A Tregs insufficiency is central to autoimmune and inflammatory diseases pathophysiology and low dose interleukin-2 (IL-2LD) can specifically activate Tregs.
To assess IL-2LD therapeutic potential and select diseases for further clinical development, we performed an open-label, phase 2a, disease-finding, \"basket trial\" involving patients with one of 13 different autoimmune diseases.
81 patients treated with IL-2LD (1 million IU/day) for 5 days, followed by fortnightly injections. The first 48 patients received diluted Proleukin®, while the subsequent 33 received ready-to-use ILT-101®. The primary endpoint was the change in Tregs at day-8 compared to baseline. Key secondary endpoints included clinical efficacy assessments using the Clinical Global Impression (CGI) scale, disease-specific scores, and EuroQL-5D-5L.
Our study unveiled a universal and significant expansion and activation of Tregs, without concomitant Teffs activation, across all 13 autoimmune diseases. Both Proleukin® and ready-to-use ILT-101® demonstrated identical effects on Tregs. CGI scores reflecting activity, severity, and efficacy were significantly reduced in the overall patient population. Disease-specific clinical scores improved in five of the six disease cohorts with at least six patients, namely ankylosing spondylitis, systemic lupus erythematosus, Behçet\'s disease, Sjögren\'s syndrome, and systemic sclerosis. Urticaria was the only severe adverse event related to treatment.
IL-2LD was well-tolerated, exhibiting specific Treg activation and clinical improvements across the 13 autoimmune diseases.
Tregs stimulation by IL-2LD is a promising therapeutic strategy and IL-2LD holds considerable promise for integration into combinatorial therapeutic approaches.

No injection treatment has been proven to be effective in wrist osteoarthritis. When conservative measures fail, its management involves invasive surgery. Emergence of biotherapies based on adipose derived stem cells (ADSC) offers promising treatments for chondral degenerative diseases. Microfat (MF) and platelets-rich plasma (PRP) mixture, rich in growth factors and ADSC could be a minimally invasive injectable option in the treatment of wrist osteoarthritis. The aim of this uncontrolled prospective study was to evaluate the safety of a 4 mL autologous MF-PRP intra-articular injection, performed under local anesthesia. The secondary purpose was to describe the clinical and MRI results at 12 months of follow-up. Patients\' data collected were: occurrence of adverse effects, Visual analog scale (VAS), Disabilities of the Arm, Shoulder and Hand score (DASH) and Patient-Rated Wrist Evaluation (PRWE) scores, wrist strength, wrist range of motion and 5-level satisfaction scale. No serious adverse event was recorded. A statistically significant decrease in pain, DASH, PRWE and force was observed at each follow-up. Our preliminary results suggest that intra-articular autologous MF and PRP injection may be a new therapeutic strategy for wrist osteoarthritis resistant to medical symptomatic treatment prior to surgical interventions.

BACKGROUND: Eskenazi Health in Indianapolis, Indiana, USA. services diverse communities in Central Indiana, including the Hispanic/Latinx community. It has been postulated that this population experiences toxicities at a higher rate and with a faster onset than the general population when treated with chemotherapy or biotherapy. The published clinical trials that have evaluated chemotherapy/biotherapy efficacy and toxicity have not adequately represented the Hispanic/Latinx population. This retrospective analysis aims to analyze the incidence and severity of adverse drug events in the Hispanic/Latinx population compared to the general study population.
METHODS: A retrospective chart review included patients reported as Hispanic/Latinx in the electronic medical record who had breast cancer, colon cancer, acute myeloid leukemia, or multiple myeloma currently receiving chemotherapy/biotherapy and/or received chemotherapy/biotherapy during the study period. Seventy-three instances of patients receiving chemotherapy/biotherapy and 46 unique patients were included in the final analysis.
RESULTS: Of the 73 instances, 29 (40%) had toxicity at baseline prior to chemotherapy/biotherapy received during the study period. Of those 29 baseline toxicities, 26 (90%) of them had new toxicity during the study period. Of the 73 instances, 62 (85%) experienced toxicities during the study period.
CONCLUSIONS: Ethnicity has a proven effect on medication efficacy and safety, but the specific impact of ethnicity on chemotherapy/biotherapy toxicity risk has not been well elucidated. This study found that a majority (85%) of Hispanic/Latinx patients treated with chemotherapy/biotherapy experienced toxicity of any grade, and the majority (90%) patients who had prior toxicity experienced another toxicity.

