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Background CD163 and calprotectin have been proposed as biomarkers of active renal vasculitis. This study aimed to determine whether the combination of serum/urine calprotectin (s/uCalprotectin) and urinary soluble CD163 (suCD163) increases their individual performance as activity biomarkers. Methods We included 138 patients diagnosed with ANCA vasculitis (n = 52 diagnostic phase, n = 86 remission). The study population was divided into the inception (n = 101) and the validation cohorts (n = 37). We determined the s/uCalprotectin and suCD163 concentration using enzyme-linked immunoassay at the diagnostic or at the remission phase. Receiver operating characteristic (ROC) curves were conducted to assess the biomarkers’ classificatory values. We elaborated a combinatorial biomarker model in the inception cohort. The ideal cutoffs were used in the validation cohort to confirm the model's accuracy in the distinction between active disease and remission. We added the classical ANCA vasculitis activity biomarkers to the model to increase the classificatory performance. Results The concentrations of sCalprotectin and suCD163 were higher in the diagnostic compared with the remission phase (P = .013 and P Conclusions In patients with ANCA vasculitis, a predictive model combining sCalprotectin, suCD163 and haematuria could be useful in detecting active kidney disease.

BACKGROUND AND PURPOSE Glutamic acid decarboxylase antibodies (GAD-Ab) are sometimes associated with chronic drug-resistant focal epilepsy. Clinically, it may manifest as mesial temporal lobe epilepsy (mTLE), with GAD-Ab patients difficult to distinguish. Therefore, the aim of this study is to compare brain metabolism of patients with mTLE and high serum titers of GAD-Ab (>2000 UI/ml) to those with mTLE and hippocampal sclerosis (HS) and confirmed GAD-ab negativity. METHODS Images from PET studies were normalized to an SPM 12 template. Voxel to voxel comparisons were made using a two-sample one-tailed t-test. RESULTS In both patients with GAD-Ab and controls (mTLE-HS), hypometabolism in mesial temporal lobe areas was observed. When comparing the two groups, GAD-Ab patients had statistically significant reduced metabolism in both insulae and medial inferior frontal-hypothalamus area (p < 0.001). CONCLUSIONS Hypometabolism in mesial temporal lobe areas together with hypometabolism in insulae and medial inferior frontal-hypothalamus may be characteristic of patients with epilepsy and GAD-ab. This PET pattern could be a useful diagnostic tool to identify GAD-Ab patients.

Objective To follow prospectively a group of patients with seizures or epilepsy and suggestive clinical features of autoimmune aetiology and find out how many are finally diagnosed with acute symptomatic seizures (ASS) secondary to autoimmune encephalitis or autoimmune-related epilepsy, and how many develop epilepsy. Methods Consecutive patients meeting the inclusion criteria from 2010 to 2018 were identified. Patients were classified as confirmed, probable autoimmune, non-autoimmune, or unknown. Results One-hundred and nine patients were included, 64 (48.7 %) women, mean age 55.2 years (SD 17.9). ASS were reported by 61 patients (56 %), while 48 presented epilepsy (44 %). During follow-up 18 patients died (16.5 %). Final diagnosis was autoimmune-relatedepilepsy (confirmed + probable) in 22 cases and ASS secondary to autoimmune encephalitis (confirmed or probable) in 27, non-autoimmune aetiologies or other diagnosis in 49 (44 %), and unknown aetiology in 11 (10.2 %). Neuronal antibodies (ab) were found in 27 patients (24.7 %). T-lymphocyte infiltration in temporal lobes was observed in 2/8 patients (20 %). Neuronal ab were more frequent in the autoimmune groups: 17 patients (29.8 %) vs 1(2.3 %), p:0.001, and they suffered more autoimmune diseases: 37 (75.5 %) vs 12 (24.48 %), p:0.0001, and 34 (69 %) vs 22 (44.9 %) p:0.027, respectively. All patients with GAD ab 17/17 (100 %) evolved to chronic disease. Four patients (29 %) with ASS secondary to autoimmune encephalitis developed epilepsy. Significance ASS secondary to autoimmune encephalitis or autoimmune-related epilepsy will be diagnosed in nearly half of patients who have been suspected of it. The only diagnostic clue is neuronal ab. Patients who have suffered ASS secondary to autoimmune encephalitis may develop epilepsy over time.

