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BACKGROUND: Enrichment strategies from clinical trials for progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) have not been tested in a real-life cohort.RESEARCH QUESTION: Do enrichment strategies for progressive ILD impact efficacy, repre-sentativeness, and feasibility in patients with SSc-ILD from the European Scleroderma Trials and Research (EUSTAR) database?STUDY DESIGN AND METHODS: We applied the inclusion criteria of major recent SSc-ILD trials (Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis [focuSSced], Scleroderma Lung Study II [SLS II], and Safety and Efficacy of Nintedanib in Systemic Sclerosis [SENSCIS]) and assessed progressive ILD, which was defined as absolute change in FVC and as significant progression (FVC decline $10%). Data were compared with all patients and with patients who did not fulfill any inclusion criteria. RESULTS: In total, 2,258 patients with SSc-ILD were included: 31.2% of the patients met SENSCIS criteria; 5.8% of the patients met SLS II criteria; 1.6% of the patients met focuSSced criteria, and 67.7% (1,529) of the patients did not meet any criteria. In the first 12 + 3 months, the absolute FVC decline in all patients and in patients who fulfilled criteria from SENSCIS was -0.1%, in patients who fulfilled criteria from focuSSced was -3.7%, and in patients who fulfilled criteria from SLS II was 2.3%, with accompanying more progressors in focuSSced. The patient populations that fulfilled the different study inclusion criteria significantly differed in various clinical parameters. In the second 12-month period, SENSCIS-enriched patients had a further absolute FVC% decline as described for the total cohort. In contrast, patients who fulfilled the focuSSced and SLS II criteria showed numeric improvement of lung function. There were no significant associations of enrichment criteria and ILD progression.INTERPRETATION: The application of enrichment criteria from previous clinical trials showed enrichment for progression with variable success, which led to selected patient populations reducing feasibility of recruitment. These findings are important for future clinical trial design and interpretation of the results of published trials.CHEST 2023; 163(3):586-598

The employability of photonics technology in the modern era’s highly demanding and sophisticated domain of aerospace and submarines has been an appealing challenge for the scientific communities. In this paper, we review our main results achieved so far on the use of optical fiber sensors for safety and security in innovative aerospace and submarine applications. In particular, recent results of in-field applications of optical fiber sensors in aircraft monitoring, from a weight and balance analysis to vehicle Structural Health Monitoring (SHM) and Landing Gear (LG) monitoring, are presented and discussed. Moreover, underwater fiber-optic hydrophones are presented from the design to marine application.

Our group, involving researchers from different universities in Campania, Italy, has been working for the last twenty years in the field of photonic sensors for safety and security in healthcare, industrial and environment applications. This is the first in a series of three companion papers. In this paper, we introduce the main concepts of the technologies employed for the realization of our photonic sensors. Then, we review our main results concerning the innovative applications for infrastructural and transportation monitoring.

Moving masses are of interest in many applications of structural dynamics, soliciting in the last decades a vast debate in the scientific literature. However, despite the attention devoted to the subject, to the best of the authors’ knowledge, there is a lack of analysis about the fate of a movable mass when it rolls or slips with friction on a structure. With the aim of elucidating the dynamics of the simplest paradigm of this system and to investigate its asymptotic response, we make reference to a two-degree-of-freedom model made of an elastically vibrating carriage surmounted by a spherical mass, facing the problem both theoretically and experimentally. In case of linear systems, the analytical solutions and the laboratory tests performed on ad hoc constructed prototypes highlighted a counterintuitive asymptotic dynamics, here called binary: in the absence of friction at the interface of the bodies’ system, the mass holds its initial position or, if nonzero damping acts, at the end of the motion it is in a position that exactly recovers the initial relative distance carriage–sphere. While the first result might be somewhat obvious, the second appears rather surprising. Such a binary behaviour is also confirmed for a Duffing-like system, equipped with cubic springs, while it can be lost when non-smooth friction phenomena occur, as well as in the case of elastic springs restraining the motion of the sphere. The obtained analytical results and the numerical findings, also confirmed by experimental evidences, contribute to the basic understanding of the role played by the damping parameters governing the systems’ dynamics with respect to its asymptotic behaviour and could pave the way for designing active or passive vibration controllers of interest in engineering.

Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups

Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Introduction. In group psychotherapy research, there are few reliable measures for tracking members’ change. This study proposes a further adaptation of the Innovative Moment Coding System for Groups (IMCS-G), a reliable method previously developed in one format of group intervention for detecting innovative moments (IMs). IMs are exceptions to the clients’ problematic narratives, organized in different levels of complexity in terms of meaning elaboration (Level 1, 2, and 3). IMCS-G consists of 7 categories (Self-Directed, Other-Directed, Explicit Mirroring, Interaction 1, Interaction 2, Collective, Voice of Group) organized in two macro-categories: Individual (e.g., change was narrated by a single participant) and Group IMs (e.g., change was co-constructed by more than one participant). Methods. Two reliable coders applied the IMCS-G to analyze the transcripts of nine sessions of a counseling group addressed to underachieving university students (N=10) and eight sessions of a brief group psychotherapy targeted to substance abusers (N=8). Agreement and reliability for IMCS-G categories and their Levels were calculated. Results. Consistently with previous studies, a strong agreement and reliability for IMCS-G categories and Levels were found in both group interventions. Furthermore, despite some differences in the frequency of IMCS-G categories and Levels, in both interventions, there was a higher frequency of Self-Directed IMs, a lower frequency of the Explicit Mirroring IMs, and a higher frequency of Level 3 Group IMs. Discussion. This study confirmed the reliability of IMCS-G in different group formats, but it also suggested rooms of improvement for some IMCS-G categories.

