Have we Made Progress in the Treatment of Asthma?

Astma je složen respiratorni poremećaj koji karakterizira izražena heterogenost u pokretačima bolesti i individualnim reakcijama na terapiju. Identificirano je nekoliko fenotipa astme, svaki definiran jedinstvenom interakcijom između genetskih i okolišnih čimbenika, uključujući upalne, kliničke karakteristike povezane s pokretačem bolesti. Različiti endotipovi astme, temeljeni na upalnom odgovoru, nazvani T2-high (T2) i T2-low astmom, doveli su do razvoja bioloških tretmana usmjerenih na različite upalne medijatore. U T2 astmi vodeće obilježje je povišena razina eozinofila u krvi i sputum, ali i drugih markera kao što su IgE u serumu, frakcija izdahnutoga dušičnog oksida i periostina. U kliničkoj praksi anti-IgE biološka terapija omalizumabom značajno je smanjila egzacerbacije astme. Dva različita humanizirana monoklonska antitijela anti-IL-5 (mepolizumab i reslizumab) te benralizumab (kao anti-IL-5Rα), značajno su smanjila rizik od egzacerbacija i poboljšala plućnu funkciju u usporedbi s placebom. Napredak u razumijevanju mehanizama T2-high (T2) i T2-low astme i biomarkera može pomoći u unapređivanju mogućnosti liječenja za mnoge pacijente s astmom koji ostaju nekontrolirani unatoč korištenju postojeće terapije.Asthma is a complex respiratory disorder characterized by marked heterogeneity in individual patient disease triggers and response to therapy. Several asthma phenotypes have been identified, each defined by a unique interaction between genetic and environmental factors, including inflammatory, clinical and trigger-related characteristics. Different endotypes of asthma, based on the inflammatory pattern, may be regarded as T2-high (T2) or T2-low asthma, have led to the development of biological treatments targeting different inflammatory mediators. The hallmarks of T2 asthma are increased levels of blood and sputum eosinophils and other markers such as serum IgE, fractional exhaled nitric oxide and periostin. In clinical practice, omalizumab, an anti-IgE antibody biologic treatment, significantly reduced asthma exacerbations. Two different anti-IL-5 humanized monoclonal antibodies, mepolizumab, reslizumab and benralizumab as anti-IL-5Rα, significantly reduced the risk of exacerbations and improved lung function compared to placebo. Improving the understanding of T2-high and T2-low mechanisms and biomarkers may help to advance treatment options for many patients with asthma who remain uncontrolled despite the use of current standard of care

