Selective adaptation of SARS-CoV-2 Omicron under booster vaccine pressure: a multicentre observational study.

BACKGROUND: High rates of vaccination and natural infection drive immunity and redirect selective viral adaptation. Updated boosters are installed to cope with drifted viruses, yet data on adaptive evolution under increasing immune pressure in a real-world situation are lacking. METHODS: Cross-sectional study to characterise SARS-CoV-2 mutational dynamics and selective adaptation over >1 year in relation to vaccine status, viral phylogenetics, and associated clinical and demographic variables. FINDINGS: The study of >5400 SARS-CoV-2 infections between July 2021 and August 2022 in metropolitan New York portrayed the evolutionary transition from Delta to Omicron BA.1-BA.5 variants. Booster vaccinations were implemented during the Delta wave, yet booster breakthrough infections and SARS-CoV-2 re-infections were almost exclusive to Omicron. In adjusted logistic regression analyses, BA.1, BA.2, and BA.5 had a significant growth advantage over co-occurring lineages in the boosted population, unlike BA.2.12.1 or BA.4. Selection pressure by booster shots translated into diffuse adaptive evolution in Delta spike, contrasting with strong, receptor-binding motif-focused adaptive evolution in BA.2-BA.5 spike (Fisher Exact tests; non-synonymous/synonymous mutation rates per site). Convergent evolution has become common in Omicron, engaging spike positions crucial for immune escape, receptor binding, or cleavage. INTERPRETATION: Booster shots are required to cope with gaps in immunity. Their discriminative immune pressure contributes to their effectiveness but also requires monitoring of selective viral adaptation processes. Omicron BA.2 and BA.5 had a selective advantage under booster vaccination pressure, contributing to the evolution of BA.2 and BA.5 sublineages and recombinant forms that predominate in 2023. FUNDING: The study was supported by NYU institutional funds and partly by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center.

Patients' Individualized Care Perceptions and Health Literacy Using an Interactive App During Breast and Prostate Cancer Treatment: Two Parallel Randomized Controlled Trials.

The use of symptom management mobile apps can reduce patients' symptom burden during cancer treatment, but the evidence is lacking about their effect on care. Moreover, if patients' health literacy can be improved, it needs to be more rigorously tested. This study aimed to evaluate patients' perceptions of individualized care and health literacy using an interactive app in two randomized trials. Patients undergoing neoadjuvant chemotherapy for breast cancer (N = 149) and radiotherapy for prostate cancer (N = 150) were consecutively included and randomized into one intervention or control group. Outcome measures were Individualized Care Scale, Swedish Functional Health Literacy Scale, and Swedish Communicative and Critical Health Literacy Scale. In the breast cancer trial, no group differences were observed regarding individualized care or health literacy. Most patients had sufficient health literacy levels. In the prostate cancer trial, intervention group patients rated higher perceived individualized care regarding decision control at follow-up than the control group. Less than half had sufficient health literacy levels and intervention group patients significantly improved their ability to seek, understand, and communicate health information. Education level explained significant variance in health literacy in both trials. Using an interactive app can positively affect individualization in care and health literacy skills among patients treated for prostate cancer, although further research is warranted.

Posterior shoulder dislocation with associated reverse Hill-Sachs lesion: clinical outcome 10 years after joint-preserving surgery.

INTRODUCTION: Posterior shoulder dislocation in association with reverse Hill-Sachs lesion is a rather rare injury. Few studies reporting results after joint-preserving surgery in these cases are available. This current study presents the clinical outcomes 10 years postoperatively. MATERIALS AND METHODS: In a prospective case series, we operatively treated 12 consecutive patients (all males) after posterior shoulder dislocation with associated reverse Hill-Sachs lesion using joint-preserving techniques. Patients received surgery in a single center between January 2008 and December 2011. The joint-preserving surgical procedure was chosen depending on the defect size and bone quality. The following outcome-measures were analyzed: Constant-Score, DASH-Score, ROWE-Score, and SF-12. Results 1, 5, and 10 years postoperatively were compared. RESULTS: Out of 12 patients, ten patients (83.3%) were followed-up with a mean follow-up interval of 10.7 years (range 9.3-12.8). The mean patient age at the time of the last follow-up was 51 years (32-66). The outcome scores at the final follow-up were: Constant 92.5 (range 70.0-100), DASH 3.2 (0.0-10.8), ROWE 91.0 (85.0-100), and SF-12 87.8 (77.5-98.3). Clinical results had improved from 1 to 5 years postoperatively and showed a tendency for even further improvement after 10 years. CONCLUSIONS: Joint-preserving surgical therapy of posterior shoulder dislocation provides excellent results when the morphology of the reverse Hill-Sachs lesion is respected in surgical decision-making. TRIAL REGISTRATION: 223/2012BO2, 02 August 2010.

