Interstitial lung disease with and without progressive fibrosing phenotype in patients with idiopathic inflammatory myopathies: data from a large multicentric cohort.

OBJECTIVES: Patients with connective tissue diseases can develop interstitial lung disease (ILD), leading to a progressive fibrosing ILD (PF-ILD) phenotype in some cases. We aimed to investigate the occurrence of PF-ILD in idiopathic inflammatory myopathies (IIMs), and factors potentially predicting this phenotype. Secondary aims were to assess the radiological pattern and factors associated with IIMs-ILD. METHODS: Patients with IIMs from our multicentric prospective cohort were retrospectively evaluated. Data were recorded at IIMs and ILD diagnosis, and during follow-up. Patients with ILD were classified according to the predominant high-resolution CT (HRCT) pattern: non-specific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP) and organising pneumonia (OP). PF-ILD was defined according to the 2022 American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS) and Latin American Thoracic Society (ALAT) guidelines. Univariate and multivariate analyses were performed to identify factors associated to ILD and to PF-ILD. RESULTS: Of 253 patients with IIMs, 125 (49%) had ILD: 99 (78%) at IIMs diagnosis and 26 (22%) during follow-up (21/26 within 5 years). Multivariate analysis identified anti-Jo-1, anti-MDA5, anti-Ro52, high score on manual muscle test, mechanic's hands and Raynaud's phenomenon as independently associated with ILD. The predominant HRCT pattern was NSIP (50% of patients), followed by UIP (28%) and OP (22%). At 1-year follow-up, PF-ILD occurred in 18% of IIMs-ILD. PF-ILD was predicted by anti-MDA5, heliotropic rash, xerostomia and xerophthalmia at univariate but not at multivariate analysis. CONCLUSION: Patients with IIM should be carefully screened for ILD at IIMs diagnosis and yearly during follow-up. All patients with IIMs-ILD should be carefully monitored to capture ILD progression since a consistent proportion of them are expected to develop PF-ILD.

Non-anti TNFα biologic agents for noninfectious uveitis associated with systemic inflammatory diseases: a systematic review.

INTRODUCTION: Noninfectious uveitis related to systemic inflammatory diseases represents a leading cause of blindness. Anti-TNFα agents are the first-line biologic therapy after traditional immunosuppressants, for ocular and systemic involvement. However, some patients fails anti-TNFα agents, due to primary inefficacy, loss of efficacy or adverse events. AREAS COVERED: This systematic review summarizes evidence on the efficacy and safety of non-anti-TNFα biologics in adult patients with noninfectious uveitis associated with systemic inflammatory diseases. The systematic review of PubMed and Embase yielded 3663 records, from which 16 studies were included (13 non-controlled, 3 controlled trials). Most studies focused on Behçet's syndrome (BS) and juvenile idiopathic arthritis (JIA) and assessed the efficacy of tocilizumab (n = 11), rituximab (n = 3), secukinumab (n = 1), or anakinra/canakinumab (n = 1). A body of evidence supports the use of tocilizumab BS and JIA-associated uveitis, for improving visual acuity, reducing central macular thickness, inducing ocular remission, and sparing corticosteroids. Preliminary data suggest that rituximab may represent a valid alternative, particularly in JIA, while anakinra/canakinumab might play a role in BS-associated uveitis. The role of secukinumab appears limited. EXPERT OPINION: Current evidence encourages investigations on the efficacy and safety of non-anti-TNFα agents in noninfectious non-idiopathic uveitis.

Evidence of subclinical atherosclerosis in eosinophilic granulomatosis with polyangiitis.

