimmune inflammatory conditions, patients with malignancies, hematologic diseases and patients with human immunodeficiency virus infection. Immunosuppression may be a result of a lack of neutrophil-mediated immunity, as well as a lack of humoral or cellular immunity or the use of glucocorticoids. The type of pathogens causing the infection is directly related to the underlying type of immunodeficiency, and the degree and duration of the immunosuppression. In addition to common pathogens, organisms of low native virulence can cause severe infections in immunocompromised hosts. Multiple simultaneous infections are also common in this population. Early specific microbiologic diagnoses and initiating the target therapy can help reduce morbidity and mortality. Whenever possible, the level of immunosuppression should be decreased, to improve the outcomes

Pneumonia in Immunosuppressed Patients

Plućne infekcije važan su uzrok morbiditeta i mortaliteta u imunosuprimiranih bolesnika. U posljednje se vrijeme spektar imunokompromitiranih bolesnika znatno proširio zbog povećanja broja bolesnika koji primaju imunosupresivnu terapiju nakon transplantacije organa ili u sklopu liječenja autoimunosnih upalnih bolesti, bolesnika s malignim i hematološkim bolestima te onih s infekcijom virusom humane imunodeficijencije. Imunosupresija može nastati kao posljedica neutropenije, oštećenja humoralne ili stanične imunosti ili primjene kortikosteroida. Rizik od infekcije pojedinim patogenima ovisi o vrsti imunosnog deficita te stupnju i trajanju imunosupresije. Uz uobičajene patogene oportunistički patogeni mogu uzrokovati teške infekcije u imunosuprimiranog bolesnika. Također, u tih su bolesnika česte istodobne multiple infekcije. Rano postavljanje specifične mikrobiološke dijagnoze i započinjanje ciljanoga mikrobiološkog liječenja mogu smanjiti morbiditet i mortalitet.Pulmonary infections are a significant cause of morbidity and mortality in immunocompromised hosts. In recent years, the spectrum of immunocompromised patients has significantly increased as a result of a growing number of patients receiving immunosuppressive drug regimens for the management of organ transplantation or autoimmune inflammatory conditions, patients with malignancies, hematologic diseases and patients with human immunodeficiency virus infection. Immunosuppression may be a result of a lack of neutrophil-mediated immunity, as well as a lack of humoral or cellular immunity or the use of glucocorticoids. The type of pathogens causing the infection is directly related to the underlying type of immunodeficiency, and the degree and duration of the immunosuppression. In addition to common pathogens, organisms of low native virulence can cause severe infections in immunocompromised hosts. Multiple simultaneous infections are also common in this population. Early specific microbiologic diagnoses and initiating the target therapy can help reduce morbidity and mortality. Whenever possible, the level of immunosuppression should be decreased, to improve the outcomes

