Effectiveness of the new generation transcatheter aortic valve in the real life studies. Review and meta-analysis.

OBJECTIVE: The aim of the meta-analysis was to assess post-procedural outcome of the new generation of transcatheter aortic valve implantation (TAVI) devices, focusing on the transfemoral and balloon-expandable SAPIEN 3 (Edwards Lifesciences Inc., Irvine, CA, USA), the self-expanding CoreValveTM Evolut series R and PRO (R/PRO)TM (Medtronic Inc., Minneapolis, MN, USA) and ACURATE neoTM transcatheter aortic valve (Symetis SA, a Boston Scientific company, Ecublens, Switzerland). MATERIALS AND METHODS: All observational studies were retrieved through PubMed computerized database from January 2014 until June 30th, 2019. The risk difference (RD) with the 95% confidence interval (CI) was used to assess the effectiveness of the intervention under comparison. The primary end point was 30-day mortality. Safety end points included: (i) stroke, (ii) moderate/severe paravalvular leak, and (iii) the need for new permanent pacemaker implantation. RESULTS: Meta-analysis demonstrated no significant differences as regards to either 30-day mortality or stroke for all the groups of prostheses under comparison. ACURATE neo was associated with significantly less new permanent pacemaker implantation compared to SAPIEN 3 (RD: -0.06; 95% CI -0.08 to -0.03; p<0.0001; I2=0%) or to EVOLUT R/PRO (RD: -0.06; 95% CI -0.09 to -0.02; p=0.0009; I2=0%). A significant reduction of new permanent pacemaker need was observed in the group of patients implanted with SAPIEN 3 compared to EVOLUT R/PRO (RD: -0.07; 95% CI -0.09 to -0.04; p<0.00001; I2=7%). The occurrence of moderate/severe leak was significantly increased in the group of patients implanted with ACURATE neo vs. SAPIEN 3 (RD: 0.04; 95% CI 0.02 to 0.05; p<0.00001; I2=0%). No significant differences were found between ACURATE neo vs. EVOLUT R/PRO (RD: -0.01; 95% CI -0.04 to 0.02; p=0.69; I2=0%) and between SAPIEN 3 vs. EVOLUT R/PRO (RD: -0.01; 95% CI -0.04 to 0.01; p=0.28; I2=73%). CONCLUSIONS: The results of the meta-analysis show that: (1) ACURATE neo was associated with significantly less new permanent pacemaker implantation than SAPIEN 3 and EVOLUT R/PRO; (2) SAPIEN 3 had significantly lower occurrence of moderate/severe valvular leak than ACURATE neo.

Meta-analyses on intra-aortic balloon pump in cardiogenic shock complicating acute myocardial infarction may provide biased results.

OBJECTIVE: Intra-aortic balloon pump (IABP) is the device most commonly investigated in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). Recently meta-analyses on this topic showed opposite results: some complied with the actual guideline recommendations, while others did not, due to the presence of bias. We investigated the reasons for the discrepancy among meta-analyses and strategies employed to avoid the potential source of bias. MATERIALS AND METHODS: Scientific databases were searched for meta-analyses of IABP support in AMI complicated by CS. The presence of clinical diversity, methodological diversity and statistical heterogeneity were analyzed. When we found clinical or methodological diversity, we reanalyzed the data by comparing the patients selected for homogeneous groups. When the fixed effect model was employed despite the presence of statistical heterogeneity, the meta-analysis was repeated adopting the random effect model, with the same estimator used in the original meta-analysis. RESULTS: Twelve meta-analysis were selected. Six meta-analyses of randomized controlled trials (RCTs) were inconclusive because underpowered to detect the IABP effect. Five included RCTs and observational studies (Obs) and one only Obs. Some meta-analyses on RCTs and Obs had biased results due to presence of clinical and/or methodological diversity. The reanalysis of data reallocated for homogeneous groups was no more in contrast with guidelines recommendations. CONCLUSIONS: Meta-analyses performed without controlling for clinical and/or methodological diversity, represent a confounding message against a good clinical practice. The reanalysis of data demonstrates the validity of the current guidelines recommendations in addressing clinical decision making in providing IABP support in AMI complicated by CS.