OBJECTIVES: Patients affected by eosinophilic granulomatosis with polyangiitis (EGPA) display an increased risk of atherothrombotic events compared with the general population. An increased frequency of subclinical markers of atherosclerosis has been observed in other ANCA-associated vasculitis, but no specific study focused on EGPA. We therefore evaluated subclinical atherosclerosis in EGPA patients and in a control population. METHODS: Forty EGPA patients and 80 controls matched by age, sex and traditional cardiovascular risk factors underwent sonographic assessment of common carotid artery (CCA) intima-media thickness (IMT). The presence of plaques of the CCA was also investigated. The correlation between CCA-IMT and clinical and laboratory features was also assessed. RESULTS: Median CCA-IMT was significantly higher in EGPA patients compared with controls (P = 0.002). Also, the proportion of subjects with increased CCA-IMT and with presence of plaques was significantly higher among EGPA patients (P < 0.001 for both). Moreover, within the EGPA cohort, CCA-IMT tended to increase with disease duration (P = 0.034) and corticosteroid cumulative dose (P = 0.004). No significant associations were found between CCA-IMT, ANCA status, other clinical features and therapeutic regimens. Notably, the prevalence of traditional cardiovascular risk factors was comparable in patients with vs without an increased CCA-IMT. CONCLUSION: Ultrasound markers of subclinical atherosclerosis are increased in EGPA patients as compared with controls, independently of traditional cardiovascular risk factors.

Anakinra effectiveness in refractory polyserositis: An Italian multicenter study.

OBJECTIVES: Polyserositis is an inflammatory condition involving different serosal membranes at the same time, specifically the pericardium, pleura, and peritoneum with exudates in the respective cavities. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and glucocorticoids may be effective in patients with polyserositis, but relapses often occur when these drugs are tapered or discontinued. The interleukin (IL)-1 receptor antagonist anakinra has shown a beneficial effect in idiopathic recurrent pericarditis, mostly in unresponsive patients who develop steroid dependence and/or colchicine resistance. To date, there are no data suggesting the best therapy for managing acute episodes and/or relapses of polyserositis. On this basis, we performed a retrospective study aimed at evaluating the effectiveness and safety profile of anakinra in treating patients with refractory polyserositis. METHODS: Patients with idiopathic polyserositis or rheumatic diseases presenting inflammation of 2 or more serous membranes were included. Serositis had to be confirmed by imaging tests comprising either echocardiography, abdominal ultrasound, chest or abdomen computed tomography and/or chest x-ray scan. We included patients with polyserositis who started anakinra from January 2011 to January 2019 due to a poorly controlled disease despite treatment with NSAIDs, conventional immunosuppressant drugs, or the need to minimize oral corticosteroids intake. Erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and imaging tests, were recorded to monitor serositis at baseline and either at 3, 6 and 12-month follow-up. Patients with malignancies and infectious diseases were excluded from the analysis. RESULTS: Forty-five patients with recurrent polyserositis (23 women) (mean age 43.2±15.8 years and mean disease duration 23.1±28 years) were analysed. Polyserositis was idiopathic in 26 (57.8%) patients. Thirteen patients suffered from autoinflammatory diseases, whereas 6 were affected by autoimmune diseases. Combination treatment with colchicine and NSAIDs at anakinra baseline was administered in 38/45 (84.4%) and 37/45 (82.2%) patients, respectively. After starting anakinra, 84.5% of patients experienced a resolution of serositis with a dramatic decrease in ESR and CRP (P<0.001, for both) already at 3 months, furthermore the same beneficial effect was observed up to 12 months. No relapse was seen at 3 months, whereas the median number of relapses at 6 and 12 months was 0 (interquartile range 0-1). Glucocorticoids were discontinued in 22/45 (48.9%) patients already after 3 months (P<0.001). After 12 months 32/37 (86.5%) patients were steroid-free. Similarly, NSAIDs use significantly was decreased at 3 months (7/45 [15.6%] patients, P<0.001), whereas at 12-month follow-up no patient was on NSAIDs. Urticarial rashes at anakinra injection site occurring in 3 patients were the most common adverse events. CONCLUSIONS: Anakinra appeared to be a safe and useful therapeutic choice for patients refractory to optimal anti-inflammatory therapy (NSAIDs, colchicine and corticosteroids), allowing not only a dramatic reduction of recurrences but also of corticosteroids use. Anakinra was effective both in the idiopathic forms of polyserositis and in those with an underlying rheumatic disease, suggesting a common pathogenic pathway leading to serositis onset.

Serum sodium alterations in SARS CoV-2 (COVID-19) infection: impact on patient outcome.

