Humoral Response of Different Types of SARS-CoV-2 Vaccines in Patients with Autoimmune Rheumatic Diseases: Experiences from a Serbian Cohort.

BACKGROUND: Data are scarce on the immunogenicity of coronavirus disease 2019 vaccines in patients with autoimmune rheumatic diseases (ARD). OBJECTIVES: To measure the immunoglobulin G (IgG) response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization and to evaluate clinical characteristics associated with seropositivity. METHODS: Samples were collected after the second and third doses of the three different types of vaccines in ARD patients. Seroconversion rates and IgG antibody S1/S2 titers were measured. RESULTS: The type of ARD diagnosis and previous treatment had no significant impact on the serum IgG antibody levels measured after the second (P = 0.489 and P = 0.330, respectively) and boost dose (P = 0.441 and P = 0.446, respectively). What made a significant difference regarding serum IgG antibody levels after the second dose was the type of SARS-CoV-2 vaccine. The difference was highly statistically significant for all vaccine types (P = 0.001 with the highest odds ratio for the mRNA vaccine). After the boost with the mRNA vaccine, all patients achieved a high level of serum IgG antibody levels (t = 10.31, P = 0.001). No ARD patients experienced serious post-vaccinal reactions. Eight patients developed COVID-19 before the boost dose. CONCLUSIONS: In ARDs patients, the highest level of serum IgG antibody against S1/S2 proteins was achieved with the mRNA vaccine, irrespective of the therapy applied or the type of the disease. We recommend a booster dose with mRNA vaccine in all ARDs for the highest SARS-CoV-2 protection without serious post-vaccinal reactions observed.

Circulating immune-complexes of IgG/IgM bound to B2-glycoprotein-I associated with complement consumption and thrombocytopenia in antiphospholipid syndrome.

Background: Antiphospholipid syndrome (APS) is a multisystemic autoimmune disorder characterized by thrombotic events and/or gestational morbidity in patients with antiphospholipid antibodies (aPL). In a previous single center study, APS-related clinical manifestations that were not included in the classification criteria (livedo reticularis, thrombocytopenia, leukopenia) were associated with the presence of circulating immune-complexes (CIC) formed by beta-2-glycoprotein-I (B2GP1) and anti-B2GP1 antibodies (B2-CIC). We have performed a multicenter study on APS features associated with the presence of B2-CIC. Methods: A multicenter, cross-sectional and observational study was conducted on 303 patients recruited from six European hospitals who fulfilled APS classification criteria: 165 patients had primary APS and 138 APS associated with other systemic autoimmune diseases (mainly systemic lupus erythematosus, N=112). Prevalence of B2-CIC (IgG/IgM isotypes) and its association with clinical manifestations and biomarkers related to the disease activity were evaluated. Results: B2-CIC prevalence in APS patients was 39.3%. B2-CIC-positive patients with thrombotic APS presented a higher incidence of thrombocytopenia (OR: 2.32, p=0.007), heart valve thickening and dysfunction (OR: 9.06, p=0.015) and triple aPL positivity (OR: 1.83, p=0.027), as well as lower levels of C3, C4 and platelets (p-values: <0.001, <0.001 and 0.001) compared to B2-CIC-negative patients. B2-CIC of IgM isotype were significantly more prevalent in gestational than thrombotic APS. Conclusions: Patients with thrombotic events and positive for B2-CIC had lower platelet count and complement levels than those who were negative, suggesting a greater degree of platelet activation.

A Lower Level of Post-Vaccinal Antibody Titer against Influenza Virus A H1N1 May Protect Patients with Autoimmune Rheumatic Diseases from Respiratory Viral Infections.

Background and Objectives: The concentration of antibodies against virus influenza A H1N1 in the titer (≥1:32) positively correlates with resistance to flu in healthy persons. In elderly and immune-compromised patients, an influenza vaccine may be less immunogenic. Hypothesis: A lower post-vaccinal antibody titer (≥1:16) may be sero-protective against respiratory viral infections in patients with autoimmune rheumatic diseases. Materials and Methods: Fifty patients with autoimmune rheumatic diseases (Systemic Lupus Erythematosus-24; Rheumatoid Arthritis-15; and Sjögren's Syndrome-11), who were at least 65 years old or whose relative disease duration (disease duration/age) was greater than 1/8, were examined. Thirty-four of them were vaccinated with a trivalent inactivated non-adjuvant influenza vaccine. The antibody concentration against influenza virus A H1N1 was measured using the standardized hemagglutination inhibition test and patients who got any respiratory viral infection were registered. To test the hypothesis, a correlative analysis was applied, followed by a binary logistic regression that included potential confounding variables, such as age, disease duration and therapy (personal/health-related conditions). Results: Vaccinated patients were significantly less affected by respiratory viral infections (21% vs. 75%). The lower titer considered (≥1:16) was significantly present more often among vaccinated patients (68% vs. 6%). The correlation between its presence/absence and that of respiratory viral infections was -0.34 (p < 0.05). The binary logistic regression evidenced the relevance of this correlation, confirming the hypothesis. Vaccination was associated with the 87.3% reduction in the likelihood of getting respiratory viral infections, whereas the lower antibody titer (≥1:16) was associated with the 77.6% reduction in the likelihood of getting respiratory viral infections. The vaccine was well tolerated by all patients and after vaccination no exacerbation of the underlying disease was observed. Conclusions: A lower antibody titer (≥1:16) against influenza virus A H1N1 could be protective against respiratory viral infections for certain autoimmune rheumatic diseases patients, which confirms the clinical effectiveness of influenza vaccination.

