Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan-Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8-91.5%) at month 12, 78.8% (95% CI: 78.8-85.2%) at month 24, 63.8% (95% CI: 55.1-73.8%) at month 36, and 59.9% (95% CI: 55.1-73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Therapeutic Effects of Apremilast on Enthesitis and Dactylitis in Real Clinical Setting: An Italian Multicenter Study.

INTRODUCTION: Enthesitis and dactylitis are difficult-to-treat features of psoriatic arthritis (PsA), leading to disability and affecting quality of life. OBJECTIVE: The aim of this study is to evaluate enthesitis (using the Leed enthesitis index (LEI)) and dactylitis at 6 and 12 months in patients treated with apremilast. METHODS: Patients affected by PsA from fifteen Italian rheumatological referral centers were screened. The inclusion criteria were: (a) enthesitis or dactylitisphenotype; (b) treatment with apremilast 30 mg bid. Clinical and treatment history, including PsA disease activity, were recorded. Mann-Whitney and chi-squared tests were used to assess the differences between independent groups, and Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. A p-value of <0.05 was considered statistically significant. RESULTS: The Eph cohort consisted of 118 patients (median LEI 3); the Dph cohort included 96 patients with a median dactylitis of 1 (IQR 1-2). According to an intention to treat analysis, 25% and 34% of patients with enthesitis achieved remission (i.e., LEI = 0) in T1 and T2. The remission of dactylitis was 47% in T1 and 44% in T2. The per protocol analysis (patients observed for at least 12 months) showed that both dactylitis and LEI significantly improved in T1 (median LEI 1 (IQR 1-3)) and T2 (median LEI 0 (IQR 1-2)). CONCLUSION: Eph and Dph PsA patients treated with apremilast experienced a significant improvement in enthesitis and dactylitis activity. After 1 year, enthesitis and dactylitis remission was achieved in more than one-third of patients.

Predictors of DAPSA Response in Psoriatic Arthritis Patients Treated with Apremilast in a Retrospective Observational Multi-Centric Study.

BACKGROUND: To date, only a few real-world-setting studies evaluated apremilast effectiveness in psoriatic arthritis (PsA). The aims of this retrospective observational study are to report long-term Disease Activity Index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and to analyze the predictors of clinical response. METHODS: All PsA consecutive patients treated with apremilast in fifteen Italian rheumatological referral centers were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline, 6 months, and 12 months were recorded. The Mann-Whitney test and chi-squared tests assessed the differences between independent groups, whereas the Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. Logistic regressions verified if there were factors associated with achievement of DAPSA low disease activity or remission at 6 and 12 months. RESULTS: DAPSA low disease activity or remission rates at 6 and 12 months were observed, respectively, in 42.7% (n = 125) and 54.9% (n = 161) patients. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio (OR) 0.841, 95% confidence interval (CI) 0.804-0.879; p < 0.01) and at 12 months (OR 0.911, 95% CI 0.883-0.939; p < 0.01). CONCLUSIONS: Almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. The only factor associated with achievement of low disease activity or remission at both 6 and 12 months was baseline DAPSA.

Multidisciplinary Rheuma-Derma Clinics: 5 Years of Experience at the San Marco Hospital in Catania.

