Relevance of [18F]FDG-PET/CT in the detection of colon pathology, in patients studied by bacteriemia or infectious endocarditis caused by enteropathogenic microorganisms.

PURPOSE: Association between S. gallolyticus infective endocarditis (IE) and malignant lesions of the gastrointestinal tract is well described. We hypothesize that other enteropathogenic microorganisms, such as S. viridans and E. faecalis are also related with colorectal pathology. Our aim is to determine the frequency of focal colorectal FDG deposits, suggestive of tumoral lesions and their correlation with colorectal pathology, in patients with infection caused by different commensal microorganisms of the gastrointestinal tract. METHODS: We retrospectively examined 61 patients diagnosed with bacteremia (BSI) and IE (possible or definite) according to Duke's criteria, caused by enteropathogenic microorganisms, who underwent a full-body [18F]FDG-PET/CT in our institution. We looked for colorrectal FDG deposits and morphological lesions. All IE patients underwent a complete colonoscopy and the histological results were classified into four groups: malignant lesion, premalignant lesion, benign lesion and no lesion. We evaluated the correlation between the findings of the [18F]FDG-PET/CT with the histopathological diagnosis and the involved microorganism. RESULTS: PET/CT detected 20 colorectal FDG deposits (32.79%-OR: 47.28), 2 within bacteriemic patients (16.7%) confirmed as malignant and premalignant lesions and 18 in IE group (36.6%), 17 of them corresponding to colorrectal pathology: 11 malignant, 5 premalignant and 1 benign lesions. In the IE subgroup, the colonoscopy detected colorectal lesions in 51.02% of the patients: 11malignant, 8premalignant and 6benign. We found a higher incidence of colorectal FDG deposits in Streptococcus spp. subgroup. Regarding the anatomopathological colonic findings there was a predominance of patients affected by S. viridans, followed by E. faecalis and S. gallolyticus. CONCLUSION: Patients studied by PET/CT for systemic infection, especially IE, caused by S. viridans or E. faecalis, in addition to S. gallolyticus, show a greater probability of presenting incidental colorectal FDG deposits, mostly corresponding to malignant or pre-malignant lesions. Therefore, it is necessary to carry out an exhaustive search of possible colorectal foci in these exams.

Abiotrophia spp. and Granulicatella spp. Infective Endocarditis: A Contemporary Perspective.

BACKGROUND: Abiotrophia spp. and Granulicatella spp. are Gram-positive cocci, formerly known as nutritionally variant or deficient Streptococcus. Their role as causative agents of infective endocarditis (IE) is numerically uncertain, as well as diagnostic and clinical management of this infection. The aim of our study is to describe the clinical, microbiological, therapeutic, and prognosis of patients with IE caused by these microorganisms in a large microbiology department. METHODS: Retrospective analysis of all the patients with Abiotrophia spp. and Granulicatella spp. IE registered in our centre in the period 2004-2021. RESULTS: Of the 822 IE in the study period, 10 (1.2%) were caused by Abiotrophia spp. (7) or Granulicatella spp. (3). The species involved were A.defectiva (7), G.adiacens (2) and G.elegans (1). Eight patients were male, their mean age was 46 years and four were younger than 21 years. The most frequent comorbidities were congenital heart disease (4; 40%) and the presence of intracardiac prosthetic material (5; 50%). IE occurred on 5 native valves and 5 prosthetic valve or material. Blood cultures were positive in 8/10 patients, within a mean incubation period of 18.07 hours. In the other two patients, a positive 16SPCR from valve or prosthetic material provided the diagnosis. Surgery for IE was performed in seven patients (70%) and in all cases positive 16S rRNA PCR and sequencing from valve or prosthetic material was demonstrated. Valves and/or prosthetic removed material cultures were positive in four patients. Nine patients received ceftriaxone (4 in monotherapy and 5 in combination with other antibiotics). The mean length of treatment was 6 weeks and IE-associated mortality was 20% at one year follow-up. CONCLUSIONS: Abiotrophia spp. or Granulicatella spp. IE were infrequent but not exceptional in our environment and particularly affected patients with congenital heart disease or prosthetic material. Blood cultures and molecular methods allowed the diagnosis. Most of them required surgery and the associated mortality, in spite of a mean age of 46 years, was high.

