534 SIX-MONTH EFFICACY OF INTRA-ARTICULAR HYALURONIC ACID FOR CARPOMETACARPAL JOINT OSTEOARTHRITIS

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Pulmonary hypertension in autoimmune rheumatic diseases.

Objective. Pulmonary hypertension is a severe and rapidly progressive disease, particularly frequent in patients with rheumatic diseases. The aims of this study were the following: to determine the prevalence of pulmonary hypertension in Italian patients with autoimmune rheumatic diseases, and to evaluate if the presence of a rheumatic disease in general, or of a specific autoimmune rheumatic disease, is a risk factor for the development of pulmonary hypertension. Patients and Methods. One hundred and thirteen Italian patients with connective tissue diseases (105 females, 8 males), aged 19 to 83 yrs, entered the study. Fifty-one had systemic sclerosis (SSc): 49 were females, 2 males, aged 34 to 83 yrs; 41 had limited cutaneous SSc, 8 diffuse cutaneous SSc, and 2 SSc sine scleroderma. Thirty-three patients had systemic lupus erythematosus (SLE): all but one were females, their age ranged from 19 to 82 yrs. Twenty-five had rheumatoid arthritis (RA): 21 females, 4 males, aged 26 to 45 yrs. Three females and one male, 51-77 yrs, had mixed connective tissue disease (MCTD). Systolic pulmonary arterial pressure (SPAP) was assessed by Doppler echocardiography. Results. Twenty three patients had pulmonary hypertension, which was more frequent in MCTD than in SLE (75% vs 6.1%, p=0.0002) or in AR (20%, p=0.0313). Pulmonary hypertension was more frequent in SSc than in SLE (25.5% vs 6.1%, p=0.0028) and in limited than in diffuse SSc(21.6% vs 3.9%). SPAP was significanly related to age (R=0.35, P=0.0275), with patients with pulmonary hypertension older than patients with normal SPAP (66±13 vs 52±16 yrs, p=0.0003). Conclusions. These data show a significant association between pulmonary hypertension and autoimmune rheumatic diseases. Therefore pulmonary hypertension assessment seems mandatory, at least in MCTD and SSc. However, more studies are needed to clarify the relationship between age and pulmonary hypertension and to verify whether the low prevalence of pulmonary hypertension we found in our SLE patients is related or not to their lower age

Campylobacter coli From Retail Liver and Meat Products Is More Aerotolerant Than Campylobacter jejuni

Aerotolerance in the microaerophilic species Campylobacter was previously reported and could increase bacterial survival and transmission in foods during stressful processing and storage conditions. In this study, 167 Campylobacter isolates (76 C. jejuni and 91 C. coli) were screened for aerotolerance; these strains were previously isolated from retail chicken meat, chicken livers, chicken gizzards, turkey, pork, and beef liver samples. Bacterial cultures were incubated aerobically in Mueller Hinton broth with agitation and viable cell counts were taken at 0, 6, 12, and 24 h. Approximately 47% of the screened Campylobacter isolates were aerotolerant (viable after a 12-h aerobic incubation period), whereas 24% were hyper-aerotolerant (viable after a 24-h aerobic incubation). A greater prevalence of aerotolerant strains (80%) was found among C. coli isolates as compared to C. jejuni isolates (6%). Differences in the oxidative stress response related genes were detected among C. jejuni and C. coli isolates when comparative genomics was used to analyze 17 Whole Genome Sequenced (WGS) strains from our laboratory. Genes encoding putative transcriptional regulator proteins and a catalase-like heme binding protein were found in C. coli genomes, but were absent in the genomes of C. jejuni. PCR screening showed the presence of a catalase-like protein gene in 75% (68/91) of C. coli strains, which was absent in all tested C. jejuni strains. While about 79% (30/38) of the hyper-aerotolerant C. coli strains harbored the catalase-like protein gene, the gene was also present in a number of the aerosensitive strains. The Catalase like protein gene was found to be expressed in both aerobic and microaerobic conditions with a 2-fold higher gene expression detected in aerobic conditions for an aerosensitive strain. However, the exact function of the gene remains unclear and awaits further investigation. In conclusion, aerotolerant Campylobacter strains (especially C. coli) are prevalent in various retail meats. Further studies are needed to investigate whether the genes encoding catalase-like heme binding protein and putative transcriptional regulators in C. coli strains are involved in stress response