We aimed to determine the role of serum cytokine expression in invasive aspergillosis (IA) diagnosis and outcome prediction in hematologic patients. In this multicenter study, serum cytokines (IL6, IL10, INF-gamma, IL12, IL4, TNF-alpha, IL17, and IL23) were prospectively recruited from all consecutive patients with hematologic malignances at IA diagnosis and compared to control patients matched by center, age, baseline disease, and therapeutic regimen. We included 36 patients with IA and 36 controls. Serum levels of IL6 and IL10 cytokines on day 0 were significantly increased in patients with IA when compared to controls (P = 0.001 and P = 0.025, respectively), even in those who were neutropenic. No differences were observed for the other cytokines. IL6 and IL10 predicted IA with an area under the ROC curve of 0.74 (95% CI 0.62–0.86) and 0.64 (95% CI 0.51–0.77), respectively. The best cutoff point in predicting IA was 20.85 pg/ml for IL6 (sensitivity 72.2%; specificity 77.8%; PPV 76.5% and NPV 73.7%), and 0.045 pg/ml for IL10 (sensitivity 62.9%; specificity 63.9%; PPV 62.9% and NPV 63.9%). IL6 levels were associated with increased mortality, with the best cutoff value being 65.59 pg/ml in mortality prediction. In conclusion, in addition to current tests in place, IL6 and IL10 levels—as measured in plasma—may help clinicians diagnose IA. High levels of IL6 at IA diagnosis are related with worse outcomes. Lay summary We evaluated the role of serum cytokine expression in invasive aspergillosis (IA) diagnosis and outcome. Serum levels of IL6 and IL10 are increased in patients with IA compared to controls, and IL6 levels are associated with mortality.

Therapeutic drug monitoring of infliximab can guide clinical decisions in patients with loss of response and in those who can benefit from a de-intensification. The aim of this study was to determine the impact of therapeutic drug monitoring combined with Bayesian forecasting methodology on clinical response in a real-world dataset of patients suffering from inflammatory bowel disease.We performed a single-centre prospective study with one-group pre-test/post-test design in 108 adult inflammatory bowel disease patients treated with model-based dosing of infliximab maintenance treatment. We recorded clinical activity scores (Harvey-Bradshaw index and partial Mayo) and inflammatory biomarkers per patient.The initial infliximab regimen was maintained in 49 (45.4%) patients and was adjusted in 59 (54.6%) patients (34 treatment intensifications, 9 de-intensifications and 16 treatment discontinuations or therapy replacements). The median time from intervention to index measurement was 126 (103-160) days. The overall proportion of patients in clinical remission increased from 65.7% to 80.4% (P.0001) and the median infliximab trough concentrations increased from 3.21 (0.99-5.45) to 5.13 mg/L (3.57-6.53) (P.0001). In the intensified group, the remission rate increased from 35.3% to 61.8% (P = .001) and the percentage of patients in clinical remission or with mild symptoms increased from 76.5% to 94.1%. In the de-intensification cohort, no patients experienced an increase in the Harvey-Bradshaw index or partial Mayo scores, and all patients maintained an infliximab trough concentration of5 mg/L.In our cohort of inflammatory bowel disease patients, Bayes-based optimized dosing improved the short-term efficacy of infliximab treatment.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4%80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals70 years, 2.3% between 70 and 80 years, and 6.3%80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.

