IMMUNOSENESCENCE, INFLAMMAGING AND RESILIENCE: AN EVOLUTIONARY PERSPECTIVE OF ADAPTATION IN THE LIGHT OF COVID-19 PANDEMIC

The evolution of immunology enabled the study of role of innate and adaptive immunity in systems biology network of immunosenescence and inflammaging. Due to global reduction in birth rates and reduced mortality, in year 2025 there will be about 1.2 billion of people over age of sixty, worldwide. The notion that the real age is not chronological, but the biological one led to the concept of "bioage", defining the biologic reactivity and resilience, including the immune competence of an individual. A competent immune network, systemic and mucosal is intrinsic to resilience and homeostasis of the human holobiont as the unit of evolution. In elderly, the immunosenescence could be associated with higher levels of proinflammatory mediators (such as IL-6), frialty and mortality. Proi-inflammatory state in elderly is denoted as inflammaging, characterized with low-grade (sterile) inflammation, as a physiologic response to life-long antigenic stimuli. When under control, inflammaging could be regarded as an efficient defense mechanism, oposed and regulated by anti-inflammatory pathways and molecules. Immunosensecence. The emerging concepts of "individual immunobiography" and "trained immunity" speak in favour that the immunological experience during the life would shape the ability of each individual to respond to various stimuli, strongly influencing the elements of innate and adaptive immunity, including macrophages and innate lymphoid cells. Older age is one of the main risk factors for the severe clinical picture and adverse outcome of COVID-19 infection, due to immunosenscence and chronic low-grade inflammation (inflammaging), both characterizing the immune reactioin in elderly. The senescent immune system, along with the advanc ed process of inflammaging is prone to react with uncontrolled activation of innate immune response that leads to cytokine release syndrome, tissue damage and adverse outcome of infection. Further research is aimed to nutritional and pharmacologic (immunomodulatory) interventions to influence the process of bioaging and immunosenscence, and to modulate the reaction of elderly to infection, including the COVID-19

WEATHER CONDITIONS AND THE SINO-BRONCHIAL SYNDROME IN CHILDREN IN ZAGREB

This paper deals with the dependence of the chronic sino-bronchial syndrome and respiratory tract acute diseases in children and adults (age 0-19) living in Zagreb (a town with developed industry and heavy road traffic) on meteorological elements acting on man\u27s thermal sensation. This study is based on the bioclimatic index i/H (air enthalpy and cooling power rate) and the relevant bioclimatic classification and on those meteorological elements that are included in the bioclimatic index calculation (air temperature, relative humidity, wind speed and barometric pressure). A correlation analysis method has been applied on both daily data and 3-, 5- and 7-day moving average values. All analyses have been done separately for the cold and warm part of the year. The results for the cold and warm parts of the year differ. Chronic patients react earlier to meteorological strcss than acute ones. In the cold part of the year the warm periods are critical while in the warm part of the year the cold ones are critical. Along with the air tenrperature relative humidity is also significant. For acute patients periods with high relative humidity are particularly unfavourable, both in the cold and warm periods of the year, if they last at least three days. SO2 and smoke concentration in the studied period (1988-90) was within the allowed limits and their correlation with sino-bronchial diseases, chronic or acute, was not significant

Evaluacija imunokromatografskog testa za otkrivanje galaktomanana Aspergillus spp. u uzorcima seruma i bronhoalveolarnih lavata – preliminarni rezultati

