The Relationship between Nrf2 and HO-1 with the Severity of COVID-19 Disease.

Nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) have significant roles in the development of a hyperinflammatory state in infectious diseases. We aimed to investigate the association of the serum concentrations of Nrf2 and HO-1 with the severity of COVID-19 disease. The study included 40 subjects with mild and moderately severe forms of the disease (MEWS scoring system ≤2). Twenty of the subjects had MEWS scores of 3 or 4, which indicate a severe form of the disease, and twenty subjects had a MEWS score of ≥5, which indicates a critical form of the disease. HO-1 and Nrf2 were measured using the commercially available Enzyme-Linked Immunosorbent Assay (ELISA). Subjects with the most severe form of COVID-19 (critically ill) had a lower concentration of Nrf2 that negatively correlated with the markers of hyperinflammatory response (CRP, IL-6, ferritin). This observation was not made for HO-1, and the correlation between Nrf2 and HO-1 values was not established. In the mild/moderate form of COVID-19 disease, Nrf2 was associated with an increased 1,25 dihydroxy vitamin D concentration. The results of this study show that Nrf2 has a role in the body's anti-inflammatory response to COVID-19 disease, which makes it a potential therapeutic target.

Overactive bladder symptoms in patients undergoing rigid and flexible cystoscopy.

PURPOSE: To evaluate overactive bladder (OAB) symptoms in patients undergoing diagnostic cystoscopy. Overall changes in the entire study population were assessed, as well as broken down by various subgroups. METHODS: A prospective multi-center study among consecutive 450 adults undergoing diagnostic cystoscopy was conducted. OAB-symptoms were evaluated with the validated eight-item OAB Screening Awareness Tool (OAB-V8) immediately before and on days 1, 4, and 7 after cystoscopy. Patients were distinguished between being OAB-negative and OAB-positive (< 8 and ≥ 8 sum-score, respectively). Average sum-scores and subdomains were evaluated. RESULTS: Before cystoscopy, 44.7% of patients were screened OAB-positive and 55.3% OAB-negative. Out of those being screened negative, development of de-novo OAB was noticed in 16.8%, declining to 8.1% on day 7 (p < 0.001). In patients being OAB-positive before cystoscopy, a decline of OAB-positivity was noted during follow-up (p < 0.001). No statistically significant differences were noted when broken down by gender (p = 0.92), age (p = 0.82) and type cystoscope (rigid vs. flexible, p = 0.38). Average sum-scores declined from 8.68 before cystoscopy to 6.9 during follow-up. Flexible cystoscopy was superior over rigid in four subdomains: uncomfortable urge to urinate (p = 0.04), sudden urge to urinate with little or no warning (p = 0.02), uncontrollable urge to urinate (p = 0.03), and urine loss associated with a strong desire to void (p = 0.009). CONCLUSION: OAB-symptoms are common in patients undergoing cystoscopy. Cystoscopy itself can cause de-novo OAB-symptoms. Controversially, a decline of OAB-symptoms was noted after cystoscopy when patients were screened OAB-positive before cystoscopy. Flexible scopes were superior in some subdomains.

Fatal case of West Nile encephalitis associated with acute anteroseptal ST elevation myocardial infarction (STEMI): a case report.

Cardiac involvement has rarely been reported in West Nile (WNV) infection. We report a fatal case of WNV encephalitis associated with an acute anteroseptal ST elevation myocardial infarction. The patient was hospitalized with a fever, headache, nausea and vomiting. The physical examination revealed positive meningeal signs and an altered level of consciousness. High levels of cardiac enzymes (creatine phosphokinase/MB fraction, lactate dehydrogenase, myoglobin and cardiac troponin I) and ST elevation on electrocardiogram were found. Both CSF and urine samples were positive for WNV RNA. This case highlights the need of awareness of the possibility of a WNV-related myocardial infection, including myocardial infarction.

Anxiety and depression analyses of patients undergoing diagnostic cystoscopy.

