What is new in recommendations on ophthalmological screening in patients treated with chloroquine and hydroxychloroquine? Update and literature review.

Based on the present literature, in March 2016, new recommendations of the American Academy of Ophthalmology for ophthalmic screening tests in patients treated with chloroquine and hydroxychloroquine were published. These recommendations emphasized the fact that toxicity is related to the dose calculated by real weight. The recommended hydroxychloroquine and chloroquine doses have been limited. It is no longer recommended to calculate the cumulative dose of chloroquine to establish the risk of toxicity. Kidney failure and the use of tamoxifen are proven risk factors of ocular complications in these patients. The screening agenda was established and available diagnostic methods were evaluated. Screening in patients treated with chloroquine derivatives may prevent an irreversible complication-toxic retinopathy. The present recommendations warn against making premature decision on medicine withdrawal, especially in the light of the most recent studies on their beneficial systemic influence. This paper systematizes the information on ophthalmological screening in chloroquine derivatives users.

The early clinical course of infliximab treatment in rheumatoid arthritis: results from the REMARK observational study.

OBJECTIVES: We aimed to describe patterns of disease activity during infliximab plus methotrexate (MTX) treatment and explore C-reactive protein (CRP) as a potential marker of early response. METHODS: REMARK was a phase IV, open-label, observational study of infliximab-naïve adults with rheumatoid arthritis (RA) who received infliximab 3 mg/kg plus MTX for 14 weeks. Treatment response was evaluated in 3 subgroups: patients with <1 year disease duration who were TNF-inhibitor (TNFi)-naïve, patients with ≥ 1 year disease duration who were TNFi-naïve, and patients who had previous TNFi failure or intolerance. In post hoc analyses, CRP kinetic profiles were analysed by EULAR response (good, moderate, non-response) in REMARK and in an independent replication with data from the ASPIRE study. RESULTS: In the efficacy-evaluable population (n=662), median 28-joint disease activity score (DAS28) improved from baseline to Week 14 (5.2 vs. 3.6, p<0.0001). Regardless of disease history subgroup, most patients had good or moderate EULAR responses at Weeks 2 (64.9%), 6 (74.1%), and 14 (73.6%). DAS28 and its components did not differ across patient subgroups. Disease flare occurred in 16.2% of patients. CRP levels declined markedly at Week 2, but patients who were EULAR non-responders at Week 14 showed a CRP rebound at Weeks 6 and 14. This CRP pattern was independently replicated in data from ASPIRE. Adverse events were consistent with the known risk profile of infliximab. CONCLUSIONS: Infliximab plus MTX treatment in patients with RA rapidly diminished disease activity. A unique pattern of CRP rebound was found in non-responders early in treatment.

Clinical significance of the anti-Nucleolar Organizer Region 90 antibodies (NOR90) in systemic sclerosis: Analysis of the European Scleroderma Trials and Research (EUSTAR) cohort and a systematic literature review.

BACKGROUND: The anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) reported in systemic sclerosis (SSc). Especially due to low prevalence, the clinical relevance of NOR90 in SSc remains uncertain. OBJECTIVES: To analyze the clinical associations of NOR90 in patients with SSc in a multicentric cohort. METHODS: Post-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) database, with additional information on NOR90. Further, we performed a systematic literature search, using the terms "systemic sclerosis" and "NOR90" across three databases: Medline via PubMed, Scopus, and Thomson Reuters' Web of Science Core Collection, from inception to November 1st, 2023. RESULTS: Overall, 1318 patients with SSc were included (mean age 58.3 ± 13.7 years, 81.3 % female), of whom 44 (3.3 %) were positive for NOR90. Of these, 32 were also positive for one of the SSc-criteria antibodies: 9/44 (20.5 %) for anti-topoisomerase I, 18/42 (42.9 %) for anti-centromere, and 5/40 (12.5 %) for anti-RNA polymerase III. NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal (GI) symptoms compared to NOR90-negative patients. In multivariable analysis, NOR90 remained significantly associated with lower mRSS and less frequent GI symptoms. The literature search identified 17 articles, including a total number of 87 NOR90-positive out of 3357 SSc patients, corresponding to an overall prevalence of 2.6 %. CONCLUSION: To our best knowledge, this is the largest SSc cohort tested for NOR90 to date, confirming the NOR90 prevalence in SSc patients is around 3 %.

Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). METHODS: We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). RESULTS: Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3-12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06-9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05-6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3-25.5), skin involvement (OR = 4.4; 95% CI = 1.02-19.6), and age > 65 (OR = 6.3; 95% CI = 1.18-33.7). CONCLUSIONS: In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.

The influence of N-acetyltransferase 2 polymorphism on rheumatoid arthritis activity.

OBJECTIVE: The N-acetyltransferase polymorphism is involved in the metabolism of many xenobiotics, as well as in susceptibility to some diseases such as rheumatoid arthritis (RA). The aim of this study was to investigate the influence of NAT 2 polymorphism on disease activity in RA patients. METHODS: 70 with RA were enrolled in the study. As a measure of disease activity, the number of swollen and tender joints, the duration of morning stiffness, ESR and CRP as well as disease activity based on a global physician's assessment were evaluated. The NAT2 polymorphism was determined by a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). RESULTS: The mean number of swollen and tender joints, as well as the ESR and CRP values, did not differ significantly with the acetylation genotype. Erosive RA was diagnosed in 74.5% of the slow and 40% of the fast acetylators. The risk for the development of erosive RA was 4.39 time greater in slow acetylators than in fast acetylators. CONCLUSION: NAT2 polymorphism may be a genetic risk factor for joint destruction.

FC gamma RIIa polymorphism in patients with rheumatoid arthritis.

OBJECTIVE: Polymorphism of phagocyte IgG receptor Fc gamma RIIa may modulate immune complex mediated inflammation, particularly when immune complex contain IgG2. METHODS: Fc gamma RIIa genotyping in 82 patients with rheumatoid arthritis (RA) and 148 healthy subjects was performed using the polymerase chain reaction technique with allele specific primers. RESULTS: No significant relation between Fc gamma RIIa genotypes and susceptibility to RA was observed, but extraarticular complications with high frequency were revealed in patients with R/R131 genotype. CONCLUSION: The results suggest that the Fc gamma RIIa polymorphism is not a risk factor for RA.

Effects of ionic and non-ionic contrast media on platelet function as evaluated by plasma concentration of beta-thromboglobulin.

The aim of the study was to evaluate the effects of ionic and non-ionic contrast media on platelet function. In 44 patients who underwent angiography, the plasma concentration of beta-thromboglobulin (beta TG) was measured before and after ionic contrast medium (diatrizoate) administration in 22 patients and non-ionic contrast medium (iopromide) in the other 22 patients. A significant decrease in the plasma beta TG levels after intraarterial contrast medium injection occurred in both groups of patients. No significant beta TG level changes occurred in patients with normal pre-examination beta TG levels in both groups. In patients with elevated beta TG levels before arteriography, beta TG returned to normal values after contrast medium injection in both groups. There was no significant correlation between the amount of administered contrast medium and beta TG concentration after angiography. These results suggest that platelet function is not affected by either ionic or non-ionic contrast medium in patients with normal platelet activation. In patients with enhanced platelet activation, the activation became normal after contrast medium administration.

Clinical features of familial ovarian cancer lacking mutations in BRCA1 or BRCA2.