Background: Detection of biomarkers, such as galactomannan (GM), has proven to be of great significance in early recognition of invasive aspergillosis (IA). The aim of our study was to evaluate the lateral flow assay (LFA) for the detection of GM on serum and bronchoalveolar lavage (BAL) samples previously proven positive by enzyme-linked immunosorbent assay (ELISA). Methods: The study was performed on serum and BAL samples obtained from patients with suspected IA in the period from February 2019 to January 2020, which were previously GM positive by ELISA (Platelia Aspergillus Ag, Biorad, Hercules, USA). Samples were then tested by LFA (Aspergillus Galactomannan LFA, IMMY, Oklahoma, USA) with test line intensity visually read as 1+, 2+, 3+, or 4+. Results: A total of 45 GM ELISA positive serum and/or BAL samples were obtained from 41 patients; 25 (55,6 %) were BAL and 20 (44,4 %) serum samples. LFA showed a positive result in 39 out of 45 (86,7%) GM ELISA positive samples; 22/25 (88.0 %) BAL samples and 17/20 (85.0 %) serum samples tested positive. In BAL samples, low intensity test line of 1+ was significantly more frequent in GM ELISA positive samples with optical density index (ODI) 4.0) had low intensity line of 1+ when tested with LFA. Conclusions: Results obtained by LFA are comparable to GM ELISA. Since low intensity lines were found in serum samples with high ODI, this potentially makes BAL a superior sample for LFA, at least when visual and not automated reading is done.Uvod: Određivanje galaktomanana (GM) igra značajnu ulogu u ranom otkrivanju invazivne aspergiloze (IA). Cilj je ovog istraživanja bila evaluacija imunokromatografskog testa (LFA) za određivanje GM u uzorcima seruma i bronhoalveolarnih lavata (BAL) s pozitivnim rezultatom koji su utvrđeni prethodno napravljenom ELISA metodom. Metode: Istraživanje je napravljeno na uzorcima seruma i BAL-a pacijenata sa sumnjom na IA prikupljenim u razdoblju od veljače 2019. do siječnja 2020. godine. Uzorci s pozitivnim rezultatom utvrđenim ELISA metodom (Platelia Aspergillus Ag, Biorad, Hercules, USA) testirani su s LFA (Aspergillus Galactomannan LFA, IMMY, Norman, Oklahoma, USA) s vizualnim očitavanjem testne linije u rasponu 1+, 2+, 3+, ili 4+. Rezultati: Od 41 bolesnika dobiveno je 45 pozitivnih uzoraka seruma i/ili BAL-a testiranih GM ELISA metodom; 25 (55,6 %) uzoraka BAL-a i 20 (44,4 %) uzoraka seruma. LFA je pokazao pozitivni rezultat kod 39 od 45 (86,7%) uzoraka pozitivnih GM ELISA metodom; 22/25 (88.0 %) uzoraka BAL-a i 17/20 (85.0 %) uzoraka seruma. Kod uzoraka BAL-a, testna linija slabog intenziteta 1+ bila je značajno češća kod pozitivnih uzoraka testiranih GM ELISA metodom s ODI 4.0) imala su pri testiranju s LFA testnu liniju slabog intenziteta 1+. Zaključak: Rezultati dobiveni s LFA usporedivi su s GM ELISA metodom. S obzirom da su testne linije niskog intenziteta utvrđene u uzorcima seruma s visokim ODI, uzorci BAL-a su potencijalno pogodniji uzorci za LFA, barem kad se radi o vizualnom, a ne automatiziranom očitavanju testa

1,3-Β-D-glucan in invasive fungal infection diagnostics – first Croatian experience

Invazivne gljivne infekcije (IGI) važan su problem suvremene medicine. Razlog tomu jesu rastući broj imunokompromitiranih bolesnika te visoke stope morbiditeta i mortaliteta zbog ovih infekcija. Pravodobno postavljena dijagnoza IGI-ja od presudne je važnosti jer odgađanje primjene antifungalne terapije utječe na ishod liječenja bolesnika. Kultivacija kao konvencionalna dijagnostička metoda ima nisku osjetljivost, dugo traje i nalaže uzimanje invazivnog uzorka. Zbog toga se posljednjih dvadesetak godina radi ranije i osjetljivije dijagnostike istražuju i primjenjuju fungalni biomarkeri. 1,3-β-D-glukan (BDG) fungalni je biomarker odrediv u serumu bolesnika kojim se može dokazati prisutnost ovih gljivnih patogena: Candida spp., Aspergillus spp., Acremonium, Coccidioides immitis, Fusarium spp., Histoplasma capsulatum, Trichosporon spp., Sporothrix schenckii, Saccharomyces cerevisiae i Pneumocystis jirovecii. Zbog niske razine odnosno nepostojanja BDG-a u staničnoj stijenci ovim se testom ne mogu dokazati vrste roda Cryptococcus spp. i reda Mucorales. Visoka negativna prediktivna vrijednost BDG-a u slučaju negativne vrijednosti može se iskoristiti za donošenje odluke o prekidu antifungalne terapije i biti dio strategije upravljanja primjenom antifungalnih lijekova u jedinicama intenzivnog liječenja. Kod hematoloških bolesnika BDG se može primjenjivati radi probira i u sklopu dijagnostičke obrade pri sumnji na IGI. Pouzdanost testa kod pojedinog bolesnika veća je u slučaju dvaju ili više uzastopno pozitivnih rezultata. Utjecaj antifungalne profilakse na rezultate testa BDG-a još je nejasan. Kinetiku BDG-a za sada je teško korelirati s kliničkim ishodom. Pedijatrijskim bolesnicima još nisu definirane granične vrijednosti za interpretaciju vrijednosti BDG-a iako su o tome objavljena brojna istraživanja. Trenutačno vrijedeće smjernice i dalje ne preporučuju primjenu ovoga fungalnog biomarkera kao rutinskoga dijagnostičkog testa u djece, premda može poslužiti u određenim situacijama uzimajući u obzir njegova ograničenja. BDG kao fungalni biomarker važan je napredak u dijagnostici IGI-ja te uz istodobnu primjenu ostalih dijagnostičkih metoda, ispravnu interpretaciju i racionalnu primjenu može pomoći ranijem i uspješnijem postavljanju dijagnoze i liječenju bolesnika s IGI jem.Invasive fungal infections (IFI) are an important problem of modern medicine. The reason is growing population of immunocompromised patients and high morbidity and mortality of these infections. Timely diagnosed IFI is of utmost importance because the delay of antifungal treatment has impact on treatment outcome. Cultivation as a conventional diagnostic method has low sensitivity, long duration and demands obtaining invasive samples. Therefore, in the last two decades fungal biomarkers are investigated for earlier and more sensitive diagnostics. 1,3-β-D-glucan (BDG) is a fungal biomarker in patients’ sera that enables detection of the following fungal pathogens: Candida spp., Aspergillus spp., Acremonium, Coccidioides immitis, Fusarium spp., Histoplasma capsulatum, Trichosporon spp., Sporotrix schenckii, Saccharomyces cerevisiae and Pneumocystis jirovecii. Low level and absence of BDG in the cell wall unables the detection of Cryptococcus spp. and order Mucorales with this test. High negative predictive value of BDG can be used when deciding to stop antifungal treatment and be a part of strategy for antifungal stewardship in intensive care units. In hematological patients BDG can be used as a screening method or as a part of diagnostic work-up when IFI is suspected. Reliability of test result is higher when two or more consecutive samples are positive. Influence of antifungal prophylaxis on BDG test results is still unclear. BDG kinetics and its relation to clinical outcome are still investigated. For pediatric population cut-off values for interpretation are still not defined, although many studies have been published investigating this issue. Although still not recommended by pediatric guidelines, this test can help in certain situations having in mind its limitations. BDG as a fungal marker represents the significant progress in IFI diagnostics. With simultaneous application of other diagnostic methods, exact interpretation and rational use, it can help earlier and more successful diagnostics and treatment of IFI