Neutralization of SARS-CoV-2 Variants by mRNA and Adenoviral Vector Vaccine-Elicited Antibodies.

The increasing prevalence of SARS-CoV-2 variants has raised concerns regarding possible decreases in vaccine effectiveness. Here, neutralizing antibody titers elicited by mRNA-based and adenoviral vector-based vaccines against variant pseudotyped viruses were measured. BNT162b2 and mRNA-1273-elicited antibodies showed modest neutralization resistance against Beta, Delta, Delta plus and Lambda variants whereas Ad26.COV2.S-elicited antibodies from a significant fraction of vaccinated individuals had less neutralizing titer (IC50 <50). The data underscore the importance of surveillance for breakthrough infections that result in severe COVID-19 and suggest a potential benefit by second immunization following Ad26.COV2.S to increase protection from current and future variants.

High-titer neutralization of Mu and C.1.2 SARS-CoV-2 variants by vaccine-elicited antibodies of previously infected individuals.

Recently identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants Mu and C.1.2 have spike proteins with mutations that may confer resistance to natural and vaccine-elicited antibodies. Analysis of neutralizing antibody titers in the sera of vaccinated individuals without previous history of infection and from convalescent individuals show partial resistance of the viruses. In contrast, sera from individuals with a previous history of SARS-CoV-2 infection who were subsequently vaccinated neutralize variants with titers 4- to 11-fold higher, providing a rationale for vaccination of individuals with previous infection. The heavily mutated C.1.2 spike is the most antibody neutralization-resistant spike to date; however, the avidity of C.1.2 spike protein for angiotensin-converting enzyme 2 (ACE2) is low. This finding suggests that the virus evolved to escape the humoral response but has a decrease in fitness, suggesting that it may cause milder disease or be less transmissible. It may be difficult for the spike protein to evolve to escape neutralizing antibodies while maintaining high affinity for ACE2.

Structure-based discovery of small molecules improving stability of human broadly-neutralizing anti-HIV antibody 2F5 in plant suspension cells.

The production of biopharmaceuticals in engineered plant-based systems is a promising technology that has proven its suitability for the production of various recombinant glyco-proteins that are currently undergoing clinical trials. However, compared to mammalian cell lines, the productivity of plant-based systems still requires further improvement. A major obstacle is the proteolytic degradation of recombinant target proteins by endogenous plant proteases mainly from the subtilisin family of serine proteases. In the present study, the authors screened for putative small molecule inhibitors for subtilases that are secreted from tobacco BY-2 suspension cells using an in silico approach. The effectiveness of the substances identified in this screen was subsequently tested in degradation assays using the human broadly-neutralizing anti-HIV monoclonal antibody 2F5 (mAb2F5) and spent BY-2 culture medium as a model system. Among 16 putative inhibitors identified by in silico studies, three naphthalene sulfonic acid derivatives showed inhibitory activity in in vitro degradation assays and are similar to or even more effective than phenylmethylsulfonyl fluoride (PMSF), a classical inhibitor of serine proteases, which served as positive control.

Comparison of Neutralizing Antibody Titers Elicited by mRNA and Adenoviral Vector Vaccine against SARS-CoV-2 Variants.

The increasing prevalence of SARS-CoV-2 variants has raised concerns regarding possible decreases in vaccine efficacy. Here, neutralizing antibody titers elicited by mRNA-based and an adenoviral vector-based vaccine against variant pseudotyped viruses were compared. BNT162b2 and mRNA-1273-elicited antibodies showed modest neutralization resistance against Beta, Delta, Delta plus and Lambda variants whereas Ad26.COV2.S-elicited antibodies from a significant fraction of vaccinated individuals were of low neutralizing titer (IC 50 <50). The data underscore the importance of surveillance for breakthrough infections that result in severe COVID-19 and suggest the benefit of a second immunization following Ad26.COV2.S to increase protection against the variants.

