Enterococcus-related vascular graft infection: A case series.

OBJECTIVES: We aimed to assess the frequency, management, and burden of enterococcal-related vascular graft infection. PATIENTS AND METHODS: From 2008 to 2021, data regarding all episodes of vascular graft infections initially managed or secondarily referred to our referral center were prospectively collected. We described the history and management of the infection, depending on the type of prosthesis used. RESULTS: The frequency of enterococcal-related vascular graft infections was 29/249 (12 %). Most of them were early infections (22/29, 76 %). Infections were polymicrobial (26/29, 90 %), mostly associated with Enterobacterales. Among patients with positive blood cultures, 7/8 (88 %) involved enterococci. Patients with enterococcal-related vascular graft infections were mainly (22/29, 76 %) treated with an association of antibiotics. Mortality and relapse occurred in 28 % and 7 % respectively of the cases. CONCLUSIONS: Enterococcal-related vascular graft infections occurred in patients with comorbidities, during the early period following surgery and were more frequent in cases of intra-cavitary prosthesis. Their potential virulence needs to be considered, especially in polymicrobial infections.

Dalbavancin as salvage therapy in difficult-to-treat patients for diabetes-related foot osteomyelitis.

OBJECTIVES: We aimed to describe the efficacy and safety of dalbavancin in treatment of patients with diabetes-related foot osteomyelitis with bone culture confirmation. PATIENTS AND METHODS: Between January 2019 and December 2021, all consecutive patients receiving at least one 1500 mg dose of dalbavancin for diabetes-related foot osteomyelitis were included in a retrospective study. Remission was defined as absence of relapsing infection or need for surgery at the initial or a contiguous site during 6-month follow-up from the last dose of dalbavancin. RESULTS: Thirteen patients were included. Eleven (85%) patients were surgically treated. Six (46%) patients received dalbavancin as first-line treatment and 7 (54%) as second-line treatment due to adverse events related to previous treatments. One adverse event was reported. At 6-month follow-up, 11 patients were evaluable and 9 (82%) were in remission. CONCLUSIONS: In the study, dalbavancin was well-tolerated and showed microbiological and clinical efficacy.

Are unknown co-medications, over-the-counter and off-label drug use still problems among people living with HIV? Results from a transversal survey in 23 centres in France.

INTRODUCTION: Polypharmacy can lead to drug-drug interactions (DDIs), especially with ART. The burden of co-medications, including over-the-counter (OTC) drugs and self-medications, could be underestimated. We aimed to investigate the proportion of people living with HIV (PLHIV) with declared and undeclared co-medications, as well as their potential burden. METHODS: We conducted a national, multicentre, 1 week cross-sectional study between 10 December and 16 December 2019 in 23 French hospitals amongst consecutive adult PLHIV presenting for a routine outpatient visit. A standardized questionnaire filled in by the physicians assessed all medications and other active chemical substances taken by the PLHIV. RESULTS: Overall we enrolled 496 participants from 23 centres. Median age was 50.6 years; ART regimens included an integrase inhibitor in 61% (n = 302), an NNRTI in 34% (n = 169) and a PI in 14% (n = 70) of the cases. Co-medications involved 392 (79%) PLHIV, among which 85 (17%) received polypharmacy (≥5 medications). Previously unknown co-medications or other active substances were found for 32% (n = 159) of the participants. Corticosteroids (9%, n = 46) and proton pump inhibitors (10%, n = 50) were frequently administered. These co-medications did not differ according to age range. Illegal drug use was declared by 11% (n = 54) and OTC drugs by 23% (n = 113) of PLHIV. Potential DDIs were discovered for 11% (n = 53), leading to treatment modifications in 47% (25/53) of cases. CONCLUSIONS: Potential DDIs that lead to therapeutic modifications remain significant whatever the age of PLHIV. More devoted time to identify co-medications and OTC treatment is needed in all PLHIV.

Depression and anxiety before and at the beginning of the COVID-19 pandemic and incident persistent symptoms: a prospective population-based cohort study.

