Living with axial spondyloarthritis: a cross-sectional survey of patient knowledge and perceptions.

Diagnosis and effective treatment of axial spondyloarthritis (AxSpA) are often delayed due to inadequate awareness and poor patient-physician communication. Some AxSpA patients fail to maintain an active lifestyle by exercising regularly, further worsening their disease management. The evolving concept of patient-centred care necessitates better understanding of patient awareness and their needs. We aimed to survey AxSpA patients to reflect on healthcare planning and management perspectives. Our self-administered questionnaire focused on perceptions of AxSpA diagnosis and management, particularly exploring issues of physical activity and active lifestyle. Satisfaction with AxSpA medical care and its accessibility, diagnostic delays, patient-physician communication, and support for disease management were also explored. This offline survey was arranged at the Department of Rheumatology, Immunology, and Internal Medicine of Jagiellonian University Medical College and Krakow University Hospital. We surveyed patients with AxSpA attending outpatient clinics between December 1st, 2023 and April 22nd, 2024. The questionnaire included questions on types of physical activities, barriers to exercising, satisfaction with medical care, patient-physician interactions, diagnostic delays, and use of teleconsultations. A total of 117 patients with AxSpA were enrolled (mean age 41.62 years). The majority (n = 93, 79.5%) were employed. There was a male predominance (69, 59%). The average diagnostic delay was 5.5 years. Notably, 104 (88.9%) responders perceived physical activity as a factor influencing their disease course. However, only 32 (27.35%) managed to exercise regularly (≥ 30 min, 2-3 times a week). The majority (70, 59.83%) were irregularly engaged in some form of physical activity, with 15 (12.8%) not exercising at all, and nearly half (48%) reported at least one barrier to maintaining a physically active lifestyle. Pain (32, 27.35%), fatigue (27, 23.08%), lack of motivation (17, 14.53%), and lack of time (12, 10.26%) were noted as barriers to exercising. The respondents preferred to exercise at home. The survey identified critical areas where patient dissatisfaction or uncertainty were notably prevalent: 38 (32.5%) were uncertain and 35 (30%) were dissatisfied with rehabilitation access. For spa therapy, 63 (53.85%) reported uncertainty and 23 (19.7%) expressed dissatisfaction. Only 48 (41%) were treated by a rehabilitation specialist last year. Only 23% of AxSpA patients took part in teleconsultations last year, and 65% preferred in-person visits. While AxSpA patients recognize the importance of physical activity, significant barriers exist to engaging them regularly in exercising. Addressing these barriers through personalized, motivational, and educational strategies could improve patient outcomes. Improving patient satisfaction with healthcare services, particularly in areas of rehabilitation and physician-patient communication, is crucial for improving the overall care of AxSpA patients.

Knowledge, perceptions, and practices of axial spondyloarthritis diagnosis and management among healthcare professionals: an online cross-sectional survey.

Spondyloarthritis (SpA) is a group of inflammatory disorders, including axial SpA (axSpA), characterized by inflammation in the spine and sacroiliac joints. Healthcare professionals have a crucial role in diagnosing and managing axSpA. Assessing their knowledge, perceptions, and practices is essential to enhance patient care. The objective of this study is to evaluate these factors by conducting an online survey. This online survey was performed using SurveyMonkey.com to assess healthcare professionals' knowledge, perceptions, and practices related to axSpA diagnosis, management, and monitoring. The questionnaire included questions about definitions, management strategies, monitoring approaches, treatment options, and barriers to care. Convenience sampling was used, and the data were analyzed descriptively by Microsoft Excel. One hundred sixty-four healthcare professionals participated; most respondents were rheumatologists from various geographic locations (27 countries). Most participants were familiar with axSpA definitions and diagnostic criteria, demonstrating high expertise. Variations were seen in follow-up intervals and diagnostic preferences, reflecting clinical heterogeneity. Seventy-two (43.9%) individuals had a multidisciplinary team, frequently including rheumatologists, physiotherapists, and radiologists. Of the participants, 73 (44.5%) had online/telephone follow-up sessions. The pharmacological and non-pharmacological treatment approaches varied, pointing to the importance of personalized care. Glucocorticoid use varied among countries. Recognizing inflammatory back pain, interpreting radiographs, and diagnosing early was essential to medical education. This study provides beneficial data on healthcare professionals' knowledge, perceptions, and practices regarding axSpA. While diagnostic familiarity and multidisciplinary approach are positives, there is a potential to standardize management, improve telemedicine services, remove barriers to physical activity, and optimize treatment options.