Anti-mitochondrial antibodies (AMA), directed against the E2 subunits of the 2-oxo acid dehydrogenase complexes, are markers of Primary Biliary Cholangitis (PBC), a chronic autoimmune liver disease. However, the clinical significance of subunits-specific AMA type PDC-E2 -E2 subunit of the pyruvate dehydrogenase complex-, BCOADC-E2 -E2 subunit of the branched-chain 2-oxo acid dehydrogenase complex-, OGDC-E2 -E2 subunit of the 2-oxo-glutarate dehydrogenase complex- and nPDC -native pyruvate dehydrogenase complex (M2-AMA) . Is not well known, and not all AMA specificities are associated with PBC. The aim of the study was to show the usefulness of the number and combination of subunits-specific AMA positive for the diagnosis of PBC. We detected AMA by indirect immunofluorescence (IIF-AMA) and M2-AMA by dot-blot. We studied the relationship of AMA with some clinical and laboratory variables in 307 patients (37% PBC) with positive dot-blot for M2-AMA. In PBC patients, we detected different E2 subunits of the 2-oxo acid dehydrogenase complexes antibodies (M2-AMA): 82.9% were specific for nPDC, 64.5% for PDC-E2, 44.4% for BCOADC-E2, and 9.6% for OGDC-E2. IIF and dot-blot tests achieved a Area Under the Receiver Operating Characteristic Curve (ROC AUC) of 0.674 (1: 320 cut-off titer, Sensibility (Se) 64.7%, Specificity (Sp) 63.4%) and 0.663 (three specificities M2-AMA, Se 43%, Sp 81.2%), respectively. The detection of different E2 subunits of the 2-oxo acid dehydrogenase complexes antibodies (M2-AMA) by dot-blot showed different ROC AUC: anti-PDC-E2 showed an AUC of 0.610, a Se of 43.7%, and a Sp of 76.4%. Finally, the combined detection of nPDC/BCOADC-E2/PDC-E2 reached an AUC of 0.6095, a Se of 59.6%, and a Sp of 70.2%.The identification of two M2-AMA specificities through dot-blot increased PBC odds ratio (OR) by 2.05 (p:0.031), as compared to the identification of one specificity. Moreover, the identification of three and four specificities increased OR by 4.63 (p:0.000) and by 21.53 (p:0.006), respectively. nPDC/OGDC-E2/PDC-E2 and nPDC/OGDC-E2/BCOADC-E2/PDC-E2 combinations increased PBC OR by 10.04 (p:0.034), as compared to any other combination. 1:320 and 1:640 IIF-AMA increased PBC OR by 4.93 (p:0.009) and 7.67 (p:0.001), respectively, as compared to IIF-AMA titers equal to or less than 1:160. M2-AMA dot-blot was less sensitive but more specific than IIF-AMA, with similar predictive capacity for PBC. Increased numbers of M2-AMA specificities clearly increased the risk of PBC. Some combinations were strongly related to PBC (nPDC/BCOADC-E2/PDC-E2), but others were not (one single M2-AMA, and nPDC plus PDC-E2). M2-AMA dot-blot was less sensitive but more specific than IIF-AMA, with similar predictive capacity for PBC. Increased numbers of M2-AMA specificities clearly increased the risk of PBC, being some combinations, such as nPDC/BCOADC-E2/PDC-E2, more related to PBC than others. Finally, the determination of the number of M2-AMA specificities was more useful than the particular subunit target for PBC diagnosis. In conclusion, the study of the number of M2-AMA specificities by dot-blot should definitely be considered for PBC diagnosis.

Background It is important to predict which patients infected by SARS-CoV-2 are at higher risk of life-threatening COVID-19. Several studies suggest that neutralizing auto-antibodies (auto-Abs) against type I interferons (IFNs) are predictive of critical COVID-19 pneumonia. Objectives We aimed to test for auto-Abs to type I IFN and describe the main characteristics of COVID-19 patients admitted to intensive care depending on whether or not these auto-Abs are present. Methods Retrospective analysis of all COVID-19 patients admitted to an intensive care unit (ICU) in whom samples were available, from March 2020 to March 2021, in Barcelona, Spain. Results A total of 275 (70.5%) out of 390 patients admitted to ICU were tested for type I IFNs auto-antibodies (α2 and/or ω) by ELISA, being positive in 49 (17.8%) of them. Blocking activity of plasma diluted 1/10 for high concentrations (10 ng/mL) of IFNs was proven in 26 (9.5%) patients. Almost all the patients with neutralizing auto-Abs were men (92.3%). ICU patients with positive results for neutralizing IFNs auto-Abs did not show relevant differences in demographic, comorbidities, clinical features, and mortality, when compared with those with negative results. Nevertheless, some laboratory tests (leukocytosis, neutrophilia, thrombocytosis) related with COVID-19 severity, as well as acute kidney injury (17 [65.4%] vs. 100 [40.2%]; p = 0.013) were significantly higher in patients with auto-Abs. Conclusion Auto-Abs neutralizing high concentrations of type I IFNs were found in 9.5% of patients admitted to the ICU for COVID-19 pneumonia in a hospital in Barcelona. These auto-Abs should be tested early upon diagnosis of SARS-CoV-2 infection, as they account for a significant proportion of life-threatening cases. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-021-01136-x.