PURPOSE OF INVESTIGATION: The purpose of the present study was to identify the clinical and pathologic features of ovarian cancers in patients who have a family history of breast or ovarian cancer but who do not have a mutation in the BRCA1 or BRCA2 gene. METHODS: 303 patients with ovarian cancer were reviewed for clinical features and for cancer family histories. After the exclusion of 51 patients known to carry BRCA1 or BRCA2 mutations, 24 patients with familial cancer were compared with 228 patients with non-familial cancer. RESULTS: Patients with familial cancer were more likely to have grade 2 tumors, Stage II disease and to present between ages 51 and 60 than were non-familial controls. Ten of 24 patients in the familial group presented between ages 51 and 60 with a grade 2 tumor compared to 3.0 expected (p = 0.001). CONCLUSIONS: Families of women who present with grade 2 ovarian cancer between the ages of 51 and 60 may have an unidentified ovarian cancer susceptibility gene.

[Encephalopathy in the course of idiopathic hypereosinophilic syndrome -- clinical-morphological correlations]. / Encefalopatia w przebiegu zespolu hipereozynofilowego samoistnego--korelacje kliniczno-morfologiczne.

A case of 33-year-old man, who underwent numerous hospital admissions caused by multiple progressing disseminated neurological abnormalities is presented. At first multiple sclerosis was a tentative diagnosis. Because of persistent eosinophilia, after exclusion of other causes of increased eosinophil count, idiopathic hyperoesinophilic syndrome was diagnosed. The case was confirmed neuropathologically. The authors discuss causes of idiopathic hyperoesinophilic syndrome. Very exceptional history of the syndrome, with dominant CNS involvement, is discussed.

[Backache and and related absenteeism]. / Bóle pleców i absencja chorobowa z tego powodu.

The aim of this work was to compare the outcome of the questionnaire survey of low back pain with data on related sickness absenteeism. The questionnaire was responded by 585 (88.8%) employees. Of these number 288 (49.2%) respondents complained of low back pain. Sick leaves were given to 48 (16.7%) persons who had reported low back pains in the questionnaire and to 25 (8.4%) employees of 297 who had not reported the pain and also to 4 (5.4%) persons of 57 who had not responded to the questionnaire. Among those who had not complained of low back pain and were given sick leaves, mostly short ones, there were mainly men and blue collar workers. On the basis of our survey it seems that the analysis of sickness absenteeism due to low back pain does not completely reflect the prevalence of this disease, and that epidemiological studies of the prevalence should also take into consideration relevant sickness absenteeism.

Bone tissue metabolism in men with ankylosing spondylitis.

PURPOSE: The aim of the study was the composite estimation of bone tissue metabolism in ankylosing spondylitis (AS) after having taken into account such factors as a high risk of incidence of osteoporosis in patients with AS and potential danger of permanent immobility. MATERIAL AND METHODS: Sixty-six patients with established diagnosis of AS and 63 healthy individuals in the control group were included into the study. To measure bone mineral density (BMD) the dual energy X-ray absorptiometry (DEXA) method was used. Additionally, biochemical markers of osteoporosis such as bone fraction of an alkaline phosphatase (BALP), osteocalcin (BGP) and deoxypyridinoline (Dpd) as well as many inflammatory markers of disease activity have been determined. RESULTS: In our study with AS had significantly diminished bone mineral density, as compared with health controls. The presence of osteopenia/osteoporosis was associated with longer duration of the disease and with higher age. In the overall group of AS patients bone degradation marker, Dpd, correlated with serum concentration of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP), and inversely with BMD measured in the forearm. However, no direct association could be revealed between lower bone density and markers of inflammation or inflammatory cytokines, except of IL-6 witch was significantly higher in AS patients with osteoporosis/osteopenia than those without. CONCLUSIONS: Our results indicate that disease duration and higher age are risk factors for osteoporosis in patients with AS. Inflammation might contribute to the accelerated bone loss in AS through stimulation of bone degradation.

Psychological stress in rheumatoid arthritis patients: a comparative Polish-German study: summary of the current conceptualization of the role of stress in rheumatoid arthritis.