INTRODUCTION: Early psoriatic arthritis (PsA) diagnosis is critical to prescribe timely treatment to prevent the irreversible joint damage and the many other problems that patients with PsA experience. This retrospective study aimed to highlight the benefits of a Rheuma-Derma Clinic focused on the early diagnosis and prompt treatment of PsA with a shared approach among Italian psoriasis patients. Diagnosing PsA early is the main goal to reduce joint damage and disability in the patients affected. Studies describing the results of rheuma-derma clinics aimed to reach this goal emerged in the last decade. This study presents limitations and advantages typical of retrospective designs. METHODS: A Rheuma-Derma Clinic was created in 2017 at the Rheumatology Department of the Hospital Policlinico Gaspare Rodolico of the University of Catania in San Marco, Italy. This study compared the number of patients under disease-modifying antirheumatic treatment 5 years before and after the joint clinic was created. A rheumatologist and dermatologist simultaneously assessed patients with psoriasis and/or PsA to obtain a rapid multidisciplinary diagnostic approach and a shared therapeutic strategy. In addition, demographic, clinical, and clinimetrics data were collected. RESULTS: The number of patients with PsA receiving biological disease-modifying antirheumatic drugs increased 47% (from 255 to 374 patients) before and after the joint clinic was implemented. Likewise, those receiving conventional synthetic disease-modifying antirheumatic drugs increased by 47% (from 367 to 539) as well. Additionally, for all the clinimetrics evaluated (DAS28, HAQ, BASDAI, DAPSA, PASI, PGA), there was an improvement over the 12 months under the Rheuma-Derma Clinic care. The measures that improved the most were DAPSA, PGA, PASI, and BASDAI. CONCLUSION: The implementation of the Rheuma-Derma Clinic was associated with an increase in the number of patients diagnosed, the number of patients with PsA receiving DMARD treatments, and improvements in clinimetrics among the study participants.

Apremilast retention rate in clinical practice: observations from an Italian multi-center study.

OBJECTIVE: There are few real-world setting studies focused on apremilast effectiveness (i.e., retention rate) in psoriatic arthritis (PsA). The main aim of this retrospective observational study is the assessment of apremilast 3-year retention rate in real-world PsA patients. Moreover, the secondary objective is to report the reasons of apremilast discontinuation and the factors related to treatment persistence. METHODS: In fifteen Italian rheumatological referral centers, all PsA consecutive patients who received apremilast were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline were recorded. The Kaplan-Meier curve and the Cox analysis computed the apremilast retention rate and treatment persistence-related risk factors. A p-value < 0.05 was considered statistically significant. RESULTS: The 356 enrolled patients (median age 60 [interquartile range IQR 52-67] yrs; male prevalence 42.7%) median observation period was 17 [IQR 7-34] months (7218 patients-months). The apremilast retention rate at 12, 24, and 36 months was, respectively, 85.6%, 73.6%, and 61.8%. The main discontinuation reasons were secondary inefficacy (34% of interruptions), gastro-intestinal intolerance (24%), and primary inefficacy (19%). Age and oligo-articular phenotype were related to treatment persistence (respectively hazard ratio 0.98 IQR 0.96-0.99; p = 0.048 and 0.54 IQR 0.31-0.95; p = 0.03). CONCLUSION: Almost three-fifths of PsA patients receiving apremilast were still in treatment after 3 years. This study confirmed its effectiveness and safety profile. Apremilast appears as a good treatment choice in all oligo-articular PsA patients and in those ones burdened by relevant comorbidities. Key Points • Apremilast retention rates in this real-life cohort and trials are comparable. • The oligo-articular phenotype is associated with long-lasting treatment (i.e., 3 years). • No different or more prevalent adverse events were observed.

Telemedicine in the Management of Patients with Rheumatic Disease during COVID-19 Pandemic: Incidence of Psychiatric Disorders and Fibromyalgia in Patients with Rheumatoid Arthritis and Psoriatic Arthritis.

The management of patients with immuno-rheumatological diseases has profoundly changed during the COVID-19 pandemic and telemedicine has played an important role in the disease follow-up. In addition to monitoring disease activity and any adverse events, especially infectious events, assessing the psychological situation of the patient can be fundamental. Furthermore, COVID-19 has a serious impact on mental health and, since the beginning of the pandemic, a significantly higher incidence of anxiety disorders and depressive symptoms especially in younger people was observed. In this study, we evaluated the incidence of depressive disorders, anxiety, and fibromyalgia (FM) in our patients with rheumatoid arthritis and psoriatic arthritis during the lockdown period due to the COVID-19 pandemic and we validate the use of telemedicine in the clinical management of these patients. Mental and physical stress during the COVID-19 pandemic can greatly worsen FM symptoms and intensify patients' suffering without a clinical flare of the inflammatory disease for patients affected by rheumatoid arthritis. Telemedicine has allowed us to identify patients who needed a face-to-face approach for therapeutic reevaluation even if not related to a flare of the inflammatory disease. Even if our data does not allow us to draw definitive conclusions regarding the effectiveness of telemedicine as greater than or equal to the standard face-to-face approach, we continue to work by modifying our approach to try to ensure the necessary care in compliance with safety and, optimistically, this tool will become an important part of rheumatic disease management.