Comorbidity and Prognosis in Octogenarians with Infective Endocarditis.

Background. Infective endocarditis (IE) in older patients is associated with a high morbidity, mortality, and functional impairment. The purpose of this study was to describe the current profile of IE in octogenarians and to analyze the prognostic impact of baseline comorbidities in this population. Methods. Patients ≥ 80 years and definite IE from the Spanish IE Prospective Database were included. The effect of Charlson Comorbidity Index (CCI) on in-hospital and 12-month mortality was analyzed. Results. From 726 patients, 357 (49%) had CCI ≥ 3 and 369 (51%) CCI < 3. A total of 265 patients (36.6%) died during hospital admission and 338 (45.5%) during 1-year follow-up. CCI ≥ 3 was an independent predictor of in-hospital and 1-year mortality (odds ratio 1.46, 95% confidence interval 1.07−1.99, p = 0.017; hazard ratio 1.34, 95% confidence interval 1.08−1.66, p = 0.007, respectively). Surgical management was less common in patients with high comorbidity (CCI ≥ 3 68 [19.0%] vs. CCI < 3 112 ((30.4%) patients, p < 0.01). From 443 patients with surgical indication, surgery was only performed in 176 (39.7%). Patients with surgical indication treated conservatively had higher mortality than those treated with surgery (in-hospital mortality: 147 (55.1%) vs. 55 (31.3%), p < 0.001), (1-year mortality: 172 (64.4%) vs. 68 [38.6%], p < 0.001). Conclusion. About half of octogenarians with IE had high comorbidity with CCI ≥ 3. CCI ≥ 3 was a strong independent predictor of in-hospital and 1-year mortality. Our data suggest that the underperformance of cardiac surgery in this group of patients might have a role in their poor prognosis.

Clinical characterization and outcomes of 85 patients with neurosarcoidosis.

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q < 0.001) and salivary gland (15% vs 4%, q = 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p = 0.02) in comparison with patients without NS. Neurosarcoidosis was identified in 5.5% of patients. CNS involvement prevails significantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly differentiated, and can be helpful not only in the early identification of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis.

Performance of the 2019 ACR/EULAR classification criteria for IgG4-related disease and clinical phenotypes in a Spanish multicentre registry (REERIGG4).

OBJECTIVES: Several IgG4-related disease (IgG4-RD) phenotypes have been proposed and the first set of classification criteria have been recently created. Our objectives were to assess the phenotype distribution and the performance of the classification criteria in Spanish patients as genetic and geographical differences may exist. METHODS: We performed a cross-sectional multicentre study (Registro Español de Enfermedad Relacionada con la IgG4, REERIGG4) with nine participating centres from Spain. Patients were recruited from November 2013 to December 2018. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria (AECC) were used. RESULTS: We included 105 patients; 88% had Caucasian ethnicity. On diagnosis, 86% met the international pathology consensus while 92% met the Japanese comprehensive criteria. The phenotype distribution was head and neck 25%, Mikulicz and systemic (MS) 20%, pancreato-hepato-biliary (PHB) 13%, retroperitoneal and aorta (RA) 26%. Sixteen per cent had an undefined phenotype. Seventy-seven per cent of the cases met the AECC. From the 24 patients not meeting the AECC, 33% met exclusion criteria, and 67% did not get a score ≥20 points. Incomplete pathology reports were associated to failure to meet the AECC. CONCLUSIONS: The PHB phenotype was rare among Spanish IgG4-RD patients. The MS phenotype was less frequent and the RA phenotype was more prevalent than in other, Asian patient series. An undefined phenotype should be considered as some patients do not fall into any of the categories. Three quarters of the cases met the 2019 AECC. Incomplete pathology reports were the leading causes of failure to meet the criteria.

