Антицитрулінові антитіла в діагностиці артритів у дітей

Віходячи з проведеного дослідження, описаного в роботі, можна дійти висновку, що серед дітей із різними формами артритів тільки 4,8% пацієнтів були серопозитивними за РФ, та 23,8% дітей – за рівнем АЦЦП. Прогнастичне значення підвищеного рівня АЦЦП у дітей із РеА полягає в високій вірогідності розвитку ЮРА, що обумовлює більш ретельне їх спостереження із застосуванням індивідуальних схем профілактичного лікування. При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/1128

From decision to reflection:understanding the experiences and unmet care needs of patients treated with immunotherapy for melanoma in the adjuvant or metastatic setting

BACKGROUND: Despite increased use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma, little is known about patient experiences during this treatment. This study aimed to gain an in-depth understanding of experiences and unmet care needs of patients treated in the adjuvant or metastatic setting for advanced melanoma regarding their ICI treatment trajectory.METHODS:Interviews and focus groups were conducted among 35 patients treated with ICIs in the adjuvant setting for completely resected stage III (n = 14), or in the metastatic setting for irresectable stage IV (n = 21) melanoma. A thorough thematic content analysis was conducted.RESULTS: Three main themes were identified. When (1) dealing with uncertainty in the decision-making process, adjuvant patients explored the pros and cons, whereas metastatic patients considered immunotherapy their only viable option. Both groups expressed the need for additional guidance. In (2) navigating the immunotherapy course, both perceived the trajectory as intense, experienced a major impact on their and their (close) relatives' lives, and felt the need to (re)gain control. When (3) looking back on the immunotherapy experience, metastatic patients generally felt relieved, while among adjuvant patients, feelings of doubt regarding their choice for ICIs were also reported.CONCLUSIONS: ICI treatment is perceived as intensive for both patient groups, facing both comparable and distinct challenges throughout the treatment trajectory, underscoring the need for stage-specific, individualised guidance. Options regarding flexible follow-ups, low-threshold contact and psychosocial support throughout the treatment trajectory should be explored.</p

From decision to reflection:understanding the experiences and unmet care needs of patients treated with immunotherapy for melanoma in the adjuvant or metastatic setting

BACKGROUND: Despite increased use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma, little is known about patient experiences during this treatment. This study aimed to gain an in-depth understanding of experiences and unmet care needs of patients treated in the adjuvant or metastatic setting for advanced melanoma regarding their ICI treatment trajectory.METHODS:Interviews and focus groups were conducted among 35 patients treated with ICIs in the adjuvant setting for completely resected stage III (n = 14), or in the metastatic setting for irresectable stage IV (n = 21) melanoma. A thorough thematic content analysis was conducted.RESULTS: Three main themes were identified. When (1) dealing with uncertainty in the decision-making process, adjuvant patients explored the pros and cons, whereas metastatic patients considered immunotherapy their only viable option. Both groups expressed the need for additional guidance. In (2) navigating the immunotherapy course, both perceived the trajectory as intense, experienced a major impact on their and their (close) relatives' lives, and felt the need to (re)gain control. When (3) looking back on the immunotherapy experience, metastatic patients generally felt relieved, while among adjuvant patients, feelings of doubt regarding their choice for ICIs were also reported.CONCLUSIONS: ICI treatment is perceived as intensive for both patient groups, facing both comparable and distinct challenges throughout the treatment trajectory, underscoring the need for stage-specific, individualised guidance. Options regarding flexible follow-ups, low-threshold contact and psychosocial support throughout the treatment trajectory should be explored.</p

Distal muscle weakness is a common and early feature in long-term enzyme-treated classic infantile Pompe patients