PURPOSE: To prospectively assess anxiety and depression in patients undergoing diagnostic cystoscopy. METHODS: Patients presenting for outpatient diagnostic cystoscopy were recruited from four European urological departments. Anxiety and depression were assessed with the 'Hospital Anxiety and Depression Scale' (HADS) before cystoscopy and after 1 week. Statistical analyses, including the Chi-square test, univariate, and multivariate logistic regression analyses, were carried out with SPSS v. 21 (IBM Corp., Armonk, NY). RESULTS: Prior to cystoscopy, 30.2 % of patients were anxious and 24.8 % depressive (n = 442). In the post-examination period, anxiety declined to 24.5 %, while depression was unchanged (24.4 %). Pre-cystoscopy anxiety was significantly more common in women (41.8 vs. 24.5 %, p < 0.0001), patients aged <65 years (34.9 vs. 25.9 %, p = 0.04), and in those being examined with rigid cystoscopes (35.7 vs. 23.9 %, p = 0.007). In multivariate regression analyses, female gender (OR 2.6, p < 0.0001), <65 years of age (OR 1.7, p = 0.03), and coexistence of depression (OR 7.8, p < 0.0001) were independently associated with elevated pre-cystoscopy anxiety. Anxious (OR 2.1, p = 0.03) and depressive (OR 2.1, p = 0.01) patients had higher odds of experiencing moderate or severe pain during cystoscopy. Bladder cancer diagnosis did not significantly change patient's anxiety (p = 0.23) or depression (p = 0.7) during the 1 week of follow-up. CONCLUSIONS: Women, patients aged <65 years, depressive patients and those being examined with rigid devices had higher rates of anxiety prior to cystoscopy. Anxious and depressive patients experienced more pain during cystoscopy. Bladder cancer diagnosis seems to have a minor effect on anxiety and depression during the first week after diagnosis.

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.

Endocannabinoids, Anandamide and 2-Arachidonoylglycerol, as Prognostic Markers of Sepsis Outcome and Complications.

Background: One of the major challenges in improving sepsis care is early prediction of sepsis complications. The endocannabinoid system has been intensely studied in recent years; however, little is known about its role in sepsis in humans. This study aimed to assess the prognostic role of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), as early predictors of mortality, invasive mechanical ventilation (IMV) requirement, and length of stay (LOS) in patients with sepsis. Materials and Methods: In total, 106 patients with confirmed sepsis were enrolled in this study. The patients were divided into groups according to mortality outcome (survival, N=53; nonsurvival, N=53), IMV requirement (IMV group, N=26; non-IMV group, N=80), and LOS (LOS <10 days, N=59; LOS ≥10 days, N=47). Patients' clinical status was assessed along with laboratory biomarkers as well as AEA and 2-AG concentration measurements early on admission to emergency units. AEA and 2-AG levels were measured by enzyme-linked immunosorbent assay (ELISA) using an ELISA processor, EtiMax 3000 (DiaSorin, Saluggia, Italy). The predictive value of AEA and 2-AG for the studied sepsis outcomes and complications was analyzed using univariate and multivariate analyses and receiver operating characteristic (ROC) curve analysis. Results: Two endocannabinoids showed no significant difference between survivors and nonsurvivors, although an AEA concentration <7.16 µg/L predicted mortality outcome with a sensitivity of 57% (95% confidence interval [CI] 42-71) and specificity of 80% (95% CI 66-91). AEA concentrations ≤17.84 µg/L predicted LOS ≥10 days with sensitivity of 98% (95% CI 89-100) and specificity of 34% (95% CI 22-47). When analyzing IMV requirement, levels of AEA and 2-AG were significantly lower within the IMV group compared with the non-IMV group (5.94 µg/L [2.04-9.44] and 6.70 µg/L [3.50-27.04], p=0.043, and 5.68 µg/L [2.30-8.60] and 9.58 µg/L [4.83-40.05], p=0.002, respectively). The 2-AG showed the best performance for IMV requirement prediction, with both sensitivity and specificity of 69% (p<0.001). Endocannabinoid AEA was an independent risk factor of LOS ≥10 days (odds ratio [OR] 23.59; 95% CI 3.03-183.83; p=0.003) and IMV requirement in sepsis (OR 0.79; 95% CI, 0.67-0.93; p=0.004). Conclusion: Low AEA concentration is a prognostic factor of hospital LOS longer than 10 days. Lower AEA and 2-AG concentrations obtained at the time of admission to the hospital are predictors of IMV requirement.

Impact of vaccination on the presence and severity of symptoms in hospitalized patients with an infection of the Omicron variant (B.1.1.529) of the SARS-CoV-2 (subvariant BA.1).