Case Report: Rehabilitation After Platelet-Rich Growth Factors' Intra-Articular Injections for Knee Osteoarthritis: Two Case Reports of a Home-Based Protocol.

Knee osteoarthritis (KOA) is a chronic progressive disease that can cause pain, functional impairment, and ultimately disability. A novel and promising therapeutic approach to KOA is the so-called regenerative medicine, a set of procedures designed to harness tissue regenerative capacity and optimize functional recovery. Increasing evidence points out that platelet-rich plasma (PRP) intra-articular injections can decrease pain and improve functional abilities in KOA patients. In the present case reports, we analyze two patients who were treated with PRP injections coupled with a posttreatment home-based rehabilitation program. The two patients were selected to represent two different populations: patient 1 was an 85-year-old with severe impairment of functional abilities, while patient 2 was a younger (59 years old) and more active patient. The protocol consisted in a series of exercise to be performed at home, during the five days following PRP injection for two consecutive weeks (10 days in total). The exercises were designed to reduce the inflammation after the injection, enhance the proprioceptive control of the treated lower limb, and strengthen hip and knee flexors and extensors, mainly by isometric work. Results were evaluated at two time points: before and 2 months after the first PRP injection. The outcomes considered were as follows: visual analog scale for pain, EuroQol 5 dimensions questionnaire, Tegner Activity Scale for functioning, and Knee Injury and Osteoarthritis Outcome Score (KOOS). Both patients did not report any side effects from the treatment. Improvement in patient 1 was drastic at the two months follow-up as far as pain and functional abilities are concerned. Patient 2's improvement was less evident, probably due to the higher starting point in both pain and functionality. Overall, the developed program seemed safe and was tolerated by the patients analyzed in the study, who performed it with good compliance.

Enhancement of nonlinear functionality of step-index silica fibers combining thermal poling and 2D materials deposition.

This work proposes a new route to overcome the limits of the thermal poling technique for the creation of second order nonlinearity in conventional silica optical fibers. We prove that it is possible to enhance the nonlinear behavior of periodically poled fibers merging the effects of poling with the nonlinear intrinsic properties of some materials, such as MoS2, which are deposited inside the cladding holes of a twin-hole silica fiber. The optical waves involved in a second harmonic generation process partially overlap inside the thin film of the nonlinear material and exploit its higher third order susceptibility to produce an enhanced SHG.

Versatile Multimodality Imaging System Based on Detectorless and Scanless Optical Feedback Interferometry-A Retrospective Overview for A Prospective Vision.

In this retrospective compendium, we attempt to draw a "fil rouge" along fifteen years of our research in the field of optical feedback interferometry aimed at guiding the readers to the verge of new developments in the field. The general reader will be moved at appreciating the versatility and the still largely uncovered potential of the optical feedback interferometry, for both sensing and imaging applications. By discovering the broad range of available wavelengths (0.4-120 µm), the different types of suitable semiconductor lasers (Fabry-Perot, distributed feedback, vertical-cavity, quantum-cascade), and a number of unconventional tenders in multi-axis displacement, ablation front progression, self-referenced measurements, multispectral, structured light feedback imaging and compressive sensing, the specialist also could find inspirational suggestions to expand his field of research.

Thermal Poling of Optical Fibers: A Numerical History.

