Sunday, April 4, 2021

Prevalence of hydroxychloroquine retinopathy with long-term use in a cohort of Indian patients with rheumatic diseases

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Abstract

The study aims to estimate the prevalence of hydroxychloroquine (HCQ) retinopathy in a cohort of Indian patients and analyse the associated factors. Adult patients with rheumatological disorders aged ≥ 18 years using HCQ for more than 5 years and/or having received a cumulative dose > 400 g were included. Demographic and clinical data were collected and all underwent ophthalmological tests which included Humphrey automated visual fields (AVF) and spectral domain optical coherence tomography (SD-OCT). The various clinical characteristics of the patients were compared. The study included 110 patients with a mean age of 43.5 ± 10.1 years and predominantly females. Eleven patients (10%) were diagnosed with definite HCQ retinopathy. The mean daily dose of HCQ (mg/kg of real body weight) was significantly different in the groups with and without retinopathy (5.7 ± 0.9 vs 5.1 ± 0.8, p = 0.04). Patients with retinopathy had significantly more colour vision abnormalities (odds of 16.9; confidence interval 4.1–69.1, p = 0.0001) and higher prevalence of both parafoveal and perifoveal thinning (p < 0.0001). Age, gender, duration of HCQ use, cumulative HCQ dose and body mass index were not found to be associated with retinopathy. Four out of 11 patients had abnormalities only on 30–2 protocol for AVF testing, two had abnormalities only on 10–2 protocol, whereas five patients had abnormalities on both protocols. SD-OCT abnormalities were present in all patients with retinopathy. Hydroxychloroquine retinopathy was prevalent in the study cohort and significantly associated with a higher daily dose of HCQ (mg/kg real body weight).

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Targeted high concentration botulinum toxin A injections in patients with Raynaud’s phenomenon: a retrospective single-centre experience

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Abstract

Raynaud's phenomenon is a vasospastic condition affecting hands and feet which may lead to rest pain, ischemic ulcers and gangrene. Botulinum toxin A has been shown to improve peripheral circulation and relieve vasospastic symptoms. Our aim was to assess our treatment outcomes following Botulinum toxin A injections in patients with Raynaud's phenomenon and to explore the importance of toxin concentration and injection sites. Retrospective chart review of patients with primary and secondary Raynaud's syndrome treated with Botulinum toxin A injections and a literature review was conducted. The toxin dose, injection sites, symptom relief, healing of ulcers and complications were assessed. A total of 30 treatment episodes over a 7½ year period were included. All patients had failed medical management. Botulinum toxin A injection was injected primarily in the vicinity of the palmar digital neurovascular bundle. The average total Botulinum toxin A do se injected was 156 U and the concentration was 50 U/ml. All patients reported an improvement in symptoms and healing of digital ulcers. One patient reported a temporary muscle weakness. Six patients had a single treatment episode with long term benefit. Systemic sclerosis patients had an average of 6-month interval between treatment episodes. Higher doses of Botulinum toxin A has been well tolerated with no long term adverse effects. Our study shows that targeted low volume higher concentration Botulinum toxin A injections are effective in treating Raynaud's phenomenon.

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Multiple system inflammatory syndrome associated with SARS-CoV-2 infection in an adult and an adolescent

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Abstract

Multisystem inflammatory syndrome in adults (MIS-A) is a new syndrome related with COVID-19. A case-based review was performed to present real-life experiences in terms of main findings and treatment options. We described two cases with the diagnosis of MIS and searched the literature to review all reported ≥ 18-year-old cases. The PubMed, Scopus, and Web of Science databases were searched. All relevant articles from January 2020 to February 2021 were reviewed. An adolescent and an adult patient (18 and 40 years-old, respectively) with the diagnosis of MIS were presented. Both had the consistent clinical findings with the case definition criteria. Although steroid, intravenous immunoglobulin (IVIG) and supportive care treatments have been suggested in the literature, there exists no treatment guideline for MIS-A. The clinical and laboratory findings of the patients progressively improved with the implementation of the IVIG and the pulse steroid treat ments. A total of 51 cases (≥ 18 years-old) with MIS were analyzed. Mean age was 29.4 ± 10 years. Fever (80.4%), gastrointestinal (72.5%), and respiratory symptoms (54.9%) were the predominant symptoms. Cardiovascular abnormalities were the most frequent reported findings (82.4%, 42/51). The dermatological and conjunctival findings were reported in 39.2% and 35.3% of the patients, respectively. The increased level of inflammatory biomarkers was remarkable. Most of the patients were treated successfully with steroid and IVIG. Clinicians managing adult patients should keep in mind the development risk of MIS related with SARS-CoV-2 infection to perform necessary interventions properly without delay. IVIG and pulse steroid treatments are the effective options on clinical improvement.