Troponin elevation is very common in patients with infective endocarditis and is associated with a poor outcome.

INTRODUCTION: We sought to study the prevalence of cardiac troponin T (TnT) elevation in patients with infective endocarditis (IE) and its association with in-hospital outcomes. METHODS AND RESULTS: Retrospective single-center study. From 2008 to 2018, 528 patients were diagnosed with IE and 250 (47.3%) had at least a TnT determination during hospital admission, 103 with conventional TnT assay and 147 with high-sensitive assay. Elevated TnT levels were found in 210 patients (84.0%). Compared with patients with normal TnT levels, patients with TnT elevation presented higher in-hospital mortality (5 [12.5%] vs. 77 [36.7%], p < 0.001) and more frequent complications: heart failure (9 [22.5%] vs. 106 [50.5%], p < 0.001), cardiac abscesses (4 [10.0%] vs 58 [27.6%], p = 0.03), conduction disorders (0 vs. 26 [12,4%]; p = 0.04), and involvement of the central nervous system (1 [2.5%] vs. 38 [18.1%];p = 0.02). Patients with elevated TnT had more frequent indication for surgery (24 [60.0%] vs. 179 [85.2%], p < 0.001) and were operated on more frequently (16 [40.0%] vs 123 [58.6%], p = 0.03). TnT elevation was an independent predictor of in-hospital mortality (OR 3.31; 95% CI 1.02-10.72, p = 0.05). Adding TnT data to conventional clinical models improved the predictive capability of in-hospital mortality (R2: 0.407 vs. 0.388, χ2: 85.03 vs. 80.40, p < 0.001), resulting in a net reclassification improvement of 0.29 (95% CI: 0.13-0.46, p < 0.01). CONCLUSIONS: TnT elevation is very common in patients with IE and is associated with increased in-hospital mortality and complications, thus routine monitoring should be recommended.

Randomized clinical trial analyzing maintenance of peripheral venous catheters in an internal medicine unit: Heparin vs. saline.

BACKGROUND: Peripheral venous catheters (PVCs) require adequate maintenance based on heparin or saline locks in order to prevent complications. Heparin has proven effective in central venous catheters, although its use in PVCs remains controversial. Our hypothesis was that saline locks are as effective as heparin locks in preventing problems with PVCs. The objective of the present study was to compare phlebitis and catheter tip colonization rates between PVCs locked with saline and those locked with heparin in patients admitted to an internal medicine department (IMD). METHODS: We performed a 19-month prospective, controlled, open-label, randomized clinical study of patients with at least 1 PVC admitted to the IMD of our hospital. The patients were randomized to receive saline solution (PosiFlush®, group A) or heparin (Fibrilin®, group B) for daily maintenance of the PVC. Clinical and microbiological data were monitored to investigate the frequency of phlebitis, catheter tip colonization, and catheter-related bloodstream infection (C-RBSI), as well as crude mortality, days of hospital stay, and days of antimicrobial treatment. RESULTS: We assessed 339 PVCs (241 patients), of which 192 (56.6%) were locked with saline (group A) and 147 (43.4%) with heparin (group B). The main demographic characteristics of the patients were distributed equally between the 2 study groups. The median (IQR) catheter days was 5 (3-8) for both groups (p = 0.64). The frequency of phlebitis was 17.7% for group A and 13.3% for group B (p = 0.30). The frequency of colonization of PVC tips was 14.6% and 12.2% in groups A and B, respectively (p = 0.63). Only 2 episodes of C-RBSI were detected (1 patient in group A). Saline lock was not an independent factor for phlebitis or catheter colonization. CONCLUSIONS: Our study revealed no statistically significant differences in the frequency of phlebitis and catheter tip colonization between PVCs locked with saline and PVCs locked with heparin. We suggest that PVC can be maintained with saline solution, as it is safer and cheaper than heparin.

Severe, life-threatening phenotype of primary Sjögren's syndrome: clinical characterisation and outcomes in 1580 patients (GEAS-SS Registry).