Cultural differences in experiencing individual stress in rheumatoid arthritis (RA) patients might be observed. The aim of the study was to assess quality of life and psychological stress (distress) in RA patients, and to evaluate socio-demographic and disease specific variables predicting stress of patients. The study covered 300 Polish and 137 German RA patients. SF-36v2 scale was used to evaluate the patients' health. Psychological stress was defined as the feeling of "social isolation" and "being a burden" as demanding help in everyday activities. In both countries, the mental and physical health of patients deteriorated and about 50% of patients required support in everyday activities. 95% of Polish and 62% of German patients felt rejected from social activities. For the psychological stress perceived, functional capacity class 3 and male gender were shown to be predictive in Polish patients and living in a small town - in German patients. In the Polish group, the tertiary/bachelor level of education was linked with lower distress level. RA has a serious impact on the mental health owing to a great disease burden. Awareness of impact of the disease on quality of life and psychological stress of patients should be considered in routine clinical practice.

Is prevalence of PBC underestimated in patients with systemic sclerosis?

BACKGROUND: Clinically significant primary biliary cirrhosis occurs in 2.5% of patients with systemic sclerosis. Primary biliary cirrhosis-specific autoantibodies include anti-mitochondrial, anti-glycoprotein 210, and anti-sp100 antibodies. The majority of asymptomatic anti-mitochondrial-positive subjects express histological features of primary biliary cirrhosis. Early detection of primary biliary cirrhosis is important, as timely introduction of ursodeoxycholic acid may improve prognosis. The aim was to assess the prevalence of MIT3 IgG-anti-mitochondrial, gp210, sp100 and other autoantibodies in patients with systemic sclerosis and compare the clinical and biochemical parameters in those who are primary biliary cirrhosis-specific autoantibodies positive and negative. MATERIALS/METHODS: Fifty-two consecutive patients with systemic sclerosis were included. Thirty-three suffered from limited skin SS and 19 from diffuse SS. RESULTS: Eight (15%) patients with systemic sclerosis tested positive for primary biliary cirrhosis-specific autoantibodies. No significant differences were observed between primary biliary cirrhosis-specific autoantibodies positive and negative subjects in terms of various demographic, clinical or biochemical features. A trend towards increased prevalence of chronic fatigue in primary biliary cirrhosis-specific autoantibodies positive patients was observed. CONCLUSIONS: Primary biliary cirrhosis-specific autoantibodies were detected in 15% of the systemic sclerosis patients. Since patients with primary biliary cirrhosis-specific antibodies are at high-risk or do suffer from primary biliary cirrhosis, screening for primary biliary cirrhosis-specific autoantibodies may be considered during routine assessment of systemic sclerosis.

TNF-alpha -308 promoter polymorphism in patients with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which tumour necrosis factor-alpha (TNF-alpha) plays an important role. There are, however, controversial reports that TNF-alpha promoter polymorphism may be an independent marker of susceptibility and severity of RA. The aim of the present study was to examine the TNF-alpha -308 promoter polymorphism in patients with RA. METHODS: We examined 91 patients with RA diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction (PCR) amplification was used for analysis of the polymorphism at position -308 in promoter of TNF-alpha gene. RESULTS: Distribution of TNF-alpha genotypes in RA patients did not differ from that in control subjects. Moreover, there was no association between TNF-alpha genotypes and age at disease diagnosis, disease activity in global physician's assessment, and joint and extra-articular involvement. There was also no correlation between TNF-alpha polymorphism and disease activity measures, including erythrocyte sedimentation rate (ESR), CRP, number of swollen and tender joints, and morning stiffness duration. CONCLUSIONS: We suggest that TNF-alpha -308 promoter polymorphism is not a genetic risk factor for RA susceptibility and severity.

[Incidence of malignant lymphomas in Western Maritime Provinces in the years 1980-1984]. / Wystepowanie chloniaków zlosliwych na Pomorzu Zachodnim w latach 1980-1984.