Background Infliximab (IFX) trough levels vary markedly between patients with inflammatory bowel disease (IBD), which is important for clinical response. The aim of this study was to evaluate the performance of previously developed population pharmacokinetic models in patients with IBD for dose individualization for Crohn disease (CD) and ulcerative colitis in our clinical setting. Methods The authors collected 370 trough levels prospectively from 100 adult patients with IBD who were undergoing IFX treatment between July 2013 and August 2016. The external evaluation included prediction- and simulation-based diagnostics [prediction-corrected visual predictive check, prediction- and variability-corrected visual predictive check, and normalized prediction distribution error tests]. Results In prediction-based diagnostics, the authors observed a nonsignificant overall mean relative bias of -6.87% and an acceptable imprecision of 8.45%. Approximately 100% of the prediction error was within ±30%, indicating satisfactory predictability. Simulation-based diagnostics indicated model misspecification; thus, the model may not be appropriate for simulation-based applications. Conclusions While simulation-based diagnostics provided unsatisfactory results, the prediction-based diagnostics demonstrate that the population pharmacokinetic model developed by Fasanmade et al for CD can be used to predict and design individualized IFX dose regimens that meet the individual needs of patients with CD and ulcerative colitis.

The complement system is an important effector arm of innate immunity and plays a crucial role in the defense against common pathogens. But effective defense and maintenance of homeostasis requires a careful balance between complement activation and regulation. Factor I (FI) is one of the most important regulators of the complement system. Complete FI deficiency is a rare autosomal recessive disorder typically resulting in severe, recurrent infection by encapsulated bacteria. In the present study, we describe two patients from unrelated families with complete FI deficiency diagnosed at very different ages: Patient 1 is a 60-year-old man who had experienced several severe infections (pneumonia, meningitis, sepsis) since childhood, one of which caused significant and permanent neurologic sequelae. In contrast, patient 2 was diagnosed at the age of 4 years after a single infectious episode (otitis media) and through detection of a flat beta2 peak on serum protein electrophoresis. This early diagnosis of FI deficiency enabled prompt implementation of a therapeutic intervention consisting of vaccination with encapsulated bacteria and prophylactic antibiotics. The two patients had novel homozygous mutations in the CFI gene (p.Gly162Asp and p.His380Arg) that disrupted protein function. Interestingly, p.His380Arg is the first mutation described affecting a residue of the highly conserved FI catalytic triad (His380, Asp429, and Ser525). This study illustrates the importance of early versus late diagnosis of FI deficiency and, in general, highlights the clinical relevance of prompt detection of complement system deficiencies.

