Evaluation of belimumab treatment in patients with systemic lupus erythematosus in a clinical practice setting: Results from a 24-month OBSErve study in Argentina.

OBJECTIVE: To describe clinical effectiveness of belimumab for systemic lupus erythematosus (SLE) in real-world practice in Argentina. METHODS: This retrospective, observational study analysed medical record data of patients with SLE treated with belimumab in 15 centres in Argentina. Primary endpoint: overall clinical response (assessed on a scale similar to the 6-point Physician Global Assessment) at months 6, 12, 18 and 24, all versus index (belimumab initiation). Secondary endpoints: improvement in disease activity (SELENA-SLEDAI), SLE manifestations, and corticosteroid dose change. RESULTS: Records for 81 patients (91% female) were analysed. Clinical improvements were reported for 95%, 95%, 98% and 100% patients at 6, 12, 18, and 24 months post index, respectively. Mean SELENA-SLEDAI score decreased from 11.21 at index to 4.76, 3.77, 3.86 and 2.17 at 6, 12, 18, and 24 months post index, respectively. Number of flares decreased from 1.05 at index to 0.21, 0.09, 0.22 and 0.30 at 6, 12, 18, and 24 months post index, respectively. Mean corticosteroid dose was 14.59 mg/day at index, and 6.45, 5.18, 5.17 and 4.78 mg/day at 6, 12, 18, and 24 months post index, respectively. CONCLUSIONS: Real-world patients with SLE treated with belimumab in Argentina demonstrated clinical improvements and reductions in corticosteroid dose.

Work instability in rheumatoid arthritis patients from Argentina: prevalence and associated factors.

To determine the prevalence of and associated factors to work instability (WI) in rheumatoid arthritis (RA) Argentinean patients. Observational cross-sectional study that assessing employment status in currently working RA patients. They answered the validated version of RA work instability scale (RA-WIS). High-risk WI was considered when RA-WIS was ≥17. Factors associated with high-risk WI were examined by univariable and multivariable analysis. Four-hundred and fifty RA patients were enrolled; of these, 205 patients were currently employed, but only 172 have completed questionnaires required [RA-WIS and health assessment questionnaire (HAQ-A)]. Their mean age was 49.3 ± 10.8 years; 81.3 % were female; and their mean disease duration was 8.1 ± 7.2 years. Fifty-two percent of patients were doing manual work. The mean RA-WIS score was 11.4 ± 6.8, and 41 % of patients had a high-risk WI. High-risk WI was associated with radiographic erosions (p < 0.001) and HAQ-A >0.87 (p < 0.001) in the univariable analysis, whereas in the multivariable logistic regression analysis the variables associated with a high-risk WI were as follows: HAQ-A >0.87 [odds ratio (OR) 12.31; 95 % CI 5.38-28.18] and the presence of radiographic erosions (OR 4.848; 95 % CI 2.22-10.5). In this model, having a higher monthly income (OR 0.301; 95 % CI 0.096-0.943) and a better functional class (OR 0.151; 95 % CI 0.036-0.632) were protective. Forty-one percent of RA working patients had high-risk WI. The predictors of high RA-WIS were HAQ-A ≥0.87 and radiographic erosions, whereas having a better functional class and have higher incomes were protective.

Investigating coping and stigma in people living with HIV through narrative medicine in the Italian multicentre non-interventional study DIAMANTE.

Antiretroviral therapy (ART) significantly reduced Human Immunodeficiency Virus (HIV) morbidity and mortality; nevertheless, stigma still characterises the living with this condition. This study explored patients' coping experience by integrating narrative medicine (NM) in a non-interventional clinical trial. From June 2018 to September 2020 the study involved 18 centres across Italy; enrolled patients were both D/C/F/TAF naïve and previously ART-treated. Narratives were collected at enrolment (V1) and last visit (V4) and then independently analysed by three NM specialist researchers through content analysis. One-hundred and fourteen patients completed both V1 and V4 narratives. Supportive relationships with clinicians and undetectable viral load facilitated coping. Conversely, lack of disclosure of HIV-positive status, HIV metaphors, and unwillingness to narrate the life before the diagnosis indicated internalised stigma. This is the first non-interventional study to include narratives as patient reported outcomes (PROs). Improving HIV awareness and reducing the sense of guilt experienced by patients helps to overcome stigma and foster coping.

