Serum butyrylcholinesterase as a marker of COVID-19 mortality: Results of the monocentric prospective observational study.

The COVID-19 pandemic represents an excessive burden on health care systems worldwide and the number of patients who require special care in the clinical setting is often hard to predict. Consequently, there is an unmet need for a reliable biomarker that could predict clinical outcomes of high-risk patients. Lower serum butyrylcholinesterase (BChE) activity was recently linked with poor outcomes of COVID-19 patients. In line with this, our monocentric observational study on hospitalized COVID-19 patients focused on changes in serum BChE activity in relation to disease progression. Blood samples from 148 adult patients of both sexes were collected during their hospital stay at the Clinics of Infectiology and Clinics of Anesthesiology and Intensive Care, Trnava University Hospital in alignment with routine blood tests. Sera were analyzed using modified Ellman's method. Patient data with information about the health status, comorbidities and other blood parameters were collected in pseudonymized form. Our results show a lower serum BChE activity together with progressive decline of BChE activity in non-survivors, while higher stable values were present in discharged or transferred patients requiring further care. Lower BChE activity was associated with higher age and lower BMI. Moreover, we observed a negative correlation of serum BChE activity with the routinely used inflammatory markers, C-reactive protein and interleukin-6. Serum BChE activity mirrored clinical outcomes of COVID-19 patients and thus serves as a novel prognostic marker in high-risk patients.

Cognitive changes in spinocerebellar ataxia type 2.

OBJECTIVES: Cognitive disorders and dementia occur in 19 to 42% of patients with spinocerebellar ataxia type 2 (SCA2). Neuropsychological tests can reveal executive dysfunction, impaired visual and verbal memory, tongue and speech impairment, attention disorders and impaired verbal fluency. METHODS: We performed psychiatric and neuropsychological examinations in 12 patients diagnosed with genetically confirmed SCA2 and 12 healthy volunteers matching the patients in age, gender, and length of education. The level of motor impairment was determined using the brief ataxia rating scale (BARS). The neuropsychological examination focused on testing executive functions, short-term visual and verbal memory, attention, psychomotor tempo, visual motor coordination, learning ability and comprehension ability. The tests were divided into two subgroups according to the difficulty of motor tasks. The cognitive abilities composite score (CACS) was determined by calculating the arithmetic mean of T scores of the respective tests. RESULTS: Patients with SCA2 had significantly lower CACSs (p=0.00005) compared to the healthy volunteers. Patients exhibited impaired performance in both difficult and simple motor tests. The severity of cognitive impairment was related to the age at the onset of the disease (p=0.002) but not to the duration or to the overall BARS score. CONCLUSIONS: Compared to healthy volunteers, patients with SCA2 exhibited significantly worse cognitive performance in all areas tested, including the tests of simple motor tasks. Moreover, the cognitive performance of patients worsened as the difficulty of the motor tasks increased.

Micafungin Is an Efficient Treatment of Multi Drug-Resistant Candida glabrata Urosepsis: A Case Report.

Candiduria is a common nosocomial infection in hospitalized patients, which may progress into life-threatening candidemia. Successful treatment of urosepsis requires early and effective antifungal therapy, while the available agents within three pharmacological classes each have characteristic pharmacokinetics and side effect profiles. Moreover, treatment of Candida spp. infections is becoming challenging due to increasing multi drug-resistance. Here, we present a case of candidemia resulting from a multi drug-resistant C. glabrata infection of the urinary tract. Due to resistance to fluconazole and a contraindication for amphotericin B, micafungin was used in the treatment, regardless of its unfavorable pharmacokinetic properties. Our study showed that despite the expected low levels in the urinary tract, micafungin was successful in the eradication of C. glabrata allowing full recovery of the patient. Thus, micafungin should be considered in the management of urosepsis caused by sensitive Candida spp.

Medication-related factors associated with proton pump inhibitor prescription beyond official guidelines in older adults.