Background: Enzyme replacement therapy (ERT; alglucosidase alfa) has improved the prospects for patients with classic infantile Pompe disease considerably. However, over time we noticed that many of these children exhibit distal muscle weakness at an early age, which is in contrast to the primarily proximal and axial muscle weakness in patients with late-onset Pompe disease. This was reason to study the prevalence and severity of distal muscle weakness, and the sequence of muscle involvement over time in patients that had learned to walk under ERT. Methods: In this prospective, single-center cohort study, we studied 16 classic infantile patients. We used video recordings that were made during regular standardized assessments to investigate distal muscle function (active dorsiflexion of the feet during walking; ability to use a pincer grasp/actively extend the fingers) and proximal muscle function (standing up from a supine position; raising the arms above the head). Results: Median age at start of ERT was 3.2 months (0.1–5.8 months), median age at study end was 5.6 years (2.9– 18.2 years). Six patients (6/16, 38%) initially had no evident signs of distal muscle weakness and developed a gait with active dorsiflexion of the feet. The other 10 patients never exhibited active dorsiflexion of the feet during walking. At study-end two patients showed no loss of distal muscle function. A subset of five patients (5/16, 31%) developed also weakness of the hands, particularly of the extensors of the 3rd and 4th digit. Conclusions: We found that the majority (14/16, 88%) of patients who had learned to walk exhibited distal muscle weakness of the lower extremities, while a subset (5/16, 31%) also developed weakness of the hands. The distal muscle weakness was often more serious than, and preceded the development of, the proximal muscle weakness

Effects of higher and more frequent dosing of alglucosidase alfa and immunomodulation on long-term clinical outcome of classic infantile Pompe patients

The aim of this study was to compare the long-term outcome of classic infantile Pompe patients treated with 20 mg/kg alglucosidase alfa every other week (eow) to those treated with 40 mg/kg/week, and to study the additional effect of immunomodulation. Six patients received 20 mg/kg eow and twelve 40 mg/kg/week. Five patients were cross-reactive immunologic material (CRIM)-negative, two in the 20 mg, three in the 40 mg group. We compared (ventilator-free) survival, motor outcome, infusion associated reactions (IARs), and antibody formation. From 2012 on patients >2 months in the 40 mg group also received immunomodulation with rituximab, methotrexate, and intravenous immunoglobulin (IVIG) in an enzyme replacement therapy (ERT)-naïve setting. Survival was 66% in the 20 mg group and 92% in the 40 mg group. Ventilator-free survival was 50% and 92%. Both CRIM-negative patients in the 20 mg group died, whereas all three are alive in the 40 mg group. In the 20 mg group, 67% learned to walk compared with 92% in the 40 mg group. At the age of 3 years, 33% and 92% were able to walk. Peak antibody titers ranged from 1:1250 to 1:31 250 in the 20 mg group and from 1:250 to 1:800 000 in the 40 mg group. Five patients of the 40 mg group of whom two CRIM-negative also received immunomodulation. B-cell recovery was observed between 5.7 and 7.9 months after the last dose of rituximab. After B-cell recovery titers of patients with and without immunomodulation were similar (ranges 1:6 250-1:800 000 and 1:250-1:781 250). This study shows that classic infantile patients treated with 40 mg/kg/week from the start to end have a better (ventilator-free) survival and motor outcome. Immunomodulation did not prevent antibody formation in our study

A Restricted Role for FcγR in the Regulation of Adaptive Immunity.

By their interaction with IgG immune complexes, FcγR and complement link innate and adaptive immunity, showing functional redundancy. In complement-deficient mice, IgG downstream effector functions are often impaired, as well as adaptive immunity. Based on a variety of model systems using FcγR-knockout mice, it has been concluded that FcγRs are also key regulators of innate and adaptive immunity; however, several of the model systems underpinning these conclusions suffer from flawed experimental design. To address this issue, we generated a novel mouse model deficient for all FcγRs (FcγRI/II/III/IV-/- mice). These mice displayed normal development and lymphoid and myeloid ontogeny. Although IgG effector pathways were impaired, adaptive immune responses to a variety of challenges, including bacterial infection and IgG immune complexes, were not. Like FcγRIIb-deficient mice, FcγRI/II/III/IV-/- mice developed higher Ab titers but no autoantibodies. These observations indicate a redundant role for activating FcγRs in the modulation of the adaptive immune response in vivo. We conclude that FcγRs are downstream IgG effector molecules with a restricted role in the ontogeny and maintenance of the immune system, as well as the regulation of adaptive immunity

The limited storage capacity of gonadal adipose tissue directs the development of metabolic disorders in male C57Bl/6J mice