Two-years follow-up of low-dose methotrexate and 6-methylprednisolone therapy in a patient with idiopathic retroperitoneal fibrosis.

Retroperitoneal fibrosis (RPF), also known as Ormond's disease, is a rare fibroinflammatory disease with uncertain etiology. RPF is characterized by the presence of a particular retroperitoneal fibrotic tissue which is white, woody and involving retroperitoneal structures such as the great vessels, ureters and psoas muscle. The main complication of RPF is the obstruction of local structures such as the ureters due to the fibrosis and the treatment of this aspect represents the main challenge for this pathology. RPF medical treatment consists of corticosteroids or/and immunosuppressive therapy. We report a case of a patient affected by idiopathic RPF treated with low-dose methotrexate (MTX) and 6-methylprednisolone (6-MP) for two years, describing and confirming the effectiveness and safety of a long-term low-dose MTX and 6-MP treatment associated to ureteral Double-J stenting avoiding more invasive surgical approaches.

[Advances in immunology and rheumatoid arthritis pathogenesis]. / La patogenesi dell'artrite reumatoide alla luce degli sviluppi delle conoscenze in immunologia.

The pathogenesis of Rheumatoid Arthritis (RA) is still largely unknown. From the seminal experimental studies, suggesting a multifactorial mechanism leaded by an antigen specific activation, the direct role of innate immunity in the disease progression has been recently emphasized. In the natural history of RA, characterized by the three phases of the induction, maintenance and tissue destruction, innate immunity seems to be the central player. On the other hands the recent advances about the molecules involved in the T lymphocyte activation, the T cell role in the mechanism of erosion, and the studies about chemokines in the homing and angiogenesis processes support the theory of an antigen specific activation of the adaptive immune system. Therefore, during RA, the pathogenesis of sinovitis and erosions comes from independent pathways involving either innate and adaptive immunity resulting in the final induction of the articular damage.

[The role of interleukin-12 in immune-mediated rheumatic diseases]. / Il ruolo dell'Interleuchina-12 nelle malattie reumatiche a patogenesi immunitaria.

OBJECTIVE: IL-12 is a proinflammatory cytokine produced by different antigen presenting cells. It has been shown to exert a critical role in inducing Th1 phenotype, thus initiating cell-mediated immune responses, but the significance of IL-12 in rheumatic diseases is not clear. Aim of the study was to determine IL-12 serum levels in immune rheumatic diseases and to analyse the relationship of this cytokine with main clinical and laboratory parameters. METHODS: We analysed, by ELISA, serum IL-12 levels in 114 patients with SLE, 47 with SS, 32 with SSc, 84 with RA, 138 with PA and in 17 healthy controls. We also examined main clinical and laboratory parameters, including autoantibody profile and clinical indices of disease activity. RESULTS: IL-12 serum levels were significantly higher in SLE and SS patients respect to controls. IL-12 serum levels were significantly higher in SLE patients compared to those affected by RA, PA and SSc. When we evaluated disease activity in SLE patients, we found significantly higher IL-12 serum levels in subjects with fever or in those without renal involvement, while no correlation was found in the other rheumatic immune diseases. CONCLUSIONS: These findings suggest that IL-12, modulating cell and humoral immune responses, is involved in the pathogenesis of immune rheumatic diseases, such as SLE and SS.

Effects of mud-pack treatment on plasma cytokine and soluble adhesion molecule levels in healthy volunteers.

BACKGROUND: The suggested hypothesis of a direct anti-inflammatory property of mud-pack treatment has led us to speculate that its action on the cytokine network might counteract the heat-stress-related effects on platelet and endothelial cell function often reported following hot-spring baths. Therefore, the present study was designed to investigate the effects of a cycle of 12 daily mud-pack treatments on bio-humoral markers of inflammation, as well as on markers of in vivo platelet and/or endothelial cell activation, in plasma samples obtained from healthy volunteers. METHODS: Blood samples were obtained before (T(0)), at the end of the first treatment (T(1)) and after a cycle of 12 daily mud-pack treatments (T(2)). Plasma cytokines (TNF-alpha IL-1beta, and IL-6) and adhesion molecules (sP-selectin, sE-selectin and sVCAM) levels, as well as hematocrit and complete and differential blood cell counts were determined at every time point. RESULTS: Plasma sP-selectin levels were not modified during treatment, as were not sE-selectin or sVCAM. Similarly, IL-1beta and TNF-alpha levels were unchanged through a 12 daily mud-pack treatment. Conversely, plasma IL-6 levels were significantly lowered at the end of a 20-min 47 degrees C mud-pack treatment (p<0.01). CONCLUSIONS: The lack of effects on in vivo platelet and/or endothelial cell activation suggests that hot mud-pack treatment might be used as a relatively safe procedure in patients with atherothrombotic disorders.

