TRANSPLANTACIJA PLUĆA U KLINIČKOM BOLNIČKOM CENTRU ZAGREB U HRVATSKOJ

Objective: Lung transplantation has become a standard of care for patients with a variety of non-malignant end-stage lung diseases. The aim of the study was to report on the safety and feasibility of lung transplantation at the Zagreb University Hospital Center. Methods: In this single center retrospective observational study, all consecutive patients undergoing lung transplantation at the Zagreb University Hospital Center from April 2021 until December 2022 were included. The only inclusion criterion was surgery for lung transplantation. Patient demographic and operative characteristics were reported, as well as early outcomes, including 30-day mortality, hospital stay, intensive care unit stay, duration of mechanical ventilation, and incidence of primary graft dysfunction. The degree of primary graft dysfunction was graded based on the International Society for Heart and Lung Transplantation criteria at 72 hours after transplantation with grades 0 to 3. Results: During the 21-month study period, 19 patients were successfully transplanted. There was no 30-day mortality. There was one late death at 18 months after transplantation. Median in-hospital stay was 32 days, ranging from 21 to 62 days. Mean mechanical ventilation duration was 105±58 h and median of intensive care unit stay was 6 days, ranging from 4 to 15 days. Only two (11%) patients had the highest grade 3 primary graft dysfunction. Of the remaining patients, 16 (84%) had none (grade 0) and one (5%) patient had mild primary graft dysfunction (grade 1). Conclusion: Our results suggest that lung transplantation is safely performed at the Zagreb University Hospital Center. Initial results with no operative mortality are encouraging. Further follow-up and experience are needed to make inferences on long-term outcomes of our lung transplantation patients.Cilj: Transplantacija pluća postala je standard skrbi za pacijente s nizom nemalignih plućnih bolesti u završnom stadiju. Cilj ovog istraživanja bio je izvijestiti o sigurnosti i izvedivosti transplantacije pluća u Kliničkom bolničkom centru Zagreb u Hrvatskoj. Metode: U ovu retrospektivnu opservacijsku studiju uključeni su svi uzastopni pacijenti koji su bili podvrgnuti transplantaciji pluća u Kliničkom bolničkom centru Zagreb od travnja 2021. do prosinca 2022. godine. Jedini kriterij za uključivanje bio je kirurški zahvat transplantacije pluća. Zabilježene su demografske i operativne karakteristike pacijenata, kao i rani ishodi, uključujući 30-dnevnu smrtnost, boravak u bolnici, boravak na jedinici intenzivne njege, trajanje mehaničke ventilacije i incidenciju primarne disfunkcije presatka. Stupanj primarne disfunkcije presatka ocijenjen je na temelju kriterija Međunarodnog društva za transplantaciju srca i pluća 72 sata nakon transplantacije ocjenama od 0 do 3. Rezultati: Tijekom dvadesetjednomjesečnog razdoblja istraživanja transplantacija je uspješno primijenjena u 19 pacijenata. Nije bilo 30-dnevne smrtnosti. Dogodila se jedna kasna smrt 18 mjeseci nakon transplantacije. Medijan boravka u bolnici bio je 32 dana, u rasponu od 21 do 62 dana. Prosječno trajanje mehaničke ventilacije bilo je 105±58 h, a medijanboravka u jedinici intenzivne njege bio je 6 dana, u rasponu od 4 do 15 dana. Samo dva (11 %) bolesnika imala su primarnu disfunkciju presatka najvišeg stupnja 3. Od preostalih bolesnika 16 (84 %) ih nije imalo nikakav (stupanj 0), a jedan (5%) bolesnik imao je blagi, stupanj 1. Rasprava: U ovom članku prikazujemo naše početno iskustvo s transplantacijom pluća. Transplantacija pluća bila je jedina od transplantacija solidnih organa koja se donedavno u Hrvatskoj nije rutinski izvodila, s napomenom da je prva transplantacija pluća u Hrvatskoj učinjena još 2003. godine u Klinici za torakalnu kirurgiju Jordanovac, ali se program transplantacije nije tada nastavio. Od travnja 2021. godine transplantacije pluća rutinski se izvode u našem centru i hrvatski pacijenti više ne moraju putovati u inozemstvo radi transplantacije pluća. Sveukupni nedostatak donora pluća i dalje je glavni ograničavajući čimbenik za broj transplantacija koje se izvode na godinu. Svega 20%-30% doniranih pluća iskoristi se za transplantaciju. Potrebno je kontinuirano unaprjeđenje i razvoj strategija koje će povećati broj donora i uporabljivih plućnih presadaka. Zaključak: Naši rezultati pokazuju da se transplantacija pluća sigurno izvodi u Kliničkom bolničkom centru Zagreb. Početni rezultati bez operativnog mortaliteta su ohrabrujući. Daljnje praćenje i iskustvo potrebni su za donošenje zaključaka o dugoročnim ishodima naših pacijenata s transplantacijom pluća