Impact of comorbidities on patient-reported outcomes in psoriatic arthritis: a single centre cohort study.

BACKGROUND: Comorbidities are frequent in psoriatic arthritis (PsA) and may contribute to worse health-related outcomes. Patient-reported outcomes (PROs) are used to evaluate the burden of the assessed disease. The aim of this study is to evaluate the impact of comorbidities on selected PROs in PsA. METHODS: Adult patients, diagnosed with PsA, based on CASPAR criteria, were included in this cross-sectional, observational study. Collected data encompassed the comorbidities and PROs (Health Assessment Questionnaire [HAQ], Multi-Dimensional Health Assessment Questionnaire [MDHAQ], 36-Item Short Form Health Survey [SF-36]). Standard statistic methods were performed for data assessment. RESULTS: There were 267 participants included in the study (54.7% females). The most prevalent comorbidities were cardiovascular diseases (CVD) (29.2 %). Multimorbidity was observed in 50.2% cases and was associated with poorer results of SF-36 questionnaire, regarding bodily pain (34.7 [30.1, 39.3] vs. 47.5 [43.1, 52.0]; p<0.01), physical functioning (52.1 [47.3, 56.9] vs. 63.1 [58.9, 67.4]; p<0.01) and role physical (28.5 [21.2, 35.9] vs. 42.8 [35.2, 50.4]; p<0.01). CVD were associated with poorer MDHAQFn score (ß=0.17, p<0.01), while mental disorders negatively influenced mental health (ß= -0.35, p<0.01), vitality (ß= -0.22, p<0.01), general health (ß= -0.19, p<0.01), social functioning (ß= -0.15, p=0.04) and role emotional (ß= -0.30, p<0.01) dimensions of SF-36. CONCLUSIONS: Multimorbidity exerts significant impact on physical aspects of quality of life (QoL) in PsA. CVD and mental disorders adversely influence functional capacity as well as mental and social dimensions of QoL, respectively. The impact of comorbidities should be taken into account by clinicians and researchers assessing PROs.

Artificial intelligence guided HRCT assessment predicts the severity of COVID-19 pneumonia based on clinical parameters.

BACKGROUND: The purpose of the study was to compare the results of AI (artificial intelligence) analysis of the extent of pulmonary lesions on HRCT (high resolution computed tomography) images in COVID-19 pneumonia, with clinical data including laboratory markers of inflammation, to verify whether AI HRCT assessment can predict the clinical severity of COVID-19 pneumonia. METHODS: The analyzed group consisted of 388 patients with COVID-19 pneumonia, with automatically analyzed HRCT parameters of volume: AIV (absolute inflammation), AGV (absolute ground glass), ACV (absolute consolidation), PIV (percentage inflammation), PGV (percentage ground glass), PCV (percentage consolidation). Clinical data included: age, sex, admission parameters: respiratory rate, oxygen saturation, CRP (C-reactive protein), IL6 (interleukin 6), IG - immature granulocytes, WBC (white blood count), neutrophil count, lymphocyte count, serum ferritin, LDH (lactate dehydrogenase), NIH (National Institute of Health) severity score; parameters of clinical course: in-hospital death, transfer to the ICU (intensive care unit), length of hospital stay. RESULTS: The highest correlation coefficients were found for PGV, PIV, with LDH (respectively 0.65, 0.64); PIV, PGV, with oxygen saturation (respectively - 0.53, -0.52); AIV, AGV, with CRP (respectively 0.48, 0.46); AGV, AIV, with ferritin (respectively 0.46, 0.45). Patients with critical pneumonia had significantly lower oxygen saturation, and higher levels of immune-inflammatory biomarkers on admission. The radiological parameters of lung involvement proved to be strong predictors of transfer to the ICU (in particular, PGV ≥ cut-off point 29% with Odds Ratio (OR): 7.53) and in-hospital death (in particular: AIV ≥ cut-off point 831 cm3 with OR: 4.31). CONCLUSIONS: Automatic analysis of HRCT images by AI may be a valuable method for predicting the severity of COVID-19 pneumonia. The radiological parameters of lung involvement correlate with laboratory markers of inflammation, and are strong predictors of transfer to the ICU and in-hospital death from COVID-19. TRIAL REGISTRATION: National Center for Research and Development CRACoV-HHS project, contract number SZPITALE-JEDNOIMIENNE/18/2020.