Community-Acquired Pneumonias

Izvanbolnička je pneumonija česta, potencijalno teška bolest jer je uzrok znatnog morbiditeta i mortaliteta u odraslih. Godišnja incidencija pneumonija u općoj populaciji iznosi između 5 i 11 na 1000 osoba. Najčešći uzročnici prema publiciranim epidemiološkim studijama jesu Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Haemophilus influenzae, enterokoki i Legionella pneumophila. Za dijagnozu pneumonije potreban je novonastali infiltrat na rendgenskoj snimci prsnih organa uz tipičnu kliničku sliku. Mikrobiološka se evaluacija za ambulantno liječene bolesnike ne preporučuje. Empirijsko antibiotsko liječenje u tom slučaju gotovo je uvijek uspješno. U hospitaliziranih bolesnika, posebno kod teške pneumonije, mikrobiološka identifikacija uzročnika može pozitivno utjecati na terapijski pristup i ishod liječenja, stoga je indicirano učiniti hemokulturu, urinarni test na antigene legionele i pneumokoka te kulturu sputuma. Preporučuje se uzimanje dviju hemokultura, osobito u pacijenata sa specifičnim indikacijama kao što je liječenje u jedinici intenzivnog liječenja. Hemokulture uzete prije započetog antibiotskog liječenja pozitivne su u 7 do 16% slučajeva. Određivanje urinarnih antigena preporučuje se samo kod teške pneumonije. Unatoč mikrobiološkim testovima većina hospitaliziranih pacijenata ostaje bez etiološke dijagnoze i tretiraju se empirijski. Dva biomarkera, prokalcitonin (PCT) i C-reaktivni protein (CRP) mogu pomoći u razlučivanju bakterijskih od virusnih infekcija i u odluci o uvođenju ili obustavljanju antibiotika, a trajno visoki PCT govori u prilog lošoj prognozi. Nakon potvrde dijagnoze pneumonije potrebno je procijeniti težinu bolesti te donijeti odluku o potrebi za hospitalizacijom ili ambulantnim liječenjem. U tu se svrhu rabi više bodovnih skorova od kojih najčešće Pneumonia Severity Index (PSI) i CURB-65.Community-acquired pneumonia (CAP) is a common and potentially serious disease as it is a cause of significant morbidity and mortality in adults. The annual incidence of pneumonia in the general population in adults is 5 to 11 cases per 1000 people. According to the published epidemiological studies the most common causes of CAP in Europe, Latin America and the US are Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Haemophilus influenzae, Enterococci and Legionella pneumophila. A new infiltrate on chest X-ray with typical clinical symptoms and signs is required for the diagnosis of pneumonia. Microbiological evaluation is not recommended for outpatient treatment. Empirical antibiotic therapy almost always reveals successful clinical outcomes. In hospitalized patients, especially with severe pneumonia, microbiological identification of bacteria can positively affect the therapeutic approach and the outcome of treatment. Therefore, blood cultures, urinary antigen tests for Legionella and pneumococus and sputum culture are indicated. It is recommended to take two blood cultures, especially in patients with specific indications, such as the Intensive Care Unit treatment. Blood cultures taken before starting the antibiotic treatment are positive in 7% to 16% of cases. Legionella and S. pneumoniae urinary antigen tests are recommended only in severe pneumonias. Despite microbiological tests, most hospitalized patients with CAP are without etiological diagnosis and are treated empirically. Two biomarkers, procalcitonin (PCT) and C-reactive protein (CRP) can help distinguish bacterial from viral infections. They can support a clinical decision on the initiation or discontinuation of antibiotic therapy. Persistently high PCT values suggest a poor prognosis. After confirming the diagnosis of pneumonia, it’s necessary to assess the severity of the disease and make a decision about either hospitalization or outpatient treatment. For this purpose multiple scoring systems, such as Pneumonia Severity Index (PSI) and CURB-65, are used in everyday practice

Advancement in the Mesothelioma Diagnostics in Primorsko-Goranska County of Croatia

The purpose is to find out whether the diagnostics and registration of patients with mesothelioma in the Littoral – Mountainous County of Croatia corresponds to the world trends. Further, the intention was to show the incidence of the disease and suggest the measures of prevention in the county of 400.000 inhabitants and its center Rijeka with 140.000 people. To that purpose 43 patients with mesothelioma were monitored in two groups: 25 shipyard workers, mean age 66, and 18 workers in other occupations, mean age 62. Statistically the group did not differ significantly in the incidence of placks, left or right side effusion. The pleural puncture showed the significance (p<0.05) for incidence of rouse cells. In 20 patients out of 43 mesothelioma was confirmed by taking the material for pathohistology by means of VATS (video assisted thoracoscopy) and in 14 patients by TTB (transthoracic biopsy) with CT control. Spirometric values showed moderate restrictive difficulties. Although a considerable improvement in diagnosing mesothelioma has been achieved in the last five years an improved prevention activity by occupational medicine is required not only by periodic checkups of the exposed persons and examinations for retired workers with respiratory difficulties, but also by stimulating work case histories

Pericardial effusion as the first manifestation of occupational tuberculosis in a health care worker