Vaccination coverage in healthcare workers: a multicenter cross-sectional study in Italy.

INTRODUCTION: In recent years, a phenomenon known as "vaccine hesitancy" has spread throughout the world, even among health workers, determining a reduction in vaccination coverage (VC).A study aimed at evaluating VC among healthcare workers (HCWs) in 10 Italian cities (L'Aquila, Genoa, Milan, Palermo, Sassari, Catanzaro, Ferrara, Catania, Naples, Messina) was performed. MATERIALS AND METHODS: Annex 3 of the Presidential Decree n. 445 of 28 December 2000 was used to collect information on the vaccination status of HCWs. The mean and standard deviation (SD) were calculated with regard to the quantitative variable (age), while absolute and relative frequencies were obtained for categorical data (sex, professional profile, working sector, vaccination status). The connection between VC and the categorical variables was evaluated by chi-square method (statistical significance at p < 0.05). The statistical analyses were performed by SPSS and Stata software. RESULTS: A total of 3,454 HCWs participated in the project: 1,236 males and 2,218 females.The sample comprised: physicians (26.9%), trainee physicians (16.1%), nurses (17.2%) and other professional categories (9.8%). Low VC was generally recorded. Higher VC was found with regard to polio, hepatitis B, tetanus and diphtheria, while coverage was very low for measles, mumps, rubella, pertussis, chickenpox and influenza (20-30%). CONCLUSIONS: This study revealed low VC rates among HCWs for all the vaccinations. Measures to increase VC are therefore necessary in order to prevent HCWs from becoming a source of transmission of infections with high morbidity and/or mortality both within hospitals and outside.

Detection of Chlamydia trachomatis deoxyribonucleic acid in women with tubal infertility.

OBJECTIVE: To determine the presence of Chlamydia trachomatis by in situ hybridization in fallopian tube tissues of women with distal tubal occlusion. PATIENTS: Subjects were selected from a Seattle-based study of infertility in women with distally occluded fallopian tubes undergoing reconstructive surgery. For comparison, six specimens were obtained from women undergoing surgery for noninfertility-related conditions who had normal appearing tubes. METHODS: Tissue specimens from 16 of these patients were selected for analysis by in situ hybridization and immunoperoxidase (IP) staining. RESULTS: C. trachomatis was detected in 9 of 16 women by either in situ hybridization or IP. Six of the nine were seropositive with titers ranging from 1:16 to 1:64. Tissue from 6 women with normal appearing fallopian tubes were negative by in situ hybridization. CONCLUSIONS: The demonstration of C. trachomatis deoxyribonucleic acid and/or antigens in fallopian tube tissue from infertile women with distal tubal disease suggests that C. trachomatis can persist in these tissues in an uncultivable state.

[Lactate dehydrogenase isoenzymes and alveolar inflammation in acute severe bronchiolitis in infants]. / Isoenzimi della latticodeidrogenasi e flogosi alveolare nella bronchiolite acuta severa del lattante.

The authors have tried to value in 17 children (age: 1-11 months) affected by a severe acute viral bronchiolitis, if the measurement of Lactate Dehydrogenase (LD) isoenzymes could have been used to reveal alveolar injury. In the 76.4% (13/17) of subjects areas of consolidation were demonstrated by chest's radiographic examination due either to atelectasis secondary to obstruction or to inflammation of the alveoli. These coincided with a significant increase respect to a check's group (18 children) of LD4 in 70.5% (12/17), LD3 in 35.2% (6/17) and LD5 in 29.4% (5/17) of children. The presence of an analogous electrophoretic pattern and macrophages degenerated in pulmonary alveolar proteinosis lavage effluent associated with increases in lymphocytes and mononuclear phagocytes in lung specimens from children dead for bronchiolitis help to understand the inflammatory origin of pathological modification of LD isoenzymes observed in this series of cases.