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Lung cancer mimicking systemic lupus erythematosus: case-based review

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Abstract

The aim of this study was to analyze the clinical features of lupus-like lung adenocarcinoma, thus improving both the recognition of lupus mimickers and diagnosis accuracy. We collected three cases of lung adenocarcinoma in which the clinical characteristics and laboratory profiles imitated systemic lupus erythematosus (SLE) in our hospital, and also we had a literature review using search engine. There are few reports of lung adenocarcinoma for which the clinical and laboratory profiles meet the criteria for SLE diagnosis. Follow-up and pathological biopsy are beneficial for the differential diagnosis. Few lung adenocarcinoma cases resemble SLE. Gene pleiotropy and immune dysregulation might be contributing factors. Lung adenocarcinoma should be considered in the differential diagnosis of SLE. Follow-up and pathological biopsy should be improved to enable early detection of lung adenocarcinoma-associated lupus-like conditions.

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Increased influenza vaccination rates in patients with autoimmune rheumatic diseases during the Covid-19 pandemic: a cross-sectional study

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Abstract

To assess non-compliance and potential changes in seasonal flu vaccination coverage before and during the Covid-19 pandemic in patients with autoimmune rheumatic diseases (ARDs). Consecutive patients with ARDs followed-up in 2 tertiary hospitals were telephone-interviewed (December 12–30, 2020) regarding seasonal flu vaccination during the 2019/20 and 2020/21 time periods. Self-reported disease flares that occurred after flu vaccination, as well as reasons for non-vaccination were recorded. One thousand fifteen patients were included. The rate of flu vaccination increased from 76% before to 83% during the COVID-19 pandemic (p = 0.0001). The rate of self-reported disease flares was < 1% among vaccinated patients. Reasons for not vaccination in both periods, respectively, included: 'was not recommended by their rheumatologists' (35.0vs.12.2%, p < 0.0001), 'did not feel that they would have any benefit' (36.9 vs. 32.6%), felt unsafe to do so (27.5 vs. 30.2%), or other reasons (18.9 vs. 23.8%). By multivariate analysis, age [OR = 1.03 (95% CI 1.02–1.04)] vs. [1.04 (95% CI 1.02–1.05)] and treatment with biologics [OR = 1.66 (95% CI 1.22–2.24) vs. [1.68 (95% CI 1.19–2.38)] were independent factors associated with vaccination in both periods. These findings, although are temporally encouraging, emphasize the need for continuous campaigns aiming at increasing patients' and physicians' awareness about the bene fits of vaccination.

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Knowledge gap about immune checkpoint inhibitors among rheumatologists and medical students: a survey

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Abstract

Previous studies found that physicians working in developed countries in Europe and in the USA declared insufficient knowledge concerning immune-related adverse events (irAE) following use of immune checkpoint inhibitors (ICI) in cancer treatment. We determined this knowledge gap among rheumatologists and medical students (MS) in Brazil. A web-based structured survey or a direct interview was applied to 1428 board-certified Brazilian rheumatologists and an adapted questionnaire was sent to 840 undergraduate MS attending the last 2 years of Medical Schools in Fortaleza-CE, Brazil, in September 2019. 228 (15.9%) rheumatologists and 145 (17.2%) MS answered the survey; 136 (60%) rheumatologists worked at Institutions with Oncology service. Rheumatologists had 22.6 ± 12.6 years of medical practice, most [116 (50.9%)] worked in private practice and 9 (3.9%) were on training. Fifty-three (23.4%) declared being familiar [40 (17.6%)] or very familiar [13 (5.8% )] with irAE. Almost two-thirds declared having never managed irAE and about a third (38.6%) felt confident in managing such patients. Knowledge among rheumatologists was similar regardless of having more or less than 10 years of practice (P = 0.758). Less than 5% MS declared being familiar with ICI and most have never heard of irAE. There is a large gap concerning knowledge about ICI and irAE among rheumatologists and MS in Brazil. Continuing medical education strategies are needed to improve this knowledge.