Many patients affected by COVID-19 suffer from debilitating persistent symptoms whose risk factors remained poorly understood. This prospective study examined the association of depression and anxiety symptoms measured before and at the beginning of the COVID-19 pandemic with the incidence of persistent symptoms. Among 25,114 participants [mean (SD) age, 48.72 years (12.82); 51.1% women] from the SAPRIS and SAPRIS-Sérologie surveys nested in the French CONSTANCES population-based cohort, depression and anxiety symptoms were measured with the Center for Epidemiologic Studies-Depression scale and the 12-item General Health Questionnaire before the pandemic, and with the 9-item Patient Health Questionnaire and the 7-Item Generalized Anxiety Disorder scale at the beginning of the pandemic (i.e., between April 6, 2020 and May 4, 2020). Incident persistent symptoms were self-reported between December 2020 and January 2021. The following variables were also considered: gender, age, educational level, household income, smoking status, BMI, hypertension, diabetes, self-rated health, and SARS-CoV-2 infection according to serology/PCR test results. After a follow-up of seven to ten months, 2329 participants (9.3%) had been infected with SARS-CoV-2 and 4262 (17.0%) reported at least one incident persistent symptom that emerged from March 2020, regardless of SARS-CoV-2 infection. In multi-adjusted logistic regression models, participants in the highest (versus the lowest) quartile of depressive or anxiety symptom levels before or at the beginning of the pandemic were more likely to have at least one incident persistent symptom (versus none) at follow-up [OR (95%CI) ranging from 2.10 (1.89-2.32) to 3.01 (2.68-3.37)], with dose-response relationships (p for linear trend <0.001). Overall, these associations were significantly stronger in non-infected versus infected participants, except for depressive symptoms at the beginning of the pandemic. Depressive symptoms at the beginning of the pandemic were the strongest predictor of incident persistent symptoms in both infected and non-infected participants [OR (95%CI): 2.88 (2.01-4.14) and 3.03 (2.69-3.42), respectively]. In exploratory analyses, similar associations were found for each symptom taken separately in different models. Depression and anxiety symptoms should be tested as a potential target for preventive interventions against persistent symptoms after an infection with SARS-CoV-2.

Antibody response, associated symptoms and profile of patients presumably infected by SARS-CoV-2 with taste or smell disorders in the SAPRIS multicohort study.

BACKGROUND: Taste or smell disorders have been reported as strongly associated with COVID-19 diagnosis. We aimed to identify subject characteristics, symptom associations, and antibody response intensity associated with taste or smell disorders. METHODS: We used data from SAPRIS, a study based on a consortium of five prospective cohorts gathering 279,478 participants in the French general population. In the analysis, we selected participants who were presumably infected by SARS-CoV-2 during the first epidemic wave. RESULTS: The analysis included 3,439 patients with a positive ELISA-Spike. Sex (OR = 1.28 [95% CI 1.05-1.58] for women), smoking (OR = 1.54 [95% CI 1.13-2.07]), consumption of more than 2 drinks of alcohol a day (OR = 1.37 [95% CI 1.06-1.76]) were associated with a higher probability of taste or smell disorders. The relationship between age and taste or smell disorders was non-linear. Serological titers were associated with taste or smell disorders: OR = 1.31 [95% CI 1.26-1.36], OR = 1.37 [95% CI 1.33-1.42] and OR = 1.34 [95% CI 1.29-1.39] for ELISA-Spike, ELISA-Nucleocapsid and seroneutralization, respectively. Among participants with taste or smell disorders, 90% reported a wide variety of other symptoms whereas 10% reported no other symptom or only rhinorrhea. CONCLUSIONS: Among patients with a positive ELISA-Spike test, women, smokers and people drinking more than 2 drinks a day were more likely to develop taste or smell disorders. This symptom was strongly associated with an antibody response. The overwhelming majority of patients with taste or smell disorders experienced a wide variety of symptoms.

Long-lasting Symptoms After an Acute COVID-19 Infection and Factors Associated With Their Resolution.