OBJECTIVES: To analyse the clinical features and outcomes of patients presenting with life-threatening systemic disease in a large cohort of Spanish patients with primary Sjögren's syndrome (SS). METHODS: The GEAS-SS multicentre registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS, and included more than 20 Spanish reference centres with substantial experience in the management of SS patients. By January 2018, the database included 1580 consecutive patients fulfilling the 2002 classification criteria for primary SS. Severe, life-threatening systemic disease was defined as an activity level scored as "high" in at least one ESSDAI domain. RESULTS: Among 1580 patients, 208 (13%) were classified as presenting a severe, potentially life-threatening systemic disease: 193 presented one ESSDAI domain classified as high, 14 presented two high scored domains and only one presented three high activity domains. The ESSDAI domains involved consisted of lymphadenopathy in 78 (37%) cases, CNS in 28 (13%), PNS in 25 (12%), pulmonary in 25 (12%), renal in 21 (10%), cutaneous in 19 (9%), articular in 18 (9%), haematological in 7 (3%) and muscular in 4 (2%). Patients with severe systemic disease were more frequently men (p=0.001) and had a higher frequency of anaemia (p<0.001), lymphopenia (p<0.001), rheumatoid factor (p=0.021), low C3 levels (p=0.015), low C4 levels (p<0.001) and cryoglobulins (p<0.001). From a therapeutic point of view, systemic patients received more frequently glucocorticoids (p<0.001), immunosuppressants (p<0.001), intravenous immunoglobulins (p=0.008) and rituximab (p<0.001). We found an overall mortality rate of 20% in severe systemic patients, a rate that reached to 33% in patients presenting two or more high systemic involvements; these patients had a higher frequency of low C4 levels (p=0.012) and cryoglobulins (p=0.001) in comparison with those with a single severe organ involved. CONCLUSIONS: 13% of patients with primary SS develop a potentially life-threatening systemic disease (mainly lymphoma, but also severe internal organ involvements including nervous system, the lungs and the kidneys). This subset of patients requires intensive therapeutic management with a mortality rate of nearly 20% of cases.

Impact of a training program on adherence to recommendations for care of venous lines in internal medicine departments in Spain.

A high percentage of venous lines (VLs) are placed in non-ICU patients, particularly those treated in the internal medicine department (IMD). We assessed adherence to VL care after a training program aimed at nurses and clinicians attending patients admitted to Spanish IMDs. We performed a multicenter prospective observational point prevalence study in 14 Spanish IMDs in 2013 and 2016. We included all adult patients (> 18 years) admitted to IMDs on the study day and reviewed nursing records for patients with VL in place before and after a 1-year training program during 2015. Answers from an interview with head nurses of the IMDs regarding commonly used practices in the daily management of VLs were also compared. A total of 638 and 693 patients were seen during each period, respectively, and 530 and 598 patients had ≥ 1 VL implanted (83.1 vs. 86.3%). Catheters were considered unnecessary in 12.8 and 15.0% of cases (p = 0.28). Daily recording of the need for catheter use increased from 43.8 to 71.8% (p < 0.001). Furthermore, daily monitoring of the insertion site remained very frequent (94.4 vs. 92.2%; p = 0.16). The date of insertion was recorded in 86.3 and 85.5% of cases (p = 0.73), and no combination of closed connectors with open caps increased from 74.8 to 90.3% (p < 0.001). Overall, head nurses' knowledge improved in 4 out of 14 recommendations assessed (28.6%). A simple and easy program for training on management of VLs in Spanish IMDs was associated with improved quality of care.

Treatment and outcomes in patients with IgG4-related disease using the IgG4 responder index.