[Lactate dehydrogenase isoenzymes in HIV-positive children]. / Gli isoenzimi della lattico-deidrogenasi nei bambini HIV-positivi.

Considering that in the HIV infection there is a precocious deterioration of humoral immunity with rapid turn-over of cellular B clones, we have evaluated the conduct of serum lactate-dehydrogenase activity (LD, EC 1.1.1.27) and its isoenzymes in 21 children born from HIV-positive mother respect to a control group (30 subjects). Furthermore we have checked the existence of a probable correlation between those and other clinical and immunologic parameters (total lymphocytes, CD4/CD8, immunoglobulins, classification according to the Atlanta CDC). In seropositive children we saw, respect to those evolved towards P3 stage, a significantly raising of LD4 (also vs. control group) for likely pulmonary parenchyma's damage, LD3 for B immature lymphocytes' increase and a reduction of LD1 (also vs. control group) for mature clones' decrement. Furthermore in seropositive subjects there was the existence of a direct correlation between LD1 and CD4/CD8 values. As such, the evaluation of LD isoenzymes can establish an useful element in the clinical monitoring of seropositive children.

Sexto reporte de eventos adversos con tratamientos biológicos en Argentina: Informe del registro BIOBADASAR / Sixth report of adverse events with biological treatments in Argentina: Report of the BIOBADASAR registry

Objetivo: Actualizar los resultados del registro BIOBADASAR sobre seguridad, duración y causas de interrupción del tratamiento luego de 8 años de seguimiento. Métodos: BIOBADASAR es un registro de seguridad de terapias biológicas establecido por la Sociedad Argentina de Reumatología. Se presenta la descripción de BIOBADASAR 3.0, una cohorte compuesta por 53 centros de Argentina seguidos prospectivamente desde agosto de 2010 hasta enero de 2018. Resultados: Se registraron 4656 pacientes, 6234 tratamientos [3765 casos (terapia con biológicos) y 2469 controles (terapia no biológicos)]. Se interrumpió el tratamiento en el 44,6% en los casos vs. 27,9% en los controles. Causa principal de discontinuación fue por ineficacia (40% casos vs. 32% controles). Se presentaron 3154 eventos adversos (2230 en casos vs. 924 en controles), de los cuales el 13,6% fueron graves (9,8% en casos y 3,7% en controles). El evento adverso (EA) más frecuente en ambos grupos fueron las infecciones (43,56% en casos vs. 34,31% en los controles, RR: 3,42; IC 95%: 3,02-3,88), y de ellas las de vías aéreas superiores (14,5%). Las neoplasias se presentaron en 78 casos vs. 45 en controles (RR: 1,98; IC 95%: 1,37-2,86). Conclusiones: En este sexto reporte no se observan tendencias diferentes sobre seguridad, duración y causas de interrupción del tratamiento respecto a informes previos. Las infecciones fueron el principal EA y la ineficacia, seguido por EA y la pérdida de pacientes las principales causas de suspensión del tratamiento. El advenimiento de nuevos agentes biológicos y la necesidad de control en seguridad a largo plazo, fortalece el uso de este tipo de registro.