Study of peripheral bone mineral density in patients with diffuse idiopathic skeletal hyperostosis.

Diffuse idiopathic skeletal hyperostosis (DISH) is an ossifying systemic enthesopathy which involves not only the spine but which may also appear in other sites. Degenerative, inflammatory and metabolic factors have been reported for a possible pathogenic role in the new bone growth that characterises DISH. In the present study peripheral bone mineral density (BMD) has been measured in patients affected by DISH and the results compared to those of a control group. Forty-two patients (33 females and 9 males) affected by DISH and 84 controls (66 females and 18 males) were examined. All subjects underwent radiological study of the lumbar and dorsal spine and the pelvis. BMD was evaluated using dual-energy X-ray absorptiometry and the examination was performed in the distal radius. In DISH patients the mean value of BMD was significantly higher than in controls (P<0.002), even when it was referred to sex subgroups. Statistical analysis showed significant differences between both the two male groups (P<0.002) and the two female groups (P<0.01). In the two female subgroups (DISH patients and controls) BMD was significantly inversely related to age and to the duration of the postmenopausal period. The present study showed higher BMD in DISH patients than in the control group.

Ultrasound transmission velocity of the proximal phalanxes of the non-dominant hand in the study of osteoporosis.

The aim of our study was to evaluate a quantitative ultrasound technique for measuring bone tissue at the proximal phalanxes of the non-dominant hand. We correlated the mean value of the amplitude-dependent speed of sound (AD-SoS) measured at the distal metaphysis of the last four proximal phalanxes with age, months since menopause and bone mineral density (BMD) of the lumbar spine in 264 women. We further assessed the ability of the AD-SoS to discriminate between normal and osteoporotic subjects with documented vertebral fractures. We found a positive correlation between the AD-SoS and the lumbar spine BMD, whereas the AD-SoS negatively correlated with age and months since menopause. The AD-SoS showed a higher correlation with age changes and months since menopause than BMD. The AD-SoS was significantly higher in healthy females than in osteoporotic ones (p < 0.001). Multiple logistic regression analysis showed for age-adjusted values that AD-SoS decrease is significantly associated to the presence of fracture. Our results suggest that AD-SoS is valuable in assessing age and menopause related bone loss and is useful for diagnosing osteoporosis.

Relationship of soluble interleukin-2-receptor and interleukin-6 with class-specific rheumatoid factors during low-dose methotrexate treatment in rheumatoid arthritis.

We studied the effect of a 6-month treatment with low-dose MTX in 22 RA patients, with the purpose of investigating the relationship of sIL-2R and IL-6 serum changes with those of class specific RFs. The patients with RA had higher serum levels of sIL-2R (p < 0.0001), and IL-6 (p < 0.0005) than healthy volunteers. We found that the levels of IgM-RF (p < 0.0004), IgA-RF (p < 0.002), IgG-RF (p < 0.025), sIL-2R (p < 0.017) and IL-6 (p < 0.044) as well as the main clinical and laboratory variables, were significantly reduced in RA patients treated with low dose MTX for six months. The changes from baseline of IgM-RF correlated with those of IL-6 (p < 0.023), suggesting that MTX may affect IL-6 and IgM-RF production in part by a common mechanism. In conclusion our results show that there is a relationship between IL-6 and IgM-RF changes from baseline during MTX therapy, but the hypothesis of a link between the effects of this drug on cytokine network and RF production needs further investigation.

Interleukin-6 and soluble interleukin-2-receptor in psoriatic arthritis: correlations with clinical and laboratory parameters.

