Analysis of significant factor in differential diagnosis of febrile illness of unknown etiology

Febrilna stanja nepoznatog porekla predstavljaju veliki izazov za kliničare, jer diferencijalna dijagnoza obuhvata više poremećaja, nego bilo koje drugo medicinsko stanje. Febrilnost nejasnog porekla (FUO, engl. Fever of unknown origin) su prvi put definisali Petersdorf i Besson 1961. godine kao temperaturu koja traje duže od tri nedelje, u nekoliko navrata prelazi 38,3˚S i čiji uzrok ostaje neotkriven nakon jedne nedelje hospitalnog ispitivanja. Napretkom savremene medicine postojala je potreba za nekoliko modifikacija prvobitne definicije. Trideset godina kasnije Durack i Street predlažu dve izmene koje su i danas prihvaćene kao zlatni standard u definisanju FUO. Izmene se odnose na razliku između klasičnog FUO i febrilnih stanja koja su udružena sa neutropenijom, virusom humane imunodeficijencije (HIV) i nozokomijalnim infekcijama, kao i na kraće trajanje hospitalnog ispitivanja, umesto sedam, tri dana. Febrilna stanja nejasnog porekla predstavljaju veliki izazov za kliničare jer diferencijalna dijagnoza obuhvata više poremećaja nego bilo koje drugo medicinsko stanje. Do sada je otkriveno preko 200 različitih uzročnika FUO kojima pripadaju veoma retki, ali i relativno česti klinički entiteti. Prema etiološkim uzročnicima FUO se dele u četiri velike grupe oboljenja: infektivna, maligna, reumatološka i druge bolesti koje uključuju granulomatozne bolesti, temperaturu izazvanu lekovima i izmišljenu temperaturu. Uprkos razvoju brzih laboratorijskih testova i moćnih dijagnostičkih uređaja broj nedijagnostikovanih slučajeva FUO je i dalje značajan. Ciljevi istraživanja se odnose na diferencijalnu dijagnozu između infektivnih i neinfektivnih bolesti kod bolesnika koji ispunjavaju kriterijume za febrilna nejasna stanja nepoznate etiologije, a zatim i na diferecijalnu dijagnozu između infektivnih, reumatoloških, malignih i drugih bolesti. Naši rezultati pokazuju da neinfektivne bolesti predstavljaju češći uzrok febrilnosti nepoznatog porekla u odnosu na infektivne bolesti. To ukazuje da tradicionalno vezivanje febrilnosti za infektivne bolesti, u slučaju dugotrajne febrilnosti, nema uvek svoje mesto. Rezultati istraživanja pokazuju da kliničke manifestacije i nespecifične laboratorijske analize imaju značaj u diferencijalnoj dijagnozi nejasnih febrilnih stanja. Analizom osnovnih laboratorijskih analiza utvrđeno je da postoji statistički značajna razlika između grupe infektivnih i neinfektivnih bolesti u vrednostima S-reaktivnog proteina, feritina i prokalcitonina. U cilju evaluacije analiziran je doprinos ciljanih dijagnostičkih procedura i utvrđeno je da su bakteriološke analize imale najveći značaj u grupi ciljanih laboratorijskih analiza, dok su ehosonografski pregledi imali najveći udeo u grupi vizualizirajućih procedura, Analizom citokinskog profila pokazano je da solubilni ST-2 može imati ulogu dijagnostičkog markera u evaluaciji infektivnih i neinfektivnih bolesti kod bolesnika sa nejasnim febrilnim stanjem. Najviše vrednosti sa postojanjem statistički značajne razlike u odnosu na druge grupe kod FUO bolesnika, zabeležene su u grupi reumatoloških bolesti, zbog čega sST-2, u slučaju febrilnih stanja nepoznatog uzroka, može ukazivati na reumatološke bolesti.Febrile conditions of unknown origin present a great challenge for clinicians because the differential diagnosis includes more disorders than any other medical condition. Fever of unknown origin (FUO) were first defined by Petersdorf and Besson in 1961 as fever that lasts longer than three weeks, on several occasions exceeds 38,3˚S and whose cause remains undetected after one week hospital's testing. In modern medicine, there is a need for several modifications of the original definition. Thirty years later, Durack and Street propose two changes that are today accepted as the gold standard in defining FUO. Changes relating to the difference between a conventional FUO and febrile conditions associated with neutropenia, human immunodeficiency virus (HIV) infection and nosocomial infections, as well as to shorter duration of hospital tests, instead of seven, for three days. Febrile conditions of unknown origin present a great challenge for clinicians because the differential diagnosis includes more disorders than any other medical condition. Until now has been discovered over 200 different causes of FUO they belong to a very rare, but relatively common clinical entities. According to the etiological causes of FUO are divided into four major groups of diseases: infectious, malignant, rheumatic and other diseases involving granulomatous diseases, drug-induced fever and fictional temperature. Despite the rapid development of laboratory tests, and powerful diagnostic tools FUO number of undiagnosed cases is still significant. Research goals refer to the differential diagnosis and distinction between infectious and non-infectious diseases in patients who meet the criteria for unclear febrile status of unknown etiology. They also refer to the differential diagnosis between infectious, rheumatic, cancer and other diseases. Our results show that non-infestious diseases are more frequent cause of fever of unknown origin compared to infectious diseases. This suggests that the traditional binding of fever to infectious diseases, in the case of prolonged fever, is not always apropriate. Our results show that the clinical manifestations and nonspecific laboratory tests are important in the differential diagnosis of unclear febrile illness. The analysis of basic laboratory tests demonstrated that there is a statistically significant difference between the group of infectious and non-infectious diseases in the values of C-reactive protein, ferritin and procalcitonin. We also analized the importance of targeted diagnostic procedures and demonstrated that the bacteriological analysis had the greatest significance, while echo sonographic procedures had the greatest share among vizualizing procedures. Cytokine profile analysis has shown that a soluble ST-2 may play a role as a valuable diagnostic markers for differentiation of infectious and non-infectious causes in patients with fever of unknown origin. In the group of rheumatic diseases values of sST-2 were significantly higher compared to other groups of FUO patients. Elevated levels of sST-2 in sera, in the case of febrile illness of unknown cause, may indicate rheumatic cause