Nail-patella syndrome (NPS) is a rare autosomal dominant disease characterized by nail dysplasia, aplastic or hypoplastic patellae, elbow dysplasia, and presence of iliac horns. Renal or ocular abnormalities are also associated with the disease. We report the case of a 57-year-old woman affected by NPS and having haploinsufficiency of the LMX1B gene who experienced severe bilateral chronic angle-closure glaucoma in both eyes and that was successfully managed with a flap-express procedure in the right eye. The left eye had no light perception, and medical treatment was considered. Glaucoma is the most frequent ocular abnormalities observed in association with NPS and usually presents with an open angle. Glaucoma associated with NPS typically has an early onset open-angle phenotype. In fewer cases, it may present with an angle-closure phenotype. Therefore, we emphasize the need for glaucoma case-finding protocols comprehensive of gonioscopy in NPS patients and their relatives.

Purpose To describe reoperations in the operating room for complications that occurred within the first 90 days after gel stent implantation or trabeculectomy at a single institution over 5 years. Methods In this retrospective chart review, patients who have undergone gel stent implantation with mitomycin C (MMC) or trabeculectomy with MMC were enrolled. Postoperative complications that required reoperations within the first 90 days were evaluated. Results A total of 510 surgeries were performed on 392 patients over a 57-month period by 2 glaucoma surgeons. Of these, 284 were gel stent implantation, and 226 were trabeculectomy. Combined phacoemulsification was performed in 52/284 (18.3%) in the gel stent group and in 26/226 (11.5%) of eyes in the trabeculectomy group (p = 0.03). Reoperations took place in 13/510 (2.5%) eyes, including 4/284 (1.4%) in the gel stent group, 9/226 (4.0%) in the trabeculectomy group (p = 0.07). In the gel stent group, indications for reoperation were bleb failure (2), suprachoroidal hemorrhage (1), bullous keratopathy (1). In the trabeculectomy group, indications for reoperation were bleb failure (3), overfiltration (2), persistent wound leak (2), aqueous misdirection (2). Conclusions The rates of reoperation for early postoperative complications after gel stent or trabeculectomy was low and comparable with previous studies. A slightly higher number of reoperations within 90 days was observed in the trabeculectomy group than the gel stent group despite the more significant number of combined procedures in the latter group. Bleb failure was the most common indications for reoperation in both groups. Excessive outflow was a cause of reoperation mostly in the trabeculectomy group.

In order to complete this set of three companion papers, in this last, we focus our attention on environmental monitoring by taking advantage of photonic technologies. After reporting on some configurations useful for high precision agriculture, we explore the problems connected with soil water content measurement and landslide early warning. Then, we concentrate on a new generation of seismic sensors useful in both terrestrial and under water contests. Finally, we discuss a number of optical fiber sensors for use in radiation environments.

Objectives To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. Methods SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. Results We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. Conclusion ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup.

During implant surgery procedures, surgical precision is an essential prerequisite for the functional and aesthetic success of the prosthetic crown to be placed on the dental implant. A modern implant surgical approach should be standardized as much as possible to guarantee extreme precision in the insertion of the implant into the upper and lower bone jaws. Among the most common surgical errors during implant surgery there is the over-preparation of the surgical alveolus with possible damage to the contiguous anatomical structures. To avoid this problem, in the recent years, there has been an increasing attention to the development of new control techniques. In this paper, we describe an innovative ultrasound approach, which exploits the integration of an electro-acoustic transducer with the surgical drill used for realizing the alveolus in the bone that will host the implant. Specifically, he proposed approach is based on the “time-of-flight” detection technique for measuring the thickness of the residual bone subjected to the drilling. In order to demonstrate the feasibility of the proposed approach, here we report on a detailed numerical analysis aimed at studying the propagation of ultrasonic waves through the drill-bit and through the involved tissues. The obtained results confirm the validity of our approach, and enable for a future first prototype implementation of a hi-tech surgical drill-bit, which in general is suitable not only for dental implant surgery but also for other uses in oral surgery, maxillofacial surgery and for bone surgery.

Grounded in the interdisciplinary crosstalk among physics and biological sciences, precision medicine-based diagnosis and treatment strategies have recently gained great attention for the actual applicability of new engineered approaches in many medical fields, particularly in oncology. Within this framework, the use of ultrasounds employed to attack cancer cells in tumors to induce possible mechanical damage at different scales has received growing attention from scholars and scientists worldwide. With these considerations in mind, on the basis of ad hoc elastodynamic solutions and numerical simulations, we propose a pilot study for in silico modeling of the propagation of ultrasound waves inside tissues, with the aim of selecting proper frequencies and powers to be irradiated locally through a new teragnostic platform based on Lab-on-Fiber technology, baptized as a hospital in the needle and already the object of a patent. It is felt that the outcomes and the related biophysical insights gained from the analyses could pave the way for envisaging new integrated diagnostic and therapeutic approaches that might play a central role in future applications of precise medicine, starting from the growing synergy among physics, engineering and biology.