Importance: Persistent symptoms after SARS-CoV-2 infection are an emerging public health problem. The duration of these symptoms remains poorly documented. Objective: To describe the temporal dynamics of persistent symptoms after SARS-CoV-2 infection and the factors associated with their resolution. Design, Setting, and Participants: This cross-sectional study involved 53 047 participants from 3 French adult population-based cohorts (CONSTANCES [Consultants des Centres d'Examens de Santé], E3N/E4N, and Nutrinet-Santé) who were included in a nationwide survey about SARS-CoV-2 infection. All participants were asked to complete self-administered questionnaires between April 1 and June 30, 2020. Variables included sociodemographic characteristics, comorbid conditions, COVID-19 diagnosis, and acute symptoms. Blood samples were obtained for serologic analysis between May 1 and November 30, 2020, from patients with SARS-CoV-2 infection defined as enzyme-linked immunosorbent assay immunoglobulin G antispike detection confirmed with a neutralization assay. A follow-up internet questionnaire was completed between June 1 and September 30, 2021, with details on persistent symptoms, their duration, and SARS-CoV-2 infection diagnosis by polymerase chain reaction. Main Outcomes and Measures: Persistent symptoms were defined as symptoms occurring during the acute infection and lasting 2 or more months. Survival models for interval-censored data were used to estimate symptom duration from the acute episode. Multivariable adjusted hazard ratios (HRs) were estimated for age, sex, and comorbid conditions. Factors associated with the resolution of symptoms were assessed. Results: A total of 3972 participants (2531 women [63.7%; 95% CI, 62.2%-65.2%]; mean [SD] age, 50.9 [12.7] years) had been infected with SARS-CoV-2. Of these 3972 participants, 2647 (66.6% [95% CI, 65.1%-68.1%]) reported at least 1 symptom during the acute phase. Of these 2647 participants, 861 (32.5% [95% CI, 30.8%-34.3%]) reported at least 1 persistent symptom lasting 2 or more months after the acute phase. After 1 year of follow-up, the estimated proportion of individuals with complete symptom resolution was 89.9% (95% CI, 88.7%-90.9%) with acute symptoms. Older age (>60 years; HR, 0.78; 95% CI, 0.68-0.90), female sex (HR, 0.64; 95% CI, 0.58-0.70), history of cancer (HR, 0.61; 95% CI, 0.47-0.79), history of tobacco consumption (HR, 0.80; 95% CI, 0.73-0.88), high body mass index (≥30: HR, 0.75; 95% CI, 0.63-0.89), and high number of symptoms during the acute phase (>4; HR, 0.43; 95% CI, 0.39-0.48) were associated with a slower resolution of symptoms. Conclusions and Relevance: In this cross-sectional study, persistent symptoms were still present in 10.1% of infected individuals at 1 year after SARS-CoV-2 infection. Given the high level of cumulative incidence of COVID-19, the absolute prevalent number of people with persistent symptoms is a public health concern.

Conservative surgical treatment for metatarsal osteomyelitis in diabetic foot: experience of two French centres.

AIMS: Conservative surgery (CS) for diabetic foot osteomyelitis (DFO) consists in removing all or part of the infected bone tissues without amputation, in complement with antibiotic therapy. Data on CS for DFO therapy are scarce. MATERIAL AND METHODS: We performed a retrospective analysis of all DFO episodes treated with CS between 06/2007 and 12/2017. Remission was defined by the absence of soft-tissue infection, complete sustained (i.e. > 1 month) healing of the foot ulcer, favourable (i.e., stabilisation or improvement) radiological outcome, and no need for additional surgery during a 1-year follow-up. RESULTS: During the study period, 47 episodes (in 41 patients) were analysed. Excluding deaths (all unrelated to the DFO; n = 3) or loss to follow-up before 1 year (n = 5), the remission rate was 64.2%. Most failures occurred during the first 6 months (79%, 11/14). Patients who experienced failure had a higher rate of peripheral arterial disease with arterial stenosis than patients in remission (57% vs. 24%, P = 0.03), a higher C-reactive protein rate at admission (116 ± 112 mg/L vs. 48 ± 46 mg/L, P = 0.02), and a trend for a higher rate of abscesses (29% vs. 4%, P = 0.06). At 1-year follow-up, foot ulcers related to transfer lesion were identified in 25.5% of the cases. At the last follow-up (mean 3 ± 2 years), the remission rate was 23/25 (92%). CONCLUSIONS: Our results suggest that CS is a therapeutic option in patients with localised but severe DFO. Clinicians should, however, consider the necessity of revascularisation, and higher risk of failure if surgery is performed in patients presenting with acute foot infections.