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A retrospective comparison of respiratory events with JAK inhibitors or rituximab for rheumatoid arthritis in patients with pulmonary disease

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Abstract

Janus kinase inhibitors (JAKi) are an exciting option for the treatment of rheumatoid arthritis (RA) but little is known about their safety and tolerability in patients with existing respiratory disorders. The objective was to compare pulmonary safety of JAKi versus rituximab in patients with concurrent interstitial lung disease (ILD) or bronchiectasis. We performed a retrospective electronic patient record review of patients with known ILD or bronchiectasis commencing JAKi or rituximab for the treatment of RA. Patients initiating treatment from January 2016 to February 2020 were included. Respiratory events (hospitalization or death from a respiratory cause) were compared using Kaplan–Meier survival analysis. We analysed patients who received JAKi (n = 28) and rituximab (n = 19) for a mean (SD) of 1.1 (0.62) and 2.14 (1) years respectively. Patients were predominantly female (68%), anti-CCP antibody positive (94%) and non-smoking (8 9%) with a median (IQR) percentage predicted FVC at baseline of 100% (82–115%) and percentage predicted TLCO of 62% (54.5–68%). Respiratory events occurred in five patients treated with JAKi (18%; 5 hospitalizations, 2 deaths) and in four patients treated with rituximab (21%; 3 hospitalizations, 1 death). Respiratory event rates did not differ between groups (Cox-regression proportional hazard ratio = 1.38, 95% CI 0.36–5.28; p = 0.64). In this retrospective study, JAKi for the treatment of RA with existing ILD or bronchiectasis did not increase the rate of hospitalization or death due to respiratory causes compared to those treated with rituximab. JAK inhibition may provide a relatively safe option for RA in such patients.

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Primary central nervous system lymphoma in neuropsychiatric systemic lupus erythematosus: case-based review

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Abstract

Primary central nervous system lymphoma (PCNSL) sometimes occurs in immune-compromised hosts or patients with autoimmune diseases. Some cohort studies have previously reported an increased risk of non-Hodgkin's lymphoma in systemic lupus erythematosus (SLE), while some cases of PCNSL in patients with SLE were reported. We present the case of PCNSL which developed in a patient with the active phase of neuropsychiatric SLE (NPSLE). Furthermore, we reviewed published English articles to confirm the characteristics of PCNSL related to SLE. To our knowledge, this is the first report of PCNSL occurring in NPSLE. Histology demonstrated B-cell lymphoma with a positive Epstein–Barr virus-encoded RNA. This patient recovered following surgical resection of the lymphoma, whole brain radiation therapy, intravenous infusion of rituximab (RTX), and administration of belimumab after RTX. Given the series of reviews, our report suggests that the persistence of damage in the central nervous system (CNS) and long-term exposure to immunosuppressants may impact oncogenic immune responses within the CNS, leading to PCNSL development.

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Antibody subtypes and titers predict clinical outcomes in ANCA-associated vasculitis

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Abstract

The objective of this study is to evaluate the association between antineutrophil cytoplasmic autoantibody (ANCA) subtype and ANCA titers on clinical outcomes and disease activity among a cohort of patients from Central Appalachia diagnosed with ANCA-associated vasculitis (AAV) over a 3-decade period. This is a retrospective chart review of all patients diagnosed with AAV. ANCA subtypes (myeloperoxidase (MPO) and proteinase 3 (PR3)) and titers at the time of diagnosis and at the time of relapse or last follow-up were evaluated along with patient outcomes. Outcomes of interest included relapse, development of end-stage renal disease (ESRD) and mortality. Sensitivity analysis and multivariable analysis were performed. Of the 202 patients, 111 patients were MPO-ANCA positive and 91 patients were PR3-ANCA positive. Relapse was more frequent among patients with PR3-ANCA compared to MPO-ANCA (35% vs 12%, p < 0.001). In both ANCA subgroups, the stronge st predictor of relapse was an increase in titers prior to relapse, HR 8.1 (95% CI 1.6–40), p 0.009. Patients who achieved serological remission had a lower risk of ESRD [sub-HR 0.31 (95% CI 0.11–0.89)] and mortality [HR (95% CI) 0.24 (0.07–0.7)]. PR3-ANCA was associated with higher risk of ESRD [sub-HR 3.1 (95% CI 1.1–8.5)]. There was no difference in mortality between patients with MPO-ANCA and PR3-ANCA. Our study supports the use of both ANCA subtypes and titer levels for predicting clinical outcomes in patients receiving treatment for AAV. Monitoring of ANCA antibody titers may be useful since both serological remission and increase in titers provide prognostic information.

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The association of Candida and antifungal therapy with pro-inflammatory cytokines in oral leukoplakia

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Abstract

Objectives

To study the association of Candida and antifungal therapy with pro-inflammatory cytokines (PIC) in oral leukoplakia (OL).