CRACoV-HHS: an interdisciplinary project for multi-specialist hospital and non-hospital care for patients with SARS-CoV-2 infection as well hospital staff assessment for infection exposure.

The complex course of the COVID-19 and the distant complications of the SARS-CoV-2 infection still remain an unfaded challenge for modern medicine. The care of patients with the symptomatic course of COVID-19 exceeds the competence of a single specialty, often requiring a multispecialist approach. The CRACoV-HHS (CRAcow in CoVid pandemic - Home, Hospital and Staff) project has been developed by a team of scientists and clinicians with the aim of optimizing medical care at hospital and ambulatory settings and treatment of patients with SARS-CoV-2 infection. The CRACoV project integrates 26 basic and clinical research from multiple medical disciplines, involving different populations infected with SARS-CoV-2 virus and exposed to infection. Between January 2021 and April 2022 we plan to recruit subjects among patients diagnosed and treated in the University Hospital in Cracow, the largest public hospital in Poland, i.e. 1) patients admitted to the hospital due to COVID-19 [main module: 'Hospital']; 2) patients with signs of infection who have been confirmed as having SARS-CoV-2 infection and have been referred to home isolation due to their mild course (module: 'Home isolation'); 3) patients with symptoms of infection and high exposure to SARS- CoV-2 who have a negative RT-PCR test result. In addition, survey in various professional groups of hospital employees, both medical and non-medical, and final-fifth year medical students (module: 'Staff') is planned. The project carries both scientific and practical dimension and is expected to develop a multidisciplinary model of care of COVID-19 patients as well as recommendations for the management of particular groups of patients including: asymptomatic patient or with mild symptoms of COVID-19; symptomatic patients requiring hospitalization due to more severe clinical course of disease and organ complications; patient requiring surgery; patient with diabetes; patient requiring psychological support; patient with undesirable consequences of pharmacological treatment.

Severe hypereosinophilic syndrome successfully treated with a monoclonal antibody against interleukin 5 receptor α - benralizumab.

Hypereosinophilic syndrome (HES) is a group of a rare diseases characterized by marked eosinophilia in blood or tissue and eosinophil-related clinical manifestations. Benralizumab is a humanized, monoclonal antibody against interleukin 5 (IL-5) receptor α, which is expressed on human eosinophils. Here, we present the case of a patient with severe HES in whom treatment with benralizumab, an anti-IL-5 receptor monoclonal antibody, was initiated 6 months ago. Prior to benralizumab administration, the patient was treated with glucocorticoids (GS) and mepolizumab. However, instead of the applied treatment and normal level of peripheral eosinophils the patient presented with fluctuating lower respiratory tract symptoms and recurrent exacerbations of HES. Treatment with benralizumab (30 mg s.c. every 4-6 weeks) was started, resulting in significant improvement of respiratory signs and symptoms, normalization of eosinophil count and significant reduction of the methylprednisolone dose (after 5 doses of benralizumab administration). No substantial side effects have been noted during treatment and 6-month follow-up. We argue that in the severe and relapsing course of HES, rescue treatment with benralizumab should be taken into account, particularly in cases of relative inefficacy of GS and mepolizumab.