Assessment of mobile source air toxics in an Environmental Justice Denver community adjacent to a freeway.

Air pollutant concentrations are often higher near major roadways than in the surrounding environments owing to emissions from on-road mobile sources. In this study, we quantified the gradient in black carbon (BC) and air toxics concentrations from the I-70 freeway in the Elyria-Swansea environmental justice neighborhood in Denver, Colorado, during three measurement campaigns in 2017-2018. The average hourly upwind-downwind gradient of BC concentrations from the roadway was 500-800 ng/m3, equal to an increment of approximately 30-80% above local background levels within 180 m of the freeway. When integrated over all wind directions, the gradients were smaller, approximately 150-300 ng/m3 (~11-18%) over the course of nearly four months of measurements. No statistically significant gradient in air toxics (e.g., benzene, formaldehyde, etc.) was found, likely because the uncertainties in the mean concentrations were larger than the magnitude of the gradient (<25%). This finding is in contrast to some earlier studies in which small gradients of benzene and other VOCs were found. We estimate that sample sizes of at least 100 individual measurements would have been required to estimate mean concentrations with sufficient certainty to quantify gradients on the order of ±10% uncertainty. These gradient estimates are smaller than those found in previous studies over the past two decades; more stringent emissions standards, the local fleet age distribution, and/or the steady turnover of the vehicle fleet may be reducing the overall impact of roadway emissions on near-road communities. Implications: Gradients of near-road pollution may be declining in the near-road environment as tailpipe emissions from the vehicle fleet continue to decrease. Near-road concentration gradients of mobile source air toxics, including benzene, 1,3-butadiene, and ethylbenzene, will require higher sample sizes to quantify as emissions continue to decline.

3D Printing, Augmented Reality, and Virtual Reality for the Assessment and Management of Kidney and Prostate Cancer: A Systematic Review.

Three-dimensional (3D) printing, augmented reality, and virtual reality technologies have an increasing presence in the management of prostate and kidney cancer. To assess the utility of 3D printing, augmented reality, and virtual reality for (1) quantitative outcomes, (2) surgical planning, (3) intraoperative guidance, (4) training and simulation, and (5) patient education for patients with kidney and prostate cancer a systematic literature review was performed. Existing evidence demonstrates improvement in clinical outcomes, surgical planning and intra-operative guidance, as well as training. Future studies are needed to assess the impact of 3D technologies on long-term patient-related outcomes.

[Diagnostic journey of type 1 Gaucher Disease patients: A survey including internists and hematologists]. / Parcours diagnostique des patients atteints de maladie de Gaucher de type 1 : enquête auprès de médecins internistes et hématologues.

INTRODUCTION: Gaucher disease (GD) is a rare genetic lysosomal storage disorder caused by a beta-glucocerebrosidase deficiency and responsible for a lysosomal storage disorder. GD is characterized by haematological, visceral and bone involvements. The aim of this study was to describe the diagnostic journey of type 1 GD patients as well as the role of the internist. METHODS: A retrospective multicentric study involving type 1 GD patients has been conducted in 16 centers, between 2009 and 2011. RESULTS: Fifty-five type 1 GD patients were included, under the care of an internist or an haematologist. They were originally hospitalized in 8 different specialized units. Diagnosis was established by bone-marrow aspiration in 22 patients (40%), by enzymatic assay of glucocerebrosidase activity in 15 patients (27%), and by bone-marrow biopsy in 9 patients (16%). The use of enzymatic assay became more frequent after 1990. The delay between first hospitalization due to GD symptoms and definitive diagnosis was less than one year for 38 patients. Patients with suspected GD were mainly referred to an internist physician. CONCLUSION: GD seems to be better recognized and quickly diagnosed since 1990 in spite of the multiplicity of journeys. The role of the internist seems important.

Sickness absence following breast cancer surgery: a two-year follow-up cohort study.