This review gives a perspective of the thermal poling technique throughout its chronological evolution, starting in the early 1990s when the first observation of the permanent creation of a second order non-linearity inside a bulk piece of glass was reported. We then discuss a number of significant developments in this field, focusing particular attention on working principles, numerical analysis and theoretical advances in thermal poling of optical fibers, and conclude with the most recent studies and publications by the authors. Our latest works show how in principle, optical fibers of any geometry (conventional step-index, solid core microstructured, etc) and of any length can be poled, thus creating an advanced technological platform for the realization of all-fiber quadratic non-linear photonics.

Composite material anti-resonant optical fiber electromodulator with a 3.5 dB depth.

The hollow regions of an anti-resonant fiber (ARF) offer an excellent template for the deposition of functional materials. When the optical properties of such materials can be modified via external stimuli, it offers a method to control the transmission properties of the fiber device. In this Letter, we show that the integration of a ${{\rm MoS}_2}$MoS2 film into the ARF voids allows the fiber to act as an electro-optical modulator. We record a maximum modulation depth of 3.5 dB at 744 nm, with an average insertion loss of 7.5 dB.

All-fiber sixth harmonic generation of deep UV: erratum.

This erratum corrects the mistyped pump repetition rate in Opt. Lett.42, 4671 (2017)OPLEDP0146-959210.1364/OL.42.004671.

Single is better than double: theoretical and experimental comparison between two thermal poling configurations of optical fibers.

Thermal poling, a technique to create permanently effective second-order susceptibility in silica optical fibers, has a suite of applications including frequency conversion and mixing for high harmonic generation and phase sensitive amplification, optical switching and modulation, and polarization-entangled photon pair generation. In this work, we compare both theoretically and experimentally two different electrode configurations for poling optical fibers, namely double-anode and single-anode, for two different geometries of the cladding holes. This analysis reveals that the single-anode configuration is optimal, both for the absolute value of effective χ (2) created in the fiber core, and for the simplification of the fiber fabrication process.

All-fiber sixth-harmonic generation of deep UV.

We simulate and experimentally demonstrate deep ultraviolet generation from a 1550 nm laser source in a fully fiberized system by cascading second- and third-harmonic generation using a periodically poled silica fiber and an optical sub-micron diameter fiber. Harmonic generation is achieved by harnessing intermodal phase matching in optical microfibers and a permanent χ(2) induced via thermal poling. As a result, efficient nonlinear processes can be observed, despite the low third-order nonlinear susceptibility of silica glass.

Composite material hollow antiresonant fibers.

We study novel designs of hollow-core antiresonant fibers comprising multiple materials in their core-boundary membrane. We show that these types of fibers still satisfy an antiresonance condition and compare their properties to those of an ideal single-material fiber with an equivalent thickness and refractive index. As a practical consequence of this concept, we discuss the first realization and characterization of a composite silicon/glass-based hollow antiresonant fiber.

All-fiber fourth and fifth harmonic generation from a single source.

All-fiber fourth and fifth harmonic generation from a single source is demonstrated experimentally and analyzed theoretically. Light from a fully fiberized high power master oscillator power amplifier is launched into a periodically poled silica fiber generating the second harmonic. The output is then sent through two optical microfibers that generate the third and fourth harmonic, respectively, via four wave mixing (FWM). For a large range of pump wavelengths in the silica optical transmission window, phase matched FWM can be achieved in the microfibers at two different diameters with relatively wide fabrication tolerances of up to +/-5 nm. Our simulations indicate that by optimizing the second harmonic generation efficiency and the diameters and lengths of the two microfibers, conversion efficiencies to the fourth harmonic in excess of 25% are theoretically achievable.

Phase matched parametric amplification via four-wave mixing in optical microfibers.

Four-wave mixing (FWM) based parametric amplification in optical microfibers (OMFs) is demonstrated over a wavelength range of over 1000 nm by exploiting their tailorable dispersion characteristics to achieve phase matching. Simulations indicate that for any set of wavelengths satisfying the FWM energy conservation condition there are two diameters at which phase matching in the fundamental mode can occur. Experiments with a high-power pulsed source working in conjunction with a periodically poled silica fiber (PPSF), producing both fundamental and second harmonic signals, are undertaken to investigate the possibility of FWM parametric amplification in OMFs. Large increases of idler output power at the third harmonic wavelength were recorded for diameters close to the two phase matching diameters. A total amplification of more than 25 dB from the initial signal was observed in a 6 mm long optical microfiber, after accounting for the thermal drift of the PPSF and other losses in the system.

