Transnasal endoscopic removal of malformation of the odontoid process in a patient with type I Arnold-Chiari malformation: a case report

The endoscopic endonasal approach is emerging as a feasible alternative to the trans-oral route for the resection of the odontoid process, when the latter produces a compression of the brainstem and cervicomedullary junction. This type of approach has some advantages, such as excellent pre-vertebral exposure of the cranio-vertebral junction in patients with small oral cavities and the possibility to avoid the use of mouth retractors. A typical case of a 24-year-old male patient with a previous diagnosis of type I Arnold-Chiari Malformation, suffering from a posterior dislocation of the odontoid process causing severe anterior compression of the brainstem, is presented to stress the potential of this technique. Trans-nasal endoscopic removal of the odontoid process was performed and resolution of the ventral compression of the brainstem was achieved. This report demonstrates that in selected cases, an endoscopic endonasal approach should now be considered an excellent alternative to the traditional trans-oral approach

The historical vanishing of the Blazhko effect of RR Lyr from GEOS and Kepler surveys

RR Lyr is one of the most studied variable stars. Its light curve has been regularly monitored since the discovery of the periodic variability in 1899. Analysis of all observed maxima allows us to identify two primary pulsation states defined as pulsation over a long (P0 longer than 0.56684 d) and a short (P0 shorter than 0.56682 d) primary pulsation period. These states alternate with intervals of 13-16 yr, and are well defined after 1943. The 40.8 d periodical modulations of the amplitude and the period (i.e. Blazhko effect) were noticed in 1916. We provide homogeneous determinations of the Blazhko period in the different primary pulsation states. The Blazhko period does not follow the variations of P0 and suddenly diminished from 40.8 d to around 39.0 d in 1975. The monitoring of these periodicities deserved and deserves a continuous and intensive observational effort. For this purpose we have built dedicated, transportable and autonomous small instruments, Very Tiny Telescopes (VTTs), to observe the times of maximum brightness of RR Lyr. As immediate results the VTTs recorded the last change of P0 state in mid-2009 and extended the time coverage of the Kepler observations, thus recording a maximum O-C amplitude of the Blazhko effect at the end of 2008, followed by the historically smallest O-C amplitude in late 2013. This decrease is still ongoing and VTT instruments are ready to monitor the expected increase in the next few years.Comment: 10 pages, 6 figures. Accepted for publication in MNRAS. Contents of appendix B may be requested to first autho

The joint involvement in adult onset Still's disease is characterised by a peculiar magnetic resonance imaging and a specific transcriptomic profile

Adult onset Still's disease (AOSD) is a rare systemic autoinflammatory disease, characterised by fever, arthritis, and skin rash, and joint involvement is one of its clinical manifestations. The aims of this work were to assess joint involvement, to describe main patterns of involvement, and associated clinical characteristics. In this work, we aimed at assessing the joint involvement in AOSD by using MRI, to describe main patterns and associated clinical characteristics. In addition, we aimed at assessing the global transcriptomic profile of synovial tissues in AOSD to elucidate possible pathogenic pathways involved. We also evaluated the global transcriptomic profile of synovial tissues to elucidate possible pathogenic pathways involved in the disease. Thus, AOSD patients, who underwent to MRI exam on joints, were assessed to describe patterns of joint involvement and associated clinical characteristics. Some synovial tissues were collected for RNA-sequencing purposes. The most common MRI finding was the presence of synovitis on 60.5%, mainly in peripheral affected joints, with low to intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. Bone oedema and MRI-bone erosions were reported on 34.9% and 25.6% MRI exams, respectively. Patients with MRI-bone erosions showed a higher prevalence of splenomegaly, a more frequent chronic disease course, lower levels of erythrocyte sedimentation rate, and ferritin. In AOSD synovial tissues, a hyper-expression of interleukin (IL)-1, IL-6, and TNF pathways was shown together with ferritin genes. In conclusion, in AOSD patients, the most common MRI-finding was the presence of synovitis, characterised by intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. MRI-bone erosions and bone oedema were also observed. In AOSD synovial tissues, IL-1, IL-6, and TNF pathways together with ferritin genes resulted to be hyper-expressed

Tofacitinib May Inhibit Myofibroblast Differentiation from Rheumatoid-Fibroblast-like Synoviocytes Induced by TGF-β and IL-6