RATIONALE AND AIM: Most women of working ages with limited breast cancer (BC) have returned to work within the first year after diagnosis. However, little is known about what is happening during this year regarding sickness absence and return to work. Also, the knowledge is very limited about the occurrence of part-time sickness absence after BC diagnosis. Therefore, the aim of this study was to describe occurrence, extent and length of SA during a two-year follow-up after BC surgery and to analyse the association between being SA and type of cancer treatment. METHODS: In this prospective cohort study, 497 women responded to questionnaires about different aspects of sickness absence at six occasions during two years after primary BC surgery (at baseline and after 4, 8, 12, 18 and 24 months). Treatment information was obtained from the National breast cancer register. Multinomial logistic regression was used to calculate odds ratios (OR) for likelihood of being sickness absent more than once. RESULTS: Two-thirds of the women were sickness absent at baseline; this proportion decreased, especially during the first eight months. At 24 months, 13% were sickness absent. Of all women, 27% never reported sickness absence and 14% were sickness absent at most of the six survey times. At eight months, many had shifted from full- to part-time sickness absence. Women with chemotherapy and/or advanced BC surgery had higher ORs for being sickness absent at most of the follow-ups. CONCLUSIONS: Most women returned to work within the first eight months after BC surgery and of those sickness absent after that, most had been part-time sickness absent. Thus, it is important to differentiate between part- and full-time sickness absence in future studies. Special attention should be paid to the impact of chemotherapy and type of surgery on the likelihood of being sickness absent.

Systemic sclerosis and exposure to heavy metals: A case control study of 100 patients and 300 controls.

OBJECTIVE: This case control study assessed: 1) the relationship of systemic sclerosis (SSc) related to exposure to heavy metals; and 2) the risk of SSc related to occupational exposure in male and female patients. METHODS: From 2005 to 2008, 100 patients with a definite diagnosis of SSc were included in the study; 3 age, gender, and smoking habit matched controls were selected for each patient. All SSc patients and controls underwent detection and quantification of heavy metal traces in hair samples, using multi-element inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: SSc patients exhibited higher median levels of the following metals: antimony (p=0.001), cadmium (p=0.0003), lead (p=0.02), mercury (p=0.02), molybdenum (p=0.04), palladium (p<0.0001) and zinc (p=0.0003). A marked association between SSc and occupational exposure was further found for: 1) antimony (p=0.008) and platinum (p=0.04) in male patients; and 2) antimony (p=0.02), cadmium (p=0.001), lead (p=0.03), mercury (p=0.03), palladium (p=0.0003) and zinc (p=0.0001) in female patients CONCLUSION: The results show the impact of occupational risk factors in the development of SSc for: antimony, cadmium, lead, mercury, molybdenum, palladium and zinc. Thus, occupational exposure should be systematically checked in all SSc patients at diagnosis. Finally, the association between SSc and occupational exposure may be variable according to patients' gender.

[Antineutrophil cytoplasmic antibodies associated with infective endocarditis: Literature review]. / Endocardites infectieuses associées aux anticorps anticytoplasme des polynucléaires neutrophiles (ANCA) : revue de la littérature.

Antineutrophil cytoplasmic antibodies (ANCA) associated with infective endocarditis are a rare disorder. The condition can mimic primary systemic vasculitis (i.e. granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis). Thus, a wrong diagnosis of valvular involvement related to primary systemic vasculitis can be made in patients exhibiting ANCA associated with infective endocarditis. Because treatment of both conditions is different, this wrong diagnosis will lead to dramatic consequences in these latter patients. This review reports the state of knowledge and proposes an algorithm to follow when confronted to a possible case of ANCA associated with infective endocarditis.

Can breast cancer register data on recommended adjuvant treatment be used as a proxy for actually given treatment?