Analysis of significant factor in differential diagnosis of febrile illness of unknown etiology

Febrilna stanja nepoznatog porekla predstavljaju veliki izazov za kliničare, jer diferencijalna dijagnoza obuhvata više poremećaja, nego bilo koje drugo medicinsko stanje. Febrilnost nejasnog porekla (FUO, engl. Fever of unknown origin) su prvi put definisali Petersdorf i Besson 1961. godine kao temperaturu koja traje duže od tri nedelje, u nekoliko navrata prelazi 38,3˚S i čiji uzrok ostaje neotkriven nakon jedne nedelje hospitalnog ispitivanja. Napretkom savremene medicine postojala je potreba za nekoliko modifikacija prvobitne definicije. Trideset godina kasnije Durack i Street predlažu dve izmene koje su i danas prihvaćene kao zlatni standard u definisanju FUO. Izmene se odnose na razliku između klasičnog FUO i febrilnih stanja koja su udružena sa neutropenijom, virusom humane imunodeficijencije (HIV) i nozokomijalnim infekcijama, kao i na kraće trajanje hospitalnog ispitivanja, umesto sedam, tri dana. Febrilna stanja nejasnog porekla predstavljaju veliki izazov za kliničare jer diferencijalna dijagnoza obuhvata više poremećaja nego bilo koje drugo medicinsko stanje. Do sada je otkriveno preko 200 različitih uzročnika FUO kojima pripadaju veoma retki, ali i relativno česti klinički entiteti. Prema etiološkim uzročnicima FUO se dele u četiri velike grupe oboljenja: infektivna, maligna, reumatološka i druge bolesti koje uključuju granulomatozne bolesti, temperaturu izazvanu lekovima i izmišljenu temperaturu. Uprkos razvoju brzih laboratorijskih testova i moćnih dijagnostičkih uređaja broj nedijagnostikovanih slučajeva FUO je i dalje značajan. Ciljevi istraživanja se odnose na diferencijalnu dijagnozu između infektivnih i neinfektivnih bolesti kod bolesnika koji ispunjavaju kriterijume za febrilna nejasna stanja nepoznate etiologije, a zatim i na diferecijalnu dijagnozu između infektivnih, reumatoloških, malignih i drugih bolesti. Naši rezultati pokazuju da neinfektivne bolesti predstavljaju češći uzrok febrilnosti nepoznatog porekla u odnosu na infektivne bolesti. To ukazuje da tradicionalno vezivanje febrilnosti za infektivne bolesti, u slučaju dugotrajne febrilnosti, nema uvek svoje mesto. Rezultati istraživanja pokazuju da kliničke manifestacije i nespecifične laboratorijske analize imaju značaj u diferencijalnoj dijagnozi nejasnih febrilnih stanja. Analizom osnovnih laboratorijskih analiza utvrđeno je da postoji statistički značajna razlika između grupe infektivnih i neinfektivnih bolesti u vrednostima S-reaktivnog proteina, feritina i prokalcitonina. U cilju evaluacije analiziran je doprinos ciljanih dijagnostičkih procedura i utvrđeno je da su bakteriološke analize imale najveći značaj u grupi ciljanih laboratorijskih analiza, dok su ehosonografski pregledi imali najveći udeo u grupi vizualizirajućih procedura, Analizom citokinskog profila pokazano je da solubilni ST-2 može imati ulogu dijagnostičkog markera u evaluaciji infektivnih i neinfektivnih bolesti kod bolesnika sa nejasnim febrilnim stanjem. Najviše vrednosti sa postojanjem statistički značajne razlike u odnosu na druge grupe kod FUO bolesnika, zabeležene su u grupi reumatoloških bolesti, zbog čega sST-2, u slučaju febrilnih stanja nepoznatog uzroka, može ukazivati na reumatološke bolesti.Febrile conditions of unknown origin present a great challenge for clinicians because the differential diagnosis includes more disorders than any other medical condition. Fever of unknown origin (FUO) were first defined by Petersdorf and Besson in 1961 as fever that lasts longer than three weeks, on several occasions exceeds 38,3˚S and whose cause remains undetected after one week hospital's testing. In modern medicine, there is a need for several modifications of the original definition. Thirty years later, Durack and Street propose two changes that are today accepted as the gold standard in defining FUO. Changes relating to the difference between a conventional FUO and febrile conditions associated with neutropenia, human immunodeficiency virus (HIV) infection and nosocomial infections, as well as to shorter duration of hospital tests, instead of seven, for three days. Febrile conditions of unknown origin present a great challenge for clinicians because the differential diagnosis includes more disorders than any other medical condition. Until now has been discovered over 200 different causes of FUO they belong to a very rare, but relatively common clinical entities. According to the etiological causes of FUO are divided into four major groups of diseases: infectious, malignant, rheumatic and other diseases involving granulomatous diseases, drug-induced fever and fictional temperature. Despite the rapid development of laboratory tests, and powerful diagnostic tools FUO number of undiagnosed cases is still significant. Research goals refer to the differential diagnosis and distinction between infectious and non-infectious diseases in patients who meet the criteria for unclear febrile status of unknown etiology. They also refer to the differential diagnosis between infectious, rheumatic, cancer and other diseases. Our results show that non-infestious diseases are more frequent cause of fever of unknown origin compared to infectious diseases. This suggests that the traditional binding of fever to infectious diseases, in the case of prolonged fever, is not always apropriate. Our results show that the clinical manifestations and nonspecific laboratory tests are important in the differential diagnosis of unclear febrile illness. The analysis of basic laboratory tests demonstrated that there is a statistically significant difference between the group of infectious and non-infectious diseases in the values of C-reactive protein, ferritin and procalcitonin. We also analized the importance of targeted diagnostic procedures and demonstrated that the bacteriological analysis had the greatest significance, while echo sonographic procedures had the greatest share among vizualizing procedures. Cytokine profile analysis has shown that a soluble ST-2 may play a role as a valuable diagnostic markers for differentiation of infectious and non-infectious causes in patients with fever of unknown origin. In the group of rheumatic diseases values of sST-2 were significantly higher compared to other groups of FUO patients. Elevated levels of sST-2 in sera, in the case of febrile illness of unknown cause, may indicate rheumatic cause