Tuberkuloza (TBC) zarazna je bolest, stoga je prijeko potrebno zaštititi ne samo bolesnike nego i osoblje koje dolazi u kontakt s njima, u prvom redu medicinske sestre i liječnike. Nakon kontakta s bolesnicima oboljelima od TBC-a (u kulturama pozitivne) 43-godišnji imunokompetentni medicinski tehničar, zaposlen u psihijatrijskoj bolnici, obolio je od profesionalnog diseminiranog TBC-a. Prva manifestacija bolesti bio je eksudativni perikarditis s dokazanim Mycobacterium tuberculosis (MT), dva mjeseca nakon perikardiocenteze i evakuacije 1200 mL perikardijalnog izljeva. Histološki nalaz limfnih čvorova na više lokalizacija pokazivao je granulomatoznu upalu s nekrozom. Liječenje antituberkuloticima bilo je praćeno komplikacijama. Došlo je do prolaznog, kratkotrajnog, medikamentozno toksičnog hepatitisa, dugotrajnog febriliteta, nespecifičnog ljevostranog pleuralnog izljeva i mononeuritisa desnog peronealnog živca. Liječenje je trajalo 14 mjeseci. Kao trajna posljedica razvio se fibrotoraks, koji je doveo do restriktivnih smetnji ventilacije i smanjene difuzije alveolarno-kapilarne membrane. Ovaj slučaj upozorava na potrebu poboljšanja zaštite zdravstvenih radnika koji su u kontaktu s oboljelima od tuberkuloze, kao i korisnost tuberkulinskog kožnog testa i QuantiFERON-TB testa, koji mogu rano otkriti latentni TBC.Tuberculosis (TB) is an infectious disease and, apart from protecting patients, attention must be given to protecting the persons who come in contact with them, especially nurses and medical practitioners. A 43-year-old immunocompetent male nurse developed occupationally disseminated TB after contact with patients affected by active TB (culture positive) while working in a psychiatric hospital. The first manifestation of the disease was exudative pericarditis with Mycobacterium tuberculosis (MT) confirmed two months after pericardiocentesis and evacuation of 1200 mL of pericardial effusion. Many lymph nodes showed histologic findings of granulomatous inflammation with necrosis. Treatment with antituberculosis drugs caused complications, including transient short-term medication-induced toxic hepatitis, prolonged fever, left pleural nonspecific effusion, and mononeuritis of the right peroneus nerve. The treatment lasted 14 months and led to permanent consequences, including fibrothorax with restrictive ventilation disorders and reduced diffusion of the alveolar-capillary membrane. This case highlights the need to improve the protection of health care workers who are in contact with TB patients, as well as the usefulness of the tuberculin skin test and QuantiFERON-TB test, which can be used to identify early latent TB

Diagnostic value of tumour markers in pleural effusions

Introduction: We investigated whether tumour markers carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA125), and cytokeratin 19 fragment (CYFRA 21-1) in pleural effusions and serum can be used to distinguish pleural effusion aetiology. Materials and methods: During the first thoracentesis, we measured pleural fluid and serum tumour marker concentrations and calculated the pleural fluid/serum ratio for patients diagnosed with pleural effusion, using electrochemiluminescence immunoassays. Receiver operating characteristic (ROC) analysis was carried out and the Hanley and McNeil method was used to test the significance of the difference between the areas under ROC curves (AUCs). In order to detect which tumour marker best discriminates between malignant and non-malignant pleural effusions and to establish the predictive value of those markers, discriminant function analysis (DFA) and logistic regression analysis were utilized. Results: Serum tumour markers CYFRA 21-1 and NSE as well as pleural NSE were good predictors of pleural effusion malignancy and their combined model was found statistically significant (Chi-square = 28.415, P < 0.001). Respective ROC analysis showed significant discrimination value of the combination of these three markers (AUC = 0.79). Conclusions: Serum markers showed superiority to pleural fluid markers in determining pleural fluid aetiology. Serum CYFRA 21-1 and NSE concentrations as well as pleural fluid NSE values had the highest clinical value in differentiating between malignant and non-malignant pleural effusions. The combination of these three markers produced a significant model to resolve pleural effusion aetiology