PURPOSE: To investigate the relationship between medications with a known risk of gastrointestinal bleeding and proton pump inhibitor (PPI) prescription not according to guidelines. METHODS: An analysis of the records of 592 hospitalised patients aged 65 years or older was undertaken. The number of all medicines, potentially inappropriate medicines according to the EU(7)-PIM list and the Beers Criteria 2019 and medicines with a known risk of gastrointestinal bleeding, was compared in patients with PPI prescription not given based on guidelines and in patients with no PPI prescription. RESULTS: Patients prescribed PPI not based on guidelines used more medications on average (9.6 vs. 6.4, p < 0.001), more PIMs according to the EU(7)-PIM list (2.4 vs. 1.1, p < 0.001) and the Beers criteria (2.0 vs. 0.6, p < 0.001) at hospital admission and at discharge (8.9 vs. 7.5, p < 0.001, mean number of medications), (2.0 vs. 1.2, p < 0.001, EU(7)-PIM list), (1.9 vs. 0.8, p < 0.001, Beers criteria) than patients with no PPI prescription. Patients prescribed PPI not according to guidelines were more frequently using direct oral anticoagulants (28% vs. 12.8%, p < 0.001), corticosteroids (5.3% vs. 0.7%, p = 0.025) at hospital admission and at discharge (25.9% vs. 16.5%, p = 0.018, oral anticoagulants), (6.6% vs. 1%, p = 0.006, corticosteroids), (13.3% vs. 5.4%, p = 0.004, warfarin) than patients with no PPI prescription. CONCLUSION: The number of medications, potentially inappropriate medications according to the EU(7)-PIM list and Beers criteria, and the use of direct oral anticoagulants, warfarin and corticosteroid prescriptions were the medication-related factors associated with PPI prescription not according to guidelines in elderly patients.

Outcome of thirty patients with ANCA-associated renal vasculitis admitted to the intensive care unit.

The natural course of as-yet-untreated ANCA-associated vasculitis (AAV) or complications of immunosuppressive treatment may result in rapid clinical deterioration with the need of admission to an intensive care unit (ICU). The aim of this retrospective study was to assess the outcome of patients with renal AAV admitted to the ICU in a single center. We reviewed the medical records of all 218 patients with AAV followed in our department between January 2001 and December 2006 and selected those admitted to the ICU. To assess the severity of critical illness, the Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA) score on the first ICU day were calculated. Birmingham Vasculitis Activity Score (BVAS) was calculated to represent the total disease activity. Thirty patients with AAV (11 women, 19 men; mean age 61.5 +/- 13.2 years; 20 x cANCA, 10 x pANCA positive) were included. The most common reasons for ICU admission were as follows: active vasculitis (13 patients, 43.3 %), infections (7 patients, 23.3%), and other causes (10 patients, 33.3%). The in-ICU mortality was 33.3% (10 patients). The most common cause of death was septic shock (in 5 patients). The APACHE II (33.5 vs. 23.8) and SOFA scores (11.9 vs. 6.6), but not BVAS (11.5 vs. 16.1), were statistically significantly higher in non-survivors than in survivors (p < 0.01). In conclusion, the in-ICU mortality in AAV patients may be predicted by APACHE II and SOFA scores. While active vasculitis is the most frequent reason for ICU admission, the mortality rate is highest in patients with infectious complications.

Parvovirus B19 induced lupus-like syndrome with nephritis.

We report a case of a 65-year-old man who developed an acute illness with fever, arthralgia and nephritic syndrome. Antinuclear antibodies were slightly positive and complement levels were low. Renal biopsy showed exudative diffuse proliferative endocapillary glomerulonephritis with diffuse immunoglobulin (IgG, IgA, IgM) and complement deposition (C3d, C4d, C1q) on immunofluorescence. The patient was first treated with corticosteroids and mycophenolate mofetil for suspected lupus with WHO class IV glomerulonephritis. The diagnosis was questioned and a diagnosis of parvovirus B19-associated nephritis was made based on elevation of serum IgM antibodies for parvovirus B19 and detection of parvovirus B19 DNA on renal biopsy. The immunosuppressive treatment was stopped and progressive spontaneous regression of clinical and laboratory abnormalities was observed. We conclude that human parvovirus B19 infection should be considered as a cause of lupus-like symptomatology and acute glomerulonephritis.