Background and aims Treating patients based on a treat-to-trough approach has been shown to be a cost-effective strategy for inflammatory bowel disease (IBD) patients who have become unresponsive to infliximab (IFX). However, the documented evidence for this is limited, and some controversy remains regarding the use of routine proactive therapeutic drug monitoring (TDM). To support routine TDM of IFX and regimen optimization in IBD patients, more in-depth knowledge of the covariates that affect the pharmacokinetic (PK) variability of IFX is needed. The aim of this study was to identify the characteristics of the patient, disease, and treatments that influence IFX PK and exposure in our cohort of IBD patients using a repeated-measures design. Methods We performed a prospective observational study of adult IBD patients who received IFX between July 2013 and March 2017. We obtained repeated IFX trough concentration (Cmin) measurements and implemented a previously described population pharmacokinetic model to estimate individual clearance (CL). From the individual primary parameters, the area under the curve (AUC), half-life (t1/2), and central elimination rate constant (K10) were estimated. We performed a repeated-measures analysis to evaluate whether patient characteristics, disease status, concomitant immunosuppressive therapy, and immunogenicity are associated with IFX Cmin and PK parameters. Results We collected 429 Cmin measurements from 112 patients. The median of the Cmin values was 3.62 mg/L (1.47-6.02). Antibodies to IFX (ATI) were detected in 14 patients. The predicted median AUC was 28,421 mg/h/L (22,336-36,903). The median individual predicted CL, K10, and t1/2 values were 4.77 mL/kg/day (3.88-5.90), 0.09 days (0.08-0.12), and 12.22 days (9.49-14.87), respectively. IFX Cmin, AUC, CL, and K10 were significantly influenced by ATI and serum albumin concentrations. Moreover, body weight was significantly associated with AUC, CL, and K10. Patients receiving concurrent immunosuppressive therapy had higher Cmin and AUC values and lower CL and K10 values than those treated with IFX monotherapy. We also observed high intrapatient variability in Cmin values during the study period. Conclusions In this repeated-measures study in a population of IBD patients, we observed significant associations between ATI, serum albumin concentration, concomitant immunosuppressive therapy, body weight and gender, and IFX Cmin, and CL. The high PK variability observed in this study supports the need for proactive TDM to optimize the use of IFX as early as possible in IBD patients.

Background: Antibodies to glutamic acid decarboxylase (GAD ab) have been found in patients with limbic encephalitis (LE) and chronic pharmacoresistant focal epilepsy (FE). The objectives of the study were to: (1) analyze the clinical and neuroimaging course of patients with FE+GAD ab, (2) compare these characteristics with a control group, and (3) describe the most affected cerebral areas with structural and functional imaging. Methods: Patients with FE + high titers of GAD ab and a follow-up of at least 5 years were selected. Titers of serum GAD ab exceeding 2,000 UI/ml were considered high. Evolutive clinical and radiological characteristics were studied in comparison to two different control groups: patients with bilateral or with unilateral mesial temporal sclerosis (BMTS or UMTS) of a non-autoimmune origin. Results: A group of 13 patients and 17 controls were included (8 BMTS, 9 UMTS). The most frequent focal aware seizures (FAS) reported by patients were psychic (5/13: 33%). Somatosensorial, motor, and visual FAS (4/13:32%) (p: 0.045), musicogenic reflex seizures (MRS), and a previous history of cardiac syncope were reported only patients (2/13:16% each) (p: NS). Comparing EEG characteristics between patients and controls, a more widespread distribution of interictal epileptiform discharges (IED) was observed in FE+ GAD ab patients than in controls (p:0.01). Rhythmic delta activity was observed in all controls in anterior temporal lobes while in patients this was less frequent (p: 0.001). No IED, even in 24 h cVEEG, was seen in 6 patients (46%).First MRI was normal in 4/5 (75%) patients. During the follow-up mesial temporal lobe (MTsL) sclerosis was observed in 5/8 (62%) of patients. All patients had abnormal FDG-PET study. MTL hypometabolism was observed in 10/11 (91%) patients, being bilateral in 7/11 (63%). In controls, this was observed in 16/17 (94%), and it was bilateral in 8/17 (47%) (p: NS). Insular hypometabolism was observed in 5/11 (45%) patients (P:0.002). Conclusions: Clinical, EEG, and FDG-PET findings in FE+GAD ab suggest a widespread disease not restricted to the temporal lobe. Progressive MTL sclerosis may be observed during follow-up. In comparison to what is found in patients with non-autoimmune MTL epilepsy, insular hypometabolism is observed only in patients with GAD ab, so it may be an important diagnostic clue.

