Epidemiological, Clinical, and Therapeutic Profile of Uveitis in Multiple Sclerosis: A Multicenter Study.

INTRODUCTION: Uveitis may occur during approximately 1-3% of MS patients, corresponding to 10 times higher than in the general population. The development of uveitis is not currently considered as an inflammatory relapse of MS. There are no clinical guidelines for treating. MS with concomitant uveitis requiring systemic treatment. PURPOSES: To analyze clinical and therapeutic characteristics of uveitis in patients with MS and the impact of MS treatment on the progression of uveitis. MATERIALS & METHODS: We conducted a retrospective, observational, multicenter study in France about 54 patients. RESULTS: The form of MS most frequently associated with uveitis in our study was the relapsing-remitting form (85%). The mean time of onset of uveitis was 15 months before the diagnosis of MS. The most frequent form of uveitis was bilateral panuveitis (43%), non-granulomatous (61%), synechial (52%) and non-hypertonic (93%) with progressive onset (65%) and chronic course (66%). CONCLUSION: MS-associated uveitis occurs most frequently before the diagnosis of relapsing-remitting MS in the form of panuveitis or intermediate uveitis, which is mildly inflammatory and whose main complications are macular edema, cataract and venous vasculitis. Despite their chronicity, these uveitis cases have a good visual prognosis and teriflunomide appears to have a positive effect on progression.

Supportive care in patients with cancer during the COVID-19 pandemic.

Cancer care has been profoundly impacted by the global pandemic of severe acute respiratory syndrome coronavirus 2 disease (coronavirus disease 2019, COVID-19), resulting in unprecedented challenges. Supportive care is an essential component of cancer treatment, seeking to prevent and manage chemotherapy complications such as febrile neutropenia, anaemia, thrombocytopenia/bleeding, thromboembolic events and nausea/vomiting, all of which are common causes of hospitalisation. These adverse events are an essential consideration under routine patient management, but particularly so during a pandemic, a setting in which clinicians aim to minimise patients' risk of infection and need for hospital visits. Professional medical oncology societies have been providing updated guidelines to support health care professionals with the management, treatment and supportive care needs of their patients with cancer under the threat of COVID-19. This paper aims to review the recommendations made by the most prominent medical oncology societies for devising and modifying supportive care strategies during the pandemic.

Digital health for optimal supportive care in oncology: benefits, limits, and future perspectives.

BACKGROUND: Digital health provides solutions that capture patient-reported outcomes (PROs) and allows symptom monitoring and patient management. Digital therapeutics is the provision to patients of evidence-based therapeutic interventions through software applications aimed at prevention, monitoring, management, and treatment of symptoms and diseases or for treatment optimization. The digital health solutions collecting PROs address many unmet needs, including access to care and reassurance, increase in adherence and treatment efficacy, and decrease in hospitalizations. With current developments in oncology including increased availability of oral drugs and reduced availability of healthcare professionals, these solutions offer an innovative approach to optimize healthcare resource utilization. DESIGN: This scoping review clarifies the role and impact of the digital health solutions in oncology supportive care, with a view of the current segmentation according to their technical features (connection to sensors, PRO collection, remote monitoring, self-management in real time…), and identifies evidence from clinical studies published about their benefits and limitations and drivers and barriers to adoption. A qualitative summary is presented. RESULTS: Sixty-six studies were identified and included in the qualitative synthesis. Studies supported the use of 38 digital health solutions collecting ePROs and allowing remote monitoring, with benefits to patients regarding symptom reporting and management, reduction in symptom distress, decrease in unplanned hospitalizations and related costs and improved quality of life and survival. Among those 38 solutions 21 provided patient self-management with impactful symptom support, improvement of QoL, usefulness and reassurance. Principal challenges are in developing and implementing digital solutions to suit most patients, while ensuring patient compliance and adaptability for use in different healthcare systems and living environments. CONCLUSIONS: There is growing evidence that digital health collecting ePROs provide benefits to patients related to clinical and health economic endpoints. These digital solutions can be integrated into routine supportive care in oncology practice to provide improved patient-centered care.

Scleral fixated intraocular lens by a modified technique: Methods and results.