PURPOSES: To study agreement between recommended adjuvant treatment after primary breast cancer (BC) surgery from the clinical based National Breast Cancer Register and initiated adjuvant treatment from medical records; factors associated with agreement; and reasons for discontinuation or change of planned treatment. METHOD: Included were 970 women who had undergone BC surgery, aged 20-63 years, living in Stockholm County, and literate in Swedish. EXCLUSION CRITERIA: Distant metastases, pre-surgical chemotherapy, and/or a previous BC diagnosis. Information on clinical tumor stage, surgical treatment, recommended adjuvant radiotherapy, chemotherapy, and endocrine therapy was obtained from the BC register. Type of initiated adjuvant treatments, if treatment plan was followed, and reasons for discontinuation were extracted from medical records. RESULTS: The register had high completeness and agreement was high, 94-96%, (κ 0.801-0.908) for all types of treatment. Disagreement regarding radiotherapy and chemotherapy was associated with having ≥1 lymph node metastases and more extended axillary surgery, and for radiotherapy also more extended breast surgery. There were no such associations with age, tumor size, or invasiveness. None of these factors were associated with disagreement regarding recommended versus initiated endocrine therapy. Endocrine therapy was most often discontinued (24%), mostly due to toxicity which was also the most common reason for discontinuation of chemotherapy. CONCLUSIONS: Swedish register data on recommended treatment has high validity in women aged 24-63 years, with limited BC, and demonstrates utility as a proxy for initiated treatment in this group. This is of interest since extracting data from medical records is resource demanding.

A study to examine the influence of health professionals' advice and support on work capacity and sick leave after breast cancer surgery.

PURPOSE: The aim of this study was to investigate how women, shortly after breast cancer surgery, experienced encounters with, and information from, healthcare professionals regarding work and sick leave and if these experiences were associated with self-reported work capacity and sick leave. METHODS: This is a cross-sectional study based on questionnaire data from 605 women who had had breast cancer surgery, aged 20-63 years. Exclusion criteria were known distant metastases, pre surgical therapy, and/or previous breast cancer. Data on age, type of surgery, global health, and work environment were included as covariates in multivariable logistic regression analysis. RESULTS: Five percent of the women had not received any advice concerning work or sick leave. Women reporting receiving useful advice or support related to paid work had lower risk of reporting reduced physical or psychological/social work capacity due to the cancer or treatment (OR 0.46 (95 % CI 0.26-0.81) respective OR 0.45 (95 % CI 0.26-0.77)). There were no associations between having received useful advice or support concerning work and being on sick leave. Women encouraged to take sick leave had an OR of 2.17 (95 % CI 1.39-3.37) of being sickness absent. They also to a higher extent had reduced physical and psychological/social work capacity. Women who reported to have been encouraged to work were sickness absent to a lower extent (OR 0.64; 95 % CI 0.41-0.98) and reported higher physical work capacity. CONCLUSIONS: Work and sick leave is being discussed during consultations with women with breast cancer and the advice given seems to be in line with the women's subjective work capacity.

Comparative incidence of rejection occurring in small intestinal and colonic mucosal biopsies of patients undergoing intestinal transplantation.

AIMS: To compare the diagnosis of acute cellular rejection (ACR) based on biopsies (Bx) performed simultaneously in the small bowel (SB) and colonic grafts (paired Bx) after intestinal transplantation (ITx). METHODS AND RESULTS: Retrospective study including all ITx with colon at Mount Sinai Hospital between 2009 and 2014. Paired Bx were reviewed blindly by two experienced gastrointestinal (GI) pathologists and were graded based on the VIII International Small Bowel Transplant Symposium Consensus criteria, with minor modifications for evaluation of colon biopsies. Each Bx was classified as negative or positive for ACR. Cohen's kappa statistic was used to quantify the interpathologist agreement and the agreement between SB and colonic Bx for the diagnosis of ACR. Fifteen patients underwent 51 paired Bx. The strength of agreement for the grade of ACR in the SB biopsies (kappa = 0.62) and the colonic biopsies (kappa = 0.65) was good. The inter-rater agreement was better for Bx negative for ACR and for higher grades of ACR. Overall, 74.5% of paired Bx were concordant for the presence or absence of ACR. The strength of agreement for the presence or absence of ACR between the SB and colonic Bx (kappa = 0.44) was moderate. Two cases of severe ACR were restricted to the SB allograft. CONCLUSIONS: Paired Bx in the SB and the colon are usually in agreement regarding the presence or the absence of ACR. However, colonic Bx alone may not suffice to exclude ACR following ITx. With minor modifications, the histopathological criteria of the SB may be adaptable to the colonic allograft.

Long term outcome of patients with low level of cryoglobulin (<0.05g/L).