The pathogenesis of cognitive decline after cardiac surgery: A Narrative Review

Unatoč stalnom opadanju poslijeoperacijskih komplikacija nakon kardiokirurškog zahvata razvojem suvremene medicine, učestalost poslijeoperacijskih kognitivnih poremećaja (POKP) je nepromijenjena, postavši tako najčešćom komplikacijom. Razlog tome je u još uvijek nerazjašnjenoj patogenezi POKP-a, ali i u nepostojanju opće prihvaćene definicije POKP-a među istraživačima. POKP-i imaju značajnu reperkusiju na bolesnikovo zdravlje, ali i na širu zajednicu zbog znatnih troškova liječenja i rehabilitacije bolesnika, smanjenja radne sposobnosti bolesnika i potrebe za njegovim prijevremenim umirovljenjem. Cilj ovog narativnog preglednog rada je na temelju pretraživanja dostupne literature čitateljima dati uvid u najnovija saznanja o POKP-ima nakon kardiokirurškog zahvata, s osobitim osvrtom na patogenezu POKP-a. Stoga su autori ovog rada pretraživali baze podataka Web of Science (All Databases) i Scopus u svrhu prikupljanja najnovijih spoznaja o ovoj iznimno važnoj poslijeoperacijskoj komplikaciji. Utvrdili smo kako upalni odgovor na kardiokirurški zahvat vjerojatno ima ključnu ulogu u međusobno preklapajućim mehanizmima koji su u podlozi nastanka POKP-a, te kako metodološka nedosljednost u definiranju POKP-a među istraživačima uvelike otežava istraživanje ove komplikacije.Although the rates of postoperative complications following cardiac surgery are constantly declining because of improvements in medical techniques, the incidence of postoperative cognitive decline (POCD) is still unchanged and has become the most common postoperative complication. The pathogenesis of POCD is still poorly understood, and universally accepted POCD definition has not yet been established. POCD occurrence has a significant repercussion on patient health, but also on the community, given that POCD is associated with reduced work ability, early withdrawal from the workforce and significantly increased use of healthcare resources. The purpose of this narrative review is to summarize and evaluate the latest findings based on the search of available literature, with special attention paid to the pathogenesis of POCD. Therefore, we searched the Web of Science (All Databases) and Scopus databases for the best evidence about this significant postoperative complication. We revealed that the inflammatory response to cardiac surgery plays a key role in the mutually overlapping processes included in POCD development, and that the methodological inconsistency in defining POCD among researchers makes a significant obstacle in the investigation of this issue

Medijastinalni glatkomišićni tumor nepoznatog malignog potencijala: prikaz slučaja i pregled literature - ispravak

U članku „Medijastinalni glatkomišićni tumor nepoznatog malignog potencijala: prikaz slučaja i pregled literature”, čiji su autori Veljko Flego, Darian Volarić, Koviljka Matušan Ilijaš, Ljiljana Bulat-Kardum, tiskanom u časopisu Medicina Fluminensis 2019;55:89-94, objavljena je pogrešna slika 4. U nastavku objavljujemo ispravnu sliku 4

Medijastinalni glatkomišićni tumor nepoznatog malignog potencijala: prikaz slučaja i pregled literature - ispravak

U članku „Medijastinalni glatkomišićni tumor nepoznatog malignog potencijala: prikaz slučaja i pregled literature”, čiji su autori Veljko Flego, Darian Volarić, Koviljka Matušan Ilijaš, Ljiljana Bulat-Kardum, tiskanom u časopisu Medicina Fluminensis 2019;55:89-94, objavljena je pogrešna slika 4. U nastavku objavljujemo ispravnu sliku 4