PURPOSE: A certain number of conditions can result in compromised anterior and/or posterior capsular integrity. Several surgical options have been employed for repositioning dislocated intraocular lenses in the absence of adequate capsular support. The purpose of this study is to assess the functional outcomes and complication profile of a modified surgical technique for replacing dislocated intraocular lenses. MATERIAL AND METHODS: All patients who had undergone the modified surgical procedure for dislocated intraocular lenses between 2012 and 2017 were retrospectively reviewed for visual outcomes and complications. Patient demographic characteristics, pre- and postoperative visual acuity, surgical indications, refractive outcomes, intraocular pressure and postoperative complications were recorded and analysed at baseline and at six months, which was the conclusion of the study. We also present our modified surgical technique. RESULTS: Sixty-eight eyes of sixty-eight patients (74% male) were included. Mean age at surgery was 58 years (range 4-89 years). Mean best-corrected visual acuity increased significantly from 0.80 (SD±0.2) LogMar to 0.40 (SD±0.1) LogMar (P<0.005). Median astigmatic error at the conclusion of follow-up remained stable. There were no intraoperative complications and a low postoperative complication rate (10.2%), mainly related to the surgical context. CONCLUSION: Sutureless intrascleral fixation of dislocated intraocular lenses is an option in case of deficient capsular support. Visual outcomes and complication rates are comparable to other case series.

Clinical and para-clinical description of a novel mutation for Schnyder dystrophy in a French family.

INTRODUCTION: The objective of this article is to describe the evolution of Schnyder dystrophy in 3 related patients of different ages and to highlight the discovery of a new mutation unidentified until now. CASE REPORT: We present a series of 3 cases, all first-degree relatives with no suggestion of consanguinity, of different ages (30, 40 and 59 years) and two distinct generations (mother and children). Slit lamp examination revealed the same lesions in our three patients: an early-onset corneal arcus senilis, central corneal deposits, and a gray stromal haze in the two oldest subjects. The older the patient, the more numerous and dense were these lesions. The various anterior segment OCTs showed an increase in the number of hyperreflective opacities in the anterior stroma and, in the older subject, the appearance of many posterior shadows. Monitoring of pachymetry by Pentacam® showed progressive age-related thickening. All three patients had dyslipidemia treated with statins or diet alone. In our case we proposed treatment only to subject A because of the significant impact on her visual acuity. DISCUSSION: Numerous clinical, para-clinical and genetic descriptions of this disease are found in the literature. Schnyder dystrophy is rare but not unheard of and may be discovered fortuitously or in the setting of decreased visual acuity. Genetic analysis of our family revealed a mutation of the UBIAD1 gene not described in the literature. UBIAD1 encodes the protein domain-containing UbiA prenyltransferase 1 which converts vitamin K1 into K2 and is involved in the cholesterol synthesis pathway. In the case of a mutation, it is no longer functional, leading to the accumulation of cholesterol crystals. Given the clinical context and the presence of this variant of the reference sequence in all relatives, its pathogenesis is strongly suspected in our family. The originality of our article is to present the progression of the same pathology in 3 patients with the same mutation at different ages and degrees of severity. This notion of progressive worsening and the need to treat late in the majority of cases are found in literature. CONCLUSION: The discovery of a new variant within the UBAID1 gene suggests its pathogenesis in view of the clinical features available to us. The dystrophy is initially asymptomatic before the high number of deposits becomes disabling.

[Retinal vasculitis and systemic diseases]. / Vascularites rétiniennes et maladies systémiques.

Retinal vasculitis (RV) is an inflammation of retinal blood vessels that can be associated with uveitis or be isolated, and can induce vascular occlusion and retinal ischemia. Visual acuity can be severely affected in case of macular involvement or neovessel formation. The diagnosis relies on fundoscopy and fluorescein angiography. Systemic diseases may be associated with RV, the most frequently encountered are Behçet's disease, sarcoidosis or multiple sclerosis, all predominantly associated with venous involvement, whereas systemic lupus erythematosus and necrotizing vasculitis are less frequently observed and predominantly associated with arterial or mixed vasculitis. Treatments are usually aggressive in order to preserve a good visual acuity and to reduce retinal inflammation and chronic ischemia. Steroids, immunosuppressive drugs, retinal laser photocoagulation, intravitreal anti-VEGF injections are usual treatments and more recently, anti-TNFalpha monoclonal therapeutic antibodies have been shown to be very successful.