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

TLR7 gene and protein in non-small cell lung cancer

UVOD: Karcinom pluća vodeći je uzrok smrti od malignih bolesti širom svijeta. Kronična upala, kronična izloženost štetnim tvarima, narušena funkcija urođene i stečene imunosti uz genetske mutacije dovode do promjene u staničnom mikrookolišu i smatraju se najčešćim uzrokom ove teške bolesti. Ovim istraživanjem želimo dokazati povezanost genetičkih biomarkera (polimorfizama) s nastankom i razvojem karcinoma pluća nemalih stanica (NSCLC). ----- ISPITANICI I METODE: U istraživanje je uključeno 450 ispitanika s dijagnozom NSCLC-a te 1283 zdravih ispitanika. Genotipizacijom je određena učestalost polimorfizama TLR7 gena i njhova povezanost s TNM statusom. Metodom RT-PCR ispitana je razina ekspresije TLR7 gena i IFNγ u uzorcima tumorskog tkiva uz analizu limfocita u tumorskom mikrookolišu. ----- REZULTATI: U ispitivanoj populaciji pronašli smo dva najčešća polimofizma TLR7 gena; rs5935436 CT i rs12843803 TG koji su povezani s nastankom NSCLC-a. Prisutnost polimorfnog biljega rs12843803 TG statistički je značajno povezana sa stupnjem zahvaćenosti limfnih čvorova. Rezultati analize profiliranja tumorskog mikrookoliša pokazali su da je stupanj infiltracije CD8+ limfocita T u tumorsku stromu statistički značajno povišen o genotipu rs5935436 CT. ----- ZAKLJUČAK: Rezultati ovog istraživanja pokazuju povezanost nasljedno uvjetovane povećane ekspresije TLR7 gena, rizika za razvoj karcinoma pluća nemalih stanica i obilježja tumorskog okoliša, što može poslužiti kao osnova za daljnja istraživanja protutumorske terapije usmjerene na funkciju TLR7 gena.INTRODUCTION: Lung cancer is the leading cause of death in the group of malignant diseases worldwide. Chronic inflammation, chronic exposure to harmful substances, impaired innate and acquired immune function with genetic mutations lead to changes in the cellular microenvironment and they are considered to be the most common cause of this severe disease. We want to prove the association of cancergenetic biomarkers (polymorphisms) with non-small cell lung cancer (NSCLC). ----- SUBJECTS AND METHODS: The study included 450 patients with NSCLC and 1283 healthy respondents. We used genotyping to determine the frequency of TLR7 gene polymorphisms and their association with TNM status. The level of TLR7 gene and IFNγ expression in tumor tissue samples were examined by RT-PCR with analysis of the tumor microenvironment. ----- RESULTS: In our study rs5935436 CT and rs12843803 TG were the most common polymorphisms of the TLR7 gene associated with the formation of NSCLC. The presence of the polymorphic marker rs12843803 TG was significantly associated with the degree of lymph node metastases. We analysed the tumor microenvironment and showed that the degree of CD8 infiltration into the tumor stroma was significantly higher in patients with rs5935436 CT genotype. ----- CONCLUSION: This study confirmed an association between hereditary increased TLR7 gene expression, risk of non-small cell lung cancer and tumor microenvironment. This data can be useful for the further research on anticancer therapy focused on TLR7 gene function

TLR7 gene and protein in non-small cell lung cancer

UVOD: Karcinom pluća vodeći je uzrok smrti od malignih bolesti širom svijeta. Kronična upala, kronična izloženost štetnim tvarima, narušena funkcija urođene i stečene imunosti uz genetske mutacije dovode do promjene u staničnom mikrookolišu i smatraju se najčešćim uzrokom ove teške bolesti. Ovim istraživanjem želimo dokazati povezanost genetičkih biomarkera (polimorfizama) s nastankom i razvojem karcinoma pluća nemalih stanica (NSCLC). ----- ISPITANICI I METODE: U istraživanje je uključeno 450 ispitanika s dijagnozom NSCLC-a te 1283 zdravih ispitanika. Genotipizacijom je određena učestalost polimorfizama TLR7 gena i njhova povezanost s TNM statusom. Metodom RT-PCR ispitana je razina ekspresije TLR7 gena i IFNγ u uzorcima tumorskog tkiva uz analizu limfocita u tumorskom mikrookolišu. ----- REZULTATI: U ispitivanoj populaciji pronašli smo dva najčešća polimofizma TLR7 gena; rs5935436 CT i rs12843803 TG koji su povezani s nastankom NSCLC-a. Prisutnost polimorfnog biljega rs12843803 TG statistički je značajno povezana sa stupnjem zahvaćenosti limfnih čvorova. Rezultati analize profiliranja tumorskog mikrookoliša pokazali su da je stupanj infiltracije CD8+ limfocita T u tumorsku stromu statistički značajno povišen o genotipu rs5935436 CT. ----- ZAKLJUČAK: Rezultati ovog istraživanja pokazuju povezanost nasljedno uvjetovane povećane ekspresije TLR7 gena, rizika za razvoj karcinoma pluća nemalih stanica i obilježja tumorskog okoliša, što može poslužiti kao osnova za daljnja istraživanja protutumorske terapije usmjerene na funkciju TLR7 gena.INTRODUCTION: Lung cancer is the leading cause of death in the group of malignant diseases worldwide. Chronic inflammation, chronic exposure to harmful substances, impaired innate and acquired immune function with genetic mutations lead to changes in the cellular microenvironment and they are considered to be the most common cause of this severe disease. We want to prove the association of cancergenetic biomarkers (polymorphisms) with non-small cell lung cancer (NSCLC). ----- SUBJECTS AND METHODS: The study included 450 patients with NSCLC and 1283 healthy respondents. We used genotyping to determine the frequency of TLR7 gene polymorphisms and their association with TNM status. The level of TLR7 gene and IFNγ expression in tumor tissue samples were examined by RT-PCR with analysis of the tumor microenvironment. ----- RESULTS: In our study rs5935436 CT and rs12843803 TG were the most common polymorphisms of the TLR7 gene associated with the formation of NSCLC. The presence of the polymorphic marker rs12843803 TG was significantly associated with the degree of lymph node metastases. We analysed the tumor microenvironment and showed that the degree of CD8 infiltration into the tumor stroma was significantly higher in patients with rs5935436 CT genotype. ----- CONCLUSION: This study confirmed an association between hereditary increased TLR7 gene expression, risk of non-small cell lung cancer and tumor microenvironment. This data can be useful for the further research on anticancer therapy focused on TLR7 gene function