During rheumatoid arthritis (RA), the pathogenic role of resident cells within the synovial membrane is suggested, especially for a population frequently referred to as fibroblast-like synoviocytes (FLSs). In this study, we assess the markers of myofibroblast differentiation of RA-FLSs by ex vivo observations and in vitro evaluations following the stimulation with both TGF-β and IL-6. Furthermore, we investigated the possible inhibiting role of tofacitinib, a JAK inhibitor, in this context. Myofibroblast differentiation markers were evaluated on RA synovial tissues by immune-fluorescence or immune-histochemistry. RA-FLSs, stimulated with transforming growth factor (TGF-β) and interleukin-6 (IL-6) with/without tofacitinib, were assessed for myofibroblast differentiation markers expression by qRT-PCR and Western blot. The same markers were evaluated following JAK-1 silencing by siRNA assay. The presence of myofibroblast differentiation markers in RA synovial tissue was significantly higher than healthy controls. Ex vivo, α-SMA was increased, whereas E-Cadherin decreased. In vitro, TGF-β and IL-6 stimulation of RA-FLSs promoted a significant increased mRNA expression of collagen I and α-SMA, whereas E-Cadherin mRNA expression was decreased. In the same conditions, the stimulation with tofacitinib significantly reduced the mRNA expression of collagen I and α-SMA, even if the Western blot did not confirm this finding. JAK-1 gene silencing did not fully prevent the effects of stimulation with TGF-β and IL-6 on these features. TGF-β and IL-6 stimulation may play a role in mediating myofibroblast differentiation from RA-FLSs, promoting collagen I and α-SMA while decreasing E-Cadherin. Following the same stimulation, tofacitinib reduced the increases of both collagen I and α-SMA on RA-FLSs, although further studies are needed to fully evaluate this issue and confirm our results

Vitamin D increases the production of IL-10 by regulatory T cells in patients with systemic sclerosis

OBJECTIVES: Vitamin D status influences the risk to develop autoimmune diseases affecting the percentage and/or functions of regulatory T cells (Tregs). Since low levels of 25 (OH) D have been decreased in patients with systemic sclerosis (SSc), we aimed to study the effect of Vitamin D3 (cholecalciferol) supplementation on Tregs frequencies and functions. METHODS: Peripheral blood and sera samples were obtained from 45 SSc patients and controls (HC). A number of eighteen SSc patients had consumed Cholecalciferol (orally) at the dose of 25.000 UI/month for 6 months at the time of enrollment. 25(OH)D serum levels were measured and VDR polymorphisms, were genotyped by polymerase chain reaction (PCR). Tregs isolated from peripheral blood mononuclear cells were in vitro expanded and a suppression assay was performed. Flow cytometry analysis was then carried out. Finally, IL-10 production was assayed by ELISA. RESULTS: Low serum levels of 25(OH)D were detected in SSc patients. The percentage of Tregs in SSc patients was similar to controls, but, among SSc patients, it was higher in those patients taking cholecalciferol. Tregs capability to suppress T cell proliferation was impaired in SSc patients and not restored after in vitro pre-treatment with the active form of Vitamin D (1,25(OH)2D3); but at the same time the production of IL-10 was increased in treated samples obtained from patients. The lack of response of Tregs from SSc patients to 1,25(OH)2D3 treatment in vitro was not due to altered Vitamin D/VDR signalling. CONCLUSIONS: Altogether, our results indicate that the increased production of IL-10 by 1,25(OH)2D3 -treated Tregs could provide a "suppressive" cytokine milieu able to modulate immune response but it is not sufficient to restore the immune suppressive functions of Tregs

Serological Response to BNT162b2 Anti-SARS-CoV-2 Vaccination in Patients with Inflammatory Rheumatic Diseases: Results From the RHEUVAX Cohort

Objective: In the light of the current COVID-19 epidemic and the availability of effective vaccines, this study aims to identify factors associated with non-response to anti-SARS-CoV-2 vaccines as immunological alteration associated with immune rheumatic diseases (IRD) and immunosuppressive medications may impair the response to vaccination. Methods: Volunteers in the health profession community with IRD, age, and sex-matched controls (CTRL) who underwent vaccination with two doses of BNT162b2 were recruited for this study. Anti-Trimeric Spike protein antibodies were assayed eight ± one weeks after the second vaccine dose. Univariate and logistic regression analyses were performed to identify factors independently associated with non-response and low antibody titers. Results: Samples were obtained from 237 IRD patients (m/f 73/164, mean age 57, CI 95% [56-59]): 4 autoinflammatory diseases (AI), 62 connective tissue diseases (CTD), 86 rheumatoid arthritis (RA), 71 spondylarthritis (SpA) and 14 vasculitis (Vsc). 232 CTRL were recruited (m/f 71/161, mean age 57, CI 95% [56-58]). Globally, IRD had a lower seroconversion rate (88.6% vs 99.6%, CI 95% OR [1.61-5.73], p<0.001) and lower antibody titer compared to controls (median (IQR) 403 (131.5-1012) versus 1160 (702.5-1675), p<0.001). After logistic regression, age, corticosteroid (CCS), Abatacept and Mycophenolate Mofetil (MMF) use were associated with non-response. Lower antibody titer was associated with the use of MMF, ABA, CCS, Rituximab, tumor necrosis factor inhibitor, JAK inhibitors, and higher age. Conclusion: The response to anti-SARS-CoV-2 vaccines is often impaired in IRD patients under treatment and may pose them at higher risk of severe COVID-19. Specific vaccination protocols are desirable for these patients