BACKGROUND: IgG4-related disease (IgG4-RD) is an autoimmune disease triggering an inflammatory cascade that leads to fibrosis. Outcome measures are limited and treatment options remain underexplored. OBJECTIVES: To assess the variation of the IgG4 responder index (IgG4-RI) in a cohort of IgG4-RD patients and to explore their treatments and outcomes. METHODS: We studied the clinical phenotype, severity of the disease and response to treatment in an ambispective multicenter cohort study including 14 different hospitals in Spain. All patients met the 2012 international consensus on pathology criteria for diagnosis. RESULTS: Sixty-eight patients were included, with a mean age of 53.4 years and predominance of male sex. The most commonly involved tissues were: retroperitoneum (33%), orbital pseudotumor (28%) and maxillary and paranasal sinuses (24%). IgG4-RI values were higher in patients with multiorgan disease and before treatment. After being treated, IgG4-RI values were lower, in accordance with the high rates of treatment response. Most patients received: glucocorticoids (GC), surgery, azathioprine (AZA), mofetil mycophenolate or rituximab. GC alone, GC plus surgery and GC plus AZA were given in the most of the IgG4-RD disease activity episodes. All treatments had high response rates but relapses and flares were common. CONCLUSIONS: IgG4-RI is a promising outcome measure in IgG4-RD, but still in development. Treatment algorithms are ill defined. GC and rituximab are the drugs with more evidence available. Disease modifying anti-rheumatic drugs may have a role in IgG4-RD and warrant more prospective studies.

Characterization and risk estimate of cancer in patients with primary Sjögren syndrome.

BACKGROUND: The purpose of this study is to characterize the risk of cancer in a large cohort of patients with primary Sjögren syndrome (SjS). METHODS: We had analyzed the development of cancer in 1300 consecutive patients fulfilling the 2002 SjS classification criteria. The baseline clinical and immunological characteristics and systemic activity (ESSDAI scores) were assessed at diagnosis as predictors of cancer using Cox proportional hazards regression analysis adjusted for age at diagnosis and gender. The sex-and age-specific standardized incidence ratios (SIR) of cancer were estimated from 2012 Spanish mortality data. RESULTS: After a mean follow-up of 91 months, 127 (9.8%) patients developed 133 cancers. The most frequent type of cancer was B-cell lymphoma (including 27 MALT and 19 non-MALT B-cell lymphomas). Systemic activity at diagnosis of primary SjS correlated with the risk of hematological neoplasia and cryoglobulins with a high risk of either B-cell or non-B-cell lymphoma subtypes. Patients with cytopenias had a high risk of non-MALT B-cell and non-B-cell cancer, while those with low C3 levels had a high risk of MALT lymphomas and those with monoclonal gammopathy and low C4 levels had a high risk of non-MALT lymphomas. The estimated SIR for solid cancer was 1.13 and 11.02 for hematological cancer. SIRs for specific cancers were 36.17 for multiple myeloma and immunoproliferative diseases, 19.41 for Hodgkin lymphoma, 6.04 for other non-Hodgkin lymphomas, 5.17 for thyroid cancer, 4.81 for cancers of the lip and oral cavity, and 2.53 for stomach cancer. CONCLUSIONS: One third of cancers developed by patients with primary SjS are B-cell lymphomas. The prognostic factors identified at SjS diagnosis differed according to the subtype of B-cell lymphoma developed. Primary SjS is also associated with the development of some non-hematological cancers (thyroid, oral cavity, and stomach).

Patterns of drug therapy in newly diagnosed Spanish patients with systemic lupus erythematosus.