OBJECTIVES: The emergence of SARS-CoV-2 variants raised questions about the extent to which vaccines designed in 2020 have remained effective. We aimed to assess whether vaccine status was associated with the severity of Omicron SARS-CoV-2 infection in hospitalized patients. METHODS: We conducted an international, multi-centric, retrospective study in 14 centres (Bulgaria, Croatia, France, and Turkey). We collected data on patients hospitalized for ≥24 hours between 1 December 2021 and 3 March 2022 with PCR-confirmed infection at a time of exclusive Omicron circulation and hospitalization related or not related to the infection. Patients who had received prophylaxis by monoclonal antibodies were excluded. Patients were considered fully vaccinated if they had received at least two injections of either mRNA and/or ChAdOx1-S or one injection of Ad26.CoV2-S vaccines. RESULTS: Among 1215 patients (median age, 73.0 years; interquartile range, 57.0-84.0; 51.3% men), 746 (61.4%) were fully vaccinated. In multivariate analysis, being vaccinated was associated with lower 28-day mortality (Odds Ratio [95% Confidence Interval] (OR [95CI]) = 0.50 [0.32-0.77]), intensive care unit admission (OR [95CI] = 0.40 [0.26-0.62]), and oxygen requirement (OR [95CI] = 0.34 [0.25-0.46]), independent of age and comorbidities. When co-analysing these patients with Omicron infection with 948 patients with Delta infection from a study we recently conducted, Omicron infection was associated with lower 28-day mortality (OR [95CI] = 0.53 [0.37-0.76]), intensive care unit admission (OR [95CI] = 0.19 [0.12-0.28]), and oxygen requirements (OR [95CI] = 0.50 [0.38-0.67]), independent of age, comorbidities, and vaccination status. DISCUSSION: Originally designed vaccines have remained effective on the severity of Omicron SARS-CoV-2 infection. Omicron is associated with a lower risk of severe forms, independent of vaccination and patient characteristics.

Ureterorenoscopic treatment of ureteral stones--influence of operator's experience and skill on the procedure outcome.

AIM: To observe the influence of operating urologist's education and adopted skills on the outcome of ureterorenoscopy treatment of ureteral stones. METHODS: The study included 422 patients (234 men, 55.4%) who underwent ureterorenoscopy to treat ureteral stones at the Urology Department of Clinical Hospital Center Split, Croatia, between 2001 and 2009. All interventions were carried out with a semi-rigid Wolf ureteroscope and an electropneumatic generator used for lithotripsy. The operating specialists were divided into two groups. The first group included 4 urologists who had started learning and performing endoscopic procedures at the beginning of their specialization and the second group included 4 urologists who had started performing endoscopic procedures later in their careers, on average more than 5 years after specialization. RESULTS: Radiology tests confirmed that 87% (208/238) of stones were completely removed from the distal ureter, 54% (66/123) from the middle ureter, and 46% (28/61) from the proximal ureter. The first group of urologists completed significantly more procedures successfully, especially for the stones in the distal (95% vs 74%; P = 0.001) and middle ureter (66% vs 38%; P = 0.002), and their patients spent less time in the hospital postoperatively. CONCLUSION: Urologists who started learning and performing endoscopic procedures at the beginning of their specialization are more successful in performing ureteroscopy. It is important that young specialists receive timely and systematic education and cooperate with more experienced colleagues.

Prospective, multi-institutional pain assessment of 150 women undergoing diagnostic cystoscopy.

BACKGROUND: The aim of this study was to prospectively assess women's pain during rigid and flexible diagnostic cystoscopy and afterwards during a one-week follow-up. METHODS: Prospective, multi-institutional trial analyzing numeric rating scales (NRS) of women undergoing diagnostic cystoscopy. Pain categories: no (0 points), mild (1-3), moderate (4-6) and severe pain (7-10). Assessing of pain before, during cystoscopy, and at day 1, 4 and 7 of follow-up. RESULTS: A total of 150 women undergoing rigid (N.=85) or flexible (N.=65) diagnostic cystoscopy were analyzed. Women undergoing flexible cystoscopy were more frequently pain-free (64.6% vs. 40%, P=0.003) and experienced mild pain less frequently (27.7% vs. 52.9% vs. P=0.002). No significant differences were noted among moderate (6.2% vs. 5.9%, P=0.95) and severe pain (1.5% vs. 1.2%, P=0.85). Patients undergoing their first (P=0.14) and repeat cystoscopy (P=0.08) had similar pain perception. In multivariate logistic regression analyses, women undergoing flexible cystoscopy had a 2.6 increased chance of being pain-free (OR=2.6, CI: 1.28-5.11, P=0.08) and their odds of experiencing mild pain were significantly lower (OR=0.34, CI: 0.17-0.71, P=0.004). The likelihood of experiencing moderate (OR=1.1, CI: 0.28- 4.4, P=0.83) or severe pain (OR=2.42, CI: 0.11-51.79, P=0.57) differed insignificantly. CONCLUSIONS: Rigid and flexible cystoscopies were well-tolerated by most women. However, flexible cystoscopy was associated with a higher likelihood of being pain-free and lower chances of experiencing mild pain. Patients' previous experience with cystoscopy did not influence pain perception.