Decreased number of regulatory T lymphocytes is related to inflammation and number of CD8+ T cells expressing programmed cell death protein-1 in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder related to recurrent infections, as well as a range of non-infectious manifestations including autoimmune and inflammatory disorders. We hypothesized that patients with CVID and different clinical phenotypes would demonstrate alterations in lymphocyte T subsets, including T lymphocytes expressing programmed cell death protein 1 (PD-1), and regulatory T lymphocytes. We performed flow cytometry in two CVID groups: group 1 with infections only, and group 2 with infections and concomitant noninfectious manifestations. Patients were 18-59 years old (mean 35.8 years of age). Increased proportions of CD8+PD-1+ T cells and reduced regulatory T cells were associated with lymphadenopathy. Amount of regulatory T cells correlated with CD8+PD-1+ T lymphocytes (r = 0.54; p = 0.013), and with CRP (r = -0.64; p = 0.004). Forty percent of patients expressed manifestations in addition to infections (group 2), and they had reduction in number of regulatory T cells [8 (3-12) vs. 24 (11-26)/µl; p = 0.034), naive CD4+ T lymphocytes [36 (27-106) vs. 149 (81-283)/µl; p = 0.034], and elevated C-reactive protein (CRP) [5.33 (3.15-8.82) vs. 1 (1-2.16) mg/l; p = 0.003] in comparison to group 1. In conclusion, the amount of CD8+ T cells expressing PD-1 is associated with lymphadenopathy and number of regulatory T cells in patients with CVID. Patients with CVID and non-infectious complications have increased level of inflammation and alterations in regulatory T cells.

Efficacy and Safety of Human Intravenous Immunoglobulin 10% (Panzyga®) in Patients with Primary Immunodeficiency Diseases: a Two-Stage, Multicenter, Prospective, Open-Label Study.

PURPOSE: To assess the efficacy and safety of panzyga® (intravenous immunoglobulin 10%) in preventing serious bacterial infections (SBIs) in patients with primary immunodeficiency diseases (PIDs), a prospective, open-label, multicenter, phase 3 study and an open-label extension study were undertaken. METHODS: Initially, the study drug (infusion rate ≤0.08 mL/kg/min) was administered at intervals of 3 or 4 weeks for 12 months, followed by 3 months of panzyga® at infusion rates increasing from 0.08 to 0.14 mL/kg/min. The primary endpoint in the main study was the rate of SBIs per patient-year on treatment. Secondary outcomes included non-serious infections, work/school absence, episodes of fever, quality of life, and adverse events (AEs). RESULTS: The main study enrolled 51 patients (35% female, mean age 26.8 years), with 21 participating in the extension study. The rate of SBIs per patient-year was 0.08 in the total population; there were four SBIs in the 4-weekly treatment group (2/30 patients) and none in the 3-weekly group (n = 21). Compared with 4-weekly treatment, 3-weekly treatment was associated with a higher rate of upper respiratory tract infections (RTIs), ear infections, and work/school absences, but a lower rate of lower RTIs and fever. Treatment was generally well tolerated; no AE led to treatment withdrawal or death. CONCLUSIONS: Overall, the use of panzyga® in patients with antibody-deficient PID was associated with a low rate of AEs and was effective in preventing SBIs, exceeding US FDA and European Medicines Agency recommendations for efficacy.

Endothelial dysfunction is independent of inflammation and altered CCR7 T cell expression in patients with ankylosing spondylitis.

OBJECTIVES: The accumulation of CCR7 (chemokine receptor 7) positive cells in the vessel wall may be involved in endothelial dysfunction and subsequent accelerated atherogenesis. CCR7 plays a crucial role in T cell and monocyte migration/homing and in priming of naive T lymphocytes in non-lymphoid tissues in chronic inflammatory diseases. Our objective was to investigate the endothelial function and inflammation-driven expression of CCR7 on T lymphocytes in patients with ankylosing spondylitis (AS). METHODS: We performed flow cytometry to assess the distribution of peripheral blood T cell subpopulations in the context of serum inflammatory markers (TNF-α, IL-6, sICAM-1) and asymmetric dimethylarginine (ADMA) in 38 patients with AS with active disease, and in 20 healthy controls. RESULTS: Patients with AS demonstrated higher ADMA (0.74±0.2 µmol/l vs. 0.64±0.15 µmol/l; p=0.03), as well as elevated inflammatory markers (TNFα, IL-6, sICAM-1) and increased proportions of circulating CCR7-positive lymphocytes largely attributable to elevated CD8+ naive T cells (47.1±17 vs. 34.3±13.1%; p=0.005). However, ADMA did not correlate with either CCR7-positive lymphocytes or inflammatory markers. CONCLUSIONS: We found an increased percentage of peripheral CCR7 T cells accompanied by endothelial dysfunction in patients with AS. The lack of direct associations between ADMA and inflammation may suggest the presence of other pathogenic mechanisms contributing to accelerated atherogenesis and increased cardiovascular risk in AS.