OBJECTIVES: This is the first Spanish multicentric inception lupus cohort, formed by SLE patients attending Spanish Internal Medicine Services since January 2009. We aimed to analyse drug therapy during the first year of follow-up according to disease severity. METHODS: 223 patients who had at least one year of follow-up were enrolled upon diagnosis of SLE. Therapy with prednisone, pulse methyl-prednisolone, hydroxychloroquine, immunosuppressives and calcium/vitamin D was analysed. RESULTS: Prednisone was given to 65% patients, at a mean (SD) daily dose of 11 (10) mg/d. 38% patients received average doses >7.5 mg/d during the first year. Patients with nephritis and with a SLEDAI ≥6 were treated with higher doses of prednisone. 81% of patients were treated with hydroxychloroquine, with higher frequency among those with a SLEDAI ≥6 (88% vs. 68%, p<0.001). The use of immunosuppressive drugs and methyl-prednisolone pulses was higher in patients with a baseline SLEDAI ≥6, however, differences were no longer significant when patients with lupus nephritis were excluded. The use of calcium/vitamin D increased with the dose of prednisone, however, 43% of patients on medium-high doses of prednisone did not take any calcium or vitamin D. CONCLUSIONS: This study gives a real-world view of the current therapeutic approach to early lupus in Spain. The generalised use of hydroxychloroquine is well consolidated. There is still a tendency to use prednisone at medium to high doses. Pulse methyl-prednisolone and immunosuppressive drugs were used in more severe cases, but not as steroid sparing agents. Vitamin D use was suboptimal.

IgG4-Related Disease: Results From a Multicenter Spanish Registry.

IgG4-related disease (IgG4-RD) is a rare entity consisting of inflammation and fibrosis that has been described in multiple organs. Concrete diagnostic criteria have been established recently and there is a lack of large series of patients.To describe the clinical presentation, histopathological characteristics, treatment and evolution of a series of IgG4-RD Spanish patients.A retrospective multicenter study was performed. Twelve hospitals across Spain included patients meeting the current 2012 consensus criteria on IgG4-RD diagnosis.Fifty-five patients were included in the study, 38 of whom (69.1%) were male. Median age at diagnosis was 53 years. Thirty (54.5%) patients were included in the Histologically Highly Suggestive IgG4-RD group and 25 (45.5%) in the probable IgG4-RD group. Twenty-six (47.3%) patients had more than 1 organ affected at presentation. The most frequently affected organs were: retroperitoneum, orbital pseudotumor, pancreas, salivary and lachrymal glands, and maxillary sinuses.Corticosteroids were the mainstay of treatment (46 patients, 83.6%). Eighteen patients (32.7%) required additional immunosuppressive agents. Twenty-four (43.6%) patients achieved a complete response and 26 (43.7%) presented a partial response (<50% of regression) after 22 months of follow-up. No deaths were attributed directly to IgG4-RD and malignancy was infrequent.This is the largest IgG4-RD series reported in Europe. Patients were middle-aged males, with histologically probable IgG4-RD. The systemic form of the disease was frequent, involving mainly sites of the head and abdomen. Corticosteroids were an effective first line treatment, sometimes combined with immunosuppressive agents. Neither fatalities nor malignancies were attributed to IgG4-RD.

Systemic involvement in primary Sjogren's syndrome evaluated by the EULAR-SS disease activity index: analysis of 921 Spanish patients (GEAS-SS Registry).

OBJECTIVE: To evaluate systemic involvement in primary SS in a large cohort of Spanish patients using the EULAR-SS disease activity index (ESSDAI) definitions. METHODS: Systemic involvement was characterized using ESSDAI definitions for the 10 clinical domains (constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, peripheral nervous system, central nervous system and muscular). ESSDAI scores at diagnosis, during follow-up and cumulated at the last visit were calculated. RESULTS: The cohort consisted of 921 patients. After a mean follow-up of 75 months, 77 (8%) patients still had an ESSDAI score of zero at the last visit. Organ by organ, the percentage of patients who developed activity during the follow-up (ESSDAI score ≥ 1 at any time) ranged between 1.4% and 56%, with articular, pulmonary and peripheral neurological involvement being the most common. Logistic multivariate regression analysis showed the following features at diagnosis and had the closest association with systemic activity (statistically significant independent variables in at least two domains): cryoglobulinaemia in five domains; anaemia, lymphopenia and low C3 levels in three domains each and age <35 years in two domains. Sicca features, ANA and RF at diagnosis were not associated with a higher cumulated activity score in any clinical domain. CONCLUSION: Primary SS is undeniably a systemic disease, with the joints, lungs, skin and peripheral nerves being the most frequently involved organs. Cytopenias, hypocomplementaemia and cryoglobulinaemia at diagnosis strongly correlated with higher cumulated ESSDAI scores in the clinical domains. Clinically the ESSDAI provides a reliable picture of systemic involvement in primary SS.