OBJECTIVE: In this study we evaluated the relationships of IL-6 and sIL-2R levels with the main clinical and laboratory parameters in PsA patients with peripheral polyarthritis. METHODS: Serum levels of IL-6 and sIL-2R were measured by an enzyme immunoassay kit in patients with peripheral (< 4 joints) PsA (n = 47), with RA (n = 41), or with psoriasis (N = 15) and in healthy volunteers (n = 15) RESULTS: The patients with PsA had higher serum levels of IL-6 and sIL-2R than healthy volunteers and psoriatic patients, while they showed lower levels of IL-6 and sIL-2R than RA patients. We found abnormal values for IL-6 and sIL-2R in 63.8% and 57.4% of PsA patients, respectively. IL-6 levels correlated with the number of painful and swollen joints, RAI, physician's assessment, CRP and ESR, while sIL-2R levels correlated only with the number of swollen joints, the physician's assessment and ESR. IL-6 and sIL-2R correlated with each other. CONCLUSION: Our study shows that IL-6 and sIL-2R may play a role in the pathogenetic mechanism of psoriatic arthritis.

Interleukin-6 and soluble interleukin-2 receptor in juvenile chronic arthritis: correlations with clinical and laboratory parameters.

We sought to determine whether levels of interleukin-6 and soluble interleukin-2 receptor were correlated with clinical parameters including functional capacity indices such as Steinbrocker's class and the Juvenile Arthritis Functional Assessment Report (JAFAR) score, with tests for inflammation, and/or with immunological parameters in 24 patients with active polyarticular or pauciarticular juvenile chronic arthritis. Levels of interleukin-6 and soluble interleukin-2 receptor were significantly higher in juvenile chronic arthritis patients than in healthy controls (p < 0.005 and p < 0.00005, respectively). Interleukin-6 levels were correlated with the following parameters: number of painful joints (p < 0.025); Ritchie's index (p < 0.025); visual analog scale pain score (p < 0.025); Steinbrocker's class (p < 0.025); JAFAR score determined by patients (p < 0.05); JAFAR score determined by parents (p < 0.05); erythrocyte sedimentation rate (p < 0.0002); and serum levels of C-reactive protein (p < 0.0003), hemoglobin (p < 0.05), albumin (p < 0.025), and alpha 2-globulins (p < 0.025). Levels of soluble interleukin-2 receptor did not correlate with any of the parameters studied. Levels of interleukin-6 and soluble interleukin-2 receptor were not correlated with each other. Abnormal levels of interleukin-6 or soluble interleukin-2 receptor were not significantly associated with the presence of antinuclear antibodies, IgM-rheumatoid factor, IgA rheumatoid factor or anticardiolipin antibodies. Our findings suggest that interleukin-6 is a useful parameter for assessing juvenile chronic arthritis and that the potential clinical value of elevated levels of soluble interleukin-2 receptor in this disease needs to be further evaluated in longitudinal studies.

Comparison of ultrasound transmission velocity with computed metacarpal radiogrammetry and dual-photon absorptiometry.

The aim of our study was to evaluate the validity of a quantitative US technique for measuring the bone density of the proximal phalanges of the nondominant hand compared with computed metacarpal radiogrammetry and dual-photon absorptiometry (DPA) of the lumbar spine. Mean US bone velocity (UBV) correlated with mean metacarpal cortical index (MCI), with mean metacarpal bone density (MBD) and with bone mineral density (BMD) of the lumbar spine, whereas it was correlated negatively with age and menopause duration. The average UBV was significantly higher in premenopausal women than in postmenopausal women, and higher in normal lumbar DPA patients than in reduced lumbar DPA patients. We conclude that the US evaluation of the nondominant hand proximal phalanges may be a new alternative way for measuring bone mass in screening of osteoporosis.

Comparison of cyclosporin A and methotrexate in the treatment of psoriatic arthritis: a one-year prospective study.