AIMS/HYPOTHESIS: White adipose tissue (WAT) consists of various depots with different adipocyte functionality and immune cell composition. Knowledge of WAT-depot-specific differences in expandability and immune cell influx during the development of obesity is limited, therefore we aimed to characterise different WAT depots during the development of obesity in mice. METHODS: Gonadal WAT (gWAT), subcutaneous WAT (sWAT) and mesenteric WAT (mWAT) were isolated from male C57Bl/6J mice with different body weights (approximately 25–60 g) and analysed. Linear and non-linear regression models were used to describe the extent of WAT depot expandability and immune cell composition as a function of body weight. RESULTS: Whereas mouse sWAT and mWAT continued to expand with body weight, gWAT expanded mainly during the initial phase of body weight gain. The expansion diminished after the mice reached a body weight of around 40 g. From this point on, gWAT crown-like structure formation, liver steatosis and insulin resistance occurred. Mouse WAT depots showed major differences in immune cell composition: gWAT consisted mainly of macrophages, whereas sWAT and mWAT primarily contained lymphocytes. CONCLUSIONS/INTERPRETATION: Marked inter-depot differences exist in WAT immune cell composition and expandability. The limited storage capacity of gWAT seems to direct the development of metabolic disorders in male C57Bl/6J mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-015-3594-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Comparison of osteoblast and cardiomyocyte differentiation in the embryonic stem cell test for predicting embryotoxicity in vivo

One of the most studied alternative embryotoxicity assays is the embryonic stem cell test, in which the effect of compounds on cardiomyocyte differentiation is evaluated (subsequently termed the ESTc). This single differentiation endpoint may limit the predictive value of the assay. We recently published a novel embryonic stem cell based osteoblast differentiation assay (subsequently termed the ESTo), in which we studied the effect of six embryotoxic compounds. Differentiation is monitored via the differential expression of three genes related to osteogenesis (Runx2, SPARC and collagen type I). In the current study, we evaluated the effect of 14 additional compounds in the ESTo, to assess its added value as compared to the ESTc. To this end, we compared the effects of the compounds in the ESTo to their effects in the ESTc and to their published in vivo developmental toxicity profiles. The results show that there is a high overall correlation between compound potencies as regards inhibition of osteoblast and cardiomyocyte differentiation. Moreover, the results in both the ESTo and ESTc showed a significant correlation to in vivo developmental toxicity potency ranking of compounds tested. Interestingly, the embryotoxic effect of TCDD could only be detected using the ESTo, which can be explained based on its mechanism of action and its known inhibitory effect on osteogenesis. The results of TCDD suggest that incorporating the ESTo into a testing battery together with the ESTc could improve the overall predictive value of the battery

Comparison of osteoblast and cardiomyocyte differentiation in the embryonic stem cell test for predicting embryotoxicity in vivo

One of the most studied alternative embryotoxicity assays is the embryonic stem cell test, in which the effect of compounds on cardiomyocyte differentiation is evaluated (subsequently termed the ESTc). This single differentiation endpoint may limit the predictive value of the assay. We recently published a novel embryonic stem cell based osteoblast differentiation assay (subsequently termed the ESTo), in which we studied the effect of six embryotoxic compounds. Differentiation is monitored via the differential expression of three genes related to osteogenesis (Runx2, SPARC and collagen type I). In the current study, we evaluated the effect of 14 additional compounds in the ESTo, to assess its added value as compared to the ESTc. To this end, we compared the effects of the compounds in the ESTo to their effects in the ESTc and to their published in vivo developmental toxicity profiles. The results show that there is a high overall correlation between compound potencies as regards inhibition of osteoblast and cardiomyocyte differentiation. Moreover, the results in both the ESTo and ESTc showed a significant correlation to in vivo developmental toxicity potency ranking of compounds tested. Interestingly, the embryotoxic effect of TCDD could only be detected using the ESTo, which can be explained based on its mechanism of action and its known inhibitory effect on osteogenesis. The results of TCDD suggest that incorporating the ESTo into a testing battery together with the ESTc could improve the overall predictive value of the battery