OBJECTIVES: To date, no studies have yet assessed the characteristics of non-HCV patients with low level of cryoglobulin (≤0.05 g/L). The aims of the current study were thus to: 1) determine the prevalence of cryoglobulin ≤0.05 g/L in patients with non-HCV cryoglobulin; and 2) compare clinical features and long term outcome, including organ complications and mortality rate, between non-HCV patients with cryoglobulin level ≤0.05 g/L and those exhibiting cryoglobulin level >0.05 g/L. METHODS: Among 6379 cryoglobulin testing, cryoglobulin was detected in 618 patients (9.69% of cases); of these 618 patients, 453 non-HCV patients were included in the study. The medical records of these patients were reviewed. RESULTS: Of the 453 non-HCV cryoglobulin-positive patients, 265 (58.6%) exhibited cryoglobulin level ≤0.05 g/L. We showed that patients with cryoglobulin level ≤0.05 g/L had: 1) less commonly: palpable purpura (p<0.001), digital ulcers (p=0.006), peripheral neurologic involvement (p=0.03) and renal impairment (p=0.03); and 2) lower median values of ESR (p<0.001) and C-reactive protein (p=0.001). The patients with cryoglobulin level ≤0.05 g/L less often experienced infections (p=0.04) and hematological malignancies (p=0.01); both groups did not differ regarding prevalence of connective tissue diseases and solid tumors. Mortality rate was as high as 13.6% in patients with cryoglobulin level ≤0.05 g/L; death was mainly due to: solid tumors (16.6%), cardiovascular complications (13.8%), hematological malignancies (11.1%), infections (8.3%), pulmonary/renal complications of cryoglobulin (8.3%) and connective tissue diseases (8.3%). CONCLUSION: Our study shows a high prevalence of cryoglobulin level ≤0.05 g/L in clinical practice. Our findings further underscore that non-HCV cryoglobulin level ≤0.05 g/L may be responsible for severe renal and neurological complications, leading to high morbidity and mortality in these patients. Thus, our data suggest that both appropriate therapy and close follow-up may be required to improve such patients' outcome.

Changes in importance of work and vocational satisfaction during the 2 years after breast cancer surgery and factors associated with this.

PURPOSE: The purpose of this study is to investigate how women, during the 2 years following breast cancer surgery, rate importance of work and vocational satisfaction, and baseline factors associated with rating over time. METHODS: A prospective cohort study of 692 women aged 20-63 included about 4 weeks after a first breast cancer surgery. Register data on treatment and data from six repeated questionnaires during a 2-year follow-up (at baseline, 4, 8, 12, 18, 24 months) were used in two-way mixed repeated analysis of variance and mixed repeated measures analysis of covariance. RESULTS: The women rated importance of work (m = 3.74; sd 0.88) (maximum 5) and vocational satisfaction (m = 4.30; sd 1.38) (maximum 6) high during the 2 years. Women with planned chemotherapy rated lower vocational satisfaction and especially so at 4 months after inclusion (F 1, 498 = 8.20; p = 0.004). Higher age, better physical, and mental/social work ability at baseline influenced rating of vocational satisfaction. Supportive colleagues was an important covariate that significantly affected ratings of importance of work as well as vocational satisfaction, i.e., women with better support rated on average higher on these outcomes. The effect of chemotherapy disappeared after including the abovementioned baseline covariates. CONCLUSIONS: Women diagnosed with breast cancer in the following 2 years rate importance of work and vocational satisfaction high, which are associated to lower work ability and social support. IMPLICATIONS FOR CANCER SURVIVORS: Work is a very important aspect in life also after a cancer diagnosis, which has to be acknowledged when discussing treatment and rehabilitation plans with women with breast cancer. Furthermore, workplace support needs to be assessed as this is an influential factor.

Game of 'Somes: Protein Destruction for Mycobacterium tuberculosis Pathogenesis.

The proteasome system of Mycobacterium tuberculosis is required for causing disease. Proteasomes are multisubunit chambered proteases and, until recently, were only known to participate in adenosine triphosphate (ATP)-dependent proteolysis in bacteria. In this review, we discuss the latest advances in understanding how both ATP-dependent and ATP-independent proteasome-regulated pathways contribute to M. tuberculosis virulence.

Efficacy of anti-TNF alpha in severe and/or refractory Behçet's disease: Multicenter study of 124 patients.

OBJECTIVE: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). METHODS: We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. RESULTS: Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. CONCLUSION: Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab).