The association between sonographic enthesitis with sonographic synovitis and tenosynovitis in psoriatic arthritis patients.

OBJECTIVES: To examine the association between sonographic enthesitis with sonographic synovitis and tenosynovitis in PsA patients, and the association between sonographic enthesitis and clinical characteristics. METHODS: Consecutive PsA patients that fulfilled the ClASsification criteria for Psoriatic ARthritis (CASPAR) were prospectively recruited. Each patient was evaluated by comprehensive clinical and sonographic assessment (greyscale and Doppler), the latter including 52 joints, 40 tendons and 14 entheses [according to MAdrid Sonography Enthesitis Index (MASEI) plus lateral epicondyles] performed by an experienced sonographer blinded to the clinical data. The US enthesitis score was further categorized to inflammatory (hypoechogenicity, thickening, bursitis and Doppler) and structural (enthesophytes/calcifications and erosions) subcategories. Multivariate linear regression models assessed the association between enthesitis and the selected variables. RESULTS: A total of 158 PsA patients [mean (s.d.) age 52.3 (13) years, 88 (55.7%) females] were analysed. Multivariate linear regression analyses showed a significant association between sonographic enthesitis and sonographic synovitis (ß = 0.18, P = 0.008) and between sonographic enthesitis and sonographic tenosynovitis (ß = 0.06, P = 0.02). These associations were derived from the enthesitis inflammatory subcategory of the MASEI (P < 0.05). Associations between enthesitis and synovitis were also demonstrated on the level of the elbow, knee and ankle joints (P < 0.05). In addition, sonographic enthesitis was significantly associated with older age, male sex, swollen joint count, CRP level and physical occupation. CONCLUSIONS: Sonographic enthesitis is associated with sonographic synovitis and tenosynovitis. The severity of sonographic enthesitis may represent a marker for inflammatory activity in other musculoskeletal domains.

Synovial monocytes from psoriatic and rheumatoid arthritis patients are modulated differently by TNF inhibitors and glucocorticoids: an ex-vivo study.

OBJECTIVES: Synovial monocytes (expressing CD14+CD16+) affect pro-inflammatory responses in the synovium microenvironment of psoriatic arthritis (PsA) and rheumatoid arthritis (RA). The effect of various drugs on those cells was evaluated. METHODS: Synovial fluid mononuclear cells (SFMCs) from PsA (n=29) and RA (n=11) patients were cultured with biologics or glucocorticoids (GCs). CD14+CD16+ cells were analysed by flow cytometry. TNF secretion was assessed by ELISA and changes in cytokine and matrix metalloproteinase-9 (MMP-9) mRNA by qPCR. RESULTS: TNF inhibitors (i) [adalimumab (ADA) and infliximab (IFX)] significantly reduced the %CD14+CD16+ cells (p<0.04 and p<0.02, respectively) compared to IL-17Ai, IL-12/23i, and GCs in PsA patients' SFMCs. Similarly, those TNFi reduced the %CD14+CD16+ cells (p<0.05 and p<0.02, respectively) compared to IL-6Ri, CD20i and GCs in RA patients' SFMCs. TNFi (ADA p<0.01, IFX p=0.0003), and GCs (p<0.05) reduced TNF levels in PsA patients SFMCs supernatants. IFX down-regulated IL-1ß mRNA (p<0.005) while GCs betamethasone (BET) (p<0.01) and methylprednisolone acetate (MPA) (p<0.005) led to IL-1ß up-regulation. IFX down-regulated IL-8 and MMP-9 (p<0.01) and up-regulated IL-10 (p<0.005), and GCs did so to a greater extent (for IL-8, BET p<0.0001 and MPA p<0.005, for MMP-9, BET and MPA p<0.0001 and for IL-10, BET and MPA p<0.0001). CONCLUSIONS: TNFi but not GCs reduced the inflammatory monocytes. Both TNFi and GCs inhibited TNF secretion but differently modulated IL-1ß, IL-8, MMP-9 and IL-10 gene expression. Our data point to TNFi as a modulator of synovial monocytes.

Sex-Based Differences in Sonographic and Clinical Findings Among Patients With Psoriatic Arthritis.

OBJECTIVE: To investigate sex-based sonographic differences in patients with psoriatic arthritis (PsA). METHODS: The study population included consecutive prospectively recruited patients with PsA, as determined by the CASPAR (Classification for Psoriatic Arthritis) criteria, who underwent clinical and physical examinations, followed by a detailed ultrasound (US) evaluation (greyscale and Doppler). US evaluation included 52 joints, 40 tendons, and 14 points of entheses (Modified Madrid Sonographic Enthesis Index [MASEI] plus lateral epicondyles) performed by an experienced sonographer blinded to the clinical data. The US score was based on the summation of a semiquantitative score for synovitis, tenosynovitis, and enthesitis. The US enthesitis score was categorized into inflammatory lesions (ie, hypoechogenicity, thickening, bursitis, and Doppler) and structural lesions (ie, enthesophytes/calcifications and erosions). RESULTS: The study population of 158 patients included 70 males and 88 females. The males had higher rates of employment (P = 0.01), Psoriasis Area and Severity Index scores (P = 0.04), and mean swollen joint counts (P = 0.04). The total US score and its subcategory scores-the synovitis and tenosynovitis scores-were similar for both sexes, whereas the total enthesitis score and its subcategory score-the inflammatory enthesitis score-were significantly higher for the males compared to the females (P = 0.01 and P = 0.005, respectively). Hypoechogenicity, thickening, and enthesophytes were more prevalent in males compared to females (P < 0.05). Multivariate ordinal logistic regression models showed that male sex was associated with a higher US inflammatory enthesitis score compared to female sex (odds ratio 1.96, P = 0.02). CONCLUSION: Sonographic enthesitis was more prevalent in males compared to females with PsA. These differences were not reflected by enthesitis disease activity scores derived from clinical assessment.

Ultrasound, magnetic resonance imaging and radiography of the finger joints in psoriatic arthritis patients.

OBJECTIVES: To report the discrepancies and agreements between US, MRI and radiography of the hand in PsA, and to compare the sensitivity and specificity of US and radiography to MRI as the gold standard imaging study in PsA. METHODS: All of the 100 prospectively recruited consecutive PsA patients underwent clinical assessment and concomitant radiographic, US and MRI studies of the MCP, PIP and DIP joints of one hand. Synovitis, flexor tenosynovitis, extensor paratenonitis, erosions and bone proliferations were identified and scored. All readers were blinded to clinical data, and agreement was calculated based on prevalence-adjusted bias-adjusted kappa (PABAK). RESULTS: The prevalence of synovitis, flexor tenosynovitis, extensor paratenonitis and erosions was similar for US and MRI, while that of bone proliferation was significantly increased in US and radiography compared with MRI (P < 0.001). The absolute agreement between US and MRI was good-to-very good for synovitis (85-96%, PABAK = 0.70-0.92), flexor tenosynovitis (93-98%, PABAK = 0.87-0.96) and extensor paratenonitis (95-98%, PABAK = 0.90-0.97). Agreement between US, MRI and radiography was 96-98% (PABAK = 0.92-0.97) for erosions and 71-93% (PABAK = 0.47-0.87) for bone proliferations. Sensitivity of US with MRI as gold standard was higher for synovitis (0.5-0.86) and extensor paratenonitis (0.63-0.85) than for flexor tenosynovitis (0.1-0.75), while the specificity was high for each pathology (0.89-0.98). CONCLUSION: There is very good agreement between US and MRI for the detection of inflammatory changes in finger joints in PsA. US, radiography and MRI have a good-to-very good agreement for destructive changes.

Role of ultrasound for assessment of psoriatic arthritis patients with fibromyalgia.

OBJECTIVE: To investigate whether ultrasonography (US), as an objective imaging modality, can optimise the evaluation of disease activity in psoriatic arthritis (PsA) patients with concomitant fibromyalgia syndrome (FMS). METHODS: The study population included 156 consecutive PsA patients who were recruited prospectively and fulfilled the ClASsification criteria for Psoriatic ARthritis criteria. The patients underwent complete clinical evaluation including assessment of fulfilment of the 2016 fibromyalgia classification criteria. All of the patients underwent US evaluation including 52 joints, 40 tendons and 14 entheses. The US score was based on the summation of a semiquantitative score (including synovitis, tenosynovitis and enthesitis). Scoring was performed by a sonographer blinded to the clinical data. Spearman's correlation coefficient and multivariate linear regression models were used to examine the association of FMS with clinical and the US scores. RESULTS: Forty-two patients (26.9%) with coexisting PsA and FMS were compared with 114 (73.1%) PsA patients without FMS. Patients with PsA and FMS had significantly increased scores for clinical composite indices, including non-Minimal Disease Activity, Composite Psoriatic Disease Activity Index (CPDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS) (p<0.001). In contrast, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with CPDAI, DAPSA and PASDAS (p<0.001) in the PsA without FMS but not in the PsA with FMS group. FMS was significantly associated with higher clinical scores (p<0.001) but not with the US score (multivariable linear regression models). CONCLUSIONS: US has significantly greater value than composite clinical scores in the assessment of disease activity in PsA patients with FMS.

The Effect of Tocilizumab on Inflammatory Markers in Patients Hospitalized with Serious Infections. Case Series and Review of Literature.

BACKGROUND: The human anti-IL-6 receptor antibody tocilizumab (TCZ) has been approved for the treatment of rheumatoid arthritis (RA) and giant cell arteritis (GCA). It is observed that CRP levels drop quickly after starting TCZ treatment. This may lead to misinterpretation of laboratory results when accessing the patient with infectious disease while on TCZ. We conducted this study to report cases treated with tocilizumab who developed serious infections with special reference to levels of CRP and to review the literature on the effect of tocilizumab on acute phase response (APR) during infections. METHODS: The files of RA and GCA patients hospitalized in the Tel Aviv medical center between 2009-2019 were reviewed. Cases of patients with RA and GCA treated with tocilizumab who were hospitalized due to severe infections were reviewed with special emphasis on the duration of treatment, type of infection, and APR. RESULTS: We identified nine admissions. Seven patients were treated with tocilizumab for RA, two for GCA. The diagnosis was pneumonia in three cases, osteomyelitis in one, cellulitis in one, endocarditis due to Whipple disease in one, abscess of cervix uteri in one, meningitis in one, and perforated diverticulitis in one. The mean CRP levels on admission were 4.75 mg/L (normal range, up to 5 mg/L). All cases were diagnosed correctly on admission. CONCLUSIONS: CRP levels may not correctly reflect the severity of infectious diseases during tocilizumab treatment. Increased awareness of the masking effect of tocilizumab on the APR during infection is needed in order to avoid a delay in the diagnosis.

Prevalence of Nonradiographic Sacroiliitis in Patients With Psoriatic Arthritis: A Real-life Observational Study.

OBJECTIVE: To establish the prevalence of nonradiographic sacroiliitis within a real-life sample of patients with psoriatic arthritis (PsA), using pelvic radiographs and magnetic resonance imaging (MRI) of sacroiliac joints (SIJs). METHODS: This cross-sectional study included 107 consecutive adults with PsA (Classification Criteria for Psoriatic Arthritis criteria). Participants completed clinical and laboratory evaluation, pelvic radiographs scored for radiographic sacroiliitis according to the modified New York (mNY) criteria, and noncontrast MRI of SIJs, scored by the Berlin score and categorized into active sacroiliitis using the 2016 Assessment of Spondyloarthritis international Society (ASAS) criteria and the presence of structural sacroiliitis. RESULTS: Radiographic sacroiliitis/mNY criteria were detected in 28.7% (n = 29), confirmed by MRI-detected structural lesions in 72.4% (n = 21). Active sacroiliitis was detected by MRI in 26% (n = 28) of patients, with 11% (n = 11) qualifying for nonradiographic sacroiliitis. Patients with radiographic and nonradiographic sacroiliitis had similar clinical characteristics, except for a longer duration of psoriasis (PsO) and PsA in the radiographic subgroup (PsO: 23.8 ± 12.5 vs 14.1 ± 11.7 yrs, P = 0.03; PsA: 12.3 ± 9.8 vs 4.7 ± 4.5 yrs, P = 0.02, respectively). Inflammatory back pain (IBP) was reported in 46.4% (n = 13) with active sacroiliitis and 27% (n = 3) with nonradiographic sacroiliitis. The sensitivity of IBP for detection of nonradiographic sacroiliitis was low (27%) and moderate for radiographic sacroiliitis (52%), whereas specificity ranged from 72% to 79% for radiographic and nonradiographic sacroiliitis, respectively. CONCLUSION: The prevalence of active sacroiliitis among a real-life population of patients with PsA was 26%. However, the prevalence of nonradiographic sacroiliitis was low (11%) compared to the radiographic sacroiliitis (28.7%) seen in patients with longer disease duration. IBP was not a sensitive indicator for the presence of early-stage sacroiliitis that was commonly asymptomatic.

Soluble ST2 and CXCL-10 may serve as biomarkers of subclinical diastolic dysfunction in SLE and correlate with disease activity and damage.

OBJECTIVE: Subclinical myocardial dysfunction has been reported to occur early in systemic lupus erythematous (SLE). The study aim was to search for biomarkers of subclinical myocardial dysfunction which may correlate with disease activity in SLE patients. METHODS: This is a prospective, controlled, cross-sectional study of 57 consecutive patients with SLE and 18 controls. Serum samples were obtained to determine serum soluble ST2 (sST2), CXCL-10 and high-sensitivity troponin (hs-troponin) levels. All participants underwent an echocardiographic tissue Doppler study. RESULTS: sST2, CXCL-10 and hs-troponin levels were higher in patients with higher SLE disease activity (SLEDAI). sST2 and CXCL-10 levels were higher in patients with more disease damage as measured by the SLE damage index. Measures of diastolic dysfunction, as assessed by echocardiographic tissue Doppler negatively correlated with log CXCL-10: including E/A; E/e'lateral and E/e'septal, while E/e' positively correlated with CXCL-10. Diastolic dysfunction parameters also correlated with log sST2 levels, a negative correlation was seen with E/e'lateral and a positive correlation was seen with E/e'. Systolic dysfunction parameters positively correlated with hs-troponin: LVED, LVES, IVS, LVMASS and LVMASS index. In a multivariate analysis, sST2 and CXCL-10 were found to be significantly different in SLE vs. healthy controls, independent of each other and independent of cardiovascular risk factors. CONCLUSIONS: Soluble ST2 and CXCL-10 are markers of disease activity and accrued damage in SLE and may serve as sensitive biomarkers for detection of subclinical diastolic dysfunction, independent of traditional cardiovascular risk factors.

Empirical antibiotics targeting gram-positive bacteria for the treatment of febrile neutropenic patients with cancer.

BACKGROUND: The pattern of infections among neutropenic patients with cancer has shifted in the last decades to a predominance of gram-positive infections. Some of these gram-positive bacteria are increasingly resistant to beta-lactams and necessitate specific antibiotic treatment. OBJECTIVES: To assess the effectiveness of empirical anti-gram-positive (antiGP) antibiotic treatment for febrile neutropenic patients with cancer in terms of mortality and treatment failure. To assess the rate of resistance development, further infections and adverse events associated with additional antiGP treatment. SEARCH METHODS: For the review update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (May 2012 to 2017), Embase (May 2012 to 2017), LILACS (2012 to 2017), conference proceedings, ClinicalTrials.gov trial registry, and the references of the included studies. We contacted the first authors of all included and potentially relevant trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing one antibiotic regimen versus the same regimen with the addition of an antiGP antibiotic for the treatment of febrile neutropenic patients with cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias, and extracted all data. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated. A random-effects model was used for all comparisons showing substantial heterogeneity (I2 > 50%). Outcomes were extracted by intention-to-treat and the analysis was patient-based whenever possible. MAIN RESULTS: Fourteen trials and 2782 patients or episodes were included. Empirical antiGP antibiotics were tested at the onset of treatment in 12 studies, and for persistent fever in two studies. The antiGP treatment was a glycopeptide in nine trials. Eight studies were assessed in the overall mortality comparison and no significant difference was seen between the comparator arms, RR of 0.90 (95% CI 0.64 to 1.25; 8 studies, 1242 patients; moderate-quality data). Eleven trials assessed failure, including modifications as failures, while seven assessed overall failure disregarding treatment modifications. Failure with modifications was reduced, RR of 0.72 (95% CI 0.65 to 0.79; 11 studies, 2169 patients; very low-quality data), while overall failure was the same, RR of 1.00 (95% CI 0.79 to 1.27; 7 studies, 943 patients; low-quality data). Sensitivity analysis for allocation concealment and incomplete outcome data did not change the results. Failure among patients with gram-positive infections was reduced with antiGP treatment, RR of 0.56 (95% CI 0.38 to 0.84, 5 studies, 175 patients), although, mortality among these patients was not changed.Data regarding other patient subgroups likely to benefit from antiGP treatment were not available. Glycopeptides did not increase fungal superinfection rates and were associated with a reduction in documented gram-positive superinfections. Resistant colonisation was not documented in the studies. AUTHORS' CONCLUSIONS: Based on very low- or low-quality evidence using the GRADE approach and overall low risk of bias, the current evidence shows that the empirical routine addition of antiGP treatment, namely glycopeptides, does not improve the outcomes of febrile neutropenic patients with cancer.

The Effect of the Presence of Fibromyalgia on Common Clinical Disease Activity Indices in Patients with Psoriatic Arthritis: A Cross-sectional Study.

OBJECTIVE: To study the effect of the presence of fibromyalgia (FM) on common clinical disease activity indices in patients with psoriatic arthritis (PsA). METHODS: Seventy-three consecutive outpatients with PsA (mean age 51.7 yrs; 42 females, 57.5%) were enrolled in a prospective cross-sectional study. FM was determined according to American College of Rheumatism criteria (2010 and 1990). All patients underwent clinical evaluation of disease activity and completed the Health Assessment Questionnaire (HAQ), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Dermatology Life Quality Index, and the Leeds Enthesitis Index (LEI). Disease activity was evaluated using the Composite Psoriatic Disease Activity Index (CPDAI), minimal disease activity (MDA), and the Disease Activity Index for Psoriatic Arthritis (DAPSA) scores. RESULTS: The overall prevalence of FM was 17.8% (13 patients), and all but 1 were women (12 patients, 92.3%, p = 0.005). CPDAI and DAPSA scores were significantly higher in patients with coexisting PsA and FM (9.23 ± 1.92 and 27.53 ± 19.23, respectively) than in patients with PsA only (4.25 ± 3.14 and 12.82 ± 12.71, respectively; p < 0.001 and p = 0.003). None of the patients with FM + PsA met the criteria for MDA, whereas 26 PsA-only patients did (43.3%, p = 0.003). HAQ, BASDAI, and LEI scores were significantly worse in patients with PsA and associated FM. CONCLUSION: Coexisting FM is related to worse scores on all tested measures in patients with PsA. Its influence should be taken into consideration in the treatment algorithm to avoid unnecessary upgrading of treatment.

Bilateral Neuroretinitis and a Unilateral Superior Hemivein Occlusion with Frosted Branch Angiitis Pattern Presenting Simultaneously in Behçet's Disease.

PURPOSE: To report a unique case of Behçet's disease that presented with atypical ocular manifestations. METHODS: Case report. RESULTS: A 23-year-old homosexual male presented with bilateral anterior uveitis, vitritis, neuroretinitis and a unilateral superior hemivein occlusion with frosted branch angiitis pattern. These were accompanied by systemic findings of recurrent oral aphthous ulcers, erythema nodosum, and neurological and gastrointestinal involvement. A positive HLA-B51 examination supported the diagnosis of Behçet's disease. CONCLUSION: Neuroretinitis and frosted branch angiitis may be the clinical manifestations of Behçet's disease and may present simultaneously.

Empirical antibiotics targeting Gram-positive bacteria for the treatment of febrile neutropenic patients with cancer.

BACKGROUND: The pattern of infections among neutropenic cancer patients has shifted in the last decades to a predominance of Gram-positive infections. Some of these Gram-positive bacteria are increasingly resistant to beta-lactams and necessitate specific antibiotic treatment. OBJECTIVES: To assess the effectiveness of empirical antiGram-positive (antiGP) antibiotic treatment for febrile neutropenic cancer patients in terms of mortality and treatment failure. To assess the rate of resistance development, further infections and adverse events associated with additional antiGP treatment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 7), MEDLINE (1966 to 2013), EMBASE (1982 to 2013), LILACS (1982 to 2013), conference proceedings, and the references of the included studies. First authors of all included and potentially relevant trials were contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing one antibiotic regimen to the same regimen with the addition of an antiGP antibiotic for the treatment of febrile neutropenic cancer patients. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias, and extracted all data. Risk ratios (RR) with 95% confidence intervals (CI) were calculated. A random-effects model was used for all comparisons showing substantial heterogeneity (I(2) > 50%). Outcomes were extracted by intention to treat and the analysis was patient-based whenever possible. MAIN RESULTS: Thirteen trials and 2392 patients or episodes were included. Empirical antiGP antibiotics were tested at the onset of treatment in 11 studies, and for persistent fever in two studies. The antiGP treatment was a glycopeptide in nine trials. Seven studies were assessed in the overall mortality comparison and no significant difference was seen between the comparator arms, RR of 0.82 (95% CI 0.56 to 1.20, 852 patients). Ten trials assessed failure, including modifications as failures, while six assessed overall failure disregarding treatment modifications. Failure with modifications was significantly reduced, RR of 0.76 (95% CI 0.68 to 0.85, 1779 patients) while overall failure was the same, RR of 1.00 (95% CI 0.79 to 1.27, 943 patients). Sensitivity analysis for allocation concealment and incomplete outcome data did not change the results. Both mortality and failure did not differ significantly among patients with Gram-positive infections, but the number of studies in the comparisons was small. Data regarding other patient subgroups likely to benefit from antiGP treatment were not available. Glycopeptides did not increase fungal superinfection rates and were associated with a reduction in documented Gram-positive superinfections. Resistant colonisation was not documented in the studies. AUTHORS' CONCLUSIONS: Current evidence shows that the empirical routine addition of antiGP treatment, namely glycopeptides, does not improve the outcomes of febrile neutropenic patients with cancer.

Efficacy and safety of aminoglycoside monotherapy: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study sought to compare the efficacy and adverse effects of any aminoglycoside as a single antibiotic with other antibiotics for the treatment of patients with infection. METHODS: Systematic review of the literature and meta-analysis. We searched for randomized controlled trials comparing the efficacy of single aminoglycoside antibiotic treatment with one or more non-aminoglycoside antibiotic for patients with infection in the Cochrane Library, MEDLINE, EMBASE, LILACS, databases of ongoing trials and conference proceedings. Two reviewers assessed trial eligibility, quality and extracted data. Pooled relative risks (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. RESULTS: The search yielded 37 trials of which 26 included patients with urinary tract infection. Aminoglycosides were equally effective as comparators in the analysis of the primary outcomes, all-cause mortality (RR 1.11, 95% CI 0.68, 1.81, 9 trials, 503 patients) and treatment failure (RR 1.10, 95% CI 0.96, 1.27, 32 trials, 1890 patients). Aminoglycosides were associated with a significantly higher rate of bacteriological failure at end of therapy (RR 1.44, 95% CI 1.21, 1.72, 27 trials, 1668 patients). Subgroup analyses according to quality of trial, type of antibiotics, source of infection and rate of clinical sepsis did not alter the outcomes. Less adverse effects in total but more nephrotoxic effects were observed in patients treated with aminoglycosides. CONCLUSIONS: The present data support the use of aminoglycosides for urinary tract infections. The paucity of trials including patients with sepsis or reporting on mortality precludes firm recommendations for patients with infections other than of the urinary tract.

Benefit of appropriate empirical antibiotic treatment: thirty-day mortality and duration of hospital stay.

