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Purpose: Acid-base derangement has been poorly described in patients with coronavirus disease 2019 (COVID-19). Considering the high prevalence of pneumonia and kidneys injury in COVID-19, frequent acid-base alterations are expected in patients admitted with SARS-Cov-2 infection. The study aimed to assess the prevalence of acid-base disorders in symptomatic patients with a diagnosis of COVID-19., Methods: The retrospective study enrolled COVID-19 patients hospitalized at the University Hospital of Modena from 4 March to 20 June 2020. Baseline arterial blood gas (ABG) analysis was collected in 211 patients. In subjects with multiple ABG analysis, we selected only the first measurement. A pH of less than 7.37 was categorized as acidemia and a pH of more than 7.43 was categorized as alkalemia., Results: ABG analyses revealed a low arterial partial pressure of oxygen (PO 2 , 70.2 ± 25.1 mmHg), oxygen saturation (SO 2 , 92%) and a mild reduction of PO 2 /FiO 2 ratio (231 ± 129). Acid-base alterations were found in 79.7% of the patient. Metabolic alkalosis (33.6%) was the main alteration followed by respiratory alkalosis (30.3%), combined alkalosis (9.4%), respiratory acidosis (3.3%), metabolic acidosis (2.8%) and other compensated acid-base disturbances (3.6%). All six patients with metabolic acidosis died at the end of the follow-up., Conclusion: Variations of pH occurred in the majority (79.7%) of patients admitted with COVID-19. The patients experienced all the type of acid-base disorders, notably metabolic and respiratory alkalosis were the most common alterations in this group of patients., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Acute kidney injury (AKI) is a severe complication of coronavirus disease-2019 (COVID-19). This study aims to evaluate incidence, risk factors and case-fatality rate of AKI in patients with COVID-19., Methods: We reviewed the health medical records of 307 consecutive patients with COVID-19 hospitalized at the University Hospital of Modena, Italy., Results: AKI was diagnosed in 69 out of 307 (22.4%) COVID-19 patients. Stages 1, 2, or 3 AKI accounted for 57.9%, 24.6% and 17.3%, respectively. AKI patients had a mean age of 74.7 ± 9.9 years. These patients showed higher serum levels of the main markers of inflammation and higher rate of severe pneumonia than non-AKI patients. Kidney injury was associated with a higher rate of urinary abnormalities including proteinuria (0.44 ± 0.85 vs 0.18 ± 0.29 mg/mg; P =  < 0.0001) and microscopic hematuria (P = 0.032) compared to non-AKI patients. Hemodialysis was performed in 7.2% of the subjects and 33.3% of the survivors did not recover kidney function after AKI. Risk factors for kidney injury were age, male sex, CKD and higher non-renal SOFA score. Patients with AKI had a mortality rate of 56.5%. Adjusted Cox regression analysis revealed that COVID-19-associated AKI was independently associated with in-hospital death (hazard ratio [HR] = 4.82; CI 95%, 1.36-17.08) compared to non-AKI patients., Conclusion: AKI was a common and harmful consequence of COVID-19. It manifested with urinary abnormalities (proteinuria, microscopic hematuria) and conferred an increased risk for death. Given the well-known short-term sequelae of AKI, prevention of kidney injury is imperative in this vulnerable cohort of patients., (© 2021. Japanese Society of Nephrology.)

Background: Patients with COVID-19 experience multiple clinical conditions that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder closely associated with severe complications. This study aimed to estimate prevalence, risk factors and outcome of hypokalemia in a cohort of patients with confirmed COVID-19., Methods: A retrospective analysis was conducted on 290 non-ICU admitted patients with COVID-19 at the tertiary teaching hospital of Modena, Italy, from February 16 to April 14, 2020., Results: Hypokalemia was detected in 119 out of 290 patients (41%) during hospitalization. Mean serum potassium was 3.1 ± 0.1 meq/L. The majority of patients (90.7%) patients experienced only a mild decrease in serum potassium level (3-3.4 mEq/L). Hypokalemia was associated with hypocalcemia, which was detected in 50% of subjects. Urine potassium-to-creatinine ratio, measured in a small number of patients (n = 45; 36.1%), revealed an increase of urinary potassium excretion in most cases (95.5%). Risk factors for hypokalemia were female sex (odds ratio (OR) 2.44; 95% CI 1.36-4.37; P 0.003) and diuretic therapy (OR 1.94, 95% CI 1.08-3.48; P 0.027). Hypokalemia, adjusted for sex, age and SOFA score, was not associated with ICU transfer (OR 0.52; 95% CI 0.228-1.212; P = 0.131), in-hospital mortality (OR, 0.47; 95% CI 0.170-1.324; P = 0.154) and composite outcome of ICU transfer or in-hospital mortality (OR 0.48; 95% CI 0.222-1.047; P = 0.065) in our cohort of patients., Conclusions: Hypokalemia was a frequent disorder in subjects with COVID-19. Female sex and diuretic therapy were identified as risk factors for low serum potassium levels. Hypokalemia was unrelated to ICU transfer and death in this cohort of patients.

Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, is known to be able to rapidly reduce acute phase reactants. Although complement components are part of the acute phase, no data are available on a possible effect of tocilizumab on complement proteins. Serum levels of complement components C3 and C4 were retrospectively assessed in 19 consecutive rheumatoid arthritis patients eligible for tocilizumab treatment. Tocilizumab was found to reduce all known acute phase reactants, including C3 and C4 levels. C3 and C4 were found to decrease as early as 4 weeks after the first tocilizumab infusion. On average, C3 decreased by 24.02, 27.35, 33.62, and 32.81%, as compared to pre-treatment values, after 1, 3, 6, and 12 months of therapy, respectively; likewise, C4 decreased by 44.74, 43.40, 54.33, and 54.56% at the same time points with respect to pre-treatment values. A discrete proportion of patients (38.46 and 30.76% for C3 and C4, respectively) displayed subnormal complement serum levels early (4 weeks) after initiation of tocilizumab treatment, which raised suspicion for complement consumption. However, no circulating immunocomplexes were found nor did any patient ever display clinical features of immunocomplex disease during a median follow-up of 38 months. After 12 months of therapy, 68.75 and 56.25% of patients had abnormally low C3 and C4 serum levels, respectively. Reduction in C3 and C4 serum levels should be included among the anti-inflammatory effects exerted by tocilizumab and are thus to be considered as an expected outcome of the mechanism of action of this drug.

Screening for active tuberculosis (TB) and latent TB infection (LTBI) is mandatory to the initiation of biological therapy in patients with rheumatic diseases. To determine the prevalence of LTBI in patients with rheumatoid arthritis before treatment with biological therapy (anti-TNF, abatacept, and tocilizumab) and the rate of TB conversion during treatment in rheumatoid arthritis (RA) patients, we evaluated the file of 275 patients with RA treated with biological agents. We considered patients with negative baseline TB screening (tuberculin skin test (TST); quantiferon TB gold in tube (QFT-GIT); chest x-ray) and with rescreening for a TB assay every year. Twenty-six patients (10.6%) resulted positive to TB screening at baseline. Two hundred and forty-nine patients (mean age 55.3 ± 11.9; median 55.8 years, range 16-81.9; 210 female) with TB screening negative at baseline were enrolled. One hundred and sixty-eight (67.5%) patients were treated with anti-TNF, 37 (14.9%) patients with abatacept, and 44 (17.7%) patients with tocilizumab. After a period of 12-120 months (median 24), 34 (13.6%) patients displayed conversion of at least one screening assay. Out of the 34 patients with conversion, 6 (16.2%) were treated with abatacept, 7 (15.9%) with tocilizumab, and 21 (12.5%) with anti-TNF. During the follow-up period, no patients developed active TB. Our study shows that a proportion of patients (13.6%) converts at least one TB screening assay during biological therapy. This study underscores the American College of Rheumatology advice for annual screening in some or all biologically treated patients.

Purpose: To assess the serum profile of factors involved in endothelial, T-cell, and fibroblast interplay in patients with Raynaud's phenomenon (RP) associated with nailfold vodeocapillaroscopy (NVC) scleroderma findings and/or systemic sclerosis (SSc) marker autoantibodies, recently labeled as early SSc patients., Methods: Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), CCL2, CXCL8, IL-13, IL-33, and transforming growth factor-β (TGF-β) were measured in 24 early SSc patients, 48 definite SSc patients, and 24 osteoarthritis/fibromyalgia controls by multiplex suspension immunoassay. All SSc patients were investigated for the presence/absence of preclinical and clinical organ involvement, SSc marker autoantibodies, and NVC abnormalities., Results: Serum sICAM-1, CCL2, CXCL8, and IL-13 were increased in all SSc patients as compared to controls, and paralleled the severity of the disease subset (early SSc < limited cutaneous SSc < diffuse cutaneous SSc; p < 0.0001). Surprisingly, IL-33 was significantly higher in early SSc patients as compared to both controls (p < 0.01) and definite SSc patients (p < 0.05). In early SSc there were no differences in the investigated markers according to the functional and serological features assessed., Conclusions: Our study suggests that an endothelial, T-cell and fibroblast activation can be present in patients with early SSc and it is associated with a distinct profile of circulating factors involved in the cross-talk of these cells. The marked increase of IL-33 in early SSc patients suggests new routes of investigation of cell-cell dynamics in target tissues predating overt disease manifestations, thus opening to new therapeutic approaches.