TLR7 gene and protein in non-small cell lung cancer

UVOD: Karcinom pluća vodeći je uzrok smrti od malignih bolesti širom svijeta. Kronična upala, kronična izloženost štetnim tvarima, narušena funkcija urođene i stečene imunosti uz genetske mutacije dovode do promjene u staničnom mikrookolišu i smatraju se najčešćim uzrokom ove teške bolesti. Ovim istraživanjem želimo dokazati povezanost genetičkih biomarkera (polimorfizama) s nastankom i razvojem karcinoma pluća nemalih stanica (NSCLC). ----- ISPITANICI I METODE: U istraživanje je uključeno 450 ispitanika s dijagnozom NSCLC-a te 1283 zdravih ispitanika. Genotipizacijom je određena učestalost polimorfizama TLR7 gena i njhova povezanost s TNM statusom. Metodom RT-PCR ispitana je razina ekspresije TLR7 gena i IFNγ u uzorcima tumorskog tkiva uz analizu limfocita u tumorskom mikrookolišu. ----- REZULTATI: U ispitivanoj populaciji pronašli smo dva najčešća polimofizma TLR7 gena; rs5935436 CT i rs12843803 TG koji su povezani s nastankom NSCLC-a. Prisutnost polimorfnog biljega rs12843803 TG statistički je značajno povezana sa stupnjem zahvaćenosti limfnih čvorova. Rezultati analize profiliranja tumorskog mikrookoliša pokazali su da je stupanj infiltracije CD8+ limfocita T u tumorsku stromu statistički značajno povišen o genotipu rs5935436 CT. ----- ZAKLJUČAK: Rezultati ovog istraživanja pokazuju povezanost nasljedno uvjetovane povećane ekspresije TLR7 gena, rizika za razvoj karcinoma pluća nemalih stanica i obilježja tumorskog okoliša, što može poslužiti kao osnova za daljnja istraživanja protutumorske terapije usmjerene na funkciju TLR7 gena.INTRODUCTION: Lung cancer is the leading cause of death in the group of malignant diseases worldwide. Chronic inflammation, chronic exposure to harmful substances, impaired innate and acquired immune function with genetic mutations lead to changes in the cellular microenvironment and they are considered to be the most common cause of this severe disease. We want to prove the association of cancergenetic biomarkers (polymorphisms) with non-small cell lung cancer (NSCLC). ----- SUBJECTS AND METHODS: The study included 450 patients with NSCLC and 1283 healthy respondents. We used genotyping to determine the frequency of TLR7 gene polymorphisms and their association with TNM status. The level of TLR7 gene and IFNγ expression in tumor tissue samples were examined by RT-PCR with analysis of the tumor microenvironment. ----- RESULTS: In our study rs5935436 CT and rs12843803 TG were the most common polymorphisms of the TLR7 gene associated with the formation of NSCLC. The presence of the polymorphic marker rs12843803 TG was significantly associated with the degree of lymph node metastases. We analysed the tumor microenvironment and showed that the degree of CD8 infiltration into the tumor stroma was significantly higher in patients with rs5935436 CT genotype. ----- CONCLUSION: This study confirmed an association between hereditary increased TLR7 gene expression, risk of non-small cell lung cancer and tumor microenvironment. This data can be useful for the further research on anticancer therapy focused on TLR7 gene function