Metastatic gastric cancer presenting with shoulder-hand syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Shoulder-hand syndrome is a relatively rare clinical entity classified as a complex regional pain syndrome type 1 and consisting essentially of a painful 'frozen shoulder' with disability, swelling, vasomotor or dystrophic changes in the homolateral hand. The pathophysiology is not completely clear but a predominant 'sympathetic' factor affecting the neural and vascular supply to the affected parts seems to be involved. Shoulder-hand syndrome has been related to many surgical, orthopedic, neurological and medical conditions; it is more often seen after myocardial infarction, hemiplegia and painful conditions of neck and shoulder, such as trauma, tumors, cervical discogenic or intraforaminal diseases and shoulder calcific tendinopathy, but has also been associated with herpetic infections, brain and lung tumors, thoracoplasty and drugs including phenobarbitone and isoniazid. The diagnosis of shoulder-hand syndrome is primarily clinical, but imaging studies, particularly bone scintigraphy, may be useful to exclude other disorders.</p> <p>Case presentation</p> <p>We report the case of a 67-year-old woman who presented with shoulder-hand syndrome as the initial manifestation of gastric cancer which had metastasized to bone.</p> <p>Conclusion</p> <p>Wider investigations are advisable in patients with atypical shoulder-hand syndrome. To the best of the authors' knowledge this is the first case of shoulder-hand syndrome associated with metastatic gastric cancer.</p

Nailfold videocapillaroscopy and serum VEGF levels in scleroderma are associated with internal organ involvement

Purpose: Nailfold videocapillaroscopy (NVC) identifies the microvascular hallmarks of systemic sclerosis (SSc) and vascular endothelial growth factor (VEGF) and may play a pivotal role in the associated vasculopathy. The aim of the present study was to compare NVC alterations with clinical subsets, internal organ involvement, and serum VEGF levels in a cohort of selected SSc cases. Methods: We studied 44 patients with SSc who were evaluated within 3\ua0months from enrollment by NVC, skin score, severity index, pulmonary function tests, carbon monoxide diffusing capacity (DLCO), echocardiography, pulmonary high-resolution computed tomography (HRCT), gastroesophageal (GE) endoscopy or manometry or X-ray, and serum autoantibodies. Serum VEGF-A levels were determined by ELISA in 72 SSc patients and 31 healthy controls. Results: Giant capillaries were inversely correlated with age (p\ua0=\ua00.034, r\ua0=\ua0 120.34) and to the extent of reticular pattern at HRCT (p\ua0=\ua00.04, r\ua0=\ua0 120.5). Avascular areas were directly correlated with capillaroscopy skin ulcer risk index (CSURI) (p\ua0=\ua00.006, r\ua0=\ua0+0.4) and severity index (p\ua0=\ua00.004, r\ua0=\ua0+0.5). The mean capillary density was directly correlated to the ulcer number (p\ua0=\ua00.02, r\ua0=\ua0+0.4) and to DLCO/alveolar volume (p\ua0=\ua00.02, r\ua0=\ua0+0.4) and inversely correlated with severity index (p\ua0=\ua00.01, r\ua0=\ua0 120.4) and skin score (p\ua0=\ua00.02, r\ua0=\ua0 120.4). Serum VEGF levels were higher in the SSc population vs controls (p\ua0=\ua00.03) and inversely correlated with DLCO (p\ua0=\ua00.01, r\ua0= 120.4) and directly with ground-glass and reticular pattern at HRCT (p\ua0=\ua00.04, r\ua0=\ua0+0.4 for both). Conclusions: Our data suggest the importance of NVC not only for the diagnosis, but also for the global evaluation of SSc patients. Of note, serum VEGF levels may act as a biomarker of interstitial lung involvement

Atypical cardiac defects in patients with RASopathies: Updated data on CARNET study

Background: RASopathies are a set of relatively common autosomal dominant clinically and genetically heterogeneous disorders. Cardiac outcomes in terms of mortality and morbidity for common heart defects (such as pulmonary valve stenosis and hypertrophic cardiomyopathy) have been reported. Nevertheless, also Atypical Cardiac Defects (ACDs) are described. The aim of the present study was to report both prevalence and cardiac outcome of ACDs in patients with RASopathies. Methods: A retrospective, multicentric observational study (CArdiac Rasopathy NETwork—CARNET study) was carried out. Clinical, surgical, and genetic data of the patients who were followed until December 2019 were collected. Results: Forty‐five patients out of 440 followed in CARNET centers had ACDs. Noonan Syndrome (NS), NS Multiple Lentigines (NSML) and CardioFacioCutaneous Syndrome (CFCS) were present in 36, 5 and 4 patients, respectively. Median age at last follow‐up was 20.1 years (range 6.9–47 years). Different ACDs were reported, including mitral and aortic valve dysfunction, ascending and descending aortic arch anomalies, coronary arteries dilation, enlargement of left atrial appendage and isolated pulmonary branches diseases. Five patients (11%) underwent cardiac surgery and one of them underwent a second intervention for mitral valve replacement and severe pericardial effusion. No patients died in our cohort until December 2019. Conclusions: Patients with RASopathies present a distinct CHD spectrum. Present data suggest that also ACDs must be carefully investigated for their possible impact on the clinical outcome. A careful longitudinal follow up until the individuals reach an adult age is recommended

Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice

<p>Abstract</p> <p>Background</p> <p>Inflammation may contribute to the pathogenesis of various forms of pulmonary hypertension (PH). Recent studies in patients with idiopathic PH or PH associated with underlying diseases suggest a role for interleukin-6 (IL-6).</p> <p>Methods</p> <p>To determine whether endogenous IL-6 contributes to mediate hypoxic PH and lung inflammation, we studied IL-6-deficient (IL-6^-/-) and wild-type (IL-6^+/+) mice exposed to hypoxia for 2 weeks.</p> <p>Results</p> <p>Right ventricular systolic pressure, right ventricle hypertrophy, and the number and media thickness of muscular pulmonary vessels were decreased in IL-6^-/-mice compared to wild-type controls after 2 weeks' hypoxia, although the pressure response to acute hypoxia was similar in IL-6^+/+and IL-6^-/-mice. Hypoxia exposure of IL-6^+/+mice led to marked increases in IL-6 mRNA and protein levels within the first week, with positive IL-6 immunostaining in the pulmonary vessel walls. Lung IL-6 receptor and gp 130 (the IL-6 signal transducer) mRNA levels increased after 1 and 2 weeks' hypoxia. In vitro studies of cultured human pulmonary-artery smooth-muscle-cells (PA-SMCs) and microvascular endothelial cells revealed prominent synthesis of IL-6 by PA-SMCs, with further stimulation by hypoxia. IL-6 also markedly stimulated PA-SMC migration without affecting proliferation. Hypoxic IL-6^-/-mice showed less inflammatory cell recruitment in the lungs, compared to hypoxic wild-type mice, as assessed by lung protein levels and immunostaining for the specific macrophage marker F4/80, with no difference in lung expression of adhesion molecules or cytokines.</p> <p>Conclusion</p> <p>These data suggest that IL-6 may be actively involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling in mice.</p

Cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results

BACKGROUND: RASopathies are developmental disease caused by mutations in genes encoding for signal transducers of the RAS-MAPK cascade. The aim of the present study was to provide a comprehensive description of morbidity and mortality in patients with molecularly confirmed RASopathy. METHODS: A multicentric, observational, retrospective study was conducted in seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET). Clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. Multivariable regression analysis was used to assess the impact of mutated genes on number of interventions and overall prognosis. RESULTS: Cardiac defects occurred in 80.3% of cases, almost half of them underwent at least one intervention. Overall, crude mortality was 0.29/100 patients-year. Cumulative survival was 98.8%, 98.2%, 97.7%, 94.3%, at 1, 5, 10, and 20 years, respectively. Restricted estimated mean survival at 20 years follow-up was 19.6 years. Ten patients died (2.7% of the entire cohort; 3.4% of patients with cardiac defect). Patients with hypertrophic cardiomyopathy (HCM) and age < 2 years or young adults, as well as subjects with biventricular obstruction and PTPN11 mutations had a higher risk of cardiac death. CONCLUSIONS: The risk of intervention was higher in individuals with Noonan syndrome and pulmonary stenosis carrying PTPN11 mutations. Overall, mortality was relatively low, even though the specific association between HCM, biventricular outflow tract obstructions and PTPN11 mutations appeared to be associated with early mortality, including immediate post-operative events and sudden death

Data on cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results

A comprehensive description of morbidity and mortality in patients affected by mutations in genes encoding for signal transducers of the RAS-MAPK cascade (RASopathies) was performed in our study recently published in the International Journal of Cardiology. Seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET), collaborated in this multicentric, observational, retrospective data analysis and collection. In this study, clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Cardiac defects, crude mortality, survival rate of patients with 1) hypertrophic cardiomyopathy (HCM) and age <2 years or young adults; 2) individuals with Noonan syndrome and pulmonary stenosis carrying PTPN11 mutations; 3) biventricular obstruction and PTPN11 mutations; 4) Costello syndrome or cardiofaciocutaneous syndrome were analysed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. In particular, with this Data In Brief (DIB) paper, the authors aim to report specific statistic highlights of the multivariable regression analysis that was used to assess the impact of mutated genes on number of interventions and overall prognosis