The associations between COMT and MAO-B genetic variants with negative symptoms in patients with schizophrenia

Negative symptoms of schizophrenia, including anhedonia, represent a heavy burden on patients and their relatives. These symptoms are associated with cortical hypodopamynergia and impaired striatal dopamine release in response to reward stimuli. Catechol-O-methyltransferase (COMT) and monoamine oxidase type B (MAO-B) degrade dopamine and affect its neurotransmission. The study determined the association between COMT rs4680 and rs4818, MAO-B rs1799836 and rs6651806 polymorphisms, the severity of negative symptoms, and physical and social anhedonia in schizophrenia. Sex-dependent associations were detected in a research sample of 302 patients with schizophrenia. In female patients with schizophrenia, the presence of the G allele or GG genotype of COMT rs4680 and rs4818, as well as GG haplotype rs4818-rs4680, which were all related to higher COMT activity, was associated with an increase in several dimensions of negative symptoms and anhedonia. In male patients with schizophrenia, carriers of the MAO-B rs1799836 A allele, presumably associated with higher MAO-B activity, had a higher severity of alogia, while carriers of the A allele of the MAO-B rs6651806 had a higher severity of negative symptoms. These findings suggest that higher dopamine degradation, associated with COMT and MAO-B genetic variants, is associated with a sex-specific increase in the severity of negative symptoms in schizophrenia patients

ANHEDONIA IN SCHIZOPHRENIA: MINI-REVIEW

The perception of reward exerts a powerful influence on human behavior. While anhedonia might occur in healthy individuals, its prevalence and severity are much higher in psychiatric patients, particularly those with depression and schizophrenia. Anhedonia is a negative symptom, and presumably a trait marker in schizophrenia. Recent research confirmed that anhedonia is a complex construct, consisting of anticipatory, consummatory, and reward learning components. In general, schizophrenia patients show anticipation deficits, and a substantial portion of them have physical (PA) and social anhedonia (SA). The relationship between anhedonia and psychopathology appears bidirectional. While gene-environment interactions affect reward circuity, anhedonia modulates clinical features, such as suicidality and nicotine consumption. Future clinical research employing longitudinal designs may shed more light on the dynamics and treatment of anhedonia in schizophreni

The association between catechol-O-methyl transferase and monoamine oxidase type B gene polymorphisms and anhedonia in patients with schizophrenia

Cilj ovog istraživanja je bio istražiti povezanost polimorfizama za katehol-O-metil transferazu (COMT) rs4680 i rs4818 i monoaminooksidazu tipa B (MAO-B) rs1799836 i rs6651806 s anhedonijom i drugim negativnim simptomima kod bolesnika sa shizofrenijom. Presječno istraživanje obuhvatilo je 302 bolesnika (58.9% muških, medijan godina 42). Glavni rezultati: nositeljice G alela (povezanog s većom aktivnošću COMT-a) za COMT rs4680 i rs4818 imale su izraženije negativne simptome u odnosu na ispitanice bez G alela. COMT rs4818-rs4680 haplotip G-G je kod ispitanica bio povezan s izraženijim negativnim simptomima. Muški nositelji MAO-B rs1799836 A alela imali su izraženiju alogiju prema nositeljima G alela. Ispitanice s fizičkom i socijalnom anhedonijom imale su veću frekvenciju pojavljivanja MAO-B rs6651806 A alela od ispitanica bez navedenih podtipova anhedonije, ali su nositeljice A alela imale manje depresivnih simptoma od nositeljica C alela. Muški nositelji MAO-B rs6651806 A alela imali su izraženije negativne simptome nego nositelji C alela, dok je MAO-B rs1799836-rs6651806 haplotip G-C kod muških ispitanika bio povezan s manje izraženim negativnim simptomima. Zaključno, rezultati istraživanja pokazali su postojanje složene i spolno specifične povezanosti polimorfizama COMT i MAO-B i anhedonije te negativnih simptoma u shizofreniji, te ističu povezanost između slabog istraženog polimorfizma MAO-B rs6651806 i određenih skupina simptoma shizofrenije.The aim of the study was to investigate the association of catechol-O-methyl transferase (COMT) rs4680 and rs4818, and monoamine oxidase type B (MAO-B) rs1799836 and rs6651806 polymorphisms, with anhedonia and other negative symptoms in patients with schizophrenia. This cross-sectional study included 302 patients (58.9% males, median age 42). Main findings: Female carriers of the COMT rs4680 and rs4818 G-allele (related to higher COMT activity) had more severe negative symptoms, compared to females without G allele. COMT rs4818-rs4680 G-G haplotype in females was associated with more severe negative symptoms. Male MAO-B rs1799836 A-allele carriers had more severe alogia than G-allele carriers. Females with physical and social anhedonia had higher frequency of MAO-B rs6651806 A-allele, than females without such anhedonia subtypes, but female A-allele carriers had less severe depressive symptoms than C-allele carriers. Male carriers of MAO-B rs6651806 A-allele had more prominent negative symptoms than C-allele carriers, while MAO-B rs1799836-rs6651806 G-C haplotype in males was associated with less severe negative symptoms. Those findings implicate complex, but sex-specific associations between COMT and MAO-B polymorphisms with anhedonia and negative symptoms in schizophrenia, and highlight the relationship between poorly known MAO-B rs6651806 polymorphism and several symptom domains in schizophrenia