Objective: Update the results of the BIOBADASAR registry on safety, duration and causes of treatment interruption after 8 years of follow-up. Methods: BIOBADASAR is a safety record of biological therapies established by the Argentine Society of Rheumatology. The description of BIOBADASAR 3.0 is presented, a cohort of 53 centers in Argentina followed prospectively from August 2010 to January 2018. Results: 4656 patients were registered, 6234 treatments [3765 cases (therapy with biologicals) and 2469 controls (non-biological therapy)]. Treatment was interrupted in 44.6% in cases vs. 27.9% in controls. Main cause of discontinuation was due to inefficiency (40% cases vs. 32% controls). There were 3154 adverse events (2230 in cases vs. 924 in controls), of which 13.6% were tombs (9.8% in cases and 3.7% in controls). The most frequent adverse event (AE) in both groups were infections (43.56% in cases vs. 34.31% in controls, RR: 3.42, 95% CI: 3.02-3.88), and the upper airway pathways (14.5%). Neoplasms were published in 78 cases versus 45 controls (RR: 1.98, 95% CI: 1.37-2.86). Conclusions: In this article, there are no different trends regarding safety, duration and causes of interruption of treatment compared to previous reports. Infections were the main causes of treatment discontinuation. The advent of new biological agents and the need for control over long-term security, strengthens the use of this type of registration.

[Lactate dehydrogenase and its isoenzymes in respiratory diseases in children]. / La latticodeidrogenasi ed i suoi isoenzimi nella patologia respiratoria del bambino.

Total Lactate Dehydrogenase (LD, EC 1.1.1.27) activity in serum and LD isoenzymes were quantified in 161 children (51 with pneumonia at the time of diagnosis, 60 hospitalized for asthma in acute period and 50 healthy subjects) to ascertain the relationship of these markers with injury of lung tissue. No statistical variations, between different groups in total activity, were found. Significantly decreased proportions of LD1 (p less than 0.000001) and of LD2 (p less than 0.000001) with simultaneous increase of LD4 (p less than 0.000001) and LD5 (p less than 0.000001) resulted in children with pneumonia, as to asthmatic or healthy subjects. Investigators conclude that LD should be determined in every patient with pneumonia because of the presence of a specific LD isoenzyme pattern.

Detection of Chlamydia trachomatis deoxyribonucleic acid in monkey models (Macaca nemestrina) of salpingitis by in situ hybridization: implications for pathogenesis.

OBJECTIVE: Our purpose was to determine whether Chlamydia trachomatis persists in tubal tissues from monkey pocket models of chlamydial salpingitis and tubal infertility and to relate its presence to disease progression and histopathologic mechanisms. STUDY DESIGN: In situ hybridization was used to detect Chlamydia deoxyribonucleic acid in a monkey pocket model of salpingitis and in the direct tubal inoculation monkey model of tubal infertility. Results were correlated with culture and immunocytochemistry results and histopathologic characteristics. RESULTS: Chlamydia deoxyribonucleic acid was detected in the mucosa, submucosa, and deep tissues in the pocket model. In addition, it was present in peritubal adhesions from the direct inoculation model. Deoxyribonucleic acid was found at sites of inflammation and when culture and immunocytochemistry studies were negative. CONCLUSION: The presence of Chlamydia trachomatis deoxyribonucleic acid at sites of inflammation and tissue damage in monkey models of chlamydial salpingitis and tubal infertility suggests that Chlamydia persists and may be directly involved in the stimulation of the immune-mediated tissue destruction associated with Chlamydia trachomatis infections.

[Serum lactate-dehydrogenase isoenzymes in HIV positive children. A longitudinal study]. / Gli isoenzimi della lattico-deidrogenasi nei bambini con infezione da HIV. Studio longitudinale.

The impairment of humoral immunity with rapid turn-over of cellular B clones in children with HIV infection is known as well as the conduct of LDH isoenzymes in B cell lymphoproliferative diseases like Burkitt's lymphoma. Therefore, serum lactate-dehydrogenase activity (LD, EC 1.1.1.27) and its isoenzymes have been evaluated twice (within 12 months) in 11 children with HIV infection with respect to a control group (30 subjects). Furthermore, the relationship between those and other clinical and immunologic parameters (total lymphocytes, CD4/CD8, immunoglobulins, classification according to the Atlanta CDC 1987) has been studied. HIV infected children have shown a significant decrease in LD1 rates, which was directly correlated to CD4/CD8 values. After the follow-up, this correlation became even more significant. Thus, these findings may suggest the usefulness of LDH isoenzymes evaluation as a marker of disease activity in children with HIV infection.