We described nailfold videocapillaroscopy (NVC) findings and estimated the prevalence of serum anti-nuclear (ANA) and extractable nuclear antigen autoantibodies (ENA) in a cohort of sarcoidosis patients, comparing them with adequate healthy controls (HCs) and with primary Raynaud’s phenomenon patients (PRPs). NVC findings were also correlated with the occurrence of autoantibodies, current treatment, laboratory parameters, variables of lung function and whole-body imaging data. Twenty-six patients with sarcoidosis were assessed through NVC, laboratory parameters, pulmonary function tests, chest-X ray and 18- fluorodeoxyglucose positron emission tomography/computed tomography. The NVC parameters and ANA/ENA dosage were recorded also in 30 PRPs and 30 HCs. Sarcoidosis patients showed a higher rate of capillary dilations and nonspecific abnormalities and a lower mean capillary absolute number than PRPs and HCs (p p p

Newly developed Doppler techniques enable the sampling of slow vascular flows and the extrapolation of spectral parameters in distal arterioles. The aim of this study was to investigate the role of spectral analysis performed by means of ultra-high frequency ultrasound (US) in the evaluation of the peripheral vascular bed of systemic sclerosis (SSc) patients.Both hands of 33 patients affected by diffuse cutaneous SSc and 34 volunteers were evaluated with a US machine equipped with 33-9 MHz and 18-5 MHz transducers. Proximal resistive index and the peak systolic velocity (pRI and pPSV, respectively), were calculated at the level of the second interdigital artery. The distal resistive index (dRI) was calculated at the level of a nailfold arteriole of the third finger. All SSc patients had been previously divided into 4 subgroups according to their nailfold videocapillaroscopic (NVC) patterns following accepted criteria.SSc patients showed a significantly slower systolic velocity at the level of the second interdigital artery (pPSV [SD] = 8.38 [3] cm/s vs pPSV [SD] = 11.14 [4.5] cm/s; P = .005) and a higher dRI (dRI [SD] = 0.65 (0.14) vs dRI [SD] = 0.57 [0.11); P = .0115). No differences were found between the pRI values measured in the SSc patients and those of the controls (pRI [SD] = 0.76 [0.11] vs pRI [SD] = 0.73 [0.12]; P = .359]. The subgroup analysis did not show any significant difference when pPSV, pRI and dRI were compared among NVC morphological patterns.High-resolution Doppler analysis of digital distal arterioles may disclose subtle abnormalities in the downstream microvasculature of SSc patients that could be missed when the examination is performed at a more proximal level and/or using lower Doppler frequencies.

Following previous work by some of the present authors based on the linear arch static analysis (LASA), which models the masonry material as a no-tension material according to Heyman (Heyman, J., The Stone Skeleton, Int. J. Solids Struct., vol. 2, no. 2, pp. 249–279, 1966) and on the safe theorem of the limit analysis (LA), an in-depth numerical study of a case study based on a masonry spiral staircase in Nisida, near Naples, is here presented by means of an accurate finite element (FE) model. The nonlinear FE model has been obtained by the use of the ANSYS Parametric Design Language (APDL), and a precise representation of all the material involved and of the boundary conditions, has been obtained. The results confirm that LASA can be an alternative to much more complex numerical analyses, such as FE, but it cannot account for the main cause of collapse or stress redistribution in these type of structures, that is sagging and subsidences. The results are presented and discussed in some detail.

Objective: To evaluate whether the addition of colchicine to standard of care (SOC) results in better outcomes in hospitalized patients with COVID-19. Design: This interventional, multicenter, randomized, phase 2 study, evaluated colchicine 1.5 mg/day added to SOC in hospitalized COVID-19 patients (COLVID-19 trial) and 227 patients were recruited. The primary outcome was the rate of critical disease in 30 days defined as need of mechanical ventilation, intensive care unit (ICU), or death. Results: 152 non-anti-SARS-CoV-2-vaccinated patients (colchicine vs controls: 77vs75, mean age 69.1±13.1 vs 67.9±15 years, 39% vs 33.3% females, respectively) were analyzed. There was no difference in co-primary end-points between patients treated with colchicine compared to controls (mechanical ventilation 5.2% vs 4%, ICU 1.3% vs 5.3%, death 9.1% vs 6.7%, overall 11 (14.3%) vs 10 (13.3%) patients, P=ns, respectively). Mean time to discharge was similar (colchicine vs controls 14.1±10.4 vs 14.7±8.1 days). Older age (>60 years, P=0.025), P/F40 U/L (P60 years) patients with comorbidities are characterized by worse outcome.