Glucocorticoids (GC) represent a mainstay in the therapeutical strategies of many autoimmune diseases, but their role in systemic sclerosis (SSc) is controversial. The main objective of this review is to assess the extent of and the factors associated with GC use in SSc patients, taking into account data from cohort studies and registries. We performed a search in MEDLINE databases updated to April 2013. The pooled prevalence and factors associated with GC utilization in both SSc patients collectively considered and in any of the two subsets of the disease were calculated. The pooled prevalence was 0.36 (95 % confidence interval (CI) 0.28-0.43) for overall sample. In six studies, data about the GC prescription in the two different subsets of the disease were available. The pooled prevalence was 0.52 (95 % CI 0.49-0.55) in diffuse and 0.33 (95 % CI 0.31-0.35) in limited cutaneous disease patients. Five papers reporting data about the dose of GC prescribed showed a pooled prevalence of 0.89 (95 % CI 0.87-0.91) for a daily dose of <15 mg of prednisone equivalent. Huge heterogeneity was identified across studies (I (2) > 75 %). No significant correlation was detected between the extent of GC utilization and either the percentage of concomitant immunosuppressants intake (p = 0.347), diffuse subset (p = 0.720) or female sex (p = 0.913). Despite the limited evidence for their effectiveness, GC are frequently prescribed in SSc patients, mostly in those with the diffuse subset. The variability in the extent of their utilization in different centres is considerable and suggests the need to develop treatment recommendations.

The aim of the present study was to evaluate the concentration of cell-free DNA (cf-DNA) in the plasma of patients with systemic sclerosis (SSc) and to examine the correlation of cf-DNA with clinical variables of the disease. The study population consisted of 122 SSc patients and 16 healthy controls. Epidemiological and clinical data were collected by direct assessment. The beta-globin gene was used to determine the total amount of DNA in the plasma by real-time quantitative PCR analysis. cf-DNA was found in all patients (mean concentration 1,420.7 copies/ml) and controls (mean concentration 1,462.5), with no significant difference. In SSc patients, no correlation was found between cf-DNA and the type of organ involvement, but patients with active disease presented significantly higher cf-DNA concentrations than those with inactive disease (p < 0.05). Our data suggest that cf-DNA could provide a useful biomarker for the assessment of disease activity in SSc patients.

Both oral and intravenous high-dose cyclophosphamide (CYC) regimens are associated with serious side effects when used for the treatment of systemic sclerosis (SSc). The aim of the present trial was to test the safety of low-dose intravenous CYC in patients with SSc. Eight SSc patients, in whom CYC treatment was warranted, were studied at baseline and after 6 months' intravenous CYC treatment (500 mg pulses at weeks 0, 1, 2, 6, 10, 14, 18 and 22). Side effects probably related to CYC treatment were carefully investigated. The development of amenorrhea was assessed during the period of treatment and over the following 12 months. The therapy was well tolerated overall. No patient discontinued treatment because of side effects. Leukopenia, premature ovarian failure, hemorrhagic cystitis, microscopic hematuria and liver toxicity were never detected. The most common adverse events were mild and self-limiting nausea and weakness. Our data suggest that low-dose intravenous CYC is relatively safe, at least in the short term. Further studies are needed to assess both the efficacy and the long-term safety.

Our objective was to investigate the phenotype of helper T cells in the peripheral blood of patients with systemic sclerosis (SSc). PBMC from 15 patients with SSc and 15 sex- and age-matched controls were investigated for lymphocyte subpopulations (CD3, CD4, CD8, CD19, CD16/CD56, CD3-DR); IL-2, IL-4, and IFN-gamma mRNAs; and the relative cytokines in their cytoplasm. The last assay was carried out both in unstimulated and in PMA-activated PBMC. SSc patients presented a higher percentage of activated T cells, CD3+ DR+ (19.7 +/- 9.9 vs 5.1 +/- 2.5%; P < 0.0001); 12 of them presented IFN-gamma mRNA-positive cells; and none IL-2 or IL-4 mRNAs. Under basal conditions, PBMC from six SSc patients contained IL-2, IL-4, and IFN-gamma (i.e., they showed both Th1 and Th2 activation), and 1 IFN-gamma only. PMA-stimulated PBMC of patients differed from those of controls only in the increased percentage of IFN-gamma positive cells (52 +/- 12 vs 37 +/- 11%; P < 0.01). Our study demonstrates that Thl activation occurs in the peripheral blood of SSc patients. This evidence must be faced with from both a pathogenetic and a therapeutical point of view.