Performs a systematic review of the literature that aims to summarise all available evidence of anti-interleukin-1 (IL-1) therapies in patients with familial Mediterranean fever (FMF). Source: ...National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Autoinflammatory diseases (AIDs) are a group of rare monogenetic disorders characterized by recurrent episodes of fever and systemic inflammation. A major pathologic hallmark of AIDs is excessive ...inflammasome assembly and activation, often the result of gain-of-function mutations in genes encoding core inflammasome components, including pyrin and cryopyrin. Recent advances in lipidomics have revealed that dysregulated metabolism of lipids such as cholesterol and fatty acids, especially in innate immune cells, exerts complex effects on inflammasome activation and the pathogenesis of AIDs. In this review, we summarize and discuss the impact of lipids and their metabolism on inflammasome activation and the disease pathogenesis of the most common AIDs, including familial Mediterranean fever, cryopyrin-associated periodic syndromes, and mevalonate kinase deficiency. We postulate that lipids hold diagnostic value in AIDs and that dietary and pharmacologic intervention studies could represent a promising approach to attenuate inflammasome activation and AID progression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Familial Mediterranean Fever (FMF) is the most prevalent genetic autoinflammatory disorder. In most patients, treatment with colchicine can prevent attacks of fever and inflammation. However, 5%-10% ...of patients are resistant to colchicine treatment, while a similar percentage cannot tolerate colchicine in doses needed to prevent attacks. For these patients, Canakinumab, a full human antibody against IL-1β, has been approved recently by the FDA and EMA. In this article, we present a systematic review of the long-term efficacy, safety, and tolerability of Canakinumab in FMF patients who cannot tolerate colchicine or who are resistant to colchicine treatment.
The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS), one of the autoinflammatory syndromes, is caused by mutations in the gene coding for mevalonate kinase (MVK). We conducted the ...current study to assess the genetic, laboratory, and clinical features as well as the complications and course of disease in patients with genetically confirmed HIDS. In addition, we studied the quality of life and course of life in a selection of patients. Follow-up data were obtained by a questionnaire sent to all physicians of patients in the International HIDS Database. In addition, we assessed the course of life and quality of life in Dutch patients aged >16 years using validated quality of life instruments. Data were obtained from 103 patients from 18 different countries. The median age of first attack was 6 months (range, 0-120 mo), with a median period of 9.9 years from onset of disease to diagnosis. The most frequent symptoms that accompanied attacks of fever were lymphadenopathy, abdominal pain, arthralgia, diarrhea, vomiting, skin lesions, and aphthous ulcers. Amyloidosis was a severe but infrequent complication (2.9%). The median serum IgD level was 400 U/mL. IgD levels were normal in 22% of patients. The 4 most prevalent mutations (V377I, I268T, H20P/N, P167L) accounted for 71.5% of mutations found. The frequency of attacks decreased with the patient's increasing age, although 50% of patients over the age of 20 years still had 6 or more attacks per year. Many drugs have been tried in HIDS. Some patients responded to high-dose prednisone (24.4% response). Anakinra and etanercept can also be effective (33.3% response). Quality of life was determined in a subgroup of patients (n = 28). Social functioning, general health perception, and vitality were significantly lower in patients with HIDS than in controls, as were autonomy and social development. In addition, HIDS had an adverse impact on educational achievements and employment status. In conclusion, HIDS is an early-onset disease that is accompanied by an array of inflammatory symptoms. Although the frequency of attacks decreases during the patient's life, many patients continue to have frequent attacks. HIDS impairs several aspects of quality of life.
Acute appendicitis is a common surgical emergency worldwide. Exaggerated immune responses could be associated with appendicitis. This study aimed at characterizing immune responses towards a large ...variety of gut commensals and pathogens, and pattern recognition receptor (PRR) ligands, and investigating the course of systemic inflammation in a prospective cohort of acute appendicitis patients. PBMC responses of 23 patients of the cohort and 23 healthy controls were characterized more than 8 months post-surgery. Serum cytokine levels were measured in 23 patients at the time of appendicitis and after one month. CRP, WBC and percentage of neutrophils were analyzed in the total cohort of 325 patients. No differences in PBMC responses were found between patients and controls. Stronger IL-10 responses were found following complicated appendicitis. A trend towards lower IL-8 responses was shown following gangrenous appendicitis. Serum IL-10 and IL-6 were significantly elevated at presentation, and IL-6, IL-8 and TNF-α levels were higher in complicated appendicitis. Routine biomarkers could predict severity of appendicitis with high specificities, but low sensitivities. Cytokine responses in patients following acute appendicitis did not differ from healthy controls. Higher serum cytokine levels were found in acute complicated and gangrenous cases. Further research into discriminative biomarkers is warranted.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
In recent years, the incidence of Pneumocystis jirovecii pneumonia (PJP) has increased in immunocompromised patients without human immunodeficiency virus (HIV) infection. Chemoprophylaxis ...with trimethoprim‐sulfamethoxazole (TMP‐SMX) is highly effective in preventing PJP in both HIV‐positive and ‐seronegative patients. In HIV‐positive patients, the risk of PJP is strongly correlated with decreased CD4 cell count. The role of CD4 cell count in the pathogenesis of PJP in non‐HIV immunocompromised patients is less well studied. For most immunosuppressive conditions, no clear guidelines indicate whether to start TMP‐SMX.
Method
We conducted a systematic literature review with the aim to provide a comprehensive overview on the role of CD4 cell counts in managing the risk of PJP in HIV‐seronegative patients.
Results
Of the 63 individual studies retrieved, 14 studies report on CD4 cell counts in a variety of immunosuppressive conditions. CD4 cell count were <200/μL in 73.1% of the patients.