Antimicrobial, antioxidant and DNA-binding studies of palladium(II) complexes with different chelate ligands containing nitrogen donor atoms

The antimicrobial and antioxidant activities, as well as the DNA-binding of four square-planar Pd(II) complexes, [Pd(terpy)Cl]+ (C1), [Pd(en)Cl2] (C2), [Pd(DMEAImiPr)Cl2] (C3) and [Pd(dach)Cl2] (C4) (terpy = 2,2′:6′,2′′- -terpyridine, en = ethylenediamine, dach = trans-1,2-diaminocyclohexane and DMEAImiPr = N2-((1,3-dihydro-1,3-diisopropyl-4,5-dimethyl)-2H-imidazol-2- ylidene)-N1,N1-dimethyl-1,2-ethanediamine are reported. The antimicrobial activities of the Pd(II) complexes with the appropriate ligands were tested using the microdilution method against 18 strains of microorganisms, whereby the minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC) were determined. The antibiofilm activity of [Pd(terpy)Cl]+ and the corresponding ligand were determined on a formed biofilm. The intensity of antimicrobial activity varied depending on the type of microorganism and the tested compound. The C1 complex with the corresponding ligand demonstrated significantly greater overall antimicrobial activity than C2, C3 and C4. The antibacterial activity of the C1 complex was better than its antifungal activity that was overall greater than that of the positive control, fluconazole. The greatest sensitivity for C1 and L1 was with Penicillium italicum (MIC < 0.49 μg mL-1) among the fungi, and with Proteus mirabilis ATCC 12453 (MIC = 0.98 μg mL-1) among the tested bacteria. The tested compounds show low and moderate antibiofilm activity. The complexes showed weak antioxidant properties when tested using the DPPH (1,1-diphenyl-2- -picrylhydrazyl) method. The interaction of the metal complexes C1–C4 with calf thymus DNA (CT-DNA) was further examined by absorption (UV–Vis) and emission spectral studies (EthBr displacement studies). Overall, the investigated complexes exhibited good DNA interaction ability. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 172011 and Grant no. 173032