Accuracy of endobronchial ultrasound-guided transbronchial needle aspiration in HIV-infected patients with thoracic lymphadenopathy in a tuberculosis low-burden area.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an innovative technique to explore hilar and mediastinal lymphadenopathy. We aimed to assess its diagnostic accuracy in HIV-infected patients in a tuberculosis low-burden area. A retrospective review was performed of all HIV-infected patients with thoracic lymphadenopathy referred for EBUS-TBNA between January 2012 and January 2019 in 3 Northern French Hospitals. A total of 15 patients was included during the study period. Our patients were predominantly male (80%), with a mean age of 50 ± 11 years. Six patients (43%) had a CD4 cells count of less than 200/mm3. Eleven patients (73%) were receiving antiretroviral therapy, and 7 (47%) reached undetectable viral load. Adequate lymphnode sampling was accomplished in all patients. No serious complications were reported. EBUS-TBNA led to a definitive diagnosis in 12 out of 15 patients (80%). It identified 4 neoplasia, 3 atypical mycobacterial diseases, 2 tuberculosis, 1 Castleman disease, 1 sarcoidosis, and 1 professional dustiness. In 3 cases, sampling revealed normal lymphoid tissue. Active surveillance confirmed the suspected diagnosis of HIV adenitis with regression of lymphadenopathy on antiretroviral therapy in 2 cases. In one case of negative sampling, thoracoscopy led to the diagnosis of tuberculosis. In our cohort, accuracy of EBUS-TBNA was 92%. EBUS-TBNA appeared to be a safe and accurate tool in the investigation of mediastinal lymphadenopathy in HIV-infected patients in settings of tuberculosis low-prevalence. It can avoid more invasive procedures such as mediastinoscopy.

Surgical techniques for Bone Biopsy in Diabetic Foot Infection, and association between results and treatment duration.

Surgery is an important part of the management of patients diagnosed with DFO. It consists in some selected patients, to remove all or part of the infected bone(s) or even to amputate all or part of the foot. Despite the use of sophisticated imaging techniques, it is however difficult to remove all the infected tissue while respecting the principles of an economical surgery. Bone biopsy performed at the margins of the resection permits to identify residual osteomyelitis and to adjust the post-surgical antibiotic treatment. Some recent studies have reported the way to perform bone margin biopsies and have assessed the impact of the bone results on the patient's outcome. However, the real impact of a residual osteomyelitis on the risk of recurrent DFO is still debated and questions regarding the interpretation of the results remain to be solved. Similarly, the consequences in terms of choice and duration of the antimicrobial treatment to use in case of positive bone margin are not clearly established.

Multimorbidity in Elderly Persons According to the Year of Diagnosis of Human Immunodeficiency Virus Infection: A Cross-sectional Dat'AIDS Cohort Study.

BACKGROUND: We assessed prevalence of multimorbidity (MM) according to year of human immunodeficiency virus (HIV) diagnosis in elderly people living with HIV (PLWH). METHODS: This was a cross-sectional study of MM in PLWH aged ≥70 years from the Dat'AIDS French multicenter cohort. MM was defined as at least 3 coexistent morbidities of high blood pressure, diabetes mellitus, osteoporosis, non-AIDS cancer, chronic renal failure, cardiovascular and cerebrovascular disease, obesity, undernutrition, or hypercholesterolemia. Logistic regression models evaluated the association between MM and calendar periods of HIV diagnosis (1983-1996, 1997-2006, and 2007-2018). The secondary analysis evaluated MM as a continuous outcome, and a sensitivity analysis excluded PLWH with nadir CD4 count <200 cells/µL. RESULTS: Between January 2017 and September 2018, 2476 PLWH were included. Median age was 73 years, 75% were men, median CD4 count was 578 cells/µL, and 94% had controlled viremia. MM prevalence was 71%. HBP and hypercholesterolemia were the most prevalent comorbidities. After adjustment for age, gender, smoking status, hepatitis C and hepatitis B virus coinfection, group of exposure, nadir CD4 count, CD4:CD8 ratio, and last CD4 level, calendar period of diagnosis was not associated with MM (P = .169). MM was associated with older age, CD4/CD8 ratio <0.8, and nadir CD4 count <200 cells/µL. Similar results were found with secondary and sensitivity analyses. CONCLUSIONS: MM prevalence was high and increased with age, low CD4/CD8 ratio, and nadir CD4 count <200 cells/µL but was not associated with calendar periods of HIV diagnosis. Known duration of HIV diagnosis does not seem to be a criterion for selecting elderly PLWH at risk of MM.

Listeria monocytogenes-associated endovascular infections: A study of 71 consecutive cases.