Arterial stiffness is not increased in patients with short duration rheumatoid arthritis and ankylosing spondylitis.

Patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have increased cardiovascular (CV) morbidity and mortality. Arterial stiffness is an independent predictor of CV events. The aim of the study was to assess arterial stiffness and inflammatory markers in patients with short duration chronic arthritis. We assessed carotid-femoral pulse wave velocity (PWV), augmentation index (AIx), traditional CV risk factors and inflammatory and endothelial markers in 71 chronic arthritis patients (RA and AS) and in 29 healthy controls. We did not find differences in PWV (for RA, AS and controls, respectively: 10 [8.8-10.9] versus 10.7 [9.1-11.8] versus 9.2 [8.3-11.4] m/s; p = .14) and AIx (for RA, AS and controls, respectively: 24.3 ± 11.5 versus 5.7 ± 12.4 versus 10 ± 12.8%; p = .22). Both groups of arthritis patients had active disease with significantly elevated inflammatory markers compared to controls. There were no correlations between endothelial and inflammatory markers and parameters of arterial stiffness in arthritis patients. When analyzing arthritis patients according to median of PVW, there were no significant differences in inflammatory and endothelial markers. We found that in patients with short duration active RA and AS arterial stiffness was not increased and furthermore, there was no association between markers of systemic inflammation and arterial stiffness.

Knowledge of rare diseases among health care students ­ the effect of targeted education

BACKGROUND: Poor knowledge on rare diseases (RD) results in a significant delay in their diagnosis and treatment. So far there are no standards of university education in RD. We assessed knowledge on RD among healthcare students and the effectiveness of targeted education. METHODS: We conducted an internet-based survey among students of the faculty of medicine, pharmacy and health sciences. Questions regarded personal information, definition and epidemic data on RD. The survey was used to assess the effect of targeted education about RD in an additional group of students. RESULTS: We enrolled 270 students (females: n=181; 67%), aged 22±1.7 years. Most of them (87.8%) declared to be familiar with the term RD. However only 20.7% knew the correct definition of RD, 14% knew that RD affect a significant (6-8%) proportion of population, 21.4% that there are 5-8 thousands of different RD' entities, 73.7% recognized the most common cause of RD. 12.6% knew, that the RD most frequently occur in the adulthood. Targeted education applied in the additional group of 18 students resulted in a significant improvement of students' knowledge on RD: definition (by 33%; p=0.007), percentage of population affected by RD (by 67%; p=0.001 ), total number of different RD (by 61%; p=0.003), time of onset of RD (by 61% p=0.003). CONCLUSIONS: Despite the declared recognition of the term: RD, knowledge on RD among medical students is poor independently on the year of study. However it can be improved with use of targeted education.

[Reccurent mycobacterial diseases in patients with impaired axis IL-12/INF-gamma]. / Rola ukladu IL-12/INF-gamma w nawrotowych mykobakteriozach.

Mycobacteria is a large group of pathogens that are common in environment, in soil and tap water. Although mycobacteria [non tuberculosis mycobacteria] can inhabit body surface without causing any disease in the circumstances of primary or secondary immunodeficiency can cause clinically significant organ or systemic damage. Defect of IL-12/INFgamma axis is an example of primary immunodeficiency that predispose to mycobacterial infections while protection against other microorganisms is not damaged. We present review of known defects of IL-12/IFNgamma axis and brief presentation of our own experience.

A challenging diagnosis of idiopathic multicentric Castleman disease with complex systemic presentation: A case report.