Cardiac manifestations in primary antiphospholipid syndrome and their association to antiphospholipid antibodies' types and titers-cross-sectional study of Serbian cohort.

OBJECTIVES: Antiphospholipid syndrome (APS) is multisystem autoimmune coagulopathy with antiphospholipid antibodies (aPL) in its ground, manifested as a primary disease (PAPS) or in the setting of other conditions, most commonly systemic lupus erythematosus. The objective of this cross-sectional study was to investigate various cardiac manifestations and their possible relation to aPL type and titer in a Serbian cohort of PAPS patients. METHODS: A total of 360 PAPS patients were analyzed and aPL analysis included detection of anticardiolipin antibodies (aCL: IgG/IgM), anti-ß2glycoprotein I (ß2GPI: IgG/IgM), and lupus anticoagulant (LA). Cardiac manifestations investigated were valvular lesions (comprehending valvular thickening and dysfunction not related to age and pseudoinfective endocarditis), coronary artery disease (CAD) with specific insight for myocardial infarction (MI), chronic cardiomyopathy (CMP), and acute decompensated heart failure (ADHF) as well as pulmonary hypertension (PH) and intracardiac thrombus presence. RESULTS: The prevalence of cardiac manifestations overall was 19.6%. There was a strong association between age and the majority of cardiac manifestations, as well as standard atherosclerotic risk factors. aCL IgG-positive patients had a higher prevalence of valvular lesions (p = 0.042). LA presence was significantly related to MI (p = 0.031) and PH (p = 0.044). CMP and ADHF were significantly related to higher titers of aCl IgG (p = 0.033, p = 0.025 respectively). Age and smoking were independent risk predictors for MI in PAPS with meaningful risk for LA positivity (OR 2.567 CI 0.671-9.820 p = 0.168). CONCLUSIONS: Certain cardiac manifestations in PAPS were related to certain aPL type and/or titer levels, imposing confirmation in prospective studies. Preventive actions, comprehending proper anticoagulant/antithrombotic therapy, and intense action against standard atherosclerotic risk factors are of utmost importance in this group of patients. Key Points • In Serbian patients with primary antiphospholipid syndrome (PAPS), prevalence of non-criteria cardiac manifestations was 19.6% and they were significantly related to certain antiphospholipid antibodies and titers. • Lupus anticoagulant was a meaningful predictor of myocardial infarction, enabling possible risk stratification and proper preventive and therapeutical strategies in this subgroup of PAPS patients. • Patients with high titers of aCL IgG are more prone to acute decompensated heart failure occurence, imposing careful follow-up of these patients • Based on the analysis of the Serbian PAPS cohort, even being non-criterial, cardiology manifestations are significantly present and inclusion of cardiologists in treatment and follow-up of these patients should be implied from the diagnosis establishment.

Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study.

BACKGROUND: Clostridioides difficile infection (CDI) is one of the most common healthcare-associated (HA) infections. Cancer patients, particularly haemato-oncological patients, have an increased risk for CDI due to more risk factors compared with non-cancer patients. The aim of this study was to investigate differences in outcomes associated with HA CDI in patients with solid and haematological malignancies compared with patients with no underlying malignant disease in a tertiary healthcare centre in Serbia. METHODS: A prospective cohort study was conducted including adult patients diagnosed with an initial episode of HA CDI. Their demographic and clinical characteristics associated with risk factors for CDI were documented. Outcomes such as all-cause 30-day mortality, cure of infection, diarrhoea relaps and recurrence of disease were followed. Patients were assigned to cancer and non-cancer groups. Within the cancer group, patients were divided into the solid tumour subgroup and haematological malignancy subgroup. RESULTS: During a 7-year period, HA CDI was observed in 28 (5.1%) patients with haematological malignancy, 101 (18.3%) patients with solid tumours and 424 (76.7%) non-cancer patients. Older age (OR 1.04, 95% CI 1.02 to 1.07, p<0.001), admission to the intensive care unit (ICU) (OR 2.61, 95% CI 1.37 to 4.95, p=0.003), mechanical ventilation (OR 5.19, 95% CI 2.78 to 9.71, p<0.001) and use of antibiotics prior to CDI (OR 1.04, 95% CI 1.02 to 1.06, p=0.02) were associated with increased mortality. Compared with patients with solid tumours, patients with haematological malignancy were younger (65 vs 57 years, p=0.015), did not require ICU admission (25.0% vs 0%) or mechanical ventilation (8.9% vs 0%) and were treated longer with antibiotics prior to CDI (14 vs 24 days, p=0.002). CONCLUSIONS: Patients with haematological malignancy were exposed to different risk factors for CDI associated with mortality compared with patients with solid tumours and non-cancer patients. Older age, ICU stay and mechanical ventilation, but not presence or type of cancer, predicted the all-cause 30-day mortality.