Background and purpose While HCC is an inflammation-associated cancer, CRLM develops on permissive healthy liver microenvironment. To evaluate the immune aspects of these two different environments, peripheral blood-(PB), peritumoral-(PT) and tumoral tissues-(TT) from HCC and CRLM patients were evaluated. Methods 40 HCC and 34 CRLM were enrolled and freshly TT, PT and PB were collected at the surgery. PB-, PT- and TT-derived CD4+CD25+ Tregs, M/PMN-MDSC and PB-derived CD4+CD25− T-effector cells (Teffs) were isolated and characterized. Tregs’ function was also evaluated in the presence of the CXCR4 inhibitor, peptide-R29, AMD3100 or anti-PD1. RNA was extracted from PB/PT/TT tissues and tested for FOXP3, CXCL12, CXCR4, CCL5, IL-15, CXCL5, Arg-1, N-cad, Vim, CXCL8, TGFβ and VEGF-A expression. Results In HCC/CRLM-PB, higher number of functional Tregs, CD4+CD25hiFOXP3+ was detected, although PB-HCC Tregs exert a more suppressive function as compared to CRLM Tregs. In HCC/CRLM-TT, Tregs were highly represented with activated/ENTPD-1+Tregs prevalent in HCC. As compared to CRLM, HCC overexpressed CXCR4 and N-cadherin/vimentin in a contest rich in arginase and CCL5. Monocytic MDSCs were highly represented in HCC/CRLM, while high polymorphonuclear MDSCs were detected only in HCC. Interestingly, the function of CXCR4-PB-Tregs was impaired in HCC/CRLM by the CXCR4 inhibitor R29. Conclusion In HCC and CRLM, peripheral blood, peritumoral and tumoral tissues Tregs are highly represented and functional. Nevertheless, HCC displays a more immunosuppressive TME due to Tregs, MDSCs, intrinsic tumor features (CXCR4, CCL5, arginase) and the contest in which it develops. As CXCR4 is overexpressed in HCC/CRLM tumor/TME cells, CXCR4 inhibitors may be considered for double hit therapy in liver cancer patients.

The FaSt-SWOT project is funded by the Spanish Research Agency and the European Regional Development Fund (AEI/FEDER, UE) under Grant Agreement (PID2021-122417NB-I00). The present research is conducted within the framework of the activities of the Spanish Government through the "María de Maeztu Centre of Excellence'' accreditation to IMEDEA (CSIC-UIB) (CEX2021-001198). The Spanish Ministry of Science and Innovation, the Regional Government of the Balearic Islands and the Spanish Research Council (CSIC) are acknowledged for their support to the ICTS SOCIB. A. P., B. M. and B. B. L. thank the European Union funding through the EuroSea project an Horizon 2020 research and innovation programme under grant agreement No 862626., With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001198).

Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84–1.29], p = 0.711 and HR 1.18 [0.95–1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79–1.17], p = 0.67 and HR 1.48 [1.16–1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02–1.74], p = 0.037) and OS (HR 1.26 [1.03–1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3–3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62–3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55–5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02–1.37], p = 0.031) but not OS (HR 1.05 [0.91–1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used. Interpretation: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit. Funding:Cambridge Hepatopancreatobiliary Department Research Fund.

Il dibattito pubblico sulla proposta di cambiare l’intitolazione del Liceo scientifico di Pistoia, dedicato al duca Amedeo di Savoia-Aosta, ha evidenziato il permanere di una narrazione apologetica del principe sabaudo, coltivata da ambienti conservatori e connessa a una memoria nostalgica del passato coloniale italiano. Il contributo cerca di analizzare la figura del duca d’Aosta e la sua rappresentazione pubblica, concentrandosi sui passaggi più oscuri e controversi della sua vicenda, a partire dai suoi legami con il regime fascista.

To report a case of hyphema after a bleb needling revision in a PreserFlo MicroShunt implantation.An 87-year-old man suffering from bilateral open angle glaucoma was referred to our hospital with a diagnosis of unsatisfactory intraocular pressure (IOP) control in the right eye, despite the maximally tolerated medical therapy. The patient underwent PreserFlo MicroShunt implantation in his right eye. About 2 months after the surgical procedure, the IOP was raised because of bleb failure for subconjunctival scarring. A needling revision was performed at the slit lamp. During the procedure blood reflux through a PreserFlo MicroShunt device from a filtering bleb to the anterior chamber was observed, causing an IOP rise. Treatment with oral acetazolamide, topical steroid, and antibiotic resulted in the complete resolution of the hyphema in 2 weeks and a significant lowering in IOP.This is the first reported case of blood reflux to the anterior chamber through a PreserFlo MicroShunt implant after a needling procedure.

