GDF-15 Levels and Other Laboratory Findings as Predictors of COVID-19 Severity and Mortality: A Pilot Study.

Growth differentiation factor 15 (GDF-15) is a stress-induced cytokine associated with acute and chronic inflammatory states. This prospective observational study aimed to investigate the prognostic roles of GDF-15 and routine clinical laboratory parameters in COVID-19 patients. Upon the admission of 95 adult hospitalized COVID-19 patients in Croatia, blood analysis was performed, and medical data were collected. The patients were categorized based on survival, ICU admission, and hospitalization duration. Logistic regression and ROC curve methods were employed for the statistical analysis. Logistic regression revealed two independent predictors of negative outcomes: CURB-65 score (OR = 2.55) and LDH (OR = 1.005); one predictor of ICU admission: LDH (OR = 1.004); and one predictor of prolonged hospitalization: the need for a high-flow nasal cannula (HFNC) upon admission (OR = 4.75). The ROC curve showed diagnostic indicators of negative outcomes: age, CURB-65 score, LDH, and GDF-15. The largest area under the curve (AUC = 0.767, specificity = 65.6, sensitivity = 83.9) was represented by GDF-15, with a cutoff value of 3528 pg/mL. For ICU admission, significant diagnostic indicators were LDH, CRP, and IL-6. Significant diagnostic indicators of prolonged hospitalization were CK, GGT, and oxygenation with an HFNC upon admission. This study reaffirms the significance of the commonly used laboratory parameters and clinical scores in evaluating COVID-19. Additionally, it introduces the potential for a new diagnostic approach and research concerning GDF-15 levels in this widespread disease.

Syndrome of inappropriate antidiuretic hormone secretion as an adverse reaction of ciprofloxacin: a case report and literature review.

Antidiuretic hormone (ADH) is secreted by the posterior pituitary gland. Unsuppressed release of ADH leads to hyponatremia. This condition is referred to as syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hereby, a case report is presented on ciprofloxacin-induced SIADH. A 67-year-old male patient was examined in the emergency room with symptoms of lethargy, headache, lack of attention, and a generally depressed mood lasting for three days. One week prior, empirical antimicrobial therapy involving ciprofloxacin for prostatitis was initiated. Laboratory analysis showed no relevant abnormalities except for hyponatremia (Na = 129 mmol/L). Chronic hyponatremia, thyroid dysfunction, and adrenal dysfunction were ruled out. Serum osmolality was 263 mOsmol/kg, urine osmolality was 206 mOsmol/kg, and urine sodium was 39 mmol/L. Given that all criteria for SIADH were met, ciprofloxacin was discontinued, and fluid restriction was advised. Four days later, the patient's serum sodium concentrations nearly normalized (Na = 135 mmol/L), and all symptoms resolved. The Naranjo Scale yielded a score of 8, supporting the likelihood of a probable adverse reaction to ciprofloxacin. This case is presented to raise awareness among clinicians about the potential of ciprofloxacin to cause even mild hyponatremia.

Tick-Borne Encephalitis Virus: A Comprehensive Review of Transmission, Pathogenesis, Epidemiology, Clinical Manifestations, Diagnosis, and Prevention.

Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, can cause serious infection of the central nervous system in humans, resulting in potential neurological complications and fatal outcomes. TBEV is primarily transmitted to humans through infected tick bites, and the viral agent circulates between ticks and animals, such as deer and small mammals. The occurrence of the infection aligns with the seasonal activity of ticks. As no specific antiviral therapy exists for TBEV infection, treatment approaches primarily focus on symptomatic relief and support. Active immunization is highly effective, especially for individuals in endemic areas. The burden of TBEV infections is increasing, posing a growing health concern. Reported incidence rates rose from 0.4 to 0.9 cases per 100,000 people between 2015 and 2020. The Baltic and Central European countries have the highest incidence, but TBE is endemic across a wide geographic area. Various factors, including social and environmental aspects, improved medical awareness, and advanced diagnostics, have contributed to the observed increase. Diagnosing TBEV infection can be challenging due to the non-specific nature of the initial symptoms and potential co-infections. Accurate diagnosis is crucial for appropriate management, prevention of complications, and effective control measures. In this comprehensive review, we summarize the molecular structure of TBEV, its transmission and circulation in natural environments, the pathogenesis of TBEV infection, the epidemiology and global distribution of the virus, associated risk factors, clinical manifestations, and diagnostic approaches. By improving understanding of these aspects, we aim to enhance knowledge and promote strategies for timely and accurate diagnosis, appropriate management, and the implementation of effective control measures against TBEV infections.

SARS-CoV-2 and Plasmodium falciparum coinfection: a case report.