Ertapenem Articulating Spacer for the Treatment of Polymicrobial Total Knee Arthroplasty Infection.

Introduction. Periprosthetic joint infections (PJIs) are the primary cause of early failure of the total knee arthroplasty (TKA). Polymicrobial TKA infections are often associated with a higher risk of treatment failure. The aim of the study was to assess the efficacy of ertapenem loaded spacers in the treatment of polymicrobial PJI. Methods. There were 18 patients enrolled; nine patients with polymicrobial PJI treated with ertapenem loaded articulating spacers were compared to the group of 9 patients treated with vancomycin or ceftazidime loaded spacers. Results. Successful reimplantation with revision implants was possible in 66.67%. Ertapenem spacers were used in 6 cases in primary two-stage procedure and in 3 cases in secondary spacer exchange. Successful infection eradication was achieved in all cases; final reimplantation with revision knee arthroplasty implants was possible in 6 cases. Conclusion. Ertapenem can be successfully used as antimicrobial addition to the cement spacers in two-stage revision treatment of polymicrobial PJIs. However, this type of spacer may also be useful in the treatment of infections caused by monomicrobial extended spectrum beta-lactamases producing gram-negative bacilli. Further clinical studies are required to evaluate the efficacy and safety of ertapenem spacers in the treatment of polymicrobial and monomicrobial PJIs.

Influenza vaccination in autoimmune rheumatic disease patients.

Patients suffering from autoimmune rheumatic diseases have significantly higher risk of developing various infections compared to the healthy population. Our study included patients suffering from systemic lupus erythematosus (n = 30), rheumatoid arthritis (n = 37) or Sjögren's syndrome (n = 32), with stable underlying diseases status. In November 2010, 47 patients, including 35 subjects vaccinated annually during 2006-2010, received immunization against influenza with trivalent inactivated split vaccine, whereas 52 patients did not accept proposed vaccination in that period. The presence of viral (primarily influenza) and bacterial infections, parameters of disease activity (from the date of vaccination until April 2011), and titers of antibodies against A H1N1 were then monitored in vaccinated and unvaccinated patients. We have identified the importance of predisposing factors for influenza occurrence (i.e. previous respiratory infections and vaccinations in last five years, age, sex, type of disease and duration, medications, smoking) in those groups of patients. The incidence of influenza or bacterial complications (bronchitis) among vaccinated patients was significantly lower, compared to the non-vaccinated group. Importantly, there was no case of exacerbation of the underlying disease. The last vaccination in 2010 reduced the risk of influenza by 87%, but previous bacterial infections (bronchitis and pneumonia) increased influenza risk significantly. In the present study, we have shown the efficiency, sufficient immunogenicity and safety of modern influenza vaccine application in patients suffering from systemic lupus erythematosus, rheumatoid arthritis or Sjögren's syndrome.

Subdural tuberculous abscess of the lumbar spine in a patient with chronic low back pain.

INTRODUCTION: Despite modern imaging methods, tuberculous abscess in the subdural space of the spine can lead to misdiagnosis and to neurogical complications development, even more up to paraplegia. We presented an extremely rare case of subdural tuberculous abscess of the lumbar (L) spine and paraparesis in imunocompetent a 49-year-old patient. CASE REPORT: A patient with chronic L syndrome and a history of intervertebral (IV) disc L3 and L5 operations got severe back pain late in July 2007. At the same time the patient had a purulent collection in the left knee, and was treated with high doses of corticosteroids and antibiotics. Then, the patient got a high fever, the amplification of pain in the L spine and the development of paraparesis. Erythrocyte sedimentation rate was 108 mm/1 h, C-reactive protein 106.0 mg/L, white blood cell (WBC) 38.4 x 09/L with a left turn. Magnetic resonance imaging (MRI) of the spine was registered expansive formation in the spinal canal, from the level of the IV disc L2 to the mid-L4 vertebral body. This finding is a "spoke" in favor of the extrusion and sequestration of IV disc L3 with the cranial and caudal migration. The patient underwent an emergency neurosurgical operation. The diagnosis of subdural staphylococcal abscess of L spine was made. According to the antibiogram antibiotic therapy was applied but without effect on the course of the disease. Control MRI of the L spine showed spondylodiscitis L3/L4, abscess collection in the spinal canal and paravertebral muscle abscess. Late in September 2007 the patient underwent needle biopsy of the L3 vertebral body guided by computed tomography and the acid-fast bacilli (AFB) were found. Tuberculostatics were introduced in the therapy. Two years later the patient was without significant personal difficulties, and with normal clinical, laboratory and morphological findings. CONCLUSION: Subdural tuberculous abscess of the spine is extremely rare manifestation of spine tuberculosis. The exact and early diagnosis and adequate treatment of atypical form of spine tuberculosis are key factors of good prognosis.