© Copyright Clinical and Experimental Rheumatology 2022, Objectives: Relapsing polychondritis (RP) evolves with variable and intermittent involvement of cartilage and proteoglycan-rich structures. Ocular manifestations are present in up to two-thirds of RP patients. Necrotising scleritis (NS) and peripheral ulcerative keratitis (PUK) may be inaugural and may lead to eye perforation and vision loss. We aimed to review NS and PUK in RP, in order to characterise them, to identify successful treatment options and unmet needs. Methods: A systematic review of the currently available evidence in PubMed, EMBASE and Scopus was performed according to PRISMA, including observational studies, single case reports and case series of NS/PUK in RP. Study design, number of patients, age, gender, treatment and outcome, were extracted. Two RP patients also provided their opinion. Results: Five case reports and two case series were eligible for inclusion. We identified 10 RP patients with eye-threatening complications (NS and/or PUK), 9 adults (2 males, 7 females, aged 35-72, median age 57.6 years) and one paediatric patient (F, 11 years). Apart from glucocorticoids, cyclophosphamide was effective in 4 patients; infliximab, high-dose immunoglobulins, dapsone, or cyclosporine were also successfully employed in a case each. Surgical repair was reported in 2 cases. Conclusions: Ocular inflammation is often bilateral and recurring in RP; NS/PUK are rare complications. All patients who develop NS/PUK should be specifically questioned for RP signs and symptoms. Early institution of immunosuppressive therapies is mandatory. Increasing awareness, physicians' and patients' education and a multidisciplinary approach may help improve the prognosis of these serious complications of RP.

Egocentric augmented reality (AR) interfaces are quickly becoming a key asset for assisting high precision activities in the peripersonal space in several application fields. In these applications, accurate and robust registration of computer-generated information to the real scene is hard to achieve with traditional Optical See-Through (OST) displays given that it relies on the accurate calibration of the combined eye-display projection model. The calibration is required to efficiently estimate the projection parameters of the pinhole model that encapsulate the optical features of the display and whose values vary according to the position of the user's eye. In this article, we describe an approach that prevents any parallax-related AR misregistration at a pre-defined working distance in OST displays with infinity focus; our strategy relies on the use of a magnifier placed in front of the OST display, and features a proper parameterization of the virtual rendering camera achieved through a dedicated calibration procedure that accounts for the contribution of the magnifier. We model the registration error due to the viewpoint parallax outside the ideal working distance. Finally, we validate our strategy on a OST display, and we show that sub-millimetric registration accuracy can be achieved for working distances of ±100 mm around the focal length of the magnifier.

The SARS-CoV-2 infection causing the Coronavirus disease-19 (COVID-19) is characterized by a broad range of clinical manifestations, implicating microvascular damage with endothelial dysfunction and different organ involvement.

In recent years, efforts have been made to compare equilibrium solutions of masonry domes obtained through different methods. The research summarized in the present paper focuses on the evaluation of the equilibrium of masonry domes in the context of the classical membrane theory, in comparison with more sophisticated finite element models. In particular, we consider solutions, with vanishing tensile stresses, for domes under gravity loads. The equilibrium problem is traced back to the equilibrium of a thrust surface under the assumption of no-tension material in the sense of Heyman (i.e., no tensile strength, infinite resistance in compression, and no slide along fracture lines). A finite difference discretization of the equilibrium equation is proposed and the obtained solution is compared with results from a nonlinear finite element analysis. The good agreement of the results shows that both finite difference and finite element approaches represent reasonable and reliable alternative tools.

The adoption of extended reality solutions is growing rapidly in the healthcare world. Augmented reality (AR) and virtual reality (VR) interfaces can bring advantages in various medical-health sectors; it is thus not surprising that the medical MR market is among the fastest-growing ones. The present study reports on a comparison between two of the most popular MR head-mounted displays, Magic Leap 1 and Microsoft HoloLens 2, for the visualization of 3D medical imaging data. We evaluate the functionalities and performance of both devices through a user-study in which surgeons and residents assessed the visualization of 3D computer-generated anatomical models. The digital content is obtained through a dedicated medical imaging suite (Verima imaging suite) developed by the Italian start-up company (Witapp s.r.l.). According to our performance analysis in terms of frame rate, there are no significant differences between the two devices. The surgical staff expressed a clear preference for Magic Leap 1, particularly for the better visualization quality and the ease of interaction with the 3D virtual content. Nonetheless, even though the results of the questionnaire were slightly more positive for Magic Leap 1, the spatial understanding of the 3D anatomical model in terms of depth relations and spatial arrangement was positively evaluated for both devices.

© Copyright Clinical and Experimental Rheumatology 2022., Objectives: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. Methods: We conducted a multicentre, international, retrospective cohort study. Results: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. Conclusions: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Background/objectives: To compare the number of eye surgical procedures performed in Italy in the 2 months following the beginning of lockdown (study period) because of COVID-19 epidemic with those performed in the two earlier months of the same year (intra-year control) and in the period of 2019 corresponding to the lockdown (inter-year control). Methods: Retrospective analysis of surgical procedures carried out at 39 Academic hospitals. A distinction was made between elective and urgent procedures. Intravitreal injections were also considered. Percentages for all surgical procedures and incidence rate ratios (IRR) for rhegmatogenous retinal detachment (RRD) events were calculated. A p value Results: A total of 20,886 versus 55,259 and 56,640 patients underwent surgery during the lockdown versus intra-and inter-year control periods, respectively. During the lockdown, only 70% of patients for whom an operation/intravitreal injection was recommended, finally underwent surgery; the remaining patients did not attend because afraid of getting infected at the hospital (23%), taking public transportation (6.5%), or unavailable swabs (0.5%). Elective surgeries were reduced by 96.2% and 96.4%, urgent surgeries by 49.7% and 50.2%, and intravitreal injections by 48.5% and 48.6% in the lockdown period in comparison to intra-year and inter-year control periods, respectively. IRRs for RRDs during lockdown dropped significantly in comparison with intra- and inter-year control periods (CI: 0.65–0.80 and 0.61–0.75, respectively, p Conclusion: This study provides a quantitative analysis of the reduction of eye surgical procedures performed in Italy because of the COVID-19 epidemic.