Safety and efficacy of alternating treatment with EP2006, a filgrastim biosimilar, and reference filgrastim: a phase III, randomised, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy.

Background: In 2015, the biosimilar filgrastim EP2006 became the first biosimilar approved by the US Food and Drug Administration for commercial use in the United States, marketed as Zarxio® (Sandoz). This phase III randomised, double-blind registration study in patients with breast cancer receiving (neo)adjuvant myelosuppressive chemotherapy (TAC; docetaxel + doxorubicin + cyclophosphamide) compares reference filgrastim, Neupogen® (Amgen), with two groups receiving alternating treatment with reference and biosimilar every other cycle. Patients and methods: A total of 218 patients receiving 5 µg/kg/day filgrastim over six chemotherapy cycles were randomised 1: 1: 1: 1 into four arms. Two arms received only one product, biosimilar or reference (unswitched), and two arms (switched) received alternating treatments every other cycle (biosimilar then reference or vice versa over six cycles). Since the switch occurred from cycle 2 onwards, this analysis compared pooled switched groups to the unswitched reference group for efficacy during cycles 2-6. Safety was also assessed. Non-inferiority in febrile neutropenia (FN) rates between groups for cycles 2-6 was shown if 95% were within a pre-defined margin of - 15%. Results: A total of 109 patients switched treatment, and 52 patients received reference in all cycles. Baseline characteristics were similar between groups. The incidence of FN was 0% (reference) versus 3.4% (n = 3, switched) across cycles 2-6, with a difference of - 3.4% (95% confidence interval: -9.65% to 4.96%), showing non-inferiority. Infections occurred in 9.3% (switched) versus 9.9% (reference). Hospitalisation due to FN was low (one patient in cycle 6; switched). Adverse events related to filgrastim were reported in 42.1% (switched) versus 39.2% (reference) (all cycles). Musculoskeletal/connective tissue disorders related to filgrastim occurred in 35.5% (switched) versus 39.2% (reference) (all cycles), including bone pain (30.8% versus 33.3%). No neutralising antibodies were detected. Conclusions: There were no clinically meaningful results regarding efficacy, safety or immunogenicity when switching from reference to biosimilar filgrastim/EP2006, or vice versa.

Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer.

BACKGROUND: Following the functional and physicochemical characterization of a proposed biosimilar, comparative clinical studies help to confirm biosimilarity by demonstrating similar safety and efficacy to the reference product in a sensitive patient population. PATIENTS AND METHODS: LA-EP2006 is a proposed biosimilar that has been developed for pegfilgrastim, a long-acting form of granulocyte colony-stimulating factor for the prevention of neutropenia. The current analysis reports data pooled from two independent, multinational, prospective, randomized, controlled, double-blind phase III studies of similar design comparing the safety and efficacy of reference pegfilgrastim with LA-EP2006 in patients with breast cancer receiving myelotoxic (neo)adjuvant TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy and requiring granulocyte colony-stimulating factor. RESULTS: A total of 624 patients were randomized in the PROTECT-1 and PROTECT-2 studies (NCT01735175; NCT01516736) (LA-EP2006: n = 314; reference: n = 310). Baseline characteristics of patients were well balanced across treatment groups. The primary end point, mean duration of severe neutropenia in the first chemotherapy cycle was similar in both the LA-EP2006 and reference groups (1.05 ± 1.055 days versus 1.01 ± 0.958 days), with a treatment difference of - 0.04 days [95% confidence interval (CI): -0.19 to 0.11] that met the equivalence criteria (the 95% CI were within the defined margin of ±1 day). Secondary end points, such as the nadir of absolute neutrophil count and the incidence of febrile neutropenia, were also similar between LA-EP2006 and reference pegfilgrastim. The safety and tolerability profile of LA-EP2006 was similar to that observed with reference pegfilgrastim, and there were no reports of neutralizing antibodies. CONCLUSIONS: This pooled analysis confirms, as a part of totality of evidence approach, that the proposed biosimilar pegfilgrastim LA-EP2006 has a comparable efficacy and safety profile to reference pegfilgrastim in patients with breast cancer receiving TAC chemotherapy. CLINICAL TRIAL NUMBERS: NCT01735175 and NCT01516736.