Key Clinical Message: Idiopathic multicentric Castleman disease (iMCD) is challenging to diagnose due to clinical similarities with other conditions, such as Still's disease. Once diagnosed, iMCD may be effectively managed with the anti-interleukin-6 antibody siltuximab. Abstract: Here, we present the case of a 19-year-old Polish woman with persistent fever and enlarged lymph nodes and whose diagnosis remained inconclusive following initial clinical assessments and extensive laboratory analyses. The patient had subsequent complaints of joint pain and erythema which were suspicious of Still's disease and resolved with treatment with tocilizumab. Later, the progression of symptoms, such as lymphadenopathy, and elevated interleukin-6 levels were consistent with Castleman disease, leading to the diagnosis of idiopathic multicentric Castleman disease seven years after the patient first reported symptoms. Treatment with the anti-interleukin-6 antibody siltuximab resulted in complete symptom resolution and normalization of inflammatory parameters. No adverse events were reported due to treatment with siltuximab.

Chemerin as a Potential Marker of Resolution of Inflammation in COVID-19 Infection.

Chemerin is one of the specialized pro-resolving mediators that participate in the early phase of inflammation and contribute to the initiation of the pro-resolving response. There is a paucity of data regarding the time course of chemerin during acute infections. We aimed to evaluate the sequence of inflammatory responses in the acute COVID-19 phase throughout onset and resolution of inflammation. We evaluated changes in selected biomarkers in COVID-19 survivors on the 7-day and 28-day follow up. Chemerin was lower in patients with baseline moderate/severe disease at day 7 compared with asymptomatic patients and individuals with mild illness (7265 [5526−9448] vs. 8730 [6888−11,058] pg/mL; p = 0.03). Only in patients with moderate/severe disease, but not in those with mild symptoms, were chemerin concentrations decreased one week after infection onset compared with baseline (7265 [5526−9448] vs. 8866 [6383−10,690] pg/mL; p < 0.05) with a subsequent increase on the 28-day follow up (9313 [7353−11,033] pg/mL; p < 0.05). Resolution of inflammation in the group of moderate/severe SARS-CoV2 infection was associated with increasing serum concentrations of chemerin, contrary to pro-inflammatory cytokines and adipokines (pentraxin 3, TNFα, resistin, leptin). A similar pattern of angiopoietin-2 dynamics may suggest signs of enhanced vascularization as a consequence of acute SARS-CoV2 infection.

COVID-19 in unvaccinated patients with inborn errors of immunity-polish experience.

At the beginning of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, patients with inborn errors of immunity (IEI) appeared to be particularly vulnerable to a severe course of the disease. It quickly turned out that only some IEI groups are associated with a high risk of severe infection. However, data on the course of Coronavirus Disease 2019 (COVID-19) in patients with IEI are still insufficient, especially in children; hence, further analyses are required. The retrospective study included 155 unvaccinated people with IEI: 105 children and 50 adults (67.7% and 32.3%, respectively). Male patients dominated in the study group (94 people, 60.6%). At least two comorbidities were found in 50 patients (32.3%), significantly more often in adults (56% vs. 21%). Adult patients presented significantly more COVID-19 symptoms. Asymptomatic and mildly symptomatic course of COVID-19 was demonstrated in 74.8% of the entire group, significantly more often in children (88.6% vs. 46%). Moderate and severe courses dominated in adults (54% vs. 11.4%). Systemic antibiotic therapy was used the most frequently, especially in adults (60% vs. 14.3%). COVID-19-specific therapy was used almost exclusively in adults. In the whole group, complications occurred in 14.2% of patients, significantly more often in adults (30% vs. 6.7%). In the pediatric group, there were two cases (1.9%) of multisystem inflammatory syndrome in children. Deaths were reported only in the adult population and accounted for 3.9% of the entire study group. The death rate for all adults was 12%, 15.4% for adults diagnosed with common variable immunodeficiency, 12.5% for those with X-linked agammaglobulinemia, and 21.4% for patients with comorbidity. The results of our study imply that vaccinations against COVID-19 should be recommended both for children and adults with IEI. Postexposure prophylaxis and early antiviral and anti-SARS-CoV-2 antibody-based therapies should be considered in adults with IEI, especially in those with severe humoral immune deficiencies and comorbidity.

Preparations of intravenous immunoglobulins diminish the number and proinflammatory response of CD14+CD16++ monocytes in common variable immunodeficiency (CVID) patients.