OBJECTIVE: To compare the effectiveness and toxicity of cyclosporin A (CsA) vs low-dose methotrexate (MTX) over a period of one year in the treatment of psoriatic arthritis (PsA) with peripheral involvement. METHODS: Thirty-five patients with PsA were enrolled in a prospective, controlled, randomized trial. CsA was initially given in doses of 3 mg/kg/day to a maximum permitted dose of 5 mg/kg/day; MTX was given in oral doses of 2.5 mg every 12 hours for 3 consecutive doses each week up to a maximum dose of 15 mg/weekly. Clinical and laboratory evaluations were performed at entry and monthly thereafter. RESULTS: After 6 and 12 months the number of painful joints, the number of swollen joints, the Ritchie index, the duration of morning stiffness, grip strength, CRP, the patient's and the physician's assessment of PsA activity, as well as the PASI, were significantly improved in both treatment groups. ESR values were significantly reduced only in the MTX group (p < 0.01), which also showed a significantly increase of liver enzymes. The changes in the main clinical and laboratory parameters during the course of CsA or MTX treatment were not significantly different except for the AST and ALT levels (p < 0.05). After one year of therapy CsA and MTX were withdrawn in 41.2% and 27.8% of the patients respectively, but these differences were not statistically significant. CONCLUSION: Our one-year prospective trial shows that low-dose CsA and MTX are both effective in the treatment of PsA, but the differences in the tolerability of these drugs must be considered at the start of therapy.

Lupus erythematosus panniculitis: an immunohistochemical study.

An immunohistochemical study on a case of lupus erythematosus panniculitis (LEP), without discoid lupus erythematosus (DLE) or systemic lupus erythematosus (SLE) signs, showed that the cells in skin infiltrates were immunologically committed lymphocytes (OKT4, OKT8, OKT11 and HLA-DR positive cells) and elements of the monocyte-macrophage lineage (Leu M3 and Leu M5 positive). No immunophenotypically identifiable B-lymphocytes were seen. Immunofluorescent IgG, IgM, C3 and C4 deposits were found in blood vessel walls of the deep dermis. These findings, similar to that described in the skin changes of SLE and DLE, suggest that immunological mechanisms are operative in localized LEP, where the dermal lesions are the only expression of the disease.

Rheumatoid nodules and cyclosporin A treatment.

The authors describe the appearance of rheumatoid nodules during cyclosporin A (CsA) therapy for RA. Their course was evaluated by sonography that revealed an increase in number and size of rheumatoid nodules. The relationship between CsA treatment and the onset of nodulosis is not clear and further studies are needed to assess the role of CsA treatment in the extra-articular manifestations of rheumatoid arthritis such as rheumatoid nodules.

[Value of cytological analysis of the synovial fluid in multicentric reticulohistiocytosis. A case]. / Valeur de l'analyse cytologique du liquide synovial dans la réticulohistiocytose multicentrique. Une observation.

The authors report the case of a patient who had both multicentric reticulohistiocytosis--a systemic disease characterized by symmetric polyarthritis and papulonodular skin lesions--and an ovarian adenocarcinoma. Synovial fluid analysis found histiocytes with a ground-glass cytoplasm, binucleate giant cells, and undifferentiated cells undergoing mitosis. PAS-positive, diastase-resistant cells similar to the synovial fluid histiocytes were seen in the synovial and cutaneous biopsy specimens. These findings established the diagnosis of multicentric reticulohistiocytosis and suggested an underlying malignancy. Whether or not multicentric reticulohistiocytosis is a paraneoplastic syndrome remains unsettled. However, our report provides evidence that synovial fluid analysis can be helpful not only for the early diagnosis of multicentric reticulohistiocytosis but also for suggesting the presence of an underlying tumor, especially when arthritis is the presenting symptom.

Magnetic resonance imaging (MRI) of the brain in SLE: ECLAM and SLEDAI correlations.

Twenty-one unselected SLE patients were examined with Magnetic Resonance Imaging (MRI) for cerebral areas of high signal intensity (HSI). Nine patients (42.9%) had HSI and 6 (28.6%) had large (> or = 6 mm) lesions suggestive of cerebral involvement. Despite the lack of correlation among these lesions and clinical or immunological features, the SLEDAI and ECLAM indices were correlated to the number of large lesions (p < 0.002). Our findings suggest that brain MRI may be useful in the evaluation of SLE patients, not only those with evident neurologic symptoms, but also asymptomatic subjects with high disease activity indices.