Abstract Poromechanics plays a key role in modelling hard and soft tissue behaviours, by providing a thermodynamic framework in which chemo-mechanical mutual interactions among fluid and solid constituents can be consistently rooted, at different scale levels. In this context, how different biological species (including cells, extra-cellular components and chemical metabolites) interplay within complex environments is studied for characterizing the mechanobiology of tumor growth, governed by intratumoral residual stresses that initiate mechanotransductive processes deregulating normal tissue homeostasis and leading to tissue remodelling. Despite the coupling between tumor poroelasticity and interspecific competitive dynamics has recently highlighted how microscopic cells and environment interactions influence growth-associated stresses and tumor pathophysiology, the nonlinear interlacing among biochemical factors and mechanics somehow hindered the possibility of gaining qualitative insights into cells dynamics. Motivated by this, in the present work we recover the linear poroelasticity in order to benefit of a reduced complexity, so first deriving the well-known Lyapunov stability criterion from the thermodynamic dissipation principle and then analysing the stability of the mechanical competition among cells fighting for common space and resources during cancer growth and invasion. At the end, the linear poroelastic model enriched by interspecific dynamics is also exploited to show how growth anisotropy can alter the stress field in spherical tumor masses, by thus indirectly affecting cell mechano-sensing. GraphicAbstract

S.F.E.G., a 52–year–old woman of Filipino origin, with no previous cardiology except arterial hypertension under therapy, came to our attention for a witnessed episode of cardiac arrest at home. Rescued by the emergency medical team, who found ventricular fibrillation at presentation, and performed ACLS with ROSC obtained after 3 DC shocks. The first ECG was unremarkable (sinus rhythm, diffuse ST depression). Total body CT was negative. Admitted to the Coronary Unit, the echocardiogram was normal for cavity dimensions and kinetics, as well was coronary angiography except for “short intramyocardial course in the second segment of LAD with slight systolic "milking". In the following days, however, there was a significant rise in HsTnI (1,000 → 47,000 ng/L), with concomitant sudden ventricular bigeminy and negative anterior T waves, akinesia of the anterior apical segments of the LV at cardiac ultrasound (not present at admission), in a patient still intubated and therefore with a non–evaluable clinic. Coronary angiography was repeated, which highlighted this time significant vasospasm affecting the middle segment of the LAD, that regressed after intracoronary nitrates. She was extubated without neurological sequelae, and subjected to ICD implantation by secondary prevention. To treat the vasospastic angina she was discharged with calcium channel blockers at the maximum tolerated dosage, as per guidelines (diltiazem 120mg TID + nifedipine 60mg BID). One month later the patient returned to our attention due to worsening dyspnoea, abdominal pain and anasarca (ascites, bilateral pleural effusion, peripheral oedemas). Hospitalized in a medical setting and treated with diuretics for suspected heart failure, despite the echocardiogram showing preserved biventricular systolic function, normal diastolic function, no valve disease, no pericardial effusion. BNP was 359 pg/mL, subsequently decreasing to 148 pg/mL. After excluding every other possible causes even with total body CT, our hypothesis was that of calcium channel blocker collateral effect (vasodilatory edema). We tapered the dosage until only diltiazem 60mg TID was mainteined, obtaining a significant clinical improvement (weight loss by 10 kg), without further recurrence of coronary vasospasm. This clinical case demonstrates the potential lethality of coronary vasospasm, and a rare complication during therapy with high doses of calcium channel blockers, with very few cases described in the literature.

We aimed to evaluate joint and vessel uptake in patients with polymyalgia rheumatica (PMR) by FDG-PET and correlate it with clinical findings.Consecutive PMR patients, without clinical signs of giant cell arteritis, underwent a standardised clinical examination and FDG-PET/CT. Controls were consecutive subjects undergoing FDG-PET for the suspicion of neoplasm not confirmed by the examination. Uptake was evaluated by a qualitative visual score, using the liver uptake as reference and by the semi-quantitative mean standardised uptake value (SUV) and target-to-background ratio (TBR) methods.Eighty-four patients and 84 controls (55 women, median age 73 years, range 50-92 years in both groups) were studied. Sixteen patients were taking glucocorticoids (GC). PMR patients showed a higher articular uptake than controls. GC-treated patients showed uptake lower than GC-naïve patients, but still higher than controls. PMR patients showed a higher vascular uptake than controls in all districts except in the carotid arteries, when evaluated by the visual score. Conversely, the semi-quantitative approach yielded no significant differences. Forty-two patients (50%) showed PET evidence of large-vessel vasculitis (LVV), defined as uptake ≥ than that of the liver, and 11.9% showed LVV with vascular uptake higher than that of the liver. The correlation between clinical findings and uptake was scarce. Neither clinical nor laboratory findings could predict the presence of LVV.Patients with PMR show a typical joint pattern at FDG-PET. There are no clinical or laboratory predictors of LVV. Imaging appears to be the only tool to assess LVV in these patients.