Materials and methods

A prospective observational study where immunocompetent adult subjects with OL (30 homogenous (HL), 30 non-homogenous (NHL)) and 30 age and sex-matched healthy controls (C) with no predisposing factors for oral Candida infection were recruited. Sterile cotton swabs and ophthalmic sponges were used to sample the lesion surface in OL and buccal mucosa in C, for direct microscopy and culture for Candida and to determine levels of PIC (IL-6, IL-8. IL-17, TNF-α) by ELISA, respectively. Sampling for PIC was repeated at same sites in OL, 2 weeks after antifungal therapy.

Results

Candida was associated with 55.3% of NHL, 23.3% of HL and 13.3% of C. The oral secretary levels of PIC were raised in NHL as compared to HL and C. The levels of IL-6, IL-8, TNF-α (p<0.001) and IL-17 (p<0.01) were significantly raised in Candida positive NHL while IL-6 (p<0.05) and TNF-α (p<0.01) were significantly raised in Candida positive HL before antifungal treatment. After antifungal treatment, there was significant reduction in PIC in Candida positive NHL and HL.

Conclusions

Candida infection contributes to the inflammatory milieu in Candida associated OL which increases the risk of carcinogenesis. Antifungal therapy reduces the PIC in Candida associated OL.

Clinical relevance

Identification and elimination of predisposing factors for Candida infection, like cessation of harmful habits, maintenance of oral/denture hygiene, surveillance for Candida and antifungal therapy at intervals, are recommended in OL.

Clinical trial registration

ClinicalTrials.gov Identifier: NCT04712929

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Distinct phylogeographic patterns in populations of two oribatid mite species from the genus Pantelozetes (Acari, Oribatida, Thyrisomidae) in Central Europe

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Abstract

Oribatid mites are important decomposers of dead organic matter in soils across the world. Their origin dates back at least 380 Mya. Multiple severe climatic changes during Late Pliocene and Pleistocene shaped the migration patterns of these organisms and should be reflected in the genetic variability of their current populations. In this study, we examined the genetic diversity and phylogeographic structure as well as the evolutionary history of populations of two ecologically different oribatid mite species. Pantelozetes cavaticus is a troglophile oribatid mite known mainly from Central European caves, whereas Pantelozetes paolii is a common surface eurytopic species with Holarctic distribution. We used two molecular markers—mitochondrial cytochrome c oxidase subunit I (COI) and the nuclear D3 region of the 28S rDNA gene—to reveal phylogenetic relationships between contemporary populations. Whereas the D3 region showed minimal or no variab ility within populations, COI appeared to be a relevant marker for population studies. Phylogeographic analysis based on COI detected two lineages of P. cavaticus ('Czech' and 'Slovak'), which separated during the Late Pliocene (2.9 Mya) and revealed the existence of one new species. In contrast, three identified genetic lineages of P. paolii (radiation time 2.9 and 1.2 Mya, respectively) uncovered in this study were found to coexist in the distant sampling localities, suggesting a connection between populations even over long distances.

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Risk and clinical outcomes of COVID-19 in patients with rheumatic diseases compared with the general population: a systematic review and meta-analysis

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Abstract

Patients with rheumatic diseases are often more susceptible to different bacteria and viruses because of immune impairment, but it is not clear whether there is a higher risk of infection and a more serious course of disease for novel coronavirus (SARS-CoV-2). We performed this systematic review and meta analysis to assess the risk and clinical outcomes of COVID-19 in patients with rheumatic diseases compared with the general population. We searched PubMed, EMBASE, Scopus and Web of Science databases from January 1, 2020 to October 20, 2020 to determine epidemiological information related to patients with rheumatic diseases and COVID-19, including clear risk estimate or data that could be converted and extracted. We included 26 observational studies, totaling about 2000 patients with rheumatic diseases of whom were infected with COVID-19. Meta-analysis showed that the risk of COVID-19 infection in rheumatic patients was significantly higher than that in the gen eral population (OR = 1.53, 95% CI 1.24–1.88, P = 0.000). In terms of hospitalization and severe clinical outcomes associated with COVID-19, we found that rheumatic patients showed similar results to the reference population (hospitalization OR = 1.36, 95% CI 0.81–2.29, P = 0.247; admitted to ICU OR = 1.94, 95% CI 0.88–4.27, P = 0.098; death OR = 1.29, 95% CI 0.84–1.97, P = 0.248). The presence of comorbidities, hypertension, lung diseases were significantly associated with the increased risk of COVID-19-related hospitalization in rheumatic patients and anti-TNF drugs were associated with lower hospitalization risk. Older age was related to severe COVID-19. Our meta-analysis indicated that rheumatic patients were at a higher risk of COVID-19 infection but might not lead to a more serious disease process.

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