Incidence rate of malignant lymphomas was determined in the population of Western Pomerania region. The period of studies covered the years from 1980 to 1984 and the patients being over 14 years old. In the Western Pomerania region malignant lymphoma was diagnosed during that period in 528 subjects: low grade malignancy lymphomas were diagnosed in 268, therein lymphocytic lymphomas 135, with high grade malignancy 54: malignant granulomatosis 125 cases and 77 plasmocytic myelomas. The following data were taken into consideration: sex, place of residence, type of lymphoma: in case of malignant granulomatosis also the histopathologic subtype, and in multiple myeloma the type of monoclonal protein. Szczecin Voivodeship was found to have the highest incidence rate of malignant lymphoma, namely 9,1/10(5) of inhabitants: in Koszalin and Gorzów Voivodeships respectively 6.9/10(5) and 6.1/10(5) of inhabitants annually. The difference in the incidence rate in Szczecin Voivodeship and two other ones was significant (p < 0.001). No significant differences in the morbidity existed between Koszalin and Gorzów Voivodeships. In the region there was a preporderance of malignant lymphomas in relation to malignant granulomatosis. Morbidity in malignant lymphoma more frequently involved men than women. Morbidity rate of lymphoma with low and high malignancy, as well as plasmocytic myeloma increases with the age. On the other hand, in malignant granulomatosis no statistically significant differences depending on the age and sex were recorded. The incidence rate in respective groups of malignant lymphoma was the highest in Szczecin, followed by other towns in the region, being the lowest in rural environment. In our region, with regard to all malignant lymphomas, the disease is more frequently diagnosed in the advanced clinical stage.

[Secondary malignant neoplasms in patients with non-Hodgkin's lymphoma]. / Drugie nowotwory zlosliwe u chorych na chloniaki nieziarnicze.

In 1979-1987, 570 patients with non-Hodgkin's lymphomas (226 female and 344 male patients) were treated at the Department of Hematology of the Pomeranian Medical Academy and hematological outpatient clinic. The second malignant tumors were diagnosed in 25 (4.4%) patients. Two patients suffered from three malignant tumors. The most frequent combination of 2 tumors were: non-Hodgkin lymphoma and cancer of the lungs in 8 patients, non-Hodgkin lymphoma and cancer of the skin in 6 patients, non-Hodgkin lymphoma and cancer of the larynx in 4 patients, non-Hodgkin lymphoma combined with cancer of the stomach in 2 patients, and non-Hodgkin lymphoma together with cancer of the bladder in 2 patients. Moreover, non-Hodgkin lymphoma coexisted with cancer of the colon, cervix and prostate (one case of each). The authors stress the possibility of other malignant tumors in patients with non-Hodgkin lymphomas and occurrence of the subsequent neoplasms without preceding chemo- or radiotherapy.

[Gastrointestinal non-Hodgkin's lymphomas. Personal observations]. / Chloniaki zlosliwe nieziarnicze przewodu pokarmowego. Obserwacje wlasne.

The localization, symptoms, endoscopic findings, histologic type, infiltration of bone marrow, lymphoma cell presence in the blood, and results of therapy were evaluated in 18 patients with gastrointestinal lymphoma. Only 9 patients met the criteria of primary gastrointestinal lymphoma, the remaining 9 presenting an extra-nodular localization of systemic disease, i.e. secondary lymphoma. The most common site of process was stomach, and most of the patients had histologically documented a high grade malignant lymphoma. Necessity of supplementing surgery with chemo- and/or radiotherapy was discussed. Such combined treatment should give a 10-year survival time in 60% of the treated patients (confirmed with the Kaplan-Meier's method). The authors concluded that stomach is the most common localization of gastrointestinal lymphoma, and that gastrointestinal non-Hodgkin's lymphoma diagnosis should include peripheral blood and bone marrow haematological examinations which clearly rise the reliability of differentiation between primary or secondary lymphomas.