Disturbances of anticoagulation and fibrinolytic systems in monoclonal gammopathies-another mechanism of M-protein interference with hemostasis.

Monoclonal gammopathies (MG) may be associated with unique monoclonal immunoglobulin (MIg)-induced disturbances of either primary hemostasis or plasma coagulation. We have investigated the possible interference of MIg with antithrombotic systems in 49 patients with MG. Although an increase of tissue-type plasminogen activator (t-PA) activity was the most frequent abnormality in our group, defect of anticoagulation factors was found in 26.5% of patients. The relationship between MIg type and concentration and frequency of antithrombotic factor abnormalities was not found. The risk of venous thrombosis was higher in patients with the defect in comparison with the unaffected group (46% vs. 22%), but the difference was not statistically significant. Bleeding complications were markedly less frequent in the group of patients with defect of anticoagulation mechanisms (0% vs. 17%). In conclusion, we have found abnormalities in anticoagulation and/or fibrinolytic system, analogous to well-known disturbances of hemostatic mechanisms, in more than a quarter of patients with MG. The interference of M-protein with antithrombotic pathways is supposed to be another mechanism of secondary deficiencies of antithrombin III (AT III), protein C (PC), protein S (PS), plasminogen and APC resistance. Together with other factors, it could contribute to higher risk of thromboembolism in myeloma patients.

Intracellular cytokine production in ANCA-associated vasculitis: low levels of interleukin-10 in remission are associated with a higher relapse rate in the long-term follow-up.

BACKGROUND AND AIMS: Dysregulation of cell-mediated immune response likely plays a role in the pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), but it has not yet been fully established. The aim of this study was to assess the intracellular cytokine production in patients with AAV at different stages of the disease, in particular, in relation to the long-term prognosis. METHODS: We included 69 patients with AAV and 24 healthy controls. Using flow cytometry, the following intracellular cytokines (IC) were measured in all patients: interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-2 and interleukin-4 in CD3+T cells and interleukin-10 (IL-10) and interleukin 12 (IL-12) in monocytes. Patients were then prospectively followed for a median of 43 months and cytokine production was related to the long-term prognosis. RESULTS: When compared to healthy controls, increased IL-12 production was observed in AAV patients, both active (p<0.01) and in remission (p<0.05). In remission, increased IFN-gamma production was also found (p<0.01). IL-10 production was higher in active patients than in patients in remission (p<0.05) but did not differ from controls. Patients in remission who developed a relapse during follow-up had significantly lower IL-10 production than those without relapse (p<0.01). Results of this prospective study of IC production in AAV confirm findings of previous studies measuring circulating cytokine levels. CONCLUSIONS: Activation of the immune system in AAV patients is noticeable even in remission. Patients with AAV display increased IL-12 production, which seems to be counterbalanced by IL-10. Low IL-10 levels in remission are associated with a higher relapse rate in the long-term follow-up.

Treatment of lupus nephritis with cyclosporine - an outcome analysis.

BACKGROUND: The optimal therapy for lupus nephritis (LN), including the role of cyclosporine (CsA), still lacks scientifically valid clinical experience. We evaluated the efficacy of CsA in the induction and maintenance treatment of patients with biopsy-proven LN. PATIENTS AND METHODS: A total of 31 patients (25 women, 6 men, mean age 29.5 years) were enrolled in the study. The majority had proliferative LN. The mean follow-up was 85.6 +/- 24.7 months. RESULTS: CsA was used as first-line treatment in 38.7% of patients and as second-line treatment in 61.3% of patients. Complete remission was achieved in 93.5% of patients. The relapse rate was 45.2%. The mean disease-free interval was 33 months. At the end of follow-up, a total of 67.9% of the patients were in remission. The treatment led to significant improvement in proteinuria (p = 0.001) and stabilization of renal function. CONCLUSION: CsA might be an appropriate and a less toxic alternative drug for LN both as a first-choice and rescue therapy.