Adult-onset Still\'s disease (AOSD) is a rare inflammatory disease that may be life-threatening if complicated by cardiac problems. We performed a retrospective multicenter study to describe the manifestations, treatments and outcomes of cardiac involvement in AOSD.
We reviewed the medical databases of eight centers. All AOSD patients identified as fulfilling Yamagushi\'s or Fautrel\'s criteria were included in the study. Cardiac involvement, clinical manifestations, laboratory features, the course of the disease and treatments were evaluated.
We included 96 AOSD patients in this study: 28 (29%) had documented cardiac involvement (AOSD + C group) and 68 (71%) had no cardiac involvement (control group). Cardiac complications were observed at diagnosis in 89% of cases. It were pericarditis (n = 17), tamponade (n = 5), myocarditis (n = 5) and non-infectious endocarditis (n = 1). Levels of leukocytes, neutrophils and C-reactive protein were significantly higher (p = 0.02, p = 0.02 and p = 0.002, respectively in the AOSD + C group than in the control group. Admission to intensive care, and the use of biotherapy were more frequent during follow-up in the AOSD + C group than the control group (p = 0.0001 and p = 0.03 respectively). Cardiac involvement was associated with refractory form in multivariate analyzed (p = 0.01). Corticosteroids were effective with or without methotrexate in 71% of patients but not in severe involvement as myocarditis or tamponade.
Cardiac complications are frequent, inaugural, can be life-threatening and predictive of a refractory course in patients with AOSD. Systematic cardiac screening should be proposed at diagnosis and biotherapy early use should be considered especially in myocarditis.

Fournier\'s Gangrene is a fulminating necrotizing fasciitis of the perineum and genitalia. Standard treatment involves immediate excision of all necrotic tissue, aggressive antibiotic coverage, and supportive medical care. Still, the infection is commonly fatal or disfiguring. Wound treatment with disinfected blowfly larvae (maggot debridement therapy or MDT) has been shown to be highly effective, with multiple studies demonstrating effective debridement, disinfection, and promotion of granulation tissue. MDT also has been associated with preservation of viable tissue and minimised blood loss. This report describes a prospective clinical study of MDT for Fournier\'s gangrene aimed to test the hypothesis that early use of maggots could decrease the number of surgical treatments required to treat Fournier\'s gangrene. Subjects were provided with one initial surgical excision, followed by debridement using only medical grade Lucilia sericata larvae. Only two subjects were enrolled, both diabetic men. Intensive care and culture-directed antimicrobial coverage were administered as usual. Maggot debridement was associated with the disappearance of necrotic tissue, control of infection and granulation tissue growth. In both subjects, wounds healed without requiring further surgical resection or anatomical reconstruction. Maggot therapy decreased the number of surgical procedures that otherwise would have been necessary, and led to favourable outcomes.

Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatism in adults. The objective of our study was to analyze the clinical, biological and therapeutic characteristics in subjects over 60 years old.
We performed a retrospective, monocentric, descriptive study on medical records consultations. The data collection concerned subjects over 60 years of age who had been diagnosed with \"rheumatoid arthritis\" in the rheumatology and internal medicine departments of CHU Reims over a period stretching from 2010 to 2015.
Thirty-two patients were included in our study for this period. The mean age of diagnosis was 66.6 years, for a median age of 67.5 years (min: 60 years, max: 88 years). There were 22 female (69%) and 10 male (31%) patients, with a sex ratio H/F of 2.2. The mean duration of symptom progression before diagnosis was 33.2 months. What dominates our series is the inaugural involvement of the interphalangeal proximal, wrists, shoulders and metacarpophalangeal for the vast majority of cases. Oral corticosteroids were used in 27 patients and were the only treatment in 3 patients. Methotrexate (MTX) was introduced in 27 patients. Nine patients received biotherapy: it was tocilizumab (Roactemra®) for 5 patients, adalimumab (Humira®) for 2 patients, abatacept (Orencia®) for 2 patients, etanercept (Enbrel®) for 2 patients, golimumab (Simponi®) for 1 patient and infliximab (Remicade®) for one patient. In our series, 7 patients are over 75 years old at the time of diagnosis of RA.
The rheumatoid arthritis of the elderly remains a common condition and constitutes a diagnostic and therapeutic challenge. Because of the co-morbidities, the clinician\'s perception of the patient\'s overall condition and the inaccuracies in the use of certain molecules in these patients, under-treatment may, on the contrary, weaken a patient whose remission will be postponed. This was not the case in our series, with a methodical use of methotrexate as well as effective dose biotherapies.

Regulatory T cells (Tregs) prevent autoimmunity and control inflammation. Consequently, any autoimmune or inflammatory disease reveals a Treg insufficiency. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential.
We aimed to assess this potential and select diseases for further clinical development by cross-investigating the effects of ld-IL2 in a single clinical trial treating patients with 1 of 11 autoimmune diseases.
We performed a prospective, open-label, phase I-IIa study in 46 patients with a mild to moderate form of either rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Behcet\'s disease, granulomatosis with polyangiitis, Takayasu\'s disease, Crohn\'s disease, ulcerative colitis, autoimmune hepatitis and sclerosing cholangitis. They all received ld-IL2 (1 million IU/day) for 5 days, followed by fortnightly injections for 6 months. Patients were evaluated by deep immunomonitoring and clinical evaluation.
ld-IL2 was well tolerated whatever the disease and the concomitant treatments. Thorough supervised and unsupervised immunomonitoring demonstrated specific Treg expansion and activation in all patients, without effector T cell activation. Indication of potential clinical efficacy was observed.
The dose of IL-2 and treatment scheme used selectively activate and expand Tregs and are safe across different diseases and concomitant treatments. This and preliminary indications of clinical efficacy should licence the launch of phase II efficacy trial of ld-IL2 in various autoimmune and inflammatory diseases.
NCT01988506.