OBJECTIVE: Hyponatremia is the most common electrolyte disorder in hospitalized patients and occurs in about 30% of patients with pneumonia. Hyponatremia has been associated with a worse outcome in several pathologic conditions The main objective of this study was to determine whether serum sodium alterations may be independent predictors of the outcome of hospitalized COVID-19 patients. DESIGN AND METHODS: In this observational study, data from 441 laboratory-confirmed COVID-19 patients admitted to a University Hospital were collected. After excluding 61 patients (no serum sodium at admission available, saline solution infusion before sodium assessment, transfer from another hospital), data from 380 patients were analyzed. RESULTS: 274 (72.1%) patients had normonatremia at admission, 87 (22.9%) patients had hyponatremia and 19 (5%) patients had hypernatremia. We found an inverse correlation between serum sodium and IL-6, whereas a direct correlation between serum sodium and PaO2/FiO2 ratio was observed. Patients with hyponatremia had a higher prevalence of non-invasive ventilation and ICU transfer than those with normonatremia or hypernatremia. Hyponatremia was an independent predictor of in-hospital mortality (2.7-fold increase vs normonatremia) and each mEq/L of serum sodium reduction was associated with a 14.4% increased risk of death. CONCLUSIONS: These results suggest that serum sodium at admission may be considered as an early prognostic marker of disease severity in hospitalized COVID-19 patients.

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study.

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.

Leukostasis retinopathy with leukemic infiltrates as onset manifestation of chronic myeloid leukemia: a case report.

PURPOSE: To describe a case of retinopathy as onset manifestation of chronic myeloid leukemia (CML), successfully treated with leukapheresis and medical therapy. METHODS: A 28-year-old male patient presented complaining painless acute visual impairment in his right eye (RE). He reported moderate asthenia and episodes of night sweats during the previous month. His past medical history was unremarkable. BCVA at presentation was 20/80 in RE and 20/32 in left eye (LE). Fundus examination revealed venous congestion, diffuse Roth spots, and whitish macular infiltrates in both eyes. OCT showed hyperreflective foveal infiltrates, in both eyes. Blood test showed markedly elevated white blood cells (WBCs) count (430 × 103/mm3). Clinical-instrumental examination revealed hepatosplenomegaly. These features were consistent with CML. The patient was treated with leukapheresis and nilotinib. RESULTS: After 2 weeks of treatment, the WBCs count dropped (71 × 103/mm3), and the patient reported subjective improvement of symptoms. At 1-month follow-up, BCVA and retinopathy signs were improved in both eyes. OCT showed the almost complete resolution of foveal infiltrates with ellipsoid zone focal defects. At 4-months follow-up, we observed complete resolution of retinopathy. BCVA was 20/32 in RE and 20/25 in LE. OCT showed the persistence of ellipsoid zone focal defects in RE and complete anatomical restoration in LE. At 6-months follow-up, the patient was clinically well and his WBCs count was normal. CONCLUSION: In our case, the CML-related retinopathy represented the onset sign of the underlying systemic pathology, leading to proper management and treatment, with hematological normalization and resolution of the retinopathy.

Successful use of caplacizumab in a case of refractory acquired thrombotic thrombocytopenic purpura following subacute thyroiditis.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare condition mainly characterized by microangiopathic hemolytic anemia, thrombocytopenia, reported in approximately three cases per one million adults per year. Some reports describing co-occurrence of aTTP and other autoimmune disorders, as Graves' thyroiditis, are reported. To the best of our knowledge this is the first report describing co-occurrence of subacute thyroiditis and aTTP. The patient was refractory to conventional therapy with plasma exchange, steroids and rituximab but was successfully treated with the addition of caplacizumab, an anti-VWF bivalent variable-domain-only immunoglobulin fragment that inhibits interaction between VWF multimers and platelets.

Prompt Predicting of Early Clinical Deterioration of Moderate-to-Severe COVID-19 Patients: Usefulness of a Combined Score Using IL-6 in a Preliminary Study.

BACKGROUND: The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. OBJECTIVE: The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of patients with noncritical COVID-19. METHODS: A total of 208 patients with noncritical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained on admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. RESULTS: Clinical worsening occurred in 63 patients (16 = died; 39 = transferred to intensive care unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (P = .005), C-reactive protein (CRP) (P = .003), and SaO2/FiO2 (P = .014) were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an area under the curve = 0.88 (95% confidence interval: 0.83-0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14- or 21-day worsening and in predicting death occurring during all the follow-up. CONCLUSIONS: Combining IL-6, CRP, and SaO2/FiO2 in a score may help clinicians to identify on admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.

New findings on type 2 diabetes in first-generation Chinese migrants settled in Italy: Chinese in Prato (CHIP) cross-sectional survey.

BACKGROUND: Chinese people are one of the fastest growing immigrant populations in Europe, and their health has become a key issue to host nations. Although type 2 diabetes (T2DM) is a big burden among migrant populations, data on Chinese immigrants in Europe are limited. METHODS: A cross-sectional survey was performed in 2014, adopting principles of community-based participatory research to investigate T2DM, diagnosed by the American Diabetes Association fasting criteria, in Chinese first-generation migrants aged 16 to 59 years settled in Prato (Italy). Association with different factors was investigated using logistic regression. RESULTS: Of the 1608 participants, 177 had T2DM (11.0%), 119 being newly diagnosed (7.4%). Among subjects with diabetes, 58 (32.8%) were aware of the disease; among subjects with diabetes aware of their condition, 46 (79%) were treated with glucose lowering drugs. Age-standardized (World Health Organization 2001 population) prevalence of T2DM was 9.6% (95% CI 9.1 to 10.2%), being 12.0% (95% CI 11.0 to 12.9%) in men, and 7.8% (95% CI 7.1 to 8.4%) in women. At adjusted logistic regression, diabetes was associated with hypertension, current smoking, adiposity indices (waist circumference, waist-to-hip ratio, waist-to-height ratio, and body mass index), and high triglycerides. T2DM, adiposity indices, and high triglycerides were not associated with duration of stay in Italy. CONCLUSIONS: The high prevalence of T2DM among first-generation Chinese immigrants in Europe stresses the need for specific health programs for T2DM early diagnosis, treatment, and prevention. There is an urgent need for policies to support this group because current policies will produce major social and economic costs. Copyright © 2016 John Wiley & Sons, Ltd.

Sleep History and Hypertension Burden in First-Generation Chinese Migrants Settled in Italy: The CHIinese In Prato Cross-Sectional Survey.

Migration flows from China are largely directed towards the South of Europe, Chinese being now the third largest overseas-born population in Italy. The aim of the study was to investigate hypertension burden and self-reported sleep disorders among 1608 first-generation Chinese migrants aged 16 to 59 years settled in Prato and recruited in a cross-sectional survey. Hypertension was defined as systolic BP ≥ 140  mm Hg and/or diastolic BP ≥ 90  mm Hg or self-reported antihypertensive treatment; potential impact of sleep disorders was analyzed by logistic regression adjusted for age, sex, marital status, education, health insurance, current smoking, parental hypertension, alcohol drinking, overweight or obesity, central obesity, diabetes, high total cholesterol, and high triglycerides. Among the 1608 participants, 21.7% were hypertensive (age-standardized prevalence 19.2%; 95% Cl: 18.5-20.0); 54% of hypertensive subjects were aware of their condition; 70% of aware hypertensive subjects received drugs, and 39% of treated subjects had blood pressure controlled. Self-reported snoring increased the risk of hypertension; when compared with no snoring, the age- and sex-adjusted OR for hypertension of snoring 3 to 6  d/week was 2.11 (95% Cl: 1.48-3.01) and 2.48 (95% Cl: 1.79-3.46) of snoring every day. When compared with a sleep duration ≤ 5  hours, subjects with sleep duration of 7  hours had reduced risk of high triglycerides (adjusted OR: 0.66; 95% Cl: 0.43-0.95).Despite a high level of awareness, low treatment rates for hypertension were observed among Chinese participants, independently of health insurance. Sleep history is to be considered in screening and prevention programs.