We have studied the effect of intravenous immunoglobulins (IVIG) on monocyte subpopulations and cytokine production in patients with CVID. The absolute number of CD14(+)CD16(++) monocytes decreased on average 2.5-fold 4h after IVIG and after 20h returned to the baseline. The cytokine level in the supernatants of peripheral blood mononuclear cells (PBMC) after ex vivo LPS stimulation demonstrated the >2-fold decrease in TNF production 4h after IVIG. The TNF expression, which is higher in the CD14(+)CD16(++) monocytes, was decreased in these cells by IVIG in 4/7 CVID cases. In vitro exposure of the healthy individuals' monocytes to the IVIG preparation resulted in reduced TNF production, which was overcome by blockade of the FcγRIIB in the CD14(+)CD16(++) CD32B(high) monocytes. Our data suggest that reduction in the number of CD14(+)CD16(++) monocytes and the blockade of their cytokine production via triggering CD32B can contribute to the anti-inflammatory action of IVIG.

[Two siblings with an IL-12 and IFN-γ production disorder diagnosed with pulmonary mycobacteriosis caused by M. kansasii. Mendelian susceptibility to mycobacterial infection: an overview of literature]. / I Oddzial Chorób Pluc Krakowskiego Szpitala Specjalistycznego im. Jana Pawla II Ordynator: dr n. med. P. Nalepa.

Two previously healthy siblings were diagnosed with pulmonary mycobacteriosis caused by M. kansasii. During examination both patients were diagnosed with an interleukin 12 (IL-12) and interferon γ (IFN-γ) production disorder of the stimulated lymphocytes. The given genetic defect conditions the occurrence of the Mendelian susceptibility to mycobacterial infection (MSMD). The patients fulfilled clinical, radiological, and bacteriological criteria for diagnosis of mycobacteriosis laid out by American Thoracic Society in 2007. After 13 months of standard treatment the ailments receded, and radiological remission, as well as a 12-month-lasting sputum negativity was achieved. The prognosis for the patients remains uncertain. The genetic conditioning to mycobacterial infections may cause disease recurrences or other mycobacterial illnesses. The patients will need to be checked systematically by pulmonologist. It is not known whether the offspring of the patients are exposed to general Baccillus Calmette-Guérin infection due to the compulsory vaccinations against tuberculosis, and whether the risk of complications is higher than the potential risk of coming down with hematogenous TB in childhood.

Pharmacokinetics of a novel human intravenous immunoglobulin 10% in patients with primary immunodeficiency diseases: Analysis of a phase III, multicentre, prospective, open-label study.

Intravenous immunoglobulin (IVIG) therapy is commonly used to treat patients with primary antibody deficiency. This prospective, open-label, non-randomised, multicentre, phase III trial investigated the pharmacokinetics of a new 10% liquid IVIG product (panzyga®; Octapharma) in 51 patients aged 2-75 years with common variable immunodeficiency (n = 43) or X-linked agammaglobulinaemia (n = 8). Patients were treated with IVIG 10% every 3 (n = 21) or 4 weeks (n = 30) at a dose of 200-800 mg/kg for 12 months. Total immunoglobulin G (IgG) and subclass concentrations approximately doubled from pre- to 15 min post-infusion. The maximum concentration of total IgG (mean ±â€¯SD) was 21.82 ±â€¯5.83 g/L in patients treated 3-weekly and 17.42 ±â€¯3.34 g/L in patients treated 4-weekly. Median trough IgG concentrations were nearly constant over the course of the study, remaining between 11.0 and 12.2 g/L for patients on the 3-week schedule and between 8.10 and 8.65 g/L for patients on the 4-week schedule. The median terminal half-life of total IgG was 36.1 (range 18.5-65.9) days, with generally similar values for the IgG subclasses (26.7-38.0 days). Median half-lives for specific antibodies ranged between 21.3 and 51.2 days for anti-cytomegalovirus, anti-Haemophilus influenzae, anti-measles, anti-tetanus toxoid, anti-varicella zoster virus antibodies, and anti-Streptococcus pneumoniae subtype antibodies. Overall, IVIG 10% demonstrated pharmacokinetic properties similar to those of other commercial IVIG 10% preparations and 3- or 4-weekly administration achieved sufficient concentrations of IgG, IgG subclasses, and specific antibodies, exceeding the recommended level needed to effectively prevent serious bacterial infections.