1,3-Β-D-glukan u dijagnostici invazivnih gljivnih infekcija – prva iskustva u Hrvatskoj [1,3-Β-D-glucan in invasive fungal infection diagnostics – first Croatian experience]

Invasive fungal infections (IFI) are an important problem of modern medicine. The reason is growing population of immunocompromised patients and high morbidity and mortality of these infections. Timely diagnosed IFI is of utmost importance because the delay of antifungal treatment has impact on treatment outcome. Cultivation as a conventional diagnostic method has low sensitivity, long duration and demands obtaining invasive samples. Therefore, in the last two decades fungal biomarkers are investigated for earlier and more sensitive diagnostics. 1,3-β-D-glucan (BDG) is a fungal biomarker in patients’ sera that enables detection of the following fungal pathogens: Candida spp., Aspergillus spp., Acremonium, Coccidioides immitis, Fusarium spp., Histoplasma capsulatum, Trichosporon spp., Sporotrix schenckii, Saccharomyces cerevisiae and Pneumocystis jirovecii. Low level and absence of BDG in the cell wall unables the detection of Cryptococcus spp. and order Mucorales with this test. High negative predictive value of BDG can be used when deciding to stop antifungal treatment and be a part of strategy for antifungal stewardship in intensive care units. In hematological patients BDG can be used as a screening method or as a part of diagnostic work-up when IFI is suspected. Reliability of test result is higher when two or more consecutive samples are positive. Influence of antifungal prophylaxis on BDG test results is still unclear. BDG kinetics and its relation to clinical outcome are still investigated. For pediatric population cut-off values for interpretation are still not defined, although many studies have been published investigating this issue. Although still not recommended by pediatric guidelines, this test can help in certain situations having in mind its limitations. BDG as a fungal marker represents the significant progress in IFI diagnostics. With simultaneous application of other diagnostic methods, exact interpretation and rational use, it can help earlier and more successful diagnostics and treatment of IFI

Thermography in patients with inflammatory bowel disease and colorectal cancer: evidence and review of the method

Background and Purpose: There is a need for a simple, noninvasive and reproducible test that could accurately reflect the inflammatory activity and neoplastic lesions, and that could be used safely and repeatedly during the biological course of inflammatory and neoplastic bowel disease. During past few decades, the joint efforts of professionals have resulted in evolution of technological advances in infrared sensor technology, thus developing the new methods that enabled the use of thermal imaging in biomedical research and clinical medicine. The aim of this viewpoint was to present, and comment on,the possibility of thermal imaging in assessing inflammatory disease activity and the existence of neoplastic bowel lesions. Materials and Methods: The authors presented thermal images of several patients (n=6: five patients with inflammatory bowel disease and one female patient with colorectal cancer), and one female healthy individual, describing the tem erature patterns and commenting on the possible thermographic signs of underlying disease. Results: Inflammatory bowel disease and colorectal cancer show a clear change in the thermal pattern of the abdominal surface and a different pattern of histogram temperature distribution. Conclusion: This review has indicated the potential of infrared thermography as a feasible and noninvasivemethod in additional evaluation of patients with various manifestations of inflammatory bowel disease and also of colon cancer

Successful separation of xypho-omphalopagus conjoined twins with extrauterine twin-twin transfusion syndrome: a case report

Conjoined twining is a rare medical phenomenon, with an overall prevalence of 1.47 per 100 000 births. This report describes a successful separation of xypho-omphalopagus conjoined twins complicated by unbalanced blood shunting through the porto-systemic anastomoses within the shared liver parenchyma. Significant extrauterine twin-twin transfusion syndrome caused by unbalanced shunting is an extremely rare, and probably under-recognized, hemodynamic complication in conjoined twins necessitating urgent separation. Progressive deterioration with a poor outcome can be prevented if the condition is recognized in a timely manner

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