Prospective multi-institutional study analyzing pain perception of flexible and rigid cystoscopy in men.

OBJECTIVE: To evaluate pain perception in men undergoing flexible or rigid diagnostic cystoscopy. METHODS: This is a prospective multi-institutional analysis of men undergoing cystoscopy in 4 European departments of urology. Pain perception was assessed with an 11-point numeric rating scale. Pain categories were as follows: no (0 points), mild (1-3), moderate (4-6), and severe pain (7-10). Assessment of pain was before, during cystoscopy, and at days 1, 4, and 7 of follow-up. RESULTS: A total of 300 cystoscopies were analyzed (150 rigid and 150 flexible). Men undergoing flexible cystoscopy were more frequently free of pain (58.7% vs 24%; P <.0001). Mild pain (54% vs 30.7%; P <.0001) and moderate pain (18.7% vs 9.3%; P = .02) were more common with rigid devices. No significant differences were prevalent in severe pain perception (3.3% vs 1.3%; P = .25). Patients, who had previous experience with cystoscopy reported similar pain levels as patients naïve to cystoscopy, regardless if rigid (P = .92) or flexible (P = .26) devices were used. Pain decreased to the baseline during the 1-week follow-up after both, flexible and rigid cystoscopy. In multivariate regression analyses, rigid cystoscopy was an independent predictor for not being pain free (odds ratio [OR] = 0.15; confidence interval [CI] = 0.08-0.28; P <.0001), for experiencing mild pain (OR = 2.57; CI = 1.57-4.19; P <.0001), and for moderate pain (OR = 2.39; CI = 1.13-5.07; P = .02). Severe pain was seldom with both devices, and thus, no statistical difference was found. CONCLUSION: Flexible diagnostic cystoscopy caused less pain than rigid cystoscopy in men. Patient's previous experience with cystoscopy did not influence pain sensation. The type of cystoscope itself was identified as an independent risk factor of pain perception.

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.

Biopsies of the normal-appearing urothelium in primary bladder cancer.

AIM: The aim of the study was to determine the incidence of "positive" findings in biopsies of the normal-appearing urothelium near primary cancer and their influence on therapeutic decisions. MATERIALS AND METHODS: Between January 2001 and October 2008, in 230 patients with primary bladder cancer during initial resection of tumor, we also performed random biopsy of surrounding normal-appearing urothelium. We analyzed retrospectively the number and type of positive biopsy findings and their impact on further treatment. RESULTS: There were 40% of patients (92/230) whose normal-appearing urothelium biopsy revealed pathological findings such as tumor tissue, Tis, and dysplasia. In 24.4% of patients, the stage of the primary tumor was Ta (32/131), in 50% it was T1 stage (30/61), and in 79% T2 stage (30/38). When we assessed the grade of malignancy, we found 18% of biopsies with G1 tumors (16/88), 33% with G2 tumors (19/59), and 69% with G3 tumors (57/83). Tumor tissue that was found in the normal-appearing urothelium in biopsy specimens in 13% of patients was in stage Ta (17/131), in 16% it was T1 stage (10/61), and in 39% of patients, the tumor was in T2 stage (15/38). Pathological findings of random biopsies were crucial in changing therapeutical decisions in 4.6% (9/192) of patients. CONCLUSION: Biopsy of the normal-appearing urothelial tissue is easy to perform and may help in identifying patients with high risk of disease progression and recurrence. Based on our results and results from the literature we recommend this simple tool as part of the routine management during transurethral resection of primary bladder cancer.