BACKGROUND: Listeria monocytogenes-associated endovascular infections are not well characterized. METHODS: Retrospective study of 71 culture-proven cases reported to the French National Reference Center for Listeria from 1993 to 2018. RESULTS: Seventy-one cases were identified: 42 with vascular aneurysms/prosthetic infections, 27 with endocarditis, 2 with both. Fifty-eight were men (82%); median age was 75 years [46-92]; 93% reported co-morbidities (66/71), including 50% with immunosuppressive conditions. Vascular infections consisted of infected aneurysms (68%) or prosthetic graft infections (32%); vascular rupture was reported in 25/42 (60%). Tissue samples grew L. monocytogenes in 98% (43/44) and blood cultures in 64% (27/42). Endocarditis cases involved prosthetic or native valves or intracardiac devices in respectively 62% (18/29), 28% (8/29) and 10% (3/29). Infected valves were aortic (62%, 16/26), mitral (31%, 8/26) or both (8%, 2/26); 38% patients required surgery; 45% displayed heart failure; 17% had concomitant neurolisteriosis. In-hospital mortality in vascular infections was 12% (5/42) and 41% (12/29) for Lm-associated endocarditis. CONCLUSIONS: Endovascular listeriosis is a rare but severe infection. It manifests as vascular infections and endocarditis, mostly in older patients with vascular or cardiac valve prosthetic devices and co-morbidities. Mortality in Lm-associated endocarditis is twice higher than with other pathogens, requiring prompt recognition and treatment.

Routine drug resistance testing in proviral HIV-1 DNA: Prevalence of stop codons and hypermutation, and associated factors.

We investigated the presence of stop codons (SC) and/or hypermutation (HM) in HIV-1 DNA sequences generated for routine drug resistance testing in proviral HIV-1 DNA, and sought for associated factors. At least one SC was identified in 6.2% of HIV-1 DNA sequences, among which 54.8% were hypermutated. The defective virus group (SC w/o HM) was similar to the non-SC group regarding the characteristics of HIV-1 infection, and before drug exposure. In addition, the HIV-1 DNA levels were not different between both groups. Sequences with SC/HM displayed a higher proportion of RAMs. The impact of the SC/HM associated RAMs on clinical responses requires further investigation.

Mycobacterium mucogenicum bacteremia: major role of clinical microbiologists.

INTRODUCTION: Mycobacterium mucogenicum is a rare but emerging cause of infections, especially in immunocompromised patients. CASE PRESENTATION: We describe a new case of M. mucogenicum catheter-related bloodstream infection in a 34-year-old woman with ovarian cancer. M. mucogenicum was at first considered as a contaminant, and susceptibility testing was not performed. Usual susceptibility of M. mucogenicum motivated prescription of clarithromycin and moxifloxacin. Finally, our isolate was confirmed susceptible to both drugs. Clinical outcome was favorable with no relapse of infection after antibiotics discontinuation despite concomitant chemotherapy. CONCLUSION: Our case illustrates the need for a clinician-microbiologist dialogue in case of suspected M. mucogenicum infection to avoid delaying appropriate management.

Calendar trends in sexual behaviours in a cohort of HIV-infected MSM at the era of treatment as prevention of HIV infection.

BACKGROUND: With the advent of treatment as prevention of HIV infection (TasP), we assessed trends in sexual behaviours between 2000 and 2017 among HIV-infected MSM enrolled in the French ANRS PRIMO cohort. METHODS: At each cohort visit, a clinical questionnaire including laboratory values was completed and a self-administered questionnaire was used to collect sexual behaviours, that is, the number, type (steady/casual) and HIV status (positive or negative/unknown) of partners, and condom use. The possible influence of viral load (undetectable/detectable) measured at the preceding visit on the evolution over time of sexual behaviour was assessed with logistic regression models fitted by generalized estimating equations (GEE), taking into account longitudinal data. RESULTS: We analyzed data from 10657 follow-up visits by 1364 MSM. Overall, whatever the considered behavioural variable: at least one sexual partner, steady and/or casual, condomless sex with steady, casual partners, serodiscordant or not, we observed a calendar increase with a particularly more marked rise from 2010 (P < 0.0001). Inconsistent condom use did not differ according to the viral load status (detectable vs. undetectable). Trends in inconsistent condom use increased across different generations of MSM, as defined by the year they were diagnosed with HIV infection. CONCLUSIONS: 'Having a sexual partner' and condomless sex, both increased in frequency between 2000 and 2017. Viral load status did not influence condom use as could have been expected from the 2008 Swiss Statement.