Long-term outcome of patients with antineutrophil cytoplasmic autoantibody-associated vasculitis with renal involvement.

BACKGROUND: Despite treatment, renal involvement in antineutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis is still associated with significant long-term mortality and remains an important cause of end-stage renal failure. METHODS: We retrospectively analyzed a series of 61 consecutive patients with newly diagnosed ANCA-associated renal vasculitis (54.1% Wegener's granulomatosis, 23% renal-limited vasculitis, 16.4% microscopic polyangiitis, 4.9% Churg-Strauss syndrome) diagnosed between 1986 and 1997. RESULTS: The median creatinine level at diagnosis was 221.5 (63-762) micromol/l, i.e. 2.5 (0.7-8.6) mg/dl, 32.8% were dialysis-dependent. All patients were treated with cyclophosphamide. Remission was achieved in 87% of patients. Relapses occurred in 44.7%. The median renal disease-free interval was 62.5 (0-138) months. The estimated patient survival at 5 and 10 years was 78.3 and 62.2%, respectively. Mortality was associated with age (p = 0.04 when age limit 50 years) and advanced renal failure (p = 0.038 when compared dialysis-dependent and independent patients). Estimated renal survival time at 5 and 10 years was 69.2 and 55.8%, respectively. At the end of follow-up, 50.8% of patients were in complete remission, 31% had died. The median serum creatinine level was 137.5 (77-469) micromol/l, i.e. 1.56 (0.87-5.3) mg/dl, 24.6% of patients were on regular dialysis treatment. CONCLUSION: Patient survival, relapse rate and mortality were comparable to similar reports. In view of the severity of the renal disease and the length of follow-up, renal survival was very good. Despite effective treatment, the long-term outcome of patients with ANCA-associated renal vasculitis remains unsatisfactory.

Secondary membranous nephropathy--one center experience.

INTRODUCTION: Secondary membranous nephropathy (MN) is most commonly seen in the setting of autoimmune disease, infection, and neoplasia, and with certain therapeutic agents. The aim of our study was to analyze the presenting features and outcome of the patients with secondary MN. PATIENTS AND METHODS: We retrospectively studied patients with secondary MN diagnosed between the years 1991-2002. In this period, we performed a total of 1874 renal biopsies. MN was diagnosed in 129 cases. RESULTS: In 40 patients (31%), an underlying primary cause was verified (70% women, 30% men, median age 49.5 years). In 18 patients (45%), the disease was drug induced, 11 patients (27.5%) had autoimmune disease, seven patients (17.5%) solid tumors, three patients (7.5%) hepatitis B, and one patient was diagnosed with both hepatitis B and prostate carcinoma. At presentation, median proteinuria was 4.09 g/24 h; 60% were nephrotic. Most of the patients had normal renal function with a median serum creatinine 79 micromol/L and a median GFR 1.285 ml/s. The patients were treated according to the underlying disease. At the end of the follow-up, the patients with drug-induced MN were in complete remission after the discontinuation of the drug. The patients with autoimmune disease were treated with immunosuppression, most of them with very good results. The outcome of the patients with neoplasia was much worse. CONCLUSION: A thorough and repeated exclusion of secondary forms of MN has significant prognostic and therapeutic implications, especially in drug-induced and autoimmune MN.

Silica and asbestos exposure in ANCA-associated vasculitis with pulmonary involvement.

Silica and asbestos exposure are thought to belong to the triggering factors of antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis. We carried out a study to find out whether patients with pulmonary involvement attributable to ANCA-associated vasculitis (AAV) have been exposed to silicon-containing materials. Thirty-one patients (12 women, 19 men, median age 51 years) were interviewed using a structured questionnaire. Occupational exposure to silicon-containing chemicals was reported by 22.6% of the patients (12.9% to SiO2, 9.7% to asbestos), compared with 0% of control subjects (p<0.05). Our findings support the pathophysiologic role of silica in AAV.