Determination of glycated hemoglobins in the rat: comparison between two different chromatographic methods and application in experimental diabetology.

Due to the unusual presence of several different hemoglobin components in the rat, determination of glycated hemoglobin (Hb) has been considered difficult and often unreliable in this animal species. In the present study, we compare a fully automated high-performance liquid chromatographic (HPLC) method of analysis of glycated hemoglobin that has been assessed for clinical use with an affinity chromatography technique using boronate micro-columns; we used blood samples taken from Sprague-Dawley rats of various ages and streptozotocin-diabetic rats. In nondiabetic rats, the sum of HbA1c and other minor glycated hemoglobins separated by the HPLC method is close to the total glycated hemoglobin obtained by affinity chromatography for each age group of animals. In diabetic rats, the glycated hemoglobins measured by whatever method show a linear increase during the first 3 weeks following streptozotocin administration, with the difference that glycated hemoglobin values obtained by affinity chromatography are markedly higher than those obtained by HPLC technique. Interestingly, a comparative determination of glycated hemoglobin in diabetic patients gives the same results with both methods. Therefore, it appears that in the rat, unlike man, at high glucose concentrations glycation occurs preferentially at the amino groups of hemoglobin components, which are not separated by the HPLC method. Our results indicate that while affinity chromatography should be used to detect the total extent of hemoglobin glycosylation in diabetic rats, the utilization of rapid and automatized HPLC procedures can be a very convenient alternative for the determination of glycated hemoglobin in both euglycemic and hyperglycemic rats.

Detection of Chlamydia trachomatis in fallopian tube tissue in women with postinfectious tubal infertility.

OBJECTIVE: Biopsy tissues from women with postinfectious tubal infertility were studied for the presence of Chlamydia trachomatis. STUDY DESIGN: Tubal biopsy specimens from 25 women with postinfectious tubal infertility undergoing laparoscopy for repair of fallopian tubes were evaluated by culture, in situ hybridization. Immunocytochemistry, and transmission electron microscopy for the presence of Chlamydia trachomatis. Serum was also tested for Chlamydia trachomatis antibodies. RESULTS: Chlamydia trachomatis was detected in postinfectious tubal biopsy specimens in three of 25 patients by culture, 12 of 24 by in situ hybridization, 15 of 22 by immunoperoxidase stain, and two of 10 by transmission electron microscopy. Serum antibody against Chlamydia trachomatis was detected in 15 of 21 patients. CONCLUSION: Chlamydia trachomatis deoxyribonucleic acid or antigens were detected at a high percentage (19/24 women) in the biopsy tissues of the fimbrial and peritubal adhesions by in situ hybridization or immunoperoxidase stain, suggesting a persistent infection in these women even after antibiotic treatment.

Effects of doxycycline and antiinflammatory agents on experimentally induced chlamydial upper genital tract infection in female macaques.

To evaluate the effects of antimicrobial and antiinflammatory drugs on oviductal pathology in chronic chlamydial upper genital tract infection, the fallopian tubes of 40 female Macaca nemestrina were inoculated with Chlamydia trachomatis and randomly assigned to treatment with doxycycline (n = 10), doxycycline plus ibuprofen (n = 10), doxycycline plus triamcinolone (n = 10), or placebo (n = 10). Before therapy, all animals were positive for culture or ligase chain reaction (or both), and laparoscopy demonstrated the presence of upper genital tract pathology. After therapy, cervical cultures remained positive in 5 animals given placebo versus 0 given doxycycline alone (P = .03), 0 given doxycycline plus ibuprofen (P = .03), and 1 given doxycycline plus triamcinolone (P = .14). At hysterectomy, neither gross nor histologic pathology was affected by any of the treatment regimens, but immunocytochemistry and in situ hybridization evidence of persistent tubal infection was significantly more frequent among animals given placebo or doxycycline plus antiinflammatory agents than among those given doxycycline alone.

Detection of Chlamydia pneumoniae in atherosclerotic plaques in the walls of arteries of lower extremities from patients undergoing bypass operation for arterial obstruction.