The association between catechol-O-methyl transferase and monoamine oxidase type B gene polymorphisms and anhedonia in patients with schizophrenia

Cilj ovog istraživanja je bio istražiti povezanost polimorfizama za katehol-O-metil transferazu (COMT) rs4680 i rs4818 i monoaminooksidazu tipa B (MAO-B) rs1799836 i rs6651806 s anhedonijom i drugim negativnim simptomima kod bolesnika sa shizofrenijom. Presječno istraživanje obuhvatilo je 302 bolesnika (58.9% muških, medijan godina 42). Glavni rezultati: nositeljice G alela (povezanog s većom aktivnošću COMT-a) za COMT rs4680 i rs4818 imale su izraženije negativne simptome u odnosu na ispitanice bez G alela. COMT rs4818-rs4680 haplotip G-G je kod ispitanica bio povezan s izraženijim negativnim simptomima. Muški nositelji MAO-B rs1799836 A alela imali su izraženiju alogiju prema nositeljima G alela. Ispitanice s fizičkom i socijalnom anhedonijom imale su veću frekvenciju pojavljivanja MAO-B rs6651806 A alela od ispitanica bez navedenih podtipova anhedonije, ali su nositeljice A alela imale manje depresivnih simptoma od nositeljica C alela. Muški nositelji MAO-B rs6651806 A alela imali su izraženije negativne simptome nego nositelji C alela, dok je MAO-B rs1799836-rs6651806 haplotip G-C kod muških ispitanika bio povezan s manje izraženim negativnim simptomima. Zaključno, rezultati istraživanja pokazali su postojanje složene i spolno specifične povezanosti polimorfizama COMT i MAO-B i anhedonije te negativnih simptoma u shizofreniji, te ističu povezanost između slabog istraženog polimorfizma MAO-B rs6651806 i određenih skupina simptoma shizofrenije.The aim of the study was to investigate the association of catechol-O-methyl transferase (COMT) rs4680 and rs4818, and monoamine oxidase type B (MAO-B) rs1799836 and rs6651806 polymorphisms, with anhedonia and other negative symptoms in patients with schizophrenia. This cross-sectional study included 302 patients (58.9% males, median age 42). Main findings: Female carriers of the COMT rs4680 and rs4818 G-allele (related to higher COMT activity) had more severe negative symptoms, compared to females without G allele. COMT rs4818-rs4680 G-G haplotype in females was associated with more severe negative symptoms. Male MAO-B rs1799836 A-allele carriers had more severe alogia than G-allele carriers. Females with physical and social anhedonia had higher frequency of MAO-B rs6651806 A-allele, than females without such anhedonia subtypes, but female A-allele carriers had less severe depressive symptoms than C-allele carriers. Male carriers of MAO-B rs6651806 A-allele had more prominent negative symptoms than C-allele carriers, while MAO-B rs1799836-rs6651806 G-C haplotype in males was associated with less severe negative symptoms. Those findings implicate complex, but sex-specific associations between COMT and MAO-B polymorphisms with anhedonia and negative symptoms in schizophrenia, and highlight the relationship between poorly known MAO-B rs6651806 polymorphism and several symptom domains in schizophrenia

The association between catechol-O-methyl transferase and monoamine oxidase type B gene polymorphisms and anhedonia in patients with schizophrenia