Risk of Progressive Multifocal Leukoencephalopathy in the Combination Antiretroviral Therapy Era in the French Hospital Database on Human Immunodeficiency Virus (ANRS-C4).

Background: Risk factors for progressive multifocal leukoencephalopathy (PML) in individuals with human immunodeficiency virus (HIV) infection are poorly documented in the era of combination antiretroviral therapy (cART). Methods: We studied HIV-1-infected individuals aged ≥15 years who had no history of PML and were prospectively followed up between 1997 and 2011 in the French Hospital Database on HIV (FHDH-ANRS CO4) cohort. Cox models were used to calculate adjusted hazard ratios (HRs), focusing on sub-Saharan origin, suggested to be protective, and recent cART initiation, potentially associated with an increased risk of PML. Results: PML developed in 555 individuals, in 57 during the first 6 months of cART. From 1997-2000 to 2009-2011, the incidence fell from 1.15 (95% confidence interval [CI], .98-1.31) to 0.49 (.37-.61) per 1000 person-years. Sub-Saharan African origin had no clear influence (HR, 0.80; 95% CI, .58-1.11). Compared with men who have sex with men, injection drug users (IDUs) were at higher risk (HR, 1.80 [95% CI, 1.32-2.45] for male and 1.68 [1.13-2.48] for female IDUs). When IDUs were excluded, hepatitis C virus seropositivity was associated with an increased risk (HR, 1.40; 95% CI, 1.02-1.93). Compared with no cART initiation, initiation <6 months previously was associated with PML onset (HR, 4.91; 95% CI, 2.42-9.95). Conclusions: Recent cART initiation is associated with an increased risk of PML, as are injection drug use and hepatitis C virus seropositivity. Sub-Saharan African origin had no protective effect.

Treatment options for diabetic foot osteomyelitis.

INTRODUCTION: Diabetic foot osteomyelitis therapeutical options are based on antibiotic therapy and surgical resection of the infected bone(s). Surgical and medical approaches of patients suffering from a diabetic foot osteomyelitis do not oppose but are complementary and need to be discussed as a tailored manner. Areas covered: The aim of the present article is to discuss data issued from the most recent guidelines of the Infectious Diseases Society of America and the International Working Group on the Diabetic Foot on the management of the diabetic foot infection and from a search in the current literature using the terms diabetic foot osteomyelitis and treatment/therapy/therapeutical in both PubMed and Medline, restricted to the last five years. Expert opinion: Surgical removal of the entire infected bone(s) has been considered in the past as the standard treatment but medical approach of these patients has now proven efficacy in selected situations. The current emergence of bacteria, especially among Gram negative rods, resistant to almost all the available antibiotics gradually augments the complexity of the management of these patients and is likely to decrease the place of the medical approach and to worsen the outcome of these infections in the next future.

Effect of in vitro and in vivo anakinra on cytokines production in Schnitzler syndrome.

IL-1 receptor antagonist anakinra is usually highly efficient in Schnitzler syndrome (SS), a rare inflammatory condition associating urticaria, fever, and IgM monoclonal gammopathy. In this study, we aimed to assess lipopolysaccharide (LPS)-induced production of inflammatory cytokines by peripheral blood mononuclear cells (PBMCs) before and after 1 month of anakinra in patients with SS. LPS-induced production of IL-1ß, IL-6 and TNFα was assessed by enzyme-linked immunosorbent assay with and without anakinra in vitro, and before and after 1 month (in vivo condition) of treatment in 2 patients with SS. Spontaneous production of IL-1ß, IL-6 and TNF-α by PBMCs was similar in the patients and the healthy controls and was almost undetectable. Stimulation with LPS caused a higher release of cytokines from the patients than from the healthy controls. Before in vivo anakinra start, in vitro adjunction of anakinra reduced the high LPS-induced production of IL-1ß and TNFα in both patients and of IL-6 in one patient. After 1 month of treatment with anakinra, while the patients had dramatically improved, there was also a marked reduction in LPS-induced cytokines production, which was almost normalized in one patient. This study shows an abnormal LPS-induced inflammatory cytokines production in SS, which can be decreased or even normalized by in vitro and in vivo anakinra.