Surgical site infection after caesarean section. Space for post-discharge surveillance improvements and reliable comparisons

Surgical site infections (SSI) after caesarean section (CS) represent a substantial health system concern. Surveying SSI has been associated with a reduction in SSI incidence. We report the findings of three (2008, 2011 and 2013) regional active SSI surveillances after CS in community hospital of the Latium region determining the incidence of SSI. Each CS was surveyed for SSI occurrence by trained staff up to 30 post-operative days, and association of SSI with relevant characteristics was assessed using binomial logistic regression. A total of 3,685 CS were included in the study. A complete 30 day post-operation follow-up was achieved in over 94% of procedures. Overall 145 SSI were observed (3.9% cumulative incidence) of which 131 (90.3%) were superficial and 14 (9.7%) complex (deep or organ/space) SSI; overall 129 SSI (of which 89.9% superficial) were diagnosed post-discharge. Only higher NNIS score was significantly associated with SSI occurrence in the regression analysis. Our work provides the first regional data on CS-associated SSI incidence, highlighting the need for a post-discharge surveillance which should assure 30 days post-operation to not miss data on complex SSI, as well as being less labour intensive

Safety and efficacy of intra-articular anti-tumor necrosis factor \u3b1 agents compared to corticosteroids in a treat-to-target strategy in patients with inflammatory arthritis and monoarthritis flare

The aim of this study was to assess safety and efficacy of ultrasonography (US)-guided intra-articular injections using tumor necrosis factor (TNF) blockers compared to corticosteroids in rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients, experiencing refractory monoarthritis despite the current systemic therapy. Eighty-two patients were randomized to receive three intra-articular injections monthly of either corticosteroid or TNF blockers. Primary endpoints were the safety and an improvement greater than 20% for visual analogic scales of involved joint pain in patients injected with anti-TNF\u3b1. Further clinical, US, and magnetic resonance imaging (MRI) evaluations were considered secondary endpoints. Intra-articular TNF blockers are a safe strategy, determining a significant reduction of patient and physician reported clinical outcomes and US/MRI scores, in RA and PsA patients, when compared to intra-articular injections of corticosteroids. US guidance excluded the possibility to inject the drug in the wrong site, maximizing local effects, reducing systemic effects, and increasing the safety of the procedure. Patients with inflammatory monoarthritis could be successfully treated with US-guided intra-articular TNF blockers that are a safe and well tolerated procedure, to achieve a longstanding clinical and radiological good clinical response and/or disease remission

Impaired immunogenicity to COVID-19 vaccines in autoimmune systemic diseases. High prevalence of non-response in different patients’ subgroups

Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53–1203) vs 825 (451–1542) BAU/mL, p < 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p < 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p < 0.0001), or rituximab (p < 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals

Unfolding dermatologic spectrum of Behçet’s disease in Italy: real-life data from the International AIDA Network Behçet’s disease Registry

Behçet’s disease (BD) is a heterogeneous multifactorial autoinflammatory disease characterized by a plethora of clinical manifestations. Cutaneous lesions are considered hallmarks of the disease. However, their evolution over time and a thorough description are scarcely reported in non-endemic regions. The aim of this study was to detail BD skin manifestations and their evolution over time in Italy, as well as the dermatological prognostic impact of specific cutaneous features in long-standing disease. Data were collected in a double fashion, both retrospectively and prospectively, from the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to BD, between January 2022 and December 2022. A total of 458 Italian patients were included. When assessing skin manifestations course, the constant or sporadic presence or absence of cutaneous involvement between onset and follow-up was considered. Oral ulcers (OU) (88.4%) and genital ulcers (GU) (52.6%), followed by skin involvement (53.7%) represented the most common presenting mucocutaneous manifestations at disease onset. Up to the time of enrolment into the AIDA registry, 411 (93.8%) patients had suffered from OU and 252 (57.9%) from GU; pseudofolliculitis (PF) accounted for the most common skin manifestation (170 patients, 37.1%), followed by erythema nodosum (EN) (102 patients, 22.3%), skin ulcers (9 patients, 2%) and pyoderma gangrenosum (4 patients, 0.9%). A prospective follow-up visit was reported in 261/458 patients; 24/148 (16.2%) subjects with skin involvement as early as BD onset maintained cutaneous lesions for the entire period of observation, while 120 (44.1%) patients suffered from sporadic skin involvement. Conversely, 94/113 (83.2%) with no skin involvement at disease onset did not develop skin lesions thereafter. At follow-up visits, cutaneous involvement was observed in 52 (20%) patients, with a statistically significant association between PF and constant skin involvement (p = 0.031). BD in Italy is characterized by a wide spectrum of clinical presentations and skin manifestations in line with what is described in endemic countries. Patients with skin disease at the onset are likely to present persistent cutaneous involvement thereafter; mucocutaneous lesions observed at the onset, especially PF, could represent a warning sign for future persistent skin involvement requiring closer dermatological care