Choledochal cyst mimicking Mirizzi's syndrome: a case report.

Choledochal cysts are cystic dilatations of the intra or extra-hepatic biliary tract with an incidence of 1 case per 150.000 live births. Cysts usually are diagnosed in childhood, but diagnosis can be delayed until adulthood in the 20-50% of cases. Clinical manifestations comprise abdominal pain with biliary or pancreatic features. Mirizzi's syndrome is a late and rare complication, that occurs in 1% of patients with cholelithiasis due to extrinsic compression of the common bile duct by stones impacted either in the gallbladder or in the cystic duct. Clinical symptoms include extrahepatic obstructive jaundice, ascending cholangitis, or, in the later course, cholecystocholedocal fistula. For both pathologies the Endoscopic Retrograde Cholangio Pancreatography and the Magnetic Resonance Cholangio Pancreatography should lead to the diagnosis with a sensibility and a specificity up to 100%. We report the case of a 66 year old patient admitted to the Emergency Department of our hospital for jaundice and abdominal pain, whom both the endoscopic and radiologic examination showed a Mirizzi's syndrome but surgery revealed a type I choledocal cyst.

Postoperative hypocalcemia: assessment timing.

180 total thyroidectomy case studies performed by the same operator in the years 2006-2010, all done with sutureless technique (Ligasure precise(®)). The monitoring of patients involved a dose of serum calcium on the 1st, 2nd, 3rd and seventh post-operative, before the ambulatory monitoring of the patient. Treatment of post-operative thyroidectomy also includes the administration from the first day of post-surgery, of 2 g/day of calcium (calcium lactate gluconate 2940 mg, calcium carbonate 300 mg). Hypocalcemia was observed in 27 cases (15%) of which 23/180 (12.8%) were transitional and 4/180 (2.2%) were permanent. The average postoperative hospitalization was 2.5 days with a minimum of 30 h. The peak of hypocalcemia was of 11 patients on the first postoperative day (40.7%) in 6 patients on the second postoperative day (22.2%), in 8 patients on the third postoperative day (29.6%), in 1 patient on the fourth postoperative day (3.7%) and in another one on the fifth postoperative day (3.7%). The second postoperative day is crucial for the determination of early discharge (24-30 h). When the surgeon identifies and manages to preserve at least 3 parathyroid glands during surgery, the risk of hypocalcemia together with evaluations of serum calcium on the first and second post-operative day, eliminates the hypocalcemic risk.

Choledochal cyst mimicking Mirizzi's syndrome A case report.

Choledochal cysts are cystic dilatations of the intra or extra-hepatic biliary tract with an incidence of 1 case per 150.000 live births. Cysts usually are diagnosed in childhood, but diagnosis can be delayed until adulthood in the 20-50% of cases. Clinical manifestations comprise abdominal pain with biliary or pancreatic features. Mirizzi's syndrome is a late and rare complication, that occurs in 1% of patients with cholelithiasis due to extrinsic compression of the common bile duct by stones impacted either in the gallbladder or in the cystic duct. Clinical symptoms include extrahepatic obstructive jaundice, ascending cholangitis, or, in the later course, cholecystocholedocal fistula. For both pathologies the Endoscopic Retrograde Cholangio Pancreatography and the Magnetic Resonance Cholangio Pancreatography should lead to the diagnosis with a sensibility and a specificity up to 100%. We report the case of a 66 year old patient admitted to the Emergency Department of our hospital for jaundice and abdominal pain, whom both the endoscopic and radiologic examination showed a Mirizzi's syndrome but surgery revealed a type I choledocal cyst.