High amount of polyclonal free light chains (FLC) are reported in systemic autoimmune diseases (SAD) and we took advantage of the PRECISESADS study to better characterize them. Serum FLC levels were explored in 1979 patients with SAD (RA, SLE, SjS, Scl, APS, UCTD, MCTD) and 614 healthy controls. Information regarding clinical parameters, disease activity, medications, autoantibodies (Ab) and the interferon α and/or γ scores were recorded. Among SAD patients, 28.4% had raised total FLC (from 12% in RA to 30% in SLE and APS) with a normal kappa/lambda ratio. Total FLC levels were significantly higher in SAD with inflammation, active disease in SLE and SjS, and an impaired pulmonary functional capacity in SSc, while independent from kidney impairment, infection, cancer and treatment. Total FLC concentrations were positively correlated among the 10/17 (58.8%) autoantibodies (Ab) tested with anti-RNA binding protein Ab (SSB, SSA-52/60 kDa, Sm, U1-RNP), anti-dsDNA/nucleosome Ab, rheumatoid factor and negatively correlated with complement fractions C3/C4. Finally, examination of interferon (IFN) expression as a potential driver of FLC overexpression was tested showing an elevated level of total FLC among patients with a high IFNα and IFNγ Kirou\'s score, a strong IFN modular score, and the detection in the sera of B-cell IFN dependent factors, such as TNF-R1/TNFRSF1A and CXCL10/IP10. In conclusion, an elevated level of FLC, in association with a strong IFN signature, defines a subgroup of SAD patients, including those without renal affectation, characterized by increased disease activity, autoreactivity, and complement reduction.

UNASSIGNED: Granulomatous Lung Diseases (GLD) encompasses a wide range of infectious and non-infectious conditions characterized by chronic inflammatory response. However, different GLD may share similar imaging findings. In this context, the purpose of this study was to outline the etiological profile and their imaging features in patients with GLD who underwent lung biopsy.
UNASSIGNED: Patients with granulomatous lesions in lung biopsies and previous chest CT performed from 2014 to 2017 at our institution had imaging data reviewed by three blinded radiologists. The imaging features were analyzed according to the Fleischner Society glossary. Categorical data were represented by absolute (n) and relative (%) frequency. The contingency matrices were analyzed by Pearson\'s Chi-square test. Interreader agreement was assessed by calculating the intraclass correlation coefficient, using kappa (κ) statistic.
UNASSIGNED: Thirty-eight of 75 (50.7%) patients were women with a mean age of 59 ± 39 years. Infection was the most common cause of GLD (47/75, 62.7%) and Histoplasma capsulatum (27/75, 36%) was the most prevalent etiology. Nodular pattern was the most common imaging feature in histoplasmosis cases (25/27, 92.6%), whereas it occurred in half of cases (24/48) of GLD of other causes (p < 0.05). Among patients with tuberculosis, the second etiology of GLD in our study population, the most common imaging pattern was centrilobular micronodules (3/7, 42.9%), significantly more frequent than in other causes of GLD (6/68, 8.8%). Interreader agreement in detecting imaging features was almost perfect (κ = 0.88-1.00), except the nodular pattern, which had substantial agreement (κ = 0.73).
UNASSIGNED: In our study population, the main etiologies found in patients with granulomatous disease who underwent lung biopsy were fungal or mycobacterial disease, specially histoplasmosis and tuberculosis, and nodular pattern with focal distribution was the most common imaging finding which was detected with substantial interreader agreement.

UNASSIGNED: Focused cardiac ultrasound (FOCUS) examination using a portable device is increasingly used for bedside diagnosis of cardiovascular diseases. This is a 4-week pilot project aiming to teach medical students to perform FOCUS to detect valvular heart lesions.
UNASSIGNED: Patients undergoing routine transthoracic echocardiography (TTE) were recruited by third year medical students who performed physical examination (PE) and FOCUS after 6-hour training to detect significant (moderate-to-severe) valvular lesions. Performance of FOCUS and PE was compared to TTE as reference using kappa statistics.
UNASSIGNED: 10 medical students performed 212 PE and FOCUS on 107 patients with mean age 63.7 ± 14.9 years. TTE detected 126 significant valvular lesions of which FOCUS correctly identified 54 lesions (κ = 0.45) compared to 32 lesions by PE (κ = 0.28, p < 0.01). FOCUS was better than PE in identifying mitral stenosis (κ = 0.51 vs. 0.17), aortic stenosis (κ = 0.45 vs. 0.16) and tricuspid regurgitation (κ = 0.39 vs. 0.09, all p < 0.01). Students became more proficient in performing FOCUS examination with time.
UNASSIGNED: Teaching junior medical students to perform and interpret FOCUS was feasible after brief training and better than PE in detecting significant valvular lesions. Further studies are warranted to determine the utility of incorporating this new technology into mainstream medical training.

It is aimed to investigate the central antinociceptive effect of protocatechuic acid and the involvement of stimulation of opioidergic, serotonin 5-HT2A/2C, α2-adrenergic and muscarinic receptors in protocatechuic acid-induced central analgesia in mice. Time-dependent antinociceptive effects of protocatechuic acid at the oral doses of 75, 150 and 300 mg/kg were tested in hot-plate (integrated supraspinal response) and tail-immersion (spinal reflex) tests in mice. To investigate the mechanisms of action; the mice administered 300 mg/kg protocatechuic acid (p.o.) were pre-treated with non-specific opioid antagonist naloxone (5 mg/kg, i.p.), serotonin 5-HT2A/2C receptor antagonist ketanserin (1 mg/kg, i.p.), α2-adrenoceptor antagonist yohimbine (1 mg/kg, i.p.) and non-specific muscarinic antagonist atropine (5 mg/kg, i.p.), respectively. The antinociceptive effect of protocatechuic acid was observed at the doses of 75, 150 and 300 mg/kg in tail-immersion test, at the doses of 150 and 300 mg/kg in hot-plate test at different time interval. The enhancement in the latency of protocatechuic acid-induced response to thermal stimuli was antagonized by yohimbine, naloxone and atropine in tail-immersion test, while it was antagonized only by yohimbine and naloxone pretreatments in hot-plate test. These results indicated that protocatechuic acid has the central antinociceptive action that is probably organized by spinal mediated cholinergic and opiodiergic, also spinal and supraspinal mediated noradrenergic modulation. However, further studies are required to understand how protocatechuic acid organizes the interactions of these modulatory systems. As a whole, these findings reinforce that protocatechuic acid is a potential agent that might be used for pain relief. Additionally, the clarification of the effect and mechanisms of action of protocatechuic acid will contribute to new therapeutic approaches and provide guidance for new drug development studies.