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

Allergy – A Modern Epidemic

Učestalost alergijskih bolesti u svijetu u dramatičnom je porastu posljednjih 20-30 godina. Ovaj porast osobito je izražen u dječjoj dobi. Procjenjuje se da 30-40% osoba u svijetu boluje od jedne ili više alergijskih bolesti, stotine milijuna osoba pate zbog alergijskog rinitisa, a oko 300 milijuna ima astmu. Prevalencija je astme u odraslih i djece između 1-18% s najvećom prevalencijom u zemljama engleskoga govornog područja. Hrvatska s učestalosti od 8% dječje astme spada u zemlje s umjerenim pobolom. U pokušaju da se objasne epidemiološki trendovi u astmi nastale su teorije koje su definirale nove rizične faktore za razvoj i porast astme i alergija. Higijenska hipoteza tumači da izostala, odnosno smanjena izloženost nekim infekcijama rano u djetinjstvu može uzrokovati porast rizika od razvoja alergije. Prema epigenskoj teoriji porast alergijskih bolesti događa se zbog okolišne ekspozicije intrauterino ili rano u životu (duhanu, prometnom onečišćenju, endotoksinima i folatima iz prehrane), što posreduje adaptaciju gena na okoliš.The global incidence of allergic diseases has been on a dramatic increase over the last 20-30 years. This increase is especially pronounced during childhood. It is estimated that 30-40% of people worldwide suffer from one or more allergic diseases, hundreds of millions from allergic rhinitis, and around 300 million have asthma. The prevalence of asthma in adults and children is between 1 and 18% and it is the highest in the English-speaking world. With an 8% incidence of childhood asthma, Croatia belongs to countries with a moderate frequency. In an attempt to explain the epidemiological trends in asthma, theories that defi ne new risk factors for the development and rise of asthma and allergies have emerged. The hygiene hypothesis holds that absent or reduced exposure to certain infections in early childhood can lead to an increased risk of developing allergies. According to epigenetic theory, the increase in allergic diseases is due to environmental exposure (tobacco, traffi c pollution, endotoxins and folates from the diet), either during intrauterine development or early in life, which mediates in gene adaptation to the environment

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

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

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

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

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

Mediastinal smooth muscle tumor of uncertain malignant potential: case report and literature review

Cilj: glatkomišićni tumori su lejomiomi i lejomiosarkomi. Postoji rijetka skupina, u kojoj se biološki potencijal tumora ne može utvrditi; to su glatkomišićni tumori nepoznatog malignog potencijala. Cilj je prikazati pacijenta s takvim tumorom, koji je nastao iz glatkog mišićnog tkiva medijastinuma. Prikaz slučaja: 48-godišnji muškarac, subfebrilan, bolovi u grudnom košu sa širenjem u leđa. Kompjutorizirana tomografija toraksa pokazala je oštro ograničenu cističnu tvorbu stražnjeg medijastinuma. Ezofagogastroduodenoskopija je otkrila u srednjoj trećini jednjaka pritisak izvana, a rendgen pasaža jednjaka jednjak lučno potisnut izvana prema desno i ventralno. Bronhoskopijom je utvrđeno da je membranozni dio lijevog glavnog bronha blago ekstramuralno komprimiran. Učinjen je kirurški zahvat, torakotomija lijevo i potpuno odstranjenje tumora medijastinuma. Patohistološki nalaz pokazao je područje nekroze, tumorsko tkivo građeno od vretenastih stanica, koje pokazuju blagu polimorfiju. Imunohistokemijska analiza tumora bila je pozitivna na glatkomišićni aktin (SMA) i dezmin, a negativna na S100 i CD34, što potvrđuje podrijetlo tumora iz glatkomišićnih stanica. Dodatna imunohistokemijska analiza utvrdila je da proliferacijski biljeg Ki-67 iznosi 5,9 %, a p16 je pozitivan u više od 50 % tumorskih stanica. Zaključni patološki nalaz je glatkomišićni tumor nepoznatog malignog potencijala. Pacijent je praćen 48 mjeseci nakon operacije, bez recidiva tumora ili znakova metastaza. Zaključak: Patohistološka dijagnoza može biti otežana, općenito, ali posebno u rijetkim novotvorevinama. Prikazani slučaj pokazuje da ponekad nije moguće utvrditi radi li se o benignom ili malignom glatkomišićnom tumoru. Tada se postavlja dijagnoza glatkomišićnog tumora nepoznatog malignog potencijala, ovdje smještenog u medijastinumu. Nakon kirurškog odstranjenja neoplazme potrebno je redovito pratiti pacijenta, kako bi se utvrdio recidiv bolesti i provelo dodatno liječenje.Aim: Smooth muscle tumors are divided into leiomyomas and leiomyosarcomas. The aim is to present a patient with a rare tumor called smooth muscle tumor of uncertain malignant potential. Case report: The reported patient was a 48-year-old male, subfebrile, with chest pain. Chest computed tomography showed a sharply limited cystic formation of the posterior mediastinum. Esophagogastroduodenoscopy revealed outside compression in the middle third of the esophagus, and X-ray of the esophageal passage showed that the esophagus was pressed from the outside to the right and ventral. Bronchoscopy determined that the membranous part of the left main bronchus was slightly extramurally compressed. A left thoracotomy and an extirpation of the mediastinal tumor were performed. In pathohistology area of necrosis and tumor tissue composed of spindle cells were identified, which showed mild polymorphia. Immunohistochemical findings included positive smooth muscle actin (SMA) and desmin markers, negative S100 and CD34 markers, Ki-67 was 5.9%, and p16 was positive in more than 50% of tumor cells. The patient was followed up for 48 months, with no signs of tumor recurrence. Conclusion: Pathohistological diagnosis can be difficult, particularly in cases of rare neoplasms. The reported case shows that sometimes it is not possible to determine if smooth muscle tumor is benign or malignant. Therefore, the diagnosis of smooth muscle tumor of uncertain malignant potential is established, in our case the tumor was located in the mediastinum. After surgical removal of the neoplasm, the patient should be followed up regularly in order to detect disease recurrence and to give additional treatment