BACKGROUND: A rare case of coinfection of Plasmodium falciparum and SARS-CoV-2 disease in Croatia is presented in this report. METHODS: We tracked epidemiological and laboratory findings in a patient with SARS-CoV-2 and Plasmodium falciparum coinfection. A complete blood count was performed using the Sysmex XN-2000 analyser (Sysmex Corporation, Kobe, Japan), coagulation analyses were performed using the BCS XP coagulometer (Siemens Healthineers AG, Erlangen, Germany). Procalcitonin (PCT) and Interleukin-6 (IL-6) were measured by electrochemiluminescence immunoassay (ECLIA) using the Cobas e411 (Roche Diagnostics GmbH, Mannheim, Germany) analyser and high sensitivity troponin I (hsTnI) was measured using the Dimension EXL with LM analyser (Siemens Healthcare Diagnostics, Newark, USA). All other biochemistry analyses were performed using the Olympus AU680 (Beckman Coulter, Brea, California, USA) analyser. White blood cell differential analysis has been performed by examining the blood smear using the CellaVision DM1200 (CellaVision AB, Lund, Sweden) automatic analyser. RESULTS: Even though the patient's initial health condition was disturbed, as a result of the physician's comprehensive anamnesis accompanied by laboratory findings, prompt diagnosis and appropriate therapy were assured, and consequently, the patient recovered. CONCLUSION: In a pandemic, testing each febrile patient for the SARS-CoV-2 virus is of essential importance. However, the possibility of coinfection with another infectious disease agent cannot be disregarded.

Quantification of Antiviral Cytokines in Serum, Cerebrospinal Fluid and Urine of Patients with Tick-Borne Encephalitis in Croatia.

BACKGROUND: Tick-borne encephalitis virus (TBEV) is one of the most significant arboviruses affecting the human central nervous system (CNS) in Europe. Data on cytokine response in TBEV infection are limited. METHODS: We analyzed the cytokine response in serum, cerebrospinal fluid (CSF) and urine samples of patients with TBE. The control group consisted of patients with 'febrile headache' who had normal CSF cytology. The panel included 12 cytokines: TNF-α, IL-6, Th1 (IL-2, IFN-γ), Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), Th17 (IL-17A, IL-17F), Th22 (IL-22) cytokines and IL-10. RESULTS: TBE patients were more likely to have increased levels of IL-6 and IFN-γ in CSF compared to controls (85.7% vs. 58.8% and 85.7% vs. 47.1%, respectively). However, concentrations of IL-6 (the most abundant cytokine in the CSF of both groups), IL-10 and IL-9 were lower in TBEV patients compared with controls, but the difference was statistically significant for IL-9 only (p = 0.001). By analyzing the cytokine levels in different clinical samples, all measured cytokines were detected in the serum, with the highest concentrations found for IFN-γ, TNF-α, IL-10, IL-17F and IL-22. Higher concentrations of cytokines in the CSF compared with serum were observed for IL-5, IL-6 and IL-22. All cytokines except IL-13 were detectable in urine but in a small proportion of patients, except for IL-22, which was detectable in 95.8% of patients. CONCLUSIONS: Cytokine composition in different clinical samples of TBE patients reveals a different network of early innate immune response cytokines, Th1, Th2, Th9, Th22, Th17 and anti-inflammatory cytokines.

Mushroom poisoning.

In the research we included a total of 207 subjects with the dismissal diagnosis of "mycetismus", who were treated at the Department of Infectious Diseases, General Hospital Osijek, during the 1983-1992 period. 32 of them were children. There were 44.93% of men, 39.61% of women and 15.45% of children. The latent time > 6 hours was determined in 51 (25%) and < 6 hours in 75% of subjects. In 156 of patients with the latent time > 6 hours, "false" poisoning occured, while 51 patients experienced real mushroom toxins poisoning. At the admission to the hospital, in patients with the latent time > 6 hours, a pathological PT (protrombine time) was established only in women, leukocytosis in both women and children, increased concentration of GGT (gamma-glutamin-transferase) in men, increased AST (aspartate-aminotransferase) and ALT (alanin-aminotransferase) only in women, and increased urea in both women and children. After 24 hours, control measuring established high values of AST and ALT extended PT uremia and exalted amount of ammonia in blood in 11 of patients (2 men, 7 women and 2 children). They had severe liver and kidney damage, the most probably caused by Amanita phalloides toxins. The latent time lasted 9 to 13 hours. Of the 11 above mentioned patients, 2 women, aged 74 and 43, and one girl, aged 6, died. No pathological laboratory parameters were established in 40 of subjects with the latent time of 6 and more hours, and the disease manifested through vomiting and diarrhea that lasted for several days. These subjects most probably suffered from mushroom toxins poisoning. Mushroom toxins irritate the mucuous membrane of the gastrointestinal tract, and there are many such poisonous mushrooms. There were no mortalities in this group of subjects.

Encephalitis or encephalopathy during an influenza-A epidemic.

Six female patients with encephalitis, mean age 36.5 (17-60) years, were admitted to the hospital during the 2000-2001 influenza A (H1N1) epidemic in the Osijek--Baranja County. In three (50.0%) patients, the manifestation of encephalitis occurred on day 4 or 5, and in two (33.3%) patients within 24-48 hours of the onset of influenza symptoms. The disease manifestations included headache, elevated body temperature, generalized fatigue, and consciousness disturbance through coma. Three (50.0%) patients had grand mal seizures. Pathologic electroencephalography findings were recorded in all six (100%) patients, whereas computed tomography showed cerebral edema in three (50.0%) patients. Elevated levels of hepatic enzymes and peripheral blood leukopenia were found in two (33.3%) patients in whom encephalitis developed early upon the onset of influenza. One (16.6%) of these patients died, whereas permanent sequels remained in the other two (33.3%) patients.