The "rods and rings" (RR) antinuclear antibody (ANA) pattern is believed to be restricted to hepatitis C virus (HCV) infection and related to the treatment. This is a 4-year retrospective study of all patients with RR pattern from the 20,000 serum samples received at the Hospital Universitari de Bellvitge for ANA testing. Two control groups with HCV patients without RR pattern: ANA-positive (n = 74) and ANA negative (n = 75) were included. Eighty-seven patients had samples with the RR pattern. Seventy-three were infected with HCV (prevalence of 15% in the HCV population). The RR pattern could not be related to ribavirin treatment, clinical status, biochemistry data, hepatic fibrosis, IL28B genotype, HCV genotype or the presence of autoantibodies related with autoimmune hepatitis. As 14 cases presented other diseases, mainly of autoimmune origin, the presence of RR antibodies may also be explained by alterations in immune regulation caused by autoimmunity or HCV in a particular genetic background.

The severity of Pseudomonas aeruginosa (PA) infection may be determined by the interaction with the host immune system. We designed a prospective study to assess the relationship between the inflammatory response and the clinical presentation and outcome of PA infection. We also investigated whether there are differences in the inflammatory response depending on the resistance profile of PA. Interleukin-6 (IL-6), IL-10, procalcitonin (PCT), and C-reactive protein (CRP) were measured. Sixty-nine infection episodes were recorded; 40 caused by non-multidrug-resistant (non-MDR) strains [29 (73%) respiratory; 8 (20%) bacteremia], 12 by MDR non-extensively drug-resistant (MDR-non-XDR) [9 (75%) respiratory; 3 (25%) bacteremia], and 17 by XDR strains [9 (53%) respiratory; 7 (41%) bacteremia]. All inflammatory parameters were significantly higher in patients who developed acute organ dysfunction and bacteremia. PCT levels were higher in patients with early mortality [p = 0.050]. Inflammatory biomarkers were higher in patients with XDR than in those with non-MDR PA [IL-6 430 (67-951) vs. 77 (34-216), p = 0.02; IL-10 3.3 (1.5-16.3) vs. 1.3 (0-3.9), p = 0.02; and PCT 1.1 (0.6-5.2) vs. 0.3 (0.1-1.0), p = 0.008]. The intensity of inflammatory response was associated with the severity of PA infection, particularly if bacteremia occurred. Only PCT was documented useful to predict the outcome. XDR infections presented a higher inflammatory response; related in part to the larger number of bloodstream infections in this group.

Objectives It has been suggested that statins have an effect on the modulation of the cytokine cascade and on the outcome of patients with community-acquired pneumonia (CAP). The aim of this prospective, randomised, double-blind, placebo-controlled trial was to determine whether statin therapy given to hospitalised patients with CAP improves clinical outcomes and reduces the concentration of inflammatory cytokines. Setting A tertiary teaching hospital in Barcelona, Spain. Participants Thirty-four patients were randomly assigned and included in an intention-to-treat analysis (19 to the simvastatin group and 15 to the placebo group). Intervention Patients were randomly assigned to receive 20 mg of simvastatin or placebo administered in the first 24 h of hospital admission and once daily thereafter for 4 days. Outcome Primary end point was the time from hospital admission to clinical stability. The secondary end points were serum concentrations of inflammatory cytokines and partial pressure of arterial oxygen/fractional inspired oxygen (PaO2/FiO2) at 48 h after treatment administration. Results The trial was stopped because enrolment was much slower than originally anticipated. The baseline characteristics of the patients and cytokine concentrations at the time of enrolment were similar in the two groups. No significant differences in the time from hospital admission to clinical stability were found between study groups (median 3 days, IQR 2–5 vs 3 days, IQR 2–5; p=0.47). No significant differences in PaO2/FiO2 (p=0.37), C reactive protein (p=0.23), tumour necrosis factor-α (p=0.58), interleukin 6 (IL-6; p=0.64), and IL-10 (p=0.61) levels at 48 h of hospitalisation were found between simvastatin and placebo groups. Similarly, transaminase and total creatine kinase levels were similar between study groups at 48 h of hospitalisation (p=0.19, 0.08 and 0.53, respectively). Conclusions Our results suggest that the use of simvastatin, 20 mg once daily for 4 days, since hospital admission did not reduce the time to clinical stability and the levels of inflammatory cytokines in hospitalised patients with CAP. Trial registration number ISRCTN91327214.