Elevated markers of inflammation and endothelial activation and increased counts of intermediate monocytes in adult survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Adult survivors of childhood malignancy are prone to accelerated atherogenesis and late cardiovascular complications. Plaque formation is initiated by recruitment of monocytes and T-cells into the intima, mediated by adhesion molecules and chemokines expressed by activated endothelial cells. AIM: To assess markers of inflammatory activity, endothelial activation as well as monocyte heterogeneity in adult survivors of childhood acute lymphoblastic leukemia (ALL) who had been treated with chemotherapy without cranial irradiation. METHODS AND RESULTS: We studied 27 (age: 18-28 years) healthy survivors of childhood ALL and 20 controls (age: 20-31 years). Flow cytometry was used to identify monocyte subsets: classical CD14(++)CD16(-), intermediate CD14(++)CD16(+) and nonclassical CD14(+)CD16(++) monocytes which were further characterized by their expression of HLA-DR and ß2-integrins CD11b/CD18 and CD11c/CD18. In ALL survivors we found increased levels of pentraxin-3 (median [interquartile range]: 0.63 [0.36-0.94] vs. 0.40 [0.32-0.57] ng/ml; p = 0.03), soluble vascular cell adhesion molecule-1 (687 [597-761] vs. 558 [534-702]ng/ml; p = 0.02), osteoprotegerin (mean ± SD: 5.24 ± 1.00 vs. 4.42 ± 1.34 pmol/l; p = 0.02) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (107.0 ± 23.6 vs. 89.5 ± 18.9 pg/ml; p = 0.01), whereas C-reactive protein, interleukin 6 and 18, TNF-α, monocyte chemotactic protein-1 and soluble intercellular adhesion molecule-1 were unchanged. Former ALL patients exhibited elevated counts of intermediate monocytes (6.3 ± 4.0 vs. 4.3 ± 1.5% of blood monocytes; p = 0.03). CD11b/CD18 and CD11c/CD18 expression on intermediate monocytes tended to be higher in ALL survivors (1917 ± 993 vs. 1396 ± 673 MFI [median fluorescence intensity]; p = 0.06 and 3883 ± 1445 vs. 3185 ± 645 MFI; p = 0.05, respectively). CONCLUSION: Our findings suggest chronic inflammatory activation and immune dysregulation in adult survivors of childhood ALL, which can translate into late cardiovascular morbidity.

Elevated asymmetric dimethylarginine in young adult survivors of childhood acute lymphoblastic leukemia: a preliminary report.

BACKGROUND: Adult survivors of childhood malignancy are predisposed to late cardiovascular (CV) complications. Our aim was to estimate plasma levels of the endogenous nitric oxide formation inhibitor asymmetric dimethylarginine (ADMA), in long-term survivors of childhood acute lymphoblastic leukemia (ALL) treated with only chemotherapy. METHODS: ADMA and its isomer symmetric dimethylarginine (SDMA) were measured in 25 former ALL patients (aged 18-28 years) who had survived without recurrent disease ≥ 5 years from completing chemotherapy without cranial irradiation, and in 20 healthy controls (aged 20-31 years). RESULTS: Characteristics of the both groups were similar, except for lower high-density lipoproteins-cholesterol (HDL-C) in ALL survivors. Compared to controls, the former ALL patients exhibited significant, albeit small, rises in levels of ADMA (0.63 ± 0.09 [SD] vs. 0.57 ± 0.07 µmol/L; p=0.016), but not SDMA, with a consequently increased ADMA to SDMA ratio (1.08 ± 0.22 vs. 0.91 ± 0.16; p=0.004). The effect of former ALL on ADMA was attenuated (intergroup p=0.10 [ANCOVA]) upon adjustment for HDL-C (ADMA vs. HDL-C regression coefficient: -0.065 ± 0.030 [SEM]; p=0.03). CONCLUSIONS: ADMA is elevated in adult childhood ALL survivors, which can reflect late detrimental chemotherapy effects, partially related to minor lipid profile changes. Whether these subtle ADMA elevations might herald future CV morbidity, remains to be elucidated.