Early diagnosis and treatment is paramount in rheumatoid arthritis (RA). Nowadays, there is a need for quick and non-invasive imaging modalities, for which laser speckle contrast analysis (LASCA), a technique that assesses the peripheral blood perfusion (PBP) on a microvascular level, seems to be a promising candidate. The goal of this pilot study was to examine whether the expected increased PBP in active synovitis in RA patients can be detected by LASCA.Thirty RA patients with active synovitis in a finger joint and 44 healthy controls (HC) underwent LASCA examination. The PBP measured over the finger joints was expressed in perfusion units (PU). For the final analysis, all 30 RA patients were matched by age and gender to 30 HC. For the primary analysis the mean difference in PU between joints with active synovitis compared to matched HC, adjusted for type of joint (MCP/PIP), finger, surface and side of hand and for the matching variables (age and gender), was calculated using a multilevel linear model. For the secondary analysis this mean difference in PU was calculated on a monoarticular level.The primary analysis showed an estimated mean difference of 8.79 PU (95%CI -7.79-25.37 PU; p=0.299). For the secondary analysis on a monoarticular level, none of the estimated mean differences differed significantly.In this pilot study examining the use of LASCA in RA, no significant difference in estimated mean PBP between joints with active synovitis in RA and joints without active synovitis in HC could be detected.

BACKGROUND/OBJECTIVE The aim of this study was to explore the associations between nailfold videocapillaroscopy (NVC) and pulmonary function tests (PFTs) in systemic sclerosis (SSc) patients. METHODS This was a longitudinal study with follow-up of unselected Brazilian SSc patients. Baseline clinical examination, serological workup, high-resolution chest tomography, and NVC were performed. Pulmonary function test was performed at baseline and after 24 months. Pulmonary function test worsening over time was defined as either a ΔFVC decline ≥10% or a ΔFVC decline ≥5% and

ObjectiveFibromyalgia (FM) is a chronic musculoskeletal pain syndrome of unknown aetiopathogenesis. Its development and maintenance are related to the interplay of biological, psychological, and contextual factors. Among the contextual factors, sociodemographic aspects are poorly elucidated. This study aimed to evaluate the relationships between sociodemographic/ clinical factors and symptom severity measures using a web-based registry of patients with FM.MethodsAdult patients with an ACR 2010/2011 diagnosis of FM underwent a clinical evaluation and were asked to complete questionnaires covering their sociodemographic data (gender, age, marital status, educational level), and disease-specific measures (the revised Fibromyalgia Impact Questionnaire (FIQR), and the Polysymptomatic Distress Scale (PDS)).ResultsData relating to 3,221 patients (3001 women and 220 men) was collected. The ANOVA showed significant difference in mean FIQR scores when the five marital conditions (cohabiter, married, separated/divorced, single, widowed) were compared ( F 3.321, p< 0.01). While males and females were found to have comparable FIQR scores, the interaction between gender and marital status indicated that separated/divorced males have higher FIQR scores (F 5.684, p=0.001). The multiple regression analysis demonstrated that patients who reported lower educational level experienced more severe FM symptoms, as scored with FIQR (p

Cardiovascular diseases (CVDs) are among the most common causes of access to the Emergency Department and among the leading causes of death worldwide. Accurate diagnostic algorithms are mandatory to ensure a rapid life-saving treatment. However, non-specific clinical presentation and unnecessary referrals to other subspecialties may lead to misinterpretation of the diagnosis and delays. In recent years, the development of imaging technologies has allowed Computed Tomography (CT) to play a prominent role in the concepts of CVD rule-in and rule-out. An optimization strategy for CT protocols is needed to reduce variability and improve image quality. A correct diagnostic suspicion is crucial, as different districts (i.e., heart, aorta and pulmonary circulation) may require different investigation techniques. Additionally, the CVD pre-test probability assessment is highly correlated with CT accuracy. The purpose of this narrative review is to analyze the current role of CT in the approach to the CVDs in the ED, and to analyze the main strategies of CT optimization.

Active vitamin D is a true steroid hormone with pleiotropic biological effects that go beyond the classical concept of bone metabolism regulation. In fact, adequate serum levels of 25-hydroxyvitamin D (>40 ng/mL) are required to support several biological functions, including the control of innate and adaptive immunity in course of infectious, inflammatory and autoimmune diseases. SARS-CoV-2 is responsible for the COVID-19 pandemic and deficient/insufficient serum levels of 25-hydroxyvitamin D are reported in very large cohorts of patients. Of note, vitamin D is involved in different pathophysiological processes, such as expression of SARS-CoV-2 receptor (ACE2), activation of innate (neutrophils with their extracellular traps, monocytes/macrophages, dendritic cells, natural killer cells) and adaptive (T and B lymphocytes) immune cells and clinical manifestations, such as coagulation/thrombotic disorders and acute respiratory distress syndrome. Randomized clinical trials regarding vitamin D supplementation in COVID-19 patients have shown favorable effects on the control of inflammation markers, arterial oxygen saturation/inspired fraction of oxygen ratio, admission to hospital intensive care units and mortality. A target of serum 25-hydroxyvitamin D > 50 ng/mL has been identified as protective for the course of COVID-19, potentially playing an ancillary role in the treatment of the disease.