Cilj ovog istraživanja je bio istražiti povezanost polimorfizama za katehol-O-metil transferazu (COMT) rs4680 i rs4818 i monoaminooksidazu tipa B (MAO-B) rs1799836 i rs6651806 s anhedonijom i drugim negativnim simptomima kod bolesnika sa shizofrenijom. Presječno istraživanje obuhvatilo je 302 bolesnika (58.9% muških, medijan godina 42). Glavni rezultati: nositeljice G alela (povezanog s većom aktivnošću COMT-a) za COMT rs4680 i rs4818 imale su izraženije negativne simptome u odnosu na ispitanice bez G alela. COMT rs4818-rs4680 haplotip G-G je kod ispitanica bio povezan s izraženijim negativnim simptomima. Muški nositelji MAO-B rs1799836 A alela imali su izraženiju alogiju prema nositeljima G alela. Ispitanice s fizičkom i socijalnom anhedonijom imale su veću frekvenciju pojavljivanja MAO-B rs6651806 A alela od ispitanica bez navedenih podtipova anhedonije, ali su nositeljice A alela imale manje depresivnih simptoma od nositeljica C alela. Muški nositelji MAO-B rs6651806 A alela imali su izraženije negativne simptome nego nositelji C alela, dok je MAO-B rs1799836-rs6651806 haplotip G-C kod muških ispitanika bio povezan s manje izraženim negativnim simptomima. Zaključno, rezultati istraživanja pokazali su postojanje složene i spolno specifične povezanosti polimorfizama COMT i MAO-B i anhedonije te negativnih simptoma u shizofreniji, te ističu povezanost između slabog istraženog polimorfizma MAO-B rs6651806 i određenih skupina simptoma shizofrenije.The aim of the study was to investigate the association of catechol-O-methyl transferase (COMT) rs4680 and rs4818, and monoamine oxidase type B (MAO-B) rs1799836 and rs6651806 polymorphisms, with anhedonia and other negative symptoms in patients with schizophrenia. This cross-sectional study included 302 patients (58.9% males, median age 42). Main findings: Female carriers of the COMT rs4680 and rs4818 G-allele (related to higher COMT activity) had more severe negative symptoms, compared to females without G allele. COMT rs4818-rs4680 G-G haplotype in females was associated with more severe negative symptoms. Male MAO-B rs1799836 A-allele carriers had more severe alogia than G-allele carriers. Females with physical and social anhedonia had higher frequency of MAO-B rs6651806 A-allele, than females without such anhedonia subtypes, but female A-allele carriers had less severe depressive symptoms than C-allele carriers. Male carriers of MAO-B rs6651806 A-allele had more prominent negative symptoms than C-allele carriers, while MAO-B rs1799836-rs6651806 G-C haplotype in males was associated with less severe negative symptoms. Those findings implicate complex, but sex-specific associations between COMT and MAO-B polymorphisms with anhedonia and negative symptoms in schizophrenia, and highlight the relationship between poorly known MAO-B rs6651806 polymorphism and several symptom domains in schizophrenia

The Associations of Neutrophil–Lymphocyte, Platelet–Lymphocyte, Monocyte–Lymphocyte Ratios and Immune-Inflammation Index with Negative Symptoms in Patients with Schizophrenia

Neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR) and systemic immune-inflammation index (SII index) are increasingly used as indicators of inflammation in different conditions, including schizophrenia. However, their relationship with negative symptoms, including anhedonia, is largely unknown. Included were 200 patients with schizophrenia and 134 healthy controls (HC), assessed for physical anhedonia (PA), using the Revised Physical Anhedonia Scale (RPAS), and social anhedonia (SA) by the Revised Social Anhedonia Scale (RSAS). Patients were rated by the Positive and Negative Syndrome Scale (PANSS), the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS). Most of the negative symptoms were in a weak to moderate positive correlations with blood cell inflammatory ratios, namely, between NLR and MLR with PANSS negative scale, CAINS, and BNSS, and in male patients, between PLR and PANSS negative scale and CAINS. Fewer correlations were detected in females, but also in a positive direction. An exception was SA, given the negative correlation between its severity and the SII index in females, and its presence and higher PLR in males. While different negative symptoms were associated with subclinical inflammation, the relationship between SA and lower inflammatory markers deserves further exploration

The Associations of Neutrophil–Lymphocyte, Platelet–Lymphocyte, Monocyte–Lymphocyte Ratios and Immune-Inflammation Index with Negative Symptoms in Patients with Schizophrenia

Neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR) and systemic immune-inflammation index (SII index) are increasingly used as indicators of inflammation in different conditions, including schizophrenia. However, their relationship with negative symptoms, including anhedonia, is largely unknown. Included were 200 patients with schizophrenia and 134 healthy controls (HC), assessed for physical anhedonia (PA), using the Revised Physical Anhedonia Scale (RPAS), and social anhedonia (SA) by the Revised Social Anhedonia Scale (RSAS). Patients were rated by the Positive and Negative Syndrome Scale (PANSS), the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS). Most of the negative symptoms were in a weak to moderate positive correlations with blood cell inflammatory ratios, namely, between NLR and MLR with PANSS negative scale, CAINS, and BNSS, and in male patients, between PLR and PANSS negative scale and CAINS. Fewer correlations were detected in females, but also in a positive direction. An exception was SA, given the negative correlation between its severity and the SII index in females, and its presence and higher PLR in males. While different negative symptoms were associated with subclinical inflammation, the relationship between SA and lower inflammatory markers deserves further exploration