PURPOSE: To study surgically excised vascular tissue from lower extremities for the presence of Chlamydia pneumoniae, to extend the previously described association of the organism with atherosclerosis. METHODS: Arterial biopsy specimens obtained from femoral and popliteal arteries during bypass operation for claudication were examined by immunocytochemical analysis and polymerase chain reaction for the presence of organisms. RESULTS: C. pneumoniae was detected in atherosclerotic plaques by either method in either artery of 11 of 23 patients (48%). Eight of 21 popliteal and three of 18 femoral arteries had positive results. CONCLUSIONS: Detection of C. pneumoniae in peripheral arteries indicates that the organism is widespread in atherosclerosis of the vascular system.

Specificity of detection of Chlamydia pneumoniae in cardiovascular atheroma.

Chlamydia pneumoniae is commonly detected in atherosclerotic plaque but the frequency of detection in non-cardiovascular (CV) tissues has not been well determined. In this study, archival autopsy tissue specimens from both CV and non-CV sites from 38 patients were tested by polymerase chain reaction and immunocytochemistry to detect C. pneumoniae. In addition, 33 surgical granuloma biopsy specimens were also tested. C. pneumoniae was detected most frequently in coronary artery tissue (34%) but was also detected in specimens from lung (13%), liver (10%), spleen (5%), bone marrow (10%), and lymph node (8%). The organism was detected in 3 of 33 granuloma specimens. These findings suggest that C. pneumoniae demonstrates a tropism for CV tissues and is either not widely distributed to non-CV tissues or does not persist chronically in those tissues after initial infection.

Specificity of detection of Chlamydia pneumoniae in cardiovascular atheroma: evaluation of the innocent bystander hypothesis.

Chlamydia pneumoniae has been detected in atherosclerotic plaque, raising the question of whether this detection is specific to atheromatous tissue. To evaluate this question, we tested cardiovascular and non-cardiovascular tissue samples from 38 autopsy cases by polymerase chain reaction and immunocytochemistry. We also tested 33 granuloma biopsy specimens, as the organism has been detected in macrophages. C. pneumoniae was detected in coronary artery tissue from 13 (34%), lung from 5 (13%), liver from 4 (10%), and spleen from 2 (5%) of the 38 autopsy cases (P < 0.05 for comparison of proportion of positive coronary arteries with that of each of the other types of tissue). Of the 21 cases with at least one positive tissue sample, 11 had only a positive cardiovascular tissue (coronary artery, venous bypass graft, or myocardium), 7 had both cardiovascular and non-cardiovascular positive tissues, and 3 had only a non-cardiovascular positive tissue. C. pneumoniae was thus detected relatively infrequently in non-cardiovascular tissues, and its detection in these tissues was usually in association with its detection in cardiovascular tissue from the same patient. The organism was also infrequently detected in granulomatous tissue (3/33 specimens). These findings demonstrate that C. pneumoniae is more frequently found in atherosclerotic than normal tissue and support the hypothesis that C. pneumoniae has a role in the pathogenesis of atherosclerosis.

Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues.

Chlamydia pneumoniae TWAR has been associated with coronary heart disease by seroepidemiologic studies and direct detection of the organism in atheromatous lesions of coronary arteries and aorta. In this study, 38 fresh tissue specimens from patients with coronary artery lesions that were treated by directional coronary atherectomy were tested for C. pneumoniae. Twenty-three specimens were from patients with primary lesions and 15 were from patients with restenoses. C. pneumoniae was detected by polymerase chain reaction (PCR), immunocytochemical stain (ICC), or both in 20 of 38 specimens. Using cell identity markers, the organism was localized to macrophages. Ultrastructural evidence of the organism was found in the 2 specimens examined by transmission electron microscopy, which were also positive by both ICC and PCR. C. pneumoniae was found more frequently in tissues from restenoses than in primary lesions (P = .17). There was no relation between the frequency of detection of the organism and C. pneumoniae-specific antibody titers.