Summary Background Preliminary criteria for the very early diagnosis of systemic sclerosis (VEDOSS) have been previously proposed to identify signs and symptoms in patients with Raynaud's phenomenon. Patients with all signs or symptoms of the VEDOSS criteria already fulfil the 2013 American College of Rheumatology–European League Against Rheumatism (ACR–EULAR) classification criteria for systemic sclerosis. However, prospective data for the evolution to fulfilling these criteria do not exist. We therefore aimed to determine the clinical value of the VEDOSS criteria to identify patients with Raynaud's phenomenon who progress to systemic sclerosis within 5 years. Methods The VEDOSS project was a multicentre, longitudinal registry study done in 42 European Scleroderma Trial and Research group centres located in 20 countries in Europe, North America, and South America. Patients with Raynaud's phenomenon were eligible for enrolment. Those who had fulfilled the 1980 ACR or the 2013 ACR–EULAR classification criteria for systemic sclerosis, as well as of any other ACR or EULAR classification criteria for other definite connective tissue diseases at enrolment were excluded. Data were recorded each year during follow-up visits and included the four VEDOSS criteria (ie, positivity for antinuclear antibodies [ANAs], puffy fingers, systemic sclerosis-specific autoantibodies, and abnormal nailfold capillaroscopy). The primary endpoint was the fulfilment of the 2013 ACR–EULAR classification criteria for systemic sclerosis (ie, progression from enrolment to follow-up). Proportion of progressors and VEDOSS criteria interaction were reported descriptively. Predictors of progression of the distinct VEDOSS criteria interactions were determined based on the point prevalence at 5 years. To investigate the intermediate course of progression of the distinct VEDOSS criteria and their combinations, Kaplan-Meier analysis was done. Results Between March 1, 2010, and Oct 4, 2018, we enrolled 1150 patients with Raynaud's phenomenon in the VEDOSS database. 764 (66·4%) of 1150 patients met the VEDOSS criteria for study inclusion. Of the 764 patients, 553 (72·4%) had at least one available follow-up visit and the median duration of follow-up was 3·6 years (IQR 1·7–5·8). The mean age was 45·9 years (SD 15·0), 507 (91·7%) of 553 participants were female, and the median time since the onset of Raynaud's phenomenon was 4·0 years (IQR 1·7–10·0). At baseline, 401 (73·7%) of 544 patients with Raynaud's phenomenon had detectable ANA, with 208 (39·5%) of 527 patients positive for systemic sclerosis-specific autoantibodies. Nailfold capillaroscopy abnormalities were present in 182 (36·0%) of 505 patients and puffy fingers were detected in 96 (17·8%) of 540 at baseline. 1885 follow-up visits were recorded. 254 (45·9%) of 553 patients completed the study with progression or a 5-year follow-up; of whom, 133 reached the primary endpoint, resulting in an overall progression rate of 52·4%. The absence of ANA at baseline was the factor most strongly associated with a lack of progression within 5 years, with only four (10·8%) of 37 ANA-negative patients progressing. Conversely, positivity at baseline for systemic sclerosis-specific autoantibodies and puffy fingers was the combination having the highest risk of progression (16 [94·1%] of 17). Interpretation Our results from the VEDOSS project offers a useful tool for a stratified risk approach to patients with Raynaud's phenomenon. The absence of ANA is a strong protective factor that identifies patients with very low risk of developing systemic sclerosis whereas the presence of one or two VEDOSS criteria in patients with Raynaud's phenomenon confers a progressively higher risk for systemic sclerosis over time. This stratification tool can be used both for clinical management and to inform early interventional trials. Funding European Scleroderma Trial And Research and World Scleroderma Foundation.

Food acceptance in different larval stages of Macrobrachium carcinus was evaluated by investigating the stage at which the ingestion of inert moist diet food begins and by the incidence of Artemia nauplii and inert moist diet in the digestive tract throughout development. Two experiments were carried out: in the first study, the acceptance of the inert diet was evaluated in 60 larvae of each stage (I to XII) fed ad libitum after two hours of fasting. The inert diet was 100% accepted at zoea stage V. In the second study, newly hatched larva was then kept in larval tanks and fed with Artemia nauplii and inert moist diet simultaneously. Fifteen minutes after feeding, 50 specimens of each larval stage were examined and evaluated for the ingestion of these foods. Larvae at stage I did not feed, while larvae at stage II consumed both live and inert food. From the stage of zoea IX, the exclusive consumption of Artemia nauplii was not verified. These data indicate that feeding M. carcinus in larviculture can be initiated at stage II with inert moist diet and Artemia nauplii, and an exclusive supply of inert moist diet from stage IX can be recommended.

It is well known that the heat is an enemy of both virus and microbes. Starting from this consideration we discuss the possibility of using a microwave approach for a safe and cheap sterilization of closed rooms.