OBJECTIVE: AIDS (acquired immune deficient syndrome), a deadly human infectious disease is caused by HIV (human immunodeficiency viruses) infection. Patient\'s mortality was eventually reduced to one-fourth by combined chemotherapy (usually 3 chemical drugs simultaneously) than earlier HIV/AIDS treatments (single drug or vaccine) in the clinic.
RESULTS: Combined treatments against HIV/AIDS are still incurable for all patients despite a high rate of patient\'s survival. Basic viral pathological study and advancing drug development systems for curable medications are indispensable nowadays and in the future.
CONCLUSIONS: Up to date, therapeutic trinity (combined therapy) against HIV/AIDS is generally among chemical drugs. In this article, several forms of other therapeutic attempts for effectively curing efforts against HIV/AIDS are proposed-including the development of next generation therapeutic HIV vaccines and schedules, new categories of bio-therapy, different pathways of immune-modulation, herbal medicines in general (allopathic, Ayurveda and traditional Chinese medicines), high quality of physical exercises, and especially therapeutic combinations guided by latest medical discovery and principles (new forms of therapeutic trinity against HIV-induced pathogenesis and human mortality).

OBJECTIVE: To report the characteristics of uveitis cases occurring while on biologic therapy or disease-modifying antirheumatic drugs (DMARDs) reported to the French national pharmacovigilance database.
METHODS: All the uveitis cases occurring in patients with chronic rheumatologic diseases, chronic inflammatory intestinal diseases or connective tissue diseases, while treated with DMARDs and/or biologic therapies between 2000 and 2015 and reported to the French National Pharmacovigilance Database were collected.
RESULTS: During the study period, 32 cases of uveitis were reported (15 men, 17 women). Two patients were treated with one DMARD alone, 24 with biologic therapy alone, and six with both treatments. Anterior uveitis was diagnosed in 19 patients (8 cases were bilateral); intermediate uveitis was found (unilaterally) in one patient; posterior and diffuse uveitis occurred in 5 and 2 cases respectively. Five cases were inconclusive with regard to the anatomical type of uveitis. The uveitis was of infectious origin in 5 cases: 2 toxoplasmosis, 2 herpes virus and 1 tuberculosis. In the 27 other cases, it was not possible to state whether the uveitis was associated with the underlying disease (uncontrolled) or a side effect of the biologic/DMARD treatments. The occurrence of the uveitis led to 9 switches in biologic therapy and 13 discontinuations of treatment (8 complete discontinuations, 5 discontinuations only until uveitis remission was obtained). In 4 cases, the treatments were not modified. The database does not specify the ultimate course or rheumatologic disease activity at the time of the uveitis.
CONCLUSIONS: The presence of uveitis while on biologic therapy must not be taken to indicate a therapeutic failure, especially if the ocular manifestation is isolated. In the case of uveitis occurring in patients treated with biologic therapies and/or DMARDs, infectious complications should be ruled out.

OBJECTIVE: To see whether the frequency and features of septic arthritis (SA) complicating rheumatoid arthritis (RA) have changed over the last 35years.
METHODS: This retrospective single-center study included all patients hospitalized at the rheumatology department for SA bacteriologically documented by synovial fluid and/or blood culture samples. The periods 1979-2002 (before biotherapies) and 2003-2013 (the era of biotherapies) were compared.
RESULTS: Between 1979 and 2013, 64/514 (12.5%) SA presented with a RA - 21/157 (13.4%) in the 2003-2013 period and 43/357 (12.0%) in the 1979-2002 period. Over the past decade, median age of RA SA patients increased (61 vs. 68 years; P<0.02) and predominant gender became males (52% vs. 40%). The features of the RA remained unchanged: history (18 vs. 16years), rheumatoid factor (95% vs. 87%), and corticosteroids (91% vs. 81%). Over the last decade 24% (vs. 0; P<0.003) of the patients received a biologic DMARD: etanercept (n=2), adalimumab (n=1), rituximab (n=1), tocilizumab (n=1). Proportion of polyarticular infection had decreased strongly (9.5% vs. 37%; P<0.02). Proportion of Staphyloccus aureus infections remained stable, but there was a higher incidence of MRSA infections (31 vs. 6%; P<0.05). Blood cultures less often tested positive (29% vs. 47%; NS). Case fatality rate had fallen slightly in RA SA (5% vs. 9%; NS), but not in non-RA SA cases (7% vs. 6%; NS).
CONCLUSIONS: This study brings reassuring findings - in the era of biotherapies, the rate of septic arthritis amongst patients with RA has not increased, and the most severe septic polyarticular forms are on the decline.