PURPOSE: We evaluated the effect of inappropriate antibiotic treatment on mortality and duration of hospital stay in medical inpatients with bacterial infections. SUBJECTS AND METHODS: Two cohorts of febrile adult patients (excluding patients with acquired immune deficiency syndrome and organ transplant recipients), hospitalized in three medical centers in Israel, Italy, and Germany, were included. Patients' data were collected prospectively. Initial empirical treatment was defined as appropriate if an antibiotic prescribed within 24 hours of the first encounter with the patient matched the in vitro susceptibility of a pathogen deemed to be the likely cause of infection. The results of cultures and serologic or direct tests, and data on outcomes were collected 30 days after initiation of empirical treatment. RESULTS: A total of 920 patients (26% of 3529 included patients) had microbiologically documented infections, and mortality data were available for 895 patients (97%). Inappropriate initial antibiotic treatment was prescribed in 36% of patients (N=319). All-cause 30-day mortality rates were 20.1% (N=64) and 11.8% (N=68) in patients who received inappropriate and appropriate treatment, respectively (odds ratio=1.88, 95% confidence interval [CI], 1.29-2.72, P=.001). When adjustment was made for medical center and other variables, the association between inappropriate with mortality was significant (odds ratio=1.58, 95% CI, 0.99-2.54, P=.058). In all 3 medical centers, the mean duration of hospital stay was at least 2 days longer for patients who were prescribed inappropriate antibiotic treatment (overall P=.002). This association was consistent after adjusting for other variables (P=.006). CONCLUSION: Appropriate empirical antibiotic treatment is associated with a better survival and shortened duration of hospital stay in medical patients with bacterial infections.

Empirical antibiotics against Gram-positive infections for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To assess the value of empirical anti-Gram-positive antibiotics for the treatment of febrile neutropenia. METHODS: Systematic review and meta-analysis of randomized controlled trials comparing antibiotics with anti-Gram-positive spectrum to control or placebo, in addition to the same baseline antibiotic regimen in both arms. We searched MEDLINE, EMBASE, LILACS, the Cochrane Library, conference proceedings, and references. No restrictions on inclusion were imposed. Two reviewers independently applied selection criteria, carried out quality assessment, and extracted the data. Relative risks with 95% confidence intervals were pooled using the fixed effect model. The primary outcome assessed was all-cause mortality. RESULTS: Thirteen studies met inclusion criteria, including 2392 participants. Glycopeptides were assessed in nine trials. Empirical anti-Gram-positive antibiotics were assessed for the initial treatment in 11 studies, and for persistent fever in two. No significant difference in all-cause mortality was seen [RR 0.86 (0.58-1.26), seven studies, 852 participants]. Overall failure at end of therapy occurred equally [RR 1.00 (0.79-1.27), six studies, 943 participants]. Failure associated with treatment modifications was more frequent in the control arm when empirical initial glycopeptides were assessed [RR 0.70 (0.61-0.80), five studies, 1178 participants]. Bacterial superinfections, mainly Gram-positive, were detected less frequently in the intervention arm. Adverse events were significantly more common with the additional antibiotic, and nephrotoxicity was significantly more common with additional glycopeptides [RR 1.88 (1.10-3.22), six studies, 1282 participants]. No significant heterogeneity was present in these comparisons. CONCLUSIONS: The use of glycopeptides can be safely deferred until the documentation of a resistant Gram-positive infection.

Older age and second skin cancer as prognostic factors in localized malignant melanomas.

Of the numerous prognostic factors for patients with localized malignant melanoma (LMM), none is superior to the simple parameter of tumor thickness. The aim of the present study was to better define prognostic factors for this disease. Between January 1992 and December 1994, 188 consecutive patients with LMM were treated at the Rabin Medical Center. Patient and tumor characteristics were retrospectively examined as potential prognostic factors. Patients (n=173) who had had at least two-year follow-up were included in the overall survival (OS) analysis, and 159 patients for whom accurate data on recurrent disease were available were included in the disease-free survival (DFS) analysis. At a median follow-up of 85 months (range 24-114), 48 patients (30%) had recurrent disease which resulted in death in 35 (20%). The five-year OS and DFS rates for the entire group were 82 and 72%, respectively. On univariate analysis, female gender, age younger than 75 years, metachronous or synchronous second skin cancer (including melanoma), light skin color, tumor thickness and TNM stage were predictive of both OS and DFS. Tumor location and ulceration, correlated with only one endpoint, OS or DFS, respectively. On multivariate analysis, three factors retained statistical significance with regard to both OS and DFS: tumor thickness (p=0.000 for both), second skin cancer (p=0.02 for both), and age (p=0.04 for both). Alongside the well-established predictive factor of tumor thickness in LMM, older age and the presence of a second skin cancer also have prognostic significance. The prognostic importance of the latter is reported here for the first time.