Conclusion
CD4 cell count <200/μL is a sensitive biomarker to identify non‐HIV immunocompromised patients who are at risk for PJP. Measuring CD4 cell counts could help clinicians identify patients who may benefit from TMP‐SMX prophylaxis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
7.
Interleukin-1 Blockade: An Update on Emerging Indications Mistry, Anoop; Savic, Sinisa; van der Hilst, Jeroen C H
BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy,
06/2017, Volume:
31, Issue:
3
Journal Article
Peer reviewed
Open access
Interleukin (IL)-1 is a pro-inflammatory cytokine that induces local and systemic inflammation aimed to eliminate microorganisms and tissue damage. However, an increasing number of clinical ...conditions have been identified in which IL-1 production is considered inappropriate and IL-1 is part of the disease etiology. In autoinflammatory diseases, gout, Schnitzler's syndrome, and adult-onset Still's disease, high levels of inappropriate IL-1 production have been shown to be a key process in the etiology of the disease. In these conditions, blocking IL-1 has proven very effective in clinical studies. In other diseases, IL-1 has shown to be present in disease process but is not the central driving force of inflammation. In these conditions, including type 1 and 2 diabetes mellitus, acute coronary syndrome, amyotrophic lateral sclerosis, and several neoplastic diseases, the benefits of IL-1 blockade are minimal or absent.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Five quality indicators of empirical antibiotic therapy for sepsis were tested•Full local guideline adherence was 46%; adherence to antibiotic choice alone was 68%•The acceptance rate for ...microbiological advice within the first 3 days was 87%•De-escalation was the most frequent recommendation by multidisciplinary consultants•Full adherence to guidelines was associated with lower mortality and shorter length of stay
To perform an audit of empirical antibiotic therapy (EAT) of sepsis at the emergency department and to analyse the impact of an antimicrobial stewardship (AMS) programme on process and patient outcomes.
A prospective, single-centre cohort study including patients with sequential organ failure assessment (SOFA) score ≥2 from whom blood cultures were taken was conducted between February 2019 and April 2020. EAT was assessed using eight applicable inpatient quality indicators (IQIs) for responsible antibiotic use. Patient outcomes were hospital length-of-stay (LOS), ICU admission, ICU LOS, and in-hospital mortality.
The audit included 900 sepsis episodes in 803 patients. Full guideline adherence regarding choice and dosing was 45.9%; adherence regarding choice alone was 68.1%. EAT was active against all likely pathogens in 665/787 (84.5%) episodes. In the guideline non-adherent group, choice of EAT was inappropriate in 122/251 (48.6%) episodes. Changes within 3 days occurred in 335/900 (37.2%) episodes. Treating physicians changed administration route more often, whereas microbiological/infectious disease (ID)/AMS consultant advice resulted in de-escalation and discontinuation (P = 0.000). Guideline-adherent choice was associated with significantly shorter LOS (6 (4-11) vs. 8 (5-15) days). Full adherence was associated with significantly lower mortality (23 (6.4%) vs. 48 (11.3%)) and shorter LOS (6 (4-10) vs. 8 (5-14) days).
Five global quality indicators of EAT were measurable in routine clinical practice. Full adherence to guidelines was only moderate. Adherence to guidelines was associated with better patient outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Belgium was among the first countries in Europe with confirmed coronavirus disease 2019 (COVID-19) cases. Since the first diagnosis on February 3rd, the epidemic has quickly evolved, with Belgium at ...the crossroads of Europe, being one of the hardest hit countries. Although risk factors for severe disease in COVID-19 patients have been described in Chinese and United States (US) cohorts, good quality studies reporting on clinical characteristics, risk factors and outcome of European COVID-19 patients are still scarce.
This study describes the clinical characteristics, complications and outcomes of 319 hospitalized COVID-19 patients, admitted to a tertiary care center at the start of the pandemic in Belgium, and aims to identify the main risk factors for in-hospital mortality in a European context using univariate and multivariate logistic regression analysis.
Most patients were male (60%), the median age was 74 (IQR 61-83) and 20% of patients were admitted to the intensive care unit, of whom 63% needed invasive mechanical ventilation. The overall case fatality rate was 25%. The best predictors of in-hospital mortality in multivariate analysis were older age, and renal insufficiency, higher lactate dehydrogenase and thrombocytopenia. Patients admitted early in the epidemic had a higher mortality compared to patients admitted later in the epidemic. In univariate analysis, patients with obesity did have an overall increased risk of death, while overweight on the other hand showed a trend towards lower mortality.
Most patients hospitalized with COVID-19 during the first weeks of the epidemic in Belgium were admitted with severe disease and the overall case fatality rate was high. The identified risk factors for mortality are not easily amenable at short term, underscoring the lasting need of effective therapeutic and preventative measures.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Campylobacter fetus (C. fetus) is a rare condition and mostly seen in elderly or immunocompromised patients. We present the first case of C. fetus spondylodiscitis in a virologically suppressed HIV ...seropositive patient with low back pain. MRI was performed and showed spondylodiscitis of the L4–L5 region. Empirical antibiotic therapy with flucloxacillin was started after blood cultures were drawn and an image-guided disc biopsy was performed. Blood cultures remained negative. The anaerobic culture of the puncture biopsy of the disc revealed presence of C. fetus after which the antibiotic treatment was switched to ceftriaxone. Guided by the susceptibility results, the therapy was switched to ciprofloxacin orally for 6 weeks after which the patient made full clinical, biochemical and radiographic recovery. Since no other immune-deficient conditions were noted, it is important to highlight that patients with HIV infection with restored CD4 counts and complete virological suppression can still be susceptible for infections caused by rare pathogens. Low back pain should raise suspicion for these conditions and should be examined properly.
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