Core competencies in internal medicine.

The working group on Competencies of Internal Medicine from the Spanish Society of Internal Medicine (SEMI) proposes a series of core competencies that we consider should be common to all European internal medicine specialists. The competencies include aspects related to patient care, clinical knowledge, technical skills, communication skills, professionalism, cost-awareness in medical care and academic activities. The proposal could be used as a working document for the Internal Medicine core curriculum in the context of the educational framework of medical specialties in Europe.

Effects of fluvastatin extended-release (80 mg) alone and in combination with ezetimibe (10 mg) on low-density lipoprotein cholesterol and inflammatory parameters in patients with primary hypercholesterolemia: a 12-week, multicenter, randomized, open-label, parallel-group study.

BACKGROUND: Combining lipid-lowering agents with complementary mechanisms of action can provide greater cholesterol reductions than using either agent alone, improving achievement of target low-density lipoprotein cholesterol (LDL-C) levels. OBJECTIVES: The aim of this study was to assess the effects of fluvastatin extended-release (XL) 80 mg/d administered alone or combined with ezetimibe 10 mg/d on plasma lipid levels and inflammatory parameters in patients with primary hypercholesterolemia. The tolerability of both regimens was also evaluated. METHODS: In this multicenter, randomized, open-label, parallel-group study, patients with hypercholesterolemia were randomized in a 1:1 ratio to receive fluvastatin XL 80 mg/d alone or in combination with ezetimibe 10 mg/d for 12 weeks. The primary end point was the percentage change from baseline to week 12 in LDL-C level with fluvastatin XL + ezetimibe combination therapy compared with fluvastatin XL alone. Plasma concentrations of inflammatory biomarkers were measured at baseline and week 12. Proportions of patients who achieved National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goals were calculated. Tolerability was assessed by the monitoring and recording of all adverse events (AEs) and laboratory values. RESULTS: A total of 82 patients were enrolled (mean [SD] age, 50.0 [12.0] years; 44% male; 100% white; mean [SD] weight, 73.5 [14.9] kg; combination group, 38 patients; monotherapy group, 44). Fluvastatin XL + ezetimibe and fluvastatin XL monotherapy were associated with significant decreases from baseline in mean LDL-C level (by 49.9% and 35.2%, respectively; between-group difference, P < 0.001). Fluvastatin XL + ezetimibe was associated with significantly greater reductions from baseline than fluvastatin XL monotherapy in total cholesterol (38.2% vs 27.5% P < 0.001), triglycerides (21% vs 3.8% P = 0.02) and apolipoprotein B (34.8% vs 22.5% P < 0.001). NCEP ATP III LDL-C goals were achieved by 87% of patients receiving fluvastatin XL + ezetimibe and 67% of patients receiving fluvastatin XL monotherapy (between-group difference, P = 0.042). The combination was associated with significantly lowered high-sensitivity C-reactive protein (hs-CRP) levels in patients with high baseline hs-CRP (>2 mg/L; P < 0.02), >1 cardiovascular risk factor (P < 0.05), or hypertension (P = 0.015); both regimens were associated with significantly reduced plasma levels of interleukin-1B. No significant between-group differences in the incidences of AEs were found. Most AEs were mild or moderate in intensity. Headache was the most common AE, occurring in 5/44 (11.4%) patients in the fluvastatin XL group and 2/38 (5.3%) patients in the fluvastatin XL + ezetimibe group. One serious AE (convulsive crisis) occurred in a patient receiving fluvastatin XL + ezetimibe, but was not suspected to be related to study medication. CONCLUSION: Fluvastatin XL in combination with ezetimibe was found to be well-tolerated and effective, allowing the majority (87%) of these patients with primary hypercholesterolemia to achieve current treatment goals, and reduced hs-CRP levels in patients at higher cardiovascular risk.