Clinical manifestations, therapy and outcome of pandemic influenza A (H1N1) 2009 in hospitalized patients.

BACKGROUND/AIM: Increasing number of epidemiological and clinical studies to date showed that the pandemic influenza A (H1N1) 2009, by its characteristics, significantly differs from infection caused by seasonal influenza. Therefore, the information about clinical spectrum of manifestations, risk factors for severe form of the disease, treatment and outcome in patients with novel flu are still collected. METHODS; A total of 98 patients (mean age 32 +/- 15 years, range 14-88 years) with the signs and symptoms of novel influenza were treated in the Clinic for Infectious and Tropical Diseases, Military Medical Academy. There were 74 (75.5%) patients with suspected influenza A (H1N1) 2009, 10 (10.2%) with the likelihood and 14 (14.3%) with the confirmed influenza. In all the patients we registered the basic demographic data, risk factors for severe disease, symptoms and signs of influenza, laboratory tests and chest radiography. We analyzed antiviral therapy use and disease outcome (survived, died). RESULTS: The average time from the beginning of influenza A (H1N1) to the admission in hospital was 3 days (0-16 days) and from the moment of hospitalization to the Intensive Care Unit (ICU) admission was 2 days (0-5 days). There were 49 (50.0) patients, 20-29 years of age and 5 (5.1) patients older than 65. A total of 21 (21.4%) patients were with underlying disease, 18 (18.4%) were obese, 19 (19.4) were cigarette smokers. All of the patients had fever, 81 (82.6%) cough, while dyspnea and diarrhea were registered in 4 of the patients. In more than 75% of the patients laboratory tests were within normal limits. The real-time polymerase chain reaction (PCR) test for identification of influenza A (H1N1) 2009 was positive in 14 (77.8%), while pneumonia was verified in 30 (30.7%) of the patients. Six (6.1%) patients, mean age of 45 +/- 14 years (31-59 years) were admitted to the ICU, of whom five (5.1%) had Adult Respiratory Distress Syndrome (ARDS). Risk factors were registered more frequently in the patients with acute respiratory failure (14.2% vs 4.9%, p < 0.05). A total of 67 (68.4%) patients received oseltamivir, 89 (90.1%) was applied to antibiotics and 64 (65.3%) were treated with a combined therapy. Antiviral therapy was applied to 43 (43.3%) patients in the first 48 hours from the onset of the disease, of whom only one (3.4) developed ARDS. Fatal outcome was noted in 2.0% of the patients (2 of 98 patients) and in 33.3% of the patients treated in the ICU. CONCLUSION: Novel influenza A (H1N1) is most commonly manifested as a mild acute respiratory disease, which usually affects young healthy adults. A small number of the patients develop severe illness with acute respiratory failure and death. Patients seem to have benefit from antiviral therapy especially in first 48 hours.

[Infective endocarditis of a rare etiology (Serratia marcescens)]. / Infektivni endokarditis retke etiologije (Serratia marcescens).

Infective endocarditis (IE) is a unique diagnostic and therapeutic challenge. It is a severe disease, fatal before penicillin discovery. Atypical presentations frequently led to delayed diagnosis and poor outcome. There was little information about the natural history of the vegetations during medical treatment or the relation of morphologic changes in vegetation to late complications. Application of a new diagnostic criteria and echocardiography, increased the number of definite diagnosis. Trans-thoracic and trans-esophageal echocardiography had an established role in the management of patients with IE. The evolution of vegetation size, its mobility, and consistency, the extent of the disease, and the severity of valvular regurgutation were related to late complications. With therapeutic options including modern antibiotic treatment and early surgical intervention IE turned out to be a curable disease. Reduction in mortality also depended on prevention. Antibiotic prophylaxis of IE was important, but low mortality was also the result of early treatment, especially in the event of early recognition of symptoms and signs of the disease.